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SECTION 1. SHORT TITLE. This Act may be cited as the ``Inclusive Home Design Act of 2003''. SEC. 2. DEFINITIONS. As used in this Act: (1) Accessible route.--The term ``accessible route'' means a continuous unobstructed path that-- (A) can be negotiated by a person with a disability using a wheelchair; and (B) is safe for and usable by people with other disabilities and people without disabilities. (2) Covered dwelling unit.--The term ``covered dwelling unit'' means a dwelling unit that-- (A) is a detached single family house, a townhouse or multi-level dwelling unit (whether detached or attached to other units or structures), or a ground- floor unit in a building of three or fewer dwelling units; (B) is designed as, or intended for occupancy as, a residence; (C) was designed, constructed, or commissioned, contracted or otherwise arranged for design or construction, by any person or entity who, at any time during the design or construction, received Federal financial assistance for any program or activity; and (D) is made available for first occupancy after the expiration of the one-year period beginning on the date of the enactment of this Act. (3) Environmental controls.--The term ``environmental controls'' means, for a dwelling unit, any switches or devices that control or regulate lights, temperature, fans, doors, security system features, or any other feature included in the new construction of the unit. (4) Federal financial assistance.--The term ``Federal financial assistance'' means-- (A) any assistance that is provided or otherwise made available by the Secretary of Housing and Urban Development or the Secretary of Veterans Affairs, or any program or activity or such agencies, through any grant, loan, contract, or any other arrangement, after the expiration of the one-year period beginning on the date of the enactment of this Act, including-- (i) grants, subsidies, or any other funds; (ii) services of Federal personnel; (iii) real or personal property or any interest in or use of such property, including-- (I) transfers or leases of the property for less than the fair market value or for reduced consideration; and (II) proceeds from a subsequent transfer or lease of the property if the Federal share of its fair market value is not returned to the Federal Government; (iv) any tax credit, mortgage or loan guarantee or insurance; and (v) community development funds in the form of obligations guaranteed under section 108 of the Housing and Community Development Act of 1974 (42 U.S.C. 5308); or (B) any assistance that is provided or otherwise made available by the Secretary of Agriculture under title V of the Housing Act of 1949 (42 U.S.C. 1471 et seq.). (5) Person or entity.--The term ``person or entity'' includes one or more individuals, corporations (including not- for-profit corporations), partnerships, associations, labor organizations, legal representatives, mutual corporations, joint-stock companies, trusts, unincorporated associations, trustees, trustees in cases under title 11 of the United States Code, receivers, and fiduciaries. SEC. 3. VISITABILITY REQUIREMENT. It shall be unlawful for any person referred to in section 2(2)(C) with respect to a covered dwelling unit to fail to ensure that such dwelling unit contains at least one level that complies with the following requirements: (1) Accessible entrance.-- (A) In general.--Except as provided in subparagraph (B), the level shall contain at least one entrance to the dwelling unit that-- (i) is accessible to, and usable by, people with disabilities such that all rooms on the level are connected by an accessible route; (ii) does not contain any steps or any door threshold that exceeds one-half inch in height; and (iii) is located on a continuous unobstructed path from the public street or driveway that serves the unit, which path-- (I) at no point has a slope exceeding one inch in rise for every 12 inches in length; (II) has a width of not less than 36 inches; (III) has a cross slope not greater than two percent of the width; (IV) is an accessible route; and (V) may include curb ramps, parking access aisles, walks, and ramps. (B) Exceptions.--The provisions of clauses (ii) and (iii) of subparagraph (A) shall not apply to a covered dwelling unit if-- (i) the finished grade of the site is too steep to provide a path having a slope meeting the requirements of subclause (I) of subparagraph (A)(iii) at the front, side, or back of the unit; (ii) there is no driveway serving the unit; and (iii) there is no alley or other roadway capable of providing vehicular access to the rear of the unit. (2) Accessible interior doors.--All doors that are designed to allow passage within the level shall have an unobstructed opening of at least 32 inches when the door is open at a 90- degree angle. (3) Accessible environmental controls.--All environmental controls located on the level shall be located on the wall-- (A) at least 15 inches, but not more than 48 inches, above the floor; or (B) in the case of environmental controls located directly above a counter, sink, or appliance, not more than three inches above such counter, sink, or appliance. (4) Accessible habitable space and bathroom.--The level shall contain the following: (A) Habitable space.--At least one indoor room that has an area of not less than 70 square feet and contains no side or dimension narrower than seven feet. (B) Bathroom.--At least one bathroom that contains, at a minimum, the following: (i) Clear floor space.--Clear floor space of 30 by 48 inches centered on and contiguous to the sink, which is not encroached by the swing path of the bathroom door. (ii) Accessible sink and toilet.--A sink and a toilet that each allow for a parallel or head-on approach by a person in a wheelchair. (iii) Reinforced walls.--Walls that are reinforced to be capable of supporting grab bars that resist shear and bending forces of a minimum of 250 pounds, as follows: (I) All walls adjacent to the toilet shall have horizontal backing reinforcements, each at least 33 inches, but not more than 36 inches, above the floor, and sufficient to allow for a 24-inch grab bar on the wall behind the toilet and another 42- inch grab bar. (II) If a bathtub is present in the bathroom, such reinforcements shall include (aa) two backing reinforcements on the back wall of the bathtub, each at least 24 inches long and not more than 24 inches from the head end wall and not more than 12 inches from the foot end wall, one in a horizontal position at least 33 inches, but not more than 36 inches, above the floor, and one 9 inches above the rim of the bathtub, (bb) one backing reinforcement on the foot end wall of the bathtub, at least 24 inches long and located at the front edge of the bathtub, and (cc) one backing reinforcement on the head end wall of the bathtub, at least 12 inches long and located at the front edge of the bathtub. (III) If a shower is present in the bathroom, such reinforcements shall include backing reinforcements on at least two walls on which the control valve is not located, each at least 33 inches, but not more than 36 inches, above the floor. SEC. 4. ENFORCEMENT. (a) Requirement for Federal Financial Assistance.--Each applicant for Federal financial assistance shall submit an assurance to the Federal agency responsible for such assistance that all of its programs and activities will be conducted in compliance with this Act. (b) Approval of Architectural and Construction Plans.-- (1) Submission.--Any applicant for or recipient of Federal financial assistance who designs, constructs, or commissions, contracts, or otherwise arranges for design or construction of a covered dwelling unit shall submit architectural and construction plans for such unit to the State or local department or agency that is responsible, under applicable State or local law, for the review and approval of construction plans for compliance with generally applicable building codes or requirements (in this subsection referred to as the ``appropriate State or local agency''). (2) Determination of compliance.-- (A) Condition of federal housing assistance.--The Secretary of Housing and Urban Development may not provide any Federal financial assistance under any program administered by such Secretary to a State or unit of general local government (or any agency thereof) unless the appropriate State or local agency thereof is, in the determination of the Secretary, taking the enforcement actions under subparagraph (B). (B) Enforcement actions.--The enforcement actions under this subparagraph are-- (i) reviewing any plans for a covered dwelling unit submitted pursuant to paragraph (1) and approving or disapproving such plans based upon compliance of the dwelling unit with the requirements of this Act; and (ii) consistent with applicable State or local laws and procedures, withholding final approval of construction or occupancy of a covered dwelling unit unless and until such compliance is determined. (c) Civil Action for Private Persons.--Any person aggrieved by an act or omission that is unlawful under this Act may commence a civil action in an appropriate United States district court or State court against any person or entity responsible for any part of the design or construction of a covered dwelling unit no later than two years after the occurrence or termination of the alleged unlawful conduct under this Act. For purposes of this section, a violation involving a covered dwelling unit that is not designed or constructed in conformity with the requirements of this Act shall not be considered to terminate until the violation is corrected. (d) Enforcement by Attorney General.--Whenever the Attorney General has reasonable cause to believe that any person or group of persons has violated this Act, the Attorney General may commence a civil action in any appropriate United States district court. The Attorney General may also, upon timely application, intervene in any civil action brought under subsection (c) by a private person if the Attorney General certifies that the case is of general public importance. (e) Relief.--In any civil action brought under this section, if the court finds that a violation of this title has occurred or is about to occur, it may award to the plaintiff actual and punitive damages, and subject to subsection (g), may grant as relief, as the court finds appropriate, any permanent or temporary injunction, temporary restraining order, or other order (including an order enjoining the defendant from violating the Act or ordering such affirmative action as may be appropriate). (f) Attorney's Fees.--In any civil action brought under this section, the court, in its discretion, may allow the prevailing party, other than the United States, a reasonable attorney's fee and costs. (g) Effect on Certain Sales, Encumbrances, and Rentals.--Relief granted under this section shall not affect any contract, sale, encumbrance, or lease consummated before the granting of such relief and involving a bona fide purchaser, encumbrancer, or tenant, without actual notice of a civil action under this title. SEC. 5. EFFECT ON STATE LAWS. Nothing in this Act shall be constructed to invalidate or limit any law of a State or political subdivision of a State, or of any other jurisdiction in which this Act shall be effective, that grants, guarantees, or provides the same rights, protections, and requirements as are provided by this Act, but any law of a State, a political subdivision thereof, or other such jurisdiction that purports to require or permit any action that would violate this Act shall to that extent be invalid. SEC. 6. DISCLAIMER OF PREEMPTIVE EFFECT ON OTHER ACTS. Nothing in this Act shall limit any right, procedure, or remedy available under the Constitution or any other Act of the Congress. SEC. 7. SEVERABILITY OF PROVISIONS. If any provision of this Act of the application thereof to any person or circumstances is held invalid, the remainder of the Act and the application of the provision to other persons not similarly situated shall not be affected thereby.

Inclusive Home Design Act of 2003 - Requires, with exceptions, newly constructed, federally assisted single family houses and town houses to include at least one level that complies with the following accessibility features for persons with disabilities: (1) accessible entrance; (2) accessible interior doors; (3) accessible environmental controls; and (4) accessible habitable space and an accessible bathroom. Requires: (1) each applicant for Federal financial assistance to submit compliance assurances to the relevant Federal agency, and (2) each person who arranges for design or construction of a covered dwelling to submit architectural and construction plans for State or local approval. Prohibits Federal financial assistance to a State or local government unit unless the recipient is taking certain enforcement actions with regard to covered dwellings. Permits: (1) private civil actions in a United States District Court or State court for violations under this Act; and (2) the Attorney General to commence civil actions or intervene in civil actions under this Act.

we consider some unknown parameters @xmath6 $ ] , @xmath17 and @xmath18 . for @xmath19 , we consider an i.i.d . family @xmath20 of poisson measures on @xmath21 with intensity measure @xmath22 , independent of an i.i.d . family @xmath23 of bernoulli@xmath5-distributed random variables . we also consider the system of equations , for @xmath24 , @xmath25 here and in the whole paper , @xmath26 means @xmath27}$ ] and @xmath28 means @xmath29 . the solution @xmath30 is a family of @xmath0 counting processes ( that is , a.s . integer - valued , cdlg and non - decreasing ) . the following well - posedness result is more or less well - known , see e.g. brmaud - massouli @xcite and @xcite ( we will apply directly the latter reference ) . [ wp ] assume that @xmath8 is locally integrable and fix @xmath19 . the system has a unique cdlg @xmath31-adapted solution @xmath30 such that @xmath32<\infty$ ] for all @xmath33 , where @xmath34\times[0,\infty)),i=1,\dots , n)\lor \sigma(\theta_{ij}\,:\ , i , j=1,\dots , n)$ ] . let us provide a brief heuristic description of this process . we have @xmath0 individuals and @xmath35 stands for the number of actions of the @xmath4-th individual until @xmath1 . we say that @xmath3 _ influences _ @xmath4 if and only if @xmath36 ( with possibly @xmath37 ) . each individual @xmath4 acts , at time @xmath1 , with rate @xmath38 . in other words , each individual has an _ autonomous rate of action _ @xmath13 as well as a _ subordinate rate of action _ @xmath39 , which depends on the number of actions of the individuals that influence him , with a weight @xmath40 and taking into account the age of these actions through @xmath8 . if for example @xmath41}$ ] , then the subordinate rate of action of @xmath4 is simply @xmath42 times the total number of actions , during @xmath43 $ ] , of all the individuals that influence him . .2 cm as is well - known , a phase - transition occurs for such a model , see hawkes - oakes @xcite ( or @xcite for such considerations on large networks ) : setting @xmath44 , @xmath45 in the subcritical case where @xmath46 , we will see that @xmath47 increases linearly with time , at least on the event where the family @xmath23 behaves reasonably ; @xmath45 in the supercritical case where @xmath48 , we will see that @xmath47 increases exponentially fast with time , at least on the event where the family @xmath23 behaves reasonably . .2 cm the limit theorems , and thus the statistical inference , completely differ in both cases , so that the present paper contains essentially two independent parts . .2 cm we will not study the critical case where @xmath49 because it is a very particular case . however , it would be very interesting to understand what happens _ near _ the critical case . our results say nothing about this problem . recalling that @xmath50 , we will work under one of the two following conditions : either for some @xmath51 , @xmath52 or @xmath53 in many applications , @xmath8 is smooth and has a fast decay , so that , except in the critical case , either @xmath54 is satisfied for all @xmath51 or @xmath55 is satisfied . hawkes processes have been introduced by hawkes @xcite and oakes - hawkes @xcite have found a noticeable representation of such processes in terms of galton - watson trees . since then , there has been a huge literature on hawkes processes , see e.g. daley and vere - jones @xcite for an introduction , massouli @xcite , brmaud - massouli @xcite and @xcite for stability results , brmaud - nappo - torrisi @xcite , zhu @xcite and @xcite for limit theorems , etc . hawkes processes are used in various fields of applications : @xmath45 earthquake replicas in seismology , see helmstetter - sornette @xcite , kagan @xcite , ogata @xcite , bacry - muzy @xcite , @xmath45 spike trains for brain activity in neuroscience , see grn et al . @xcite , okatan et al . @xcite , pillow et al . @xcite , reynaud et al . @xcite , @xmath45 genome analysis , see reynaud - schbath @xcite , @xmath45 various fields of mathematical finance , see ait - sahalia et al . @xcite , bauwens - hautsch @xcite , hewlett @xcite , bacry et al . @xcite , bacry - muzy @xcite , @xmath45 social networks interactions , see blundell et al . @xcite and zhou et al . @xcite . .2 cm concerning the statistical inference for hawkes processes , only the case of fixed finite dimension @xmath0 has been studied , to our knowledge , in the asymptotic @xmath56 ( for possibly more general shapes of interaction ) . some parametric and nonparametric estimation procedures for @xmath13 and @xmath8 have been proposed , with or without rigorous proofs . let us mention ogata @xcite , bacry - muzzy @xcite , @xcite , the various recent results of hansen et al . @xcite and reynaud et al . @xcite , as well as the bayesian study of rasmussen @xcite . in many applications , the number of individuals is very large ( think of neurons , financial agents or of social networks ) . then we need some estimators in the asymptotic where @xmath0 and @xmath1 tend simultaneously to infinity . this problem seems to be completely open . .2 cm we assume that we observe @xmath57}$ ] ( or , for convenience , @xmath58}$ ] ) , that is all the actions of the individuals on some ( large ) time interval . .2 cm in our point of view , we only observe the activity of the individuals , we do not know the _ graph of interactions_. a very similar problem was studied in @xcite , although in fixed finite dimension @xmath0 . our goal is to estimate @xmath9 , which can be seen as the main characteristic of the graph of interactions , since it represents the proportion of open edges . we consider @xmath13 and @xmath8 as nuisance parameters , although this is debatable . in the supercritical case , we will be able to estimate @xmath9 without estimating @xmath13 nor @xmath8 . in the subcritical case , we will be able to recover @xmath9 estimating only @xmath13 and the integral @xmath59 of @xmath8 . in any case , we will _ not _ need to provide a nonparametric estimation of @xmath8 , and we believe it is a very good point : it would require regularity assumptions and would complicate a lot the study . .2 cm the main goal of this paper is to provide the basic tools for the statistical estimation of hawkes processes when both the graph size and the observation time increase . of course , this is only a toy model and we have no precise idea of real world applications , although we can think e.g. of neurons spiking : they are clearly numerous ( so @xmath0 is large ) , we can only observe their activities ( each time they spike ) , and we would like to have an idea of the graph of interactions . see again @xcite for a more convincing biological background . think also of financial agents : they are also numerous , we can observe their actions ( each time they buy or sell a product ) , and we would like to recover the interaction graph . we quickly describe the expected _ chaotic _ behavior of @xmath30 as @xmath60 . we refer to sznitman @xcite for an introduction to _ propagation of chaos_. extending the method of ( * ? ? ? * theorem 8) , it is not hard to check , assuming that @xmath61 , that for each given @xmath62 and @xmath63 , the sample @xmath64})_{i=1,\dots , k}$ ] goes in law , as @xmath10 , to a family @xmath65})_{i=1,\dots , k}$ ] of i.i.d . inhomogeneous poisson processes with intensity @xmath66 , unique locally bounded nonnegative solution to @xmath67 . .2 cm on the one hand , approximate independence is of course a good point for statistical inference . on the other hand , the mean - field limit ( i.e. the @xmath68 s ) depends on @xmath9 and @xmath8 only through @xmath66 and thus through @xmath14 , which is a negative point : the mean - field limit is _ unidentifiable_. the situation is however not hopeless because roughly , the mean - field limit _ does not _ hold true for the whole sample @xmath69 and is less and less true as time becomes larger and larger . for @xmath19 and for @xmath30 the solution to , we introduce @xmath70 . we mention in the following remark , that we will prove later , that the number of actions per individual increases linearly in the subcritical case . [ rksc ] assume @xmath71 . then for all @xmath72 , @xmath73 we next introduce @xmath74 @xmath75 in the last expression , @xmath76 is required to be such that @xmath77 . [ mr ] assume @xmath54 for some @xmath78 . for @xmath79 , put @xmath80 : it holds that @xmath81 and that @xmath82 as @xmath56 . there is a constant @xmath83 depending only on @xmath9 , @xmath13 , @xmath8 and @xmath84 such that for all @xmath85 , all @xmath86 , all @xmath79 , @xmath87 we will easily deduce the following corollary . [ mc ] assume @xmath54 for some @xmath78 . for @xmath79 , put @xmath80 . there is a constant @xmath83 depending only on @xmath9 , @xmath13 , @xmath8 and @xmath84 such that for all @xmath85 , all @xmath86 , all @xmath79 , @xmath88 where @xmath89 with @xmath90 and @xmath91 defined by @xmath92 ^ 2}{u[u-\phi_1(u , v , w ) ] } , \quad \phi_3(u , v , w)=\frac{1-u^{-1}\phi_1(u , v , w)}{\phi_2(u , v , w)}.\ ] ] we did not optimize the dependence in @xmath84 : in many applications , @xmath54 holds for all @xmath51 . for @xmath19 and for @xmath30 the solution to , we set @xmath70 . we will check later the following remark , which states that the mean number of actions per individual increases exponentially in the supercritical case . [ rkaz ] assume @xmath55 and consider @xmath93 uniquely defined by @xmath94 . then @xmath95\big)=1.\ ] ] we next introduce @xmath96{{{\mathbf 1}}}_{\{{{\bar z}}^n_t>0\ } } \quad \hbox{and } \quad { { \mathcal p}}^n_t=\frac{1}{{{\mathcal u}}^n_t+1}{{{\mathbf 1}}}_{\{{{\mathcal u}}^n_t\geq 0\}}.\end{aligned}\ ] ] [ mr2 ] assume @xmath55 and consider @xmath93 defined in remark [ rkaz ] . for all @xmath97 , there is a constant @xmath98 ( depending only on @xmath99 ) such that for all @xmath19 , all @xmath79 , all @xmath85 , @xmath100 in practise , we may of course not know if we are in the subcritical or supercritical case . [ decid ] ( i ) under @xmath71 , there are some constants @xmath101 depending only on @xmath102 such that for all @xmath19 , all @xmath79 , @xmath103 . .2 cm \(ii ) under @xmath55 , for all @xmath97 , there is a constant @xmath104 depending only on @xmath105 such that for all @xmath19 , all @xmath79 , @xmath106 . it is then not hard to check that , with the notation of corollary [ mc ] and theorem [ mr2 ] , under @xmath54 ( for some @xmath107 ) or @xmath55 , the estimator @xmath108 which is based on the observation of @xmath109 , i=1,\dots , n}$ ] , converges in probability to @xmath9 , with the same speed of convergence as in corollary [ mc ] ( under @xmath54 for some @xmath107 ) or as in theorem [ mr2 ] ( under @xmath55 ) . in subection [ sbi ] , we will see on a toy model that there is no real hope to find an estimator of @xmath9 with a better precision than @xmath110 , where @xmath15 is something like the mean number of jumps per individual during @xmath111 $ ] . consequently , we believe that the precision we found in corollary [ mc ] is almost optimal , since then @xmath112 by remark [ rksc ] and since we reach the precision @xmath113 for any @xmath114 ( if @xmath8 has a fast decay ) , so that the loss is arbitrarily small . similarly , the precision found in theorem [ mr2 ] is rather satisfying , since then @xmath115 by remark [ rkaz ] and since we reach the precision @xmath116 for any @xmath97 , so that the loss is , here also , arbitrarily small . .2 cm the main default of the present paper is that the constants in corollary [ mc ] and in theorem [ mr2 ] strongly depend on the parameters @xmath117 . they also depend on @xmath84 in the subcritical case . in particular , it would be quite delicate to understand how they behave when approaching , from below or from above , the critical case . there are two main limitations in our setting . .2cmassuming that the @xmath118 s are i.i.d . is of course a strong assumption . what we really need is that the family @xmath23 satisfies similar properties as those shown in subsection [ smat ] ( in the subcritical case ) and in subsection [ rm2 ] ( in the supercritical case ) . this clearly requires that the family @xmath23 is not too far from being i.i.d . , and it does _ not _ suffice that @xmath119 . however , we believe that all the conclusions of the present paper are still true if one assumes that @xmath120 is i.i.d . and that @xmath121 for all @xmath122 , which might be the case in some applications where the interactions are symmetric . a rigorous proof would require some work but should not be too hard . we will study this problem numerically at the end of the paper . .2 cm assuming that we observe all the population is also rather stringent . it would be interesting to study what happens if one observes only @xmath123}$ ] , for some @xmath124 large but smaller than @xmath0 . it is not difficult to guess how to adapt the estimators to such a situation ( see section [ num ] for precise formulae ) . the theoretical analysis would require a careful and tedious study . again , we will discuss this numerically . we denote by @xmath125 the conditional probability knowing @xmath23 . we introduce @xmath126 , @xmath127 and @xmath128 accordingly . .2 cm for two functions @xmath129 , we introduce ( if it exists ) @xmath130 . the functions @xmath131 will play an important role in the paper . observe that , since @xmath132 , @xmath133 . we adopt the conventions @xmath134 and @xmath135 . we also adopt the convention that @xmath136 for @xmath137 . .2 cm all the finite constants used in the upperbounds are denoted by @xmath83 , the positive constants used in the lowerbounds are denoted by @xmath138 and their values change from line to line . they are allowed to depend only on @xmath13 , @xmath9 and @xmath8 ( and on @xmath84 under @xmath54 ) , but never on @xmath0 nor on @xmath1 . any other dependence will be indicated in subscript . for example , @xmath104 is a finite constant depending only on @xmath13 , @xmath9 , @xmath8 and @xmath139 ( and on @xmath84 under @xmath54 ) . in the next section , we try to give the main reasons why our estimators should be convergent , which should help the reader to understand the strategies of the proofs . we also briefly and formally introduce a gaussian toy model in section [ sbi ] to show that the rates of convergence we obtain are not far from being the best we can hope for . in section [ swpmf ] , we prove proposition [ wp ] ( strong existence and uniqueness of the process ) and check a few more or less explicit formulae concerning @xmath140 of constant use . section [ souc ] is devoted to the proof of theorem [ mr ] and corollary [ mc ] ( main results in the subcritical case ) . theorem [ mr2 ] ( main result in the supercritical case ) is proved in section [ surc ] . we check proposition [ decid ] in section [ htd ] . finally , we illustrate numerically the results of the paper and some possible extensions in the last section . this section is completely informal and the symbol @xmath141 means nothing precise . for example , `` @xmath142 $ ] for @xmath1 large '' should be understood as `` we hope that @xmath143 $ ] tends to @xmath144 as @xmath56 in probability or in another sense . '' we assume that @xmath145 and try to explain the asymptotics of @xmath140 and where the three estimators @xmath146 , @xmath147 and @xmath148 come from . we introduce the matrices @xmath149 and @xmath150 , which exists with high probability because @xmath151 . we also set @xmath152 and @xmath153 . .2 cm fixing @xmath0 and knowing @xmath23 , we expect that @xmath142 $ ] for @xmath1 large by a law of large numbers . next , it is not hard to check that @xmath154=\mu t + n^{-1}\sum_{j=1}^n \theta_{ij } { { \int_0^t}}\varphi(t - s ) { { { \mathbb{e}}_\theta}}[z^{j , n}_s]ds$ ] . assume now that @xmath155 $ ] exists for each @xmath24 . then , using that @xmath156 for @xmath1 large , we find that the vector @xmath157 must solve @xmath158 , where @xmath159 is the @xmath0-dimensional vector with all coordinates equal to @xmath144 . this implies that @xmath160 . we thus expect that @xmath142\simeq \mu \ell_n(i ) t$ ] . .2 cm based on this and setting @xmath161 , we expect that @xmath162 for large values of @xmath1 , whence @xmath163 . .2 cm knowing @xmath23 , @xmath47 should resemble , roughly , a poisson process , so that it should approximately hold true that @xmath164 $ ] . thus @xmath165 should resemble @xmath166 ) + { \mathbb{e}}[{\mathbb{v}{\rm ar}_\theta\,}(z^{1,n}_t)]\simeq { \mathbb{v}{\rm ar}\,}({{{\mathbb{e}}_\theta}}[z^{1,n}_t ] ) + { \mathbb{e}}[z^{1,n}_t]$ ] , which itself resembles @xmath167-{{{\mathbb{e}}_\theta}}[{{\bar z}}^{n}_t])^2+{{\bar z}}^n_t \simeq n^{-1 } \mu^2 t^2 \sum_{i=1}^n ( \ell_n(i ) - \bar \ell_n)^2+{{\bar z}}^n_t$ ] . consequently , we expect that @xmath168 \simeq \mu^2 \sum_{i=1}^n ( \ell_n(i ) - \bar \ell_n)^2 $ ] for @xmath1 large . .2 cm finally , the _ temporal _ empirical variance @xmath169 ^ 2 $ ] should resemble @xmath170 $ ] if @xmath171 . thus @xmath172 ^ 2 \simeq n \delta^{-1 } { \mathbb{v}{\rm ar}_\theta\,}[{{\bar z}}^n_\delta]$ ] . introducing the martingales @xmath173 ( where @xmath174 is the compensator of @xmath175 ) , the centered processes @xmath176 $ ] , and the @xmath0-dimensional vectors @xmath177 and @xmath178 with coordinates @xmath179 and @xmath180 , we will see in section [ swpmf ] that @xmath181 , so that for large times , @xmath182 and thus @xmath183 . consequently , we hope that @xmath184 , where @xmath185 and @xmath186 . a little study shows that the martingales @xmath187 are orthogonal and that @xmath188_t = z^{j , n}_t\simeq \mu \ell_n(j)t$ ] , so that @xmath189 . finally , @xmath190={\mathbb{v}{\rm ar}_\theta\,}[\bar u^n_{t}]\simeq \mu t n^{-2 } \sum_{j=1}^n ( c_n(j))^2\ell_n(j)$ ] and we hope that @xmath191\simeq \mu n^{-1 } \sum_{j=1}^n ( c_n(j))^2\ell_n(j)$ ] if @xmath171 . .2 cm we thus need to find the limits of @xmath192 , @xmath193 and @xmath194 as @xmath10 . it is not easy to make rigorous , but it holds true that @xmath195 , where @xmath196 . this comes from @xmath197 , @xmath198 for similar reasons , etc . it is very rough , but it will imply that @xmath199 . once this is seen ( as well as a similar fact for the columns ) , we get convinced , @xmath200 being a vector of @xmath0 i.i.d . binomial@xmath201-distributed random variables , that @xmath202 , that @xmath203 and that @xmath204 . .2 cm at the end , it should be more or less true that , for @xmath205 and @xmath0 large enough and in a suitable regime , @xmath206 , @xmath207 , and @xmath208 . of course , all this is completely informal and many points have to be clarified . .2 cm observe that concerning @xmath209 , we use that @xmath47 resembles a poisson process , while concerning @xmath210 , we use that @xmath211 does not resemble a poisson process . .2 cm the three estimators @xmath212 we study in the paper resemble much @xmath213 and should converge to the same limits . let us explain why we have modified the expressions . we started this subsection by the observation that @xmath154 \simeq \mu \ell_n(i ) t$ ] , on which the construction of the estimators relies . a detailed study shows that , under @xmath54 , @xmath154= \mu \ell_n(i ) t + \chi^n_i \pm t^{1-q}$ ] , for some finite random variable @xmath214 . as a consequence , @xmath215 $ ] converges to @xmath216 considerably faster ( with an error in @xmath217 ) than @xmath218 $ ] ( for which the error is of order @xmath219 ) . this explains our modifications and why these modifications are crucial . .2cmlet us conclude this subsection with a technical issue . if @xmath220 ( which is not forbidden even in the subcritical case ) , there is a positive probability that an anomalously high proportion of the @xmath118 s equal @xmath144 , so that @xmath221 is not invertible and our multivariate hawkes process is supercritical ( on this event with small probability ) . we will thus work on an event @xmath222 on which such problems do not occur and show that this event has a high probability . we now assume that @xmath223 and explain the asymptotics of @xmath140 and where the estimator @xmath224 comes from . we introduce @xmath149 . .2 cm fixing @xmath0 and knowing @xmath23 , we expect that @xmath225 $ ] , for some random @xmath226 not depending on @xmath4 ( and with @xmath227 almost constant for @xmath0 large ) . this is typically a supercritical phenomenon , that can already be observed on galton - watson processes . fortunately , we will not really need to check it nor to study @xmath227 , essentially because we will use the ratios @xmath228 , which makes disappear @xmath227 . .2 cm next , we believe that @xmath154\simeq \gamma_n(i ) e^{\alpha_n t}$ ] for @xmath1 large , for some vector @xmath157 with positive entries and some exponent @xmath229 . inserting this into @xmath154=\mu t + n^{-1}\sum_{j=1}^n \theta_{ij } { { \int_0^t}}\varphi(t - s ) { { { \mathbb{e}}_\theta}}[z^{j , n}_s]ds$ ] , we find that @xmath230 . the vector @xmath157 being positive , it is necessarily a perron - frobenius eigenvector of @xmath231 , so that @xmath232 is its perron - frobenius eigenvalue ( i.e. its spectral radius ) . we now consider the normalized perron - frobenius eigenvector @xmath233 such that @xmath234 and conclude that @xmath235 for all @xmath24 , where @xmath236^{1/2 } h_n$ ] . .2 cm exactly as in the subcritical case , the empirical variance @xmath165 should resemble @xmath167-{{{\mathbb{e}}_\theta}}[{{\bar z}}^{n}_t])^2+{{\bar z}}^n_t \simeq n^{-1}k_n^2e^{2\alpha_n t } \sum_{i=1}^n ( v_n(i ) - \bar v_n)^2+{{\bar z}}^n_t$ ] . since we also guess that @xmath237 , where @xmath238 , we expect that for @xmath1 large , @xmath239\simeq ( \bar v_n)^{-2}\sum_{i=1}^n ( v_n(i ) - \bar v_n)^2 $ ] . .2 cm we now search for the limit of @xmath240 as @xmath10 . roughly , @xmath241 , whence , starting from @xmath242 , we see that @xmath243 , where @xmath159 is the @xmath0-dimensional vector with all coordinates equal to @xmath144 . consequently , @xmath244 , where @xmath245 . in other words , @xmath233 is almost colinear to @xmath246 , and @xmath200 is a vector of @xmath0 i.i.d . binomial@xmath201-distributed random variables . it is thus reasonable to expect that @xmath247 . .2 cm all in all , we hope that for @xmath0 and @xmath1 large and in a suitable regime , @xmath248 . .2 cm finally , let us mention that @xmath249 ( see remark [ rkaz ] ) because @xmath250 , because @xmath251 and because @xmath252 . this last assertion follows from the fact that @xmath241 , so that the largest eigenvalue of @xmath253 should resemble @xmath254 , whence that of @xmath231 should resemble @xmath9 . .2 cm of course , all this is not clear and has to be made rigorous . let us mention that we will use a quantified version of the perron - frobenius of g. birkhoff @xcite . as we will see , the projection onto the eigenvector @xmath233 will be very fast ( almost immediate for @xmath0 very large ) . .2 cm as in the subcritical case , we will have to work on an event @xmath255 , of high probability , on which the @xmath118 s behave reasonably . for example , to apply the perron - frobenius theorem , we have to be sure that the matrix @xmath231 is irreducible , which is not a.s . true . consider @xmath256 and two unknown parameters @xmath257 and @xmath258 $ ] . for @xmath19 , consider an i.i.d . family @xmath23 of bernoulli@xmath5-distributed random variables , put @xmath259 and , conditionally on @xmath23 , consider a family @xmath260 of independent inhomogeneous poisson processes with intensities @xmath261 . we observe @xmath109 , i=1,\dots , n}$ ] and we want to estimate @xmath9 in the asymptotic @xmath262 . .2 cm this problem can be seen as a strongly simplified version of the one studied in the present paper , with @xmath263 in the subcritical case and @xmath93 in the supercritical case . roughly , the mean number of jumps per individual resembles @xmath264 , which is of order @xmath1 when @xmath263 and @xmath265 else . .2 cm there is classically no loss of information , since @xmath266 is known , if we only observe @xmath267 : after a ( deterministic and known ) change of time , the processes @xmath267 become _ homogeneous _ poisson processes with unkown parameters ( conditionally on @xmath23 ) , and the conditional law of a poisson process on @xmath111 $ ] knowing its value at time @xmath1 does not depend on its parameter . .2 cm we next proceed to a gaussian approximation : we have @xmath268g_i$ ] and @xmath269 , for two independent i.i.d . families @xmath270 , @xmath271 of @xmath272-distributed random variables . using finally that @xmath273 in our asymptotic , we conclude that @xmath274 , which is @xmath275-distributed . .2 cm our toy problem is thus the following : estimate @xmath9 when observing a @xmath0-sample @xmath276 of the @xmath275-distribution . we assume that @xmath277 is known , which can only make easier the estimation of @xmath9 . as is well - known the statistic @xmath278 is then _ sufficient _ and is the best estimator ( in all the usual senses ) , for @xmath19 and @xmath79 fixed , of @xmath279 , so that @xmath280 is more or less the best estimator of @xmath281 . but @xmath282 , whence @xmath283 . it is thus not possible to estimate @xmath281 with a better precision than @xmath284 . this of course implies that we can not estimate @xmath9 with a better precision than @xmath284 . we first give the conditionally on @xmath23 , we can apply directly ( * ? ? ? * theorem 6 ) , of which the assumption is satisfied here , see ( * ? ? ? * remark 5-(i ) ) : conditionally on @xmath23 , there is a unique solution @xmath285 to such that @xmath286<\infty$ ] for all @xmath33 . since now @xmath23 can only take a finite number of values , we immediately deduce that indeed @xmath287<\infty$ ] for all @xmath33 . we carry on with a classical lemma . recall that @xmath135 by convention . [ soluce ] consider @xmath288 , @xmath289 , @xmath290 locally bounded and assume that @xmath291 is locally integrable . if @xmath292 for all @xmath33 , then @xmath293 . the equation @xmath294 with unkown @xmath295 has at most one locally bounded solution . indeed , consider two such solutions @xmath296 , observe that @xmath297 satisfies @xmath298 , and conclude that @xmath299 by the generalized gronwall lemma , see e.g. ( * ? ? ? * lemma 23-(i ) ) . we thus just have to prove that @xmath300 is locally bounded and solves @xmath301 . we introduce @xmath302 , which is locally bounded because @xmath8 is locally integrable and which satisfies @xmath303 . we use ( * ? ? ? * lemma 23-(ii ) ) to conclude that @xmath304 is locally bounded . consequently , @xmath305}|g_s| \times \sum_{n\geq 0 } k^n_t$ ] is locally bounded . finally , we write @xmath306 as desired . we next introduce a few processes . [ processes ] assume only that @xmath8 is locally integrable , fix @xmath19 and consider the solution @xmath285 to . for each @xmath307 , we introduce the martingale ( recall that @xmath308 was defined in ) @xmath309 where @xmath310 is the compensated poisson measure associated to @xmath311 . we also introduce @xmath312 } |m^{i , n}_s|$ ] , as well as the ( conditionally ) centered process @xmath313.\ ] ] for each @xmath33 , we denote by @xmath314 ( resp . @xmath178 , @xmath315 , @xmath177 ) the @xmath0-dimensional vector with coordinates @xmath35 ( resp . @xmath180 , @xmath316 , @xmath179 ) . we also set @xmath317 , @xmath318 and @xmath319 . we refer to jacod - shiryaev ( * ? ? ? * chapter 1 , section 4e ) for definitions and properties of pure jump martingales and of their quadratic variations . [ mo ] since the poisson measures @xmath311 are independent , the martingales @xmath320 are orthogonal . more precisely , we have @xmath321_t=0 $ ] if @xmath322 , while @xmath323_t = z^{i , n}_t$ ] ( because @xmath35 counts the jumps of @xmath320 , which are all of size @xmath144 ) . consequently , @xmath324= { { { \mathbf 1}}}_{\{i = j\}}{{{\mathbb{e}}_\theta}}[z^{i , n}_{s\land t}]$ ] . we now give some more or less explicit formulas . we denote by @xmath159 the @xmath0-dimensional vector with all entries equal to @xmath144 and we set @xmath149 for @xmath325 . [ fonda ] assume only that @xmath8 is locally integrable . we have ( recall that @xmath326 ) : @xmath327= & \mu \sum_{n\geq 0 } \big[{{\int_0^t}}s \varphi^{\star n}(t - s ) ds \big ] a_n^n { { \mathbf 1}_n},\\ \label{fundc}{{\mathbf u}}^n_t= & \sum_{n\geq 0 } { { \int_0^t}}\varphi^{\star n}(t - s ) a_n^n { { \mathbf m}}^n_s ds.\end{aligned}\ ] ] the first expression is not difficult : starting from , @xmath328 using ( * ? ? ? * lemma 22 ) , we see that @xmath329 , whence indeed , @xmath330 which is nothing but . taking conditional expectations in , we find that @xmath331=\mu { { \mathbf 1}_n}t + { { \int_0^t}}\varphi(t - s ) a_n { { { \mathbb{e}}_\theta}}[{{\mathbf z}}^n_s ] ds$ ] and thus also @xmath332 . since now @xmath8 is ( a.s . ) locally integrable , since @xmath333 and @xmath178 are ( a.s . ) locally bounded , as well as @xmath331 $ ] and @xmath177 , and directly follow from lemma [ soluce ] . here we consider the subcritical case . we first study the large @xmath0-asymptotic of the matrix @xmath334 , which plays a central role in the rest of the section . in subsection [ sconv ] , we finely study the behavior of @xmath131 . in subsection [ ssa ] , we handle a few computations to be used several times later . subsections [ se1 ] , [ se2 ] and [ se3 ] are devoted to the studies of the three estimators @xmath146 , @xmath147 and @xmath148 . we conclude the proofs of theorem [ mr ] and corollary [ mc ] in subsection [ sconc ] . we use the following standard notation : for @xmath335 and @xmath336 , we set @xmath337 and @xmath338 . for @xmath339 $ ] , we denote by @xmath340 the operator norm on @xmath341 associated to @xmath342 . we recall that @xmath343 and that for all @xmath344 , @xmath345 we assume that @xmath346 . for each @xmath19 , we introduce the @xmath347 random matrix @xmath231 defined by @xmath149 , as well as the event @xmath348$}\big\ } , \hbox { where } a=\frac{1+\lambda p}{2 } \in ( \lambda p,1).\ ] ] on @xmath222 , the @xmath347 matrix @xmath349 is well - defined and we introduce , for each @xmath24 , @xmath152 , @xmath153 , as well as @xmath350 and @xmath351 . we of course have @xmath352 . let us remark once for all that , with @xmath353 , @xmath354$}\big\ } \subset \big\ { \sup_{i=1,\dots , n } \max\{\ell_n(i),c_n(i)\ } \leq c \big\},\\ \label{omegancons2 } \omega_n^1 \subset \big\ { { { { \mathbf 1}}}_{\{i = j\ } } \leq q_n(i , j)\leq { { { \mathbf 1}}}_{\{i = j\ } } + \lambda c n^{-1 } \;\hbox { for all $ i , j=1,\dots , n$}\big\}.\end{gathered}\ ] ] indeed , is straightforward since @xmath355 . to check , we first observe that @xmath356 . next , we use that @xmath357 while , for @xmath358 , @xmath359 . thus @xmath360 for all @xmath361 . hence on @xmath222 , it holds that @xmath362 as desired . by , it suffices to prove that @xmath364 and @xmath365 . since @xmath366 and since @xmath367 ( the transpose of @xmath231 ) has the same law as @xmath231 , it actually suffices to verify the first inequality . first , @xmath368 , where @xmath369 is binomial@xmath201-distributed for each @xmath4 . consequently , @xmath370 . since @xmath371 , we can use the hoeffding inequality @xcite to obtain @xmath372 as desired . [ interro ] assume that @xmath151 . it holds that @xmath373 \leq \frac c { n^2},\\ { \mathbb{e}}\big[{{{\mathbf 1}}}_{\omega_n^1}\big|\frac 1 n \sum_{i=1}^n \ell_n(i)(c_n(i))^2 - \frac 1 { ( 1-\lambda p)^3 } \big|^2 \big ] \leq \frac c { n^2 } , \\ { \mathbb{e}}\big[{{{\mathbf 1}}}_{\omega_n^1}\big|\sum_{i=1}^n ( \ell_n(i)-\bar\ell_n)^2 - \frac{\lambda^2p(1-p)}{(1-\lambda p)^2 } \big| \big ] \leq \frac c { \sqrt n}.\end{gathered}\ ] ] recall that @xmath159 is the @xmath0-dimensional vector of which all the coordinates equal @xmath144 . let @xmath374 ( resp . @xmath375 ) be the vector with coordinates @xmath376 ( resp . @xmath377 ) . we also introduce , for all @xmath24 , @xmath196 and @xmath378 , as well as the corresponding vectors @xmath379 and @xmath380 . let us observe that , with obvious notation , @xmath381 and @xmath382 . finally , we introduce the vectors @xmath383 we recall that @xmath384 and we introduce @xmath385 . _ step 1 . _ we introduce the event @xmath386 the inclusion comes from the fact that a.s . , @xmath387 for any @xmath388 . since @xmath389 with @xmath390 i.i.d . and binomial@xmath201-distributed , it is very classical that for any @xmath114 , @xmath391\leq c_\alpha$ ] ( uniformly in @xmath0 ) , we have similarly @xmath392\leq c_\alpha$ ] , so that @xmath393 point ( i ) is clear , because @xmath398 is nothing but the empirical mean of @xmath399 independent bernoulli@xmath5-random variables . points ( ii ) and ( iii ) are very classical , since @xmath400 is the empirical variance of @xmath0 independent binomial@xmath201-random variables . we now prove ( iv ) : @xmath401=\sum_{i=1}^n { \mathbb{e}}\big[\big(\sum_{j=1}^n \frac{\theta_{ij}}n ( l_n(j)-\bar l_n)\big)^2\big ] = \frac 1n { \mathbb{e}}\big[\big(\sum_{j=1}^n \theta_{1j } ( l_n(j)-\bar l_n)\big)^2\big]\ ] ] by symmetry . we now write @xmath397\leq 4 n^{-1}(i_n+j_n+k_n)$ ] , where @xmath402 , \quad j_n={\mathbb{e}}\big[\big(\theta_{11 } ( l_n(1)- p)\big)^2\big],\quad k_n={\mathbb{e}}\big[\big(\sum_{j=2}^n \theta_{1j}(l_n(j)-p ) \big)^2\big].\ ] ] first , @xmath403 \leq c$ ] by ( i ) . next , it is obvious that @xmath404 ( because @xmath405 and @xmath406 $ ] ) . finally , the random variables @xmath407 being i.i.d . and centered ( for @xmath408 ) , we may write @xmath409 \leq ( n-1 ) { \mathbb{e}}\big[(l_n(2)-p)^2\big ] \leq c,\ ] ] since @xmath410 follows a binomial@xmath201-distribution . this completes the step . we start from @xmath415 , whence @xmath416 . since @xmath417 , we see that @xmath418 ( here @xmath419 is the usual scalar product on @xmath420 ) and thus @xmath421 it only remains to check that @xmath422 , which follows from @xmath423 and the fact that @xmath424 ; and that @xmath425 , which is clear since @xmath426 . _ let @xmath429 be the smallest integer such that @xmath430 . we check that for all @xmath431 , @xmath432 using step 3 and that @xmath433 , we write @xmath434 . but on @xmath222 , @xmath435 and @xmath436 , see and . hence , for @xmath431 , on @xmath414 , we have @xmath437 . since @xmath438 , the conclusion follows . _ we now prove that for @xmath431 , @xmath439 \leq \frac c { n^{2}}.\ ] ] using step 3 , we know that on @xmath414 , @xmath440 , whence @xmath441 where @xmath442 . consequently , @xmath443 , and we only have to prove that @xmath444 \leq c n^{-2}$ ] . to this end , we write @xmath445 , where @xmath446 and @xmath447 . first , since @xmath448 on @xmath222 by , we can write @xmath449 \leq c { \mathbb{e } } [ ( \sum_{j=1}^n ( c_n(j)-p))^2]=c n^2 { \mathbb{e}}[(\bar c_n -p)^2 ] \leq c$ ] , the last inequality coming from step 2-(i ) since @xmath450 . next , we use the cauchy - schwarz inequality : @xmath451 on @xmath414 by step 4 . consequently , @xmath452 \leq c { \mathbb{e}}[||x_n||_2 ^ 2]^{1/2}{\mathbb{e}}[||c_n - p{{\mathbf 1}_n}||_2 ^ 2]^{1/2}$ ] . but @xmath453\leq c$ ] by step 2-(ii ) and we have seen at the end of step 1 that @xmath454\leq c$ ] . _ here we verify that , still for @xmath431 , @xmath455\leq \frac c { n^{2}}.\ ] ] we write , using that @xmath456 , @xmath457 first , since @xmath458 on @xmath222 , we have @xmath459 \leq c n^{-2}$ ] by step 5 . it thus suffices to verify that @xmath460\leq c$ ] , where @xmath461 and @xmath462 . first , it holds that @xmath463 because @xmath464 . hence @xmath465 . but on @xmath414 , we know from step 4 that @xmath466 , and it obviously also holds true that @xmath467 . we thus conclude that @xmath468\leq c { \mathbb{e}}[||x_n||_2 ^ 4 ] ^{1/2}{\mathbb{e}}[||y_n||_2 ^ 4 ] ^{1/2}={\mathbb{e}}[||x_n||_2 ^ 4 ] $ ] by symmetry . using finally step 2-(ii ) , we deduce that indeed , @xmath468\leq c$ ] . next , since @xmath469 on @xmath222 by , we can write @xmath470 . we conclude as previously that @xmath471\leq c$ ] . _ step 7 . _ the goal of this step is to establish that , for all @xmath431 , @xmath472 \leq \frac{c}{\sqrt n}.\ ] ] starting from step 3 , we write @xmath473 thus @xmath474 where we used that @xmath433 and that @xmath475 on @xmath414 , as checked at the end of step 3 . using now that @xmath476 and @xmath477 on @xmath222 and that @xmath466 on @xmath414 by step 4 , we conclude that , still on @xmath414 , @xmath478 since now @xmath479 \leq c n^{-1}$ ] by step 2-(iv ) , since @xmath395\leq c$ ] by step 2-(ii ) and since @xmath480 \leq c$ ] ( see the end of step 1 ) , we deduce that @xmath481\leq \frac{c}{n}.\ ] ] next , we observe that @xmath482 on @xmath414 by step 4 and since @xmath192 is bounded on @xmath222 . hence @xmath483 \leq \frac{c}{\sqrt n } { \mathbb{e}}[||x_n|| _ 2 ^ 2]^{1/2 } \leq \frac{c}{\sqrt n}\ ] ] by step 2-(ii ) . to complete the step , it only remains to verify that @xmath484 \leq \frac{c}{\sqrt n}.\ ] ] we naturally write @xmath485 , where @xmath486,\\ b_n''=&(1-\lambda p)^{-2}{\mathbb{e}}\big[{{{\mathbf 1}}}_{\omega_n^1\cap{{\mathcal a}}_n}\big|||x_n||_2 ^ 2 - p(1-p)\big|\big].\end{aligned}\ ] ] step 2-(iii ) directly implies that @xmath487 . using that @xmath192 is bounded on @xmath222 , we deduce that @xmath488 . thus @xmath489^{1/2}{\mathbb{e } } [ ||x_n||_2 ^ 4]^{1/2}.\ ] ] step 2-(ii ) and step 5 imply that @xmath490 as desired . _ it remains to conclude . it clearly suffices to treat the case where @xmath431 , because @xmath491 and @xmath492 are uniformly bounded on @xmath222 by , so that the inequalities of the statement are trivial when @xmath493 ( if the constant @xmath83 is large enough ) . since @xmath192 is ( uniformly ) bounded on @xmath222 , we have @xmath494 \leq { \mathbb{e}}\big[{{{\mathbf 1}}}_{\omega_n^1 \cap { { \mathcal a}}_n } \big|\bar\ell_n - \frac{1}{1-\lambda p } \big|^2\big ] + c \pr(({{\mathcal a}}_n)^c).\ ] ] the first term is bounded by @xmath495 ( by step 5 ) , as well as the second one ( use the last inequality of step 1 with @xmath496 ) . finally , observe that @xmath498 is bounded by @xmath499 on @xmath222 , so that by step 7 , @xmath500 \leq \frac c { \sqrt n } + c n \pr(({{\mathcal a}}_n)^c ) \leq \frac c { \sqrt n}.\ ] ] we used the last inequality of step 1 with @xmath501 . in view of and , it will be necessary for our purpose to study very precisely the behavior of @xmath131 , which we now do . the following statements may seem rather tedious , but they are exactly the ones we need . recall that @xmath135 and that @xmath136 for @xmath137 by convention . \(iii ) for @xmath515 , for @xmath508 , we put @xmath516 . it holds that @xmath517 , for all @xmath33 , all @xmath518 . furthermore , there is a family @xmath519 satisfying @xmath520 such that , for all @xmath521 , @xmath522 with @xmath523 . we introduce some i.i.d . random variables @xmath524 with density @xmath525 and set @xmath526 as well as @xmath527 for all @xmath361 . we observe that , by the minkowski inequality , @xmath528 \leq n^q { \mathbb{e}}[x_1^q]\leq c n^q$ ] , since @xmath529=\lambda^{-1}\int_0^\infty s^q \varphi(s)ds<\infty$ ] by assumption . to check ( i ) , we use that @xmath530 has for density @xmath531 , so that we can write @xmath532 = \lambda^nt-\lambda^n{\mathbb{e}}[s_n]+{{\varepsilon}}_n(t),\ ] ] where @xmath533 $ ] . we clearly have that @xmath534=n\kappa$ ] , that @xmath535 and that @xmath536= n\lambda^n \kappa$ ] . finally , @xmath537 \leq \lambda^n t^{1-q } { \mathbb{e}}[s_n^q ] \leq c n^q \lambda^n t^{1-q}$ ] . to check ( ii ) , we observe that @xmath511 is obvious because @xmath538 and that , since @xmath528 \leq c n^q$ ] , @xmath539 we write @xmath540 , which implies that @xmath541 . next , we see that @xmath542 . finally , using the two previous bounds , @xmath543 because @xmath544 $ ] by assumption . we finally prove ( iii ) and thus consider @xmath545 and @xmath515 . we start from @xmath546 duds.\end{aligned}\ ] ] using another ( independent ) i.i.d . family @xmath547 of random variables with density @xmath525 and setting @xmath548 ( or @xmath549 if @xmath550 ) , we may write @xmath551.\end{aligned}\ ] ] this precisely rewrites @xmath552 $ ] , which implies that @xmath553 . we next introduce @xmath554,\ ] ] which is nothing but @xmath555 , where @xmath556 $ ] obviously satisfies @xmath557 . thus @xmath558 , where @xmath559 . finally , it is clear that , since @xmath512 , @xmath560 this is , as usual , bounded by @xmath561 . recall , which asserts that @xmath331= \mu \sum_{n\geq 0 } [ { { \int_0^t}}s \varphi^{\star n}(t - s ) ds ] a_n^n { { \mathbf 1}_n}$ ] . using that @xmath568 , we deduce that @xmath569||_r \leq \mu t \sum_{n\geq 0 } \lambda^n |||a_n|||_r^n ||{{\mathbf 1}_n}||_r$ ] . this is clearly bounded , on @xmath222 , by @xmath570 , which proves ( i ) . using next lemma [ conv]-(i ) , @xmath331= \mu \sum_{n\geq 0 } [ \lambda^n t - n \lambda^n \kappa + { { \varepsilon}}_n(t ) ] a_n^n { { \mathbf 1}_n}$ ] , where @xmath571 . hence @xmath572-{{{\mathbb{e}}_\theta}}[{{\mathbf z}}^n_s]= \mu ( t - s ) \sum_{n\geq 0 } \lambda^n a_n^n { { \mathbf 1}_n}+ \mu\sum_{n\geq 0 } [ { { \varepsilon}}_n(t)-{{\varepsilon}}_n(s)]a_n^n{{\mathbf 1}_n}.\ ] ] but @xmath573 on @xmath222 . thus , still on @xmath222 , since @xmath574 and @xmath51 , @xmath575 - \mu(t - s ) \ell_n \big\|_r \leq c(1 \land s^{1-q } ) \sum_{n\geq 0 } n^q \lambda^n |||a_n|||_r^n ||{{\mathbf 1}_n}||_r \leq c ( 1\land s^{1-q } ) ||{{\mathbf 1}_n}||_r.\ ] ] since @xmath323_t = z^{i , n}_t$ ] by remark [ mo ] , the doob inequality implies that @xmath576 } |m^{i , n}_r - m^{i , n}_s|^4\big]\leq c { { { \mathbb{e}}_\theta } } [ ( z^{i , n}_{t}-z^{i , n}_s)^2]$ ] . also , the cauchy - schwarz inequality tells us that @xmath577\leq n^{-1}\sum_{i=1}^n { { { \mathbb{e}}_\theta}}[(z^{i , n}_t - z^{i , n}_s)^2]\leq \sup_{i=1,\dots , n}{{{\mathbb{e}}_\theta}}[(z^{i , n}_t - z^{i , n}_s)^2]$ ] . hence we just have to prove that @xmath578 \leq c ( t - s)^2 $ ] . recalling that @xmath579 $ ] , we have to show that , on @xmath222 , ( a ) @xmath580-{{{\mathbb{e}}_\theta}}[z^{i , n}_s])^2 \leq c ( t - s)^2 $ ] and ( b ) @xmath581 \leq c(t - s)^2 $ ] . to prove ( a ) , we use ( ii ) with @xmath582 and find that , on @xmath222 , @xmath154-{{{\mathbb{e}}_\theta}}[z^{i , n}_s]\leq \mu ( t - s ) ||\ell_n||_\infty + c ||{{\mathbf 1}_n}||_\infty \leq c ( t - s)$ ] , since @xmath374 is bounded on @xmath222 and since @xmath583 by assumption . to prove ( b ) , we use to write @xmath584 , where we have set @xmath585 as in lemma [ conv ] . we deduce that @xmath586= \sum_{m , n\geq 0 } { { \int_0^t}}{{\int_0^t}}\beta_m(s , t , u)\beta_n(s , t , v)\sum_{j , k=1}^n a_n^m(i , j ) a_n^n(i , k ) { { { \mathbb{e}}_\theta}}[m^{j , n}_u m^{k , n}_v ] dvdu.\ ] ] by remark [ mo ] , @xmath587={{{\mathbf 1}}}_{\{j = k\}}{{{\mathbb{e}}_\theta}}[z^{j , n}_{u\land v}]$ ] . using now ( ii ) with @xmath588 and @xmath582 , we see that @xmath589-\mu t\ell_n(j)$ ] satisfies @xmath590 on @xmath222 . we thus write @xmath581=i+j$ ] , where @xmath591 first , using only that @xmath592 is uniformly bounded on @xmath222 and that @xmath593 , we find @xmath594 on @xmath222 , whence @xmath595 by . we conclude that @xmath596 . next , we realize that , with the notation of lemma [ conv]-(iii ) , @xmath597 but we know that @xmath598 . hence @xmath599 , since @xmath374 is bounded on @xmath222 and since , as already seen , @xmath600 is also bounded on @xmath222 . we conclude that @xmath601 \leq c(t - s ) \leq c ( t - s)^2 $ ] on @xmath222 , as desired . we recall that @xmath602 , that the matrices @xmath231 and @xmath603 and the event @xmath222 were defined in notation [ ssimp ] , as well as @xmath152 and @xmath604 . the goal of this subsection is to establish the following estimate . [ esti1lem ] assume @xmath54 for some @xmath51 . then on @xmath222 , for @xmath79 , @xmath607 - \mu \bar \ell_n \big| \leq c t^{-q } \quad \hbox{and}\quad { { { \mathbb{e}}_\theta } } [ |\bar u^n_t|^2 ] \leq c t n^{-1}.\ ] ] applying lemma [ if]-(ii ) with @xmath608 , we immediately find , on @xmath222 , @xmath607 - \mu \bar \ell_n \big| \leq n^{-1}\big\| { { { \mathbb{e}}_\theta}}\big [ \frac{{{\mathbf z}}^n_{2t}-{{\mathbf z}}^n_t}{t}\big ] - \mu \ell_n \big\|_1 \leq cn^{-1 } t^{-q } ||{{\mathbf 1}_n}||_1=ct^{-q}.\ ] ] next , we deduce from that @xmath609 , whence @xmath610^{1/2 } \leq n^{-1 } \sum_{n\geq 0 } { { \int_0^t}}\varphi^{\star n}(t - s ) { { { \mathbb{e}}_\theta}}\big[\big(\sum_{i , j=1}^n a_n^n(i , j)m^{j , n}_s\big)^2\big]^{1/2 } ds\ ] ] by the minkowski inequality . but recalling remark [ mo ] , i.e. @xmath611={{{\mathbf 1}}}_{\{j = l\}}{{{\mathbb{e}}_\theta}}[z^{j , n}_s]$ ] , @xmath612= & \sum_{j=1}^n \big ( \sum_{i=1}^n a_n^n(i , j)\big)^2 { { { \mathbb{e}}_\theta}}[z^{j , n}_s ] \leq |||a_n|||_1^{2n } \sum_{j=1}^n{{{\mathbb{e}}_\theta}}[z^{j , n}_s].\end{aligned}\ ] ] we know from lemma [ if]-(i ) with @xmath608 that @xmath613\leq c n s$ ] on @xmath222 . hence , still on @xmath222 , @xmath610^{1/2 } \leq \frac c { n } \sum_{n\geq 0 } |||a_n|||_1^{n}{{\int_0^t}}\sqrt{ns } \varphi^{\star n}(t - s ) ds \leq \frac { ct^{1/2 } } { n^{1/2 } } \sum_{n\geq 0 } \lambda^n |||a_n|||_1^{n } \leq \frac{c t^{1/2}}{n^{1/2}}\ ] ] as desired . it suffices to write @xmath614 \leq 2 { { { \mathbb{e}}_\theta}}\big[\big|{{\mathcal e}}^n_t - { { { \mathbb{e}}_\theta}}[{{\mathcal e}}^n_t]\big|^2\big ] + 2 \big|{{{\mathbb{e}}_\theta}}[{{\mathcal e}}^n_t ] - \mu \bar \ell_n \big|^2\ ] ] and to observe that @xmath615|=| \bar u^{n}_{2 t } - \bar u^n_t|/t \leq |\bar u^{n}_{2t}|/t + |\bar u^{n}_{t}|/t$ ] , whence finally @xmath614 \leq \frac4{t^2 } ( { { { \mathbb{e}}_\theta}}[|\bar u^{n}_{2t}|^2 ] + { { { \mathbb{e}}_\theta}}[|\bar u^{n}_{t}|^2 ] ) + 2 \big|{{{\mathbb{e}}_\theta}}[{{\mathcal e}}^n_t ] - \mu \bar \ell_n \big|^2.\ ] ] then the proposition immediately follows from lemma [ esti1lem ] . we recall that @xmath616 ^ 2 - n{{\mathcal e}}^n_t /t$ ] where @xmath602 , that the matrices @xmath231 and @xmath603 and the event @xmath222 were defined in notation [ ssimp ] , as well as @xmath152 and @xmath604 . we also introduce @xmath617 ^ 2 $ ] . [ esti2 ] assume @xmath54 for some @xmath51 . then for @xmath79 , a.s . , @xmath618 \leq c \big(1+\sum_{i=1}^n \big[\ell_n(i)-\bar\ell_n\big]^2\big)^{1/2 } \big(\frac n { t^{q } } + \frac { \sqrt n}t + \frac 1 { \sqrt t } \big).\ ] ] we write @xmath620 , where @xmath621 ^ 2- \sum_{i=1}^n [ ( z^{i , n}_{2t}-z^{i , n}_{t})/t - \mu\bar\ell_n]^2 \big|,\\ \delta^{n,2}_t = & \big|\sum_{i=1}^n [ ( z^{i , n}_{2t}-z^{i , n}_{t})/t - \mu\ell_n(i)]^2- n{{\mathcal e}}^n_t /t \big|,\\ \delta^{n,3}_t = & 2 \big|\sum_{i=1}^n [ ( z^{i , n}_{2t}-z^{i , n}_{t})/t - \mu\ell_n(i)][\mu\ell_n(i)-\mu\bar\ell_n]\big|.\end{aligned}\ ] ] we next write @xmath622 , where @xmath623\big]^2 - n{{\mathcal e}}^n_t /t \big|,\\ \delta^{n,22}_t = & \sum_{i=1}^n \big [ { { { \mathbb{e}}_\theta}}[(z^{i , n}_{2t}-z^{i , n}_{t})/t]- \mu\ell_n(i)\big]^2,\\ \delta^{n,23}_t = & 2 \big|\sum_{i=1}^n \big[(z^{i , n}_{2t}-z^{i , n}_{t})/t - { { { \mathbb{e}}_\theta}}[(z^{i , n}_{2t}-z^{i , n}_{t})/t]\big ] \big [ { { { \mathbb{e}}_\theta}}[(z^{i , n}_{2t}-z^{i , n}_{t})/t]- \mu\ell_n(i)\big ] \big|.\end{aligned}\ ] ] we will also need to write , recalling that @xmath176 $ ] , @xmath624 ^ 2 - n{{\mathcal e}}^n_t /t \big| \leq \delta^{n,211}_t+\delta^{n,212}_t+\delta^{n,213}_t,\ ] ] where @xmath625\big\ } \big| , \\ \delta^{n,212}_t = & \big|\sum_{i=1}^n { { { \mathbb{e}}_\theta}}\big[\big((u^{i , n}_{2t}-u^{i , n}_{t})/t\big)^2\big ] -{{{\mathbb{e}}_\theta}}[n{{\mathcal e}}^n_t /t ] \big| , \\ \delta^{n,213}_t = & \big|n{{\mathcal e}}^n_t /t-{{{\mathbb{e}}_\theta}}[n{{\mathcal e}}^n_t /t ] \big|.\end{aligned}\ ] ] finally , we will use that @xmath626 , where @xmath627\big ] \big[\mu\ell_n(i)-\mu\bar\ell_n\big]\big| , \\ \delta^{n,32}_t = & 2 \big|\sum_{i=1}^n \big[{{{\mathbb{e}}_\theta}}[(z^{i , n}_{2t}-z^{i , n}_{t})/t ] - \mu\ell_n(i)\big ] \big[\mu\ell_n(i)-\mu\bar\ell_n\big]\big|.\end{aligned}\ ] ] to summarize , we have to bound @xmath628 , @xmath629 , @xmath630 , @xmath631 , @xmath632 , @xmath633 , @xmath634 and @xmath635 . only the term @xmath629 is really difficult . in the following lemma , we treat the easy terms . we do not try to be optimal when not useful : for example in ( iv ) below , some sharper estimate could probably be obtained with more work , but since we already have a term in @xmath636 ( see lemma [ esti2l4 ] ) , this would be useless . we also recall that we do not really try to optimize the dependence in @xmath84 : it is likely that @xmath217 could be replaced by @xmath637 here and there . we write @xmath648\big\|_1 \big\| { { { \mathbb{e}}_\theta}}[({{\mathbf z}}^{n}_{2t}-{{\mathbf z}}^{n}_{t})/t ] - \mu\ell_n\big\|_\infty.\ ] ] applying lemma [ if]-(ii ) with @xmath582 , we deduce that @xmath649 - \mu\ell_n\|_\infty \leq c t^{-q}$ ] . lemma [ if]-(i ) with @xmath608 gives us that @xmath650\|_1]\leq 2t^{-1 } \|{\mathbb{e}}_\theta[{{\mathbf z}}^{n}_{2t}+{{\mathbf z}}^{n}_{t}]\|_1 \leq c n$ ] . we thus find that indeed , @xmath640 \leq c n t^{-q}$ ] . we work on @xmath222 . recalling that @xmath656 , we may write @xmath655 \leq t^{-2}\sum_{i=1}^n a_i$ ] , where @xmath657|$ ] . now we infer from that @xmath658 , so that @xmath659 , where @xmath660 we have set @xmath661 as in lemma [ conv ] and the only thing we will use is that @xmath662 . recalling that @xmath320 is a martingale with quadratic variation @xmath323_t = z^{i , n}_t$ ] , see remark [ mo ] , we deduce that @xmath663={{{\mathbb{e}}_\theta}}[z^{i , n}_{2 t } -z^{i , n}_{t}]$ ] . hence @xmath664 + 2 { { { \mathbb{e}}_\theta}}[(m^{i , n}_{2t}-m^{i , n}_t ) r^{i , n}_t]=b_i+d_i,\ ] ] the last equality standing for a definition . we first write @xmath665 duds.\ ] ] but we know that @xmath666={{{\mathbf 1}}}_{\{j = k\}}{{{\mathbb{e}}_\theta}}[z^{j , n}_{s\land u}]$ ] by remark [ mo ] and that @xmath667 \leq c t$ ] on @xmath222 by lemma [ if]-(i ) ( with @xmath582 ) . hence @xmath668 but @xmath669 on @xmath222 by , so that @xmath670 . next , we start from @xmath671 ds.\ ] ] as previously , we see that @xmath672=0 $ ] if @xmath322 and that @xmath673={{{\mathbb{e}}_\theta}}[z^{i , n}_{2t\land s } -z^{i , n}_{t\land s } ] \leq c t$ ] on @xmath222 ( by lemma [ if]-(i ) ) , whence @xmath674 on @xmath222 by again . finally , @xmath675 , so that @xmath655 \leq t^{-2}\sum_{i=1}^n a_i \leq c t^{-1}$ ] on @xmath222 . we work on @xmath222 and start with point ( i ) . first , it is clear , since @xmath690 $ ] , that @xmath691 . then we infer from that @xmath692 but we know ( see remark [ mo ] ) that @xmath693\leq c { { { \mathbf 1}}}_{\{i = j\ } } t$ ] by lemma [ if]-(i ) ( with @xmath582 ) . thus @xmath694 recalling , @xmath695 . point ( i ) is checked . point ( iii ) is checked similarly as ( ii ) , provided we verify that @xmath700 . this is obvious if @xmath701 because the martingales @xmath320 and @xmath702 are orthogonal , and relies on the fact , if @xmath703 , that @xmath704^{1/2 } { { { \mathbb{e}}_\theta}}\big[\big|\int_0^s m^{i , n}_{\tau-}dm^{i , n}_\tau\big|^2\big]^{1/2}\leq c t^{3/2}.\ ] ] the last inequality uses that @xmath705={{{\mathbb{e}}_\theta}}[z^{i , n}_x]\leq c t$ ] by remark [ mo ] and lemma [ if]-(i ) and that @xmath706\leq c t^2 $ ] . indeed , we have @xmath707_s= \int_0^s ( m^{i , n}_{\tau-})^2d z^{i , n}_{\tau-}\leq ( m^{i , n,*}_s)^2 z^{i , n}_s$ ] , whence @xmath708 \leq { { { \mathbb{e}}_\theta}}[(m^{i , n,*}_s)^2 z^{i , n}_s ] \leq { { { \mathbb{e}}_\theta}}[(m^{i , n,*}_s)^4]^{1/ 2}{{{\mathbb{e}}_\theta}}[(z^{i , n}_s)^2]^{1/2},\ ] ] which is bounded by @xmath709 by lemma [ if]-(iii ) . for point ( iv ) , we assume e.g. that @xmath710 and first note that @xmath711={{{\mathbb{e}}_\theta}}[m^{k , n}_r{{{\mathbb{e}}_\theta}}[m^{k , n}_sm^{l , n}_u |{{\mathcal f}}_r]]={{{\mathbb{e}}_\theta}}[(m^{k , n}_r)^2m^{l , n}_{u\land r}]\ ] ] because the martingales @xmath712 and @xmath713 are orthogonal . since @xmath714_r = z^{k , n}_r$ ] , it holds that @xmath715 . using that @xmath716 and @xmath713 are orthogonal , we conclude that @xmath717={{{\mathbb{e}}_\theta}}[z^{k , n}_r m^{l , n}_{u\land r}]={\mathbb{c}{\rm ov}_\theta\,}(z^{k , n}_r , m^{l , n}_{u\land r})$ ] . since @xmath718 , we conclude using point ( ii ) . point ( vi ) is harder . recall that @xmath686 , so that clearly , @xmath722 $ ] . we assume e.g. that @xmath710 and we observe that @xmath723={{{\mathbb{e}}_\theta } } [ m^{k , n}_r { { { \mathbb{e}}_\theta}}[m^{k , n}_sm^{a , n}_um^{b , n}_v |{{\mathcal f}}_r ] ] = { { { \mathbb{e}}_\theta}}[(m^{k , n}_r)^2m^{a , n}_{u\land r}m^{b , n}_{v\land r}]\ ] ] because @xmath712 , @xmath720 and @xmath721 are orthogonal . we thus have to prove that for all @xmath724 $ ] with @xmath725 , @xmath726|\leq c n^{-2}t$ ] . we write @xmath715 as in the proof of ( iv ) . the three martingales @xmath716 , @xmath720 and @xmath721 being orthogonal , we find @xmath727= { { { \mathbb{e}}_\theta}}[z^{k , n}_rm^{a , n}_{u}m^{b , n}_{v}]={{{\mathbb{e}}_\theta}}[u^{k , n}_rm^{a , n}_{u}m^{b , n}_{v}]$ ] . we next write , starting again from , @xmath728=\sum_{n\geq 0 } \int_0^r \varphi^{\star n}(r - x ) \sum_{j=1}^na_n^n(k , j ) { { { \mathbb{e}}_\theta}}[m^{j , n}_x m^{a , n}_{u}m^{b , n}_{v } ] dx.\ ] ] but @xmath729|$ ] is zero if @xmath730 because the martingales @xmath731 , @xmath720 and @xmath721 are orthogonal , and is bounded by @xmath732 else by point ( iv ) . as a consequence , @xmath733|\leq c n^{-1}t \sum_{n\geq 0 } \lambda^n ( a_n^n(k , a)+a_n^n(k , b ) ) = c n^{-1}t ( q_n(k , a)+q_n(k , b)).\ ] ] since @xmath734 and @xmath735 , this is bounded by @xmath736 by . for ( vii ) , we assume e.g. that @xmath710 and @xmath737 and we recall that @xmath738 . we have @xmath739 first , @xmath740 . indeed , assuming e.g. that @xmath741 , we have @xmath742 \\ = & { { { \mathbb{e}}_\theta}}[m^{k , n}_rm^{a , n}_u { { { \mathbb{e}}_\theta}}[(m^{k , n}_s - m^{k , n}_r)(m^{a , n}_v - m^{a , n}_r ) |{{\mathcal f}}_r]]\\ & + { { { \mathbb{e}}_\theta}}[m^{k , n}_rm^{a , n}_u ( m^{a , n}_r - m^{a , n}_u ) { { { \mathbb{e}}_\theta}}[m^{k , n}_s - m^{k , n}_r|{{\mathcal f}}_r]]\end{aligned}\ ] ] and in both terms , the conditional expectation vanishes . next , we write as usual @xmath715 and @xmath743 . by orthogonality of the martingales @xmath716 and @xmath744 , we find @xmath745 we deduce from points ( i ) and ( iii ) , since @xmath738 , that @xmath746 . we now treat @xmath124 . it vanishes if @xmath747 , because @xmath748=0 $ ] . we thus assume that @xmath749 . we write as usual @xmath750 and @xmath751 + 2{\mathbb{e}}\big[\big(\int_u^r m^{k , n}_{\tau-}dm^{k , n}_\tau\big ) m^{a , n}_u(m^{a , n}_v - m^{a , n}_u ) \big]\\ & + { { { \mathbb{e}}_\theta}}[(z^{k , n}_r - z^{k , n}_{u } ) m^{a , n}_u(m^{a , n}_v - m^{a , n}_u ) ] .\end{aligned}\ ] ] the first term vanishes ( because @xmath752=0 $ ] ) , as well as the second one ( because @xmath753=0 $ ] by orthogonality of the involved martingales ) . consequently , @xmath754= { { { \mathbb{e}}_\theta}}[(u^{k , n}_r - u^{k , n}_{u } ) m^{a , n}_u(m^{a , n}_v - m^{a , n}_u ) ] .\ ] ] using and recalling that @xmath755 , we find @xmath756 dx.\ ] ] but @xmath757|\leq c n^{-1 } t$ ] if @xmath758 by ( iv ) , while @xmath757|\leq c t^{3/2}$ ] if @xmath759 by lemma [ if]-(iii ) . thus @xmath760 \leq c \big[q_n(k , a)t^{3/2 } + n^{-1}\sum_{j=1}^n q_n(k , j ) t \big].\ ] ] but @xmath734 implies that @xmath761 by , while @xmath762 . as a conclusion , @xmath763 . of course , @xmath764 is treated similarly , and this completes the proof of point ( vii ) . point ( viii ) is obvious : it suffices to use the hlder inequality to find @xmath765^{1/4}{{{\mathbb{e}}_\theta}}[(m^{l , n}_s)^4]^{1/4}{{{\mathbb{e}}_\theta}}[(m^{a , n}_u)^4]^{1/4 } { { { \mathbb{e}}_\theta}}[(m^{b , n}_v)^4]^{1/4},\ ] ] which is bounded by @xmath709 by lemma [ if]-(iii ) . we first note that @xmath767 \big[\ell_n(i)-\bar\ell_n\big]\big|.\ ] ] since @xmath768 is centered ( its conditional expectation @xmath126 vanishes ) , @xmath766=4\mu^2t^{-2 } \sum_{i , j=1}^n \big[\ell_n(i)-\bar\ell_n\big]\big[\ell_n(j)-\bar\ell_n\big ] { \mathbb{c}{\rm ov}_\theta\,}(u^{i , n}_{2t}-u^{i , n}_{t},u^{j , n}_{2t}-u^{j , n}_{t}).\ ] ] using now lemma [ covted]-(i ) , we deduce that @xmath769 on @xmath222 . using furthermore that @xmath770[\ell_n(j)-\bar\ell_n]\leq [ \ell_n(i)-\bar\ell_n]^2+[\ell_n(j)-\bar\ell_n]^2 $ ] and a symmetry argument , we conclude that @xmath766\leq c t^{-1 } \sum_{i , j=1}^n \big[\ell_n(i)-\bar\ell_n\big]^2 ( { { { \mathbf 1}}}_{\{i = j\}}+n^{-1 } ) = c t^{-1 } \sum_{i=1}^n \big[\ell_n(i)-\bar\ell_n\big]^2,\ ] ] which was our goal . we as usual work on @xmath222 . we first note that @xmath771=t^{-4}\sum_{i , j=1}^n a_{ij}$ ] , where @xmath772 but recalling and setting @xmath773 $ ] for all @xmath774 and @xmath775 , @xmath776 concerning @xmath777 , we will only use that , on @xmath222 , @xmath778 the last inequality coming from . a direct computation starting from shows that @xmath779 let us now denote by @xmath780}|{\mathbb{c}{\rm ov}_\theta\,}(m^{k , n}_rm^{l , n}_s , m^{a , n}_um^{b , n}_v)|$ ] . we can write , recalling , @xmath781 using some symmetry arguments , we find that @xmath782 $ ] , where @xmath783 using lemma [ covted]-(v)-(viii ) , from which @xmath784 , we deduce that @xmath785 . next we use lemma [ covted]-(vi)-(viii ) , that is @xmath786 , whence @xmath787 . finally , we use lemma [ covted]-(vii)-(viii ) , i.e. @xmath788 and find that @xmath789 . all in all , we have proved that @xmath790 , which completes the proof . it suffices to recall that @xmath791 and to use lemmas [ esti2l1 ] , [ esti2l2 ] , [ esti2l3 ] and [ esti2l4 ] : this gives , on @xmath222 , @xmath792\leq c\big(\frac{n}{t^{2q}}+\frac 1 t + \frac n { t^q } + \frac{n^{1/2}}{t^{3/2 } } + \big[\sum_{i=1}^n [ \ell_n(i)-\bar \ell_n]^2\big]^{1/2}\frac{1}{t^{1/2 } } + \frac{n^{1/2}}t \big).\ ] ] recalling that @xmath79 , the conclusion immediately follows . we recall that , for @xmath793 such that @xmath794 is an integer , we have set @xmath602 , @xmath795 ^ 2 $ ] and @xmath796 . the matrices @xmath231 and @xmath603 and the event @xmath222 were defined in notation [ ssimp ] , as well as @xmath152 and @xmath153 . we finally introduce @xmath797 . the aim of the subsection is to verify the following result . [ esti3 ] assume @xmath54 for some @xmath798 . then a.s . , for @xmath799 and @xmath800 $ ] such that @xmath794 is a positive integer , @xmath801 \leq c \big(\sqrt{\frac \delta t } + \frac n { \delta^{(q+1)/2}}+ \frac { t}{\delta^{q/2 + 1 } } \big).\ ] ] recall that we do not try to optimize the dependence in @xmath84 . we first write @xmath802 where @xmath803 ^ 2- \sum_{a = t/\delta+1}^{2t/\delta}\big[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } - \delta \mu \bar \ell_n\big]^2 \big|,\ ] ] @xmath804 ^ 2- \!\!\sum_{a = t/\delta+1}^{2t/\delta}\big[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } - { { { \mathbb{e}}_\theta}}[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } ] \big]^2 \big|,\ ] ] @xmath805\big]^2\\ & \hskip3 cm - { { { \mathbb{e}}_\theta}}\big[\sum_{a = t/\delta+1}^{2t/\delta}\big[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } - { { { \mathbb{e}}_\theta}}[\bar z^n_{a\delta } -\bar z^n_{(a-1)\delta } ] \big]^2\big ] \big|,\end{aligned}\ ] ] @xmath806 \big]^2\big]\\ & \hskip2cm- \frac { n}t { { { \mathbb{e}}_\theta}}\big[\sum_{a = t/\delta+1}^{2t/\delta}\big[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } - { { { \mathbb{e}}_\theta}}[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } ] \big]^2\big ] - { { \mathcal w}}^n_{\infty,\infty}\big|.\end{aligned}\ ] ] using that @xmath813 , @xmath814 \big| \big[\delta \mu \bar \ell_n + { { { \mathbb{e}}_\theta}}[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } ] + 2(z^n_{a\delta}-\bar z^n_{(a-1)\delta } ) \big],\ ] ] whence @xmath815\leq \frac n t \sum_{a = t/\delta+1}^{2t/\delta } \big|\delta \mu \bar \ell_n - { { { \mathbb{e}}_\theta}}[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta } ] \big| \big[\delta \mu \bar \ell_n + 3{{{\mathbb{e}}_\theta}}[\bar z^n_{a\delta}-\bar z^n_{(a-1)\delta}]\big].\ ] ] but we deduce from lemma [ if]-(ii ) with @xmath608 that , since @xmath816 , @xmath817 \big| \leq c t^{1-q},\ ] ] whence also @xmath818 \leq \delta \mu \bar \ell_n + ct^{1-q } \leq \delta \mu \bar \ell_n + c$ ] . we conclude that @xmath815\leq c \frac n { t } \sum_{a = t/\delta+1}^{2t/\delta } t^{1-q}\big[4\delta \mu \bar \ell_n + c\big].\ ] ] since @xmath192 is bounded on @xmath222 and since @xmath819 , we find @xmath812\leq c ( n / t)(t/\delta)t^{1-q}\delta \leq cn t^{1-q}$ ] . [ esti3l3 ] assume @xmath54 for some @xmath51 . almost surely on @xmath222 , for all @xmath821 , @xmath822 where @xmath823 is a @xmath824-measurable finite random variable and where @xmath825 satisfies , for some deterministic constant @xmath83 , the inequality @xmath826 . _ here we show that @xmath832= \mu \ell_n(j ) s -x_j^n + r_j^n(s)$ ] , with , for some constant @xmath83 , for all @xmath833 , @xmath834 by , we have @xmath832=\mu \sum_{n\geq 0 } ( \int_0^s r \varphi^{\star n } ( s - r ) dr ) \sum_{l=1}^n a_n^n(j , l)$ ] , whence by lemma [ conv]-(i ) , @xmath835=\mu \sum_{n\geq 0 } ( \lambda^n s - n \lambda^n \kappa + { { \varepsilon}}_n(s ) ) \sum_{l=1}^n a_n^n(j , l)= \mu \ell_n(j ) s -x_j^n + r_j^n(s).\ ] ] we have used that @xmath836 and we have set @xmath837 and @xmath838 . we obviously have @xmath839 on @xmath222 and , since @xmath840 by lemma [ conv]-(i ) , @xmath841 , still on @xmath222 . _ here we verify that @xmath844 on @xmath222 . using that @xmath845 by lemma [ conv]-(ii ) and that @xmath846 is bounded by step 2 ( and does not depend on time ) , @xmath847 the conclusion follows , since @xmath848 on @xmath222 . _ we next check that @xmath849 on @xmath222 . using the bound on @xmath850 ( see step 2 ) , we start from @xmath851 where , using that @xmath852 ( whence @xmath853 if @xmath854 ) and a symmetry argument , latexmath:[\ ] ] we set @xmath1461 , which corresponds to the ( quite arbitrary ) choice @xmath1462 , and @xmath1463 let us explain briefly how we have modified the estimators when observing only @xmath1447 , i=1,\dots , k}$ ] . we adopt the notation of section [ heu ] , in particular @xmath149 , and we follow the considerations therein . in the subcritical case , we recall that @xmath150 and that @xmath152 . following closely the argumentation of subsection [ heusou ] , we expect that , for @xmath1 ( and @xmath1464 ) large and in a suitable regime , we should have @xmath1465 ( where @xmath1466 ) , @xmath1467 , and @xmath1468 . recalling now that @xmath1469 and that @xmath200 is a vector composed of i.i.d . binomial@xmath201 random variables , we expect that @xmath1470\simeq \mu/(1-\lambda p)$ ] and @xmath1471 for @xmath0 , @xmath124 and @xmath1 large . for the last estimator , one first has to get convinced , following again the arguments of subsection [ heusou ] , that @xmath1472 if @xmath1473 while @xmath1474 if @xmath1475 . since we still have @xmath1476 , we find that @xmath1477 ^ 2 + ( n - k)\big[\frac{k\lambda p}{n(1-\lambda p)}\big]^2 \big ) = \frac{\mu}{(1-\lambda p)^3}+ \frac{(n - k)\mu}{k(1-\lambda p)}.\ ] ] recalling that @xmath1478 , we conclude that @xmath1479 . for @xmath0 , @xmath124 , @xmath1 and @xmath1464 large , we thus should have @xmath1480 we introduce the conjectured limit of @xmath1481 as @xmath56 : @xmath1482 in the supercritical case , we follow subsection [ heusur ] and deduce that for @xmath1 large , we should have @xmath1483 , where @xmath233 is the perron - frobenius eigenvector of @xmath231 and where @xmath1484 . recalling now that @xmath233 is almost colinear to @xmath379 and that @xmath200 is a vector composed of i.i.d . binomial@xmath201 random variables , we conclude that indeed , it should hold that @xmath1485)^{-2}{\mathbb{v}{\rm ar}\,}(v_n(1))\simeq 1/p-1 $ ] for @xmath0 , @xmath124 and @xmath1 large , whence @xmath1486 . here we introduce the conjectured limit of @xmath1487 as @xmath56 : @xmath1488 from now on , we assume that @xmath1489 for some @xmath1490 , which satisfies all our assumptions and is easy to simulate . we also always assume that @xmath1491 and @xmath1492 , whence @xmath1493 . we did not find interesting different behaviors when using other values . on all the pictures below , we plot the time evolution of the three quartiles , using @xmath1494 simulations , of @xmath1495 , as a function of time @xmath1496 $ ] . we always choose @xmath1497 in such a way that @xmath1498 , so that on the right of all the pictures below , we always have more or less the same quantity of data ( for a given value of @xmath124 ) . the curves are not smooth because we use only @xmath1494 simulations , but this already takes a lot of time . for a given simulation , we say that the choice is _ good _ when @xmath1499 and @xmath46 or @xmath1500 and @xmath48 . when the choice is almost always good ( that is , for a large proportion of the simulations ) , we also indicate below the picture the three quartiles of @xmath1501 , where @xmath1502 is the conjectured limit as @xmath56 of @xmath1503 , given by @xmath1504 when @xmath46 and @xmath1505 when @xmath48 . we start with the independent case . as the pictures below show , the estimation of @xmath9 is more precise in the fairly supercritical case . also , around the critical case , @xmath1503 is far from always making the good choice , but this does not , however , produce too bad results . on the contrary , the estimation of @xmath9 when @xmath9 is very small does not work very well . observe that the results with @xmath1506 are most often not better than those with @xmath1507 . this is not so surprising for a given value of @xmath1497 , since our rate of convergence resembles @xmath1508 in the subcritical case and something similar in the supercritical case .

we consider a population of @xmath0 individuals , of which we observe the number of _ actions _ until time @xmath1 . for each couple of individuals @xmath2 , @xmath3 may or not _ influence _ @xmath4 , which we model by i.i.d . bernoulli@xmath5-random variables , for some unknown parameter @xmath6 $ ] . each individual acts _ autonomously _ at some unknown rate @xmath7 and acts _ by mimetism _ at some rate proportional to the sum of some function @xmath8 of the ages of the actions of the individuals which influence him . the function @xmath8 is unknown but assumed , roughly , to be decreasing and with fast decay . the goal of this paper is to estimate @xmath9 , which is the main characteristic of the _ graph of interactions _ , in the asymptotic @xmath10 , @xmath11 . the main issue is that the mean field limit ( as @xmath12 ) of this model is unidentifiable , in that it only depends on the parameters @xmath13 and @xmath14 . fortunately , this mean field limit is not valid for large times . we distinguish the subcritical case , where , roughly , the mean number @xmath15 of actions per individual increases linearly and the supercritical case , where @xmath15 increases exponentially . although the nuisance parameter @xmath8 is non - parametric , we are able , in both cases , to estimate @xmath9 without estimating @xmath8 in a nonparametric way , with a precision of order @xmath16 , up to some arbitrarily small loss . we explain , using a gaussian toy model , the reason why this rate of convergence might be ( almost ) optimal .

endoscopic hemostasis 2 , interventional radiology 3 , and surgical treatment 4 are reportedly effective for controlling colonic diverticular bleeding . however , achieving hemostasis is often difficult with these methods when the bleeding source is uncertain . barium impaction therapy was reported to be an effective alternative 5 . however , with this method , which does not require identification of a diverticulum responsible for bleeding , it is often difficult to apply pressure to the deep colon ( right - sided colon ) . therefore , the internal intestinal pressure required for the impaction to achieve hemostasis may not be produced . we report a novel technique using an enteroscopic overtube with balloon , which allows sufficient barium filling while applying pressure to the diverticulum . among patients who visited our hospital with the chief complaint of bloody stools and who were diagnosed as having colonic diverticular bleeding from the deep colon by exclusion , three with poorly controlled bleeding during hospitalization were administered a novel technique ( table 1 ) . for diagnosis , upper and lower gastrointestinal endoscopy and contrast - enhanced computed tomography ( ct ) were concurrently performed . diverticular bleeding from the deep colon was diagnosed by exclusion in patients meeting all of the following criteria : lower gastrointestinal endoscopy revealing diverticula and fresh clots in the deep colon , failure to confirm bleeding from a responsible diverticulum and to provide definitive diagnosis , detection of brown stools in the small intestine to exclude small intestinal bleeding , and indication of the absence of mucosal lesions that could cause bleeding , such as angiectasis , inflammation , and ulcers of the colonic mucosa . the upper gastrointestinal endoscopy excluded upper gastrointestinal bleeding , and contrast - enhanced ct could not identify the responsible blood vessel . deep colonic diverticular bleeding was considered if spontaneous hemostasis had been achieved before observation . moreover , in these three patients , neither endoscopic treatment nor interventional radiology was performed because the bleeding source was difficult to identify with endoscopy and contrast - enhanced ct . all three patients had achieved spontaneous hemostasis at the time of this study . the treatment was performed to prevent recurrent bleeding . an enteroscope ( sif type q260 , olympus , tokyo , japan ) with an overtube ( single - use splinting tube , olympus ) ( fig . 1 ) was inserted , and the scope was removed when the tube reached the cecum ( fig . overtube ( single - use splinting tube , olympus , tokyo , japan ) . b balloon inflated in the ascending colon at the midpoint between the cecum and hepatic flexure , followed by barium filling . e barium filling of the entire colon completed . an enema catheter ( double balloon enema catheter with 3-pipe isolation check valve ; kaigen pharma co. , ltd . , osaka , japan ) was connected to an overtube , and the balloon was initially inflated around the midpoint between the cecum and the hepatic flexure to close the colon cavity . the intestinal tract was filled with barium and was sufficiently pressurized for 3 minutes without regurgitation into the small intestine side . the balloon was subsequently inflated at sites equally dividing the total colon into eight parts , with filling and maintaining being repeated in stages , eventually filling the entire colon ( fig . in all three patients , the entire colon could be filled with a total volume of barium of about 1200 ml to 1500 ml without adverse events such as perforation . abdominal radiography on the day following treatment showed barium remnants in the diverticulum ( fig.3 ) . barium in the intestinal tract outside the diverticulum was excreted without additional laxatives , with no ileus symptoms , diverticulitis , or appendicitis . cases of colonic diverticulosis are increasing annually 6 , resulting in more cases with diverticular diseases 7 . the endoscopic identification rate of diverticular bleeding sources was reportedly 38 % , the hemostasis rate 88 % , and the recurrent bleeding rate 22 % 8 . several reports have described the usefulness of barium impaction therapy , which is an option for patients whose bleeding source can not be identified ( table 2 ) 2 8 9 10 11 12 13 . however , recurrent bleeding rates with barium impaction therapy and endoscopic treatment were similar 14 . the rate of recurrent bleeding from deep colonic diverticulum is higher than with endoscopic treatment . one explanation is the difficulty in applying pressure to the deep colon with the conventional method of barium impaction via the rectum . although there is no clear evidence of the hemostatic mechanism of barium impaction , various effects have been reported , such as a tamponade action , direct blood clotting , mucosal protection , and exposed blood vessel clotting 2 12 15 . regarding the concentration of barium , previous studies used concentrations ranging from 20 w / v% to 200 w / v% 2 5 8 9 10 11 12 13 . we used a concentration of 200 w / v% in this study , although we were uncertain about whether a higher concentration barium impaction could provide better results because there were no studies on this issue . further studies investigating the hemostatic mechanism of barium impaction as well as the optimal concentration for the treatment are required . to , throughout the colon ; ac , ascending colon ; tc , transverse colon ; dc , descending colon ; sc , sigmoid colon ; nr , not reported ; right - sided , transverse or proximal colon ; left - sided , descending or distal colon ; bilateral colon , around the entire colon . in contrast to the conventional method , pressure is directly applied to the deep colon via barium filling under balloon occlusion . we adjusted the barium injection pressure so that barium did not pass back through the ileocecal valve into the small intestine , as regurgitation of barium into the small intestine side might lead to decreased pressure in the large intestine . these three patients received barium impaction therapy using an enteroscopic overtube with balloon after endoscopy to rule out intestinal mucosal damage due to crohn s disease , ulcerative colitis , ischemic enteritis , intestinal tuberculosis , intestinal behcet s disease , or infectious enteritis . ensuring safety will be one of the future challenges since no evidence is available to support the association between intestinal pressure and perforation . the perforation risk will increase in patients with these intestinal disorders because their affected mucosae will be more fragile than normal mucosae . the pressure from barium impaction may not extend to the small intestine in patients with valve deformity , and as a result of this pressure , the colon may perforate . therefore , barium impaction therapy with an enteroscopic overtube with balloon should not be used in patients in whom an intestinal disorder causing mucosal damage was detected using endoscopy or those with an ileocecal valve deformity . moreover , although it seems that more diverticula can be filled with barium by the application of pressure than by using the conventional method , it can be expected that the application of pressure simultaneously increases the risk of diverticulitis . even in patients in whom this method is performed and whose abdominal pain , fever , and other symptoms suggest diverticulitis , we have to diagnose the condition without a ct scan , because the presence of barium in the intestinal tract causes the appearance of artifacts , making diagnosis with ct extremely difficult . other disadvantages are the requirement for an enteroscope , which is not widely available in general hospitals , the relatively high cost of the overtube , and the greater manpower requirements for the procedure . the limitation of this novel technique is no evidence of its therapeutic effects in this case series , which describes only three cases . although this technique may significantly increase the risk of complications in comparison to the conventional method , it should provide more benefits than risks through its therapeutic effects on hemostasis and long - term prevention of recurrence . a prospective comparative study is required to validate long - term recurrence prevention rates and the safety of this novel barium impaction therapy technique . ap , angina pectoris ; ht , hypertension ; ra , rheumatoid arthritis ; hl , hyperlipidemia ; mr , mitral regurgitation ; mvr , mitral valve replacement ; hu , hyperuricemia ; nsaids , nonsteroidal anti - inflammatory drugs ; l - asp , low - dose aspirin ; to , throughout the colon ; ac , ascending colon ; sc , sigmoid colon .

background and aims : in hemostasis for colonic diverticular bleeding , the incidence of recurrent bleeding is higher in deep colonic diverticulum than in shallow . we aimed to improve and evaluate barium impaction therapy using an enteroscopic overtube with balloon . patients and method : we performed barium impaction therapy in three patients with a diagnosis of deep colonic diverticular bleeding . the tip of the overtube was inserted to reach the cecum using the conventional method . after deflating the colon , the enteroscope was removed . the balloon in the tube was inflated , followed by barium filling via the tube . sufficient pressure was applied by ensuring no regurgitation into the small intestine side . the entire colon was continuously filled with barium in stages . results : post - treatment bleeding was controllable without adverse events in all three patients . conclusion : this novel barium impaction therapy using an enteroscopic overtube with balloon was effectively performed without adverse events .

consider the following weighted @xmath0-statistics : @xmath1 where @xmath2 is a nonstationary time series , @xmath3 , the kernel @xmath4 and the weights @xmath5 are symmetric and borel measurable functions . many important time and spectral domain problems in the analysis of nonstationary time series boil down to the investigation of weighted @xmath0-statistics in the form of ( [ eq : ustat ] ) . for instance , in various situations one may be interested in estimating parameter functions @xmath6 over time @xmath7 , where @xmath8 is the marginal distribution of @xmath9 at time @xmath7 . in this case many nonparametric estimators of @xmath10 are asymptotically equivalent to the weighted @xmath0-statistics @xmath11 where @xmath12 is two - dimensional kernel function , and @xmath13 is a bandwidth that restricts the estimation in a neighborhood of @xmath7 . additionally , after the nonparametric fitting one may want to specify or test whether the parameter function is of certain parametric forms . in this case many @xmath14 distance based test statistics are of the form ( [ eq : ustat ] ) with degenerate kernels ; that is , kernels @xmath4 such that @xmath15= 0 $ ] for every @xmath16 and @xmath17 . see , for instance , the @xmath14 distance based quantile specification test in @xcite . furthermore , in spectral analysis of the nonstationary time series @xmath18 , both the periodogram @xmath19 and the classic smoothed periodogram estimate of the spectral density @xmath20 are in the form of ( [ eq : ustat ] ) with kernel @xmath21 . here @xmath22 stands for the imaginary unit , @xmath23 is a kernel function and @xmath24 is a window size satisfying @xmath25 with @xmath26 . note that in every example above , @xmath27 involves a tuning parameter ( either bandwidth or window size ) which varies with the sample size @xmath28 . hence it is important to write the weights as a function of @xmath28 in ( [ eq : ustat ] ) . the purpose of the paper is to establish an asymptotic theory for ( [ eq : ustat ] ) through the angle of fourier analysis . to illustrate the main idea , suppose that @xmath29 is absolutely integrable on @xmath30 for some function @xmath31 . then under mild conditions @xmath32 admits the fourier representation @xmath33 . consequently @xmath34 can be written as @xmath35 where @xmath36 . note that in ( [ eq : fourier_repre ] ) the complex structure of @xmath34 is reduced to a process of quadratic forms @xmath37 through the aid of fourier transformation . the multiplicative structure of the quadratic forms makes in - depth asymptotic investigations possible for a wide class of nonstationary time series . furthermore , the continuous structure of @xmath38 in @xmath17 makes a stochastic equi - continuity and continuous mapping argument possible which is shown to be powerful compared to the discrete spectral decomposition methods used in the literature . with the aid of the above structural simplifications , in this paper we are able to establish a uniform approximation scheme of @xmath39 by a process of gaussian quadratic forms . as a consequence we establish a unified asymptotic theory for a class of nondegenerate and degenerate weighted @xmath0-statistics with reflexible weight functions . both central and noncentral limit theorems are developed for a wide class of nonstationary time series with both smoothly and abruptly changing data generating mechanisms over time . the established theory can be applied to many problems in the study of nonstationary time series , including topics such as nonparametric estimation and specification , periodogram and spectral density inferences discussed above . in ( [ eq : ustat ] ) , if the summation is taken over indices @xmath40 , then the statistics are commonly called weighted @xmath41-statistics in the literature . for many problems that are of practical importance , statistical theory for the @xmath41- and @xmath0-statistics can be established with essentially the same techniques . since the seminal papers of @xcite and @xcite , the analysis of @xmath0- and @xmath41-statistics has attracted much attention in the statistics and probability literature . it seems that most efforts have been put in un - weighted @xmath41- or @xmath0-statistics with @xmath42 for stationary data . see , for instance , @xcite , @xcite , huskova and janssen ( @xcite ) , @xcite , @xcite and beutner and zhle ( @xcite ) for various approaches for nondegenerate and degenerate un - weighted @xmath41- and @xmath0-statistics . we also refer to the monographs of @xcite , @xcite and @xcite for more references . as we observe from the examples in the beginning of this , it is important to consider weighted @xmath0-statistics with sample size dependent weights in the study of nonstationary time series . there are a small number of papers discussing weighted @xmath0- or @xmath41-statistics in the literature . see , for instance , @xcite , @xcite , @xcite and @xcite for weighted @xmath41- and @xmath0-statistics of independent data and @xcite for weighted nondegenerate @xmath41-statistics of stationary time series . for most of the above discussions , the weights are not allowed to be sample size dependent . exceptions include @xcite who discovered a very deep result that @xmath43 implies asymptotic normality of a very wide class of weighted degenerate @xmath0-statistics for independent data , where @xmath44 is the eigenvalue of the matrix @xmath45 with the maximum absolute value . there the proof heavily depended on the martingale structure of degenerate @xmath0-statistics of independent data and is hard to generalize to the time series setting . in this paper , from a fourier analysis angle , we generalize the result of @xcite and show that , for many temporally dependent processes , @xmath46 implies asymptotic normality of @xmath34 for a class of degenerate kernels and weight functions . quadratic forms are special cases of ( [ eq : ustat ] ) with @xmath21 . there are many papers in the literature devoted to the analysis of such statistics . see , for instance , @xcite , @xcite , gtze and tikhomirov ( @xcite ) , @xcite and bhansali , giraitis and kokoszka ( @xcite ) , among others . it seems that most of the results are on independent or stationary data . exceptions include @xcite who recently studied asymptotic normality of a class of quadratic forms with banded weight matrix for @xmath47-mixing nonstationary time series . for independent data , gtze and tikhomirov ( @xcite ) , among others , established deep theoretical results indicating that distributions of generic quadratic forms can be approximated by those of corresponding gaussian quadratic forms . in this paper , we generalize this type of result and show that the laws of a wide class of quadratic forms for nonstationary time series can be well approximated by the distributions of corresponding quadratic forms of independent gaussian random variables . consequently , central and noncentral limit theorems are established for the latter class of quadratic forms for nonstationary time series . the rest of the paper is organized as follows . in section [ sec : pre ] we shall introduce the class of absolutely convergent fourier transformations and the piece - wise locally stationary time series models used in this paper . sections [ sec : nondegen ] and [ sec : degen ] establish the asymptotic theory for nondegenerate and degenerate @xmath0-statistics , respectively . theory for quadratic forms will be covered in section [ sec : degen ] as a special case of degenerate @xmath0-statistics . in section [ sec : app ] , we shall apply our theory to the problems of nonparametric estimation as well as spectral analysis of nonstationary processes . several examples will be discussed in detail . finally , the theoretical results are proved in section [ sec : proof ] . we first introduce some notation . for a vector @xmath48 , let @xmath49 . let @xmath22 be the imaginary unit . for a complex number @xmath50 , write @xmath51 . for @xmath52 , denote by @xmath53 the collection of functions @xmath54 such that @xmath55 . for a function @xmath56 , denote by @xmath57 its fourier transform , that is , @xmath58 . for a borel set @xmath59 in @xmath60 , denote by @xmath61 the collection of all borel sets in @xmath59 . for a random vector @xmath62 , write @xmath63 ( @xmath64 ) if @xmath65^{1/q } < \infty$ ] and @xmath66 . denote by @xmath67 the weak convergence . the symbol @xmath68 denotes a generic finite constant which may vary from place to place . following the classic notation , a function @xmath69 is said to belong to @xmath70 if there exists a function @xmath71 , @xmath72 , such that @xmath73 and @xmath74 the class @xmath70 is called the wiener ring or wiener algebra , naming after norbert wiener for his fundamental contributions in the study of absolutely convergent fourier integrals . due to its importance in various problems , the possibility to represent a function as an absolutely convergent fourier integral has been intensively studied in mathematics , and various sufficient conditions are continuously being discovered in recent years . for a relatively comprehensive survey , we refer to liflyand , samko and trigub ( @xcite ) . for the study of @xmath0-statistics of dependent data , we need to further define the subclass @xmath75 of @xmath70 as follows . we call @xmath76 for some @xmath77 if @xmath78 with representation ( [ eq : w0 ] ) and @xmath79 where @xmath80 . note that @xmath81 . in order for @xmath82 , it is necessary that @xmath83 is uniformly continuous on @xmath30 and vanishes at @xmath84 . however , the above conditions are generally not sufficient . generally speaking , the fourier transform of a smoother function tends to have a lighter tail at infinity . the latter fact implies that stronger smoothness conditions are needed to insure @xmath82 . [ prop : ac ] suppose that a symmetric function @xmath85 . [ liflyand , samko and trigub ( @xcite ) , theorem 10.11 ] . assume that @xmath83 is uniformly continuous on @xmath30 and vanishes at @xmath84 . let @xmath83 and its partial derivative @xmath86 be locally absolutely continuous on @xmath87 in each variable . further let each partial derivative @xmath86 and @xmath88f$ ] exist and belong to @xmath89 for some @xmath90 . then @xmath82 . if @xmath83 satisfies @xmath91 , where @xmath92 and @xmath93 , then @xmath76 for any @xmath94 . proposition [ prop : ac ] gives some easily checkable sufficient conditions for @xmath82 and @xmath75 based on the smoothness of its partial derivatives . in the literature , numerous other sufficient conditions based on various notions of smoothness or variation are available ; see , for instance , the review of liflyand , samko and trigub ( @xcite ) . we point out here that the conditions in proposition [ prop : ac ] are not minimal sufficient . for instance , the function @xmath95 for any @xmath96 . but the latter function is not differentiable on @xmath30 . thanks to the fast computation of fourier transforms , in practice when facing specific choice of @xmath83 , condition ( [ eq : w0delta ] ) with @xmath97 can also be checked via numerical computation . for an observed process @xmath98 , consider the class of nonstationary time series models of the form [ zhou ( @xcite ) , definition 1 ] @xmath99}(t_k),\qquad k=1,2,\ldots , n,\ ] ] where @xmath100 are @xmath101 unknown ( but nonrandom ) break points with @xmath102 , and @xmath103 , @xmath104 is the indicator function , @xmath105\times{{\mathbb{r}}}^{\mathbb{n}}\rightarrow { { \mathbb{r}}}$ ] are @xmath106)\times\mathfrak{b}({{\mathbb{r}}})^{\mathbb{n}}$ ] , @xmath107-measurable functions , @xmath108 , @xmath109 and @xmath110 s are i.i.d . random variables . recall that @xmath3 . we observe from ( [ eq : std_cons ] ) that the data generating mechanism could break at the points @xmath111 , @xmath112 and hence lead to structural breaks of @xmath9 at the latter points . on the other hand , note that if @xmath113 are smooth functions of @xmath7 for each @xmath16 , then the data generating mechanisms change smoothly between adjacent break points . as a consequence @xmath114 is approximately stationary in any small temporal interval between adjacent break points . by the above discussion , we shall call the class of time series in the form of ( [ eq : std_cons ] ) piece - wise locally stationary ( pls ) processes . time series in the form of ( [ eq : std_cons ] ) constitute a relatively large class of nonstationary time series models which allow the data generating mechanism to change flexibly over time . in particular , when the number of the break points @xmath115 , then ( [ eq : std_cons ] ) reduces to the locally stationary time series models in @xcite . on the other hand , if for each @xmath116 , @xmath117 does not depend on @xmath7 , then ( [ eq : std_cons ] ) is a piece - wise stationary time series which is studied , for instance , in davis , lee and rodriguez - yam ( @xcite ) , among others . process ( [ eq : std_cons ] ) can be viewed as a time - varying nonlinear system with @xmath110 s being the inputs and @xmath118 s being the outputs . the functions @xmath119 can be viewed as time - varying filters of the system . from this point of view , we adapt the following dependence measures of @xmath18 in zhou ( @xcite ) : @xmath120 where @xmath121 is a coupled version of @xmath122 with @xmath123 in @xmath122 replaced by an i.i.d . copy @xmath123 ; that is , @xmath124 and @xmath125 is an i.i.d . copy of @xmath126 . we observe from ( [ eq : pdm ] ) that @xmath127 measures the impact of the system s inputs @xmath128-steps before on the current output of the system . when @xmath129 decays fast to zero as @xmath128 tends to infinity , we have short memory of the series as the system tends to fast `` forget about '' past inputs . we refer to section 2 on page 728 of zhou ( @xcite ) and section 4 on pages 27062708 of @xcite for more examples of linear and nonlinear nonstationary time series of the form ( [ eq : std_cons ] ) and detailed calculations of the dependence measures ( [ eq : pdm ] ) . suppose that , for some function @xmath31 , @xmath130\in w_0({{\mathbb{r}}}^2)$ ] and @xmath131 . then @xmath34 defined in ( [ eq : ustat ] ) admits the representation ( [ eq : fourier_repre ] ) with @xmath132 . now define @xmath133={{\mathbb{e}}}\bigl[h(x_j , x ) \bigr]=\int_{{{\mathbb{r}}}^2}g(t , s)l(x)\exp(itx){{\mathbb{e}}}\bigl[\beta _ j(s)\bigr ] \,dt\,ds\ ] ] and @xmath134 $ ] . then elementary calculations using the hoeffding s decomposition show that @xmath34 can be decomposed as @xmath135,\ ] ] where @xmath136\bigr\ } , \\ d_n&=&\int_{{{\mathbb{r}}}^2}g(x , y)\sum _ { k , j}w_n(t_k , t_j ) \gamma_k(x)\gamma _ j(y ) \,dx \,dy.\end{aligned}\ ] ] here @xmath137 and @xmath138 are the nondegenerate and degenerate part of @xmath34 , respectively . to investigate the limiting behavior of @xmath137 , we need the following conditions : for some @xmath139 $ ] , @xmath140\in w_0^{\eta}({{\mathbb{r}}}^2)$ ] for some function @xmath31 . the function @xmath141 is differentiable with derivative @xmath142 . @xmath143 for all @xmath144 , @xmath145 , where @xmath68 is a finite constant independent of @xmath144 and @xmath145 . @xmath146 and @xmath147 for some @xmath148 . define @xmath149 , @xmath150 . let @xmath151 for @xmath152 . let @xmath153 . for sequences @xmath154 , @xmath155 and @xmath156 , define @xmath157 assume that there exist sequences @xmath158 with @xmath159 and @xmath160 , such that @xmath161 @xmath162 for some @xmath163 and sufficiently large @xmath28 . the dependence measures @xmath164 for some @xmath165 and @xmath148 . a few comments on the regularity conditions are in order . the role of @xmath166 in ( a1 ) is to lighten the tail of @xmath167 and hence make it absolutely integrable on @xmath30 . some typical choices of @xmath166 are @xmath168 for kernels @xmath4 with algebraically increasing tails and @xmath169 $ ] for kernels @xmath4 with exponentially increasing tails . since the function @xmath166 controls the tail behavior of the kernel @xmath4 , condition ( a1 ) essentially poses some smoothness requirement on @xmath4 . in practice , proposition [ prop : ac ] or direct numerical computations can be used to check @xmath170 . condition ( a2 ) posts some moment restrictions on @xmath171 and @xmath172 . the requirement @xmath173 is mild and in particular it is always satisfied when @xmath174 is piece - wise monotone or piece - wise convex with finite many pieces . consequently , the latter inequality holds for functions @xmath175 or @xmath169 $ ] listed above . condition ( a3 ) requires that @xmath176 can be divided into big blocks and small blocks such that the sum of squares of @xmath177 in the small blocks is negligible and @xmath177 in the big blocks satisfy a lindeberg type condition . condition ( a3 ) can be checked easily in practice . examples [ ex:1][ex:3 ] below verify ( a3 ) for some frequently used weight functions . by the proof of theorem [ thm : clt_nondegen ] in section [ sec : proof ] , @xmath178 . condition ( a4 ) avoids degenerate kernels with @xmath179 and other degenerate cases with non - gaussian limits . for instance , if @xmath180 , @xmath181 and @xmath182 , where @xmath183 is a weakly stationary time series , then we have that @xmath184 fails to be asymptotically normal . note in this case @xmath185 and @xmath186 . finally ( a5 ) requires that the dependence measures of @xmath114 decay exponentially fast to zero . the theoretical results of the paper can be derived with @xmath187 decaying polynomially fast to zero at the expense of much more complicated conditions and proofs . for presentational simplicity and clarity we assume exponentially decaying dependence measures throughout the paper . [ thm : clt_nondegen ] under conditions , we have @xmath188 theorem [ thm : clt_nondegen ] establishes a central limit result for the nondegenerate part of @xmath34 . due to nonstationarity , @xmath189 $ ] is @xmath128-dependent . consequently asymptotic investigations for @xmath137 are much more difficult than the stationary case . thanks to the structural simplification by the fourier transformation , we are able to control the dependence structure of @xmath137 and establish the above central limit results . by theorem [ thm : clt_nondegen ] , if the degenerate part @xmath138 is asymptotically negligible compared to @xmath137 , then clt for @xmath34 can be derived . to this end , the following theorem [ thm : order_degen ] is crucial . assume that there exist functions @xmath190 and a @xmath191 , such that @xmath192 for all integers @xmath193 . condition ( a6 ) requires that , for each fixed @xmath28 , the weight function @xmath194 grows algebraically fast at any @xmath195 . ( a6 ) is mild and is satisfied by most frequently used weight functions . in particular , if @xmath196 is lipschitz continuous in the sense that @xmath197 for every @xmath198 and @xmath199 , then @xmath200 can be chosen as @xmath201 . [ thm : order_degen ] assume that conditions and hold with @xmath202 therein replaced by @xmath203 . further assume and . then @xmath204 and @xmath205 . theorem [ thm : order_degen ] investigates the order of @xmath138 . observe that if @xmath206 s are independent with @xmath21 , then simple calculations yield @xmath207 . for many important weight functions ( see , e.g. , examples [ ex:1][ex:3 ] below ) @xmath208 and the order established in theorem [ thm : order_degen ] is sharp . for un - weighted @xmath41-statistics of stationary mixing data , deep theoretical results on the order of the degenerate part of @xmath41-statistics were obtained in @xcite and @xcite , among others . our theorem [ thm : order_degen ] extends the latter results to weighted @xmath0-statistics of nonstationary processes from a fourier analysis angle . [ coro : clt_nondegen ] assume that conditions and hold with @xmath202 therein replaced by @xmath203 . further assume that and hold and @xmath209\rightarrow \infty$ ] . then we have @xmath210 . corollary [ coro : clt_nondegen ] is an immediate consequence of theorems [ thm : clt_nondegen ] and [ thm : order_degen ] . corollary [ coro : clt_nondegen ] establishes a clt for @xmath34 . it is clear from the definitions of @xmath211 and @xmath212 that @xmath213 . examples [ ex:1][ex:3 ] below verify @xmath214\rightarrow\infty$ ] and condition ( a3 ) for some frequently used weight functions . [ ex:1 ] consider the case where @xmath215 for some symmetric function @xmath83 on @xmath216\times[0,1]$ ] such that @xmath217 for all @xmath218 and @xmath219 in @xmath216 $ ] . note that the classic un - weighted @xmath0-statistics are contained in this case with @xmath220 . elementary calculations yield @xmath221 , where @xmath222 , @xmath223 , @xmath224 and @xmath225 . hence @xmath209\rightarrow \infty$ ] provided that @xmath83 is not a constant zero function . additionally , it is elementary to check that ( a3 ) is satisfied for every sequence @xmath158 , @xmath159 and @xmath160 provided that @xmath83 is not always @xmath226 . [ ex:2 ] in this example we investigate weight functions in the form @xmath227 , where @xmath228 $ ] , @xmath229 is a continuously differentiable function and @xmath230 with @xmath231 . this type of weights may appear in nonparametric estimation of nonstationary time series . assume that @xmath229 is absolutely integrable and its first - order partial derivatives are bounded on @xmath30 . then elementary calculations show that @xmath232 , @xmath224 and @xmath233 for any @xmath234 . therefore @xmath209\rightarrow \infty$ ] provided that @xmath71 is not always zero and ( a3 ) is satisfied for every sequence @xmath158 , @xmath235 and @xmath160 provided that @xmath71 is not always @xmath226 . similar results hold for @xmath236 or @xmath237 . [ ex:3 ] consider the class of weights @xmath238 , where @xmath239 is a continuously differentiable and nonconstant function on @xmath240 and @xmath241 with @xmath242 . this type of weight functions may appear , for instance , in nonparametric specification tests and spectral analysis of @xmath114 . further assume that @xmath243 is absolutely integrable on @xmath240 with bounded derivatives . after some simple algebra , we have @xmath244 . therefore @xmath209\rightarrow \infty$ ] and ( a3 ) is satisfied for every sequence @xmath245 , @xmath159 and @xmath160 . without loss of generality , throughout section [ sec : degen ] we assume @xmath246 for some constants @xmath247 . in this section we shall investigate the class of degenerate @xmath0-statistics for which @xmath248=0 $ ] for every @xmath128 and @xmath17 . then it is clear that @xmath249 in ( [ eq : decomp ] ) and @xmath250 . before we state the theoretical results , we need to post the following regularity conditions : define @xmath251^{1/2}+ \biggl[\sum _ { k=1}^nw^2_n(1,t_k ) \biggr]^{1/2}.\ ] ] assume that @xmath252 . further assume that for some @xmath253 , @xmath254^{1/2}=o(1).\ ] ] if @xmath255 , then @xmath256^{1/2}=o(1)$ ] for some @xmath253 . for @xmath257 and @xmath258 $ ] , define @xmath259 let @xmath260 . for @xmath116 , define the long - run covariances @xmath261 $ ] and @xmath262 $ ] . assume that for all @xmath263 and all @xmath264 with @xmath265 and @xmath266 , @xmath267 is positive definite for @xmath268 $ ] , @xmath116 if @xmath269 . replace @xmath267 by @xmath270 in the above assumption for all other functions @xmath271 . @xmath272 for @xmath273 $ ] and @xmath116 . condition ( a7 ) posts some restrictions on the smoothness of the weight function @xmath5 . condition ( a8 ) is a mild technical condition . in particular , elementary calculations show that ( a7 ) and ( a8 ) are satisfied by weight functions in example [ ex:1 ] . we have ( a7 ) and ( a8 ) hold if @xmath274 under the additional assumption that @xmath275 in example [ ex:2 ] . for weights considered in example [ ex:3 ] , we have ( a7 ) and ( a8 ) hold when @xmath276 under the extra assumption that @xmath277 . by definition , @xmath267 and @xmath278 are the spectral density matrices of the time series @xmath279 and @xmath280 at frequency 0 , respectively . hence it is clear that the latter spectral density matrices are positive semi - definite . condition ( a9 ) is mild , and it requires that the latter spectral density matrices are nonsingular . finally , condition ( a10 ) means that the data generating mechanism @xmath113 changes smoothly between adjacent break points . the following theorem investigates the asymptotic behavior of degenerate weighted @xmath0-statistics : [ thm : degen ] write @xmath281 . let condition be condition when @xmath271 therein is replaced by @xmath282 . assume that conditions , and hold with @xmath202 therein replaced by @xmath283 for some @xmath148 . assume and . then there exist constants @xmath284 with @xmath285 and i.i.d . standard normal random variables @xmath286 such that for any bounded and continuous function @xmath239 @xmath287-{{\mathbb{e}}}\biggl[h \biggl(\sum_{j=1}^\infty\alpha _ { n , j } \bigl(z_j^2 - 1\bigr)\biggr)\biggr ] \biggr|\rightarrow0.\ ] ] let @xmath288 be a centered two - dimensional gaussian process defined on @xmath216\times{{\mathbb{r}}}$ ] with the covariance function @xmath289=\int_0^{\min(t_1,t_2)}\xi _ { \zeta ( t ) } \bigl(t,(s_1,s_2)^{\top}\bigr ) \,dt,\ ] ] where @xmath290 if @xmath291 , @xmath116 , @xmath292 and @xmath293.\ ] ] define the complex - valued gaussian process @xmath294 and let @xmath295 , \qquad t\ge1/n.\ ] ] let @xmath296 . then by the classic gaussian process theory [ see , for instance , @xcite , chapter 1.2 ] , the real part of @xmath297 is a quadratic form of i.i.d . gaussian random variables @xmath298 the coefficients @xmath299 , @xmath300 in theorem [ thm : degen ] correspond to the eigenvalues of the latter gaussian quadratic form . theorem [ thm : degen ] establishes a general asymptotic result for degenerate @xmath0-statistics with smooth weight functions . define the lvy prokhorov metric @xmath301 where @xmath302 is the @xmath303-neighborhood of @xmath59 . then ( [ eq : degen ] ) is equivalent to @xmath304 in other words , the distribution of @xmath305 can be well approximated asymptotically by that of a weighted sum of i.i.d . centered @xmath306 random variables . an important observation from ( [ eq : degen ] ) is that if @xmath307 , then @xmath308 . consequently @xmath305 is asymptotically normal . on the other hand , if @xmath309 uniformly in @xmath128 as @xmath310 , then @xmath311 and therefore @xmath305 converges to a mixture of i.i.d . centered @xmath312 random variables . in the following , corollaries [ coro : clt_degen ] to [ coro : nonclt - degen2 ] explore the above discussions in detail . [ coro : clt_degen ] let @xmath313 be the eigenvalues of the matrix @xmath314 with @xmath315 . assume that @xmath46 . then under the conditions of theorem [ thm : degen ] , we have for any bounded and continuous function @xmath239 @xmath316 -{{\mathbb{e}}}h\bigl\ { n\bigl(0 , \var[d_n]\bigr)\bigr\}\bigr|\rightarrow0.\ ] ] note that by lemma 4 in zhou ( @xcite ) , @xmath317=o(1)$ ] . corollary [ coro : clt_degen ] asserts that @xmath318 implies @xmath319 and hence the asymptotical normality of @xmath138 . in the literature , @xcite derived that @xmath43 implies asymptotic normality of a very wide class of weighted degenerate @xmath0-statistics of independent data based on very deep martingale techniques . the martingale arguments depended heavily on the independence assumption and are hard to generalize to dependent data . from a fourier analysis point of view , corollary [ coro : clt_degen ] generalizes the latter result to a class of weighted degenerate @xmath0-statistics of nonstationary time series with smooth weights . a particular case of this type is example [ ex:3 ] where the weight matrix is toeplitz . from standard toeplitz matrix theory we have @xmath320 , and hence ( [ eq : clt_degen ] ) holds for this type of weight matrices . [ coro : nonclt - degen1 ] suppose that : @xmath321 and @xmath322 satisfies ( [ eq:1 ] ) with @xmath30 therein replaced by @xmath216\times[0,1]$ ] ; or : @xmath323 , where @xmath324 and @xmath325 and @xmath326 are continuous functions defined on @xmath216 $ ] . then under the conditions of theorem [ thm : degen ] , there exist constants @xmath327 with @xmath328 and i.i.d . standard normal random variables @xmath286 such that @xmath329 [ coro : nonclt - degen2 ] suppose : @xmath330 for some @xmath331 $ ] , where @xmath332 has support @xmath333\times[-1,1]$ ] and satisfies ( [ eq:1 ] ) with @xmath30 therein replaced by @xmath333\times [ -1,1]$ ] and @xmath230 ; or : @xmath334 for some @xmath335 $ ] , where @xmath324 , @xmath230 and @xmath336 and @xmath337 are continuous functions on @xmath338 with support @xmath333 $ ] . then under the conditions of theorem [ thm : degen ] , there exist constants @xmath339 with @xmath328 and i.i.d . standard normal random variables @xmath286 such that @xmath329 corollaries [ coro : nonclt - degen1 ] and [ coro : nonclt - degen2 ] are proved in the online supplement of the paper , zhou ( @xcite ) . corollaries [ coro : nonclt - degen1 ] and [ coro : nonclt - degen2 ] establish that @xmath138 converges to a mixture of i.i.d . centered @xmath306 random variables for four classes of smooth weight functions which are absolutely integrable on @xmath30 . note that the classic un - weighted @xmath0-statistics belong to cases ( a ) and ( b ) in corollary [ coro : nonclt - degen1 ] . in the literature , @xcite , among others , derived asymptotic distributions of un - weighted @xmath41-statistics for stationary time series . corollary [ coro : nonclt - degen1 ] generalizes the latter results to a class of weighted @xmath0-statistics of nonstationary data . weight functions in corollary [ coro : nonclt - degen2 ] may appear , for instance , in nonparametric estimation of nonstationary time series . quadratic forms of a centered nonstationary process @xmath114 are of the form @xmath340 clearly @xmath341 is a special case of the degenerate @xmath0-statistics with @xmath21 . hence the theory established above applies to this class of statistics . however , due to the special multiplicative structure , the asymptotic theory for @xmath341 can be established with weaker conditions . the following proposition follows from the corresponding proofs of theorem [ thm : degen ] and corollaries [ coro : clt_degen ] to [ coro : nonclt - degen2 ] . [ prop : quad ] assume that conditions and hold and holds with @xmath202 therein replaced by @xmath342 . further assume that @xmath343>0 $ ] for @xmath344 and @xmath268 $ ] . . then we have that conclusions of theorem [ thm : degen ] and corollaries [ coro : clt_degen ] to [ coro : nonclt - degen2 ] hold with @xmath138 therein replaced by @xmath341 . by the proof of theorem [ thm : degen ] , on a possibly richer probability space , there exist i.i.d . standard normal random variables @xmath346 , such that @xmath347 the above equation asserts that @xmath341 can be well approximated a quadratic form of independent gaussian random variables . in the literature , gtze and tikhomirov ( @xcite ) , among others , established deep theoretical results showing that distributions of quadratic forms of independent data can be approximated by those of corresponding gaussian quadratic forms . in ( [ eq : quad_approx ] ) , we generalize these results to a class of quadratic forms of nonstationary time series with smooth weights . let @xmath8 be the marginal distribution function of @xmath114 at time @xmath7 ; namely @xmath8 is the distribution of @xmath348 . under various situations one is interested in estimating the quantity @xmath349 for all @xmath228 $ ] . here @xmath4 is assumed to be a symmetric function . for instance , if @xmath350 , then @xmath10 is the time - varying variance function of the process @xmath114 . in the statistics literature , enormous efforts have been put on nonparametric estimation of parameter functions @xmath351 in the form @xmath352 $ ] ; see , for instance , the monographs of @xcite and @xcite and the citations therein . note that @xmath351 is a special case of ( [ eq : estimation ] ) with @xmath353/2 $ ] . on the other hand , however , it seems that there are few results on nonparametric inference of general parameter functions in the form of @xmath10 in ( [ eq : estimation ] ) . one of the major difficulties , especially in the case of time series applications , lies in the lack of corresponding theoretical results on weighted @xmath0-statistics for dependent data . define @xmath354 assume @xmath355 is smooth at @xmath356 for some @xmath357 . by the first - order local taylor expansion of @xmath355 , @xmath358 can be estimated by @xmath359 , where @xmath360 here for presentational simplicity we assume that @xmath361 where @xmath362 and @xmath363 is the collection of continuously differentiable and symmetric density functions with support @xmath333 $ ] . furthermore , the bandwidth @xmath13 satisfies @xmath230 with @xmath231 . estimator ( [ eq : local_linear ] ) is an extension of the classic local linear kernel methods [ @xcite ] to second - order parameter functions of the form ( [ eq : estimation ] ) . meanwhile , if higher - order taylor expansions of @xmath364 are used in ( [ eq : local_linear ] ) , then one obtains local polynomial estimations of @xmath365 . it is easy to see that the asymptotic behavior of @xmath366 is decided by that of the @xmath0-statistics @xmath367 . the following proposition , which is proved in zhou ( @xcite ) , investigates the limiting distribution of @xmath368 : [ prop : local - linear ] assume that conditions and hold with @xmath202 therein replaced by @xmath203 . further assume that and hold and @xmath364 is @xmath369 in a neighborhood of @xmath356 . then under the above assumptions of @xmath23 and @xmath13 , we have @xmath370\rightarrow n(0,1),\ ] ] where @xmath371 . consider the kernel @xmath350 . then @xmath10 in ( [ eq : estimation ] ) equals @xmath372={{\mathbb{e}}}[g_{\zeta ( t)}(t,{\mathcal{f}}_0)-{{\mathbb{e}}}g_{\zeta(t)}(t,{\mathcal{f}}_0)]^2 $ ] . in particular , @xmath373 $ ] . for this variance kernel @xmath374 , we can choose @xmath375 and assume that @xmath376<\infty$ ] , @xmath377 . then @xmath271 satisfies condition ( a2 ) with @xmath202 therein replaced by 8 . by proposition [ prop : ac ] , condition ( a1 ) is satisfied with @xmath378 . furthermore , condition ( a3 ) is satisfied by example [ ex:2 ] and the assumption that @xmath379 . note that @xmath189=(x^2 - 2x{{\mathbb{e}}}[x_j]+{{\mathbb{e}}}[x^2_j])/2 $ ] does not always equal @xmath226 . hence the kernel is nondegenerate . meanwhile , @xmath380 + { { \mathbb{e}}}\bigl[g^2_{\zeta(s)}(s,{\mathcal{f}}_0)\bigr]-2{{\mathbb{e}}}\bigl[g_{\zeta(t)}(t,{\mathcal{f}}_0)\bigr]{{\mathbb{e}}}\bigl[g_{\zeta(s)}(s , { \mathcal{f}}_0)\bigr].\ ] ] assuming that @xmath381 $ ] and @xmath382 $ ] are @xmath383 in a neighborhood of @xmath384 , then @xmath355 is @xmath383 in a neighborhood of @xmath356 . further assume that @xmath384 is not a break point of the time series and condition ( a10 ) . by the local stationarity of @xmath114 in the neighborhood of @xmath384 , we have that @xmath385 , where @xmath386 note that @xmath387 is the spectral density of the stationary sequence @xmath388 at frequency @xmath226 . hence condition ( a4 ) holds provided @xmath389 . finally , we have under the other regularity assumptions of proposition [ prop : local - linear ] that @xmath390\rightarrow n(0,1),\ ] ] where @xmath391\int_{-1}^1x^2k(x ) \,dx$ ] . consider a pls time series @xmath114 defined in ( [ eq : std_cons ] ) . assume further that @xmath392=0 $ ] and @xmath393 , @xmath150 . then we can define its spectral density at time @xmath7 as @xmath394,\ ] ] where @xmath395 $ ] is the @xmath16th - order auto covariance of @xmath114 at time @xmath7 . write the classic periodogram of the series @xmath114 @xmath396 consider also the classic smoothed periodogram estimate of the spectral density @xmath397 where @xmath398 is an even function , and @xmath399 is a block size satisfying @xmath25 with @xmath400 . the analysis of @xmath401 depends heavily on the theory of quadratic forms for nonstationary processes . for strictly stationary time series , the asymptotic behaviors of the periodogram and spectral density estimates have been intensively studied in the literature . see , for instance , @xcite , @xcite , @xcite , @xcite and @xcite among others . on the other hand , however , there are few corresponding results for nonstationary time series . exceptions include , among others , @xcite who studied the asymptotic behavior of the periodogram for short memory locally stationary linear processes and dette , preuss and vetter ( @xcite ) who studied the behavior of the averaged spectral density estimates for locally stationary gaussian linear processes . in this section we shall investigate the behaviors of @xmath402 and @xmath401 for linear and nonlinear pls time series . the following is a key theorem which establishes a gaussian approximation result for fourier transforms of nonstationary time series . theorem [ thm : ftransform_normal_appr ] could be of separate interest in spectral analysis of nonstationary processes . let @xmath403 be a sequence of frequencies of interest . for @xmath404 , define @xmath405 and @xmath406 . write @xmath407 and @xmath408 . [ thm : ftransform_normal_appr ] assume that @xmath409 is @xmath410 in @xmath7 on @xmath411 $ ] for any @xmath243 , @xmath116 , @xmath412 . further assume that conditions and hold with @xmath202 therein replaced by 4 and @xmath413}f(t,\lambda)>0 $ ] . : if @xmath414 for some constants @xmath415 and @xmath416 , then on a possibly richer probability space , there exist i.i.d . two - dimensional standard normal random vectors @xmath417 , such that @xmath418 where @xmath419 $ ] . if @xmath420 or @xmath421 , then on a possibly richer probability space , there exist i.i.d . standard normal random variables @xmath422 , such that @xmath423 based on theorem [ thm : ftransform_normal_appr ] , we have the following corollary on the behavior of the periodogram for nonstationary time series . [ coro : periodogram ] under the conditions of theorem [ thm : ftransform_normal_appr ] , we have : if the frequency @xmath424 satisfies @xmath425 , then @xmath426 where @xmath427 stands for the exponential distribution with mean 1 . if @xmath420 or @xmath421 , then @xmath428 converges in distribution to a @xmath306 random variable . the condition @xmath429 is important for the validity of theorem [ thm : ftransform_normal_appr ] and corollary [ coro : periodogram ] . by ( ii ) of lemma 5 in zhou ( @xcite ) , we have if @xmath430 for some finite constant @xmath68 , then @xmath431 where @xmath432 . therefore the real and imaginary parts of @xmath433 are no longer uncorrelated , and the periodogram does not converge to an @xmath427 distribution . similar results hold for frequencies near @xmath421 . this is drastically different from the stationary case where it is well known that the real and imaginary parts of @xmath433 are asymptotically independent and @xmath434 . indeed , note that if @xmath435 does not change with @xmath7 , then we have @xmath436 in ( [ eq : im_corr ] ) . due to the time - varying nature of @xmath435 , the behavior of fourier transforms near frequency 0 or @xmath421 is complicated for nonstationary time series . the following proposition investigates the asymptotic behavior of @xmath401 for pls time series . [ prop : spectral - density ] assume that @xmath362 is even . then under the conditions of theorem 4 and the assumption that @xmath25 with @xmath437}\log^2 n)\rightarrow0 $ ] , we have : if @xmath438 , then @xmath439 ^ 2 \,dt\int_{0}^1f^2(t , \lambda ) \,dt\biggr);\ ] ] and : if @xmath420 or @xmath421 , then @xmath440 ^ 2 \,dt\int_{0}^1f^2(t , \lambda ) \,dt\biggr).\ ] ] proposition [ prop : spectral - density ] , which is proved in zhou ( @xcite ) , establishes the asymptotic normality of @xmath401 for a class of nonstationary nonlinear processes . simple calculations show that @xmath441 . hence @xmath401 is a consistent estimator of the averaged energy at frequency @xmath424 over time . an important observation from proposition [ prop : spectral - density ] is that the asymptotic variance of @xmath401 is determined by @xmath442 , the averaged squared spectral density over time . the latter quantity should be estimated if one wishes to construct confidence intervals for @xmath443 . proof of theorem [ thm : clt_nondegen ] let @xmath444\}$ ] , @xmath445 . note that @xmath446 . to prove the theorem , we need to deal with the dependence structure of @xmath447 first . according to ( [ eq : fourier_repre ] ) , @xmath448\biggr\ } \gamma _ k(t ) \,dt\,ds\\[-2pt ] & : = & \int _ { { { \mathbb{r}}}^2}g(t , s)\xi_{k}(s)\gamma_k(t ) \,dt\,ds.\end{aligned}\ ] ] let @xmath449\ } $ ] . by lemmas 1 and 2 in zhou ( @xcite ) , the dependence measures @xmath450 & & \qquad\le \int _ { { { \mathbb{r}}}^2}\bigl|g(t , s)\bigr|\bigl|\xi_{k}(s)\bigr|\bigl\|\gamma _ k(t)-\gamma_{k , r}(t)\bigr\|_p \,dt\,ds \\ & & \qquad\le \int _ { { { \mathbb{r}}}^2}\bigl|g(t , s)\bigr|\bigl|\xi_{k}(s)\bigr|\bigl\ { \bigl\|l(x_k)\bigr\|_{2p}|t|^{\eta } \bigl[\delta _ { x}(r,\eta2p)\bigr]^\eta+\delta_{l(x)}(r , p)\bigr \ } \,dt\,ds \\ & & \qquad\le\int_{{{\mathbb{r}}}^2}c\bigl(1+|t|^{\eta } \bigr)\bigl|g(t , s)\bigr|\bigl|\xi_{k}(s)\bigr|\rho_1^r\end{aligned}\ ] ] for some @xmath451 , where @xmath452 . on the other hand , note that @xmath453\bigr|\le\sum_{j=1}^n\bigl|w_n(t_k , t_j)\bigr| \bigl\|l(x_j)\bigr\|\le cw_{k,\cdot}.\ ] ] hence @xmath454 . as a second step , we shall approximate @xmath137 by the sum of an @xmath399-dependent sequence . define @xmath455 $ ] , where @xmath456 . for @xmath457 , define the projection operator @xmath458-{{\mathbb{e}}}[\cdot| { \mathcal{f}}_{j-1}].\ ] ] elementary manipulations show that @xmath459 $ ] . hence by jensen s inequality , @xmath460 \bigr\|_p&\le&\|{\mathcal{p}}_{k - r}z_k\|_p+\|{\mathcal{p}}_{k - r}z_{k,\{m\}}\|_p\le2\|{\mathcal{p}}_{k - r}z_k \|_p \nonumber \\[-8pt ] \\[-8pt ] \nonumber & \le & 2\|z_{k}-z_{k , r}\|_p \le cw_{k,\cdot}\rho_1^r.\end{aligned}\ ] ] note that @xmath461-{{\mathbb{e}}}[z_k|\tilde{{\mathcal{f}}}_{k , k - j-1}]\}$ ] and the summands form a martingale difference sequence . by burkholder s inequality , @xmath462-{{\mathbb{e}}}[z_k|\tilde{{\mathcal{f}}}_{k , k - j-1 } ] \bigr\|_p^2 \\ & \le&c\sum_{j = m}^\infty \|z_k - z_{k , j}\|_p^2\le cw^2_{k,\cdot}\rho_1^{2m}.\end{aligned}\ ] ] therefore @xmath463 \bigr\|_p\le\|z_{k,\{m\}}-z_k\|_p\le cw_{k,\cdot } \rho_1^{m}.\ ] ] by ( [ eq:8 ] ) , ( [ eq:9 ] ) and burkholder s inequality , for any @xmath464 , @xmath465 \biggr\|_p^2\le\sum_{k=1}^n \biggl\|{\mathcal{p}}_{k - r}[z_k - z_{k,\{m\}}]\biggr\|_p^2 \le cw^{(n)}\rho_1^{2\max(m , r)}.\ ] ] observe that @xmath466=\sum_{r=0}^\infty\sum_{k=1}^n{\mathcal{p}}_{k - r}[z_k - z_{k,\{m\}}]$ ] . therefore @xmath467 \biggr\|_p&\le & \sum_{r=0}^\infty\biggl\|\sum _ { k=1}^n{\mathcal{p}}_{k - r}[z_k - z_{k,\{m\ } } ] \biggr\|_p \nonumber \\[-8pt ] \\[-8pt ] \nonumber & \le & c\sqrt{w^{(n)}}m\rho_1^m.\end{aligned}\ ] ] inequality ( [ eq:10 ] ) shows that @xmath137 can be well approximated by the sum of the @xmath399-dependent sequence @xmath468\ } $ ] . in particular , let @xmath469 . then clearly approximation error in ( [ eq:10 ] ) can be made as @xmath470 for any @xmath471 . in the final step we shall prove a central limit theorem for @xmath472\}$ ] . define the big blocks and small blocks @xmath473\bigr\ } \quad\mbox { and } \\ r_j&=&\sum_{k = l_n+1}^{s_n}\bigl \{z_{(j-1)m+k,\{m\}}-{{\mathbb{e}}}[z_{(j-1)m+k,\{m\ } } ] \bigr\},\end{aligned}\ ] ] @xmath474 . note that @xmath475 s are independent and @xmath476 s are also independent . then similar to the proof of ( [ eq:10 ] ) , we can obtain @xmath477-\var[n_{n,\{m\}}]|=o(w^{(n)})$ ] , @xmath478 , @xmath479 therefore by condition ( a3 ) , @xmath480 by ( [ eq:10 ] ) , @xmath481 . by condition ( a4 ) , ( [ eq:11 ] ) and ( [ eq:12 ] ) , @xmath482/w^{(n)}\ge c/2\qquad \mbox{for sufficiently large } n.\ ] ] now by ( [ eq:11 ] ) , @xmath483)^{p/2}}\le c\frac{\sum_{j}a_j^{p/2}}{[w^{(n)}]^{p/2}}\le \biggl\{\frac{\max a_j}{[w^{(n ) } ] } \biggr \}^{p/2 - 1}\frac{\sum_{j}a_j}{w^{(n)}}.\ ] ] hence by condition ( a3 ) , @xmath484)^{p/2}\rightarrow0 $ ] . therefore by the lyapunov clt , @xmath485}\rightarrow n(0,1)$ ] . now by ( [ eq:10])([eq:12 ] ) , the theorem follows . proof of theorem [ thm : order_degen ] for any fixed @xmath486 , define @xmath487 we shall first determine the order of magnitude of @xmath488 . for complex - valued random variables @xmath489 and @xmath490 , define @xmath491 and@xmath492={{\mathbb{e}}}[(x-{{\mathbb{e}}}x)(\bar{y}-{{\mathbb{e}}}\bar{y})]$ ] . note that , by ( a6 ) and the symmetry of @xmath493 , @xmath494 \\ & \le&\sum_{k , j}\sum _ { l , m}w^2_n(t_k , t_j)\bigl| \cov\bigl[\gamma_l(x)\gamma _ m(y),\gamma_k(x ) \gamma_j(y)\bigr]\bigr| \\ & & { } + 2^{p/2}\sum _ { k , j}\sum_{l , m}f_n(t_k , t_j)\bigl|w_n(t_k , t_j)\bigr| \rho ^p_{k , j}(l , m)\\ & & \hspace*{63pt}{}\times\bigl|\cov\bigl[\gamma_l(x ) \gamma_m(y),\gamma_k(x)\gamma _ j(y)\bigr]\bigr| \\ & : = & \sum_{k , j}w^2_n(t_k , t_j ) \varrho_{k , j}(x , y;0)\\ & & { } + 2^{p/2}\sum_{k , j}f_n(t_k , t_j)\bigl|w_n(t_k , t_j)\bigr| \varrho_{k , j}(x , y;p),\end{aligned}\ ] ] where @xmath495 and @xmath496\bigr|.\ ] ] we will omit the subscripts @xmath497 in @xmath498 in the sequel for simplicity . let @xmath499 we shall first show that @xmath500 by the symmetry of @xmath501 and @xmath502 , we only need to consider the case @xmath503 and @xmath504 . now if @xmath505 , then @xmath506 if @xmath507 , then @xmath508 in summary , @xmath509 . similarly , @xmath510\bigr|&\le & c\bigl(|x|^{\eta } + 1 \bigr ) \bigl(|y|^{\eta}+1\bigr)r_1^{\rho^*(l , m ) } \nonumber \\[-8pt ] \\[-8pt ] \nonumber & \le & c \bigl(\bigl|(x , y)\bigr|^{2\eta}+1\bigr)r_1^{\rho^*(l , m)}\end{aligned}\ ] ] for some @xmath511 . observe that for @xmath512 , the number of pairs @xmath513 such that @xmath514 is at most @xmath515 . now by ( [ eq:14 ] ) and ( [ eq:15 ] ) , we obtain that , for @xmath516 , @xmath517 \\[-8pt ] \nonumber & \le & c\bigl(\bigl|(x , y)\bigr|^{2\eta}+1 \bigr).\end{aligned}\ ] ] note that the constant @xmath68 does not depend on @xmath518 . now by ( [ eq:16 ] ) , we obtain @xmath519 therefore by condition ( a1 ) , @xmath520 the theorem follows . proof of theorem [ thm : degen ] let @xmath296 . recall the definition of @xmath521 in ( [ eq:40 ] ) . we shall show that the two processes @xmath522 and @xmath523 are close in the sense that @xmath524 \,dx\,dy\biggr ] \nonumber \\[-8pt ] \\[-8pt ] \nonumber & & \qquad{}- { { \mathbb{e}}}h\biggl[\int_{{{\mathbb{r}}}^2}g(x , y)\bigl[\varpi_n(x , y)-{{\mathbb{e}}}\varpi_n(x , y)\bigr ] \,dx\,dy\biggr ] \biggr|\rightarrow0\end{aligned}\ ] ] for any bounded and continuous @xmath243 . for any @xmath525 , define the region @xmath526 , and let @xmath527 . note that , by lemma 4 in zhou ( @xcite ) , we have @xmath528 \,dx\,dy\biggr\| \\ & & \qquad\le \int_{\bar{a}(s)}\bigl|g(x , y)\bigr| \bigl\|\varrho_n(x , y)-{{\mathbb{e}}}\varrho_n(x , y)\bigr\| \,dx\,dy \\ & & \qquad\le c\int _ { \bar{a}(s)}\bigl|g(x , y)\bigr|\bigl(1+\bigl|(x , y)\bigr|^{\eta}\bigr ) \,dx\,dy.\end{aligned}\ ] ] observe that @xmath529 is independent of @xmath28 and converges to @xmath226 as @xmath530 . similar inequality holds for @xmath531 \,dx\,dy$ ] . hence , to prove ( [ eq:23 ] ) , one only need to show that , for each fixed @xmath199 , ( [ eq:23 ] ) holds with @xmath30 therein replaced by @xmath532 . to this end , we shall first show that , for any @xmath533 and any bounded and continuous @xmath534 , @xmath535 we shall only prove the case @xmath536 since similar arguments apply to general @xmath399 . consider the case @xmath537 . by corollary 2 of @xcite , we have , on a possibly richer probability space , a sequence a i.i.d . 4-dimensional standard normal random vectors @xmath538 , such that @xmath539 \\[-8pt ] \nonumber & & \qquad = o_{{\mathbb{p}}}\bigl(n^{1/4}\log ^2 n\bigr).\end{aligned}\ ] ] define the complex - valued random variables @xmath540_{1}+i[\sigma ^{1/2}_{j^*}(t_j,(x , y)^\top)\zz_j]_{2}$ ] and @xmath541_{3}+i[\sigma ^{1/2}_{j^*}(t_j,(x , y)^\top)\times \zz_j]_{4}$ ] , where @xmath542_{r}$ ] denotes the @xmath101th element of @xmath543 . define the quadratic form @xmath544 note that @xmath545\gamma_{j}(y)\biggr|\\ & & { } + \biggl| \sum_{k , j}w_n(t_k , t_j ) \bigl[\gamma _ { j}(y)-z^{**}_{j } \bigr]z^{*}_{k}\biggr|.\end{aligned}\ ] ] using the summation by parts technique and similar to the proof of inequality ( 12 ) in zhou ( @xcite ) , we have @xmath546 . now by the above inequality and lemma 3 in zhou ( @xcite ) , we obtain @xmath547\bigr|=o_{{\mathbb{p}}}(1).\ ] ] by condition ( a10 ) , we have that @xmath548 is continuous on @xmath549 $ ] , @xmath116 . therefore elementary calculations show that , on a possibly richer probability space , @xmath550\bigr|=o_{{\mathbb{p}}}(1).\ ] ] hence ( [ eq:24 ] ) with @xmath536 follows from ( [ eq:31 ] ) and ( [ eq:32 ] ) . now consider the case @xmath551 . if @xmath552 , then @xmath553 and @xmath554 . hence ( [ eq:24 ] ) trivially holds . if @xmath31 is not a constant , then ( [ eq:24 ] ) follows from similar and simpler arguments as above by considering the covariance matrix @xmath555 . in summary , ( [ eq:24 ] ) follows . as a second step toward ( [ eq:23 ] ) , we prove that @xmath556 is tight on @xmath557 , where @xmath558 is the collection of all complex - valued continuous functions on @xmath532 equipped with the uniform topology . note that @xmath559 \nonumber \\ & & \qquad = i\int_{y_2}^{y_1}\rho^{(1)}_n(x_2,y ) \,dy + i\int_{x_2}^{x_1}\rho^{(2)}_n(x , y_2 ) \,dx\\ & & \qquad\quad{}-\int_{x_2}^{x_1}\int_{y_2}^{y_1 } \rho^{(3)}_n(x , y ) \,dx\,dy,\nonumber\end{aligned}\ ] ] where @xmath560 $ ] , @xmath561 @xmath562 $ ] and @xmath563\ ] ] with @xmath564 $ ] . by the proof of lemma 4 in zhou ( @xcite ) , we have @xmath565 by ( [ eq:33 ] ) and ( [ eq:34 ] ) , we have , for any fixed @xmath566 and @xmath253 , @xmath567\bigr| \bigr\|_{2+\epsilon } \nonumber \\[-8pt ] \\[-8pt ] \nonumber & & \qquad = o(\delta).\end{aligned}\ ] ] define @xmath568|$ ] . by ( [ eq:35 ] ) and a standard chaining technique , we have for each fixed @xmath569 @xmath570 hence @xmath571 is tight on @xmath532 . by standard smooth gaussian process techniques , it is easy to see that @xmath572 is tight on @xmath532 . since both processes are relatively compact on @xmath532 and the differences of their finite dimensional distributions converge in the sense of ( [ eq:24 ] ) , we have for any bounded and continuous function @xmath573 , @xmath574 since @xmath575 , we have @xmath576 is continuous on @xmath557 . hence ( [ eq:23 ] ) follows . finally , note that @xmath577 s are independent complex - valued gaussian processes , @xmath578 . by the classic gaussian process theory [ see , e.g. , @xcite , chapter 1.2 ] , we have @xmath579 can be represented as ( in the sense of equality in distribution ) @xmath580 where @xmath581 and @xmath582 denotes real and imaginary parts of a complex number , respectively , @xmath583 s are @xmath584 matrix functions and @xmath585 s are independent 2-dimensional standard normal random vectors . hence it is straightforward to see that @xmath586 \,dx\,dy$ ] is a quadratic form of i.i.d . standard normal random variables @xmath587 moreover , by the arguments of lemma 4 in zhou ( @xcite ) , we have @xmath588 \,dx\,dy\|=o(1)$ ] . hence @xmath589 \,dx\,dy=\sum_{j=1}^\infty \alpha_{n , j}\bigl(z_j^2 - 1\bigr)\ ] ] with @xmath590 . as we can see from the proof of ( [ eq:30 ] ) , the positive - definiteness requirement on @xmath267 and @xmath270 in ( a9 ) is to facilitate a gaussian approximation result in @xcite . we point out that the positive - definiteness requirement can be weakened to the assumption that certain block sums of the latter long - run covariance matrices are positive definite . see remark 2 of @xcite . for presentational simplicity , we shall stick to the everywhere positive definiteness assumption in this paper . proof of corollary [ coro : clt_degen ] we shall prove this corollary by showing that @xmath591 converges to a gaussian measure on @xmath557 . by the tightness of @xmath571 and the arguments in the proof of theorem [ thm : degen ] , it suffices to show that any finite dimensional distribution of the latter sequence of measures converges to a ( multivariate ) normal distribution . to this end , we will only show that @xmath592 converges to a gaussian distribution for any @xmath593 since all other cases follow by similar arguments and the cramer wold device . here @xmath594 , @xmath595 and @xmath596 . consider the case @xmath537 . then by the proof of ( [ eq:31 ] ) , we have @xmath597\bigr|=o_{{\mathbb{p}}}(1),\ ] ] where @xmath598 . recall the definitions of @xmath599 and @xmath600 in ( [ eq:36 ] ) . note that @xmath601 is a quadratic form of i.i.d . normal random variables . more specifically , @xmath602 can be written as @xmath603 where @xmath604 is a length @xmath605 vector of i.i.d . standard normal random variables , @xmath606 is a @xmath607 block diagonal matrix , @xmath59 is the @xmath608 matrix with @xmath609th and @xmath610th elements equaling 1 and all other entries equaling 0 and @xmath611 denotes the kronecker product . let @xmath612 . by condition ( a9 ) , @xmath613 is positive definite with eigenvalues bounded both above and below . then it is easy to see that there exist constants @xmath247 , such that @xmath614 . by the lyapunov clt , to prove the asymptotic normality of @xmath615 , it suffices to show that the @xmath616 , where @xmath617 is the eigenvalue of @xmath618 with the maximum absolute value . by the basic property of kronecker product , we have that the eigenvalues of @xmath618 are the products of the eigenvalues of @xmath619 and @xmath59 . hence it is clear that @xmath620 . the case when @xmath551 or @xmath621 follows similarly . sketch of proof of theorem [ thm : ftransform_normal_appr ] theorem [ thm : ftransform_normal_appr ] follows from lemma 5 in the online supplement of the paper with @xmath622 for some finite constant @xmath623 together with a careful check of the proof of theorem 1 in @xcite with @xmath624 and @xmath625 therein . the author is grateful to the two anonymous referees for their careful reading of the manuscript and many helpful comments .

we investigate the behavior of fourier transforms for a wide class of nonstationary nonlinear processes . asymptotic central and noncentral limit theorems are established for a class of nondegenerate and degenerate weighted @xmath0-statistics through the angle of fourier analysis . the established theory for @xmath0-statistics provides a unified treatment for many important time and spectral domain problems in the analysis of nonstationary time series , ranging from nonparametric estimation to the inference of periodograms and spectral densities .

gordon moore s well - known and often cited prediction still holds @xcite , the fact is that for the past few years , cpu speeds have hardly been improving . instead , the number of cores within a single cpu is increasing . this situation poses a challenge for software development in general and research in particular : a hardware upgrade will , most of the time , fail to double the serial execution speed of its predecessor . however , since this commodity hardware is present in practically all modern desktop computers , it creates an opportunity for the parallel exploitation of these computing resources to enhance the performance of complex algorithms over large data sets . the challenge is thus to deliver the computing power of multi - core systems in order to tackle a computationally time - consuming problem , the completion of which is unfeasible using traditional serial approaches . moreover , by accessing many such computing nodes through a network connection , even more possibilities are available . a traditional approach when dealing with computationally expensive problem solving is to simplify the models in order to be able to execute their calculations within a feasible amount of time . clearly , this method increases the introduced error level , which is not an option for a certain group of simulations , e.g. , those dealing with disaster contingency planning and decision support @xcite . the conducted simulations during the planning phase of a radio network also belong to this group . their results are the basis for the decision making prior to physically installing the base stations and antennas that will cover a certain geographical area . a greater deviation of these results increases the probability of making the wrong decisions at the time of the installation , which may considerably increase the costs or even cause mobile - network operators to incur losses . various groups have successfully deployed high - performance computing ( hpc ) systems and techniques to solve different problems dealing with spatial data @xcite . this research has confirmed that a parallel paradigm such as master - worker , techniques like work pool ( or task farming ) and spatial - block partitioning are applicable when dealing with parallel implementations over large spatial data sets . however , it is well known that parallel programming and hpc often call for area experts in order to integrate these practices into a given environment @xcite . moreover , the wide range of options currently available creates even more barriers for general users wanting to benefit from hpc . in this paper , we combine some of the known principles of hpc and introduce a new approach in order to improve the performance speed of a gis module for radio - propagation predictions . the efficiency improvement is based on overlapping process execution and communication in order to minimize the idle time of the worker processes and thus improve the overall efficiency of the system . to this end , we save the intermediate calculation results into an external database ( db ) instead of sending them back to the master process . we implement this approach as part of a parallel radio - prediction tool ( prato ) for the open - source geographic resources analysis support system ( grass ) @xcite . for its architecture , we have focused on scalability , clean design and the openness of the tool , inspired by the grass gis . this makes it an ideal candidate for demonstrating the benefits and drawbacks of several reviewed patterns , while tackling the radio - coverage predictions of big problem instances , e.g. , real mobile networks containing thousands of transmitters over high - resolution terrains , and big - scale simulations covering the whole country . in order to assess the benefits and drawbacks of various reviewed approaches from the performance point of view , we evaluate prato in a distributed computing environment . furthermore , by presenting a detailed description of its design and implementation , we provide an analysis of the patterns achieving higher efficiency levels , so that they can be adopted for general task parallelization in the grass gis . the paper is organized as follows . section [ sec : related - work ] gives an overview of the relevant publications , describing how they relate to our work . section [ sec : description - of - the - radio - coverage - prediction - tool ] gives a description of the radio - coverage prediction problem , including the radio - propagation model . section [ sec : design - and - implementation ] concentrates on the design principles and implementation details of the radio - propagation tool , for the serial and parallel versions . section [ sec : simulations ] discusses the experimental results and their analysis . finally , section [ sec : conclusion ] draws some conclusions . the task - parallelization problem within the grass environment has been addressed by several authors in a variety of studies . for example , in @xcite , the authors present a collection of grass modules for a watershed analysis . their work concentrates on different ways of slicing raster maps to take advantage of a message passing interface ( mpi ) implementation . in the field of high - performance computing , the authors of @xcite presented implementation examples of a grass raster module , used to process vegetation indexes for satellite images , for mpi and ninf - g environments . the authors acknowledge a limitation in the performance of their mpi implementation for big processing jobs . the restriction appears due to the computing nodes being fixed to a specific spatial range , since the input data are equally distributed among worker processes , creating an obstacle for load balancing in heterogeneous environments . using a master - worker technique , the work by @xcite abstracts the grass data types into its own _ struct _ and mpi data types , thus not requiring the grass in the worker nodes . the data are evenly distributed by row among the workers , with each one receiving an exclusive column extent to work on . the test cluster contains heterogeneous hardware configurations . the authors note that data - set size is bounded by the amount of memory on each of the nodes , since they allocate the memory for the whole map as part of the set - up stage , before starting the calculation . regarding the data sets during the simulations , the largest one contains 3,265,110 points . they conclude that the data - set size should be large enough for the communication overhead to be hidden by the calculation time , so that the parallelization pays off . in @xcite , the authors employ a master - worker approach , using one worker process per worker node . the complete exploitation of the computing resources of a single computing node is achieved with openmp . the experimental environment features one host . the horizon - composition algorithm presents no calculation dependency among the spatial blocks . consequently , the digital elevation model ( dem ) may be divided into separate blocks to be independently calculated by each worker process . the authors present an improved algorithm that can also be used to accelerate other applications like visibility maps . the tasks are dynamically assigned to idle processes using a task - farming paradigm over the mpi . also , in @xcite there is no calculation dependency among the spatial blocks . the experimental evaluation is made over multiple cores of one cpu and a gpu , communicated using a master - worker setup . in @xcite , the authors present a parallel framework for gis integration . based on the principle of spatial dependency , they lower the calculation processing time by backing it with a knowledge database , delivering the heavy calculation load to the parallel back - end if a specific problem instance is not found in the database . there is an additional effort to achieve the presented goals , since the implementation of a fully functional gis ( or `` thick gis '' as the authors call it ) is required on both the desktop client and in the parallel environment . an agent - based approach for simulating spatial interactions is presented in @xcite . the authors approach decomposes the entire landscape into equally - sized regions , i.e. , a spatial - block division as in @xcite , which are in turn processed by a different core of a multi - core cpu . this work uses multi - core cpus instead of a computing cluster . some years ago , grid computing received the attention of the research community as a way of accessing the extra computational power needed for the spatial analysis of large data sets @xcite . however , several obstacles are still preventing this technology from being more widely used . namely , its adoption requires not only hardware and software compromises with respect to the involved parts , but also a behavioral change at the human level @xcite . the coverage planning of radio networks is a key problem that all mobile operators have to deal with . moreover , it has proven to be a fundamental issue , not only in lte networks , but also in other standards for mobile communications @xcite . one of the primary objectives of mobile - network planning is to efficiently use the allocated frequency band to ensure that some geographical area of interest can be satisfactorily reached with the base stations of the network . to this end , radio - coverage prediction tools are of great importance as they allow network engineers to test different network configurations before physically implementing the changes . nevertheless , radio - coverage prediction is a complex task , mainly due to the several combinations of hardware and configuration parameters that have to be analyzed in the context of different environments . the complexity of the problem means that radio - coverage prediction is a computationally - intensive and time - consuming task , hence the importance of using fast and accurate tools ( see section [ sub : computational - complexity ] for a complexity analysis of the algorithm ) . additionally , since the number of deployed transmitters keeps growing with the adoption of modern standards @xcite , there is a clear need for a radio - propagation tool that is able to cope with larger work loads in a feasible amount of time ( see section [ sub : computational - complexity ] for the running time of the serial version ) . in this work , we present prato : a high - performance radio - propagation prediction tool for gsm ( 2 g ) , umts ( 3 g ) and lte ( 4 g ) radio networks . it is implemented as a module of the grass gis . it can be used for planning the different phases of a new radio - network installation , as well as a support tool for maintenance activities related to network troubleshooting in general and optimization in particular . specifically , automatic radio - coverage optimization requires the evaluation of millions of radio - propagation predictions in order to find a good solution set , which is unfeasible using other serial implementations of academic or commercial tools @xcite . as a reference implementation , we used the publicly available radio - coverage prediction tool , developed in @xcite . the authors of this work developed a modular radio - coverage tool that performs separate calculations for radio - signal path loss and antenna radiation patterns , also taking into account different configuration parameters , such as antenna tilting , azimuth and height . the output result , saved as a raster map , is the maximum signal level over the target area , in which each point represents the received signal from the best serving transmitter . this work implements some well - known radio - propagation models , e.g. , okumura - hata @xcite and cost 231 @xcite . the latter is explained in more detail in section [ sub : cost-231-model ] . regarding the accuracy of the predicted values , the authors @xcite report comparable results to those of a state - of - the - art commercial tool . to ensure that our implementation is completely compliant with the previously mentioned reference , we have designed a comparison test that consists of running both tools with the same set of input parameters . the test results from prato and the reference implementation were identical in all the tested cases . prato uses the cost-231 walfisch - ikegami radio - propagation model @xcite , which was introduced as an extension of the well - known cost hata model @xcite . the suitability of this model comes from the fact that it distinguishes between line - of - sight ( los ) and non - line - of - sight ( nlos ) conditions . in this work , as well as in the reference implementation @xcite , the terrain profile is used for the los determination . in this context , a nlos situation appears when the first fresnel zone is obscured by at least one obstacle @xcite . we include a correction factor , based on the land usage ( clutter data ) , for accurately predicting the signal - loss effects due to foliage , buildings and other fabricated structures . this technique is also adopted by other propagation models for radio networks , like the artificial neural networks macro - cell model developed in @xcite . consequently , we introduce an extra term for signal loss due to clutter ( @xmath0 ) to the walfisch - ikegami model @xcite , defining the path loss as @xmath1 where @xmath2 is the attenuation in free space and is defined as @xmath3 if there is los between the transmitter antenna and the mobile , the path loss @xmath4 is defined as @xmath5 whereas the path loss for nlos conditions is determined as @xmath6 here , @xmath7 is the distance ( in kilometers ) from the transmitter to the receiver point , @xmath8 is the frequency ( in mhz ) , @xmath9 represents the diffraction from rooftop to the street , and @xmath10 represents the diffraction loss due to multiple obstacles . consequently , the total path loss from the antenna to the mobile device is calculated as in equation ( [ eq : cost231 ] ) , where the attenuation in free space and due to clutter are also taken into account . this section describes the different functions contained in the serial version of prato , which is implemented as a grass module . their connections and data flow are depicted in , where the parallelograms of the flow diagram represent the input / output ( i / o ) operations . our design follows a similar internal organization as the radio - planning tool presented in @xcite , but with some important differences . first , the modular design was avoided in order to prevent the overhead of i / o operations between the components of a modular architecture . second , our approach employs a direct connection to an external database server for intermediate result saving , instead of the slow , built - in grass database drivers . to explicitly avoid tight coupling with a specific database vendor , the generated output is formatted in plain text , which is then forwarded to the db . any further processing is achieved by issuing a query over the database tables that contain the partial results for each of the processed transmitters . ] this step starts by calculating which receiver points , @xmath11 , are within the specified transmission radius ( see `` _ _ transmission radius _ _ '' in ) . the transmission radius is defined around each transmitter in order to limit the radio - propagation calculation to a reasonable distance . for these points , the los and nlos conditions are calculated with respect to the transmitter ( see `` calculate los / nlos '' in ) . the following step consists of calculating the path loss for an isotropic source ( or omni antenna ) . this calculation is performed by applying the walfisch - ikegami model , which was previously defined in equation ( [ eq : cost231 ] ) , to each of the points within the transmission radius around the transmitter . shows an example result of the isotropic path - loss calculation , only including the map area within the transmission radius . the color scale is given in db , indicating the signal loss from the isotropic source of the transmitter , located at the center . notice the hilly terrain is clearly distinguished due to los and nlos conditions from the signal source . this step considers the antenna radiation diagram of the current transmitter and its influence over the isotropic path - loss calculation ( see `` calculate antenna influence '' in ) . working on the in - memory results generated by the previous step , the radiation diagram of the antenna is taken into account , including the beam direction , the electrical and the mechanical tilt . shows the map area within the transmission radius , where this calculation step was applied to the results from . notice the distortion of the signal propagation that the antenna has introduced . in this step , the path - loss prediction of the transmitter is saved in its own database table ( see `` save transmitter path - loss to db '' in ) . this is accomplished by connecting the standard output of the developed module with the standard input of a database client . naturally , the generated plain text should be understood by the db itself . the final radio - coverage prediction , containing the aggregation of the partial path - loss results of the involved transmitters , is created in this step ( see `` create final coverage prediction '' in ) . the received signal strength from each of the transmitters is calculated as the difference between its transmit power and the path loss for the receiver s corresponding position . this is done by executing an sql query over the tables containing the path - loss predictions of each of the processed transmitters . finally , the output is generated , using the grass built - in modules @xmath12 and @xmath13 , which create a raster map using the query results as the input . the final raster map contains the maximum received signal strength for each individual point , as shown in . in this case , the color scale is given in dbm , indicating the strongest received signal strength from the transmitters . ] @xmath14 digital elevation model ( dem ) of the whole area . @xmath15 @xmath16 signal losses due to land usage of the whole area . @xmath15 @xmath17 transmitter configuration data . @xmath18 @xmath19 @xmath20 dem area within transmission radius of @xmath21 @xmath22 @xmath23 clutter area within transmission radius @xmath21 @xmath22 @xmath24 lineofsight ( @xmath25 ) @xmath26 @xmath27 pathloss ( @xmath28 ) @xmath26 @xmath29 antenna diagram of @xmath21 @xmath30 @xmath27 antennainfluence ( @xmath31 ) @xmath22 @xmath32 @xmath33 pathlossaggregation ( @xmath34 ) @xmath22 @xmath35 in this section , the time complexity of the radio - coverage prediction algorithm is presented , for which the pseudo code is listed in table [ tab : pseudocode - radio_coverage_algorithm ] . the algorithm starts by loading the input , i.e. , the dem and the clutter data . both regular square grids ( rsgs ) should account for the same area and resolution , consequently containing the same number of pixels , @xmath36 . the transmitter data is then loaded into set @xmath37 , the cardinality of which is denoted as @xmath38 . for each transmitter @xmath39 , a smaller subarea of the dem and clutter data ( denoted @xmath40 and @xmath41 , respectively ) is delimited around @xmath21 , based on a given transmission radius . the number of pixels within this sub - area is denoted as @xmath42 , and its value is the same for all @xmath39 . the visibility for an rsg cell is computed using the _ lineofsight _ function , by walking from the antenna of the transmitter to the given element , along the elements intersected by a los , until either the visibility is blocked , or the target is reached @xcite . regarding the _ pathloss _ function , whenever a receiver point is in nlos , the walking path from the transmitter has to be inspected for obstacles , calculating the diffraction losses for each of them , i.e. , @xmath10 from equation ( [ eq : cost231_nlos ] ) . hence , its quadratic complexity , which dominates the complexity of the algorithm , together with _ lineofsight _ , resulting in an algorithmic complexity denoted by @xmath43 although @xmath44 will generally be many orders of magnitude smaller than @xmath45 , its computational - time complexity is relevant for practical use . for example , assuming the radio - coverage prediction for one transmitter completes in around 15 seconds using a serial implementation , the prediction for a mobile network comprising 10,240 transmitters would have an execution time of almost two days . the implementation methodology adopted for prato follows a multi - paradigm , parallel programming approach in order to fully exploit the resources of each of the nodes in a computing cluster . this approach combines a master - worker paradigm with an external db . to efficiently use a shared memory multi - processor on the worker side , and to effectively overlap the calculation and communication , prato uses posix threads @xcite . to use the computing resources of a distributed memory system , such as a cluster of processors , prato uses the mpi @xcite . the mpi is a message - passing standard that defines the syntax and semantics designed to function on a wide variety of parallel computers . the mpi enables multiple processes , running on different processors of a computer cluster , to communicate with each other . it was designed for high performance on both massively parallel machines and on workstation clusters . in order to make the text clearer and to differentiate between the programming paradigms used from here on , we will refer to a posix thread simply as a ` thread ' and a mpi process as a ` process ' . by maintaining our focus on the practical usability and performance of prato , we are introducing a parallel implementation to overcome the computational - time constraints that prevent a serial implementation of the radio - coverage prediction algorithm from tackling big problem instances in a feasible amount of time . a major drawback of the grass as a parallelization environment is that it is not thread - safe , meaning that concurrent changes to the same data set have an undefined behavior @xcite . one technique to overcome this problem is to abstract the spatial data from the grass . for example , in @xcite , the authors achieve the grass abstraction by introducing a _ point _ structure with four _ double _ attributes , where each pixel of the rsg is mapped to an instance of this structure . another possibility is for one of the processes , e.g. , the master , to read entire rows or columns of data before dispatching them for processing to the workers @xcite . in this case , an independence between row / column calculations is required , which is a problem - specific property . in our case , we propose to achieve the grass abstraction by loading the spatial data into a 2d matrix ( or matrices ) of basic data - type elements , e.g. , _ float _ or _ double _ depending on the desired accuracy . the geographical location of each element is calculated as the geographical location of the matrix plus the element offset within it . the advantage of this technique is having the geographical location of each pixel readily available with a minimum memory footprint . moreover , a convenient consequence of this abstraction schema is that worker processes are completely independent of the grass , thus significantly simplifying the deployment of the parallel implementation over multiple computing hosts . in the area of geographical information science , the master - worker paradigm has been successfully applied by several authors @xcite . however , sometimes this technique presents certain issues that prevent the full exploitation of the available computing resources when deployed over several networked computers . additionally , such issues are difficult to measure when the parallelization involves only one computing node @xcite , i.e. , no network communication is required , or only a few processes deployed over a handful of nodes @xcite . specifically , we are referring to network saturation and idle processes within the master - worker model . generally speaking , a single communicating process , e.g. , the master , is usually not able to saturate the network connection of a node . using more than one mpi process per node might solve this problem , but possible rank - ordering problems may appear , thus restricting the full utilization of the network @xcite . another issue appears when the master process executes the mpi code , in which case other processes sleep , making a serial use of the communication component of the system . consequently , the master process becomes the bottleneck of the parallel implementation as the number of worker processes it has to serve grows . this situation is also common when dealing with the metadata of a spatial region , which may relate to several elements of a rsg , making it a frequent cause of load imbalance @xcite . in our case , the transmitter configuration and its antenna diagram represent metadata that are complementary to the sub - region that a transmitter covers . hybrid mpi - openmp implementations @xcite , in which no mpi calls are issued inside the openmp - parallel regions , also fail to saturate the network @xcite . a possible solution to this problem is to improve the communication overlap among the processes . to this end , we have implemented non - blocking point - to - point mpi operations , and an independent thread in the worker process to save the intermediate results to a db . we use one such database system per computer cluster , which also serves the input data to the grass , in order to aggregate the partial results of the path - loss predictions or to visualize them . it is important to note that any kind of database system may be used . by this we mean relational , distributed @xcite or even those of the nosql type @xcite . nevertheless , in this study we use a central relational database system , since they are the most popular and widely available ones . additionally , the non - blocking message - passing technique used to distribute the work - load among the nodes provides support for heterogeneous environments . as a result , computing nodes featuring more capable hardware receive more work than those with weaker configurations , thus ensuring a better utilization of the available computing resources despite hardware diversity and improved load balancing . the master process , for which the flow diagram is given in , is the only component that runs within the grass environment . as soon as the master process starts , the input parameters are read . this step corresponds to `` read input data '' in , and it is carried out in a similar way as in the serial version . the next step delivers the metadata that is common to all the transmitters and the whole region to all the processes ( see `` metadata broadcasting '' in ) . before distributing the work among the worker processes , the master process proceeds to decompose the loaded raster data into 2d matrices of basic - data - type elements , e.g. , _ float _ or _ double _ , before dispatching them to the multiple worker processes . in this case , the decomposition applies to the dem and the clutter data only , but it could be applied to any point - based data set . in the next step , the master process starts an asynchronous message - driven processing loop ( see `` processing loop '' in ) , the main task of which is to assign and distribute the sub - region and configuration data of different transmitters among the idle worker processes . the flow diagram shown in illustrates the `` processing loop '' step of the master process . in the processing loop , the master process starts by checking the available worker processes , which will calculate the radio - coverage prediction for the next transmitter . it is worth pointing out that this step also serves as a stopping condition for the processing loop itself ( see `` any worker still on ? '' in ) . the active worker processes inform the master process that they are ready to compute by sending an idle message ( see `` wait for idle worker '' in ) . the master process then announces to the idle worker process that it is about to receive new data for the next calculation , and it dispatches the complete configuration of the transmitter to be processed ( see `` send keep - alive message '' and `` send transmitter data '' steps , respectively , in ) . this is only done in the case that there are transmitters for which the coverage prediction has yet to be calculated ( see `` any transmitters left ? '' in ) . the processing loop of the master process continues to distribute the transmitter data among the worker processes , which asynchronously become idle as they finish the radio - prediction calculations they have been assigned by the master process . when there are no more transmitters left , all the worker processes announcing they are idle will receive a shutdown message from the master process , indicating to them that they should stop running ( see `` send stop message '' in ) . the master process will keep doing this until all the worker processes have finished ( see `` any worker still on ? '' in ) , thus fulfilling the stopping condition for the processing loop . finally , the last step of the master process is devoted to creating the final output of the calculation , e.g. , a raster map ( see `` create final coverage prediction '' in ) . the final coverage prediction of all the transmitters is an aggregation from the individual path - loss results created by each of the worker processes during the `` processing loop '' phase in , which provides the source data for the final raster map . the aggregation of the individual transmitter path - loss results is accomplished by issuing an sql query over the database tables containing the partial results , in a similar way as in the serial version . an essential characteristic of the worker processes is that they are completely independent of the grass , i.e. , they do not have to run within the grass environment nor use any of the grass libraries to work . this aspect significantly simplifies the deployment phase to run prato on a computer cluster , since no grass installation is needed on the computing nodes hosting the worker processes . one possibility to overcome the thread - safety limitation of the grass is to save the transmitter path - loss predictions through the master process , thus avoiding concurrent access . however , for the workers to send intermediate results back to the master process , e.g. , as in @xcite , is a major bottleneck for the scalability of a parallel implementation . the scalability is limited by the master process , because it must serially process the received results in order to avoid inconsistencies due to concurrent access . instead , our approach allows each of the worker processes to output its intermediate results into a db , i.e. , each path - loss prediction in its own table . additionally , worker processes do this from an independent thread , which runs concurrently with the calculation of the next transmitter received from the master process . in this way , the overlap between the calculation and communication significantly hides the latency created by the result - dumping task , thus making better use of the available system resources . the computations of the worker processes , for which the flow diagram is given in , begin by receiving metadata about the transmitters and the geographical area from the master process during the initialization time ( see `` receive broadcasted metadata '' in ) . after the broadcasted metadata are received by all the worker processes , each one proceeds to inform the master process that it is ready ( i.e. , in an idle state ) to receive the transmitter - configuration data that defines which transmitter path - loss prediction to perform ( see `` send idle message '' in ) . if the master process does not give the instruction to stop processing ( see `` has stop message arrived ? '' in ) , the worker process collects the sub - region spatial data and the transmitter configuration ( see `` receive transmitter data '' in ) . in the event that a stop message is received , the worker process will wait for any result - dumping thread to finish ( see `` wait for result - dump thread '' in ) before shutting down . the coverage calculation itself follows a similar design as the serial version ( see `` coverage calculation '' in ) . as mentioned before , the worker process launches an independent thread to save the path - loss prediction of the target transmitter to a database table ( see `` threaded save path - loss to db '' in ) . it is important to note that there is no possibility of data inconsistency due to the saving task being executed inside a thread , since path - loss data from different workers belong to different transmitters and are , at this point of the process , mutually exclusive . similar to @xcite , the message - passing technique used in this work enables a better use of the available computing resources , both in terms of scalability and load balancing , while introducing a negligible overhead . this last point is supported by the experimental results , introduced in section [ sub : strong - scalability ] . the first reason to implement the message - passing technique is to support heterogeneous computing environments . in particular , our approach focuses on taking full advantage of the hardware of each computing node , thus explicitly avoiding the bottlenecks introduced by the slowest computing node in the cluster . this problem appears when evenly distributing the data among the worker processes on disparate hardware , as in @xcite , being more noticeable with a larger number of computing nodes and processes . in other words , computing nodes that deliver better performance have more calculations assigned to them . moreover , in real - world scenarios , it is often the case that a large number of dedicated computing nodes featuring exactly the same configuration is difficult to find , i.e. , not every organization owns a computer cluster . a second reason for selecting a message - passing technique is related to the flexibility it provides for load balancing , which is of greater importance when dealing with extra data or information besides just spatial data @xcite . this can be seen in , where the master process , before delivering the spatial subset and transmitter - configuration data , sends a message to the worker process , indicating that it is about to receive more work . this a priori meaningless message plays a key role in correctly supporting the asynchronous process communication . notice that the subset of spatial data that a worker process receives is directly related to the transmitter for which the prediction will be calculated . similar to @xcite , this problem - specific property enables the use of a data - decomposition technique based on a block partition of spatial data , e.g. , the dem and clutter data . in general , there are many different ways a parallel program can be executed , because the steps from the different processes can be interleaved in various ways and a process can make non - deterministic choices @xcite , which may lead to situations such as race conditions @xcite and deadlocks . a deadlock occurs whenever two or more running processes are waiting for each other to finish , and thus neither ever does . to prevent prato from deadlocking , message sending and receiving should be paired , i.e. , an equal number of send and receive messages on the master and worker sides @xcite . depicts the master - worker message passing , from which the transmitter - data transmission has been excluded for clarity . notice how each idle message sent from the worker process is paired with an answer from the master process , whether it is a keep - alive or a stop message . considering the large computational power needed for predicting the radio - coverage of a real mobile network , the use of a computer cluster is recommended . a computer cluster is a group of interconnected computers that work together as a single system . computer clusters typically consist of several commodity pcs connected through a high - speed local - area network ( lan ) with a distributed file system , like nfs @xcite . one such system is the degima cluster @xcite at the nagasaki advanced computing center ( nacc ) of the nagasaki university in japan . this system ranked in the top 500 list of supercomputers until june 2012 , and in june 2011 it held third place in the green 500 list as one of the most energy - efficient supercomputers in the world . this section presents the simulations and analyses of the parallel version of prato . our aim is to provide an exhaustive analysis of the performance and scalability of the parallel implementation in order to achieve the objectives of this work . the most common usage case for prato is to perform a radio - coverage prediction for multiple transmitters . therefore , a straight - forward parallel decomposition is to divide a given problem instance by transmitter , for which each coverage prediction is calculated by a separate worker process . the following simulations were carried out on 34 computing nodes of the degima cluster . the computing nodes are connected by a lan , over a gigabit ethernet interconnect . as mentioned before , the reason for using a high - end computer cluster such as degima is to explore by experimentation the advantages and drawbacks of the introduced methods . however , this does not imply any loss of generality when applying these principles over a different group of networked computers , i.e. , not acting as a computer cluster . each computing node of degima features one of two possible configurations , namely : * intel core i5 - 2500 t quad - core processor cpu , clocked at 2.30 ghz , with 16 gb of ram ; and * intel core i7 - 2600k quad - core processor cpu , clocked at 3.40 ghz , also with 16 gb of ram . during the simulation runs , the nodes equipped with the intel i5 cpu host the worker processes , whereas the master process and the postgresql database server ( version 9.1.4 ) each run on a different computing node , featuring an intel i7 cpu . the database server performs all its i / o operations on the local file system , which is mounted on an 8 gb ram disk . during the simulations , the path - loss predictions of 5,120 transmitters occupied less than 4 gb of this partition . all the nodes are equipped with a linux 64-bit operating system ( fedora distribution ) . as the message passing implementation we use openmpi , version 1.6.1 , which has been manually compiled with the distribution - supplied gcc compiler , version 4.4.4 . to test the parallel performance of prato , we prepared different problem instances that emulate real radio networks of different sizes . in order to create the synthetic test data - sets with an arbitrary number of transmitters , we used the real data of a group of 2,000 transmitters , which we randomly replicate and distribute over the whole target area . the configuration parameters of these 2,000 transmitters were taken from the lte network deployed in slovenia by telekom slovenije , d.d . the path - loss predictions were calculated using the walfisch - ikegami model . the digital elevation model has an area of 20,270 km@xmath46 , with a resolution of 25 m@xmath46 . the clutter data extends over the same area and resolution , containing different levels of signal loss due to land usage . for all the points within a radius of 20 km around each transmitter , we assume that the receiver is positioned 1.5 m above the ground , and the frequency is set to 1,843 mhz . this set of simulations is meant to analyze the scalability of the parallel implementation in cases where the workload assigned to each process ( one mpi process per processor core ) remains constant as we increase the number of processor cores and the total size of the problem , i.e. , the number of transmitters deployed over the target area is directly proportional to the number of processor cores and worker processes . we do this by assigning a constant number of transmitters per core , while increasing the number of cores hosting the worker processes . here we test for the following numbers of transmitters per worker / core : @xmath47 , by progressively doubling the number of worker processes from 1 to 64 . problems that are particularly well - suited for parallel computing exhibit computational costs that are linearly dependent on the size of the problem . this property , also referred to as algorithmic scalability , means that proportionally increasing both the problem size and the number of cores results in a roughly constant time to solution . the master - worker ( mw ) configuration performs result aggregation continuously , i.e. , while receiving the intermediate results from the worker processes . in contrast , the master - worker - db ( mwd ) setup performs the result aggregation as the final step . with this set of experiments , we would like to investigate how the proposed mwd technique compares with the classic mw approach in terms of scalability when dealing with different problem instances and numbers of cores . an important fact about the presented simulations when using multi - threaded implementations is to avoid oversubscribing a computing node . for example , if deploying four worker processes over a quad - core cpu , the extra threads will have a counter effect on the parallel efficiency , since the cpu resources would be exhausted , which slows the whole process down . for this reason , we have deployed three worker processes per computing node , leaving one core free for executing the extra threads . the results represent the best running time out of a set of 20 independent simulation runs , in which we randomly selected both the transmitters and the rank ordering of the worker processes . the collected running times for the weak - scalability experiments are shown in . all the measurements express wall - clock times in seconds for each setup and problem instance , defined as the number of transmitters per process ( tx / process ) . the wall - clock time represents the real time that elapses from the start of the master process to its end , including the time that passes while waiting for the resources to become available . the running - time improvements of the master - worker - db against the master - worker setup are shown in table [ tab : weak_scaling - time_gain ] . ] .running - time gain ( in percent ) of the simulations for the weak - scalability of the mwd setup relative to the classic mw approach.[tab : weak_scaling - time_gain ] [ cols="^,^,^,^,^,^,^,^ " , ] the time measurements observed from the weak - scalability results show that the classic mw approach performs well for up to four worker processes . when using eight worker processes , the mw setup is practically equivalent to the mwd approach , indicating that the master process is being fully exploited . when increasing the problem size and the number of worker processes to 16 , the running - time gain is already clear , favoring the mwd configuration . this gain keeps growing , although slower , as we increase the number of worker processes to 32 and 64 , confirming our hypothesis that in a classic mw approach , the parallel efficiency is bounded by the capacity of the master process to serve an increasing number of worker processes . interestingly , the gain when using 32 and 64 worker processes is almost the same . after further investigation , we found the reason for this behavior was due to the lan being completely saturated by the worker processes . consequently , they have to wait for the network resources to become available before sending or receiving data , which is not the case when running the mw setup . therefore , using the mwd approach we hit a hardware constraint , meaning that the bottleneck is no longer at the implementation level . moreover , since the master process is far from overloaded when serving 64 worker processes , we can expect the mwd approach will keep scaling if we use a faster network infrastructure , e.g. , 10-gigabit ethernet or infiniband . certainly , the parallel version of prato , when using the mwd approach , scales better when challenged with a large number of transmitters ( 5,120 for the biggest instance ) over 64 cores . this fact shows prato would be able to calculate the radio - coverage prediction for real networks in a feasible amount of time , since many operational radio networks have already deployed a comparable number of transmitters , e.g. , the 3 g network within the greater london authority area , in the uk @xcite . not being able to achieve perfect weak scalability using the mwd setup is due to a number of factors . specifically , the overhead time of the serial sections of the parallel process grow proportionally with the number of cores , e.g. , aggregation of the intermediate results , although the total contribution of this overhead remains low for large problem sizes . moreover , the communication overhead grows linearly with the number of cores used . consequently , we can confirm the findings of @xcite , who concluded that the data - set size should be large enough for the communication overhead to be hidden by the calculation time , for parallelization to be profitable in terms of a running - time reduction . this set of simulations is meant to analyze the impact of increasing the number of computing cores for a given problem size , i.e. , the number of transmitters deployed over the target area does not change , while only the number of worker processes used is increased . here we test for the following number of transmitters : \{1,280 , 2,560 , 5,120 } , by gradually doubling the number of workers from 1 to 64 for each problem size . ] similar to the weak - scalability experiments , these time measurements show that when applying a classic mw approach the running - time reduction starts flattening when more than eight worker processes are used . moreover , the running times for 16 , 32 and 64 worker processes are the same , i.e. , it does not improve due to the master process being saturated . in contrast , when using our mwd technique , the running - time reduction improves for up to 32 worker processes , after which there is no further improvement since the network is being fully exploited . these results clearly show that when applying parallelization using a larger number of worker processes , the master process becomes the bottleneck of the mw approach . when using the mwd configuration , a steady running - time reduction is observed , until a hardware constraint is hit , e.g. , the network infrastructure . we have also measured the overhead of sending / receiving asynchronous messages in order to support heterogeneous systems , which is lower than 0.02% of the total running time for the mw experiments , and 0.01% for the mwd experimental set . in order to further analyze how well the application scales using the mw and mwd approaches , we measured the performance of the parallel implementation in terms of its speedup , which is defined as @xmath48 where @xmath49 is the number of cores executing the worker processes . as the base case for comparisons we chose the parallel implementation running on only one core and decided against using the serial implementation . we consider that the serial implementation is not a good base comparison for the parallel results as it does not reuse the resources between each transmitter - coverage calculation and it does not overlap the i / o operations with the transmitter computations . in practice , this means that several concatenated runs of the serial version would be considerably slower than the parallel but single worker implementation . ] ] using the speedup metric , linear scaling is achieved when the obtained speedup is equal to the total number of processors used . however , it should be noted that a perfect speedup is almost never achieved , due to the existence of serial stages within an algorithm and the communication overhead of the parallel implementation . shows the average speedup of the parallel implementation for up to 64 worker processes , using the standard mw method and our mwd approach . the average speedup was calculated for the three different problem instances , i.e. , 1,280 , 2,560 , and 5,120 transmitters deployed over the target area . the number of transmitters used in these problem sizes is comparable to several real - world radio networks that were already deployed in england , e.g. , hampshire county with 227 base stations , west midlands with 414 base stations , and greater london authority with 1,086 base stations @xcite . note that it is common for a single base station to host multiple transmitters . the plotted average speedup clearly shows the minimal overhead of the mwd approach when using a small number of worker processes . this overhead accounts for the final aggregation of the intermediate results at the db , which in the mw configuration is performed along worker processing . like before , the db component allows the parallel implementation to fully exploit the available computing resources when deploying a larger number of worker processes , until the network - speed limit is met . of course , these results are directly correlated with the wall - clock times shown in . another measure to study how well prato utilizes the available computing resources considers the parallel efficiency of the implementation , i.e. , how well the parallel implementation makes use of the available processor cores . the definition of parallel efficiency is as follows @xmath50 where @xmath51 is the speedup as defined in equation ( [ eq : speedup ] ) , and @xmath49 is the number of cores executing worker processes . shows the average parallel efficiency of the parallel implementation for different problem sizes as we increase the number of processing cores . like for the speedup measure , we have calculated the average parallel efficiency from the three problem instances analyzed . the ideal case for a parallel application would be to utilize all the available computing resources , in which case the parallel efficiency would always be equal to one as we increase the core count . from the plot in , we can see that the efficiency of the mwd approach is better than in the mw case for larger number of processes and as long as there is still capacity at the lan level . in accordance to the previous analysis , the under utilization of the computing resources is more significant when the master process is overloaded ( in the mw case ) than when the network infrastructure is saturated ( in the mwd case ) . the lower efficiency is directly proportional to the number of idle worker processes that are waiting for the master process ( mw case ) or for network access ( mwd case ) . overall , the experimental results confirm that the objective of fully exploiting the available hardware resources is accomplished when applying our mwd approach , thus improving the scalability and efficiency of prato when compared with a traditional mw method . we have presented prato , a parallel radio - coverage prediction tool for radio networks . the tool , as well as the patterns for exploiting the computing power of a group of networked computers , i.e. , a computer cluster , are intended to be used for spatial analysis and decision support . the introduced mwd technique , which combines the use of a database system with a work - pool approach , delivers improved performance when compared with a traditional mw setup . moreover , the presented system provides parallel and asynchronous computation , that is completely independent of the gis used , in this case the grass environment . consequently , a gis installation is needed on only one of the nodes , thus simplifying the required system setup and greatly enhancing the applicability of this methodology in different environments . the extensive simulations , performed on the degima cluster of the nagasaki advanced computing center , were analyzed to determine the level of scalability of the implementation , as well as the impact of the presented methods for parallel - algorithm design aimed at spatial - data processing . the conducted analyses show that when using the mwd approach , prato is able to calculate the radio - coverage prediction of real - world mobile networks in a feasible amount of time , which is not possible for a serial implementation . moreover , the experimental results show prato has a better scalability than the standard mw approach , since it is able to completely saturate the network infrastructure of the cluster . these promising results also show the great potential of our mwd approach for parallelizing different time - consuming spatial problems , where databases form an intrinsic part of almost all gis . furthermore , the automatic optimization of radio networks , where millions of radio - propagation predictions take part in the evaluation step of the optimization process , are also excellent candidates for this approach . indeed , this last point is currently undergoing extensive research and it is already giving its first results . encouraged by the favorable results , further work will include abstracting the introduced mwd principle into a multi - purpose parallel framework such as charm++ @xcite , which provides a functionality for overlapping execution and communication , as well as fault tolerance . in addition , as prato is also a free and open - source software project , it can be readily modified and extended to support , for example , other propagation models and post - processing algorithms . this characteristic provides it with a clear advantage when compared to commercial and closed - source tools . this project was co - financed by the european union , through the european social fund . hamada acknowledges support from the japan society for the promotion of science ( jsps ) through its funding program for world - leading innovative r&d on science and technology ( first program ) . zhaoya gong , wenwu tang , david a bennett , and jean - claude thill . parallel agent - based simulation of individual - level spatial interactions within a multicore computing environment . , 27(6):11521170 , 2013 . qunying huang , chaowei yang , karl benedict , abdelmounaam rezgui , jibo xie , jizhe xia , and songqing chen . using adaptively coupled models and high - performance computing for enabling the computability of dust storm forecasting . , 27(4 ) , 2013 . howard xia , henry l bertoni , leandro r maciel , andrew lindsay - stewart , and robert rowe . radio propagation characteristics for line - of - sight microcellular and personal communications . , 41(10):14391447 , 1993 .

geographical information systems are ideal candidates for the application of parallel programming techniques , mainly because they usually handle large data sets . to help us deal with complex calculations over such data sets , we investigated the performance constraints of a classic master - worker parallel paradigm over a message - passing communication model . to this end , we present a new approach that employs an external database in order to improve the calculation / communication overlap , thus reducing the idle times for the worker processes . the presented approach is implemented as part of a parallel radio - coverage prediction tool for the grass environment . the prediction calculation employs digital elevation models and land - usage data in order to analyze the radio coverage of a geographical area . we provide an extended analysis of the experimental results , which are based on real data from an lte network currently deployed in slovenia . based on the results of the experiments , which were performed on a computer cluster , the new approach exhibits better scalability than the traditional master - worker approach . we successfully tackled real - world data sets , while greatly reducing the processing time and saturating the hardware utilization . grass , gis , parallel , radio , propagation , simulation .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Restore the Partnership Act''. SEC. 2. ESTABLISHMENT. There is established a permanent bipartisan commission to be known as the ``National Commission on Intergovernmental Relations'' (in this Act referred to as the ``Commission''). SEC. 3. DECLARATION OF PURPOSE. In order to facilitate the fullest cooperation and coordination between all levels of government in an increasingly complex society, it is essential that a commission be established to give continuing attention to intergovernmental issues. It is intended that the Commission, in the performance of its duties, will-- (1) bring together representatives of Federal, State, and local governments for the consideration of common problems; (2) provide a forum for discussing the administration and coordination of Federal aid and other programs requiring intergovernmental cooperation; (3) give critical attention to the conditions, controls, and oversight involved in the administration of such Federal programs; and (4) encourage discussion and study during the early stages of emerging public challenges that are likely to require intergovernmental cooperation. SEC. 4. MEMBERSHIP. (a) Number and Appointment.--The Commission shall be composed of 30 members, as follows: (1) 6 appointed by the President of the United States, 3 of whom shall be officers of the executive branch of the government, and 3 private citizens, each of whom shall have experience or familiarity with relations between the levels of government. (2) 3 appointed by the President of the Senate, who shall be Members of the Senate. (3) 3 appointed by the Speaker of the House of Representatives, who shall be Members of the House. (4) 4 appointed by the President from a panel of at least 8 Governors submitted by the National Governors' Association. (5) 4 appointed by the President from a panel of at least 8 members of State legislative bodies submitted by the National Conference of State Legislatures. (6) 4 appointed by the President from a panel of at least 8 mayors submitted jointly by the National League of Cities and the United States Conference of Mayors. (7) 4 appointed by the President from a panel of at least 8 elected county officers submitted by the National Association of Counties. (8) 2 tribal officials appointed by the Secretary of the Interior from a panel of at least 4 submitted by the National Congress of American Indians. (b) Political and Geographical Composition.-- (1) The members appointed from private life under paragraph (1) of subsection (a) shall be appointed without regard to political affiliation. (2) Of each class of members enumerated in paragraphs (2) and (3) of subsection (a), 2 shall be from the majority party of the respective houses. (3) Of each class of members enumerated in paragraphs (4), (5), (6), and (7) of subsection (a), not more than 2 shall be from any 1 political party. (4) Of each class of members enumerated in paragraphs (5), (6) and (7) of subsection (a), not more than 1 shall be from any 1 State. (5) At least 2 of the appointees under paragraph (6) of subsection (a) shall be from cities with a population of less than 500,000. (6) At least 2 of the appointees under paragraph (7) of subsection (a) shall be from counties with a population of less than 50,000. (7) 1 of the appointees under paragraph (8) of subsection (a) shall be from a gaming tribe and 1 shall be from a non- gaming tribe. (c) Terms.-- (1) In general.--The term of office of each member of the Commission shall be 2 years. Members shall be eligible for reappointment. Except as provided in paragraph (2), members shall serve until their successors are appointed. (2) Termination of service in official position from which originally appointed.--Where any member ceases to serve in the official position from which originally appointed under section 3(a), his or her place on the Commission shall be deemed to be vacant. (3) Vacancies in membership.--Any vacancy in the membership of the Commission shall be filled in the same manner in which the original appointment was made; except that where the number of vacancies is fewer than the number of members specified in paragraphs (4), (5), (6), and (7) of section 3(a), each panel of names submitted in accordance with the aforementioned paragraphs shall contain at least 2 names for each vacancy. SEC. 5. ORGANIZATION OF COMMISSION. (a) Initial Meeting.--The President shall convene the Commission not later than 90 days after the date of enactment of this Act at such time and place as the President may designate. (b) Chairman and Vice Chairman.--The Commission shall designate a Chairman and a Vice Chairman from among members of the Commission. (c) Quorum.--13 members of the Commission shall constitute a quorum, but 2 or more members, representing more than 1 of the class of members enumerated in section 4(a), shall constitute a quorum for the purpose of conducting hearings. SEC. 6. DUTIES OF COMMISSION. The Commission shall-- (1) engage in such activities and make such studies and investigations as are necessary or desirable in the accomplishment of the purposes set forth in section 2; (2) consider, on its own initiative, mechanisms for fostering better relations between the levels of government; (3) make available technical assistance to the executive and legislative branches of the Federal Government in the review of proposed legislation to determine its overall effect on all levels of government; (4) recommend, within the framework of the Constitution, the most desirable allocation of governmental functions, responsibilities, and revenues among the levels of government; (5) recommend methods of coordinating and simplifying tax laws and administrative policies and practices to achieve a more orderly and less competitive fiscal relationship between the levels of government and to reduce the burden of compliance for taxpayers; and (6) submit an annual report to the President and the Congress on or before January 31 of each year. The Commission may also submit such additional reports to the President, to Congress or any committee of Congress, and to any unit of government or organization as the Commission may deem appropriate. SEC. 7. POWERS AND ADMINISTRATIVE PROVISIONS. (a) Hearings and Sessions.--The Commission or, on the authorization of the Commission, any subcommittee or members thereof, may, for the purpose of carrying out the provisions of this Act, hold such hearings, take such testimony, and sit and act at such times and places as the Commission deems advisable. Any member authorized by the Commission may administer oaths or affirmations to witnesses appearing before the Commission or any subcommittee or members thereof. (b) Cooperation by Federal Agencies.--Each department, agency, and instrumentality of the executive branch of the government, including independent agencies, is authorized and directed to furnish to the Commission, upon request made by the Chairman or Vice Chairman, such information as the Commission deems necessary to carry out its functions under this Act. (c) Executive Director.--The Commission shall have power to appoint and remove an Executive Director. The Executive Director shall be paid at the rate of basic pay for level III of the Executive Schedule. Such appointment shall be made solely on the basis of fitness to perform the duties of the position and without regard to political affiliation. (d) Staff.--Subject to such rules and regulations as may be adopted by the Commission, the Executive Director shall have the power-- (1) to appoint, fix the compensation of, and remove such other personnel as he deems necessary; and (2) to procure temporary and intermittent services to the same extent as is authorized by law. (e) Applicability of Other Laws to Employees.--Except as otherwise provided in this Act, persons in the employ of the Commission under subsections (c) and (d)(1) shall be considered Federal employees for all purposes. (f) Maximum Compensation of Employees.--No individual in the employ of the Commission under subsection (d)(1) shall be paid compensation for such employment at a rate in excess of the highest rate provided for under the General Schedule. SEC. 8. REIMBURSEMENT. Members of the Commission shall be entitled to reimbursement for travel, subsistence, and other necessary expenses incurred by them in the performance of their duties as members of the Commission. SEC. 9. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated such sums as may be necessary to carry out the provisions of this Act. SEC. 10. RECEIPT OF FUNDS; CONSIDERATION BY CONGRESS. The Commission is authorized to receive funds through grants, contracts, and contributions from State and local governments and organizations thereof, and from nonprofit organizations. Such funds may be received and expended by the Commission only for purposes of this Act. In making appropriations to the Commission, Congress shall consider the amount of any funds received by the Commission in addition to those funds appropriated to it by Congress.

Restore the Partnership Act - Establishes a permanent, bipartisan National Commission on Intergovernmental Relations. Requires the Commission to: (1) engage in activities and studies necessary to give continuing attention to intergovernmental issues in order to facilitate cooperation and coordination among all levels of government; (2) consider mechanisms for fostering better relations among the levels of government; (3) make available technical assistance to the federal executive and legislative branches in the review of proposed legislation to determine its overall effect on all levels of government; (4) recommend, within the framework of the Constitution, the most desirable allocation of government functions, responsibilities, and revenues among the levels of government; (5) recommend methods of coordinating and simplifying tax laws and administrative policies and practices to achieve a more orderly and less competitive fiscal relationship among the levels of government and to reduce the burden of compliance for taxpayers; and (6) submit an annual report to the President and Congress.

orofacial clefts ( ofc ) are a common congenital malformation of the head and neck and the prevalence in nigeria is 0.5 per 1000 live births . the incidence rate of cleft lip , cleft palate , and cleft lip and palate in blacks ranges from 0.18 to 1.67 per 1,000 . affected children often have difficulty feeding and require multidisciplinary medical and surgical care from birth to adulthood . the impact of ofc is manifold , affecting the patients themselves and their immediate family on one hand and the society they belong to on the other [ 4 , 5 ] . it affects physical functions such as speech , biting , sucking , and swallowing and has diverse psychological effects on both the patient and their parents . these psychological effects lead to different reactions , some as drastic as infanticide [ 79 ] . different attempts have been made to quantify the psychological effects of the unaesthetic appearance of the cleft child and the impact of cleft lip repair on aesthetics [ 1013 ] . cleft lip repair is undertaken as early as 3 months of age , once the child is able to withstand the trauma of surgery , so as to reduce its psychosocial trauma on the parents . this repair , though undertaken by surgeons , necessitates multidisciplinary intervention and includes the inputs of orthodontists , speech therapists , pediatricians , and counselors [ 7 , 15 ] . the health and well - being of the patients are dependent upon the clinical expertise of those who serve them . in addition , society as a whole is affected by the quality of their care because the potential of the affected individual for a positive contribution to the community is inevitably influenced by the adequacy of treatment . there is a responsibility amongst cleft service givers to increase awareness about the availability , timing , advantages , and modalities of repair to counter the mostly negative attitudes of individuals and societies towards such a deformity . nigeria , the most populous country in africa and the most populous black nation in the world with a population of over 160 million people and a crude birth rate of 44 per 1000 , has an estimated prevalence rate of 0.5 per 1000 . this estimated average of 3,360 ofc births per year combines with a significant number of unrepaired adult patients to present a huge disease burden . awareness campaigns are imperative if all these clefts are to be repaired and if the psychosocial burden on cleft patients is to be alleviated . the database of smile train , a us - based nongovernmental organization , ngo , that partners with ofc service providers to conduct free cleft surgeries all over nigeria , has , however , recorded less than 7,000 free surgeries done in the country since inception more than ten years ago . this low figure indicates a lack of awareness by patient and public of the availability of free treatment . this is despite the far spread of institutions known to perform cleft surgeries whether in consonance with or independent of the smile train . some private ngos and privately owned hospitals and dental clinics also offer cleft lip repair services . it would seem that awareness about the availability of repair services available at these institutions , as well as others spread around these zones , is not enough , necessitating efforts at raising awareness and community mobilization . awareness - raising is a means of alerting specific groups and the public in general to the existence of ofc and the need to address it . it is a two - way street , fostering communication and information exchange in order to improve mutual understanding , whilst mobilizing communities and the wider society to bring about the necessary change in attitudes and behavior . community mobilization , on the other hand , is a capacity - building process through which community members , groups , or organizations plan carry out and evaluate activities on a participatory and sustained basis to improve their health and other conditions either on their own initiative or stimulated by others . the opportunity to provide free surgical care for ofc has opened a new vista for research and treatment outcomes in nigeria and can only be enhanced by well - informed communities who are aware of the challenges faced by these babies and their parents and the pivotal role of ofc repair in mitigating them . the aim of this study is to survey the ofc service providers in nigeria and assess the effectiveness of their community mobilization and awareness processes . this was a nationwide cross - sectional descriptive study undertaken on all known orofacial cleft service providers in all geopolitical zones of nigeria , including federally funded teaching hospitals and medical centers , nongovernmental organizations , and private dental clinics . three ( 3 ) ngos , 2 private dental clinics , and 10 federal government - owned orofacial cleft centers were included in the study . federal government - funded organizations were categorized as government - owned organizations ( goos ) , while private dental clinics and ngos were grouped as nongovernment owned organizations ( ngoos ) . a structured self - administered questionnaire ( the appendix ) elicited information regarding methods of creating awareness and mobilizing target communities that were employed by the ofc services studied . the questionnaire also extracted information regarding financial and organizational commitments towards community mobilization and awareness - raising . all statistical analyses were performed using microsoft excel for mac and spss for mac ( version 18.0 spss inc . , chicago , il ) . descriptive statistics were used and results expressed as frequencies and percentages in tables and charts . fifteen ( 15 ) centers distributed across the 6 geopolitical zones of nigeria were included in the study , and majority ( 60% ) was located in the northern region of the country . of the fifteen , 10 were federal and 5 were privately owned institutions , including 3 ngos and 2 dental clinics . a total of 4648 cleft had been repaired , 50.8% by the 10 government - owned organizations ( goos ) and 49.2% by the 5 nongovernment owned organizations ( ngoos ) . table 1 presents the demographic and other features of the ofc service providers located in the six regions of the country . six ( 6 ) of the 10 goos did not have community mobilization groups as compared to 4 of the 5 ngoos that did . also , only 1 of the 10 provided formative assessment of the community perception of cleft lip and palate as compared to 2 of the 5 ngoos that did . all of the organizations provided cleft anomaly educational information to cleft care receivers ( table 3 ) . seven ( 7 ) of the 10 goos , however , did not provide training on feeding of cleft lip and palate patients and 9 of the 10 did not have formal training on advocacy skills as part of the community awareness training . these and other parameters related to community awareness are depicted in table 3 . majority of the ngoos combined multiple gatekeepers while gaining access to the community ( table 4 ) , as compared to the goos that gained access predominantly through primary healthcare centers or local government area chairmen ( table 4 ) . media employed by all organizations to create community awareness included print , electronic , and other more traditional media . both sets of institutions seemed to prefer print to electronic or other traditional types of media , although the ngoos employed a greater variety of media than the goos ( table 5 ) . most subjects thought the most effective media were radio and posters ( table 6 ) while 11 of the 15 organizations studied ( 7 goos and 4 ngoos ) indicated their preference for a separate body , distinct from the surgical service , to handle awareness campaigns ( table 7 ) . community mobilization engages all sectors of the population in a community - wide effort to address a health , social , or environmental challenge . it brings together policy makers and opinion leaders , local , state , and federal government , professional groups , religious groups , businesses , and individual community members . it empowers individuals and groups to take some kind of action to facilitate change . to our knowledge , no prior study has been done on community mobilization and awareness creation involving the smile train free cleft repair services . in our study , the ngoos were more likely to engage in community mobilization than goos . one possible reason for this is the fact that the government hospitals are referral , tertiary - care centers and would not , ordinarily , need to mobilize the community to access their services . this is not the case with the ngoos that may need to create community awareness for their services to have the desired impact . a community is not merely a collection of individuals but a system that transcends those individuals . as a system it has various dimensions : technological , economic , political , institutional , ideological , and perceptual . participation of communities is an essential element of community mobilization , but it is important to recognize that all participation is not equal . as community participation increases , community ownership and capacity increase , with the result that community action and continuous improvement in the quality of community life are more likely to be sustained over time . every community has opinion leaders , the people who make things happen in the community by virtue of their roles or positions . these people are the gatekeepers and should not be bypassed if community mobilization is to be effective . these opinion leaders are kings , chiefs / emirs , traditional leaders , religious leaders , political leaders , women leaders , youth leaders , and so forth . in this study , ngoos were more aggressive in engaging all types of gatekeepers in the community . to mobilize the community for any particular intervention , to do an effective community mobilization , a lot must therefore be known about the nature of communities in general and this information can be obtained through formal or informal research into the target community . our study shows that formative assessment is undertaken by very few of the organizations involved in cleft care in nigeria . in generating awareness , it is important to make formative assessment of the community 's concept of cleft lip and palate . once communities understand the causes and consequences of clefts , they will be supportive of efforts at surgical repair . in order to boost community mobilization for orofacial cleft services in a low socioeconomic environment like nigeria , it is essential that certain steps ( information dissemination , awareness raising , motivation , community mobilization , and total awareness ) are prudently followed , to achieve the desired goals . community mobilization , at its best , does not merely raise community awareness about cleft lip services ; rather , it is a comprehensive strategy that includes the community action cycle . the primary ingredients of a successful community mobilization program , termed success factors , consist of trained staff ; adequate budget for media / publicity , transportation , and training ; and educational materials . the employment of most of these ingredients may explain why the 5 ngoos studied repaired almost as many clefts as the 10 goos ( table 1 ) . the 10 federal government - owned cleft centers had operated 2360 ( 50.8% ) , while the 5 nongovernment owned organizations had performed 2288 surgeries ( 49.2% ) as per their records . this is more remarkable when the relative numbers of years these institutions had been into cleft care are taken into consideration ( table 1 ) . this may also however be linked to the fact that ofc repair is the priority service provided by some of the ngoos studied , whereas cleft repair is a minor part of the activities in the government institutions . furthermore , official bureaucracy in government institutions causes a lot of delay in access to care whereas such delays are not encountered at the ngoos . there is a statistically significant relationship between the level of educational attainment and the knowledge about cleft deformities . this finding buttresses the need to adapt the medium and content of cleft deformity campaigns to the perceived level of education of the community . to create awareness among the less literate members of the society , the communication medium should be visual , and to make the message acceptable and reliable , a variety of media are required . most ngoos in our study employed a variety of media , none more so than the grassroot smile initiative ( table 1 ) , an ngo , which employed all the mediums listed and who , unsurprisingly , posted the highest number of cleft surgeries . the owotade study showed that the most preponderant source of information about cleft deformities was family members . in our study , we described that source of information as word of mouth , and it was not employed prominently by most of the institutions studied . the study instead showed a preference for radio and posters by both ngoos and goos . radios are affordable and most stations broadcast in local language and so , community members have closeness to this device . posters are visual devices that can pass messages across at a glance and can be placed in multiple prominent places at once , cutting across all socioeconomic , educational , and locational divides . it is also the experience of the authors that motor parks and drivers stationed therein were a veritable method of awareness creation . commercial drivers travel across communities and are able to spread the news of cleft care through handbills , fliers , and word of mouth . advocacy is a set of actions , big or small , that aims to influence people who hold power to create positive change . a successful advocacy campaign comprises a variety of actions that are deliberately planned to be complementary and build on each other . the goals must , in turn , be specific , measurable , achievable , realistic , and time - bound . advocacy is necessary to raise the awareness level of communities to cleft lip and palate services . people need to know about the availability of free cleft clinics and it would be important to identify the most effective ways of informing and sensitizing them about such services . this study showed that less than 30% of cleft service providers had any formal training in advocacy skills ( table 3 ) . for a cleft repair service to grow , building community understanding is a challenge that must be addressed head on by the service providers . the primary goal of awareness is fostering improved mutual understanding and mobilization of communities in such a way as to direct traffic to available cleft services . awareness is a two - way process where communities realize and understand that clefts can be repaired and know the appropriate action to take to benefit from such services . awareness raising is a multiway communication or interaction process which provides opportunities for dialogue , mutual learning , and trust - building , helping to empower communities and strengthen their interest . enhanced public awareness enables better - informed community participation and sustainable appreciation and patronage of the cleft services . the objective of community sensitization and awareness strategies is to ensure the community actively participates in the cleft care available to them . the methods of sensitization and awareness - raising include organizing workshops with communities ; experience sharing from success stories ; community participation and involvement ; engaging the mass media and other institutions ; using printed materials ; involving popular personalities ; implementing school programs ; and meeting gatekeepers . the ngoos focused more on awareness raising and community sensitization than the goos . as indicated earlier , the about 7,000 free surgeries done in the country since inception of the smile train more than ten years ago are less than the estimated disease burden when prevalence and incidence values are taken into consideration [ 1 , 1618 ] . possible explanations for the low number of treated orofacial clefts in nigeria are poverty ; patient 's inability to afford transportation cost to treatment centers ; fear of surgery ; and misconception that other parts of the body may be cut to repair the cleft defect . religious beliefs indicating that attempts to repair the defect amounted to questioning god 's work have also been observed during interaction with some patients and patient relatives . yet some others see the defect as a source of livelihood ( as the children are used for alms begging ) . in order for the number of orofacial cleft repairs done by both sets of institutions to approach the estimated disease burden , ( the study could only account for 4646 in table 1 ) the discussed ingredients of community mobilization and awareness - creation have to be employed more strategically and aggressively by the government and nongovernment owned institutions alike . the government institutions may also need to have dedicated cleft units that make cleft repairs a priority service and empower such units with the authority to control their activities . also , there may be a need to establish awareness - creation and community mobilization subunits in these institutions to increase their impact in their locales . when asked if they would prefer to have an independent organization handle community mobilization , 11 of the 15 organizations ( 7 goos and 4 ngoos ) said yes to a separate body handling awareness campaign . this is an indication of the workload involved in awareness campaign and the difficulty of superimposing such demands on an organization that is more designed to delivering surgical care . a dedicated budget and independent awareness group will undoubtedly increase the efficiency of the cleft care organization in both government - owned and nongovernment owned institutions alike . the nongovernment owned organizations appear to be more aggressive in community mobilization and awareness - creation for free cleft surgical services , and this has reflected in the patient turnout , when compared with government - owned organizations , which , generally have been involved in the provision of cleft care for longer periods . community mobilization requires skill and dedication , which necessitate formal training and make it essential for organizations to have dedicated programs and , if possible , budgets in order to be able to fully mobilize the community .

background . the opportunity to provide free surgical care for orofacial clefts has opened a new vista and is enhanced by well - informed communities who are aware of the free surgical services available to them . it is the responsibility of cleft care providers to adequately inform these communities via a combination of community mobilization and awareness creation . methods . this was a nationwide , cross - sectional descriptive study of all orofacial cleft service providers in nigeria using a structured , self - administered questionnaire . results . a total of 4648 clefts have been repaired , 50.8% by the ten government - owned and 49.2% by the five nongovernment - owned organizations included in the study . the nongovernment - owned institutions seemed to be more aggressive about community mobilization and awareness creation than government - owned ones , and this was reflected in their patient turnout . most of the organizations studied would prefer a separate , independent body to handle their awareness campaign . conclusion . community mobilization requires skill and dedication and may require formal training or dedicated budgets by government - owned and nongovernment - owned institutions alike . organizations involved in cleft care provision must take community mobilization and awareness seriously if the largely unmet needs of orofacial cleft patients in nigeria are to be tackled .

A Staten Island grand jury on Wednesday ended the criminal case against a white New York police officer whose chokehold on an unarmed black man led to the man’s death, a decision that drew condemnation from elected officials and touched off a wave of protests. The fatal encounter in July was captured on videos and seen around the world. But after viewing the footage and hearing from witnesses, including the officer who used the chokehold, the jurors deliberated for less than a day before deciding that there was not enough evidence to go forward with charges against the officer, Daniel Pantaleo, 29, in the death of the man, Eric Garner, 43. Officer Pantaleo, who has been on the force for eight years, appeared before the grand jury on Nov. 21, testifying that he did not intend to choke Mr. Garner, who was being arrested for allegedly selling loose cigarettes. He described the maneuver as a takedown move, adding that he never thought Mr. Garner was in mortal danger. ||||| NEW YORK (AP) — A New York City grand jury cleared a white police officer Wednesday in the videotaped chokehold death of an unarmed black man who had been stopped on suspicion of selling loose, untaxed cigarettes, a lawyer for the victim's family said. The decision in Staten Island not to indict Officer Daniel Pantaleo threatened to add to the tensions that have simmered in the city since the July 17 death of Eric Garner — a case that sparked outrage and drew comparisons to the fatal police shooting of 18-year-old Michael Brown in Missouri. Jonathon Moore, an attorney for the victim's family, said he was told of the grand jury's decision. "I am actually astonished based on the vidence of the video tape, and the medical examiner, that this grand jury at this time wouldn't indict for anything, is really just astonishing," Moore said. The Staten Island District Attorney's office didn't immediately respond to a call. The grand jury could have considered a range of charges, from a murder charge to a lesser offense like reckless endangerment. A video shot by an onlooker and widely viewed on the Internet showed the 43-year-old Garner telling a group of police officers to leave him alone as they tried to arrest him. Pantaleo responded by wrapping his arm around Garner's neck in an apparent chokehold, which is banned under NYPD policy. The heavyset Garner, who had asthma, was heard repeatedly gasping, "I can't breathe!" A second video surfaced that showed police and paramedics appearing to make no effort to revive Garner while he lay motionless on the ground. He later died at a hospital. As with Brown's death in the St. Louis suburb of Ferguson, the Garner case sparked protests, accusations of racist policing and calls for federal prosecutors to intervene. But unlike the Missouri protests, the demonstrations in New York remained mostly peaceful. The case also prompted Police Commissioner William Bratton to order officers at the nation's largest police department to undergo retraining on use of force. The medical examiner ruled Garner's death a homicide and found that a chokehold contributed to it. A forensic pathologist hired by Garner's family, Dr. Michael Baden, agreed with those findings, saying there was hemorrhaging on Garner's neck indicative of neck compressions. Police union officials and Pantaleo's lawyer have argued that the officer used a takedown move taught by the police department, not a chokehold, because he was resisting arrest and that Garner's poor health was the main reason he died. There was no immediate comment from Pantaleo's attorney nor the Patrolmen's Benevolent Association, a union that has strongly backed the officer. ||||| These crawls are part of an effort to archive pages as they are created and archive the pages that they refer to. That way, as the pages that are referenced are changed or taken from the web, a link to the version that was live when the page was written will be preserved.Then the Internet Archive hopes that references to these archived pages will be put in place of a link that would be otherwise be broken, or a companion link to allow people to see what was originally intended by a page's authors.The goal is to fix all broken links on the web . Crawls of supported "No More 404" sites.

– Another high-profile grand jury investigation has resulted in no charges for a white police officer accused in a black civilian's death. This time, it's Staten Island, where a grand jury today chose not to indict NYPD officer Daniel Pantaleo in the death of Eric Garner in July, reports the New York Times. Garner, who was unarmed, died after being subdued by a group of officers who accused him of selling unlicensed cigarettes. Pantaleo was seen using a chokehold on Garner, a move banned by the NYPD, as Garner repeatedly said, "I can't breathe." Police have been preparing for Ferguson-like protests in the wake of the decision. "I am actually astonished based on the evidence of the video tape, and the medical examiner, that this grand jury at this time wouldn't indict for anything, is really just astonishing," an attorney for Garner's family tells AP. (The medical examiner earlier had ruled the death a homicide.) Staten Island District Attorney Daniel Donovan said the grand jury of 23 found "no reasonable cause" to indict the officer. The 43-year-old Garner had been a father of six. Pantaleo, who at 29 is an eight-year veteran of the NYPD, still could lose his job because of departmental charges, reports the Daily News.

figure [ inv1 ] depicts an involution @xmath192 on @xmath136 under which @xmath193 is invariant , has its boundary components interchanged , and @xmath194 . then @xmath192 extends to an involution of @xmath99 since its restriction to @xmath195 coincides with the restriction to @xmath139 of the standard involution of @xmath137 . evidently @xmath196 and @xmath197 . figure [ inv2 ] depicts an involution @xmath198 on @xmath142 under which each of the annuli @xmath199 , and @xmath200 are invariant . further , it interchanges the components of @xmath201 and as in the previous paragraph , @xmath198 extends to an involution of @xmath100 . note that @xmath202 for @xmath203 . next consider the orientation preserving involution @xmath204 on @xmath104 . by construction we have @xmath205 for @xmath203 , and therefore @xmath206 where @xmath207 is a homeomorphism whose restriction to @xmath208 is isotopic to @xmath209 . the latter fact implies that @xmath210 is isotopic to a homeomorphism @xmath211 which commutes with @xmath212 . hence , @xmath213 is isotopic to @xmath212 through orientation preserving involutions whose fixed point sets consist of two points . in particular , @xmath192 and @xmath198 can be pieced together to form an orientation preserving involution @xmath214 . for each slope @xmath43 on @xmath6 , @xmath215 extends to an involution @xmath216 of the associated dehn filling @xmath217 , where @xmath218 is the filling solid torus . orbifold theorem applies to our situation and implies that @xmath44 has a geometric decomposition . in particular , @xmath2 is a seifert fibred manifold whose base orbifold is of the form @xmath219 , a @xmath37-sphere with three cone points of orders @xmath220 respectively . it follows immediately from our constructions that @xmath221 and @xmath222 are @xmath1-balls . thus @xmath223 and since @xmath224 , it follows that @xmath225 is a @xmath1-ball . more precisely , @xmath226 is an orbifold @xmath227 , where @xmath228 is a 3-ball , @xmath229 is a properly embedded 1-manifold in @xmath228 that meets @xmath230 in four points , and @xmath0 is the double branched cover of @xmath227 . we will call @xmath227 a _ tangle _ , and if we choose some identification of @xmath231 with a standard model of ( @xmath232 , _ four points _ ) , then @xmath227 becomes a _ marked _ tangle . capping off @xmath230 with a 3-ball @xmath233 gives @xmath234 . then , if @xmath43 is a slope on @xmath6 , we have @xmath235 , where @xmath236 is the rational tangle in @xmath233 corresponding to the slope @xmath43 . hence @xmath237 where @xmath238 is the link in @xmath239 obtained by capping off @xmath229 with the rational tangle @xmath236 . we now give a more detailed description of the tangle @xmath227 . for @xmath166 , let @xmath240 , @xmath241 , @xmath242 , and @xmath243 . figure [ quo1 ] gives a detailed description of the branch sets in @xmath244 , @xmath245 , @xmath246 with respect to the corresponding branched covering maps . note that @xmath228 is the union of @xmath247 , and a product region @xmath248 from @xmath249 to @xmath250 which intersects the branch set @xmath229 of the cover @xmath251 in a @xmath37-braid . in fact , it is clear from our constructions that we can think of the union @xmath252 as a @xmath52-braid " in @xmath253 with two fat strands " formed by @xmath254 . see figure [ filling](a ) . by an isotopy of @xmath253 fixing @xmath250 , and which keeps @xmath253 , @xmath249 , and @xmath255 invariant , we may untwist the crossings between the two fat strands in figure [ filling](a ) so that the pair @xmath256 is as depicted in figure [ filling](b ) . the slope @xmath5 is the boundary slope of the planar surface @xmath51 , and hence the rational tangle @xmath257 appears in figure [ filling](b ) as two short horizontal arcs in @xmath233 lying entirely in @xmath258 . since @xmath259 , @xmath260 is a tangle of the form shown in figure [ filling6](a ) . recall that @xmath2 is a seifert fibred manifold with base orbifold of type @xmath261 , and is the double branched cover of @xmath262 . write @xmath263 . [ type ] @xmath264 is a montesinos link of type @xmath265 . by thurston s orbifold theorem , the seifert fibering of @xmath2 can be isotoped to be invariant under @xmath266 . hence the quotient orbifold is seifert fibered in the sense of bonahon - siebenmann , and so either @xmath264 is a montesinos link or @xmath267 is seifert fibred . from figure 6(a ) we see that @xmath264 is a 2-component link with an unknotted component and linking number @xmath268 . but the only link @xmath264 with this property such that @xmath267 is seifert fibred is the hopf link ( see @xcite ) , whose @xmath37-fold cover is @xmath269 . thus @xmath264 must be a montesinos link . since the base orbifold of @xmath2 is @xmath219 , @xmath264 has type @xmath270 ( c.f 12.d of @xcite ) . it s easy to check that any montesinos link @xmath264 of the type described in the lemma [ type ] has two components , one of which , say @xmath271 , is a trivial knot , and the other , @xmath272 , a trefoil knot . our goal is to use the particular nature of our situation to show that the branch set @xmath264 can not be a montesinos link of type @xmath265 , and thus derive a contradiction . from figure [ filling ] , we see that @xmath229 has a closed , unknotted component , which must be the component @xmath271 of the montesinos link of type @xmath265 described above . then @xmath273 , which we denote by @xmath274 . now delete @xmath271 from @xmath228 and let @xmath275 be the double branched cover of @xmath228 branched over @xmath274 . then @xmath275 is a compact , connected , orientable @xmath1-manifold with boundary a torus which can be identified with @xmath6 . in particular , if we consider @xmath3 and @xmath5 as slopes on @xmath276 , then both @xmath277 and @xmath278 are the lens space @xmath135 , since they are @xmath37-fold covers of @xmath239 branched over a trefoil knot . hence the cyclic surgery theorem of @xcite implies that @xmath275 is either a seifert fibred space or a reducible manifold . @xmath275 is not a seifert fibred space . suppose @xmath275 is a seifert fibred space , with base surface @xmath40 and @xmath279 exceptional fibres . if @xmath40 is non - orientable then @xmath275 contains a klein bottle , hence @xmath280 does also . but since non - orientable surfaces in @xmath135 are non - separating , this implies that @xmath281 , which is clearly false . thus @xmath40 is orientable . if @xmath275 is a solid torus then clearly @xmath282 implies @xmath283 ( mod @xmath1 ) , contradicting the fact that @xmath284 . thus we assume that @xmath275 is not a solid torus , and take @xmath285 to be the slope on @xmath276 of a seifert fibre . then @xmath286 is reducible @xcite so @xmath287 , and @xmath277 is a seifert fibred space with base surface @xmath40 capped off with a disk , and @xmath288 or @xmath289 exceptional fibres , according as @xmath290 or @xmath291 . since @xmath277 is a lens space and @xmath275 is nt a solid torus , we must have that @xmath40 is a disk , @xmath292 , and @xmath290 . similarly @xmath293 . in particular , without loss of generality @xmath294 in @xmath295 . the base orbifold of @xmath275 is of the form @xmath296 , with @xmath297 . then @xmath298 is the abelian group defined by generators @xmath299 and the single relation @xmath300 . suppose @xmath301 in @xmath298 . then @xmath302 is presented by the matrix @xmath303 . similarly , since @xmath304 in @xmath298 , @xmath305 is presented by @xmath306 . but the determinants of these matrices differ by @xmath307 , so they can not both be @xmath1 in absolute value . this completes the proof of the lemma . thus @xmath275 is reducible , say @xmath308 where @xmath309 and @xmath310 is closed . consideration of @xmath2 and @xmath12 shows that @xmath311 and @xmath312 , and so theorem 2 of @xcite implies that @xmath313 . it follows that any simple closed curve in @xmath276 which represents either @xmath3 or @xmath5 is isotopic to the core curve of @xmath314 . let @xmath315 denote the meridional slope of @xmath314 . then @xmath316 is a basis of @xmath295 and up to changing the sign of @xmath3 we have @xmath317 . since @xmath318 , we can find a homeomorphism between the pair @xmath319 and the tangle shown in figure [ nk20](a ) , with the @xmath5 , @xmath3 , and @xmath320 fillings shown in figures [ nk20](b ) , ( c ) and ( d ) respectively . ( we show the case @xmath321 ; the other possibility can be handled similarly . ) recall that in figure [ filling](b ) , the slope @xmath5 corresponds to the rational tangle consisting of two short `` horizontal '' arcs in the filling ball @xmath233 . it follows that under the homeomorphism from the tangle shown in figure [ nk20](a ) to @xmath319 shown in figure [ filling](b ) , the tangle @xmath260 ( resp . @xmath322 ) is sent to a rational tangle of the form shown in figure [ filling6](a ) ( resp . [ filling6](b ) ) . from figure [ nk20](d ) we see that @xmath238 is a link of three components @xmath323 , where @xmath324 is a trivial knot which bounds a disk @xmath325 disjoint from @xmath326 and which intersects @xmath230 in a single arc ; see figure [ filling6](b ) . push the arc @xmath327 with its two endpoints fixed into @xmath328 along @xmath325 , and let @xmath329 be the resulting knot ( see part ( c ) of figure [ filling6 ] ) . then there is a disk @xmath330 ( which is a subdisk of @xmath325 ) satisfying the following conditions : * @xmath331 . * @xmath330 is disjoint from @xmath326 . * the interior of @xmath330 is disjoint from @xmath233 . perusal of figure [ filling6 ] ( c ) shows that the following condition is also achievable . * @xmath332 has a single arc component , and this arc component connects the two boundary components of @xmath250 and is outermost in @xmath330 amongst the components of @xmath333 . among all disks in @xmath239 which satisfy conditions ( 1)(4 ) , we may assume that @xmath330 has been chosen so that * @xmath332 has the minimal number of components . [ parallel ] suppose that @xmath332 has circle components . then each such circle separates @xmath334 from @xmath335 in @xmath250 . let @xmath336 be a circle component of @xmath332 . then @xmath336 is essential in @xmath337 , for if it bounds a disk @xmath338 in @xmath337 , then an innermost component of @xmath339 will bound a disk @xmath340 . we can surger @xmath330 using @xmath341 to get a new disk satisfying conditions ( 1)(4 ) above , but with fewer components of intersection with @xmath250 than @xmath330 , contrary to assumption ( 5 ) . next since the arc component of @xmath332 connects the two boundary components of @xmath250 , @xmath336 can not separate the two boundary components of @xmath250 from each other . lastly suppose that @xmath336 separates the two points of @xmath342 . then @xmath336 is isotopic to a meridian curve of @xmath326 in @xmath239 . but this is impossible since @xmath336 also bounds a disk in @xmath330 and is therefore null - homologous in @xmath343 . the claim follows . it follows from claim [ parallel ] that there are disjoint arcs in @xmath250 , one , say @xmath344 , which connects the two points of @xmath345 and is disjoint from @xmath330 , and @xmath346 the other . hence we obtain a `` 2-bridge link '' of two components one fat , one thin in @xmath239 by capping off the `` @xmath52-braid '' in @xmath253 with @xmath344 and @xmath347 in @xmath348 and with @xmath349 and @xmath350 in the @xmath1-ball @xmath351 ( see figure [ filling7](a ) ) . furthermore , since the disk @xmath330 gives a disk bounded by the `` fat knot '' which is disjoint from the `` thin knot '' , the link is a trivial link . now it follows from the standard presentation of a @xmath37-bridge link as a @xmath52-plat ( see 12.b of @xcite ) , that there is an isotopy of @xmath253 , fixed on the ends @xmath352 and on the two fat strands , taking the `` 4-braid '' to one of the form shown in figure [ filling7](b ) . hence @xmath227 has the form shown in figure [ filling8](a ) . the filling rational tangle @xmath353 is of the form shown in figure [ filling8](b ) . since the component @xmath354 of @xmath355 has to be a trefoil , there are only two possibilities for the number of twists in @xmath260 ; see figure [ filling8b ] . the two corresponding possibilities for @xmath264 are shown in figure [ filling9 ] . but these are montesinos links of the form @xmath356 and @xmath357 , respectively . this final contradiction completes the proof of theorem [ rf ] under the assumptions of case ( a ) of lemma [ gluing ] . in this case we choose an involution @xmath192 on @xmath136 as shown in figure [ inv3 ] . then @xmath358 , @xmath359 ( @xmath360 ) , and the restriction of @xmath192 on @xmath138 extends to an involution of @xmath137 whose fixed point set is a core circle of this solid torus . thus we obtain an involution @xmath192 on @xmath99 . the quotient of @xmath137 by @xmath192 is a solid torus @xmath361 whose core circle is the branch set . further , @xmath362 is a longitudinal annulus of @xmath361 . the quotient of @xmath136 by @xmath192 is also solid torus @xmath363 in which @xmath364 is a longitudinal annulus . figure [ inv3 ] depicts @xmath363 and its branch set . it follows that the pair @xmath365 is identical to the analogous pair in section [ case a ] ( see figure [ quo1 ] ) . next we take @xmath198 to be the same involution on @xmath100 as that used in section [ case a ] . an argument similar to the one used in that section shows that @xmath192 and @xmath198 can be pieced together to form an involution @xmath215 on @xmath0 . from the previous paragraph we see that the quotient @xmath366 and its branch set are the same as those in section [ case a ] . hence the argument of that section can be used from here on to obtain a contradiction . this completes the proof of theorem [ rf ] in case ( b ) .

we show that the distance between a finite filling slope and a reducible filling slope on the boundary of a hyperbolic knot manifold is at most one . v c u _ 2sl(2,c ) ps . psl(2,c ) _ _ _ let @xmath0 be a knot manifold , i.e. a connected , compact , orientable @xmath1-manifold whose boundary is a torus . a knot manifold is said to be _ hyperbolic _ if its interior admits a complete hyperbolic metric of finite volume . let @xmath2 denote the manifold obtained by dehn filling @xmath0 with slope @xmath3 and let @xmath4 denote the distance between two slopes @xmath3 and @xmath5 on @xmath6 . when @xmath0 is hyperbolic but @xmath2 is nt , we call the corresponding filling ( slope ) an _ exceptional _ filling ( slope ) . perelman s recent proof of thurston s geometrisation conjecture implies that a filling is exceptional if and only if it is either reducible , toroidal , or seifert fibred . these include all manifolds whose fundamental groups are either cyclic , finite , or very small ( i.e. contain no non - abelian free subgroup ) . sharp upper bounds on the distance between exceptional filling slopes of various types have been established in many cases , including : @xmath7 : : @xmath8 if both @xmath3 and @xmath5 are reducible filling slopes @xcite @xmath7 : : @xmath8 if both @xmath3 and @xmath5 are cyclic filling slopes @xcite @xmath7 : : @xmath8 if @xmath3 is a cyclic filling slope and @xmath5 is a reducible filling slope @xcite @xmath7 : : @xmath9 if @xmath3 is a cyclic filling slope and @xmath5 is a finite filling slope @xcite @xmath7 : : @xmath9 if @xmath3 is a reducible filling slope and @xmath5 is a very small filling slope @xcite @xmath7 : : @xmath10 if both @xmath3 and @xmath5 are finite filling slopes @xcite @xmath7 : : @xmath10 if @xmath3 is a reducible filling slope and @xmath5 is a toroidal filling slope @xcite @xcite @xmath7 : : @xmath11 if both @xmath3 and @xmath5 are toroidal filling slopes @xcite in this paper we give the sharp upper bound on the distance between a reducible filling slope and finite filling slope . [ rf ] let @xmath0 be a hyperbolic knot manifold . if @xmath2 has a finite fundamental group and @xmath12 is a reducible manifold , then @xmath8 . example 7.8 of @xcite describes a hyperbolic knot manifold @xmath0 and slopes @xmath13 on @xmath6 such that @xmath12 is reducible , @xmath14 is finite cyclic , @xmath15 is finite non - cyclic , and @xmath16 . in fact there are hyperbolic knot manifolds with reducible and finite fillings for every finite type : cyclic , dihedral , tetrahedral , octahedral and icosahedral , in the terminology of [ bz1 ] ; see [ k ] . a significant reduction of theorem [ rf ] was obtained in @xcite . before describing this work , we need to introduce some notation and terminology . denote the octahedral group by @xmath17 , the binary octahedral group by @xmath18 , and let @xmath19 be the usual surjection . we say that @xmath3 is an _ @xmath20-type _ filling slope if @xmath21 for some integer @xmath22 coprime to @xmath23 and the image of @xmath24 under the composition @xmath25 is @xmath26 . clearly @xmath27 . it is shown in 3 of @xcite that @xmath28 is independent of the choice of isomorphism @xmath29 . a lens space whose fundamental group has order @xmath30 will be denoted by @xmath31 . [ almost ] let @xmath0 be a hyperbolic knot manifold . if @xmath2 has a finite fundamental group and @xmath12 is a reducible manifold , then @xmath9 . further , if @xmath32 , then @xmath33 , @xmath34 , and @xmath3 is an @xmath20-type filling slope for some @xmath35 . this is theorem 1.1 of @xcite except that that theorem only claimed that @xmath3 is an @xmath20-type filling slope for some @xmath27 . since @xmath36 contains @xmath37-torsion , the argument of the last paragraph of the proof of theorem 2.3 of @xcite ( see page 1026 of that article ) shows that @xmath38 . thus , in order to prove theorem [ rf ] , we are reduced to considering the case where @xmath33 , @xmath34 , and @xmath3 is an @xmath20 type filling slope for some @xmath38 . we do this below . we also assume that @xmath39 in order to derive a contradiction . an _ essential surface _ in @xmath0 is a compact , connected , orientable , incompressible , and non - boundary parallel , properly embedded @xmath37-submanifold of @xmath0 . a slope @xmath5 on @xmath6 is called a _ boundary slope _ if there is an essential surface @xmath40 in @xmath0 with non - empty boundary of the given slope @xmath5 . a boundary slope @xmath5 is called _ strict _ if there is an essential surface @xmath40 in @xmath0 of boundary slope @xmath5 such that @xmath40 is neither a fiber nor a semi - fiber . when @xmath0 has a closed essential surface @xmath41 , let @xmath42 be the set of slopes @xmath43 on @xmath6 such that @xmath41 is compressible in @xmath44 . a slope @xmath45 is called a _ singular slope _ for @xmath41 if @xmath46 and @xmath47 for each @xmath48 . since @xmath49 is finite , the first betti number of @xmath0 is @xmath50 , @xmath2 is irreducible by @xcite , and neither @xmath3 nor @xmath5 is a singular slope by theorem 1.5 of @xcite . as @xmath12 is reducible , @xmath5 is a boundary slope . further , by proposition 3.3 of @xcite we may assume that up to isotopy , there is a unique essential surface @xmath51 in @xmath0 with boundary slope @xmath5 . this surface is necessarily planar . it is also separating as @xmath12 is a rational homology @xmath1-sphere , and so has an even number of boundary components . this number is at least @xmath52 since @xmath0 is hyperbolic . [ o2 ] if @xmath39 , then @xmath3 is of type @xmath53 . according to theorem [ rf ] , we must show that @xmath3 does not have type @xmath20 for @xmath54 . let @xmath55 be the unique non - trivial curve . ( we refer the reader to 6 of @xcite for notation , background results , and further references on @xmath56 character varieties . ) since @xmath5 is not a singular slope , proposition 4.10 of @xcite implies that the regular function @xmath57 , has a pole at each ideal point of @xmath58 . ( we have identified @xmath59 with its image in @xmath60 under the hurewicz homomorphism . ) in particular , the culler - shalen seminorm @xmath61 is non - zero . hence there is a non - zero integer @xmath62 such that for all @xmath63 we have @xmath64 where @xmath65 is the algebraic intersection number of the two classes ( c.f . identity 6.1.2 of @xcite ) . fix a class @xmath66 satisfying @xmath67 , so in particular @xmath68 . we can always find such a @xmath69 so that @xmath70 according to proposition 8.1 of @xcite , if @xmath71 is a slope satisfying @xmath72 ( mod @xmath28 ) , then @xmath73 . hence @xmath74 . consideration of @xmath75 and @xmath76 then shows that @xmath77 . if @xmath39 , then @xmath51 has exactly four boundary components . we continue to use the notation developed in the proof of the previous lemma . by case 1 of 8 of @xcite we have @xmath78 and so @xmath62 is either @xmath37 or @xmath1 . we claim that @xmath79 . to prove this , we shall suppose that @xmath80 and derive a contradiction . it follows from the method of proof of lemma 5.6 of @xcite that @xmath21 has exactly two irreducible characters with values in @xmath56 corresponding to a representation @xmath81 with image @xmath17 and a representation @xmath82 with image @xmath83 ( the dihedral group of order 6 ) . further , @xmath82 is the composition of @xmath81 with the quotient of @xmath17 by its unique normal subgroup isomorphic to @xmath84 . it follows from proposition 7.6 of @xcite that if @xmath80 , the characters of @xmath81 and @xmath82 lie on @xmath58 and provide jumps in the multiplicity of zero of @xmath85 over @xmath86 . lemma 4.1 of @xcite then implies that both @xmath87 and @xmath88 are non - trivial . by the previous lemma , @xmath3 is a slope of type @xmath53 . thus @xmath87 has order @xmath37 . since @xmath89 and @xmath82 factors through @xmath81 , @xmath88 also has order 2 . next we claim that @xmath69 lies in the kernel of the composition of @xmath82 with the abelianisation @xmath90 . to see this , note first that @xmath5 is non - zero in @xmath91 since @xmath92 . thus exactly one of @xmath69 and @xmath93 is zero in @xmath94 . ( recall that duality implies that the image of @xmath95 in @xmath94 is @xmath96 . ) since @xmath5 lies in the kernel of @xmath82 , it follows that @xmath88 is sent to zero in @xmath97 . but then @xmath88 has order @xmath1 in @xmath83 , contrary to what we deduced in the previous paragraph . thus @xmath79 . now apply the argument at the end of the proof of proposition 6.6 of @xcite to see that @xmath98 . hence @xmath51 has four boundary components . the four - punctured @xmath37-sphere @xmath51 cuts @xmath0 into two components @xmath99 and @xmath100 . if @xmath101 denotes the copy of @xmath51 in @xmath102 then @xmath0 is the union of @xmath99 and @xmath100 with @xmath103 and @xmath104 identified by a homeomorphism @xmath105 . the boundary of @xmath51 cuts @xmath6 into four annuli @xmath106 listed in the order they appear around @xmath6 , where @xmath107 are contained in @xmath99 and @xmath108 are contained in @xmath100 . the arguments given in the proof of lemma 4.5 of @xcite show that for each @xmath109 , the two annuli @xmath110 and @xmath111 in @xmath112 are unknotted and unlinked . this means that there is a neighbourhood of @xmath113 in @xmath112 which is homeomorphic to @xmath114 , where @xmath115 is a thrice - punctured @xmath37-sphere and @xmath116 is the interval @xmath117 $ ] , such that @xmath118 , and the exterior of @xmath114 in @xmath112 is a solid torus @xmath119 . we label the boundary components of @xmath115 as @xmath120 ( @xmath121 ) so that @xmath122 for @xmath123 . let @xmath124 be the two sphere in @xmath12 obtained from @xmath51 by capping off @xmath125 with four meridian disks from the filling solid torus @xmath126 . these disks cut @xmath126 into four @xmath37-handles @xmath127 ( @xmath128 ) such that the attaching annulus of @xmath127 is @xmath129 for each @xmath130 . let @xmath131 be the manifold obtained by attaching @xmath127 to @xmath112 along @xmath129 ( @xmath123 ) . then @xmath132 is a once - punctured @xmath133 and @xmath134 a once - punctured @xmath135 . it follows from the description above that @xmath99 is obtained from @xmath136 and @xmath137 by identifying @xmath138 with an annulus @xmath139 in @xmath140 whose core curve is a @xmath141 curve in @xmath140 . we can assume that @xmath139 is invariant under the standard involution of @xmath137 whose fixed point set is a pair of arcs contained in disjoint meridian disks of @xmath137 . note that the two boundary components of @xmath139 are interchanged under this map . similarly , @xmath100 is obtained from @xmath142 and @xmath143 by identifying @xmath144 with an annulus @xmath145 in @xmath146 whose core curve is a @xmath147 curve in @xmath146 . again we can suppose that @xmath145 is invariant under the standard involution of @xmath143 which interchanges the two boundary components of @xmath145 . see figures [ inv1 ] and [ inv2 ] . the map @xmath148 is constrained in several ways by our hypotheses . for instance , the fact that @xmath6 is connected implies that @xmath149 for some @xmath150 . other conditions are imposed by the homology of @xmath0 . [ gluing ] we can assume that either + @xmath151 @xmath152 , and @xmath153 , or + @xmath154 @xmath155 and @xmath156 . without loss of generality we can suppose that @xmath157 . hence , as @xmath6 is connected , one of the following four possibilities arises : * @xmath158 and @xmath153 . * @xmath159 and @xmath156 . * @xmath160 and @xmath161 , or * @xmath162 and @xmath153 . let @xmath163 be represented , respectively , by @xmath164 , @xmath165 , and a core of @xmath119 , @xmath166 . then @xmath167 is the abelian group generated by @xmath168 , subject to the relation @xmath169 since @xmath170 , we may orient @xmath171 , @xmath172 so that in @xmath173 we have @xmath174 . then @xmath173 is the quotient of @xmath175 by this relation together with the additional relations corresponding to the four possible gluings : * @xmath176 , @xmath177 * @xmath178 , @xmath179 * @xmath180 , @xmath176 * @xmath181 , @xmath177 taking @xmath182 coefficients , equation ( i ) allows us to eliminate @xmath183 , while ( ii ) gives @xmath184 . hence @xmath185 , where the @xmath182 summand is generated by @xmath186 and @xmath187 is defined by generators @xmath188 , and relations @xmath184 plus those listed in ( a ) , ( b ) , ( c ) and ( d ) above . thus @xmath189 in cases ( a ) and ( b ) , and @xmath190 in cases ( c ) and ( d ) . since @xmath191 , we conclude that cases ( c ) and ( d ) are impossible .

in the last years many papers have been devoted to experimental and theoretical studies of bose - einstein interference effects @xcite in multiparticle production . it has been argued that these studies may allow for the reconstruction of space - time development of the interactions . in particular , different possibilities of implementing interference effects into monte carlo generators used for high energy hadroproduction processes were discussed . in this note we add some points to this discussion . we present in detail some aspects of the weight method of implementing be effect in the mc generators . in particular , we try to establish to what extent one may reconstruct the two - particle weight function ( related to the wigner function ) from the data on be effect . for this purpose we use the data on multiparticle production with highest statistics available - the hadronic decays of @xmath0 s produced in @xmath1 collisions . a short summary of various methods of implementing interference effects into monte carlo generators is presented in the next section . in the third section we discuss the data from different lep experiments on two - particle correlations from @xmath0 hadronic decays which were used for analyzing the bose - einstein effect . section 4 is devoted to the analysis of data in terms of the weight model . in particular , various choices of two - particle weight factors used in this method are compared . last section contains some conclusions and outlook for further investigations . the standard discussion of the be effect in multiparticle production @xcite starts from the classical space - time source emitting identical bosons with known momenta . thus the most natural procedure is to treat the original monte carlo generator as the model for the source and to symmetrize the final state wave function @xcite . this may be done in a more proper way using the formalism of wigner functions @xcite . in any case , however , the monte carlo generator should yield both the momenta of produced particles and the space - time coordinates of their creation ( or last interaction ) points . even if we avoid troubles with the uncertainty principle by using the wigner function approach , such a generator seems reliable only for heavy ion collisions . it has been constructed also for the @xmath2 collisions @xcite , but localizing the hadron creation point in the parton - based monte carlo program for lepton and/or hadron collisions is a rather arbitrary procedure , and it is hard to say what does one really test comparing such a model with data . it seems to be the best procedure to take into account the interference effects before generating events . unfortunately , this was done till now only for the jetset generator for a single lund string @xcite , and a generalization for multi - string processes is not obvious . no similar modifications were yet proposed for other generators . the most popular approach , applied since years to the description of be effect in various processes , is to shift the final state momenta of events generated by the pythia/ + jetset generators @xcite . the prescription for a shift is such as to reproduce the experimentallly observed enhancement in the ratio @xmath3 which is a function of a single invariant variable @xmath4 . the value of this function is close to one for the default jetset / pythia generator . one parametrizes often this ratio by @xmath5 where @xmath6 and @xmath7 are parameters interpreted as the source radius and `` incoherence strength '' , respectively . after performing the shifts , all the cm 3-momenta of final state particles are rescaled to restore the original energy . in more recent versions of the procedure @xcite `` local rescaling '' is used instead of the global one . in any case , each event is modified and the resulting generated sample exhibits now the `` be enhancement '' : the ratio ( [ eq : ratio ] ) is no longer close to one , and may be parametrized as in ( [ eq : factor ] ) . there is no theoretical justification for this procedure , so it should be regarded as an imitation rather than implementation of the be effect . its success or failure in describing data is the only relevant feature . unfortunately , whereas the method is very useful for the description of two - particle inclusive spectra , it fails to reproduce ( with the same fit parameters @xmath6 and @xmath7 ) the three - particle spectra @xcite and the semi - inclusive data @xcite . this could be certainly cured , e.g. , by modifying the shifting procedure and fitting the parameters separately for each semi - inclusive sample of data . however , the fitted values of parameters needed in the input factor ( [ eq : factor ] ) used to calculate shifts are quite different from the values one would get fitting the resulting ratio ( [ eq : ratio ] ) to the same form @xcite . this was shown recently in a much more detailed study @xcite . thus it seems to be very difficult to learn something reliable on the space - time structure of the source from the values of fit parameters in this procedure . all this has led to the revival of weight methods , known for quite a long time @xcite , but plagued with many practical problems . the method is clearly justified within the formalism of the wigner functions , which allows to represent ( after some simplifying assumptions ) any distribution with the be effect built in as a product of the original distribution ( without the be effect ) and the weight factor , depending on the final state momenta @xcite . with an extra assumption of factorization in momentum space , we may write the weight factor for the final state with @xmath8 identical bosons as @xmath9 where the sum extends over all permutations @xmath10 of @xmath8 elements , and @xmath11 is a two - particle weight factor reflecting the effective source size . a commonly used simple parametrization of this factor for a lorentz symmetric source is @xmath12 , \label{eq : wf}\ ] ] the only free parameter is now @xmath13 , representing the inverse of the effective source size . in fact , the full weight given to each event should be a product of factors ( [ eq : weight ] ) calculated for all kinds of bosons ; in practice , pions of all signs should be taken into account . only direct pions and the decay products of @xmath14 and @xmath15 should be taken into account , since for other pairs much bigger @xmath6 should be used , resulting in negligible contributions . the main problem of the weight methods is that weights do change not only the bose - einstein ratio ( [ eq : ratio ] ) , but also many other distributions . thus with the default values of free parameters ( fitted to the data without weights ) we find inevitably some discrepancies with data after introducing weights . we want to make clear that this can not be taken as a flaw of the weight method . there is no measurable world `` without the be effect '' , and it makes not much sense to ask , if this effect changes e.g. the multiplicity distributions . if any model is compared to the data without taking the be effect into account , the fitted values of its free parameters are simply not correct . they should be refitted with weights , and then the weights recalculated in an iterative procedure . this , however , may be a rather tedious task . therefore we use a simple rescaling method proposed by jadach and zalewski @xcite . instead of refitting the free parameters of the mc generator , we rescale the be weights ( calculated according to the procedure outlined above ) with a simple factor @xmath16 , where @xmath8 is the global multiplicity of `` direct '' pions , and @xmath17 and @xmath18 are fit parameters . their values are fitted to minimize @xmath19 ^ 2/n^0(n ) \label{eq : chi2}\ ] ] where @xmath20 is the number of events for the multiplicity @xmath8 without weights , and @xmath21 is the weighted number of events . this rescaling restores the original multiplicity distribution @xcite . in addition , the single longitudinal and transverse momentum spectra are also restored by this rescaling @xcite . obviously , for a more detailed analysis of the final states , single rescaling may be not enough . e.g. , since different parameters govern the average number of jets and the average multiplicity of a single jet , both should be rescaled separately to avoid discrepancy with data . let us stress once again that such problems arise due to the use of generators with improperly fitted free parameters , and do not suggest any flaw of the weight method . another problem is that our formula for weights ( [ eq : weight ] ) is derived using some approximations , which are rather difficult to control @xcite . we can justify them only _ a posteriori _ from the phenomenological successes of the weight method . last but not least , the main practical difficulty with formula ( [ eq : weight ] ) is the factorial increase of the number of terms in the sum with increasing multiplicity of identical pions @xmath8 . for high energies , when @xmath8 often exceeds 20 , a straightforward application of formula ( [ eq : weight ] ) is impractical @xcite , and some authors @xcite replaced it with simpler expresssions , motivated by some models . it is , however , rather difficult to estimate their reliability . we have recently proposed two ways of dealing with this problem . one method consists of a truncation of the sum ( 3 ) up to terms , for which the permutation @xmath22 moves no more than 5 particles from their places @xcite . however , it is difficult to claim a priori that such a truncation does not change the results which would be obtained using the full series ( 2 ) . therefore a second way of an approximate calculation of the sum ( 2 ) was proposed @xcite . since this sum , called a permanent of a matrix built from weight factors @xmath23 , is quite familiar in field theory , one may use a known integral representation and approximate the integral by the saddle point method . however , this method is reliable only if in each row ( and column ) of the matrix there is at least one non - diagonal element significantly different from zero . thus the prescription should not be applied to the full events , but to the clusters , in which each momentum is not far from at least one other momentum . the full weight is then a product of weights calculated for clusters , in which the full event is divided . the considerations presented above suggested the necessity of combining these two methods . after dividing the final state momenta of identical particles into clusters , we used for small clusters exact formulae presented in @xcite . for large clusters ( with more than five particles ) we compared two approximations ( truncated series and the integral representation ) to estimate their reliability and the sensitivity of the final results to the method . obviously , the results depend also on the clustering algorithm : if we restrict each cluster to particles very close in momentum space , the neglected contributions to the sum ( [ eq : weight ] ) from permutations exchanging pions from different clusters may be non - negligible , and if the cluster definition is very loose , the saddle point approximation may be unreliable . this was then also checked to optimize the algorithm used . we found that the truncated series approximation was sufficient in all cases we checked on @xcite . our method was already applied to the analysis of @xmath24 production @xcite . extremely high statistics collected in lep for the hadronic decays of @xmath0-s produced in the @xmath1 collisions allowed to investigate in detail many interesting effects . in particular , the interference effects due to the bose - einstein statistics for pions were analyzed in several experiments . the notorious difficulty in measuring the bose - einstein interference effects ( be effects ) in the multiparticle production is the proper choice of reference sample . in the early investigations the ratio of numbers of `` like - to - unlike '' charged pion pairs was analyzed as a function of three- or four - momentum difference squared @xmath25d^3p_1 d^3p_2}{\int\rho_2^{+-}(p_1,p_2)\delta[(p_1-p2)^2+q^2]d^3p_1d^3p_2 } \label{eq:6}\ ] ] obviously , the denominator has breit - wigner peaks around the values of @xmath26 corresponding to masses of resonances in the @xmath27system ( and other peaks due to the maxima in mass spectra from 3-pion resonances ) which are absent in the numerator . to estimate properly the be effects one should subtract these maxima , or to exclude the `` resonance regions '' from the @xmath26 range used in fitting @xmath28 to the chosen function . therefore recently a more common choice for the denominator was the `` uncorrelated background '' formed e.g. by choosing pairs of `` like sign '' pions from different events , which led to the definition presented in the former section ( [ eq : ratio ] ) . here the main problem comes from neglecting the energy - momentum conservation effects ( present in the numerator and absent in the denominator ) . however , for high energies and restricted range of momenta ( e.g. the `` central region '' , often used for the analysis ) such effects are expected to be rather small . this method is easy to apply for hadronic or heavy ion collisions , where the initial momenta form the natural symmetry axis in the cm frame . for @xmath0 decays the typical events are not aligned with the momenta of the initial @xmath1 pair . thus the momenta chosen from different events should be rotated to the same symmetry axis before calculating @xmath26 . unfortunately , such a procedure is not well - defined : using sphericity , thrust or other variables one obtains different values of rotation angles . moreover , the three- and many - jet events do not have well - defined symmetry axis , and limiting the analysis to the two - jet events would be rather arbitrary ( and dependent on the jet definition ) . * fig.1 . * _ a ) the be ratio @xmath28 ( 6 ) from the opal data ( black points ) and from the jetset mc without be effect ( open points ) ; b ) the double ratio @xmath29 ( 7 ) from the same data . solid lines are fits to the form ( 8) [ 25 ] . _ therefore the best strategy seems to be using monte carlo generators , which are rather reliable for the process under discussion . instead of analyzing the be ratio @xmath28 one considers the `` double ratio '' , i.e. the ratio of @xmath30 given by the data and @xmath31 computed from the mc generated events @xmath32 analogous `` double ratio '' has been defined also for the first definition of the `` be ratio '' ( [ eq : ratio ] ) @xcite . the results obtained for two double ratios are inconsistent . in the following we use only the definition ( [ eq:7 ] ) , preferred recently by the experimental groups @xcite . the data with largest statistics has been presented by the opal group both for @xmath29 and for @xmath28 . they compared the parameter values from the fits ( with resonance regions excluded ) to the function @xmath33(1+\alpha x^2 ) . \label{eq:8}\ ] ] the data ( based on 3.6 milion of events ) were shown for @xmath34 and for @xmath35 @xcite . we remind here in fig.1 the data and fits for @xmath36 and @xmath37 . the values of @xmath7 and r differ quite significantly , as shown in table i. table i. fits to opal data . [ cols="<,^,^,^",options="header " , ] @xmath13 is not a best measure of `` width in momentum space '' when one compares different shapes of the weight factor . it seems more natural to use @xmath38 , which is just the average value of @xmath4 for a given weight factor @xmath39 if we define @xmath40 as the `` effective source size '' we find a close relation between the fitted values of @xmath6 and the input values of @xmath41 . the ratio @xmath42 , quoted in the last column of table ii , is in the range @xmath43 for almost all values of @xmath13 and all shapes of the weight factor . the first obvious conclusion from fig . 4 is that the fits to the two experimental sets of data are strongly different . this is partly due to the gamow correction for the effect of electromagnetic final state interactions , which was used by opal and neglected by aleph . since it has been recently argued that this correction badly overestimates the effect @xcite , we have shown also an estimate for the opal point without gamow correction ( obtained using the values for correction quoted in ref . now the two data points are much closer , but still they differ significantly . the values resulting from our generated samples cover quite a wide range both in @xmath7 and r. certainly it is possible to reproduce any of the experimental values by a suitable choice of the form and free parameters of our weight factors . however , we do not think it would give a valuable information on the `` proper '' choice of the weight factor reflecting the `` real '' space - time structure of the source . there are a few reasons for such scepticism . first , as noted in the previous section , the shape of `` experimental '' @xmath29 strongly depends on the quality of `` reference mc '' . since we know that already at @xmath44 the influence of ( poorly described ) @xmath45 and @xmath46 contributions distorts the shape , the fitted values of @xmath6 around @xmath47 are not very reliable . the situation is even less clear if one fits wider range of q using a more elaborate ansatz for @xmath29 ( e.g. ( [ eq:8 ] ) ) . here the choice of `` cut out resonance region '' may influence quite significantly the fit results . moreover , the method of implementing the be effect may influence the resonance contribution . for our method the absence of peaks or bumps in the double ratio for `` mc with weights '' over `` mc without weights '' ( as seen , e.g. , in fig . 3 ) suggests that this is not the case ( the oscillations shown in fig . 2 ) of ref . @xcite may result from lower statistics ) . this should be also checked for any other method . second , the choice of `` direct '' pions affected by the be effects described in section 2 ( although the same in our method and in the sjoestrand s momentum shift method ) is by no means unique . in fact , even for the fastest - decaying resonances the effective `` source radius '' for the decay products should not be exactly the same as for the `` real direct pions '' . thus the choice of a single value of @xmath13 in our weight factor is certainly an oversimplification . the total exclusion of the decay products of long - living resonances is also an approximation : some of them may be born quite close to the collision point and contribute to the visible be effect . the selection and treatment of `` direct '' pions included in calculating weights ( or subject to the momentum shift in the sjestrand s method ) influences strongly the resulting value of @xmath7 . third , the standard fitting method of be ratios or double ratios is also a subject of criticism @xcite . more plausible methods suggest bigger uncertainties of the fit parameters . the situation would not improve if we add the other published data , which used much lower statistics @xcite or different form of the fitted function @xcite . one may shortly summarize that it is too early to deduce details of the source space - time structure from the existing data , even if we assume the applicability of all the assumptions used in formulating the weight method . another interesting feature is the relative stability of our results with respect to the detailed shape of two - particle weight factor . the fitted values of @xmath7 fall in the range of values 0.2 - 0.5 for all the functions considered . they are highest for the step function , lower for `` diffuse step function '' , still lower for a gaussian and lowest for the exponent . one may summarize that for the same `` half width '' of the weight factor function one gets higher value of @xmath7 if the function stays longer near the value of 1 at small q. as already noted , @xmath7 depends much stronger on the percentage of pions counted as `` direct '' . the values of @xmath7 below 1 reflect mainly the percentage of direct like - sign pion pairs , which was already observed when using sjstrand s method of be effect implementation @xcite . a new result is the observed relative insensitivity of the results on the oscillations in the two - particle weight factor . in fact , the oscillation half - period serves as an effective range of correlations if it is smaller than @xmath13 . therefore @xmath41 is almost the same for all the values of @xmath13 quoted in the table ii . the non - positive oscillating values of weight factor for larger q do not result in the values of @xmath29 oscillating around 1 , as one could naively expect ; averaging over many pairs in each event and over many events kills any trace of oscillations . this is quite important , as many simple forms of weight factor in space - time ( e.g. the step function ) results in oscillating form in momentum space . on the other hand , there is an obvious dependence of fitted values of r on the parameter @xmath13 ( or @xmath41 ) , which determine how fast the weight factor decreases with increasing q. @xmath42 has quite similar values for various shapes of the weight factors and various values of @xmath13 . thus in our method r reflects in some sense the `` source size '' , as expected . as already noted , this is true also for the oscillations in momentum space . increasing @xmath13 one increases also fitted values of @xmath7 , but this effect is weaker . we have analyzed the data on be effect in multihadron states obtained from @xmath0 decays within the framework of the weight method of implementing the effect . we show that the resonance contributions are not satisfactorily described by the standard mc generators , which makes the analysis of `` double ratio '' data quite difficult . in particular , the choice of the `` proper '' two particle weight factor which would describe the data best is obviously dependent on the way the data are processed . thus one should improve ( if possible ) the quality of mc generators before drawing any serious conclusion on the agreement or disagreement between the models and data on the be effect . the alternative is to elaborate better methods of preparing the `` reference sample '' using only the like - sign pairs , which are much less affected by the resonance effects . on the other hand , we found that the analysis makes no great difference between the positively defined and oscillating weight factors in momentum space , provided they correspond to similar `` half - width '' . this means that the results are not too strongly dependent on the `` sharpness of the source boundary '' in space - time ; one may hope to recover the proper `` source size '' in our method . let us stress that the analysis presented in this paper is just the first step : we do not discuss the anisotropy of source nor the time dependence reflected in the be effect . also , we do not consider here the possibilities of comparing the effect for selected classes of events ( defined i.e. by multiplicity , by event shape parameters or by some special triggers ) . in our opinion , the weight method is well suited to discuss these subjects and we hope to consider them in near future . the authors are grateful to a. biaas for useful remarks . the financial support from kbn grants no 2 p03b 086 14 and no 2 p03b 010 15 are acknowledged . a. gagatek provided patient assistance with figure preparations . 99 r. hanbury - 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we discuss the bose - einstein interference effect in multiparticle production . after a short review of various methods of implementation of this effect into monte carlo generators the weight method is presented in more detail and used to analyze the data for hadronic @xmath0 decays . in particular , we consider the possibility of deducing the two - particle weight factor from the experimental data . 23.0 cm 16.0 cm -1.0 cm 0.0 cm 0.0 cm k. fiakowski , r. wit _ m. smoluchowski institute of physics + jagellonian university + 30 - 059 krakw , ul.reymonta 4 , poland _ pacs : 13.85.-t , 13.90.+i + _ keywords : _ monte carlo , bose - einstein correlations , @xmath0 decay + august , 1999 +

Woman arrested after posting photos of allegedly abused porch dog wants answers Image 1 of / 4 Caption Close Image 1 of 4 This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) Image 2 of 4 This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) Image 3 of 4 This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) Image 4 of 4 This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) This dog, allegedly left outside on a balcony for a week, was the subject of Facebook posts that led to a northwest Harris County woman's arrest Nov. 3, 2015. (Via Facebook) Woman arrested after posting photos of allegedly abused porch dog wants answers 1 / 4 Back to Gallery It's been two weeks since Amber Cammack noticed a dog that she said had its mouth tied shut and never seemed to leave a neighboring balcony at her northwest Harris County condominium. After Cammack posted photos of the dog on Facebook, concern over its welfare went viral. She ended up getting arrested when the Harris County Sheriff's Office received complaints of harassment from other residents. She spent a night in the Harris County Jail at 1200 Baker St., triggering a protest Thursday afternoon in front of that lock-up. Cammack was joined by her attorney, Randall Kallinen, and about 25 supporters carrying placards decrying animal cruelty and supporting "porch pooch." Authorities, however, say a veterinarian and an animal protection investigator have examined the pit bull mix named June, who reportedly is in good health and is now back with her owner, rather than the condo dweller who had been caring for her. Harris County District Attorney Devon Anderson, acknowledging that the photos on Facebook painted an unhappy picture, said during a news conference that the story had a happy ending. No charges of animal cruelty would be filed in the case, she said, because there was no evidence to support it. "The pictures are bad," Anderson said. "I'm a dog owner. You'll never see my dog with a muzzle, or stuck on a porch with a diaper. Nobody in this office condones that or thinks that person was properly caring for that dog." Anderson's office also declined to file formal charges against Cammack, who on Thursday disputed the story's happy ending and called for an apology from Harris County Sheriff Ron Hickman for her arrest. She said the reason she posted photos on Facebook was because she tried every other avenue to report what she thought was inhumane treatment but got no response. Once the posts got widely distributed, Cammack said, she got a call from the sheriff on Monday, advising her that she would be arrested if she didn't remove the posts. "When the sheriff himself calls you and threatens you with arrest, that is an extreme chill on your right to freedom of expression," Kallinen said in a statement. Ryan Sullivan, a spokesman for the sheriff's office, wrote in an email that deputies responded to a complaint Monday from the Villas of Westador condominium regarding "continuous harassment of the residents." Sullivan said deputies took multiple statements alleging that Cammack "had repeatedly published allegations of animal abuse on social media sites, including their personal information, their physical locations, security access information, personal vehicle information, and more." Deputies contacted the district attorney's office, which it says initially accepted the misdemeanor charges for repeated electronic harassment. Cammack spoke with the sheriff and other members of the command staff. Sullivan said. "After a lengthy discussion, Sheriff Hickman advised Ms. Cammack that repeated posting of personal information to social media could result in arrest should the District Attorney move to file charges," the statement said. Cammack wasn't satisfied with the outcome Thursday. She questioned whether an investigator with the Society for the Prevention of Cruelty to Animals had examined the dog. Christina Paaske, a representative of the rescue group Pitbulls of Houston, who also spoke at the news conference, said she had examined the dog in a private meeting with the owner at the suggestion of sheriff's deputies. Paaske said the dog couldn't apply pressure to her rear left leg, but Anderson said the veterinarian's report attributed that to a limp from an old injury. Paaske also said the dog was "emaciated" but, in spite of her condition, was "kissing everyone and wagging her tail." ||||| I'M JENNIFER BAUER, CHANNEL 2 NEWS. AN UPDATE TO A STORY WE FIRST BROUGHT YOU AT 5:00 TODAY. THIS IS VIDEO THAT HAS GONE VIRAL AND HAS HOUSTON AND THE ENTIRE NATION TALKING TONIGHT. IMAGES OF ALLEGED DOG ABUSE. SOME ARE OUTRAGED THAT NOBODY IS BEING CHARGED WITH A CRIME. NEW TONIGHT WE'RE HEARING FROM A WOMAN WHO LIVES IN THIS HOME WHERE THIS DOG WAS BEING KEPT. CHANNEL 2'S KEITH GARVIN LIVE TONIGHT WITH NEW DETAILS ON THIS DEVELOPING STORY. KEITH? Reporter: DOMINIQUE, WE'RE OUTSIDE THE D.A.'S OFFICE AND THIS IS A STORY THAT HAS TOUCHED THE HEARTS OF ANIMAL LOVERS ACROSS THE COUNTRY. IT HAS THE HARRIS COUNTY DISTRICT ATTORNEY SPEAKING OUT AND FOR THE FIRST TIME, WE'RE HEARING FROM THE WOMAN WHO HEADS THE HOME WHERE THE DOG WAS STAYING. OTHER THAN MY NEIGHBOR, NOBODY ELSE ATTEMPTED TO KNOCK ON THE DOOR, ASK ABOUT THE DOG, INQUIRE ABOUT THE DOG, ONR ANY OF THE ABOVE. Reporter: SHE DOESN'T WANT HER FACE SHOWN BUT SHE WANTS TO TELL HER SIDE AFTER BEING CAUGHT UP IN A SWIRL OF CONTROVERSY INVOLVING THE PUBLICKY THAT'S BECOME KNOWN AS THE PORCH POOCH. THE STORE WENT VIRAL AFTER ONE NOBODY POSTED VIDEOS ONLINE SHOWING THE DOG IN ABUSESIVE CONDITIONS. -- ABUSIVE CONDITIONS. PEOPLE WERE UPSET ABOUT THE DOG HAVING A STRING AROUND HUR MOUTH AND THE DIAPER. THE DIAPER WAS DUE TO THE DOG HAVING LOOSE STOOLS. Reporter: SHE IS JUNE. THE PUPPY SEEN IN THE PHOTOS AND VIDEO WHO BUCKMAN SAYS IS A 6 MONTH LAB/GERMAN SHEPHERD MIX. SHE SAYS JUNE BELONGS TO HER SON'S FRIEND. IT'S LED THE DISTRICT ATTORNEY TO SPEAK OUT. THE SPCA DID CONDUCT AN INVESTIGATION INTO THIS MATTER. Reporter: IN RESPONSE TO ALLEGATIONS, HER OFFICE FAILED TO PROTECT THE DOG, ANDERSON DEFENDED HERSELF ON THE COUNTY'S FACEBOOK PAGE. AS THE OWNER OF A BEAUTIFUL DOG NAMED ELLIE, I DO NOT CONDONE HOW THIS DOG WAS TREATED. BUT UNDER TEXAS LAW, THERE IS NO PROBABLE CAUSE TO WARRANT CRIMINAL CHARGES. Reporter: AND BUCKMAN ALSO TALK ABOUT THAT STRING AROUND THE DOG'S MUZZLE. SHE SAYS IT WAS NOT A WIRE BUT A SHOESTRING AND SHE SAYS THAT THE OWNER OF THE DOG HAS ADMITTED THAT THAT WAS THE WRONG THING TO DO. HOUSTON - A story involving a dog known as the "porch pooch" has gone viral and continues to have legs. The story made headlines after one of Karress Buckman's neighbors posted video and pictures online of the dog allegedly being held on a balcony in abusive conditions at a condo in north Houston. People were most upset about the dog having a string around its mouth and wearing a diaper. Quick Clicks "The diaper was due to the dog having loose stool," Buckman said. "We didn't want it to drip down on the neighbor below because she had urinated." "She" is June, the puppy seen in the infamous photos and videos that Buckman said is a 6-month-old Lab-German shepherd mix. Buckman said June belongs to a friend of her son's who was staying with the family for about a week. "Other than my neighbor below, nobody else attempted to knock on the door, ask about the dog, inquire about the dog or any of the above," Buckman said. The controversy has even led Harris County District Attorney Devon Anderson to speak out. In response to allegations, her office failed to protect the dog Anderson defended herself on the D.A. Office's Facebook page. "As the owner of a beautiful dog named Ellie, I do not condone how this dog was treated," Anderson said in the recorded message. "But under Texas law, there is no probable cause to warrant criminal charges." Buckman's neighbor, Amber Cammack, is the neighbor who posted the photos and video. Cammack was arrested after Harris County Sheriff's deputies said residents complained that Cammack posted their private information online. "I was not asking anyone to harass them. I was asking for somebody to call the S.P.C.A. if they knew anyone there, animal control, anyone who could help us," she said. The Sheriff's Office confirms Cammack talked to supervisors and even the sheriff himself who warned her she could be arrested. The Sheriff's Office said the district attorney's office accepted misdemeanor charges of repeated electronic harassment. Cammack said she spent 14 hours in jail. "I was treated like a hardcore murderer, felon," she said. The district attorney said a veterinarian checked the dog Monday and an investigator checked the dog Tuesday. Anderson said the examinations found no open wounds or marks and the dog was not dehydrated or malnourished. The district attorney chose not to file charges against Cammack and Cammack was released from jail. Anderson said the dog is back with her owner. Thursday, Kim Ogg, a crime victims' advocate, appeared at a press conference held by Cammack's attorney, Randall Kallinan, to ask the DA to fully investigate Cammack's original animal abuse report. "Since disbanding the Animal Cruelty Unit of the HCDAO, this district attorney has done nothing to protect animals from senseless cruelty. So few criminal cases have been filed since Anderson took office in 2013, it affirms nothing will be done to stop abusers and leaves the impression that animal cruelty is acceptable," Ogg said. "Reports of animal abuse must be responded to immediately. Delayed response kills animals. No response insures that even more abuse will occur. Putting a complaint form on your website and then failing to follow up on the complaints is worse than doing nothing." In response to Ogg's claims, the Harris County District Attorney Office said they do in fact have an animal cruelty division that consists of six people including, three prosecutors, two administrators and one investigator.

– About two weeks ago, a Texas woman noticed a dog on a neighbor's balcony that she suspected was being neglected: The dog, June, was wearing a diaper and was allegedly muzzled with some type of string. Amber Cammack took photos and then posted them on Facebook—a last resort, she says, after her attempts to report the alleged abuse went nowhere. She was arrested on Tuesday for her troubles. The Harris County Sheriff's Office says deputies took several statements from neighbors at the Villas of Westador condominium accusing Cammack of repeatedly publishing "allegations of animal abuse on social media sites, including their personal information, their physical locations, security access information, personal vehicle information, and more," per the Houston Chronicle. She was apparently first given a warning on Monday, when she was told she faced arrest if she didn't take down the photos. "When the sheriff himself calls you and threatens you with arrest, that is an extreme chill on your right to freedom of expression," her attorney said in a statement. She spent a night in jail and was on Thursday joined by not just her attorney but two dozen protesters carrying signs in support of the "porch pooch." The district attorney admits "the pictures are bad" but says there's no evidence of animal cruelty; the dog, who was being dog-sat for roughly a week by condo dweller Karress Buckman, is in good health and back home with its owner. Buckman explains the diaper to Click2Houston.com as being due to "loose stool. We didn't want it to drip down on the neighbor below." The DA won't be filing charges against Cammack. (See how this man used his dog as a weapon.)

A family is grieving after a Lake Orion man died south of Au Train Island Sunday afternoon. Police say the investigation is ongoing, but according to the victim's brother, the man died on a boating trip to pour his father's ashes into Lake Superior. 59-year-old Robert Louis from Lake Orion, Michigan died shortly after he and six other passengers fell out of their boat in Lake Superior near Au Train. The group was on a 19foot wooden kit boat, and were out to honor the final wishes of Louis' father. His father died just two weeks ago after years of battling Alzheimer's. "My brother literally devoted his whole life to you know, stick around and making sure dad was taken care of for the last 4 years of his life and then two weeks later we had his ashes and his was half on mom's grave and the other half on Lake Superior," Robert Louis' brother John "Joe" Louis said. Michigan State Police were dispatched to a boating accident Sunday afternoon around 6:00 p.m. "When troopers arrived they found that six boaters had been rescued by a pontoon boat that had been in the area and were currently being treated for hypothermia. The seventh passenger was not recovered immediately," Michigan State Police Trooper Alan Park said. A witness from shore told police he saw the boat take a sharp turn for reasons unknown at this time, spilling everyone on the boat into Lake Superior. Police say the the throttle was still open when everyone fell out. "What I gathered from the information was, he tried to grab the boat as it was circling around him or them and the prop hit him and I'm not sure if it made it so he couldn't swim or if it injured him bad enough to be life threatening," Alger County Sheriff's Department Officer A.J. Schirschmidt said. The Alger County Sheriff's Department and U.S. Coast Guard searched the area for about 24 hours before the body was found. "We searched for quite a while above water when the [helicopter] was around," Schirschmidt said. "The Coast Guard got some better information of kind of where they figured the accident occurred so at that time we put two divers in the water." Robert Louis' body was found by the Alger County Sheriff's Department Monday afternoon around 3:00 p.m. south of AuTrain Island. "Just everybody he met was his friend, he was very helpful, kind," Joe Louis said. "The kind of guy that would run into a building on fire to help the people, just, incredible." If you would like to donate to the Bobby Louis Memorial, please visit this GoFundMe page. Watch TV6 and FOX UP for the latest information. ||||| MUNISING, MI - Police have identified the body of a Michigan man found in Lake Superior after a large wave washed seven people off a kit-made wooden boat in a weekend accident. The victim is Robert Louis, 59, of Lake Orion, Michigan State Police said Tuesday. The rescue and recovery effort took place near Pictured Rocks National Lakeshore. Police initially said all those swept overboard in Sunday's accident near Autrain Island had been on a pontoon boat. On Tuesday, police corrected that information, saying were aboard a 19-foot wooden boat that had been constructed from a kit. The boat's owner, Tim Preston of Marquette, Louis, and five others were on board near the island's south side when a large wave hit the boat, pushing everyone overboard. Louis attempted to swim back to the boat, but drowned, police said. Authorities searched on Sunday and Monday before the Alger County dive team recovered his body Monday afternoon near the accident site. The other six boat passengers were rescued Sunday by a group on a pontoon boat that had been in the area. They were treated for hypothermia.

– A family tragedy was compounded this week in Michigan when the body of a 59-year-old man was found Monday, a day after he fell out of a boat while scattering his father's ashes on Lake Superior. WLUC reports Robert Louis' father died two weeks ago after a battle with Alzheimer's. "My brother literally devoted his whole life to ... making sure Dad was taken care of for the last four years of his life," Louis' brother, John Louis, says. On Sunday, Robert Louis and six others were on a boat on Lake Superior to scatter his father's ashes. "He had told us that he was happy to go up and spread his ashes and follow his final wishes," one of Louis' neighbors tells WJBK. It's unclear exactly what happened out on the water—MLive reports the boat was hit by a wave, but a witness tells WLUC the boat made a sudden sharp turn—but all seven aboard fell in. By the time troopers arrived, a pontoon boat had pulled six people from the water and they were being treated for hypothermia. Louis was nowhere to be found. His body was discovered following a search nearly 24 hours later. A sheriff's department officer says it appears Louis had tried to grab the boat but was hit by the propeller. Now his family is left to mourn again. John Louis says his brother was "the kind of guy that would run into a building on fire to help." A benefit concert is being held Friday in his memory at the American Legion in Lake Orion where he would often play the guitar. (A New York man honored his childhood friend ... by flushing his ashes.)

SECTION 1. SHORT TITLE. This Act may be cited as the ``Main Street Revival Act of 2017''. SEC. 2. DEFERRAL OF CERTAIN EMPLOYMENT TAXES BY SMALL BUSINESSES. (a) In General.--Section 3111 of the Internal Revenue Code of 1986 is amended by adding at the end the following new subsection: ``(f) Election by Small Businesses To Defer Payment.-- ``(1) In general.--A specified small business may elect to pay the specified first-year employment taxes of such business in installments as provided in paragraph (2). ``(2) Payment in installments.-- ``(A) In general.--If an election is made under paragraph (1), the specified first-year employment taxes shall be paid in 4 equal installments. The first installment shall be paid on the date which is one year after the end of the specified first year and each succeeding installment shall be paid on the date which is one year after the due date of the previous installment. ``(B) Acceleration of payment under certain circumstances.--If there is an addition to tax for failure to pay timely assessed with respect to any installment required under this subsection, a liquidation or sale of substantially all the assets of the taxpayer (including in a title 11 or similar case), a cessation of business by the taxpayer, or any similar circumstance, then the unpaid portion of all remaining installments shall be due on the date of such event (or in the case of a title 11 or similar case, the day before the petition is filed). ``(C) Proration of any deficiency to installments.--If an election is made under paragraph (1) to pay the specified first-year employment taxes in installments and a deficiency has been assessed, the deficiency shall be prorated to such installments. The part of the deficiency so prorated to any installment the date for payment of which has not arrived shall be collected at the same time as, and as a part of, such installment. The part of the deficiency so prorated to any installment the date for payment of which has arrived shall be paid upon notice and demand from the Secretary. This subsection shall not apply if the deficiency is due to negligence, to intentional disregard of rules and regulations, or to fraud with intent to evade tax. ``(3) Specified small business.--For purposes of this section-- ``(A) In general.--The term `specified small business' means any HUBZone business if there is a reasonable expectation as of the first day of the specified first-year that such business will not employ more than 25 full-time employees (determined under section 45R(d) by treating the specified first year as the taxable year) for such year. Such term shall not include any business unless the specified first-year of such business begins after the date of the enactment of this subsection. ``(B) Hubzone business.--The term `HUBZone business' means any employer if-- ``(i) every trade or business of such employer is actively conducted within a HUBZone, and ``(ii) a substantial portion of the services performed for such employer by its employees are performed in a HUBZone. ``(C) Hubzone.--The term `HUBZone' means any area which would be a historically underutilized business zone (as defined in section 3(p)(1) of the Small Business Act) if such section were applied without regard to subparagraphs (C), (D), and (E) thereof. ``(4) Specified first-year employment taxes.--For purposes of this section-- ``(A) In general.--The term `specified first-year employment taxes' means, with respect to any specified small business, the taxes imposed under subsections (a) and (b) with respect to wages paid during the specified first-year of such business. ``(B) Specified first-year.--The term `specified first-year' means, with respect to any specified small business, the 1-year period beginning on the first date that any employee of such business performs any service for such business. ``(5) Aggregation rules, etc.--All persons treated as a single employer under subsection (a) or (b) of section 52 or subsection (m) or (o) of section 414 shall be treated as one person for purposes of this subsection. Any reference in this subsection to any person shall include a reference to any predecessor of such person. ``(6) Trust funds held harmless.--Appropriations, deposits, and transfers to the Federal Old-Age and Survivors Trust Fund and the Federal Disability Insurance Trust Fund established under section 201 of the Social Security Act (42 U.S.C. 401) shall be made in such amount, at such time, and in such manner as such appropriations, deposits, and transfers would be made if this subsection had never been enacted.''. (b) Effective Date.--The amendment made by this section shall apply to any specified small business (as defined in section 3111(f) of the Internal Revenue Code of 1986, as added by this section) the specified first-year of which (within the meaning of such section 3111) begins after the date of the enactment of this Act.

Main Street Revival Act of 2017 This bill amends the Internal Revenue Code to allow a specified small business to pay its first-year employment taxes in four annual installments. The bill defines "specified small business" as any HUBZone business (a business operating in a historically underutilized business zone as defined by the Small Business Act) that is not reasonably expected to employ more than 25 full-time employees in its first year of operation.

delayed meconium passage of prematurity often occurs in very low birth weight infants , and especially small for gestational age ( sga ) preterm infants are at high risk of gastrointestinal ( gi ) complications[1 , 2 ] . thus , delayed meconium passage in preterm infants is becoming a more prevalent and significant problem . a prompt recognition of this entity with its risk factors resulting in early medical management is essential to avoid early surgical intervention in this vulnerable population[35 ] . aim of this study was to evaluate the effects of a strict nutrition and stool protocol that early identifies preterm infants at high risk for delayed meconium passage and possibly reduces gi complications by comparison of sga to appropriate for gestational age ( aga ) preterm infants . inclusion of all preterm infants with delayed meconium passage hospitalized at the neonatal intensive care unit of the medical university of graz , austria , a tertiary care center . infants were identified by a local data system and by the use of a strict feeding and stool protocol between 2001 and 2009 . the gestational age was defined when the mother 's last menstrual period ( lmp ) began . the study was submitted to the ethics committee of the medical university of graz and approved . clinical signs of delayed meconium passage included gastric residual volumes , abdominal distension , and bilious residua . delayed meconium passage was defined as absence of first stool following meconium within 48 hours after first feeding with breast milk . stool was assessed by quality as meconium , first stool and breast milk stool , and by quantity as few , normal or huge . to differentiate nec from sip , ultrasonography was used because it may detect signs and complications of nec before they are evident on radiographs . feeding and stool protocol : oral feeding was started as soon as possible with a daily oral intake of 8 ml / kg , assisted by intravenous supplementation . recent studies have suggested that bolus feeding promotes more normal feed - fasting hormonal concentrations that potentially benefit intestinal development and nutrient partitioning . after the first feeding with maltodextrin , infants were fed every 3 hours by nasogastric tube or bottle according to the infant 's ability with breast milk or pooled pasteurized human milk . after initiating feedings early , and providing a period of trophic feedings , we increased the volume relative rapidly over a 10-days time period . full enteral feedings were defined as an oral intake of 160 ml / kg / d[811 ] . in cases of refusal of the mother to breast - feed the newborn or insufficient amounts of breast - milk , hydrolized protein formula for the preterm infant was added . abdomen was assessed daily and documented as being normal or abnormal including progressive abdominal distension , rigidity , or tenderness . additionally vomiting and if meconium was not spontaneously passed during the first 48 h of life , defecation was stimulated by administration of an enema ( 1ml glycerine - 0.8 g/10ml - added to 9 ml saline solution 0,9% for children > 1000 g birth weight and 0,5 ml glycerine added to 4,5 ml saline solution 0,9% for children < 1000 g birth weight ) via a disposable gastric tube coated with petrolatum ( vaseline ) for protective insertion into the rectum . management of meconium obstruction syndrome included repeated enemas and at least oral application of gastrografin , an ionic x - ray contrast medium , a mixture of sodium amidotrizoate and meglumine amidotrizoate in a proportion of 10:66 . our stool protocol summarizes the entire nutrition protocol , including also the stool passage , the daily physical examination , and the required conservative and non - surgical treatment . fig 1 is an example of a normal stool protocol of an aga preterm infant . statistical analysis was performed by means of the spss package for windows , version 16.0 ( spss inc , chicago , il ) . twenty - six sga ( median ga 28 + 4 weeks , birth weight 825 grams , 46% male ) were compared to 101 aga ( median ga 28 + 3 weeks , birth weight 1168 grams , 55% male ) preterm infants ( table 1 ) . prenatal risk factors including abruption of placenta , pathological ctg or doppler flow measurement of the umbilical vessels , and vaginal haemorrhage were observed in sga compared to aga infants in 4 vs. 12% , 81 vs. 62% and 15 vs. 26% , respecttively clinical signs of delayed meconium passage did not differ significantly between groups . treatment includedenemas ( median number 6.5 vs 10.6 ) and oral gastrografin ( 92 vs 70% ) in sga compared to aga infants , respectively . one ( 3.8% ) sga compared to 9 ( 8.8% ) aga infants developed necrotizing enterocolitis ( p=0.2 ) . the perinatal characteristics , the risk factors , clinical signs and the conservative therapy of the sga and aga preterm infants with delayed meconium passage sga= small for gestational age ; aga= appropriate for gestational age ; ga = gestational age two ( 7.7% ) sga compared to five ( 4.9% ) aga infants had spontaneous distal ileum perforation ( p=0.3 ) . surgery had to be performed in six ( 23% ) sga compared to 13 ( 12.8% ) aga infants ( p=0.09 ) . morbidity did not differ between groups , but mortality rate following surgery was significantly higher in sga ( 11.5% ) compared to aga ( 2.9% ) infants ( p=0.03)(table 2 ) . results and outcome of the sga and aga preterm infants with delayed meconium passage sga : small for gestational age ; aga : appropriate for gestational age ; sip : the immaturity of the intestinal motor mechanisms and associated feeding problems are challenges in the treatment of very low birth weight ( vlbw ) infants . timing of the first and last meconium stool is critical for oral feeding tolerance and proper gastrointestinal function . ninety - five percent of healthy term infants pass their first stool within 24 hours of birth . preterm infants ( < 37 weeks gestational age ) and low birth weight ( < 1500 g ) infants have a delay in passage of the first stool and more than 80% of preterm infants pass their first stool within 48 h[15 , 16 ] . the exact reason for the delay is unclear , but a delay in maturation of the motor mechanisms of the gut has been suggested to play a major role[13 , 16 ] . additionally pre- and postnatal hemodynamic disturbances have been identified as risk factors for intestinal motility problems . obstruction of the gastrointestinal tract by tenacious meconium frequently leads to gastric residuals , a distended abdomen , and delayed food passage . recent data support the concept that rapid evacuation of meconium plays a key role in feeding tolerance[17 , 18 ] . to prevent meconium obstruction and improve feeding tolerance , data suggest major benefits for prophylactic enemas in preterm infants[5 , 1921 ] . routine glycerine enema was found to be safe and easy - to - use at the bedside . in any case of resistance the procedure was repeated until complete evacuation of meconium was achieved and breast milk stool has passed . if the infant did not pass first stool within 48 hours after first feeding with breast milk , a water soluble x - ray contrast medium , was administered orally ( gastrografin -x - ray contrast medium for oral and rectal application , schering , vienna ) . as described the contrast medium leads to a propulsive hyperactive gastrointestinal motility . by radiographic views we confirmed the correct placement of the contrast medium 4 and 12 hours after application through the upper gastrointestinal tract and the small bowel . only in rare cases , if meconium / stool did not pass after the first application of gastrografin and provided that the clinical condition of the preterm infant did not worsen , gastrografin was readministered . as reported we found gastrografin enemas being safe , diagnostic and therapeutic , however , it is not recommended for hemodynamically unstable patients . rates of surgical interventions in the sga study patients associated with delayed meconium passage were higher compared to the aga infants , but did not reach statistical significance . our results demonstrate that surgical treatment becomes significantly more hazardous in sga preterm infants[2326 ] . the reason therefore is unclear but sga is often associated with a lack of adequate oxygen supply and a reduction in the fetus stores of glycogen and lipids . this often leads to several metabolic problems and circulatory disturbance after birth , predisposing the preterm sga newborn to further problems caused by poor reserves . a limitation of our study is that is a retrospective analysis of nutrition and stool protocol . so further prospective study to evaluate delayed meconium passage of the preterm and especially sga preterm infant is needed . finally , none of the cases was diagnosed as having cystic fibrosis or hirschsprung s disease in our study we found no differences between sga and aga preterm infants regarding short term morbidity following delayed meconium passage using a strict nutrition and stool protocol .

objectivedelayed passage of stool is a result of both gestational immaturity and illness severity . small for gestational age ( sga ) preterm infants are at high risk of gastrointestinal ( gi ) complications . we aimed to analyse the effects of a strict nutrition and stool protocol on gi problems in sga compared to appropriate for gestational age ( aga ) preterm infantsmethodsretrospective cohort analysis including all preterm infants with delayed meconium passage hospitalized at the neonatal intensive care unit of the medical university of graz , austria . infants were identified by a local data system and by the use of a strict feeding and stool protocol between 2001 and 2009 . main outcome parameters included neonatal morbidity , surgical intervention and mortality.findingstwenty-six sga ( median ga 28.6 weeks , birth weight 825 grams , 46% males ) were compared to 101 aga ( median ga 28.4 weeks , birth weight 1168 grams , 55% males ) preterm infants . clinical signs of delayed meconium passage did not differ significantly between groups . differences regarding percentage of necrotizing enterocolitis , ileus , spontaneous intestinal perforation , and surgical intervention did not differ between groups . mortality rate was significantly higher in sga ( 11.5% ) compared to aga ( 2.9% ) infants ( p=0.03).conclusiondespite similar morbidity sga infants exhibited higher lethal complication rates following delayed meconium passage compared to aga infants .

Image copyright Getty Images Image caption Rebel Wilson was originally awarded the largest defamation payout in Australian history A magazine publisher has successfully appealed against the size of a record defamation payout awarded to actress Rebel Wilson in Australia. Last year, Wilson won a case against publisher Bauer Media over articles that she said had wrongly portrayed her as a serial liar. A court had ordered Bauer to pay her A$4.5m (£2.7m; $3.6m) - a record for an Australian defamation case. On Thursday, the Victorian Court of Appeal reduced the sum to A$600,000. Wilson, an Australian star of Hollywood films including Pitch Perfect and Bridesmaids, has vowed to give her compensation to charity. The size of the original payout had generated discussion in Australia over whether it could stifle future journalism that is in the public interest. Key argument overturned In court last year, Wilson successfully argued that the eight articles published by Bauer magazines in 2015 had resulted in her being sacked from two feature films. In its original finding, the Supreme Court of Victoria awarded her A$650,000 in general damages and $A3.9m for roles she had lost out on. However, the appeals court ruled that Wilson had failed to prove that Bauer was responsible for her missing out on those roles. "The court has rejected the finding that Rebel Wilson lost the opportunity to earn A$15m by being cast in lead or co-lead roles in Hollywood films from mid-2015 to the end of 2016," the judgement read. Wilson was not in court on Thursday, but in a tweet on Wednesday she said her case "was never about the money". Skip Twitter post by @RebelWilson What happens tomorrow is to do with the losers @bauermedia quibbling about how much they now have to pay me. While this case was never about the money for me, I do hope to receive as much as possible to give away to charities and to support the Australian film industry. 🐨 — Rebel Wilson (@RebelWilson) June 13, 2018 Report During the case, Wilson said the "grubby" and "completely false" articles had alleged that she lied about her name, age and upbringing in Australia. "I had to stand up to a bully, a huge media organisation, Bauer Media, who maliciously took me down in 2015," she said after winning the case. Bauer welcomed the verdict of the appeal on Thursday, arguing it had "broader implications" for the local media industry. Six Australian media firms had also attempted to appeal against the size of the original payout, but their application was dismissed by the court. ||||| SYDNEY (Reuters) - An Australian court on Thursday slashed a record libel payout for actress Rebel Wilson, saying there was insufficient evidence a series of magazine articles published by Bauer Media prevented her from getting lucrative roles in Hollywood. Cast member Rebel Wilson poses at the premiere for "Pitch Perfect 3" in Los Angeles, California, U.S., December 12, 2017. REUTERS/Mario Anzuoni The star of three “Pitch Perfect” movies and “Bridesmaids” won A$4.6 million ($3.5 million) in damages from the German publisher last year after a court found a series of articles accusing her of lying about her age, name and childhood events had cost her roles. The judge said he awarded the damages to “nail the lie” in Bauer’s articles. But Bauer, backed by a host of large Australian media companies, appealed the decision in February, arguing the damages bill was too high. On Thursday, Victoria state’s appeals court cut Wilson’s payout to just A$600,000. “For a considerable number of reasons, the critical inferences drawn by the judge could not be upheld,” three judges in the Victorian state appeals court wrote in a judgment. “There was no basis in the evidence for making any award of damages for economic loss.” The judge who determined the initial payout had relied on testimony from Wilson and two Hollywood agents that the articles, which were not published in the United States, still would have influenced movie industry decision makers, the appeals court judges added. “I look forward to appealing,” Wilson wrote early on Friday on her official Twitter account. “Everybody knows I lost money after those maliciously defamatory articles were printed about me...clearly not fair,” she said in a series of tweets. Wilson’s legal representatives were not immediately available for comment. Bauer said in a statement that it welcomed the court’s decision. When Wilson won the case last year, it was an Australian record, much higher than the A$389,000 maximum previously set, by using her “global reach” as justification.

– So much for the record $3.6 million libel payout in Rebel Wilson's successful defamation case against Bauer Media. The publisher of Australia's Woman's Day magazine successfully appealed Thursday to have the damages reduced to about $450,000, arguing Wilson failed to prove she'd lost out on two film roles as a result of articles that wrongly portrayed her as a habitual liar. "There was no basis in the evidence for making any award of damages for economic loss," the judgement reads, per Reuters. The decision comes after some concern over whether the fear of payouts of that magnitude would suppress journalism in the public interest, reports the BBC. When the damages were initially awarded, however, the judge noted "only a very substantial sum … could convince the public that Ms. Wilson is not a dishonest person." Wilson, who promised to donate her payout to charity, tweeted Wednesday "the losers" were "quibbling about how much they now have to pay me." She added, "while this case was never about the money for me, I do hope to receive as much as possible."

symptomatic patients with suspected zika virus infection were enrolled in a research study approved by the brazil ministry of health ( certificado de apresentao para apreciao tica 45483115.0.0000.0046 , no . acute zika virus infection was diagnosed for 15 patients whose serum samples tested positive by a qualitative reverse transcription pcr ( rt - pcr ) by using primers targeting the nonstructural 5 gene ( 8) . clinical samples were retested for zika virus positivity by using a separate quantitative rt - pcr ( quantitect sybr green pcr kit ; qiagen , valencia , ca , usa ) and primers targeting the envelope gene ( 9 ) . metagenomic next - generation sequencing libraries were constructed from serum rna extracts , as described ( 10,11 ; technical appendix ) . pathogen identification from metagenomic next - generation sequencing data was performed by using the sequence - based ultra - rapid pathogen identification bioinformatics pipeline ( 12 ; http://chiulab.ucsf.edu/surpi/ ) . results of the metagenomic analyses and identification of co - infections with chikungunya virus are reported elsewhere ( 13 ) . for zika virus genome sequencing , 2 isolates ( bahia07 and bahia09 ; table ) with zika virus titers > 10 copies / ml generated sufficient viral metagenomic data for complete genome assembly . for the remaining samples with lower titers , metagenomic next - generation sequencing libraries were enriched for zika virus sequencing by using xgen biotinylated lockdown capture probes ( integrated dna technologies , redwood , ca , usa ) designed to tile across all sequenced zika virus genomes > 10,000 nt in genbank ( http://www.ncbi.nlm.nih.gov/genbank ) as of march 1 , 2016 . enrichment was performed on the metagenomic libraries in pools of 8 libraries ( including zika virus negative serum sample controls ) by using the xgen lockdown probe protocol and the seqcap ez hybridization and wash kit ( roche , indianapolis , in , usa ) . eleven zika virus genomes with > 40% genome recovery ( mean 69.4% 2.0% ) were assembled ( table ) . distribution of single nucleotide variants across the 11 recovered genomes exhibited distinct patterns ( technical appendix figure 1 ) , indicating that the assembled genomes were unlikely to result from cross - contamination by a single high - titer zika virus sample . * ct , cycle threshold ; na , not applicable ; nd , not done ; neg , negative ; pos , positive ; qrt - pcr , quantitative reverse transcription pcr ; rt - pcr , reverse transcription pcr ; u , unknown . samples were collected from salvador in bahia , brazil , except for bahia05 , which was collected in camaari , bahia , brazil . assumes a genome size of 10,676 nt , the size of the prototype brazilian zika virus strain sph2015 ( ku321639 ) . multiple sequence alignment was performed by using mafft version 7 ( http://mafft.cbrc.jp/alignment/software/ ) ; maximum - likelihood ( ml ) and bayesian phylogenetic inferences were determined by using phyml version 3.0 ( http://www.atgc-montpellier.fr/phyml/ ) and beast version 1.8.2 ( http://beast.bio.ed.ac.uk/ ) , respectively . the best - fit model was calculated by using jmodeltest2 ( https://github.com/ddarriba/jmodeltest2 ; details in technical appendix ) . coding regions corresponding to the 11 complete or partial genomes from bahia were aligned with all published and available near - complete zika virus genomes and longer subgenomic regions ( > 1,500 nt ) of the asian genotype as of april 2016 ( mean sequence size 8,402 nt with 1,652 distinct nucleotide site patterns ) . the ml phylogeny was reconstructed by using the best - fit general time - reversible nucleotide substitution model with a proportion of invariant sites ( gtr+i ) . statistical support for phylogenetic nodes was assessed by using a bootstrap approach with 1,000 bootstrap replicates . a bayesian molecular clock phylogeny was estimated by using the best - fitting evolutionary model ( 2 ) ; specifically , a gtr+i substitution model with 3 components : a strict molecular clock , a bayesian skyline coalescent prior , and a noninformative continuous time markov chain reference prior for the molecular clock rate . the isolates from patients in salvador clustered together within 1 strongly supported clade ( posterior probability 1.00 , bootstrap support 100% , bahia clade c ) ( figure ; technical appendix figure 2 ) . this support is notable ; most zika virus genomes in this clade are incomplete , and uncertainty is accounted for in phylogenetic inference . the tree topology accords with previous findings ( 2,4,5 ) , and time to most recent common ancestor ( tmrca ) of the epidemic in the americas is similar to that previously estimated ( 2 ) ( american epidemic clade a ; figure ) . the overall ml and molecular clock phylogenies exhibited many well - supported internal nodes with bootstrap support > 60% and posterior probability > 0.80 ( figure ; technical appendix figure 2 ) , although several nodes near the ancestor of clade a were less well supported . timeframe of zika virus outbreaks in the americas . a molecular clock phylogeny is shown with the zika virus outbreak lineage estimated from complete and partial ( > 1,500 nt ) coding region sequences . [ philippines , 2012 ] ; jn860885 [ cambodia , 2010 ] ; and ku681081 [ thailand , 2013 ] ) are not displayed . a , b , and c denote the current american epidemic , the northeastern brazil ( maranho sequence and bahia ) , and the bahia clades , respectively ; numbers next to the clade denote posterior probabilities and bootstrap scores in percentages . taxa are labeled with the genbank accession numbers , sampling location , and sampling date . the inset graph on the left shows the posterior probability distributions of the estimated ages ( time to most recent common ancestor ) for clades a , b , and c. the posterior probability density is plotted on the vertical axis as a function of time on the horizontal axis ( tick marks designate 3-month intervals ) . estimated ages were determined with beast version 1.8.2 ( http://beast.bio.ed.ac.uk/ ) by using the best - fitting evolutionary model . brazil states : ba , bahia ; ce , cear ; ma , maranho ; pa , par ; pb , paraba ; rn , rio grande do norte ; rj , rio de janeiro ; sp , so paulo . the updated phylogenetic analyses , including the newly identified clade c , suggest that zika virus was introduced in bahia during march an isolate from maranho in northeastern brazil ( 1,000 km from bahia ) is ancestral to the bahia clade ( posterior probability 1.00 , bootstrap support 74% , northeastern brazil clade b ) ( figure ; technical appendix figure 2 ) . the tmrca of clade b ( comprising the bahia clade and the maranho sequence ) is estimated to be september 2013april 2014 , an early stage of the epidemic . this tmrca is consistent with the hypothesis that zika virus in the americas originated in brazil ( 2 ) . a previously reported sequence from bahia ( 6 ) clustered with an isolate from belm in the state of par in northern brazil , 3,000 km from bahia ( posterior probability 0.99 , bootstrap support 81% ) ( figure ; technical appendix figure 2 ) . the patient denied history of travel , suggesting that multiple zika virus lineages may circulate in bahia . our results suggest an early introduction and presence ( mid-2014 ) of zika virus in the salvador region in bahia , brazil . given the size of the cluster and statistical support for it , this lineage likely represents a large and sustained chain of transmission within bahia state . most cases of this zika virus lineage clustered closely to a sequence from maranho , and we found evidence for an additional potential introduction to bahia from par state . consequently , zika virus in salvador during mid-2014 was likely introduced from other regions in brazil rather than from outside the country . current findings of zika virus emergence in bahia state during mid-2014 are consistent with first - trimester viral infection in pregnant women corresponding to the initial reported cases of fetal microcephaly , which began in january 2015 ( 5 ) and peaked in november 2015 . broader sampling across bahia is needed to determine whether the salvador lineage ( clade c ) identified in this article comprises most zika virus cases in the state . brazil currently faces a major public health challenge from co - circulation of zika , dengue , and chikungunya viruses ( 24,14,15 ) . additional molecular surveillance in the americas and beyond is urgently needed to trace and predict transmission of zika virus . details of library construction and next - generation sequencing methods , phylogenetic analyses , and data availability for this study , including supplemental figures .

sequencing of isolates from patients in bahia , brazil , where most zika virus cases in brazil have been reported , resulted in 11 whole and partial zika virus genomes . phylogenetic analyses revealed a well - supported bahia - specific zika virus lineage , which indicates sustained zika virus circulation in salvador , bahia s capital city , since mid-2014 .

in supersymmetric theories there are various possibilities of generating an intrinsic electric dipole moment ( edm ) in microscopic systems . first of all , the neutron has already a non vanishing edm in the standard model ( sm ) , due to the uneliminable phase in the ckm matrix , or , in other words , to the misalignment between the left eigenstates of the two yukawa matrices , @xmath6 and @xmath7 , and to the charged current gauge interactions between the left - handed quarks , that make the misalignment physically significant . if further interactions are present , further misalignments and phases can become significant . for example , in the unified extensions of the sm the new gauge interactions make significant the misalignments among particles unified in the same gauge multiplet . nevertheless , without supersymmetry , due to the decoupling of heavy particles , these effects are suppressed at low energy by powers of the unification mass . in the supersymmetric extensions of the sm , one more possible source of flavour and cp violation is associated to the possibility that the scalar partners of quarks and leptons are not degenerate and point in different directions in the flavour space compared to the corresponding fermions . on the other hand , models are often considered in which the soft supersymmetry breaking terms are flavour universal and real at some energy scale @xmath8 . this can happen in models in which supersymmetry breaking is communicated to the observable sector by gravity @xcite ( in this case @xmath9 ) or when it is communicated by gauge interactions at relatively low energy @xcite . these hypotheses allow to keep under control flavour changing neutral current processes and edms due to the mixings in the fermion - scalar interactions . in this case , effects coming from the non universal radiative corrections to soft breaking parameters have to be ascribed to the yukawa couplings . as said , when the gauge group is unified , some new phases and flavour mixings otherwise inexistent or unphysical can become significant . unlike what happens without supersymmetry , if its breaking is communicated to the observable sector at a scale where the gauge group is already unified , these further phases and flavour mixings can succed in contaminating the soft breaking matrices before the heavy particle decoupling make them harmless , giving rise to important effects @xcite . besides the quark and lepton sector and their scalar partner sector , a cp source can come from the hidden supersymmetry breaking sector of the theory . as a consequence , there can be cp violating effects in the observable sector not associated to a mixing matrix and to a consequent flavour violation . as a matter of fact , even in the flavour universality hypothesis , a cp violation in the hidden sector can make the soft breaking parameters complex since the beginning . in this case , the effects are very large unless the phases are forced to be small . in this paper , we consider the effects of phases associated to the misalignment of two yukawa matrices , @xmath6 and @xmath7 , in the hypothesis that the soft supersymmetry breaking parameters are generation universal and real at an high energy scale @xmath8 . we assume that the yukawa interactions are present until @xmath8 without worring about their origin . however the minimal unified models that we consider do not give correct unification predictions for the light fermion masses , showing that , differently from the mssm case , flavour physics can not be totally decoupled from unification physics . furthermore , minimal flavour effects could be comparable to minimal unification effects @xcite . the order of magnitude of edms for the quarks @xmath2 , @xmath5 and for the electron @xmath10 depends in a crucial way on the gauge structure at the universality scale @xmath8 . we will consider therefore different gauge structures , from the minimal one ( su(3)@xmath11su(2)@xmath11u(1 ) ) to that one that unifies all fermions belonging to the same family ( so(10 ) ) , passing through the minimal unification ( su(5 ) ) , studying them from the point of view of the properties of edms under flavour transformations commuting with the gauge ones . this will allow us to give our estimates for quark and electron edms . we will consider the mssm in section [ sec : mssm ] . in refs . @xcite the calculation of the down quark edm induced by a loop with charginos has been made using numerical methods with sometimes different results . for a given value of @xmath1 , @xmath12 , bertolini and vissani claim in fact that @xmath13 can be as large as @xmath14 , inui et al . obtain @xmath15 and abel et al . get @xmath16 , all of them indicating a linear dependence on @xmath1 . the numerical calculation is used in order to solve the matricial renormalization group equations for the yukawa couplings and the soft breaking terms ; this is necessary for doing a detailed analysis at the fermi scale . unfortunatly , in the low energy lagrangian , the particular flavour structure of the ckm cp violation , at the basis of the smallness of the edms , is hidden in a large number of flavour mixing matrices . on the contrary , by studying the edms directly in terms of the parameters at the universality scale , it is easy : i ) to estimate the order of magnitude of the effect , that for @xmath12 does not much exceed @xmath17 , ii ) to display the cancellation of contributions not containing the squared light yukawa couplings , that suppress the edms , iii ) to show the raise with @xmath0 of the @xmath5 quark edm . it is also possible to obtain the relation @xmath18 between the one loop dipoles of quarks @xmath5 and @xmath19 , @xmath20 and @xmath21 ( that both contribute to @xmath13 ) . from our estimates we see that the one loop supersymmetric effects are comparable with the sm ones @xcite . it turns out that also supersymmetric contributions at higher loops are relevant . in section [ sec : unified ] we will consider unified theories . the possibility of edms for the neutron and the electron close to experimental limits in unified theories has been pointed out and analyzed in refs . @xcite in the case of moderate @xmath1 , where it is associated to the gauge group so(10 ) . the big enhancement of the neutron edm in comparison with the mssm case is due to the fact that , unlike in the mssm , in a unified theory cp can be violated also when two eigenvalues of the same yukawa matrix are vanishing @xcite . nevertheless this , as other effects @xcite , happens also in the su(5 ) case , but only when the @xmath2 quark is concerned . as the third generation yukawa coupling involved is the bottom one , the effect is proportional to @xmath4 . due to its possible interest , we also present the results of a numeric computation of @xmath3 . the @xmath5 quark contribution , as the electron edm , turns out to be very small compared with @xmath3 . we conclude section [ sec : unified ] with a short rivisitation of so(10 ) . in appendix , we give the general formulas for the one loop edms of up and down quarks and charged leptons in terms of the parameters of the lagrangian at the fermi scale . in this section we will study quark and electron edms in the minimal supersymmetric extension of the standard model , with real and generation - universal soft terms at some scale @xmath8 @xmath22 this model provides the minimal amount of cp violation and , consequently , the minimal contribution to @xmath13 in a supersymmetric theory with soft breaking terms generated at @xmath8 . in the described hypothesis , third generation yukawa couplings can not be , by themselves , a source of quark edms . in fact , let us suppose that we neglect the four light yukawa couplings in the quark sector , @xmath23 everywhere , a part for the mass that must be present in a loop diagram in order to provide the elicity flip . then , since the hypothesis is scale independent , cp violation disappears and the edms have to vanish . in fact , at @xmath24 the soft terms are universal and real , so that cp violation can only come from yukawa couplings . but , as there is a couple of degenerate eigenvalues in each yukawa matrix , all ckm phases can be eliminated using rotations in the 1 - 2 sector and phase redefinitions of the fields , just as in the standard model . more precisely , in the @xmath3 case we have to use a rotation of _ down _ left light generations , while in the @xmath20 case we have to use a rotation of _ up _ ones . this is because when we consider , for example , the edm of the quark @xmath5 , the @xmath25 mass eigenstate is fixed , and the possibility of rotating the @xmath25 and @xmath26 eigenstates is lost . in the limit of vanishing @xmath27 and @xmath28 , cp violation disappears from the theory , but also the lighest down mass eigenstate becomes not defined . thus the light yukawa couplings play a crucial role in generating the edms . let us now see in which way they intervene . to begin with a simpler case , let us consider the imaginary part of the @xmath29 term ( defined in appendix ) after one loop rescaling from @xmath8 to @xmath30 . this quantity , like the edms , vanishes in absence of cp violation and contributes to the edms themselves . the @xmath29 term does not depend on the basis in the flavour space in which the left doublets @xmath31 , @xmath32 and the right singlets @xmath33 , @xmath34 , @xmath35 are written . in other words , if we consider a transformation of the flavour components of the superfields @xmath36 , @xmath37 , @xmath38 , @xmath39 , @xmath40 commuting with the gauge group , namely a @xmath41 transformation , the yukawa couplings become @xmath42 whereas the @xmath29 term remains invariant . for what follows , most important are the @xmath43 transformations . since at @xmath8 all the parameters in the tree level lagrangian except the yukawa couplings are invariant , it is convenient to consider the @xmath29 term at the fermi scale as a function of those parameters . actually , the relation between high and low energy yukawa couplings can be inverted , so that the yukawa couplings can be considered at the fermi scale . owing to the invariance relative to transformations of the right - handed quarks , @xmath29 depends on the yukawa couplings only through their squares @xmath44 , @xmath45 and @xmath46 . moreover , if two among the @xmath47 or @xmath48 eigenvalues are equal at @xmath8 , the yukawa couplings can be made real through a transformation so that @xmath49 vanishes . therefore the rge corrections to @xmath49 must be proportional to @xmath50 . in fact , owing to the invariance relative to a generic @xmath51 transformation , @xmath29 is a sum of terms like @xmath52 { \operatorname{tr}}\bigl[({\boldsymbol{\lambda}_{\text{\textsc{e}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{e}}}^{\phantom{\dagger}}})^k\bigr ] a_{u , d}^0\ ] ] with real adimensional functions of @xmath8 and @xmath53 as coefficients . the first non vanishing supersymmetric contribution to @xmath49 is then proportional to @xmath54 ( a_u^0-a_d^0 ) \simeq \lambda_t^4 \lambda_b^4\lambda_c^2 \lambda_s^2 { j_{\mathrm{cp}}}(a_u^0-a_d^0 ) , \ ] ] where @xmath55 . if @xmath56 , @xmath49 is furtherly suppressed by lepton yukawa couplings or by small effects due to the @xmath57-@xmath58 hypercharge difference . let us consider now the imaginary part of a flavour non - invariant quantity , more precisely the imaginary part of the matrix element of a quantity @xmath59 transforming as @xmath48 ( or of a quantity @xmath60 transforming as @xmath47 ) , calculated in correspondence of left and right mass eigenstates . the imaginary parts appearing in the expressions in appendix for the edms and thus the edm themselves are examples of such quantities . in this case , the light yukawa coupling suppression is less strong and dependent on the mass eigenstate we consider , up or down , light or heavy . the general dependence of @xmath59 on the yukawa couplings is @xmath61 , where @xmath62 represents traces of @xmath63 and we suppose that @xmath64 is a real polynomial in the yukawa couplings , as it is for the one loop edms , where the yukawa couplings only come from vertices or supersymmetric rge corrections . the imaginary part of the @xmath58-@xmath25 matrix element is then proportional to the @xmath5 eigenvalue @xmath65 = \lambda_d { \operatorname{im}}\bigl [ f\bigl({\boldsymbol{\lambda}_{\text{\textsc{u}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{u}}}^{\phantom{\dagger}}},{\boldsymbol{\lambda}_{\text{\textsc{d}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{d}}}^{\phantom{\dagger } } } , { \operatorname{tr}})_{d_l d_l}\bigr].\ ] ] moreover , in getting the dependence of @xmath66 on the light yukawa couplings , it is no longer possible to consider the limit @xmath67 or @xmath68 as above for @xmath29 , because in this limit the eigenstate @xmath25 , as @xmath58 , is no longer defined . therefore @xmath66 has not to be proportional to @xmath69 but only to @xmath70 , so that the necessary dependence on the yukawa couplings is @xmath71 \propto \lambda^4_t\lambda^2_c\lambda^2_b{j_{\mathrm{cp}}}$ ] . the first non vanishing contribution to @xmath72 $ ] comes in fact from the term proportional to @xmath73 in the expression for @xmath59 . let @xmath74 be the proportionality coefficient . since higher order terms are negligible , we have @xmath75\simeq a\lambda_{d_i}{\operatorname{im}}\bigl [ ( { \boldsymbol{\lambda}_{\text{\textsc{u}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{u}}}^{\phantom{\dagger}}})^2 ( { \boldsymbol{\lambda}_{\text{\textsc{d}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{d}}}^{\phantom{\dagger } } } ) ( { \boldsymbol{\lambda}_{\text{\textsc{u}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{u}}}^{\phantom{\dagger } } } ) \bigr]_{d^l_i d^l_i}.\ ] ] had we considered a matrix @xmath60 transforming as @xmath47 , we would have found @xmath76\simeq b\lambda_{u_i}{\operatorname{im}}\bigl [ ( { \boldsymbol{\lambda}_{\text{\textsc{d}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{d}}}^{\phantom{\dagger}}})^2 ( { \boldsymbol{\lambda}_{\text{\textsc{u}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{u}}}^{\phantom{\dagger } } } ) ( { \boldsymbol{\lambda}_{\text{\textsc{d}}}^\dagger}{\boldsymbol{\lambda}_{\text{\textsc{d}}}^{\phantom{\dagger } } } ) \bigr]_{u^l_i u^l_i}.\ ] ] since the flavour dependence of the one loop edms is all contained in the arguments of imaginary parts in , all the down edms are expressable in the previous form @xmath77 $ ] with the same @xmath59 , so as for the up ones we have @xmath78 $ ] with the same @xmath60 . then there are precise and parameter independent relations between one - loop supersymmetric contributions to edms of quarks of different familiesj_{\rm cp}$ ] where @xmath79 are diagonal flavour matrices , @xmath80 , @xmath81 , etc . ] : @xmath82 so that @xmath83 eqs . show that the middle generations edms are the largest ones and allow to express the neutron edm in terms of only the @xmath2 and @xmath5 quark edms . using eqs . and , and neglecting chromoelectric dipole moment contributions , we get in fact the estimate @xmath84 from eqs . it is apparent that @xmath85 is much smaller than @xmath86 . this is because the previous combination is invariant under flavour rotations of the quark fields and thus suppressed by both @xmath87 and @xmath88 , just as the rge induced phase of @xmath29 , electron edm , strong cp angle and 3-gluon operator @xcite . owing to this large suppression , the @xmath29 term phase contributes to the neutron edm in a negligible way . show the strong rise of the edms with @xmath1 . the large @xmath1 region is therefore by far the most interesting one and it is the one that we will consider in the following . expressing all fermion masses in terms of the yukawa couplings , the weak vacuum expectation value @xmath89 and @xmath1 , the only dependence of edms on @xmath1 is in the left - right ( and r - l ) blocks of the scalar mass matrices that provide the `` elicity flip '' in the scalar sector . in the large @xmath1 region , @xmath90 so that the edms depend on @xmath1 only through the down yukawa couplings : @xmath91 . hence the down quark edms increase with @xmath0 , whereas the up quark ones increase with @xmath92 . let us consider now more closely how one loop graphs can give rise to the flavour structure of eqs . . in both the @xmath20 and @xmath3 cases there are two relevant graphs ( see appendix ) involving either charginos or gluinos . the yukawa matrices necessary to obtain the flavour structure of eqs . and come from the rge corrections to the soft breaking parameters and ( in the case of chargino exchange only ) from the vertices . each insertion of a couple of yukawa coming from rges is accompanied by a loop factor and a large logarithm , @xmath93 . in order to provide the 9 yukawa couplings of eqs . , 4 of these inserctions are necessary in the gluino diagram , giving a factor @xmath94 , whereas 3 are enough in the chargino diagram ( @xmath95 ) . to estimate the one loop contributions to @xmath20 and @xmath3 only the dependence on dimensionful parameters is missing . because of the necessary presence of a l - r scalar mass inserction as in eq . and of the behavior of the loop functions , it is @xmath96 for the chargino and gluino one loop contribution to @xmath20 respectively . in this and in the following estimates , we neglect all the numerical coefficients of order one , we choose @xmath97 and we use central values for the various known parameters , in particular , @xmath98 . moreover ` @xmath99 ' stands , in each case , for the particular combination of soft parameters written in the analytical approximation . because of @xmath100 and of @xmath101 in eq . , the corresponding contributions to @xmath3 are less interesting and totally negligible for moderate @xmath1 . at a closer inspection , these estimates turn out to be correct within an order of magnitude . as it is apparent from eq . , @xmath13 can not be much larger than @xmath17 for @xmath12 and than @xmath102 for whatever value of @xmath1 . we remark that , owing to the necessary presence of @xmath87 in all results for @xmath20 , a numerical calculation of the @xmath5 quark edm requires the knowledge of the low energy parameters with a precision of about @xmath103 in order to see the reciprocal cancellation of the terms not proportional to @xmath87 . it is at this point interesting to understand why the three - loop pure sm contributions to the neutron edm , @xmath104 @xcite , are not suppressed relative to the one - loop supersymmetric ones . a large suppression of the pure sm contribution would seem plausible because , in comparison with it , the supersymmetric one loop contributions can be enhanced by 1 . large logarithms , @xmath105 , that multiplicate the loop factors @xmath106 in the rge inserctions involved by the one loop supersymmetric diagrams ; 2 . @xmath1 factors , that can enhance the @xmath48 and @xmath107 couplings ; 3 . a particularly small effective combination of susy parameters , ` @xmath99 ' . on the other hand , the sm contributions are enhanced in different ways . in fact , in the pure sm graphs , 1 . the elicity flip can occur on an external leg , giving a factor equal to the `` constituent quark mass '' @xmath108 , equal for @xmath109 ( so that @xmath110 ) ; 2 . the yukawa couplings are expressed in terms of quark masses evaluated at low energy and therefore enhanced by qcd renormalization factors , as the strong coupling ; 3 . unlike the rge - induced contributions , that must depend in a polinomial way on the yukawa couplings , the infrared structure due to subtractions of quark propagators in the sm graphs , give rise to a mild logarithmic dependence . point iii . is particularly important in the case of quantities neutral under the quark @xmath111 flavour group ( like the electron edm , or the phase of the @xmath29-term , or the strong cp angle , or the 3-gluon operator @xcite ) that for this reason receive purely supersymmetric contributions much smaller than sm ones . due to the absolute lack of experimental interest , we avoid discussing such issues in any detail . other than one loop supersymmetric and three loop pure sm diagrams , it is also possible to have higher loop contributions , not considered before , having the two kind of enhancement . an example can be obtained from the chargino one loop diagram by adding by adding a qcd loop , that allows elicity flip on the external lines and gives a contribution to @xmath20 comparable with the previously computed one . using charged higgs exchange , it is also possible to obtain an interesting three loop contribution to @xmath13 given by @xmath112 fine tuning considerations suggest that , in the large @xmath1 region , the charged higgs are lighter than the squarks @xcite . to conclude this section , let us note that the universality scale @xmath8 can be much smaller than the unification scale if the supersymmetry breaking is transmitted at relatively low energy by gauge interactions . in this case all rge - induced contributions to @xmath13 are smaller because of their strong dependence on @xmath113 , whereas the higher loop ones , and in particular , are not . in this section , we suppose that the gauge group is unified at the universality scale @xmath8 that we will identify with the reduced planck mass . in this case , edms can be much larger than in the mssm . as seen in the previous section , the smallness of edms in the mssm is due to the light yukawa couplings , that have to be present to prevent the removal of all phases from the lagrangian , phases that at the planck scale reside only in the yukawa matrices . in fact , with regard for example to the quark @xmath5 , if @xmath114 cp violation can be removed with independent redefinitions of the right down quark and of the left doublet . if the gauge group is unified , at the planck scale the phases still reside only in the yukawa matrices , but in this case mssm multiplets belonging to the same representation of the unified group can no longer be rotated independently . hence , depending on the gauge group and on the quark in consideration , cp violation can persist even if some or all of light yukawa couplings are vanishing , making not necessary their suppressing presence in the edm expressions . let us consider first minimal su(5 ) unification . one generation is composed by two multiplets , a five - plet @xmath115 and a ten - plet @xmath116 , and the higgs fields belong to two five - plets , @xmath117 , that transforms like @xmath118 , and @xmath119 , that transforms in the conjugate way . in terms of these fields , the yukawa interactions are @xmath120 in a basis in which @xmath47 is diagonal . below the unification scale , @xmath47 and @xmath48 are the same of the previous section . five of the six phases of the ckm matrix can be removed in the mssm through independent redefinitions of the @xmath121 , @xmath122 , @xmath123 . here , it is easy to show that only three phases can be removed by independent transformations of @xmath124 , @xmath125 , so there are two more physical phases compared to the mssm ( and the sm ) . whereas two phases decouple below the unification scale in non supersymmetric models , in supersymmetric models they leave their effects in soft breaking parameters , that loose their universality and reality , before decoupling could make them harmless . is the effect of these two further phases on the edms suppressed by light yukawa couplings in this model ? the answer is no for the quark @xmath2 and yes , but in a different way compared to the mssm , for down quarks and charged leptons . in order to show that , let us suppose first that the two light @xmath47 eigenvalues , @xmath126 and @xmath127 , are vanishing . in this case , all phases in the yukawa matrices become unphysical . in fact , the first of the two interactions becomes @xmath128 and it is invariant for transformations in the @xmath129-@xmath130 sector . moreover , as it is well known , it is possible to write the most general unitary matrix @xmath131 as @xmath132 where @xmath133 are orthogonal @xmath134 matrices . then we can reabsorb @xmath135 by a redefinition of @xmath136 , reach the phase @xmath137 by defining @xmath138 and reabsorb also @xmath137 by a redefinition of @xmath139 , without affecting the diagonal interaction . since , as seen in the previous section , the limit @xmath114 is meaningful for the down quarks and for the charged leptons ( and for the top ) , this means that their edms are suppressed by light up yukawa couplings in some way . let us suppose now that the two light @xmath48 eigenvalues , @xmath27 and @xmath28 , are vanishing . in this case , two phases remain physical . in fact , the interactions become @xmath140 with a redefinition of @xmath141 , one of the three phases of @xmath142 can be reabsorbed , but not the remaining two because , if they were reabsorbed by a redefinition of some @xmath124 , they would reappear in the diagonal interaction . the two remaining phases are just those ones related with unification . since the limit @xmath143 is meaningful for up quarks ( and the bottom and the tau ) , their edms are not necessarily suppressed by light yukawa couplings . the dependence of edms on yukawa couplings can be obtained as in the mssm . changing basis in the flavour space for the su(5 ) supermultiplets @xmath144 , @xmath145 corresponds to make a @xmath146 transformation on the flavour component of the fields , relative to which the yukawa couplings transform in this way : @xmath147 as before , the down quark edms are given by @xmath77 $ ] , where the matrix @xmath59 transforms as @xmath48 . unlike the case of the mssm , this does not mean that @xmath148 . in this case we have rather @xmath149 where @xmath64 depends on the arguments in such a way that @xmath150 for a transformation . from eq . it follows that @xmath20 is proportional to @xmath27 as in the mssm . moreover , @xmath64 must depend on down yukawa couplings through their squares but it can depend on individual up yukawa couplings also through not squared couplings , provided that the total number of @xmath47 is even . this can be seen by noting that the particular flavour transformation @xmath151 , @xmath152 leaves @xmath45 and @xmath64 unchanged but it changes sign to @xmath47 . therefore , unlike the mssm , a @xmath127 suppression can be enough for the quark @xmath5 . indeed , the first non vanishing contribution to @xmath20 is proportional to @xmath153= \lambda^{}_d\lambda_t^3\lambda_b^2\lambda^{}_c { \operatorname{im}}\bigl[v^{\dagger}_{dc}\overline{v}^{}_{cb}v^t_{bt}v^{}_{td}\bigr].\ ] ] the edms of the quark @xmath19 and of the electron are suppressed in an analogous way . the up quark edms behave in a different way . they are given by @xmath78 $ ] where the matrix @xmath60 transforms as @xmath47 under the transformation . unlike the mssm , @xmath60 is not necessarily proportional to @xmath47 on the left , but can also be proportional to @xmath154 , that transforms in the same way on the left . therefore , @xmath3 is not necessarily proportional to @xmath47 , giving rise to a possible enhancement . in any case , @xmath3 must contain an odd number of up yukawa matrices , since the transformation @xmath155 , @xmath156 leaves @xmath48 unchanged but it changes sign to @xmath47 and @xmath60 . the first non vanishing contribution to @xmath3 is proportional to @xmath157= \lambda^{}_t\lambda_b^4 { \operatorname{im}}\bigl[\overline{v}^{}_{ub}v^t_{bt}v_{tb}v^{\dagger}_{bu}\bigr]\ ] ] and it exhibits the described features . in eqs . ( [ pippo],[ddu ] ) we omitted the renormalization factors for the @xmath158 matrix elements . in su(5 ) we have therefore @xmath159 . only the gluino diagram is able to give rise to the @xmath160 enhancement . in fact , the chargino diagram is explicitely proportional to the @xmath126 that appears in one of its vertices and it is negligible in this model . let us concentrate then on the gluino contribution to the quark @xmath2 , @xmath161 . the flavour structure is generated by the corrections to the mass matrices . at the unification scale , these corrections are proportional to combinations of yukawa matrices transforming as the mass matrices themselves relative to the @xmath146 group . hence the corrections to the ten - plet mass matrix , and so those to @xmath162 , @xmath163 , @xmath164 , are proportional to @xmath165 , @xmath44 , @xmath45 , etc . , whereas the corrections to the five - plet mass matrix , and so those to @xmath166 and @xmath167 , are proportional to @xmath165 , @xmath168 , etc .. all these corrections are also proportional to @xmath169 . some of them are characteristic of unification , whereas other ones are produced also below the unification scale and hence at the fermi scale they are proportional to @xmath170 . including also some approximate numerical factors , the corrections @xmath171 at the fermi scale are @xmath172 these corrections are able to generate the flavour dependence of eq . , so that we can estimate @xmath13 as @xmath173 t_zt_{\mathrm{g}}\frac{m_ta_u}{m^2_{\tilde{u } } } \frac{m_{3}}{\max(m^2_{\tilde{u } } , m^2_{3 } ) } \\ & \approx 10^{-(25\div26)}\fracwithdelims(){\tan\beta}{50}^4 \fracwithdelims(){|{\operatorname{im}}[v^2_{tb}\overline{v}^2_{ub}]|}{10^{-5 } } \fracwithdelims(){500{\,\mathrm{gev}}}{m_{\text{susy}}}^2{e\,\mathrm{cm } } , \end{split}\ ] ] where @xmath174 in the second line is the combination of supersymmetric parameters appearing in the first line and it can be even larger than @xmath175 because of the likely lightness of @xmath176 in the large @xmath1 regime . since the prediction for @xmath3 is interesting enough , we use the expressions to do an exact computation of @xmath13 that we show in figure [ fig : du ] for @xmath177 , for three values of @xmath1 , 2 , 10 and 50 , and for @xmath178|=10^{-5}$ ] . @xmath3 is plotted as a function of @xmath179 in order to exhibit the so - called `` gluino focussing '' effect @xcite . from eq . and [ fig : du ] and from the experimental limit @xmath180 @xcite it is apparent that the @xmath2 quark edm can be very large in superunified theories with large @xmath1 . let us consider now shortly the gauge group so(10 ) , whose sixteen dimensional representation `` @xmath181 '' unifies all quarks and leptons of one generation , included a right - handed neutrino . in the minimal model the two light higgs doublets belong to two different ten dimensional so(10 ) multiplets , @xmath182 and @xmath183 , and the yukawa interactions are @xmath184 in this model the situation is different from the su(5 ) case , in which the five - plets and ten - plets could be rotated independently . all six phases of @xmath185 are physically significant . moreover , it is easy to see that in this case it is not possible to remove the ckm phases neither when @xmath143 ( like in su(5 ) ) nor when @xmath114 ( unlike in su(5 ) ) . therefore neither @xmath3 nor @xmath20 are suppressed by light yukawa couplings . the @xmath2 quark edm is generated in the same way it is generated in su(5 ) and its estimate is identical . on the other hand , whereas in su(5 ) only @xmath186 ( and not @xmath187 ) has non mssm corrections , in so(10 ) the situation is symmetric under @xmath2-@xmath5 exchange , so that @xmath187 has corrections depending on @xmath48 as the @xmath186 ones depend on @xmath47 . moreover , also an approximate expression for @xmath20 can be obtained from that one for @xmath3 exchanging @xmath2 and @xmath5 . @xmath20 has therefore a linear dependence on @xmath1 . moreover , when @xmath1 is large and @xmath188 the main differences between @xmath3 and @xmath20 are due to the different combination of ckm angles and phases , @xmath189 $ ] instead of @xmath190 $ ] , and to the different rl flip , that is provided by @xmath191 and not @xmath192 . with similar phases , the ckm angles could favour @xmath20 . nevertheless , also in so(10 ) with large @xmath1 the @xmath2 quark contribution can not be forgotten . it is also interesting to estimate the corrections to the quark masses that , in su(5 ) and in so(10 ) , contribute to the strong cp violating angle @xmath193 in models without an axion . these contributions are @xmath194t_zt_{\mathrm{g } } \approx 10^{-11}\tan^4\!\beta \fracwithdelims(){|{\operatorname{im}}[\overline{v}^2_{ub}v^2_{tb}]|}{10^{-5}}\ ] ] both in su(5 ) and so(10 ) and @xmath195t_zt_{\mathrm{g } } \frac{\mu m_{3}}{m^2_{\tilde{u } } } \approx 10^{-5}\tan\beta \fracwithdelims(){|{\operatorname{im}}[\overline{v}^2_{td}v^2_{tb}]|}{10^{-4}}\ ] ] in so(10 ) . the bound @xmath196 shows that an axion is necessary in so(10 ) and also in su(5 ) if @xmath1 is large . it is interesting that the large amount of cp violation left by so(10 ) unification in the soft terms furnishes an experimental possibility to see the ` invisible ' axion @xcite . we have studied edms produced by the misalignment of two yukawa matrices in models with universality of soft breaking terms at an high energy scale from the point of view of transformation properties under flavour transformation commuting with the gauge group . in this way it is simple to get the dependence of edms from yukawa couplings , summarized in table [ tab : summary ] . on this basis , estimates are possible and effective for small and large effects . @xmath197 & \lambda_t \lambda_b^4 { \operatorname{im}}[\overline{v}^2_{ub}v^2_{tb}]\\ \,d_d & \lambda_d \lambda_t^4 \lambda_b^2 \lambda_c^2 { j_{\mathrm{cp } } } & \lambda_d \lambda_t^3 \lambda_b^2 \lambda_c { \operatorname{im}}[\overline{v}_{cd}\overline{v}_{cb}v_{tb}v_{td } ] & \lambda_b \lambda_t^4 { \operatorname{im}}[\overline{v}^2_{td}v^2_{tb}]\\ \,d_e & \lambda_e \lambda_t^4 \lambda_b^4\lambda_s^2\lambda_c^2 { j_{\mathrm{cp } } } & \lambda_e \lambda_t^3 \lambda_b^2 \lambda_c { \operatorname{im}}[\overline{v}_{cd}\overline{v}_{cb}v_{tb}v_{td } ] & \lambda_\tau \lambda_t^4 { \operatorname{im}}[\overline{v}^2_{td}v^2_{tb}]\\ \hline \end{array}\ ] ] in the case of mssm , owing to light yukawa coupling suppression , the effects given by one loop diagrams are largely below present experimental limits ( see eq . ) . therefore , the detection of a non vanishing edm for the neutron in foreseeable experiments would be an inequivocable signal of physics beyond the mssm . some interesting contribution to @xmath13 can arise also from more loop diagrams . in the case of minimal supersymmetric su(5 ) and large @xmath1 , on the contrary , the effects can be close to experimental limits with regards to neutron edm because of the contribution of @xmath2 quark , proportional to @xmath4 . for this interesting case the results of an exact computation are given by fig [ fig : du ] . the smallness of @xmath5 quark and electron edms compared with the @xmath2 quark one is also characteristic of su(5 ) . therefore su(5 ) can be distinguished from the mssm because it can give rise to a measurable edm for the neutron . moreover , su(5 ) effects can be distinguished from the so(10 ) ones and from effects coming from universal intrinsic phases in @xmath176 and @xmath29 terms @xcite because of the smallness of the electron edm . on the other hand , at least for the edms a similar pattern can be given by strong cp violation . in the case of minimal supersymmetric so(10 ) it is well known that the @xmath5 quark and electron edms can be close to the experimental limits . if @xmath1 is large , the effect is enhanced by a factor @xmath198 . also in this case , as in su(5 ) , the @xmath2 quark gives an important contribution that must be taken in account . we thank r. barbieri for conversations and help . it is possible to express the neutron edm @xmath13 in terms of the contribution of the quark @xmath199 to the neutron spin @xmath200 and of its edm @xmath201 @xcite : @xmath202 where @xmath203 , @xmath204 e @xmath205 @xcite and @xmath206 is a renormalization factor , @xmath207 . concerning the quark edms , let us consider a supersymmetric extension of standard model at the fermi scale , with minimal field contents , imposed r - parity and generic soft terms a part from a reality hypothesis on @xmath29 ( defined as the coefficient that appears in the soft breaking term @xmath208 , where @xmath191 is the coefficient of the corresponding interaction in the superpotential ) from which it follows that the chargino s and neutralino s mixing matrices can be taken real . such hypothesis is verified with very good precision in the models that we will consider . then the full expressions for the one loop edms of up and down quarks are @xmath209}\notag\\ \mbox{}&+\frac{8}{3 } e \frac{\alpha_3}{4\pi } \frac{1}{m_{3 } } { \operatorname{im}}\big{[}f^{{\tilde{g}}}_{{\mathnormal{u } } } ( \frac{m^2_u}{m^2_{3}})_{u^l_i u^r_i}\big{]}\tag{\ref{expr}a } \\ \mbox{}&+ \frac{y({{\mathnormal{u}}}_r)}{3\cos^2\!\theta_w } e \frac{\alpha}{4\pi } h_{n\tilde{b}}\frac{1}{m_{n_n } } ( \frac{t_3({{\mathnormal{u}}}_l)}{y({{\mathnormal{u}}}_l)}\cot\theta_w h_{n\tilde{w}_3 } + h_{n\tilde{b } } ) { \operatorname{im}}\big{[}f^{n}_{{\mathnormal{u } } } ( \frac{m^2_u}{m^2_{n_n}})_{u^l_i u^r_i}\big{]}\notag\\ \mbox{}&+\lambda_{u_i}^2 \frac{e}{(4\pi)^2 } h_{n \tilde{h}_{{\mathnormal{u}}}^0 } \frac{1}{m_{n_n } } h_{n \tilde{h}_{{\mathnormal{u}}}^0 } { \operatorname{im}}\big{[}f^{n}_{{\mathnormal{u}}}(\frac{m^2_u}{m^2_{n_n}})_{u^l_i u^r_i}\big { ] } \notag\\ d_{d_i } = & \mbox{}-\frac{e}{(4\pi)^2 } h^+_{n \tilde{h}^+_{\mathrm{u } } } \frac{1}{m_{\chi_n } } h^-_{n\tilde{h}^-_{\mathrm{d } } } { \operatorname{im}}\big{[}({\boldsymbol{\lambda}_{\text{\textsc{u}}}^\dagger}f^{\chi}_{{\mathnormal{d}}}(\frac{m^2_u}{m^2_{\chi_n}})_{rl } { \boldsymbol{\lambda}_{\text{\textsc{d}}}^\dagger})_{d^l_i d^r_i}\big{]}\notag\\ \mbox{}&+\frac{8}{3 } e \frac{\alpha_3}{4\pi } \frac{1}{m_{3 } } { \operatorname{im}}\big{[}f^{{\tilde{g}}}_{{\mathnormal{d } } } ( \frac{m^2_d}{m^2_{3}})_{d^l_i d^r_i}\big{]}\tag{\ref{expr}b}\\ \mbox{}&+ \frac{y({{\mathnormal{d}}}_r)}{3\cos^2\!\theta_w } e \frac{\alpha}{4\pi } h_{n\tilde{b}}\frac{1}{m_{n_n } } ( \frac{t_3({{\mathnormal{d}}}_l)}{y({{\mathnormal{d}}}_l)}\cot\theta_w h_{n\tilde{w}_3 } + h_{n\tilde{b } } ) { \operatorname{im}}\big{[}f^{n}_{{\mathnormal{d}}}(\frac{m^2_d}{m^2_{n_n}})_{d^l_i d^r_i}\big { ] } \notag\\ \mbox { } & + \lambda_{d_i}^2\frac{e}{(4\pi)^2 } h_{n \tilde{h}_{{\mathnormal{d}}}^0}\frac{1}{m_{n_n } } h_{n \tilde{h}_{{\mathnormal{d}}}^0 } { \operatorname{im}}\big{[}f^{n}_{{\mathnormal{d } } } ( \frac{m^2_d}{m^2_{n_n}})_{d^l_i d^r_i}\big{]},\notag \stepcounter{equation}\end{aligned}\ ] ] where @xmath210 and @xmath211 are respectively the third component of weak isospin and the hypercharge of the particle @xmath74 ( normalized in such a way that @xmath212 ) . @xmath213 is the gluino and @xmath214 its mass , @xmath215 , @xmath216 are the neutralinos , @xmath217 , @xmath218 , @xmath219 the charginos and @xmath119 , @xmath220 , @xmath221 their mixing matrices . @xmath222 , @xmath223 are the @xmath224 squarks mass matrices in the mass eigenstate basis of corresponding quarks @xmath225 in the right sides of we used a matrix notation . the @xmath64s are the appropriate loop functions , namely linear combinations @xmath226 , where @xmath227 and @xmath228 are the electric charges of the particles running respectively in the scalar and fermion line of the corresponding diagram ( in unity of @xmath10 ) , and @xmath229,\qquad h_2(r ) = \frac{1}{2(r-1)^3}[-2r^2\log r + 3 r^2 - 4r+1].\ ] ] in eqs . the first two contributions to edms are due to charged higgsinos and gluinos exchange and they are the dominant ones . the third ones take account of bino and neutral wino exchange and they are less important than the corresponding gluino exchange , while the last ones come from neutral higgsino exchanges and they are completely negligible . all the contributions in eqs . come from diagrams with none or two elicity flips on the vertices . the one loop diagrams in which the elicity flip occurs on an external leg are always real . as such they do not give any contribution . the diagrams with one elicity flip on the vertices would contribute only if the @xmath29 term were complex . in this case in eqs . also the mixing matrices @xmath119 would be complex and they would appear within the imaginary parts . r. barbieri , s. ferrara , and c. a. savoy , phys . 119b * , 343 ( 1982 ) ; + r. arnowitt , p. nath , and a. chamseddine , 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we study quark and electron edms generated by yukawa couplings in supersymmetric models with different gauge groups , using the edm properties under flavour transformations . in the mssm ( or if soft terms are mediated below the unification scale ) the one loop contributions to the neutron edm are smaller than in previous computations based on numerical methods , although increasing as @xmath0 . a neutron edm close to the experimental limits can be generated in su(5 ) , if @xmath1 is large , through the @xmath2-quark edm @xmath3 , proportional to @xmath4 . this effect has to be taken into account also in so(10 ) with large @xmath1 , where @xmath3 is comparable to the @xmath5 quark edm , proportional to @xmath1 .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Stop Tampering of Prescription Pills Act of 2013''. SEC. 2. ABUSE-DETERRENT TECHNOLOGY. (a) Definition.--Section 201 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321) is amended by adding at the end the following: ``(ss) The term `abuse-deterrent drug' means a drug that-- ``(1) contains as an active moiety a controlled substance that has been classified as opium, an opiate, or a derivative thereof, as such terms are defined or used in section 102 of the Controlled Substances Act; ``(2) has been formulated for oral administration; and ``(3)(A) exhibits physicochemical properties (demonstrated by in vitro, in vivo, or other testing, or some combination thereof, as determined appropriate by the Secretary) that make product manipulation significantly more difficult or ineffective in altering the characteristics of the drug for purposes of misuse or abuse when compared to drugs without such properties; or ``(B) contains one or more additional active or inactive ingredients that are intended to deter abuse through potential pharmacological effects, the effectiveness of which has been demonstrated by at least one adequate and well-controlled investigation.''. (b) Required Information in Application for Approval of Brand Name Drugs.--Section 505(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)) is amended by adding at the end the following: ``(7) Abuse-deterrent drugs.--If an application submitted under this subsection is potentially subject to refusal under subsection (d)(7), the application shall include such information as the Secretary determines necessary to demonstrate that the application is not subject to such refusal.''. (c) Approval of New Brand Name Drugs.--Section 505(d) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(d)) is amended-- (1) by inserting ``(7)(A) such drug has been formulated for oral administration; (B) such drug contains as an active moiety a controlled substance that has been classified as opium, an opiate, or a derivative thereof, as such terms are defined or used in section 102 of the Controlled Substances Act; (C) such drug is not an abuse-deterrent drug; and (D) the Secretary has previously approved pursuant to an application submitted under subsection (b) or (j) a drug that (i) contains the same active moiety; (ii) is an abuse-deterrent drug, and (iii) has not been discontinued from marketing; or'' after ``(6) the application failed to contain the patent information prescribed by subsection (b); or''; (2) by striking ``(7) based on fair'' and inserting ``(8) based on fair''; (3) by striking ``clauses (1) through (6)'' and inserting ``paragraphs (1) through (7)''; and (4) by inserting ``The Secretary may issue an order approving an application, even if paragraph (7) applies, upon a finding that paragraphs (1) through (6) and paragraph (8) do not apply and that such approval is necessary either to prevent or alleviate a drug shortage or to otherwise address a significant unmet public health need.'' before ``As used in this subsection and subsection (e)''. (d) Generic Drugs.--Section 505(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)) is amended-- (1) in paragraph (2)-- (A) subparagraph (A)-- (i) in clause (vii), by striking ``and'' at the end; (ii) in clause (viii), by striking the period at the end and inserting ``; and''; (iii) by inserting after clause (viii) the following: ``(ix) if the listed drug is an abuse-deterrent drug due to its physicochemical properties, information from comparative in vitro, in vivo, or other testing, or some combination thereof, as appropriate based on the type of data submitted for the listed drug, that demonstrates the new drug resists manipulation or the effect of manipulation to a degree at least comparable to the listed drug.''; and (iv) in the continuation text at the end of the subparagraph, by striking ``clauses (i) through (viii)'' and inserting ``clauses (i) through (ix)''; (B) in subparagraph (C)-- (i) in clause (i), by striking ``or'' at the end; (ii) in clause (ii), by striking the period at the end and inserting ``; or''; and (iii) by adding at the end the following: ``(iii) that the listed drug is an abuse-deterrent drug and one or more of the new drug's active moieties differ in any material respect (in amount or otherwise) from those of the listed drug.''; (2) in paragraph (5), by adding at the end the following: ``(G) If a drug has been approved pursuant to an application submitted under paragraph (2), and thereafter the listed drug referred to in the application becomes an abuse-deterrent drug, the drug so approved shall not be considered to be bioequivalent to, or to have the same therapeutic effect as, the listed drug (as described in paragraph (2)(A)(iv)) unless and until the drug so approved has been found by the Secretary to meet the requirements of paragraph (2)(A)(ix).''; and (3) in paragraph (6)-- (A) by striking ``(6) If a drug'' and inserting ``(6)(A) If a drug''; (B) by striking ``(A) for the'' and inserting ``(i) for the''; (C) by striking ``(B) if the'' and inserting ``(ii) if the''; and (D) by adding at the end the following: ``(B) For purposes of this paragraph and paragraph (7)(C), a withdrawal or suspension of a drug formulated for oral administration shall be considered to have been for safety or effectiveness reasons if-- ``(i) the approval of a listed drug, which is not an abuse- deterrent drug, is withdrawn or suspended, or a listed drug, which is not an abuse-deterrent drug, is withdrawn from sale; and ``(ii) the Secretary has previously approved pursuant to an application under subsection (b) a drug that-- ``(I) is in the same dosage form; ``(II) contains the same controlled substance as an active moiety; ``(III) is an abuse-deterrent drug; and ``(IV) has not been discontinued from marketing.''. (e) Withdrawal of Previously Approved Brand Name and Generic Drugs.--Section 505(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(e)) is amended-- (1) by inserting ``or (6)(A) the drug contains as an active moiety a controlled substance that has been classified as opium, an opiate, or a derivative thereof, as such terms are defined or used in section 102 of the Controlled Substances Act; (B) the drug is formulated for oral administration; (C) the drug is not an abuse-deterrent drug; and (D) the Secretary has previously approved pursuant to an application submitted under subsection (b) or (j) a drug that contains the same active moiety, is an abuse-deterrent drug, and has not been discontinued from marketing'' before ``: Provided,''; and (2) by adding at the end the following: ``The Secretary may waive the application of paragraph (6) of the first sentence of this subsection in the case of a drug intended for use in a special needs population. In withdrawing (under paragraph (6) of the first sentence of this subsection) the approval of an application with respect to any drug, the Secretary shall, on a case-by-case basis, delay the effective date of such withdrawal for a period deemed sufficient by the Secretary to give the sponsor an opportunity to obtain approval under this section for a formulation of the drug meeting the criteria described in paragraph (2) of the definition of a `abuse-deterrent drug' in section 201(ss).''. (f) Listed Drugs.--Section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)) is amended by adding at the end the following: ``(D) Beginning 60 days after the date of the enactment of the Stop Tampering of Prescription Pills Act of 2013, the Secretary shall-- ``(i) include in the list under subparagraph (A) a list of each drug or category of drugs which the Secretary has found to be abuse-deterrent drugs; and ``(ii) update the list under subparagraph (A)-- ``(I) to remove from the list of abuse-deterrent drugs any drug the Secretary later determines is not an abuse-deterrent drug; and ``(II) as required by subparagraph (C) to reflect the application of paragraph (6)(B) to drugs that are withdrawn or suspended.''.

Stop Tampering of Prescription Pills Act of 2013 - Amends the Federal Food, Drug, and Cosmetic Act to prescribe new drug application requirements for abuse-deterrent drugs: (1) containing as an active moiety (the part of the drug that makes it work the way it does) a controlled substance classified as opium, an opiate, or a derivative; (2) formulated for oral administration; (3) exhibiting physicochemical properties making them significantly more difficult or ineffective in altering the drug's characteristics for purposes of misuse or abuse; and (4) containing one or more additional ingredients intended to deter abuse through potential pharmacological effects. Requires the Secretary to refuse a new drug application for any new (brand name) drug containing opium, an opiate, or a derivative as an active moiety that is not abuse-deterrent if an abuse-deterrent drug containing the same active moiety has been approved and has not been discontinued from marketing. Authorizes the Secretary to approve an application failing to meet such requirements, however, if approval is necessary to prevent or alleviate a drug shortage or otherwise address a significant unmet public health need. Requires an abbreviated new (generic) drug application for an abuse-deterrent drug to include testing information demonstrating that the generic drug resists manipulation or the effect of manipulation to a degree at least comparable to the listed drug. Authorizes the Secretary to deny approval of a generic application if the listed drug is abuse-deterrent and one or more of the generic drug's active moieties differ in any material respect from those of the listed drug. Declares that an approved generic drug shall not be considered bioequivalent to, or as having the same therapeutic effect as, a listed drug if the listed drug becomes abuse-deterrent unless and until the generic drug demonstrates that it resists manipulation or the effect of manipulation to a degree at least comparable to the listed drug. Prescribes requirements governing when a drug which is not abuse-deterrent may have its approval withdrawn or suspended.

addiction is one of the most disturbing and problematic social phenomena in current years with known social , economic , and individual detriments . these researches demonstrated that opium and heroin are the main substances being abused while achieving a complete abstinence is the main expected outcome for treatment of addiction . detoxification is the first step of substance abuse / dependence treatment and researches about brief and cost - effective methods receive a lot of interest in iran . long - term opioid use would increase the cyclic adenyl cyclase in noradrenergic system of the locus coeruleus . hence this compensatory increase in cyclic adenyl cyclase would result in adrenergic withdrawal symptoms during rapid opioid cessation . some pharmacological agents ( opioid agonists , opioid agonist - antagonists , opioid antagonists , and alpha-2 agonists ) are studied and used in opioid detoxification . the efficacy of clonidine ( as an alpha-2 agonist ) in controlling the withdrawal symptoms is established in randomized placebo - controlled clinical trials . a review study by raith and hochhaus in 2004 in germany concludes that three main mechanisms are responsible for opioid tolerance and the withdrawal syndrome dependence which are upregulation of adenyl cyclase and nitric oxide synthetase and activation of nmda receptors . consequently the use of alpha-2 agonists ( e.g. , clonidine ) and nmda antagonists ( e.g. , dextromethorphan , ketamine ) may minimize the tolerance phenomenon and decrease the withdrawal symptoms . a randomized clinical trial by koyuncuoglu and saydam in 1990 compared the efficacy of dextromethorphan and diazepam to a combination of chlorpromazine and diazepam on treating withdrawal symptoms of heroin . they showed that those patients receiving dextromethorphan and diazepam would experience milder withdrawal symptoms . considering the detoxification phase as the first step of the treatment of opium - addicted patients and the different effect site of nmda antagonists ( e.g. , dextromethorphan ) and alpha-2 adrenergic agonists ( e.g. , clonidine ) , we decided to evaluate the synergistic effects of these medications in control and relief from opiate withdrawal symptoms . this study was performed as a double - blind randomized clinical trial in razi hospital , tabriz , iran . sixty patients , based on the results of the similar studies , were selected from among inpatients of detox and rehabilitation ward . the inclusion criteria were male sex , age range of 20 to 40 years , positive morphine test , the diagnosis of opiate dependence according to the dsm - iv - tr criteria , and mild cases of withdrawal syndrome in severity based on the clinical opiate withdrawal scale ( cows ) . the inclusion criteria were selected according to gerra et al . who previously reported the interrelation of sex and the response to detoxification as well as factors introduced by previous similar studies and studies about the effective factors in successful detoxification [ 79 ] . also , due to medical ethics observations only mild cases of withdrawal syndrome were selected . to control the withdrawal symptoms in severe cases it was possible that we change the treatment protocol and use different dosing or add other drugs . exclusion criteria included ( 1 ) psychotic patients ( 2 ) severe somatic diseases including hepatic or renal insufficiencies ( creatinine > 1.2 mg / dl , alt > 40 iu ) . after giving a written informed consent , the selected patients , based on the inclusion and exclusion criteria , were randomly allocated to two groups receiving either clonidine alone or a combination of clonidine and dextromethorphan . for blinding the study , the examining physician who fulfilled the clinical opiate withdrawal scale ( cows ) was differed from the physician who prescribed the drugs and also the prescribed drugs in one group were not clear for the patients in the other group . the first group received clonidine 0.41.2 mg per day in three divided doses according to the patient 's tolerance , clonazepam 1 mg every eight hours , and acetaminophen 500 mg every six hours . acetaminophen was used as analgesic and clonazepam was used as a sedative and anxiolytic agent according to the standard detoxification protocols . the second group received clonidine 0.41.2 mg per day in three divided doses according to the patient 's tolerance , clonazepam 1 mg every eight hours , acetaminophen 500 mg every six hours , and dextromethorphan 75 mg every six hours . tolerance of patients for effects of clonidine was evaluated by their blood pressure while the systolic blood pressure less than 90 mm hg was set as the threshold for dose modification . the other medications were selected from available preparations of the same company to obtain the same effects . all of the patients were evaluated for severity of withdrawal symptoms at the admission time and 24 , 48 , and 72 hours later by a physician blinded to the grouping of patients . the clinical opiate withdrawal scale ( cows ) was used by the american association of addiction medicine as a good indicator of clinical severity of withdrawal symptoms . cows estimates the severity of opioid withdrawal symptoms in 11 categories : resting pulse rate , sweating , restlessness , pupil size , bone or joint aches , runny nose or tearing , gastrointestinal upset , tremor , yawning , anxiety or irritability , and gooseflesh skin . the symptoms may be subdivided into four categories according to the total score as mild ( 512 scores ) , moderate ( 1324 scores ) , relatively severe ( 2536 scores ) , or very severe ( more than 36 scores ) . as it was completed by two physicians during the study , the interobserver reliability was assessed in 18 patients and the pearson 's correlation test showed positive significant correlation between evaluators ( p < 0.0001 ) with a cronbach 's alpha being 0.907 showing a high reliability . the study proposal was approved by medical ethics committee of tabriz university of medical sciences in accordance with the principles of the declaration of helsinki . the principal statistical analysis evaluated the severity of the withdrawal symptoms using a 2 2 repeated analysis of variance ( anova ) design with a group factor ( clonidine versus clonidine and dextromethorphan ) , and a repeated - measures factor ( pretreatment ; 24 , 48 , and 72 hours after admission ) . no significant differences were observed between the two groups regarding basic characteristics including withdrawal symptoms at admission time . there were no clinically significant adverse events in regard to the used drugs ' side effects during the trial . analysis of variance of the symptom severity score ( by cows ) revealed a significant group time interaction ( f = 14.25 ; p < 0.001 ) , so that patients receiving dextromethorphan plus clonidine had milder symptoms during three days . as illustrated in figure 1 , symptom severity in the two groups had a different pattern and patients receiving dextromethorphan experienced milder symptoms in all of the measurements compared to clonidine group . at admission ( baseline ) . the withdrawal symptoms were mild at baseline ( total score from five to 12 points ) . the withdrawal symptoms severity ( mean total score ) was alike between clonidine group ( 2.7 1.9 ) and dextromethorphan and clonidine group ( 3.4 2.6 ) with no significant difference ( p = 0.17 ) . this increase was more in clonidine group but without significant difference ( p = 0.18 ) compared with dextromethorphan and clonidine group ( 6 2.8 versus 5.1 2.9 ) . this increase was more in clonidine group with a significant difference ( p = 0.0001 ) compared with dextromethorphan and clonidine group ( 8 3 versus 5.3 2.6 ) . the severity of withdrawal symptoms was significantly ( p = 0.0001 ) more in clonidine group compared with dextromethorphan and clonidine group ( 9.8 5.1 versus 5.1 2.8 ) . the used drugs in this study were those used as routine agents in different diseases and had no side effects in used doses . this study shows that dextromethorphan added to clonidine regimen has a better efficacy compared to clonidine alone in controlling the mild withdrawal symptoms in male opioid addicts . in the patients receiving clonidine alone the withdrawal symptoms increased across the study and reached their most severity after 72 hours from admission , while patients who received dextromethorphan and clonidine experienced milder symptoms . the alpha-2 agonists such as clonidine may decrease the withdrawal symptoms by controlling the excess activity of the adrenergic system . clonidine is being used in the treatment of withdrawal syndrome since 1980 [ 1214 ] and a majority of detoxification regimens are using it , but its effectiveness is not optimal when used alone . n - methyl - d - aspartate ( nmda ) receptors of the glutaminergic neurotransmitter system are an activator mediator of the central nervous system ( cns ) and exist in different sites of cns . hyperstimulation of these receptors in events such as strokes , head trauma , and convulsive attacks would result in neuronal death while their decreased activity would result in schizophrenic status . kukanich and pabich ( 2004 ) report that dextromethorphan is a noncompetitive antagonist of nmda receptors that is used as an antitussive , adjuvant analgesic , alcohol , and opioid withdrawal symptom reducer . it is also used in clinical trials combined with morphine resulting an increased analgesic effect . the fact that nmda antagonists may relieve some withdrawal symptoms is a sign of association between glutaminergic and opioid neurotransmitter systems . nmda - antagonists would reduce the effects of opioids withdrawal on basal forebrain and amygdale , but they do not affect the locus cerelous . moreover it seems that nmda - antagonists would result in a delay in developing tolerance to opioid . ( 2003 ) showing that the increased expression of c - fos gene is related to withdrawal intensity in mice neonates and dextromethorphan may reduce the related mrna amount and is also effective in relief of withdrawal symptoms . the role of nmda - antagonists in opioid withdrawal relief is also described for another medication from this group , memantine , which decreased the symptoms of withdrawal in heroin - addict patients . a single - blind study by bisaga et al . ( 1997 ) evaluated the role of dextromethorphan in relief of withdrawal symptoms . they used dextromethorphan ( 75 mg five times a day ) and the result confirmed its efficacy in decreasing the withdrawal symptoms and craving . these results are confirmed by the present double - blind study as well . in a similar study ( 2007 ) , it was demonstrated that memantine solely is effective in the reduction of subjective symptoms of withdrawal syndrome and the authors recommended that memantine may be used as an adjuvant therapy in the reduction of withdrawal symptoms . simultaneously there have been efforts to increase the bioavailability of dextromethorphan as well . a group of opioid dependence patients were treated with a combination of dextromethorphan and quinidine , aiming to decrease the metabolism of dextromethorphan and dextrophan level ( quinidine inhibits the metabolism of dextromethorphan , leading to reduce of dextromethorphan metabolite , dextrorphan , levels ) . authors found that this combination was ineffective in reducing the withdrawal symptoms compared to placebo and most of the patients left the study in six days due to the severity of symptoms . in the study by bisaga et al . dextromethorphan resulted in the reduction of withdrawal symptoms in the fourth day , which is longer than our results ( reduction began in second day ) . this may decrease generalization of the results as they were highly motivated and this could influence their subjective complaints in part . this study could not include a placebo group like most of the studies in this field . dextromethorphan , as a nmda antagonist , is effective in the relief of withdrawal symptoms . hence it is very useful in increasing the efficacy of clonidine and reducing the need for opioid agonists . added dextromethorphan to clonidine resulted in symptom reduction as soon as the second day of admission while patients experienced very few side effects .

background . dextromethorphan is a noncompetitive n - methyl d - aspartate receptor antagonist that is clinically feasible for relieving the opioid withdrawal symptoms . this study compares the efficacy of a combination therapy with dextromethorphan and clonidine to treatment with clonidine alone . methods and materials . in this double - blind randomized clinical trial , patients were selected from inpatients of detox and rehabilitation ward of razi hospital , tabriz , iran . they were randomly allocated to two groups receiving either clonidine ( 0.41.2 mg / day ) or clonidine and dextromethorphan ( 300 mg / day ) . withdrawal symptoms were evaluated in the first day of admission and again 24 , 48 , and 72 hours later . results . thirty male patients completed the trial in each group . withdrawal symptoms began to decrease in the second day in patients receiving dextromethorphan and clonidine while patients receiving clonidine experienced the more severe symptoms in 72 hours . analysis of variance of the symptom severity score revealed a significant group time interaction ( f = 14.25 ; p < 0.001 ) , so that patients receiving dextromethorphan plus clonidine had milder symptoms during three days in all of the measurements compared to clonidine group . conclusion . combination therapy of dextromethorphan and clonidine would result in milder opioid withdrawal symptoms compared to clonidine alone with a reduction beginning at the second day .

achieving predictable long - term success of root canal treatment requires effective debridement and disinfection of root canal system . this is not always achieved completely because of anatomical complexity and the limitation in accessing the canal system by instruments and irrigants . candida albicans is the most common fungus seen in the root canals , 21% in primary infections and 18% in cases of retreatments . it can survive harsh conditions due to biofilm formation and the physicochemical properties of the microorganisms help them to modify according to the prevailing environmental and nutritional conditions . biofilm helps in resisting the destruction of the fungus by making them thousand times more resistant to phagocytosis , antibodies and antimicrobial agents . this is attributed to the protective barrier provided by the extracellular matrix . c. albicans is also resistant to calcium hydroxide , which is the most commonly used intracanal medicament . sodium hypochlorite has remained a popular root canal irrigant because of its antimicrobial potential and its ability to dissolve organic matter . however , it is not only irritant to the periapical tissues , but also inherently possesses certain disadvantages such as staining of instruments , burning of surrounding tissues , unpleasant taste , high toxicity , corrosive to instruments , inability to remove the smear layer , reduction in elastic modulus and flexural strength of dentin . propolis is a brownish resinous substance collected by bees mainly from plants , which is used to reinforce their hives and keep the environment aseptic . it is a potent antimicrobial , antioxidant and anti - inflammatory agent due to the presence of flavonoids , phenolics and other aromatic compounds . azadirachta indica ( neem ) is the most commonly used traditional medicinal plant of india . each part of the neem tree has some medicinal property and is thus commercially exploitable . neem elaborates a vast array of biologically active compounds that are chemically diverse and structurally complex . neem leaf and its constituents have been demonstrated to exhibit immunomodulatory , anti - inflammatory , antifungal , antibacterial , antiviral , antioxidant , antimutagenic and anticarcinogenic properties . the present study is aimed to explore newer herbal irrigants , which as potential antimicrobial agents in the inhibition of c. albicans in comparison to sodium hypochlorite . a pure culture of c. albicans atcc 10231 ( himedia , mumbai l. no . 443 - 207 ) was inoculated on sabouraud dextrose agar ( himedia , mumbai ) , incubated at 37c overnight and adjusted to an optical density of one with sterile brain - heart infusion broth . propolis ( herbal biosolutions , delhi ) was prepared by diluting a 33% commercially available alcoholic extract using warm saline in a ratio 2:1 , to form an 11% alcoholic extract . alcoholic extract of neem was prepared using 25 g of fresh neem leaves powder of 99% purity ( the indian neem tree company , mumbai ) was added to 50 ml of absolute ethanol ( sterling chemicals and alcohols pvt . ltd . , mixture was macerated for 1 - 2 min , then extract was filtered through muslin cloth for coarse residue and then through filter paper for finer residue . single rooted type 1 vertucci 's classification human mandibular premolar teeth were sectioned below the cementoenamel junction to obtain a standardized tooth length of 8 mm . the teeth were cleaned of superficial debris , calculus , tissue tags and stored in normal saline . the root canals were then instrumented using the crown down technique and rotary instruments to an apical size of protaper f3 . a total volume of 2 ml of 5% sodium hypochlorite ( prime dental products private limited , thane and maharashtra ) was used between each instrument during the cleaning and shaping procedure . the concave tooth surface was minimally grounded to achieve flat surface to enable placement in tissue culture wells exposing the root canal surface to c. albicans to form a biofilm . the samples were then sterilized by ultraviolet radiation in a biosafety cabinet ( accumax india , new delhi ) and placed in the wells of tissue culture plates . the cultured yeast was inoculated in the wells containing tooth samples at 37c for 2 days . the samples were divided into five experimental groups with 10 samples each and irrigated with 3 ml of each irrigant for 10 min . group 1 propolisgroup 2 mcjgroup 3 a. indica ( neem)group 4 5% sodium hypochloritegroup 5 sterile saline . group 3 a. indica ( neem ) group 4 5% sodium hypochlorite group 5 sterile saline . sterile paper point technique was used for sampling of root canals and inoculated in sabouraud dextrose agar and incubated at 37c for 24 h in a petridish , which was then analyzed by the digital colony counter ( spectronics india , haryana ) and the readings were subjected to statistical analysis using analysis of variance and post hoc tukey tests . a pure culture of c. albicans atcc 10231 ( himedia , mumbai l. no . 443 - 207 ) was inoculated on sabouraud dextrose agar ( himedia , mumbai ) , incubated at 37c overnight and adjusted to an optical density of one with sterile brain - heart infusion broth . propolis ( herbal biosolutions , delhi ) was prepared by diluting a 33% commercially available alcoholic extract using warm saline in a ratio 2:1 , to form an 11% alcoholic extract . alcoholic extract of neem was prepared using 25 g of fresh neem leaves powder of 99% purity ( the indian neem tree company , mumbai ) was added to 50 ml of absolute ethanol ( sterling chemicals and alcohols pvt . ltd . , mixture was macerated for 1 - 2 min , then extract was filtered through muslin cloth for coarse residue and then through filter paper for finer residue . single rooted type 1 vertucci 's classification human mandibular premolar teeth were sectioned below the cementoenamel junction to obtain a standardized tooth length of 8 mm . the teeth were cleaned of superficial debris , calculus , tissue tags and stored in normal saline . the root canals were then instrumented using the crown down technique and rotary instruments to an apical size of protaper f3 . a total volume of 2 ml of 5% sodium hypochlorite ( prime dental products private limited , thane and maharashtra ) was used between each instrument during the cleaning and shaping procedure . the concave tooth surface was minimally grounded to achieve flat surface to enable placement in tissue culture wells exposing the root canal surface to c. albicans to form a biofilm . the samples were then sterilized by ultraviolet radiation in a biosafety cabinet ( accumax india , new delhi ) and placed in the wells of tissue culture plates . the cultured yeast was inoculated in the wells containing tooth samples at 37c for 2 days . the samples were divided into five experimental groups with 10 samples each and irrigated with 3 ml of each irrigant for 10 min . group 1 propolisgroup 2 mcjgroup 3 a. indica ( neem)group 4 5% sodium hypochloritegroup 5 sterile saline . group 3 a. indica ( neem ) group 4 5% sodium hypochlorite group 5 sterile saline . sterile paper point technique was used for sampling of root canals and inoculated in sabouraud dextrose agar and incubated at 37c for 24 h in a petridish , which was then analyzed by the digital colony counter ( spectronics india , haryana ) and the readings were subjected to statistical analysis using analysis of variance and post hoc tukey tests . readings of microbial count obtained from digital colony counter after irrigation with respective irrigant were as follows : table 1 . mean and standard deviation showing inter group differences obtained from the readings of digital colony counter the mean and standard deviations obtained were as follows . microbial count was maximum in the saline group and minimum in propolis and sodium hypochlorite groups . absolute washout of c. albicans biofilm was observed in 8 out of 10 samples of propolis and sodium hypochlorite groups . neem group also showed a higher antimicrobial efficacy as compared with mcj and saline groups . saline ( negative control ) had least antimicrobial activity as expected . except for comparison between propolis and sodium hypochlorite , all the between group differences were statistically significant . the order of efficacy of different groups was as follows : propolis ~ sodium hypochlorite > neem > mcj > saline this study was conducted on c. albicans because these microorganisms are commonly encountered in recalcitrant endodontic infections . c. albicans has an initial period of adherence ( 0 - 2 h ) followed by subsequent microcolony formation ( 2 - 4 h ) . dimorphic switching occurred thereafter with a transition from budding - yeast forms to filamentous pseudo- and true - hyphal forms ( 4 - 6 h ) . micro - colonies then become interlinked by the hyphal extensions , forming a confluent monolayer ( 6 - 8 h ) . the complexity of the biofilm increases with time , taking on 3d architecture with spatial heterogeneity as it matured ( 8 - 48 h ) . the biofilm after 24 and 48 h consists of a mixture of yeast cells , pseudohyphae and true hyphae . filamentous forms were the most important factor in the 3d architecture , with yeast cells located in the basal layer . c. albicans mutants that are deficient in the production of hyphae have demonstrated an inability to form 3d biofilms . therefore , the dimorphic switching observed in this species is a pivotal factor for biofilm formation and the pathogenic potential of c. albicans , which is why the 48 h biofilm model was used . sodium hypochlorite is the most commonly used irrigating solution in clinical practice because of its tissue dissolution and antimicrobial activity , making it an irrigating solution of choice irrespective of its several undesirable characteristics such as tissue toxicity , risk of emphysema , allergic potential and disagreeable smell and taste . ayhan et al . demonstrated that sodium hypochlorite lowered colony forming units below the limit of detection after 10 s in the case of c. albicans . propolis exhibits antimicrobial , anti - inflammatory , healing , anesthetic and cariostatic properties . according to takaisi - kikuni and schilcher , it prevents fungal cell division and also breaks down fungal cell wall and cytoplasm similar to the action of some antibiotics . reported the antimicrobial action of propolis to be due to flavonoids and esters of phenolic acids . the ph chosen for propolis was six based on the results of the study conducted by ivanaji et al . since the inhibitory effect of propolis was the strongest in a slightly acidic environment ( ph = 6 ) . in an inflammatory process there is a slight decrease of ph ; thus , it would be most beneficial to use the extract of propolis of slightly acidic ph . , acetone and ethanolic extracts were found to be more active toward most microorganisms . as for neem , the ethanolic extracts performed better than the aqueous extract , therefore to standardize we prepared both our test solutions using ethanol . a study conducted grange and davey showed the antimicrobial efficacy of propolis against enterococcus species , staphylococcus aureus and c. albicans . it also showed antibacterial efficacy against escherichia coli , achromobacter , sarcina lutea and morganella morgani . a. indica ( neem ) ( ph = 6.8 ) has antimicrobial properties due to the presence of alkaloids , glycosides , saponins , flavonoids , steroids , anthraquinone and tannic acid . bohora et al . have concluded that neem leaf extract has a significant antimicrobial effect against c. albicans . acidic ethanolic extract was found to be better than aqueous extract in cases of c. albicans . neem has a wide spectrum of antimicrobial action ; against gram - negative and gram - positive microorganisms , including m. tuberculosis , m. pyogenes , streptococcus mutans and enterococcus faecalis . furthermore , effective against certain human fungi including trychophyton , epidermophyton , microsporum , trichosporon , geotricum and candida . . the beneficial antimicrobial effects may be the result of acubin , l - asperuloside , alizarin , scopoletin and other anthraquinones . showed that mcj showed no significant activity against c. albicans , which might be due to the fact stated by jainkittivong et al . who showed that in case of m. citrifolia fruit longer the contact time , higher is the inhibitory effect . the contact time found to be effective was 45 min , but in our study we took 10 min to standardize the procedure and simulate a clinical situation . it has antimicrobial action against pseudomonas aeruginosa , proteus morgaii , s. aureus , bacillus subtilis , e. coli , salmonella , shigella , e. faecalis and c. albicans . the shelf lives of ethanolic extract of propolis is 2 years , for neem leaf extract is 3 years and mcj is 3 years when not opened and 2 years after opening , if stored properly , as per the manufacturer 's instructions . compared the antibacterial activity of propolis and calcium hydroxide against c. albicans , but the drawbacks of the study was that the biofilm model was not used thereby not simulating clinical condition and other herbal irrigants were not compared in the study . bohora et al . compared the antifungal efficacy of neem leaf extract against c. albicans , but again the biofilm model was not used . until date , no study has been conducted comparing all these herbal irrigants with sodium hypochlorite in a biofilm model against c. albicans and therefore , this study holds ground for future research . according to the results of the study , we see a promising herbal irrigant in propolis against c. albicans in root canal infections . under the limitations of this study , it was concluded that : propolis performed equally well as sodium hypochlorite against c. albicans biofilm formed on extracted tooth surface.a . propolis performed equally well as sodium hypochlorite against c. albicans biofilm formed on extracted tooth surface .

introduction : endodontic infections are polymicrobial in nature . candida albicans is the most common fungus isolated from failed endodontic cases . the constant increase in antibiotic resistant strains and side - effects caused by synthetic drugs has prompted researchers to look for herbal alternatives such as propolis , morinda citrifolia and azadirachta indica ( neem ) etc . , since , the gold standard for irrigation , i.e. , sodium hypochlorite has many disadvantages.materials and methods : extracted human mandibular premolars were biomechanically prepared , vertically sectioned , placed in tissue culture wells exposing the root canal surface to c. albicans grown on sabouraud dextrose agar to form a biofilm . at the end of 2 days , all groups were treated with test solutions and control for 10 min and evaluated for candida growth and number of colony forming units . the readings were subjected to statistical analysis using analysis of variance and post hoc tukey tests.results:sodium hypochlorite and propolis groups exhibited highest antimicrobial efficacy against c. albicans with no statistically significant difference . it was followed by the a. indica ( neem ) group . m. citrifolia had limited antifungal action followed by the negative control group of saline.conclusion:according to the results of this study , propolis can be used as an effective antifungal agent similar to that of sodium hypochlorite , although long - term in vivo studies are warranted .

models of opinion formation have been studied by physicists since the 80 s and are now part of the new branch of physics called sociophysics @xcite . this recent research area uses tools and concepts of the physics of disordered matter and more recently from the network science to describe some aspects of social and political behavior @xcite . from the theoretical point of view , opinion models are interesting to physicists because they present correlations , order - disorder transitions , scaling and universality , among other typical features of physical systems @xcite . one of the most studied models to analyze the dynamics of agreement and disagreement is the voter model ( vm ) @xcite . the vm was introduced to study the competition of species @xcite and was firstly named voter model in the work of holley and ligget @xcite . it represents a very simple formulation of opinion dynamics , where each agent carries one opinion given by an ising variable @xmath7 and a randomly choosen agent takes the opinion of one of his neighbors at each time step . in other words , the vm is a paradigmatic example of nonequilibrium copying dynamics , where the agents imitate their neighbors . concerning regular lattices , this model can be exactly solved in any dimension @xcite . besides the simplicity of the model , it was shown that the two - dimensional vm represents a broad class of models , defining a kind of voter - model universality class @xcite . the vm was extended to take into account different ingredients . as examples , we can cite the generalization to three @xcite or more variables @xcite , the inclusion of special agents like zealots @xcite , introduction of memory @xcite and time - dependent transition rates @xcite , and others . the model was also studied in several types of complex networks , that have nontrivial effects on the ordering dynamics ( see @xcite and references therein ) . in addition to the interactions among individuals , it is also interesting from theoretical and practical points of view to analyze the influence of external effects on agent - based social models @xcite . in opinion dynamics , for example , these external effects act in the system as a mass media ( television , radio , ... ) . among the previous studies considering mass - media effects , one can cite the sznajd opinion model @xcite , the axelrod model of culture diversity @xcite and some other social models @xcite . the external effects make social models more realistic , and they may produce interesting results like the induction / suppression of phase transitions , the decrease of the relaxation times and the emergence / lack of consensus . in this work we study a three - state opinion model , where the agents states or opinions are represented by variables @xmath8 , @xmath9 or @xmath10 . the agents change their opinions via two competing mechanisms . two agents may interact via a voter - model dynamics , but the usual imitation process is limited by a particular feature of each agent , his conviction , a characteristic that was considered in some opinion models @xcite . in addition , there is a noise in the system that allows the agents to change their opinions to @xmath11 . we analyze the consequences of these two ingredients , convictions and noise , on opinion formation and on opinion spreading across the population . after the initial analysis , we add an external effect that acts in the system as a mass medium , and we study the consequences of the presence of this external effect on the behavior of the model . this work is organized as follows . in section 2 we present the miscroscopic rules that define the model . the numerical and analytical results are discussed in section 3 , and our conclusions are presented in section 4 . we have considered a square lattice of size @xmath12 with periodic boundary conditions as a simple representation of the social contacts among individuals . each agent @xmath13 in the population may be in one of three possible states , namely @xmath14 , @xmath9 or @xmath10 . this scenario can represent any public debate , for example an electoral process with 2 different candidates a and b where each agent ( or elector ) votes for the candidate a ( opinion @xmath15 ) , for the candidate b ( opinion @xmath9 ) or is undecided ( opinion @xmath10 ) . in addition , each agent has a conviction @xmath16 about his opinion . in the case of undecided voters , this conviction is given by @xmath17 , and for the cases of opinions @xmath15 and @xmath9 each conviction is given by a random number generated from a uniform distribution @xmath18 $ ] . the following microscopic rules control our model : * we choose a random agent @xmath13 ; * we choose at random one of his nearest neighbors , say @xmath19 ; * if @xmath20 , nothing occurs ; * on the other hand , if @xmath21 , the agent with the lower conviction , say @xmath19 , is persuaded by @xmath13 and adopt both the opinion and the conviction of @xmath13 . in other words , if @xmath22 we update @xmath23 and @xmath24 ; * if one of the two agents , say @xmath19 , is undecided ( @xmath25 ) , he follows the opinion of agent @xmath13 and take his conviction about that opinion , i.e. , we update @xmath23 and @xmath24 . * we choose at random another nearest neighbor of @xmath13 ( different from @xmath19 ) , say @xmath26 . with probability @xmath1 this agent @xmath26 becomes undecided , i.e. , we update @xmath27 and @xmath28 ; thus , the interactions are of voter - model type @xcite , but the usual imitation or copying process is limited by the agents convictions . in addition , we considered that a certain persuaded agent takes not only the opinion but also the conviction of the agent that interacted with him . in the case of undecided voters , we considered that the convictions are @xmath17 , and thus they are easily persuaded by decided voters . for undecided voters does not change qualitatively the results of the model , as discussed in the following . ] notice also that the probability @xmath1 acts as a noise in the system , and it allows the spontaneous change of opinions ( to @xmath11 ) of some agents @xcite . observe also the presence of intrinsic correlations in the system : the interacting agents @xmath13 and @xmath19 , as well as the agent @xmath26 that suffers the effect of noise are always neighbors in the square lattice . then , our dynamics inserts correlation effects on the noise itself . some consequences of these correlations are discussed in the next section . in the following we will see that the presence of such heterogeneities in the population ( convictions and noise ) affects the persuasion process and the consensus states are obtained only in the absense of noise . we will also analyze an extension of the model considering an external effect , that acts in the system as a mass medium . for the above - mentioned rules , we made the following assumptions : ( i ) as the agents interact by pairs , we have considered that if a given agent persuades another agent to change opinion ( explaining the reasons for choosing a certain candidate , for example ) , the persuaded individual will became a supporter of the choosen opinion ( candidate ) and he will influence other individuals based on the `` learned '' reasons ; ( ii ) undecided individuals or voters are passive , in the sense that they do not spread their lack of opinion to other individuals @xcite ; ( iii ) undecided agents are easily persuaded by interaction with someone that already has a formed opinion ( which explain the null convictions ) ; ( iv ) the noise @xmath1 represents the fact that some individuals in an electoral process choose a certain candidate at some time but they are not sure about their choices ( in this case , those individuals may become undecided until interact with other agents ) . in the absence of external effects , the model follows exactly the rules presented in the previous section . the initial state of the system is fully disordered , i.e. , all opinions are equally probable ( @xmath29 for each one ) . one time step in the model is defined by the application of the above - mentioned rules @xmath30 times , where @xmath31 is the total number of agents in the lattice . as a first analysis , we have considered the order parameter @xmath32 given by @xmath33 and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the absence of external effects . each graphic is a single realization of the dynamics on a square lattice of size @xmath37 and noise parameter @xmath38 ( a ) , @xmath39 ( b ) , @xmath40 ( c ) and @xmath41 ( d ) . , title="fig:",scaledwidth=40.0% ] and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the absence of external effects . each graphic is a single realization of the dynamics on a square lattice of size @xmath37 and noise parameter @xmath38 ( a ) , @xmath39 ( b ) , @xmath40 ( c ) and @xmath41 ( d ) . , title="fig:",scaledwidth=40.0% ] + and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the absence of external effects . each graphic is a single realization of the dynamics on a square lattice of size @xmath37 and noise parameter @xmath38 ( a ) , @xmath39 ( b ) , @xmath40 ( c ) and @xmath41 ( d ) . , title="fig:",scaledwidth=40.0% ] and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the absence of external effects . each graphic is a single realization of the dynamics on a square lattice of size @xmath37 and noise parameter @xmath38 ( a ) , @xmath39 ( b ) , @xmath40 ( c ) and @xmath41 ( d ) . , title="fig:",scaledwidth=40.0% ] that is the `` magnetization per spin '' of the system . in fig . [ fig1 ] we exhibit the time evolution of the order parameter for typical values of the noise @xmath1 . for all cases we have observed that in the steady states the fraction of one of the extreme opinions @xmath15 or @xmath9 are not found anymore in the population . thus , in the stationary states the magnetization is given by @xmath42 ( @xmath43 ) in the case where the opinion @xmath9 ( @xmath15 ) disappears of the system , where @xmath34 ( @xmath35 ) is the fraction of @xmath15 ( @xmath9 ) opinions . in fig . [ fig1 ] we can see that the fraction @xmath36 of @xmath11 opinions ( undecided individuals ) for long times is different from zero , except for the noiseless case @xmath38 where we have @xmath44 in the steady states . we can also see from fig . [ fig1 ] that the system reaches consensus with all opinions @xmath15 or @xmath9 only for @xmath38 . these two results can be predicted analytically , as we will see in the following . as discussed before , the initial state of the population is disordered such that the initial fraction of @xmath11 opinions is @xmath45 . we have verified numerically that the stationary fraction @xmath36 is greater than that initial value @xmath29 only for @xmath46 , as it is shown in figs . [ fig1 ] ( c ) and ( d ) . we can also see from fig . [ fig1 ] that the system needs more time to reach the steady states when we increase the noise @xmath1 . in fact , for increasing values of @xmath1 more agents will change their opinions to @xmath11 such that more interactions among agents will occur , as well as more competition among the opinions . another important result is that this final fraction @xmath36 of @xmath11 opinions is greater than the other surviving fraction ( @xmath34 or @xmath35 ) for sufficient large values of @xmath1 . an example of this behavior is exhibited in fig . [ fig1 ] ( d ) , for the case @xmath41 . we will discuss this in more details in the following . for typical values of the noise @xmath1 . each curve represents a single realization of the dynamics on a square lattice of size @xmath37 ( a ) . it is also exhibited the average stationary values of the order parameter @xmath47 and the fraction of undecided voters @xmath48 versus @xmath1 obtained numerically for the 2d case and for the mean - field ( mf ) case for populations of size @xmath49 ( b ) . each symbol is averaged over @xmath50 independent simulations . the full and dashed lines are fits with second - order polynomials for the 2d case , whereas the dotted lines are the eqs . ( [ eq4 ] ) and ( [ eq5 ] ) , as explained in the text . , title="fig:",scaledwidth=48.0% ] for typical values of the noise @xmath1 . each curve represents a single realization of the dynamics on a square lattice of size @xmath37 ( a ) . it is also exhibited the average stationary values of the order parameter @xmath47 and the fraction of undecided voters @xmath48 versus @xmath1 obtained numerically for the 2d case and for the mean - field ( mf ) case for populations of size @xmath49 ( b ) . each symbol is averaged over @xmath50 independent simulations . the full and dashed lines are fits with second - order polynomials for the 2d case , whereas the dotted lines are the eqs . ( [ eq4 ] ) and ( [ eq5 ] ) , as explained in the text . , title="fig:",scaledwidth=44.0% ] we can study the steady - state properties of the model in more details . it is shown in fig . [ fig2 ] ( a ) the time evolution of the order parameter @xmath32 for some values of the noise @xmath1 , for a lattice size @xmath37 . one can see that the stationary values of the magnetization decrease for increasing values of @xmath1 , as observed before ( see fig . [ fig1 ] ) . we have considered the time averages of the stationary values of the order parameter @xmath32 for @xmath50 independent simulations , which give us the mean values @xmath51 exhibited in fig . [ fig2 ] ( b ) . we can observe that there is no order - disorder transition : the lower value of @xmath51 is about @xmath52 . we also plotted in fig . [ fig2 ] ( b ) the average value of the fraction of undecided voters @xmath48 ( also over @xmath50 realizations ) . as expected , when we increase the noise @xmath1 the fraction of agents with opinion @xmath11 increases . as discussed above , for sufficient large values of @xmath1 the final fraction @xmath36 is greater than the other surviving fraction ( @xmath34 or @xmath35 ) . we can clearly see this behavior in fig . [ fig2 ] ( b ) : there is a threshold value @xmath53 above which the average stationary fraction @xmath48 is greater than @xmath51 . to estimate the numerical value of @xmath53 we fitted the data for @xmath51 and @xmath48 with second - order polynomials [ see the dashed and full lines in fig . [ fig2 ] ( b ) ] . in this case , we can equate the polynomials to find @xmath54 above this threshold value @xmath53 there are more undecided individuals than decided ones in the population in the stationary states . we can better understand the above - discussed behavior by deriving some equations at a mean - field ( mf ) level , following refs . the fractions @xmath34 , @xmath35 and @xmath36 of opinions @xmath15 , @xmath9 and @xmath10 , respectively , represent the probabilities of randomly choose an agent with opinion @xmath8 , @xmath9 or @xmath10 , respectively . one can consider the processes contributing to the in / out flux for @xmath36 . thus , the flux into @xmath36 is given by @xmath55 , which corresponds to the sixth rule of section 2 ( the noise effect , i.e. , the spontaneous change to opinion @xmath11 ) . on the other hand , the flux out of @xmath36 is given by @xmath56 , which corresponds to pick randomly an agent @xmath13 with opinion @xmath57 ( probability @xmath36 ) and then another random agent @xmath19 with opinion @xmath58 or @xmath9 ( complementary probability @xmath59 ) . the factor 2 in the last expression stands for the inverse case ( @xmath14 or @xmath9 and @xmath25 ) . in other words , this corresponds to the fifth rule of section 2 ( interactions among decided and undecided individuals ) . considering the normalization condition , @xmath60 , one obtains @xmath61 . taking into account that in the stationary state the fluxes into and out @xmath36 should be equal @xcite , the previous results lead to @xmath62 there are two possible solutions ( equilibrium points ) for eq . ( [ eq3 ] ) , @xmath63 and @xmath64 . a simple stability analysis of these solutions shows that the equilibrium point @xmath63 is unstable , so it can be neglected . or @xmath35 is @xmath65 , which implies that @xmath66 ( not shown ) . ] on the other hand , the another equilibrium point @xmath64 is stable , which implies that the mean - field solution for the stationary fraction of undecided individuals is given by @xmath67 the order parameter is given by @xmath68 which is equal to @xmath69 by using the normalization condition . as suggested by the simulations , the stationary fraction of one of the extreme opinions @xmath15 or @xmath9 is equal to zero . in this case , let us say that we have @xmath70 at the stationary state , which give us @xmath42 and @xmath71 notice that the above eqs . ( [ eq4 ] ) and ( [ eq5 ] ) predict three important behaviors : ( i ) there is no order - disorder transition , since the lower value of the order parameter is @xmath72 for @xmath41 ; ( ii ) the consensus states @xmath73 are obtained only for @xmath38 , and ( iii ) the stationary fraction @xmath36 of undecided agents is equal to zero only for @xmath38 . these results are in agreement with the simulations of the model on the square lattice . we can confront these analytical calculations with numerical simulations for the model in the mean - field limit . in this case , all the three involved individuals ( @xmath13 , @xmath19 and @xmath26 in the notation of the rules in section 2 ) are randomly choosen . in order to obtain the averages @xmath51 and @xmath48 , we have performed @xmath50 independent simulations of populations of size @xmath49 agents . the result is exhibited in fig . [ fig2 ] ( b ) . one can see that the numerical results in the fully - connected lattice agree with the derived eqs . ( [ eq4 ] ) and ( [ eq5 ] ) , i.e. , the stationary fraction @xmath48 of undecided individuals grows linearly with the noise @xmath1 , whereas the order parameter @xmath51 decays linearly with @xmath1 [ see the dotted lines in fig . [ fig2 ] ( b ) ] . notice also from fig . [ fig2 ] ( b ) that there is no crossing of the curves of @xmath51 and @xmath48 for the mean - field case , as can be easily seen from eqs . ( [ eq4 ] ) and ( [ eq5 ] ) . in order to clarify if the origin of crossing of the curves is a consequence of the topology or of the presence of correlations in the system ( as discussed in section 2 ) , we performed simulations with a small modification in the sixth rule of the model ( see section 2 ) . for this purpose , we choose at random the agent @xmath26 that will suffer the noise effect , which eliminates the correlations on the noise itself and keeps only the correlations due to the interactions among nearest neighbors ( @xmath13 and @xmath19 in the language of seciton 2 ) . we have verified that the quantities @xmath51 and @xmath48 can also be fitted with second - order polynomials , but different from those of the previous case . in this case , the crossing of the mentioned quantities also occurs , but in a different point , @xmath74 ( not shown ) . thus , we can conclude that the crossing of the @xmath51 and @xmath48 curves for the 2d case is a consequence of the correlations introduced by the topology on the system , i.e. , by the fact that a given agent @xmath13 can interact ( in a voter - like way ) only with one of his four nearest neighbors , that are always the same during all the dynamics . the presence of correlations on the noise causes only a shift from @xmath75 to @xmath53 of the crossing point . however , one can see from fig . [ fig2 ] ( b ) that in the limit of weak noise the mf equations describe well the two - dimensional results . thus , the second - order dependency of @xmath51 and @xmath48 on @xmath1 obtained numerically can be seen as a correction of eqs . ( [ eq4 ] ) and ( [ eq5 ] ) for the 2d case . in this case , for small values of @xmath1 the term @xmath76 can be neglected , which explains the agreement between the two approaches ( 2d and mf ) for low @xmath1 . and different lattice sizes @xmath0 ( a ) . in the inset we show the average relaxation time @xmath3 as a function of @xmath0 in the log - log scale . fitting data , we obtained @xmath4 , where @xmath5 0.9 . it is also exhibited the relaxation times for @xmath37 in the log - log scale ( b ) . data are well fitted by a log - normal distribution , eq . ( [ eqx]).,title="fig:",scaledwidth=47.0% ] and different lattice sizes @xmath0 ( a ) . in the inset we show the average relaxation time @xmath3 as a function of @xmath0 in the log - log scale . fitting data , we obtained @xmath4 , where @xmath5 0.9 . it is also exhibited the relaxation times for @xmath37 in the log - log scale ( b ) . data are well fitted by a log - normal distribution , eq . ( [ eqx]).,title="fig:",scaledwidth=45.0% ] we have also analyzed the relaxation times to consensus of the model . in this case , we have simulated @xmath77 samples of the model for @xmath38 in order to build a probability distribution of the mentioned relaxation times . in fig . [ fig3 ] ( a ) we exhibit the distributions of the relaxation times for different lattice sizes @xmath0 . as expected , when we increase @xmath0 the average relaxation time @xmath3 also increases . based on the numerical data , we have found a power - law relation between @xmath3 and @xmath0 , @xmath78 where @xmath79 ( see the inset of fig . [ fig3 ] ( a ) ) . in order to verify if the relaxation - time distribution is given by a known function , we plotted the numerical data in the log - log scale ( see fig . [ fig3 ] ( b ) for @xmath37 ) . in this case , the observed parabola suggests that the times needed to find all the agents at the end having one of the extreme opinions @xmath15 or @xmath9 are distributed according to a log - normal function . to confirm this hypothesis we fitted the data for @xmath37 with the log - normal function @xmath80 ~.\ ] ] the best fit to data is exhibited by a full line in fig . [ fig3 ] ( b ) , where the parameters are given by @xmath81 , @xmath82 and @xmath83 . the function @xmath84 is also able to fit the data for other lattice sizes @xmath0 . it is important to mention that log - normal - like distributions of the relaxation times were also observed in other opinion models @xcite . as a final comment , we have verified numerically that if we consider the convictions of the undecided agents as a random number in the range @xmath18 $ ] , as was done for the agents with @xmath8 and @xmath85 , the results are qualitatively the same . the only difference is the time needed to the system to reach the steady states . the probability distribution of the relaxation times to consensus ( for @xmath38 ) is also a log - normal , and the @xmath1-dependency of the order parameter and of the fractions of the three opinions is the same as indicated in fig . [ fig2 ] . in this sense , the key ingredients of the model are the presence of noise and the change in the agents convictions , i.e. , the fact that the persuaded individual assumes the conviction of the agent who influenced him . in the presence of external effects the system follows the rules presented in section 2 but in addition there is another source of influence . this external influence acts in the system as a mass - media effect , and is modeled here in a simple way . first , we have considered that the media is favorable to opinion @xmath15 @xcite . in addition , the media influence is measured by a parameter @xmath86 , that works as a probability of a certain individual to follow the media opinion . remember that in the previous section , in the absence of the mass media , we have chosen three different agents : a random agent @xmath13 , one of his nearest neighbors @xmath19 and after another different nearest neighbor , @xmath26 . we will consider in this section that the remaining two nearest neighbors of @xmath13 , say @xmath87 and @xmath88 , that were not affected by the interaction with @xmath13 and by the noise @xmath1 are choosen to suffer the media influence . after the application of the six rules discussed in section 2 , we consider that : * the two mentioned nearest neighbors of @xmath13 , @xmath87 and @xmath88 , are choosen ; * if @xmath87 has opinion @xmath89 or @xmath90 , he will follow the media opinion ( @xmath15 ) if his conviction is lower than the media influence , i.e. , if @xmath91 we update @xmath92 . in this case , we generate another conviction for agent @xmath87 : a real number obtained from a uniform distribution @xmath18 $ ] ; * the same rule is applied to @xmath88 : if @xmath88 has opinion @xmath93 or @xmath94 , he will follow the media opinion ( @xmath15 ) if his conviction is lower than the media influence , i.e. , if @xmath95 we update @xmath96 . in this case , we generate another conviction for agent @xmath88 : a real number obtained from a uniform distribution @xmath18 $ ] ; and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the presence of mass media . results are for lattice size @xmath37 and parameters @xmath39 and @xmath97 ( a ) , @xmath39 and @xmath98 ( b ) , @xmath99 and @xmath97 ( c ) and @xmath100 and @xmath97 ( d ) . , title="fig:",scaledwidth=40.0% ] and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the presence of mass media . results are for lattice size @xmath37 and parameters @xmath39 and @xmath97 ( a ) , @xmath39 and @xmath98 ( b ) , @xmath99 and @xmath97 ( c ) and @xmath100 and @xmath97 ( d ) . , title="fig:",scaledwidth=40.0% ] + and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the presence of mass media . results are for lattice size @xmath37 and parameters @xmath39 and @xmath97 ( a ) , @xmath39 and @xmath98 ( b ) , @xmath99 and @xmath97 ( c ) and @xmath100 and @xmath97 ( d ) . , title="fig:",scaledwidth=40.0% ] and the fractions @xmath34 , @xmath35 and @xmath36 of the agents with opinions @xmath15 , @xmath9 and @xmath10 , respectively , in the presence of mass media . results are for lattice size @xmath37 and parameters @xmath39 and @xmath97 ( a ) , @xmath39 and @xmath98 ( b ) , @xmath99 and @xmath97 ( c ) and @xmath100 and @xmath97 ( d ) . , title="fig:",scaledwidth=40.0% ] thus , if the agent @xmath87 ( @xmath88 ) has a conviction @xmath101 ( @xmath102 ) greater than the media influence @xmath86 , he will not follow the media opinion . differently from the case of a given agent , it is difficult to quantify the media conviction . thus , if a certain individual is persuaded by the media to change his opinion , we generate a conviction for him from a uniform distribution @xmath18 $ ] . in fig . [ fig4 ] we exhibit the time evolution of the order parameter @xmath32 and of the fractions of each opinion for typical values of the parameters @xmath1 and @xmath86 . we can see that the system reaches steady states for all values of the parameters as in the case with no external effects . in figs . [ fig4 ] ( a ) and ( b ) we fixed the value of the noise @xmath39 and compare the effects of varying the mass - media parameter @xmath86 . in this case , one can see that the noise parameter dominates the behavior of the system , and the fractions @xmath34 , @xmath35 and @xmath36 after a long time are similar for the two considered media parameters , namely @xmath97 and @xmath98 . on the other hand , if we compare the evolution of the system for a fixed value of the media parameter ( @xmath97 ) and different values of @xmath1 , one can observe a distinct behavior of the system [ see figs . [ fig4 ] ( c ) and ( d ) ] . in fact , in this case the fractions @xmath34 , @xmath35 and @xmath36 after many time steps are different for the two considered values of @xmath1 , namely @xmath99 and @xmath100 . in fig . [ fig5 ] ( a ) we exhibit the average stationary order parameter @xmath51 as a function of @xmath1 for typical values of the media parameter @xmath86 . we can see that for small values of @xmath1 like @xmath103 the consequences of the external effects are negligible , but for @xmath104 the media affects strongly the system . in this case , one can observe that @xmath51 decreases fast until @xmath105 for all values of @xmath86 . on the other hand , the value of the order parameter increases in the range @xmath106 , and decreases again for @xmath107 . the cause of this effect will be clear in the following . in fig . [ fig5 ] ( b ) we exhibit the average stationary fractions of opinions @xmath15 , @xmath9 and @xmath10 ( @xmath108 , @xmath109 and @xmath48 , respectively ) for two typical values of the mass - media parameter @xmath86 , namely @xmath97 ( full symbols ) and @xmath98 ( empty symbols ) . one can see that the fractions of extreme opinions @xmath108 and @xmath109 are strongly affected by the noise @xmath1 for a fixed value of the mass - media parameter @xmath86 , as was discussed above ( see fig . [ fig4 ] ) . the fraction on undecided individuals @xmath48 grows linearly with @xmath1 , i.e. , in a slower way in comparison with the case with no media [ see fig . [ fig2 ] ( b ) ] . on the other hand , for a fixed @xmath1 there are no differences between the two exhibited values of @xmath86 , except for the noiseless case @xmath38 ( see also fig . [ fig4 ] ) . in the last case , the fraction of @xmath15 ( @xmath9 ) opinions increases ( decreases ) when we increase the mass - media influence @xmath86 , as expected , since the media persuades the agents with opinions @xmath9 and @xmath10 to change to @xmath15 , and the individuals do not come back to the undecided state because @xmath38 . on the other hand , the fraction of @xmath11 opinions for @xmath38 is not affected by the variation of the parameter @xmath86 . as a function of @xmath1 for typical values of the media parameter @xmath86 ( a ) . it is also shown the average stationary fractions of the three opinions @xmath108 , @xmath109 and @xmath48 versus @xmath1 ( b ) for @xmath97 ( full symbols ) and @xmath98 ( empty symbols ) . , title="fig:",scaledwidth=47.0% ] as a function of @xmath1 for typical values of the media parameter @xmath86 ( a ) . it is also shown the average stationary fractions of the three opinions @xmath108 , @xmath109 and @xmath48 versus @xmath1 ( b ) for @xmath97 ( full symbols ) and @xmath98 ( empty symbols ) . , title="fig:",scaledwidth=46.0% ] as the media favors opinion @xmath15 , it could be expected that this opinion will be the majority opinion in the population at the steady states . however , this behavior is observed only for @xmath110 , for all values of @xmath86 in the range @xmath111 . in fig . [ fig5 ] ( b ) we exhibit two distinct cases , namely @xmath97 and @xmath98 , to illustrate this result . on the other hand , for @xmath112 the opinion contrary to the media opinion , i.e. @xmath9 , dominates the majority of the agents in the steady states [ see figs . [ fig4 ] ( d ) and [ fig5 ] ( b ) ] . in analogy with elections , this means that if there are many agents becoming undecided , the media candidate ( related to opinion @xmath15 ) will not win the election , even for a strong effect of the propaganda . this fact explains the effect observed in the order parameter for @xmath113 [ see fig . [ fig5 ] ( a ) ] . in fact , as one can write the stationary order parameter as @xmath114 and @xmath115 for @xmath112 , the value of @xmath51 in this case is greater than in the case @xmath105 since in this last case we have @xmath116 . in fig . [ fig6 ] we exhibit the average stationary values of the order parameter and of the fractions of opinions @xmath15 , @xmath9 and @xmath10 for @xmath117 . as in the case with no mass - media effects , the consensus states are only possible in the absence of noise ( @xmath38 ) , even if the media effect always persuade the agents ( @xmath117 ) . in other words , even a sufficient small noise @xmath1 leads each agent in the population to be in one of two different states , @xmath8 or @xmath11 , with the opinion contrary to the media opinion ( @xmath9 ) being extincted from the system , i.e. , we have @xmath118 for all values of @xmath1 ( see fig . [ fig6 ] ) . as a consequence , we have @xmath119 , and we observe linear behaviors of @xmath108 and @xmath48 with @xmath1 : while @xmath48 grows linearly with the increase of the noise @xmath1 , @xmath108 decays linearly with @xmath1 . for @xmath117 . , scaledwidth=52.0% ] in this work , we have studied a voter - like model on square lattices with linear sizes @xmath0 . the individuals may be in one of three distinct states , represented by opinions @xmath8 , @xmath9 or @xmath10 . the agents change their opinions via two competing mechanisms . first , two agents may interact via a voter - model dynamics , but the usual copying process is limited by the agents convictions . furthermore , we have considered that in a given interaction the persuaded agent takes the opinion and the conviction of the agent that interacted with him . to our knowledge , the presence of convictions was analyzed in some works ( see for example @xcite ) , but not as we done . the second mechanism is a noise @xmath1 , which allows agents to change their opinions to the undecided state @xmath11 . as the agents that participate of the dynamics in a given time step are nearest neighbors in the square lattice , the dynamics inserts correlation effects on the system and on the noise itself . these rules are realistic ingredients to be considered in opinion dynamics . we have verified that the system reaches consensus only in the absence of noise ( @xmath38 ) , and in this case the relaxation times are log - normally distributed . the average value of the distribution grows with the system size as @xmath120 , where @xmath121 . for @xmath122 we have observed that one of the extreme opinions @xmath15 or @xmath9 disappears of the system , and the surviving extreme opinion coexists with the @xmath10 opinion . the fraction of @xmath11 opinions in the stationary states grows fast with increasing values of @xmath1 , and a numerical analysis of the simulation data suggests that the above - mentioned surviving opinion is the majority opinion in the population for @xmath123 , being overcome by the opinion @xmath10 for @xmath124 , where @xmath125 . we extended the model to consider external effects . these effects act in the system as a mass medium ( tv , radio , ... ) and are quantified by a parameter @xmath86 . if @xmath86 is greater than the conviction of a given agent , this agent follows the media opinion , that we have considered as @xmath15 . the first consequence of the media effect appears in the stationary fraction of @xmath11 opinions , that grows linearly with the noise @xmath1 for all values of @xmath126 , i.e. , in a slower way than in the absence of external effects . in the absence of noise ( @xmath38 ) , the scenario is similar to the case with no media effect , i.e. , the system reaches consensus but in a faster way than in the case @xmath127 , but the @xmath9 opinion does not disappears of the system . in the other extreme situation , @xmath117 , the opinion @xmath9 disappears of the system in the stationary states for all values of the noise @xmath1 , and the fraction of @xmath15 opinions decays linearly with the increase of @xmath1 . for the intermediary values of @xmath86 , i.e. , in the range @xmath111 , we have observed that the opinion @xmath9 persists in the long - time limit for all values of the noise @xmath1 . based on the simulation data we verified that , for a given value of @xmath86 , the media opinion @xmath15 in the stationary states is the majority opinion in the population only for @xmath128 , being overcome by the opinion @xmath9 for @xmath129 . in other words , even a strong effect of advertising may not be enough to make winner the opinion supported by the mass media , which is a nontrivial result . the real dynamics of the human societies is very complicated . however , our model can simulate real situations in communities . in any public debate , the discrete opinions considered in our model can represent extreme favorable opinion ( @xmath8 ) , extreme unfavourable opinion ( @xmath85 ) or indecision ( @xmath11 ) . thus the order parameter in the model corresponds to the overall rating and the ordered state means there is a clear decision made . for example , in an electoral process with two different candidates a and b , each elector ( agent ) votes for the candidate a ( opinion @xmath8 ) , for the candidate b ( opinion @xmath85 ) or is undecided ( opinion @xmath11 ) . the competition of the convictions in an interaction can be seen as the competition between the persuasiveness of an agent and the resistance of the other agent to change your candidate . the noise @xmath1 represents the volatility of some individuals , that tend to spontaneously change your choices . finally , the external effect introduced in section 3.2 models the effect of advertising on the individuals choices . in fact , the electorate is susceptible to the effects of electoral surveys broadcasted by the mass media . furthermore , the occurrence of consensus states with @xmath73 are usually related to dictatorships , whereas the states with @xmath130 are desirable since they represent democracy - like situations @xcite . another example is the dynamics of agents on financial markets , where the opinions represent the decision for selling stocks ( @xmath8 ) , the decision for buying stocks ( @xmath8 ) or the decision to do nothing ( @xmath11 ) . in this case , when a pair of agents with opposite decisions @xmath15 and @xmath9 interacts , one of the two agents can be persuaded to change your choice ( the agent with lower conviction ) . the noise @xmath1 in this case represents the decision of an agent to stop their actions of selling or buying stocks , maybe due to fluctuations on the stock prices . on the other hand , the external effect models the campaign made by some companies ( in television , for example ) in order to sell their stocks . the presence of special individuals like contrarians , inflexibles , opportunists or stubborn agents was considered in some opinion models @xcite . it would be interesting to extend the present model to include the above - mentioned agents and study the impact of their actions on opinion formation . in addition , one can also study the properties of the model in various lattices and networks . the author acknowledges financial support from the brazilian funding agencies faperj and capes . we also acknowledge thoughtful remarks by anonymous referees which significantly improved the text .

in this work we study the opinion formation in a voter - like model defined on a square lattice of linear size @xmath0 . the agents may be in three different states , representing any public debate with three choices ( yes , no , undecided ) . we consider heterogeneous agents that have different convictions about their opinions . these convictions limit the capacity of persuasion of the individuals during the interactions . moreover , there is a noise @xmath1 that represents the probability of an individual spontaneously change his opinion to the undecided state . our simulations suggest that the system reaches stationary states for all values of @xmath1 , with consensus states occurring only for the noiseless case @xmath2 . in this case , the relaxation times are distributed according to a log - normal function , with the average value @xmath3 growing with the lattice size as @xmath4 , where @xmath5 0.9 . we found a threshold value @xmath6 0.9 above which the stationary fraction of undecided agents is greater than the fraction of decided ones . we also study the consequences of the presence of external effects in the system , which models the influence of mass media on opinion formation .

The National Rifle Association will send a representative to meet this week with Vice President Joseph R. Biden, who is heading a task force on gun violence, a spokesman for the group said Tuesday. The group received an invitation to attend late Friday, said spokesman Andrew Arulanandam. SEE RELATED: “We are sending a rep to hear what they have to say,” he said. Mr. Biden will meet with gun safety groups and gun victims’ groups on Wednesday and sportsmen’s and gun ownership groups on Thursday. The NRA has advocated adding armed guards to schools to prevent future mass shootings in the wake of the rampage that saw 26 people, including 20 children, murdered at a Connecticut elementary school last month. White House press secretary Jay Carney on Tuesday reiterated President Obama’s recent comments that he was skeptical putting more guns in schools would solve the problem. “But again, we look forward to hearing from a variety of organizations and civic groups and others who have insights into this problem,” Mr. Carney said. “[T]he process is designed to get input. And then the vice president’s group will assess different actions, make recommendations, and the president will decide what he would like to pursue, what he believes is the right course of action, in addition to what he has already called on Congress to do, which is pass the assault weapons ban, pass legislation that would ban high-capacity magazines, pass a bill that would close loopholes in our background check system.” Mr. Obama has asked Mr. Biden to report back to him with recommendations this month. “So [the president] is mindful of the need to act,” Mr. Carney said. “He is also mindful of the need to have a process in place, led by the vice president, that allows for consideration of a variety of ideas, because he’s made the point that this is not a problem that can be solved by gun legislation alone.” The group will also meet with representatives of the entertainment and video game industries, and members of Mr. Obama’s cabinet will meet with other stakeholder groups. Secretary of Education Arne Duncan will meet with parent, teacher and education groups, and Secretary of Health and Human Services Kathleen Sebelius will meet with mental health and disability advocates. Mr. Carney said that White House staff will continue to meet with medical groups, community organizations, child and family advocates, business owners, faith leaders and others. ||||| Washington Wire is one of the oldest standing features in American journalism. Since the Wire launched on Sept. 20, 1940, the Journal has offered readers an informal look at the capital. Now online, the Wire provides a succession of glimpses at what’s happening behind hot stories and warnings of what to watch for in the days ahead. The Wire is led by Reid J. Epstein, with contributions from the rest of the bureau. Washington Wire now also includes Think Tank, our home for outside analysis from policy and political thinkers. Sign up for Capital Journal Daybreak ||||| Washington Wire is one of the oldest standing features in American journalism. Since the Wire launched on Sept. 20, 1940, the Journal has offered readers an informal look at the capital. Now online, the Wire provides a succession of glimpses at what’s happening behind hot stories and warnings of what to watch for in the days ahead. The Wire is led by Reid J. Epstein, with contributions from the rest of the bureau. Washington Wire now also includes Think Tank, our home for outside analysis from policy and political thinkers. Sign up for Capital Journal Daybreak ||||| Vice President Biden was preparing to meet with the National Rifle Association Thursday, a day after claiming the White House could use "executive orders" to deal with gun control. The meeting is the latest in a string of sit-downs aimed at finding ways to curb gun violence, but could become heated in the wake of Wednesday's comments. After meetings with gun-safety and victims groups Wednesday, the vice president said he is "determined" to take "urgent action" to address gun violence. "This is not an exercise in photo opportunities or just getting to ask you all what your opinions are. We are vitally interested in what you have to say," Biden said. The White House has sought to avoid prejudging what Biden's recommendations would be. But the vice president hinted Wednesday that executive action -- action by the president in which Congress would not have a say -- would indeed be involved. "There are executive orders, executive action that can be taken," Biden said, adding "we haven't decided what that is yet." He also said separate legislative action would be "required." The vice president spoke out as he prepared to hear from the other side of the gun-control debate Thursday, when the nation's leading gun lobby will meet face to face with his task force in what could be a testy session. The National Rifle Association confirmed to Fox News that the group accepted an invitation to meet with the task force, which is running up against an end-of-the-month deadline to produce a set of proposals. The administration says mental health and the entertainment industry will likely be examined as part of that process. Biden has also scheduled a meeting with representatives from the entertainment and video game industries. But much of the discussion, and proposals from Democratic members of Congress, continue to center around gun control. The meetings Wednesday with gun safety groups also focused on those kinds of proposals. The NRA has been at the helm of fighting those proposals ever since the group broke its post-Connecticut silence and called for a national school security plan to install armed officers at every school in the country. The White House and the NRA have found little common ground as the two groups craft separate responses to the tragedy. White House Press Secretary Jay Carney reiterated Tuesday that President Obama is "skeptical that putting more guns in schools would solve this problem." It's unclear how the meeting Thursday will be structured. The NRA told Fox News that they are sending a representative to hear what the White House has to say. Carney, though, said the task force is "designed to get input" from others. "Then the vice president's group will assess different actions," Carney said. Gun-advocacy groups including Arizona for Gun Safety, the Brady Campaign, the Campaign to Keep Guns off Campus and Mayors Against Illegal Guns attended the meeting with Biden Wednesday. Dan Gross, president of the Brady Campaign to Prevent Gun Violence, after the meeting affirmed that administration officials "talked about ... their willingness to use executive action where that's appropriate." The Washington Post reported over the weekend that President Obama was considering measures beyond reinstating a ban on assault weapons and high-capacity magazines. According to the paper, the task force is considering measures like universal background checks for gun buyers, a national gun database, strengthening mental-health checks and tougher penalties for people carrying guns near schools or giving them to minors. Asked Monday about the report, Carney reiterated that Obama wants to "close the many loopholes in our background check system" and "supports congressional actions right away." Accelerated efforts to draft new gun control measures have alarmed gun rights groups, including the NRA, at the national and local levels. A separate last-minute effort to craft a restrictive semi-automatic weapon ban in Illinois was put on hold amid a tight deadline and intense opposition. On Capitol Hill, California Sen. Dianne Feinstein is again pushing a renewal of the federal assault-weapons ban. But Congress is also slammed with a pressing set of deadlines regarding a host of fiscal issues -- the debt ceiling, automatic spending cuts and the federal budget itself. Kentucky Sen. Mitch McConnell, the top Republican in the Senate, said the next round of fiscal deadlines will occupy the attention of Congress and push off the consideration of gun legislation for at least three months. "There will be plenty of time to take a look at their recommendations once they come forward," McConnell said of Biden's upcoming proposals during an interview Sunday on ABC's "This Week." Obama aides say the president still plans to act quickly on Biden's proposals. "I believe most Americans would disagree with the idea that in the wake of what happened in Newtown, Conn., that we should put off any action on the issue of gun violence," Carney said Monday in response to McConnell's comments. Biden's recommendations are likely to include proposals for legislation, as well as executive action Obama can sign into law without lawmakers' approval. The president already has called on Congress to reinstate a ban on military-style assault weapons, close loopholes that allow gun buyers to skirt background checks and restrict high-capacity magazines. Pro-gun lawmakers on Capitol Hill have said any comprehensive effort to respond to the Newtown shooting must include more than just tighter gun control. In addition to Biden's meetings this week, Education Secretary Arne Duncan will meet with parent and teacher groups, while Health and Human Services Secretary Kathleen Sebelius will meet with mental health and disability advocates. The White House said other meetings are also scheduled with community organizations, business owners and religious leaders. The Associated Press contributed to this report.

– Meetings of Joe Biden's gun control task force start this week, and Walmart made headlines right off when it initially declined to attend. The retailer—the largest seller of guns and ammo in the nation—apparently couldn't find anyone in its huge organization who could make it to tomorrow's meeting and turned down the invitation due to a scheduling conflict, the Wall Street Journal reported last night. But the chain did a quick 180 this morning, announcing it will send a rep to the meeting, which is focused on decreasing gun violence. "We underestimated the expectation to attend the meeting on Thursday in person," says a spokesperson, according to the Journal. The task force is meeting with gun safety and gun victims' groups today; tomorrow, it will meet with gun ownership and sportsman's groups including the National Shooting Sports Foundation. The NRA will also participate, the Washington Times reports. "We are sending a rep to hear what they have to say," says a rep. The task force will also meet with representatives from the entertainment and video game industries, and mental health issues will also be examined, Fox News reports. The group aims to build consensus around proposals for decreasing gun violence, and Biden will present recommendations to President Obama later this month.

according to the statute of the world health organization , health is considered as a personal and social value and in view of different nations , it has been considered as the most important and obvious rights and human needs . in line with achieving health , all the countries pay attention to all different groups of society . among these groups , young girls are of special importance ; because today 's young girls are tomorrow 's mothers and accordingly they would be able to play a key role in health status of themselves and community around . the major change is that this period which is so important and is considered as the turning point of adolescents , is puberty . in fact , puberty is one of the critical stage of life which its infrastructure is through foundation of adulthood and perhaps many psychological problems , infectious diseases and unsuccessful marriages , early and risky pregnancies , mother and child injuries and deaths and finally serious physical and psychological problems are rooted from this period ; therefore , this period of life is considered as an underlying period for different stages of life . this period of life is highly important in association with health ; because many health habits of individual form in this stage of life which has an important influence on health behaviors in adulthood . although puberty era , problems and quality of passing this era is important for both sexes , noticing to health of girls in puberty is of higher importance ; because young girls are in special conditions in addition with passing from the critical transition of puberty , because of their gender ( being a woman ) and consequently accepting responsibility and role of motherhood . in iran ( according to the census in 1996 ) , adolescents ( 10 - 19 years old ) were 16 million people ; in other words they constitute 27% of total population and out of this number , 7,993,875 people ( 45% ) were girls . given to allocation of high percentage of young girls population , the importance of health education is quite sensible in their health programs . addressing to health of this group of society is helpful not only for them , but also for their families , society and future generation as well , and addressing their problems in fact is investment in national development . unfortunately in practice female health programs cover more on peak of reproductive age and childbirth and do not pay necessary and required attention to the health needs of young girls and they have been forgotten like a missing ring ; while young girl would have many physical , psychological and social problems in her growth and development path particularly during puberty till marriage and so forth . nevertheless , in some societies , girls still are sacrificed due to lots of false traditions prevailing in society ; so that health , nutrition and education for girls is given less value than for boys ; however , girls have a special biological privilege since their birth that makes them more resistant to malnutrition and infection than boys , but due to problem and failure to meet health needs , this biological advantage gradually disappears . hence , one of the goals of unicef is to support girls including prioritizing their health and nutrition needs during adolescents . complications and problems of puberty era are easily preventable and health education is the most important and basic step in prevention and removing problems of this stage . the education should be implemented in order for informing the context of physical , psychological and social problems as well as in three pivots of family , school and public education . family and school are two institutions have the highest influence on formation of health behaviors in adolescents and in fact behaviors of adolescents is a reflection of these two institutions performance and both school and family should participate in educating puberty issues to youths . family as the first social base has the most important role in education and transferring health behaviors to family members . although each of family members have their own role in educating puberty issues for adolescents , position of mother is more obvious meanwhile and most of young girls learn their health behaviors from their mothers . due to higher proximity and connection of adolescent girls with mother , they would be higher under her influence . studies have shown that girls learn about physical changes and puberty from the family particularly from mothers . however , schools also have major role in achieving some behaviors related to education of puberty issues and schools are in charge of adequate educations in association with girls puberty after the family . studies have shown that most of parents , educators and adolescents are not aware of health issue during puberty ; whereas youths confront with many questions due to physical and psychological changes in this period and naturally they have many physical needs must be answered to . adolescents have the right to obtain information about puberty changes and know what has happened . certainly , it is therefore the duty of parents and teachers to provide reasonable and logical responses . due to shame or lack of knowledge most of parents can not talk about puberty and sexual issues with their children or help her ; therefore , the present study aimed to increase knowledge level of female guidance and high school students in birjand city about puberty health and reviewing the effect of education on promoting knowledge level and health of female students . this was an interventional ( per and postintervention ) study on 325 female students at guidance and high school grades in birjand city who were selected through randomized multi - stage sampling method . the schools of birjand geographically were divided into four regions and in each region two high schools and two guidance schools were randomly selected and in each school one grade was selected among the educational grades and they were enrolled the study by randomized systematic sampling which related to sample size . data collection was conducted through a researcher - made questionnaire designed based on objectives of educational course and included 20 one - score multi - choice questions for assessment of knowledge ; the validity of the questionnaire was approved by a number of faculty members . after sample selection , the questionnaires were distributed in each school in an appropriate place and then were collected after completion . thereafter , by a documented educational program , all the students in guidance and high schools were taught with identical educational content by trained instructors . the time of training in each class was designed in two 45-minute sessions and simultaneous with holding educational classes , educational pamphlets about the required subject were also distributed among the students . a month after the intervention in each school , the questionnaires of the first stage were distributed among the students selected as the study samples and then were collected after completion in an appropriate place . those who did not complete the second stage of the questionnaire for any reason were excluded from the study . the data were analyzed through software spss and paired t - test at significant level ( = 0.05 ) . in this study , 302 female students at guidance school ( n = 151 ) and high school ( n = 151 ) were studied . mean age of the students at guidance school grade was 12.9 1.1 years and in high school grade was 16.3 1.3 years . statistically there was a significant difference in mean score of knowledge of guidance and high school students before and after the intervention [ table 1 ] . comparing mean score of knowledge before and after the intervention in guidance and high school students in addition , the subjects showed a significant difference in mean score of knowledge before and after the intervention [ table 2 ] . mean score of knowledge before and after the intervention in guidance students increased 5.77 score and in high school students increased 4.6 scores and in total students increased 5.1 scores and these differences were statistically significant . comparing mean score of knowledge before and after the educational intervention in the study subjects mean score of knowledge in students regarding puberty health was 4.7 before implementation of educational program and it increased to 9.7 after the intervention . in female students at guidance school , knowledge score increased from 5.03 to 10.8 and in high school students also increased from 4.1 to 8.7 . the estimated mean difference before and after the education statistically showed a significant difference which indicates desirable increase in knowledge of students about health of puberty era . in the study of zabihi , education also had a positive impact in knowledge rate of students regarding puberty health and there was a significant relationship between knowledge of students in puberty health before and after the education ( p < 0.001 ) . other similar studies also indicated the impact of education on increased level of knowledge regarding puberty health . in three recent studies there was also reported a significant difference in knowledge rate of students before and after the educational intervention about health of puberty period . simultaneous with religious duty time , puberty is formed in girls . in this period , due to physical , psychological and social changes , the knowledge level of adolescents should be promoted so that no health risk threatens them . knowledge and awareness of girls from observing health tips during puberty can have an effective role in their performance and can decrease many subsequent problems for them . due to shame and modesty , young girls usually do not speak about problems of puberty era with their mothers ; education is the most effective goal for changing behavior and young girls and boys need knowledge and life skills to make a correct decision and positive behaviors of life . studies have shown that puberty education has a significant influence on correct way girls have with changes during puberty and modification of health behaviors . according to the results of the present study , in order to promote knowledge level of female students toward puberty issues and modification of health behaviors , it is necessary to transfer correct information to them through counseling and providing educational books and pamphlets . accordingly , in order to promote health of youths and adolescents , eastern mediterranean health organization announced that continuous health education to adolescents through schools and health services of schools for preventive health care in the first and second levels should be done for all the students as well as for maternal and child health . given to the role of health education in promoting knowledge level which finally can change behavior and improve performance , it is recommended to insert educational program in agenda of health promotion programs based on needs of different groups particularly girls and mothers .

background : puberty is one of the most critical periods in a female adolescents life . this intervening study aimed to evaluate the effect of educational program for puberty health on improving intermediate and high school female students knowledge in birjand , iran.materials and methods : in this quasi - experimental study , 325 female intermediate and high school students were selected through randomized cluster sampling during several stages . then , researcher - made questionnaire including 20 questions , each having one point regarding puberty health , was distributed . after completion of the questionnaires were gathered . following this , under a systemic educational plan all intermediate and high school selected students were given the same instruction by trained instructors . instruction time for each meeting was estimated 1.5 hours . one month after the educational program and handing out the pamphlets in schools , the previous questionnaires were again distributed among the students to fill out . at the end , 302 students who had filled out the questionnaires before and after intervention were studied.results:out of 302 students , 151 were intermediate and 151 high school students . knowledge level among intermediate students was 5.03 3.7 before intervention and was 10.8 4.8 after intervention . among high school students , the scores were 4.1 2.3 and 8.7 3.8 , respectively . there was a significant difference between pre and post intervention stages in both groups ( p < 0.001 ) . furthermore , mean knowledge grade in all the students increased from 4.6 3.1 before intervention to 9.7 4.4 after intervention ( p < 0.001).conclusion : performing educational programs during puberty has a crucial role in young girls knowledge increase . since young girls often do not share their problems with their parents and their peers during the period , instructional classes in schools provide a good opportunity for them to present their problems and finding solutions .

GREELEY, CO - DECEMBER 16, 2013: Norma Meza hugs her daughter Maria, 11, as Rosario Moreno, standing, and her husband Jose, seated, join some of the kids for dinner at the Meza's tiny home in Greeley, CO on December 16, 2013. The children seated at the table are from far right clockwise: Genoveva Meza, 14, Martin Meza jr., 17, Sergio Meza, 3, Janeth Moreno, 10, Edwin Moreno, 2, Yanna Moreno, 8. At left are brothers Jared, 5, and Ivan, 18, Moreno. The Meza family, which consists of four children, Norma and her husband Martin have taken in the Moreno family after they lost everything in the September floods. Rosario and her husband Jose have 5 children and are without a home at the moment. Norma says she will help out her best friend for as long as she needs to. The tiny house has 3 bedrooms and 2 small bathrooms and is home now to 14 people, 2 cats and 3 dogs. (Photo By Helen H. Richardson/ The Denver Post) ||||| Story highlights Some residents may be stranded well after storms end because of washed-out roads Woman rescued with baby by National Guard: "Felt like God came down and saved us" Four deaths confirmed in Colorado; 80 "unaccounted for" in Boulder County alone "Very heavy rainfall" likely for flooded areas, Colorado officials say Clear skies allowed for more evacuations and rescues in flood-devastated Colorado on Friday, but the forecast through Sunday called for more heavy rain. Even after the last of the storms, authorities can't say how long it will take to reach residents who will remain isolated by devastated roads. The confirmed death toll reached four when Boulder County officials recovered the body of a woman who had been swept away after getting out of her vehicle Thursday, Sheriff Joe Pelle said. Authorities already had recovered the body of a man who left the same car and tried to save the woman. One other death had been reported in Boulder County and one occurred in El Paso County. President Barack Obama declared an emergency for Boulder, Larimer and El Paso counties, FEMA announced Friday. The declaration allowed FEMA to bring in four rescue teams, the largest ever deployment in Colorado, officials said. More heavy rain is forecast through Sunday for the region, on top of the 15 inches some parts of the state have already received. "This isn't over," CNN meteorologist Chad Myers said. On Friday, National Guard troops using "high-profile" trucks to wade through water were evacuating the entire Boulder County town of Lyons, which had been cut off since the flooding began Wednesday night. "It just really felt like God came down and saved us. It felt great," Melinda Villa said of the National Guard's arrival at the Lyons apartment where she was stranded with her 1-month-old infant. She said, "I just felt like I was trapped. No phone, no water, barely any formula for my baby, barely any food for us." Jonathan Linenberger described a Noah's Ark-style evacuation as he, his fiancee and four dogs and three cats greeted the National Guard truck. "We had to go (through) knee-deep water, at least. We had to wade our animals across into the truck to get them there," said Linenberger. "That was the first thing you can grab, your loved ones -- and that's what we have." The National Guard also was evacuating the entire population -- 285 people -- from the town of Jamestown by helicopter, CNN affiliate KCNC-TV reported. Four helicopters were being used for rescues in Boulder County Friday, Pelle said. The sheriff said helicopters also may have to be used indefinitely to deliver food and water to residents along damaged rural roads. "Please know we're working hard," Pelle told residents who might see his televised news conference. "We're concerned about you. But you're going to have to be patient. Please know this is an unprecented event." About 80 people in Boulder County have been reported missing or "unaccounted for" by relatives, Sheriff's Cmdr. Heidi Prentup said. The University of Colorado canceled Saturday's scheduled football game against Fresno State. In Larimer County to the north, Sheriff Justin Smith surveyed the heavily damaged Big Thompson Canyon by air Friday. Some people remain stranded in homes there, he said, adding, "How we're going to get them out -- it's going to take a damn long time." However, he said the break in the rain Friday allowed school buses to begin evacuating students who had been stranded at a school. Smith described widespread damage to roads. He estimated 17 miles of Highway 34, a major artery, will need to be rebuilt. Lyons rescue The National Guard effort to get residents out of Lyons began shortly after daybreak. About 100 troops in 21 heavy vehicles able to ford high waters streamed into the city to begin moving residents out, Gov. John Hickenlooper said. Residents had been entirely cut off, without water or sewer service, in many cases without electricity, facing what Fire Chief J.J. Hoffman said in a Facebook posting was a "very large disaster." It was unclear when the evacuation would be complete. "I encourage all of you -- stay strong!" Hoffman wrote on the fire department's Facebook page. "We will make it through this, we are here for you and doing the absolute best we can with the resources we have to get to each and every one of you!" As Lyons evacuees arrived at a shelter set up in a church in nearby Longmont, they told stories of houses ripped off their foundations as the St. Vrain Creek turned into a violent river, CNN affiliate KMGH reported. KMGH reporter Theresa Marchetta said evacuees also described homes dangling off cliffs. Some people in Lyons still were awaiting rescue, evacuees said, and some residents had chosen to stay. Marchetta said evacuees told her there had been a town meeting and residents were checking on each other to ensure no one was missing. Danger elsewhere State transportation officials issued an emergency alert to residents in some of the hardest-hit counties, warning them to stay off roads because many are unstable and could give way without notice. They also closed Interstate 25 from the Wyoming line south to Denver. Part of Interstate 70 also was shut down. In Fort Collins, some residents had been urged to leave their homes. And in Denver, police responded when a man was swept into a drainage pipe with his dog. Both were saved after traveling two blocks in the water, police said on Twitter. The rains sent virtually every waterway in Boulder County coursing out of its banks, and massive water flows washed away roads and bridges, flooded homes and stressed numerous other bridges. JUST WATCHED Rescuer: We hoped for best in flood Replay More Videos ... MUST WATCH Rescuer: We hoped for best in flood 03:31 JUST WATCHED Man trapped in flooding, overturned car Replay More Videos ... MUST WATCH Man trapped in flooding, overturned car 00:58 JUST WATCHED Mom and daughter stuck in hail, flood Replay More Videos ... MUST WATCH Mom and daughter stuck in hail, flood 01:15 JUST WATCHED Deadly flooding in Colorado Replay More Videos ... MUST WATCH Deadly flooding in Colorado 01:29 In the early hours Friday, flood sirens sounded in Boulder County as emergency officials feared that debris-caked canyons might give way and send another wall of water crashing through the city of Boulder and neighboring communities. "All residents are warned to go to higher ground immediately due to the potential for flash flooding along the creek," Boulder's Office of Emergency Management said. Emergency management warned that "there are mudslides at the mouth of Boulder Canyon 400 feet long and four feet deep as the sides of the canyon give way due to the saturation from the days-long rain." Authorities continued to warn of the danger of mudslides Friday night. Hickenlooper warned an extensive recovery is ahead. "This is not going to get fixed in a week," he said. "We have lost a great deal of infrastructure." ||||| This crawl of online resources of the 114th US Congress was performed on behalf of The United States National Archives & Records Administration (NARA). ||||| Local News Rivers continued to swell, roadways crumbled, and Colorado's Front Range began to dig out from the epic destruction wrought by a historic flood that has become one of the state's worst disasters. "We're not out of the woods yet," said Boulder Police Chief Mark Beckner on Friday morning — a day that saw the skies clear but catastrophe continue. Rivers raged, highways and local roads shut down, residents remained stranded, power failed, and officials confirmed four people had died: a boyfriend and girlfriend, both 19, in Boulder; a Jamestown man; and a man who drowned in Fountain Creek in Colorado Springs. Boulder officials Saturday morning said 218 people are still unaccounted for, meaning they had not been in touch with relatives. The disaster was widespread and affected nearly everyone and everything in a swath of Colorado stretching from Pueblo to the Wyoming border — from schoolkids and college students, whose classes were canceled, to livestock, sports games and even climbers on Longs Peak. Two women from Maine who were stranded by weather below the 14,259-foot summit called for help, which could not reach them. They waited more than 48 hours before hiking to safety Friday. The University of Colorado postponed Saturday's football game against Fresno State, only the third time that has happened — the first was when President Kennedy was killed, and the second was after the Sept. 11 terrorist attacks. Residents packed sand into bags Friday afternoon, preparing for the South Platte River to crest in Kersey on Saturday and in Sterling sometime Sunday. On Friday, the river carried 50 times more water than it normally does at this time of year. The Alpine Rescue Team uses a high line and a sling across Fourmile Canyon to rescue Darian Shaw of Salina and three neighbors from 4 Mile Canyon. (Joe Amon, The Denver Post) "Everyone along the river is worried," Kersey town clerk Julie Piper said. "The phone is ringing off the wall. It just gets larger and larger." Robert Kimbrough, associate director for hydrologic data with the Colorado Water Science Center, estimated the South Platte River near Kersey was running at 23,700 cubic feet per second at 5:30 p.m. Friday — higher than the National Weather Service's predicted crest. "It has not begun to level off," he said. Gov. John Hickenlooper declared a disaster emergency in 14 counties, authorizing $6 million to pay for flood response and recovery in Adams, Arapahoe, Boulder, Broomfield, Denver, El Paso, Fremont, Jefferson, Larimer, Logan, Morgan, Pueblo, Washington and Weld. Thousands of people remained out of their homes. Many did not know whether they had a home any longer. Military helicopters rescued nearly 300 people from Jamestown — a town in Boulder County that become an island Wednesday. The Colorado National Guard drove high-clearance trucks through the water to get people out of Lyons, which was cut off when the St. Vrain River roared into a behemoth Thursday morning, flooding the town and all exit routes. Left: Norman Bowers, the fire chief of the Indian Peaks Fire Protection District, gets help from Pat Paxton, far left, to fill up several gallons of gasoline for the station in Gilpin County on Friday. With the town of Nederland out of power, this was the only station with gas between Nederland and Estes Park. Folks were driving from all of the mountain communities to fill their tanks for the long drives ahead. (Helen H. Richardson, The Denver Post) Michael Twarogowski watched the river crest near his Lyons home around 1 a.m. Thursday. He ushered his family to the car and drove to the cemetery, one of the highest points in town, and tried to sleep as heavy rain pounded the roof. Thursday morning, Twarogowski watched the landscape of Lyons change — sheds and outbuildings being gobbled up by the river and shattered against trees. Twarogowski checked on his home one last time before being evacuated Friday. It had been spared. But not far away, the sight was far more devastating: homes surrounded by water with trees and limbs pushed up against them, a metal footbridge wiped out. Some houses were swept from their foundations. Above: A Jamestown evacuee is helped off a helicopter at Boulder Municipal Airport. (Andy Cross, The Denver Post) A few miles west on U.S. 36, more than 100 stranded residents of Pinewood Springs and Big Elk Meadows frantically tried to hire private helicopters to shuttle them out of isolation. Late Friday, Air National Guard helicopters began moving people with medical needs to safety because of limited resources. Larimer County Sheriff Justin Smith said his department has requested one or two more Air National Guard helicopters but needed more. Military copters also plucked people from Big Thompson Canyon, where Smith said parts of U.S. 34 had been "washed to the bedrock." Smith flew through the canyon in a Black Hawk helicopter, seeing washed-out roads, splintered buildings and stranded people moving around on the ground assessing the damage. "I was shocked at the width of the Big Thompson in Loveland, but that doesn't compare to the canyon and 17 miles of roadway gone," he said. "There are still hundreds, if not thousands, of people who can't get out." Rivers flowing 10 times higher than normal forced new evacuations in Jefferson, Larimer and Weld counties on Friday. In Jeffco, Bear Creek flooded Evergreen's downtown district, and threatened Morrison and Kittredge downstream. Traffic remained a mess as roads were shut down, washed away or under water — from local roads to major highways including Interstates 25 and 70 and U.S. 85. Dozens of Jeffco students at the Mount Evans Outdoor Lab had to hike out during a lull in the weather to a passable roadway. And 85 students from Louisville's Fireside Elementary were expected to be helicoptered out of the CalWood Education Center near Jamestown. Reporters Joey Bunch, Kristen Leigh Painter, Kieran Nicholson, Ryan Parker, Zahira Torres, Monte Whaley and the Boulder Daily Camera contributed to this report. Help for flood victims In the wake of torrential rainstorms that have raked the Front Range, flood victims can draw some comfort in knowing there are organizations offering help. Along with opening a number of temporary shelters in Boulder, Larimer and Adams counties, the American Red Cross in Colorado is collecting donations to underwrite relief efforts. redcross.org/charitable-donations. "The best way to help out is with cash donations," said Patricia Billinger, communications director for the Red Cross in Colorado and Wyoming. Even a little bit helps. A $2 donation will pay for a snack, $2.50 underwrites a hygiene kit distributed to evacuees, while $10 will pay for a hot meal and a couple of blankets, Billinger said. The Intermountain Salvation Army also is working on flood-relief efforts. Their donation website is imsalvationarmy.org. William Porter, The Denver Post ||||| A pair of hikers made it down one of Colorado's highest peaks on their own Friday after being stranded by an ice storm for two days, the National Park Service said. In this 2010 photo, Connie Yang, of York, Maine, climbs in Pawtuckaway State Park in Nottingham, N.H. Yang and Suzanne Turell made it safely down Longs Peak in Colorado Friday, Sept. 13, 2013, after... (Associated Press) In this March 2, 2013 photo, Suzanne Turell, of York, Maine, carries a surfboard at Hampton Beach, N.H. Turell and Connie Yang made it safely down Longs Peak in Colorado Friday, Sept. 13, 2013, after... (Associated Press) The Park Service had been trying to organize its latest effort to rescue the Maine women from 14,200-foot Longs Peak after bad weather defeated a helicopter rescue, said Patrick O'Driscoll, a Park Service spokesman. "They came out on their own," said Mark Pita, a ranger inside Rocky Mountain National Park. "They are in fine condition. They were not injured." The same storm system that blasted Colorado with rain caused the ice storm at higher elevations that pinned down Connie Yang, 32, and Suzanne Turell, 33. They were hunkered down inside a tent in whiteout conditions about 800 feet below the summit. "The mountain was socked in, no visibility, 12 inches of rain, flash flooding all over the place," O'Driscoll said. Employers and family members said the two set out a week ago on a backpacking trip in Rocky Mountain National Park, with summer gear including a flyweight tent. Before their phone battery died, the women used text messages to inform a sister of Yang's in New York City of their situation. "We need help," Turell said in one of her last texts around 9 a.m. Thursday. "No injuries. Iced over. Risk of hypothermia. On south ridge." They provided coordinates of their location off a trail. An earlier text message read: "Can't move because of ice storm, don't know how long it will last. Been here for 1 day trying to wait it out." The women, from York, Maine, work for New Hampshire-based outdoor gear manufacturer NEMO Equipment Inc. Turell is the company's director of product design. Yang is director of engineering. "I knew they're smart and tough and had technical skills," David Turell, a brother of Suzanne Turell, said from his home in Durham, N.H. "The question was whether their gear was going to keep them dry and warm enough, for long enough." Park rangers said they were taking the hikers from a trailhead in the Wild Basin area of Rocky Mountain National Park to Grand Lake, Colo. _ the only way out of the park Friday. Three roads on the park's east side remained impassable Friday because of mud slides, said Rick Frost, a spokesman for the Park Service's Intermountain Region in Denver. The hikers were being taken out the park's western access road. ___ Associated Press correspondent David Sharp contributed to this report from Portland, Maine.

– The flood misery continues in Colorado, but one piece of good news has emerged: Two women trapped in an ice storm for two days on one of the state's highest mountains managed to walk down to safety, reports the AP. The same storm that has delivered devastating floods pinned the experienced hikers from Maine on Longs Peak. Their plight became known when one texted her sister that they needed help, and the families set up this Tumblr page. Park Service officials couldn't get to them and were trying to organize another rescue attempt, "but they came out on their own," says a ranger in Rocky Mountain National Park. "They are in fine condition." In Boulder, however, authorities found the body of a 19-year-old woman, bringing the state death toll to four, reports the Denver Post. (The newspaper has thorough coverage of the devastation and rescue operations, including this photo gallery.) The body of the woman's boyfriend had been recovered yesterday—authorities think she got swept away after exiting their car, and he died trying to rescue her. Forecasters, meanwhile, say heavy rain is expected to continue through Sunday, reports CNN.

Orlando Health and Florida Hospital will not bill survivors of the Pulse nightclub massacre for out-of-pocket medical expenses, officials announced Wednesday. Instead, the hospitals will write off an estimated $5.5 million or more in care. "The pulse shooting was a horrendous tragedy for the victims, their families and our entire community," Orlando Health President and CEO David Strong said. "During this very trying time, many organizations, individuals and charities have reached out to Orlando Health to show their support. This is simply our way of paying that kindness forward." Its main hospital — Orlando Regional Medical Center — treated 44 of the more than 50 victims who needed immediate medical attention from the June 12 attack that killed 49 people. The nightclub is only a couple of blocks from the Level 1 trauma center. Nine of the Pulse patients died shortly after arriving at ORMC, and their families also will not be charged, hospital officials said. One victim remains hospitalized there. At Orlando Health, bills will be sent to health insurers for patients who had coverage, but whatever those policies don't cover will be absorbed by the hospital chain, said spokeswoman Kena Lewis. At Florida Hospital, which treated a dozen of the clubgoers, officials said they would not even bill the victims' insurance for the treatment, nor will they bill for follow-up surgeries the survivors may need. "It was incredible to see how our community came together in the wake of the senseless Pulse shooting," said Daryl Tol, Florida Hospital's president and CEO. "We hope this gesture can add to the heart and goodwill that defines Orlando." Survivors welcomed the news. "I was so worried because I can't afford any of that," said Mario Lopez, 34, who was visiting from Miami when he went to the club after a friend's housewarming party. (Naseem S. Miller) "I just went out for a fun night with friends. No one expected this to happen. My life was turned upside down, and then I had to worry about how I was going to pay back the hospital." Lopez, who is uninsured, was grazed by a bullet and had fragments explode into his left side. After he was hit, he fell and split his elbow on a shard of glass. His seven-hour hospital visit left him with a new nightmare: a potential $20,000-bill. "It's a huge relief" to know he won't have to pay, he said. At Orlando Health, Lewis said the hospital would work with victims who will need future surgeries as a result of the shootings. "We can't predict the future needs of these patients, their financial situations or what the state or federal governments may require us to do for charity policies," she said. "While we can't assume the answer is free care forever, we will use our very generous charity and financial assistance policies to assess the best way" to help. As it is, the hospital chain is expecting to shoulder at least $5 million in unreimbursed care for the Pulse victims, many of whom had extensive injuries, Lewis said. Florida Hospital officials said the bills there totaled more than $525,000. As for Lopez, his physical wounds are healing, he said, but the emotional trauma still feels raw at times. "It's tough," he said. "Each day, I have my moments." ksantich@orlandosentinel.com, @katesantich, 407-420-5503 chayes@orlandosentinel.com, @Journo_Christal, 407-420-5493 ||||| The Costs Of The Pulse Nightclub Shooting Enlarge this image toggle caption John Raoux/AP John Raoux/AP Mario Perez lives in Miami, but he was in Orlando for a housewarming party Saturday, June 11. After the party, the 34-year-old went to the Pulse nightclub for Latin night. At 2 a.m., he heard gunshots. Loud. He knew it was real. "And the minute he started shooting, I got hit from the side, I got grazed by a bullet," Perez says. "My first instinct was to fall to the floor, that's what you're taught to do." He heard gunshot after gunshot after gunshot — too many to count. But then there was a brief break in the firing, and Perez ran out the back of the club. He hid inside the kitchen of a nearby 7-Eleven until police and paramedics showed up. He was taken to Orlando Regional Medical Center, and was at the emergency room from 3 a.m. until 8 a.m. The gunshot wound on his side is purple and swollen, and he has nerve damage from the bullet fragment. He cut his elbow from glass on the floor of the nightclub and needed six stitches. Perez doesn't know how much bills coming from specialists, X-rays and tests might cost him. But his bill from Orlando Regional Medical Center's emergency department is $20,000. "$20,000," Perez said. "That's the quote, that's what they told me." Perez has no health insurance. He's working for a temp agency right now and doesn't have the money to be seen by a doctor for follow-up care in Miami. So just how much will the Pulse nightclub shooting cost all of the victims? It's a difficult, if not impossible question to answer right now. At last check, 56 people had been brought to the hospital, including three patients who spent two weeks in the intensive care unit, and one patient who is still in the hospital in critical condition. Embry Howell, a senior fellow at the Urban Institute, a think tank in Washington, D.C., studied the average cost of a gunshot victim in 2010. Using that benchmark, she estimates the hospital costs from the Pulse shooting will be about $1 million. "And I would imagine that would be an underestimate," Howell said. Howell said many of the victims may be in the same boat as Mario Perez: uninsured. "They're young, primarily Latino and living in Florida," she says, a state that has not expanded Medicaid to its population. "My guess would be you have a high rate of uninsured," she concludes. Ted Miller, a researcher with the Pacific Institute for Research and Evaluation, has been studying the cost of firearm injuries for more than two decades. He used the 2011 shooting of former U.S. Rep. Gabby Giffords and 18 others in Arizona to make what he calls a conservative estimate: $4 to $7 million in medical costs and mental health costs for victims and survivors of people who died. That's lifetime medical costs for the survivors, the costs of surgery and rehab — but it doesn't count long-term costs for those who are severely injured. "They said some time ago that there were six people in ICU who would have longtime, serious consequences," Miller said. "And my guess is most of those folks will have traumatic brain injuries that will have continuing lifetime care." Miller also makes a broader estimate beyond just the medical costs. That includes the cost of the police response, the cost to employers — and the dollar value of those 49 lost lives. "I estimate that the total cost of the Orlando shooting is around $385 to $390 million," Miller says. "To put that in context, on that same day, the cost of other gunshot wounds in the U.S. was probably about $600 million. So about 1 1/2 times the cost of the Orlando incident. That tells you that there are a lot of people killed and injured by firearms every day in this country," he says. And, he explains, "Suicide deaths account for the largest share of gun violence costs." Miller's $385 million estimate doesn't include the cost of mental health counseling for people who were in the club but not physically shot — and friends and family of those there. And then there's the cost of fear: people being afraid to go out to a dance club, or maybe skipping a visit to the theme parks. Orlando Regional received 44 of the shooting victims. A hospital spokeswoman says some patients have insurance coverage, some don't. The hospital is going to look for payment sources from the community or the state, such as victim funds that are raising money across the country. But she says the hospital expects unreimbursed costs of more than $5 million. Pulse shooting victim Mario Perez is calculating his personal costs. He's worried he's going to lose his job. He's anxious knowing millions of dollars have been raised to help victims, but his bills are arriving now. He started his own GoFundMe campaign, but it's only raised about $600. "As long as it gets covered, I'm going to be fine," Perez said. "If they don't cover it, I'm stuck in a hole. I don't know what I'm going to be able to do if they don't assist me." This story is part of a reporting partnership with NPR, Health News Florida and Kaiser Health News.

– They were fortunate enough to survive a gunman’s rampage that killed 49 others at an Orlando nightclub. But in the weeks following the June 12 massacre at Pulse, many survivors who needed medical treatment found themselves living another nightmare. Besides haunting memories, they suffered debilitating injuries that required painful surgeries and ongoing care. Some were uninsured. Now, Orlando hospitals are offering relief. Orlando Health and Florida Hospital announced Wednesday they will forgive an estimated $5.5 million in unpaid medical bills, the Orlando Sentinel reports. "We hope this gesture can add to the heart and goodwill that defines Orlando," says Florida Hospital CEO Daryl Tol. NPR reported last month that when long-term care is factored in, medical bills of Pulse survivors could reach $390 million. Blocks away from the nightclub, Orlando Regional Medical Center treated 44 shooting victims. One survivor remains hospitalized there. The hospital, run by Orlando Health, will bill insurance companies but cover any remaining costs, a spokeswoman said. The families of nine people who died there will not be sent a bill. Florida Hospital said it won’t bill the insurance companies of the dozen club-goers treated there, and all future care will be covered as well. Survivors welcomed the news. "I was so worried because I can't afford any of that," Mario Lopez tells the Sentinel. Lopez, 34, was hit with bullet fragments on the left side and has no insurance to cover a $20,000 ER bill. "It’s a huge relief."

TODAY released this statement to GLAAD on July 8: Over the past few days TODAY has received a considerable response regarding our wedding contest application. The rules stated that eligible couples must be able to be legally married in New York, where we will host the wedding, therefore excluding same-sex couple applicants. Our intent was not to be discriminatory or exclusive. In 2005 when the wedding took place outside of New York, the application process was open to same-sex couples. We have listened to every voicemail and read every email. We take this feedback seriously, and we will change our application process. TODAY is a longtime supporter of the LGBT community, and GLAAD considers us an ally. We are committed to keeping those relationships strong and positive. We have opened up the application process to same-sex couples, and will extend the deadline to Monday, July 12. Moving forward, we ensure that our future wedding contests will be inclusive of all couples. To read GLAAD's statement, "You Spoke and NBC Listened: Today Show’s 'Modern Day Wedding Contest' Opened to Same-Sex Couples", click here. If you are interested in applying to become TODAY's wedding couple, click here. ||||| NBC will change the application process for the “Today” show’s “Modern Day Wedding Contest ” so that same-sex couples are permitted to participate, the network said Thursday. The change was announced after a campaign by GLAAD, the Gay and Lesbian Alliance Against Defamation, and a meeting between the organization’s representatives and the “Today” executive producer in New York. The wedding contest is a staple of the “Today” show, the most popular morning show on television. It allows viewers to vote on every detail of a couple’s wedding, which is then broadcast live on the show. GLAAD said last week it was alerted that NBC’s application for the contest only included the options “bride” and “groom.” According to GLAAD, NBC initially argued that same-sex couples could not apply because “For the “Today” show wedding, the couple must be able to be legally married in New York, which is where the wedding will take place.” GLAAD said in a blog post that it “questioned the validity of that argument since New York State legally recognizes same-sex marriages licensed in other states,” adding, “NBC mistakenly equated the marriage license with the wedding celebration.” On Tuesday the group called on its supporters to call and send e-mail messages to NBC. In doing so, it brought the gay marriage debate to the front doorstep of an American institution, the one that used to be called “America’s first family” in commercials. On Wednesday, NBC officials asked GLAAD for a meeting, and subsequent to that meeting, the network announced that its application process would be adjusted. “Our intent was not to be discriminatory or exclusive,” the network said in a statement, noting that “in 2005 when the wedding took place outside of New York, the application process was open to same-sex couples.” “Today” said it had extended the Friday deadline for wedding applicants by three days so that same-sex couples could apply, and “moving forward, we ensure that our future wedding contests will be inclusive of all couples.” Jarrett Barrios, the president of GLAAD, said in a statement, “We’re thrilled that ‘Today’ show’s ‘Modern Wedding Contest’ now recognizes what most fair-minded Americans have already concluded – a wedding celebrates love and commitment, whether the spouses are straight or gay.” Even though same-sex couples will be allowed to apply, it does not guarantee an appearance on the morning show. “Today” producers sort through all the applications and pick four finalists, and then the viewers take it from there, voting for which of the four should actually win the wedding and the all-expense-paid honeymoon. The wedding will take place on “Today” in October.

– The Today show will open its annual “Modern Day Wedding” contest to gay couples, NBC has announced, bowing to activist pressure. The gay rights group GLAAD launched a campaign to change the contest last week, the New York Times explains, after discovering the application had options only for “bride” and “groom.” NBC originally tried to argue that gay couples couldn’t be married in New York, but GLAAD pointed out that New York honors out-of-state marriage licenses. “NBC mistakenly equated the marriage license with the wedding celebration,” GLAAD wrote. NBC asked to meet with the activists on Wednesday, and yesterday announced the change of heart. “Our intent was not to be discriminatory or exclusive,” the network said in a statement. “Today is a longtime supporter of the LGBT community, and GLAAD considers us an ally.”

it is widely believed that radio - loud quasars and powerful radio galaxies ( frii - type according to the scheme of fanaroff & riley @xcite ) differ only by the orientation of their radio axes with respect to the observer s line of sight ( e.g. barthel @xcite ) . a related scenario proposes that the cores of these radio sources are dominated by beamed emission which can be significantly enhanced by doppler boosting , while the extended emission is isotropic ( e.g. orr & browne @xcite ) . these two models explain why radio loud quasars tend to have more luminous radio cores compared to frii radio galaxies with similar extended radio luminosities , and has prompted the use of the core dominance parameter , @xmath0 as a relative measure of orientation . [ in an attempt to have a meaningful , concise , and consistent notation throughout this paper , we employ the superscripts c , e , and t to refer to the core , extended , and total radio emission ( power , @xmath1 , or flux , @xmath2 ) respectively , and subscripts to indicate the rest - frame frequency ( in ghz ) . ] recently , qin et al . ( @xcite , hereafter q98 ) investigated the core and extended radio properties of four samples of quasars from the literature . they found that in core - dominated quasars , the extended radio power , @xmath3 , was inversely correlated with @xmath4 , while the core radio power , @xmath5 , was not correlated at all . in lobe - dominated quasars , on the other hand , @xmath3 was uncorrelated while @xmath5 was correlated with @xmath4 . they claimed that these correlations were in contradiction with the unified schemes and beaming models , and proposed instead that the core emission in core - dominated quasars is unbeamed and isotropic . in this _ letter _ , we show that the results found by q98 _ are _ in agreement with beaming models , given the selection criteria of the samples they studied , and that core - dominated quasars do not comprise a separate class of active galactic nucleus . in [ sec : beam ] we explain the reasons for the correlations observed ( or unobserved ) by q98 , and in [ sec : sim ] we compare the predictions of monte carlo simulations of extragalactic radio sources with the data from the samples analyzed by q98 . in beaming models , it is assumed that all radio sources are intrinsically steep - spectrum , and flat - spectrum sources are merely those where the core is boosted sufficiently strongly to dominate the total flux over the observed frequency range . the extended radio luminosity of _ all _ radio sources therefore follows the radio luminosity function for steep - spectrum sources , in which the number of sources above a given luminosity decreases sharply with luminosity . we first consider core - dominated quasars ( cdqs ) . q98 believe that @xmath5 should be correlated with @xmath4 because those sources with the most luminous cores should be those with the strongest beaming . this is obviously true at some level , since both punsly s ( 1995 ) and murphy , browne & perley s ( 1993 ) samples , which are selected on core strength , contain only strongly - beamed sources . however , we show by considering the situation in more detail that the presence or absence of correlations is controlled by selection effects , and that this simplistic belief is too nave . beaming models predict that the observed core dominance parameter should depend on the jet speed , @xmath6 , the viewing angle , @xmath7 , and the transverse ( unbeamed ) core dominance parameter , @xmath8 , as @xmath9 ( e.g. orr & browne @xcite ) , where the second term can be ignored for small values of @xmath7 . obviously , the orientation of any given source is independent of its extended radio luminosity , and let us assume for the moment that @xmath10 and @xmath8 are also independent of @xmath3 . in this case , the extended radio luminosity function ( erlf ) is separable in some form @xmath11 and sources with a given value of @xmath4 follow the same erlf as the general source population . let us examine punsly s ( @xcite ) sample , which is q98 s sample 1 . this consists of rlqs with core powers ( integrated over @xmath12 ) above @xmath13w . consider those sources with , say @xmath14 ; they need to have @xmath15w to satisfy the selection criterion . the shape of the erlf is such that about three - quarters of all such sources will lie within a factor two of this limit , and only about 1% will exceed it by an order of magnitude . most sources with @xmath16 will therefore have @xmath17w . if one now considers sources with @xmath18 , the same arguments indicate that these sources will have @xmath19w . therefore the extended radio power will be strongly inversely correlated with @xmath4 , which is exactly what is observed in punsly s sample . since the core luminosity is merely @xmath20 , the core power will be uncorrelated with @xmath4 . exactly the same argument applies for sample 2 ( from murphy et al . @xcite ) , which is a sample selected on core flux , rather than luminosity . it is the fact that these samples are selected on core strength that causes the observed correlations , and not the fact that the sources are cdqs . the maximum observable core dominance parameter is @xmath21 . for typical values of @xmath22 ( @xmath23 , e.g. guerra & daly @xcite ) and @xmath24 ( at 5ghz , simpson @xcite ; see also morganti et al . @xcite ) , this is about 20 using the defintion and canonical radio spectra of punsly ( @xcite ) . to exceed this value by nearly two orders of magnitude ( as some of punsly s sources do ) , a source must either have an unusually fast jet ( @xmath25 , @xmath26 ) or a much larger than average @xmath8 . these parameters will therefore be correlated with the observed core dominance , and so could an additional correlation with extended radio power nullify the above argument ? suppose that @xmath10 is correlated with the extended radio luminosity . this is not unreasonable since the most powerful radio sources might also produce the fastest jets . if so , sources with large @xmath4 are more likely to be drawn from the high - luminosity end of the erlf . on the other hand , @xmath8 might be anticorrelated with extended radio luminosity , since the lobe luminosity of a radio source decreases throughout its lifetime despite a constant jet power ( e.g. baldwin @xcite ) . so sources with large @xmath4 might preferentially be older sources with lower extended radio luminosities . the fact that the anticorrelation between @xmath27 and @xmath28 appears not to alter its slope at large @xmath4 indicates that either both these effects are weak , or that they have approximately the same strength and cancel each other out . we now turn to lobe - dominated quasars ( ldqs ) . hooimeyer et al.s ( @xcite ) sample of quasars ( q98 s sample 3 ) is selected on a minimum angular size , thereby requiring measurable emission from the radio lobes and excluding the most strongly - boosted , pole - on sources , but also has a bright core radio flux limit ( @xmath29jy ) , which means that it will include many cdqs . in addition , the sample is drawn from the hewitt & burbidge ( @xcite ) optical quasar catalogue and is therefore subject to uncertain selection effects . the fact that in reality it is a mix of cdqs and ldqs can serve to explain why it displays both correlations , but at a much weaker level than in samples of cdqs or ldqs alone . we do not consider it further . instead , we turn to the well - defined sample 4 , from hough & readhead ( @xcite ) which contains all double - lobed quasars from 3crr ( laing , riley & longair @xcite ) whose cores were bright enough to be mapped with the mark iii vlbi system . all sources therefore have @xmath30jy and @xmath31mjy . unlike the core - selected samples , the total flux at the selection frequency ( 178mhz ) has a negligible contribution from the flat - spectrum core , and therefore @xmath32 has no dependence on @xmath4 . neither does @xmath33 , which can be assumed to be the extended luminosity alone . the spectral index of the lobes is not expected to be physically related to core dominance , and we confirm that this is so in the sample of radio galaxies from hardcastle et al . ( @xcite ) by using the generalized spearman s rank order correlation coefficient ( isobe , feigelson & nelson @xcite ) , where we find that the two quantities are uncorrelated at greater than 90% confidence . therefore , @xmath34 will be uncorrelated with @xmath4 . on the other hand , @xmath35 , and should therefore be clearly correlated with @xmath4 , with the linear regression line having a slope of unity , in line with observations . again , it is not the nature of the sources ( ldqs ) which produces the result , but the selection criteria . in order to test whether the above arguments can explain the observations in a quantitative manner , we perform simulations of radio sources . we start with the steep spectrum radio luminosity function ( rlf1 ) of dunlop & peacock ( @xcite ) , which we assume to be equivalent to the extended luminosity of all radio sources , and consider only those sources with luminosities above the fanaroff - riley break ( i.e. frii sources ; fanaroff & riley @xcite ) , since it is only these which constitute the parent population of quasars ( e.g. urry & padovani @xcite ) . we assume that the sources are randomly oriented with respect to the observer , and that their @xmath36 values are drawn from a normal distribution with mean @xmath37 and standard deviation 0.50 . this distribution provides a good fit to the observed values of @xmath4 for frii radio galaxies and quasars from laing et al . ( @xcite ) with @xmath38 , after applying the orr & browne ( @xcite ) beaming model ( simpson et al.@xcite ; see also simpson @xcite ) . it is assumed that the radio cores have @xmath39 and the extended emission has @xmath40 ( @xmath41 ) . a jet speed @xmath42 is assumed for the purposes of simulating doppler boosting . we then subject the ensemble of sources to the selection criteria of the samples studied by q98 , and compare our regression and correlation analysis with theirs . as the samples of q98 invariably have a number of sources with incomplete information that prevent them being included in q98 s analysis , we also randomly exclude sources from our complete samples so as to have the same sample size . this ensures that the same level of randomness should exist in our simulated samples as in the real data . all our simulations assume @xmath43kms@xmath44mpc@xmath44 , @xmath45 and @xmath46 , although the significance of the correlations we find do not depend on our choice of cosmology . sample 1 ( punsly @xcite ) consists of quasars with core luminosities , integrated over the range @xmath47 , greater than @xmath13w . adopting the typical core spectrum assumed by punsly , this corresponds to @xmath48whz@xmath44 , which we adopt as our selection criterion . in figure [ fig : sample1 ] we plot the extended and core luminosities against the core dominance parameter . sample 2 ( murphy et al . @xcite ) contains sources with core fluxes @xmath49jy and spectral indices ( between 1.4 and 5ghz ) @xmath50 which are identified with quasars . this last criterion will exclude nearby sources since they would be classified as ( broad line ) radio galaxies . examining murphy et al.s sample , we elect to discard all sources from our dataset with @xmath51 to simulate this . there are in fact only about three sources at such low redshifts in a typical dataset , so the results are not strongly affected . the simulated datasets are shown in figure [ fig : sample2 ] . as discussed earlier , sample 3 ( hooimeyer et al . @xcite ) has uncertain selection criteria , and so we make no attempt to simulate it . sample 4 ( hough & readhead @xcite ) consists of sources with @xmath52jy and @xmath31mjy that are classified as quasars . since this is a much fainter core flux limit than sample 2 , we can not just apply a redshift cutoff , since many distant narrow line radio galaxies will have sufficiently bright cores . instead we require ( in addition to @xmath53 ) , that @xmath54 ( see barthel @xcite ) , which produces the sample displayed in figure [ fig : sample4 ] . .correlation coefficients , @xmath55 , and slopes of the best - fit regression lines , @xmath56 , for the three samples modelled . for each sample , the top line contains the results from the real data determined by q98 , and the bottom line contains the results from the simulated data . [ cols="^,^,>,>,>,>",options="header " , ] table [ tab : results ] presents the results of correlation and regression analysis on the simulated datasets , and clearly shows that the simulated datasets display exactly the same correlations as the real data . whether it is core or extended radio luminosity that is correlated with core dominance is therefore not due to some physical difference between cdqs and ldqs , but merely an effect caused by the sample selection criteria , as discussed in [ sec : beam ] . we note that our simulated data underproduces the number of highly core - dominated ( @xmath57 ) quasars , compared to observations . this is presumably a result of our not having incorporated a range of jet speeds into our model , since with a single speed ( @xmath22 ) such sources require a viewing angle close to the line of sight _ and _ a large value of @xmath8 . if the jet speed is a third random variable then such sources can be created if only two out of the three variables have extreme values , and this would therefore increase their frequency in our simulated universe . we have investigated the claim by qin et al . ( @xcite ) that the observed correlations between core dominance and core or extended radio luminosity in samples of core- and lobe - dominated quasars are in contradiction with the beaming models which form a part of the unified scheme for extragalactic radio sources . we have argued that these correlations are actually _ expected _ to arise from the beaming models as a natural consequence of the steepness of the ( extended ) radio luminosity function and the selection criteria of the samples . we have supported our claim by simulating quasar samples using the observed radio luminosity function and the statistics of beaming , and find that our simulated data produce results which are indistinguishable from those produced by the real data on which they are based . baldwin , j.e . 1982 , in extragalactic radio sources , ed . heeshen & c.m . wade ( dordecht : reidel ) , 21 barthel , p.d . 1989 , apj , 336 , 606 dunlop , j.s . , peacock , j.a . 1990 , mnras , 247 , 19 fanaroff , b.l . , riley , j.m . 1974 , mnras , 167 , 31p guerra , e.j . , daly , r.a . 1997 , apj , 491 , 483 hardcastle , m.j . , alexander , p. , pooley , g.g . , riley , j.m . , 1998 , mnras , 296 , 445 hewitt , a. , burbidge , g. 1987 , apjs , 63 , 1 hooimeyer , j.r.a . , barthel , p.d . , schilizzi , r.t . , miley , g.k . 1992 , a&a , 261 , 18 hough , d.h . , readhead , a.c.s . 1989 , aj , 98 , 1208 isobe , t. , feigelson , e.d . , nelson , p.i . , 1986 , apj , 306 , 490 laing , r.a . , riley , j.m . , longair , m.s . 1983 , mnras , 204 , 151 morganti , r. , oosterloo , t.a . , reynolds , j.e . , tadhunter , c.n . , migenes , v. , 1997 , mnras , 284 , 541 murphy , d.w . , browne , i.w.a . , perley , r.a . 1992 , mnras , 264 , 298 orr , m.j.l . , browne , i.w.a . 1982 , mnras , 200 , 1067 punsly , b. 1995 , aj , 109 , 1555 qin , y.p . , xie , g.z . , bai , j.m . , fan , j.h . , zheng , x.t . , wu , s.m . 1998 , a&a , 333 , 790 ( q98 ) simpson , c. , 1996 , va , 40 , 57 simpson , c. , et al . , 1998 , in preparation urry , c.m . , padovani , p. , 1995 , pasp , 107 , 803

we investigate the recent claim by qin et al . that the observed correlations ( or lack thereof ) between the core dominance parameter and the core and extended powers of samples of lobe- and core - dominated quasars is in contradiction with beaming models . contrary to their conclusion , we find that their results are in perfect agreement with such models , and support this assertion with monte carlo simulations .

the nature of the effects of higher - order corneal aberrations on lower - order corneal astigmatism has until now been poorly understood . if the corneal astigmatism differed from the manifest astigmatism , it was usually diagnosed as lenticular astigmatism through a process of exclusion . some authors have also performed studies to show that the posterior surface of the cornea can also cause astigmatism , but the amount of induction of astigmatism has been relatively small ( on the order of a fraction of a diopter).13 topography - guided ablation , market name contoura on the wavelight excimer lasers ( wavelight , erlangen , germany ) , has added yet another element of uncertainty . often the manifest refraction ( cyclopleged or not ) and the autorefraction do not correspond with the astigmatism that contoura processing results in . in parts 2 and 3 of this series , the author has shown that correcting with contoura processing through the lyra ( layer yolked reduction of astigmatism ) protocol results in correction of astigmatism in virtually all cases , and has also demonstrated that treatment on the wrong manifest astigmatism axis can result in loss of effectiveness of astigmatism correction and also induction of a whole new astigmatism on an oblique axis.4,5 we examined patients who had a significant difference between manifest refraction and contoura measured astigmatism in an effort to delineate the reasons for induction , modification , and reduction of astigmatism by the corneal aberrations . our hypothesis was that the higher - order aberrations ( hoas ) were directly modifying the lower - order astigmatism in such a way as the combination of the distortion of the two necessitated the cortical processing to pick a point of least confusion , resulting in a manifest refraction that was often significantly different from the contoura measured astigmatism / axis . figure 1 shows how with - the - rule and against - the - rule create an oval - shaped central cornea . this demonstrates the ovalization caused by these two types of lower - order astigmatism . an analysis was performed by the author in patients who had full contoura measured correction performed as per the lyra protocol , which allows for contoura processing to determine the linkage in between the aberration correction layer and the refraction correction layer . the lyra protocol is as follows : enter the manifest / cycloplegic refraction into contoura during presurgical planning.zero out the astigmatism and sphere to see ablation pattern for the aberration correction layer.enter contoura measured astigmatism and axis for the final correction . the ablation map at this point should be similar to the pentacam anterior elevation map . this will assist understanding the ablation when there is a significant discrepancy between manifest versus measured astigmatic power and axis.the sphere is now entered after adjustment for the spherical equivalent of the change in astigmatism . zero out the astigmatism and sphere to see ablation pattern for the aberration correction layer . the ablation map at this point should be similar to the pentacam anterior elevation map . this will assist understanding the ablation when there is a significant discrepancy between manifest versus measured astigmatic power and axis . the sphere is now entered after adjustment for the spherical equivalent of the change in astigmatism . aberration correction was visualized on the treatment planning page of contoura by zeroing out the refraction , and displaying contoura correction of the aberration . the change of shape to the central cornea was determined using this method , and comparison against the manifest refraction astigmatism and axis was performed . the examination of a large number of eyes resulted in six categories where manifest astigmatism was different from corneal astigmatism . all patients were analyzed using the topolyzer vario , and all patients had correction by one surgeon ( mm ) at one center using the wavelight ex500 system with contoura and the wavenet server . as part of this analysis , patients had cyclopleged manifest refractions performed to rule out the existence of lenticular accommodation of astigmatism . for purposes of this paper , a manifest refraction will be a cyclopleged one , essentially the refraction that we obtain using the phoropter with patient subjective input . all cases below each have a preoperative topography , postoperative topography , and aberration ablation pattern to determine the type of aberration . case 1 : corneal aberration induction of manifest astigmatism ( figure 2 ) preoperative manifest refraction : 1.00 , 2.758 with best - corrected visual acuity ( bcva ) of 20/20preoperative autorefraction : 0.50 , 2.50171measured contoura correction : 1.40 , 2.001postoperative refraction and vision at 3 months : plano ; 20/15 . preoperative manifest refraction : 1.00 , 2.758 with best - corrected visual acuity ( bcva ) of 20/20 preoperative autorefraction : 0.50 , 2.50171 measured contoura correction : 1.40 , 2.001 postoperative refraction and vision at 3 months : plano ; 20/15 . in this case , the hoa creates an oval that adds to the lower - order astigmatism oval , increasing the manifest astigmatism . when the hoa is treated , the amount of astigmatism correct is decreased as demonstrated by the contoura measured correction and postoperative result . case 2 : corneal aberration cancellation of manifest astigmatism ( figure 3 ) preoperative manifest refraction : 1.50 with bcva of 20/20preoperative autorefraction : 2.00measured contoura correction : 1.12 , 0.77121postoperative refraction and vision at 1 week : plano ; 20/15 . preoperative manifest refraction : 1.50 with bcva of 20/20 preoperative autorefraction : 2.00 measured contoura correction : 1.12 , 0.77121 postoperative refraction and vision at 1 week : plano ; 20/15 . this particular patient had his entire lower - order astigmatism completely cancelled out by the hoa , resulting in a manifest refraction with no astigmatism ( no astigmatism on the autorefraction also ) . the oval caused by the lower - order astigmatism is oblique ( oblique astigmatism has only been seen rarely by us ) , as is the ovalization created by the hoas , and the two ovals completely cancel each other out during manifest refraction . removing the hoa reveals the lower - order astigmatism underneath , which can be recognized as bowtie case 3 : corneal aberration cancellation via oblique aberration and cerebral processing ( figure 4 ) preoperative manifest refraction : 2.75 with bcva of 20/20preoperative autorefraction : 3.75 , 0.25150measured contoura correction : 2.40 , 0.771postoperative refraction and vision at 1 month : 0.25 ; 20/15 . preoperative manifest refraction : 2.75 with bcva of 20/20 preoperative autorefraction : 3.75 , 0.25150 measured contoura correction : 2.40 , 0.771 postoperative refraction and vision at 1 month : 0.25 ; 20/15 . this patient shows with - the - rule astigmatism on topography , but has a manifest refraction and autorefraction that essentially shows no astigmatism . the ablation pattern shows correction of trefoil , but the oval created is not along the axis expected to cancel out the corneal lower - order astigmatism . the other eye of this patient had a similar with - the - rule astigmatism on topography , similar lack of astigmatism of manifest and autorefraction , but the aberration oval was perpendicular to the lower - order astigmatism and clearly cancelled it out . this one is at an oblique angle , so it appears that somehow the patient s cerebral processing is working similar to the other eye , but somehow still cancelling out the astigmatism with an oblique aberration . it is difficult to see how even examining this aberration in three dimensions would somehow create an ovalization that was directly perpendicular to the oval created by the lower - order bowtie astigmatism . the result of contoura measured correction resulted in 20/15 vision with all astigmatism removed in both eyes . case 4 : aberration induction of astigmatism with dilation of the pupil ( figure 5 ) preoperative manifest refraction : 7.75 , 1.0075 with bcva of 20/20preoperative autorefraction : 8.00 , 0.7575measured contoura correction : 8.00 , 0.07121postoperative refraction and vision at 1 month : plano ; 20/15 . preoperative manifest refraction : 7.75 , 1.0075 with bcva of 20/20 preoperative autorefraction : 8.00 , 0.7575 measured contoura correction : 8.00 , 0.07121 postoperative refraction and vision at 1 month : plano ; 20/15 . this patient has coma directly adjacent to the pupil , causing manifest refraction and autorefraction of astigmatism . case 5 : oblique manifest astigmatism induced by corneal aberration ( figure 6 ) preoperative manifest refraction : 2.50 , 0.50155 with bcva of 20/20preoperative autorefraction : 2.75 , 0.50142measured contoura correction : 2.00 , 1.501postoperative refraction and vision at 1 month : plano ; 20/15 . preoperative manifest refraction : 2.50 , 0.50155 with bcva of 20/20 preoperative autorefraction : 2.75 , 0.50142 measured contoura correction : 2.00 , 1.501 postoperative refraction and vision at 1 month : plano ; 20/15 . bowtie astigmatism , yet both manifest and autorefraction show an oblique astigmatism of a much smaller magnitude . in this particular case the trefoil is creating an oval that is at an oblique angle cancelling out the with - the - rule astigmatism and also creating an oblique astigmatism . removing the aberration results in 1.50 d of with - the - rule astigmatism . the topography shows signs of the epithelium still becoming uniform from epithelial molding to the aberration . case 6 : pure lenticular astigmatism ( figure 7a c ) this case has a wavefront measured astigmatism of 3.5 d at 84 degrees , a manifest astigmatism of 1.75 d at 90 degrees , and a contoura measured astigmatism of 1.49 d at 81 degrees . the contoura measured astigmatism is very close to the manifest astigmatism , while the wavefront shows a much higher amount of measured astigmatism . in this case , the corneal aberration is cancelling out astigmatism that can only be coming from the lens , and treating the contoura measured will reveal astigmatism from the lens . the diagnosis of such a case is best done with wavefront measurement , and treatment of residual astigmatism can either be done with wavefront - guided or likely even wavefront - optimized correction . if the surgeon elects to treat , they must inform the patient of the need for re - treatment if cataract surgery is ever necessary . this understanding of how hoas affect lower - order astigmatism came about as an attempt to understand why the lyra protocol using the measured contoura astigmatism is effective . different theories were examined , but the underlying fact was that using the lyra protocol eliminated astigmatism , and resulted in good vision even when the manifest astigmatism / axis differed markedly from the contoura measured astigmatism / axis . over time , examining the hoa pattern of patients in relation to their lower - order astigmatism , and the changes from manifest refraction to contoura measured led to an understanding of how the hoas were interacting with the lower - order astigmatism . essentially , this understanding was reverse - engineered from the realization that the lyra protocol works and creates more uniform corneas . the author initially considered the theory that lenticular accommodation of the cornea may exist to explain some of the differences between manifest and measured refraction . this would be where the lens is capable of accommodating in such a way as to correct or even cause astigmatism . this has never been proven to exist , but was a theory that was considered . cycloplegia would actually provide a different astigmatism refraction that would be closer to or equivalent to the contoura measured astigmatism if lenticular accommodation of astigmatism was present . unfortunately , in no cases that the author examined was this demonstrated , and all patients considered for this analysis had cyclopleged refractions to rule out any accommodative aspect . what we have theorized is that peripheral or central hoas create an ovalization in the central cornea ( within the mesopic pupil ) , resulting in a deformed central ray of light forming a lower - order astigmatism . therefore , the manifest refraction is a result of the oval shapes created by lower - order and higher - order astigmatism and its resulting central ray of light interaction . corneal lower - order astigmatism essentially creates an oval shape in the center of the cornea , as shown in the figures . corneal aberrations such as trefoil and quadrafoil can also create an oval shape to the central cornea , and depending on how the two ovals of higher - order and lower - order aberration line up , it will either increase or decrease the manifest measurement of astigmatism . the author further theorizes that the central ray of light forms the main part of vision , and the refraction requested by the patient achieves the best possible correction that minimizes cerebral confusion via the addition of spherical or astigmatism glass correction . this visual impression of the patient is widely determined by the shape formed by low- and high - order aberrations that pass the central portion of the cornea and form the related focusing at the retinal level . it adds or reduces the amount of refraction ( depending on the orientation of the spherical aberration ) when the pupil widens . the dilated pupil allows the pre - existent hoa to become dominant and change the focus quality at the retinal level . this paper in contrast seeks to demonstrate that hoas can also affect the visual impression of the patient . furthermore , the autorefractometer might not be able to detect the difference between hoa and lower - order aberration , because it measures only the central 2 mm of the cornea and , therefore , the ray of light deformed by the lower - order aberrations and hoas . what we have observed across the examination of many patients is that the majority of hoas are trefoil , with a lesser amount of quadrafoil , and coma . when the aberration is examined using the treatment planning page , it was possible in some cases to see the oval created by the aberration and how it impacted the actual corneal astigmatism . unfortunately , aberrations are not two dimensional , they are three dimensional and the ovals simply do not line up in all two - dimensional ablation maps . contoura with lyra protocol results in many cases with a completely different measured astigmatism and axis versus the manifest . in the author s experience , performing this procedure has not worsened patients vision , which would occur if the hypotheses presented here were incorrect . the author surmises that it is cerebral processing that compensates for the distortion caused by hoas . the cerebral cortex must interpolate information where it becomes distorted by an hoa , and removal of that hoa would remove the need for that interpolation . although there has been some conjecture in the past that some aberrations may be good , that is , as in fighter pilots that have 20/10 vision and hoas , the author believes that the high resolution for the 20/10 vision comes from a high density of photoreceptors in the retina in these individuals , and a fighter pilot s or baseball player s high capabilities in dynamic vision testing are due to rapid cerebral interpolation to compensate for distortion created by hoas . if this is the case , then removal of the hoas on a person who is already 20/10 would result not in better snellen visual acuity ( which would be limited by retinal photoreceptor density in the macula ) , but in faster response times as cerebral processing / interpolation would no longer be necessary . furthermore , the ability to clearly see the edges of objects would allow for faster locking in by the brain for dynamic motion , likely resulting in better response time to a 95 mile per hour fastball or a fast flying opposing fighter that require responses in the milliseconds . the author now postulates that there is no such thing as a good aberration , but essentially all aberrations are bad and require cerebral processing to compensate for them . treating these hoas to make a more uniform cornea will simply allow a clear path of light that will not need to be compensated for . at this point , it should be mentioned that too much emphasis can be placed on the snellen visual acuity . we have all seen 20/15 patients who are not happy , and we have treated patients for halos who are clearly 20/15 but have 0.5 d of astigmatism and complain about their night vision . treating that residual astigmatism significantly improves the night time vision and decreases halos . in our experience , a patient who is 20/20 without halos is happier than a 20/15 with halos . an eye with 20/15 or 20/10 vision after laser correction means that the treatment allowed the retina to more fully achieve its resolution , but it does not guarantee that aberrations or incomplete treatment of the cornea will not result in a patient who is not completely happy . for purposes of visualization , with - the - rule astigmatism if the aberration also creates an oval that is horizontal , the manifest astigmatism will be greater than the corneal astigmatism . if the aberration creates a vertical oval on the same type of cornea , the manifest astigmatism will be cancelled out or less than the corneal astigmatism . depending on the axes of the two ovals the manifest and measured axis may be significantly different also . with further refinement of the contoura software , we would be able to specifically quantify the axis of the oval created by the aberration , as we can quantify the axis created by lower - order corneal astigmatism , and with that create a vector diagram that can accurately predict the axis . this would be interesting for demonstrative purposes , but in essence contoura does it for us by giving us the final result of astigmatism and axis by calculating this interaction . the author understands that separating these interactions as has been done in this paper is artificially attempting to break down complex three - dimensional interactions between the hoa and the lower - order astigmatism into a two - dimensional image for illustration purposes . we do not expect to find these interactions in every single case , but in many cases this interaction can be visualized . the main takeaway from these cases is that the interactions are mainly corneal in nature , and rarely involve the lens as has been postulated for many years via data from wavefront maps . cases 1 and 2 essentially demonstrate either cancellation or induction of astigmatism with ovalization created by the hoas that is either on the same axis or perpendicular to the oval created by the lower - order astigmatism . case number 3 demonstrated a different sort of issue , where the oval shape created by the aberration was oblique to the axis of the corneal astigmatism , yet seemed to fully cancel it out . although it is possible that the oval created centrally is not as oblique as the overall shape of the trefoil aberration in his cornea , we think just as likely it may be that cerebral processing is involved . this patient s other eye had a textbook cancellation of with - the - rule astigmatism by corneal aberration . it may very well be that there was partial compensation of the astigmatism in case 3 by the aberration , and partial compensation of the corneal astigmatism via cerebral processing . we know that manifest refraction is based simply on the point of least confusion of vision , and we know that what we see is actually subject to cerebral processing . this particular case was an anomaly , and the only one that the author has seen like this , where it seems cerebral processing somehow allowed an oblique aberration to cancel out a regular with - the - rule astigmatism . in this case , it is difficult to see even how examining this aberration in three dimensions would somehow create an ovalization that was directly perpendicular to the oval created by the lower - order bowtie astigmatism . in case 5 , we also demonstrate a case where an oblique aberration appears to cancel out a with - the - rule lower - order astigmatism . in that case , an oblique astigmatism is created on manifest refraction . in this case , there is no oblique astigmatism on manifest refraction , just a complete cancellation of with - the - rule astigmatism . cerebral processing is responsible for figure 5 , where the lines do not look parallel but actually are . this type of simple drawing is an example of how cerebral processing can be used to alter how we see things . case 4 demonstrates how coma peripheral to the pupil can result in incorrect measurement of astigmatism in a dark room with a mydriatic pupil , or during cyclopleged refraction . correction of this astigmatism results would lead to an incorrect result , as there is no actual astigmatism , but a localized distortion created by the high spot of the peripupillary coma . such a patient may have decreased or no manifest astigmatism with a meiotic pupil , as the pupil may close enough to decrease or eliminate the distortion created by the coma . removal of the coma results in a cornea that has no astigmatism on either manifest or cyclopleged refraction . not only can the coma cause a manifest astigmatism , but it can also change the axis of astigmatism of an actual lower - order corneal astigmatism , resulting in an incorrect treatment . this particular patient had astigmatism at an oblique axis on manifest , cyclopleged manifest , and also autorefraction . contoura measured showed no astigmatism at all , supported by the fact that no lower - order astigmatism is noted on the preoperative topography . similar examples can be demonstrated with corneal keratoconus patients where the predominating aberration is coma ( except in the case of central keratoconus ) . case 5 demonstrates how an oblique aberration oval changes the with - the - rule astigmatism noted on topography to an oblique manifest astigmatism . this case shows how the interaction between lower- and higher - order astigmatism can also end up with an oblique axis of astigmatism being created . in this particular case not only does the oblique oval created by the trefoil cancel out the with - the - rule astigmatism , but it also creates a tangential astigmatism at an oblique axis . after observing the interactions between higher- and lower - order astigmatism over many contoura with lyra protocol corrections , the vast majority of lower - order astigmatism is actually either with- or against - the - rule , with an axis of astigmatism usually within 15 degrees of the 90 degree and 180 degree axes . it appears that oblique manifest astigmatism seems to be mainly caused by either an oblique oval created by an aberration , or by peripupillary coma that affects the mydriatic and cyclopleged manifest measurements . this patient has minimal lower- or higher - order corneal astigmatism , but has a manifest refraction showing astigmatism . pure lenticular astigmatism appears to be more uncommon than originally thought . in the analysis of author mm s patients , since performing contoura with lyra protocol corrections , no patients had demonstrated lenticular astigmatism . contributor sl has seen 45 eyes with lenticular astigmatism several years and thousands , of eyes examined . in all cases of lenticular astigmatism there was little to no corneal aberration or corneal astigmatism present , with significant astigmatism on manifest refraction . such a case is presented here as case 6 , and the author believes that such a case should be carefully approached as the center of lenticular astigmatism may be different than the center for wavefront - optimized or wavefront - guided treatment . although theoretically a patient may exist with corneal aberration , corneal astigmatism , and lenticular astigmatism , neither the author nor the contributors have seen such a patient to this point . such a patient would have residual astigmatism after all corneal aberrations and astigmatism were eliminated . enhancement of such a patient could likely be done through wavefront - guided ablation , or even perhaps by wavefront - optimized ablation to eliminate residual astigmatism . the takeaway message , though , is that lenticular astigmatism is much less common than has been estimated . this has been a diagnosis of exclusion , as there was incomplete understanding of the nature of how hoas interact with lower - order astigmatism . while conducting literature searches for this paper , the author could not find a single study or paper proving lenticular astigmatism s existence except for the report of an unusual patient . finally , studies that analyzed posterior corneal astigmatism demonstrated only very small amounts of astigmatism , on the order of small fractions of a diopter.13 finally , it is important to note that contoura is able to calculate the linkage between the hoas and lower - order astigmatism . we do not regularly spend time finding the ovalization interactions between the hoas and lower - order astigmatism .

purposeto demonstrate how higher - order corneal aberrations can cancel out , modify , or induce lower - order corneal astigmatism.patients and methodssix representative eyes are presented that show different scenarios in which higher - order aberrations interacting with corneal astigmatism can affect the manifest refraction . wavelight contoura ablation maps showing the higher - order aberrations are shown , as are results of correction with full measured correction using the lyra ( layer yolked reduction of astigmatism ) protocol.resultshigher-order corneal aberrations such as trefoil , quadrafoil , and coma can create ovalization of the central cornea , which can interact with the ovalization caused by lower - order astigmatism to either induce , cancel out , or modify the manifest refraction . contoura processing successfully determines the linkage of these interactions resulting in full astigmatism removal . purely lenticular astigmatism appears to be rare , but a case is also demonstrated . the author theorizes that all aberrations require cerebral compensatory processing and can be removed , supported by the facts that full removal of aberrations and its linkage with lower - order astigmatism with the lyra protocol has not resulted in worse or unacceptable vision for any patients.conclusionhigher-order aberrations interacting with lower - order astigmatism is the main reason for the differences between manifest refraction and contoura measured astigmatism , and the linkage between these interactions can be successfully treated using contoura and the lyra protocol . lenticular astigmatism is relatively rare .

Three priests and a former priest in Scotland have reported the most senior Catholic clergyman in Britain, Cardinal Keith O'Brien, to the Vatican over allegations of inappropriate behaviour stretching back 30 years. The four, from the diocese of St Andrews and Edinburgh, have complained to nuncio Antonio Mennini, the Vatican's ambassador to Britain, and demanded O'Brien's immediate resignation. A spokesman for the cardinal said that the claims were contested. O'Brien, who is due to retire next month, has been an outspoken opponent of gay rights, condemning homosexuality as immoral, opposing gay adoption, and most recently arguing that same-sex marriages would be "harmful to the physical, mental and spiritual well-being of those involved". Last year he was named "bigot of the year" by the gay rights charity Stonewall. One of the complainants, it is understood, alleges that the cardinal developed an inappropriate relationship with him, resulting in a need for long-term psychological counselling. The four submitted statements containing their claims to the nuncio's office the week before Pope Benedict's resignation on 11 February. They fear that, if O'Brien travels to the forthcoming papal conclave to elect a new pope, the church will not fully address their complaints. "It tends to cover up and protect the system at all costs," said one of the complainants. "The church is beautiful, but it has a dark side and that has to do with accountability. If the system is to be improved, maybe it needs to be dismantled a bit." The revelation of the priests' complaints will be met with consternation in the Vatican. Allegations of sexual abuse by members of the church have dogged the papacy of Benedict XVI, who is to step down as pope at the end of this month. Following the announcement, rumours have swirled in Rome that Benedict's shock move may be connected to further scandals to come. The four priests asked a senior figure in the diocese to act as their representative to the nuncio's office. Through this representative, the nuncio replied, in emails seen by the Observer, that he appreciated their courage. It is understood that the first allegation against the cardinal dates back to 1980. The complainant, who is now married, was then a 20-year-old seminarian at St Andrew's College, Drygrange, where O'Brien was his "spiritual director". The Observer understands that the statement claims O'Brien made an inappropriate approach after night prayers. The seminarian says he was too frightened to report the incident, but says his personality changed afterwards, and his teachers regularly noted that he seemed depressed. He was ordained, but he told the nuncio in his statement that he resigned when O'Brien was promoted to bishop. "I knew then he would always have power over me. It was assumed I left the priesthood to get married. I did not. I left to preserve my integrity." In a second statement, "Priest A" describes being happily settled in a parish when he claims he was visited by O'Brien and inappropriate contact between the two took place. In a third statement, "Priest B" claims that he was starting his ministry in the 1980s when he was invited to spend a week "getting to know" O'Brien at the archbishop's residence. His statement alleges that he found himself dealing with what he describes as unwanted behaviour by the cardinal after a late-night drinking session. "Priest C" was a young priest the cardinal was counselling over personal problems. Priest C's statement claims that O'Brien used night prayers as an excuse for inappropriate contact. The cardinal maintained contact with Priest C over a period of time, and the statement to the nuncio's office alleges that he engineered at least one other intimate situation. O'Brien is, says Priest C, very charismatic, and being sought out by the superior who was supposed to be guiding him was both troubling and flattering. Those involved believe the cardinal abused his position. "You have to understand," explains the ex-priest, "the relationship between a bishop and a priest. At your ordination, you take a vow to be obedient to him. "He's more than your boss, more than the CEO of your company. He has immense power over you. He can move you, freeze you out, bring you into the fold … he controls every aspect of your life. You can't just kick him in the balls." All four have been reluctant to raise their concerns. They are, though, concerned that the church will ignore their complaints, and want the conclave electing the new pope to be "clean". According to canon law, no cardinal who is eligible to vote can be prevented from doing so. ||||| Cardinal Keith O'Brien, the UK's most senior Roman Catholic cleric, has resigned as the head of the Scottish Catholic church after being accused of "inappropriate acts" towards fellow priests. News that Pope Benedict had accepted the cardinal's resignation as archbishop of St Andrews and Edinburgh came after the Observer disclosed a series of allegations by three priests and one former priest. O'Brien has denied the allegations and had been expected to continue in his post as archbishop until mid-March, when he was due to retire at age 75. However, in a statement released by the church on Monday, it emerged that the pope had accepted O'Brien's resignation a week ago, on 18 February. In the statement, O'Brien apologised to any people he had let down and said he did not want the controversy to overshadow the election of the new pope. "I have valued the opportunity of serving the people of Scotland and overseas in various ways since becoming a priest," he said. "Looking back over my years of ministry, for any good I have been able to do, I thank God. For any failures, I apologise to all whom I have offended." His resignation means the cardinal will not now take part in the election of a successor to Pope Benedict. This will leave Britain unrepresented in the process, as O'Brien was the only cardinal in the British Catholic churches with a vote in the conclave. Although Cardinal Cormac Murphy-O'Connor, the archbishop emeritus of Westminster and former leader of Catholics in England and Wales, will attend pre-conclave meetings, he will not have a vote in the election itself as cardinals aged 80 and over are ineligible to vote. He is 80. O'Brien, who missed celebrating mass at St Mary's Cathedral in Edinburgh on Sunday, had been due to fly out to the Vatican on Tuesday for the conclave. His resignation is a heavy blow to the church and Benedict, whose papacy has been beset by repeated controversies over misconduct by clergy in Europe and the US and allegations of corruption and incompetence at the Vatican. However, with the Vatican and Benedict's successor facing a series of serious challenges to its reputation, O'Brien's speedy retirement will allow the church to move quickly to settle this controversy. The Observer reported that the four men came forward last week to demand his resignation largely because the complainants did not want O'Brien taking part in the papal election. O'Brien said he had already agreed with Benedict that he would step down on 17 March as he was "approaching the age of seventy-five and at times in indifferent health". The pope had now agreed he could resign immediately, he said, forcing the church to find an "apostolic administrator" to run the diocese until a new archbishop could be appointed. Confirming he would not now go to the conclave, O'Brien said: "I thank Pope Benedict XVI for his kindness and courtesy to me and on my own behalf and on behalf of the people of Scotland, I wish him a long and happy retirement. "I also ask God's blessing on my brother cardinals who will soon gather in Rome to elect his successor. I will not join them for this conclave in person. I do not wish media attention in Rome to be focused on me, but rather on Pope Benedict XVI and on his successor. However, I will pray with them and for them that, enlightened by the Holy Spirit, they will make the correct choice for the future good of the church. "May God, who has blessed me so often in my ministry, continue to bless and help me in the years which remain for me on Earth and may he shower his blessings on all the peoples of Scotland especially those I was privileged to serve in a special way in the archdiocese of St Andrews and Edinburgh." Scotland's first minister, Alex Salmond, said he had learned of the cardinal's decision with "the greatest sadness". He said: "In all of my dealings with the cardinal, he has been a considerate and thoughtful leader of the Catholic church in Scotland, stalwart in his faith but constructive in his approach. "The hugely successful visit of Pope Benedict in 2010 was a highlight of his cardinalship and symbolised the key role of the Catholic church in Scottish society." Salmond said it would be a "great pity if a lifetime of positive work was lost from comment in the circumstances of his resignation". He added: "None of us know the outcome of the investigation into the claims made against him but I have found him to be a good man for his church and country." Austen Ivereigh, a Catholic writer and co-ordinator of Catholic Voices, said he was not surprised that the church had moved so quickly following the emergence of the allegations. "I think the speed of the announcement has everything to do with the fact that these accusations were made on the eve of the papal election," he said. "It was important not to distract from the pope and the election process, and I think frankly it was a necessary act and [O'Brien] did it for the good of the church." Ivereigh said the rapid response showed both the church's "renewed transparency and accountability" and its desire for the election of Benedict's successor to proceed as uncontroversially as possible. He described O'Brien as a "very affable, warm and hospitable" man who was always unafraid to speak his mind. "He's never been considered one of the high-flying cardinals; he doesn't know Rome that well or have fluent Italian and so he's never been a cardinal who has been as significant in the Vatican as Cardinal Cormac Murphy-O'Connor," said Ivereigh. "But he's been a very stalwart defender of the Scottish church's stances on various issues and he has been valued for his forthrightness and directness – even though I think sometimes some of his pronouncements have not been judiciously phrased." Ivereigh also pointed out that although O'Brien's decision not to attend the conclave left British Catholics without a vote in the election of the next pope, it did not leave them without a voice. "It's important to remember that it's not just the conclave where cardinals bring their influence to bear," he said. "In many ways the more important time over the next few weeks will be the general congregations when the cardinals meet together before the conclave to discuss the state of the world and the state of the church – and Cardinal Murphy-O'Connor will be present at those because the over-80 cardinals are part of those discussions; they're just not allowed to vote. "I think the perspectives of the British church will still make themselves felt within the college because of Cardinal Murphy-O'Connor's presence and influence." O'Brien has been an outspoken critic of gay rights, denouncing plans for the legalisation of same-sex marriage as "harmful to the physical, mental and spiritual wellbeing of those involved". He was named bigot of the year in 2012 by the gay rights group Stonewall because of his central role in opposing gay marriage laws in Scotland. Colin Macfarlane, the director of Stonewall Scotland, called for a full inquiry into the claims against the former cardinal. "We trust that there will now be a full investigation into the serious allegations made against ex-cardinal O'Brien," Macfarlane said. "We hope that his successor will show a little more Christian charity towards openly gay people than the former cardinal did himself."

– The UK's top Roman Catholic cleric has resigned amid accusations of inappropriate behavior dating back 33 years. Cardinal Keith O'Brien was set to retire next month after voting on the next pope; but after the scandal exploded over the weekend, Pope Benedict has accepted his immediate resignation, the Guardian reports. O'Brien, staunchly anti-gay in his views, was accused by three priests and one former priest of inappropriate physical contact. He has denied the claims, but in a statement announcing his resignation, he notes, "For any failures, I apologize to all whom I have offended." He adds that he does not want the scandal to overshadow the selection of a new pope. Now that he will no longer take part, Britain will not be represented in the process, the Guardan notes. The four who complained wanted O'Brien to resign before the papal conclave, fearing that their complaints would not be addressed if he was allowed to participate. The church "tends to cover up and protect the system at all costs," says one. "The church is beautiful, but it has a dark side." The Guardian has details of the alleged inappropriate contact; one of the priests says O'Brien, who was counseling him about personal issues, initiated at least two intimate situations.

diabetes has been reported as a predisposing factor in at least 36% cases of mucormycosis . also , diabetics are 2 - 3 times more prone to develop pulmonary tuberculosis , with high chances of treatment failure . herein , we report a case of combined infection of pulmonary tuberculosis and mucormycosis in a diabetic patient . even though isolated infections have known to occur but such co - existent diseases in diabetes , with successful outcome , has not yet been reported . in view of common clinical and radiological features , a-30-year male presented with complaints of right - sided chest pain , progressive shortness of breath , low - grade fever and productive cough of three weeks duration . he was a non - smoker and had poorly controlled diabetes for last three years . he had also taken complete anti - tubercular treatment for pulmonary tuberculosis two years back . on examination , patient was tachypnoic with respiratory rate of 35/min , hemodynamically stable and afebrile . chest auscultation revealed decreased breath sounds over right hemithorax with hyper - resonant percussion note . chest radiograph revealed right - sided pneumothorax along with heterogenous opacity in left mid - zone [ figure 1 ] . right intercostal tube drainage was performed which improved patient 's distress [ figure 2 ] . blood sugar levels were markedly deranged with serial levels between 200 - 360 mg / dl . he was non - reactive for human immunodeficiency virus ( hiv ) and sputum was positive for acid - fast bacilli . the koh wet mount of sputum showed broad sparsely non - septate thin - walled hyphae with right - angle branching , characteristic of mucormycetes . x - ray of the chest showing right side pneumothorax along with left mid - zone non - homogenous opacity undergoing cavitation x - ray of the chest shows blunting of right costophrenic angle with intercostal tubein situalong with left mid - zone lung abscess and surrounding consolidation lcb mount showing sporangium , apophyses , conidiophores of lichtheimia corymbifera(lcb - x 200 ) patient was started on anti - tubercular treatment consisting of five drugs under revised national tuberculosis control program . intravenous liposomal amphotericin b ( dose - 2 mg / kg / day ) was initiated simultaneously along with adequate hydration . amphotericin b was discontinued at the end of 8 week , after obtaining negative sputum culture and ensuring clinical improvement . patient completed eight months of anti - tubercular treatment and is on regular follow - up with satisfactory improvement [ figure 4 ] . x - ray of the chest shows a small pocket of right - sided pneumothorax and thick fibrotic band in left mid - zone , likely healed lesion by impairing innate and adaptive immunity , diabetes mellitus predisposes to a variety of infections , sometimes due to unusual organisms . mucormycosis is one such uncommon but prognostically important , opportunistic infection caused by ubiquitous filamentous fungus like rhizopus , mucor , and lichtheimia species of the order mucorales . these vasotropic fungi lead to a wide severity of rhinosinocerebral , pulmonary and disseminated infections , causing extensive tissue necrosis . pulmonary involvement with mucormycosis usually occurs in severe immunosuppression and often mimics aspergillosis and tuberculosis . understandably , co - infection with mucormycosis and tuberculosis , as in our case , is liable to create management difficulties . this dreaded co - infection has scarcely been reported as isolated case reports in post - stem cell transplantation and acute myeloid leukemia . like tuberculosis , pulmonary mucormycosis presents with prolonged and refractory fever , cough , hemoptysis and chest pain . in a tuberculosis endemic country , these non - specific symptoms are very often attributed to pulmonary tuberculosis . compounding the problem , mucormycosis present as parenchymal infiltrates , consolidation , nodules , cavitation , effusion etc . , on imaging , similar to tuberculosis . microbial culture and/or histopathology is the gold standard for diagnosis of both diseases . however , its usefulness is hampered by factors like time lapse for diagnosis , need for sterile tissue ( which necessitates invasive procedure ) and low diagnostic yield ( less than 50% ) . sputum or bronchoalveolar lavage fluid cultures are usually non - diagnostic but provide suggestive diagnosis , requiring further confirmation . in our case as well , mucormycosis confirmation could not be done as the patient was unfit to undergo invasive tissue sampling . considering his underlying condition and the fatality of untreated mycosis , although , there are no consensus treatment guidelines for mucormycosis , currently , the recommended antifungal therapy includes conventional or liposomal amphotericin b. the duration of therapy is highly individualized and determined by clinical response , normalization of x - ray findings and negative culture / biopsy . co - infection with tuberculosis should be treated simultaneously , though it may increase likelihood of drug interactions , side - effects and non - compliance to treatment . recovery from immunosuppression is of utmost importance for successful outcome . despite medical and surgical treatment , co - infection with tuberculosis is likely to increase the overall mortality depending on host factors , disease stage and time of initiation of treatment . in view of rising burden of mucormycosis , high index of suspicion and comprehensive screening of diabetics and possibly all immunocompromised patients for possible co - infections is pertinent even if a single agent has been isolated . once considered fatal , diagnosis of mucormycosis should not be considered a lost battle . early diagnosis and aggressive treatment is the key to successful outcome .

uncontrolled diabetes mellitus is associated with a variety of infections which pose management difficulties . herein , we report a case of diabetic patient who developed combined pulmonary tuberculosis and mucormycosis . the case illustrates management of this rare co - infection which despite being potentially fatal was treated successfully .

the _ very _ center of our galaxy houses the variable source named sgr a * , first discovered in the radio as a compact source @xcite . the fact that this source is motionless ( to better than 1 km / s ) at the dynamical center of the galaxy @xcite , and its coincidence with the common focus of elliptical orbits of stars tracked over the last decade and a half , clearly associates it with a supermassive black hole of @xmath4 @xcite . sgr a * has been detected across the electromagnetic spectrum , at radio , submm , nir and x - ray wavelengths . at nir and x - ray wavelengths @xcite the emission is highly variable ( factors up to @xmath2160 and 27 in the x - ray and nir respectively ; @xcite , this work ) compared to the comparatively steady emission at longer wavelengths . nir peaks are detected more often than in the x - ray ( peaks occur @xmath21 and 4 times a day for x - ray and nir variable emission , respectively ; @xcite ) . some nir flares have been detected without any accompanying x - ray flare @xcite . however , when both nir and x - ray exhibit increases in emission , the peaks in emission occur simultaneously ( e.g. , * ? ? ? * ; * ? ? ? the near - infrared lightcurves from sgr a * exhibit @xmath51 hour long increases in emission that are often called ` flares ' in the literature . a number of these have exhibited very suggestive substructural features with timescales of @xmath6 minutes @xcite , possibly quasi - periodic oscillations ( qpos ) . however the existence of qpos and even the use of the term flare to describe the nir variability of sgr a * has been questioned by @xcite ( see also @xcite and @xcite ) who argue that there is no true quasi - periodicity , just a variability process with a featureless red noise power spectrum ( e.g. a power spectrum @xmath7 where @xmath8 is frequency ) . a stochastic source with a red noise power spectrum has higher variability at longer timescales and could potentially be responsible for the structures on longer timescales seen in the real lightcurves . the authors suggest that apparent flare peaks may simply be the highest observed flux excursions in such a purely stochastic source and are not isolated events . a main reason for the two rather contrasting interpretations of the variable emission from sgr a * has been that the nature of the faint emission from sgr a * and its relationship to the high flux emission is uncertain . the nir emission from the galactic center is dominated by the central cluster of bright stars , and adaptive optics at 8-meter class telescopes is required in order to separate the faint source sgr a * from the closest s - stars ( even at this resolution sgr a * is still on occasion confused with a relatively bright star ) . additional , faint stars may be present very close to sgr a * which have not yet been tracked and identified as stars from astrometric monitoring programs ( e.g. * ? ? ? * ) . while the dramatic high flux variability can be unambiguously attributed to the black hole , when a faint source is detected at the position of sgr a * , it is not necessarily clear that the source is sgr a * , faint stars , or a combination of both . accordingly , it is not clear whether sgr a * continues to emit at all at low fluxes , whether it exhibits a ` quiescent state ' ( a non- or weakly active low state ) , or whether the low flux emission continues to vary constantly with the same statistical properties as the high flux emission . cccccc & & & & & + _ brightest states _ & & _ peak fluxes _ & & & + & & & & & + gen+03 & 15 jun 2003 & 13.2 ( 10.5 + 2.7 ) & 1.10 & 0.76 & 11.0 + & & & & & + gen+03 & 16 jun 2003 & 10 ( 7.3 + 2.7 ) & 1.10 & 0.76 & 8.4 + & & & & & + mey+07 & 6 oct 2003 & 22@xmath9 & 1.2 & 0.76 & 20.1 + & & & & & + tri+07/mey+06 & 31 may 2006 & 16/23 ( + s17 ) & - & - & ( 16.7 ) 13.5@xmath10 + & & & & & + hor+07 & 31 jul 2005 & 11.6 & @xmath51.06@xmath11 & 0.52 & 6.4 + & 2 may 2006 & 26.8 & & & 14.8 + & 17 jul 2006 & 6.8 & & & 3.7 + & & & & & + do+08 & 3 may 2006 & 0.8 & @xmath51.06@xmath11 & - & 8.5 + & 20 jun 2006 & 0.65 & & & 6.9 + & 21 jun 2006 & 0.4 & & & 4.2 + & 17 jul 2006 & 0.3 & & & 3.2 + & 18 may 2007 & 0.6 & & & 6.4 + & 12 aug 2007 & 0.2 & & & 2.1 + & & & & & + eck+08 & 15 may 2007 & 24 ( + s17 ) & 0.76 & 0.76 & ( 13.9 ) 10.7 + & & & & & + this work & 5 aug 2008 & 30.7 ( + s17 ) & - & - & ( 30.7 ) 27.5 + & & & & & + & & & & & + _ faintest states _ & & & & & + & & & & & + hor+02 & 9 may 2001 & @xmath12 mjy & @xmath51.06@xmath11 & - & @xmath13 + & & ( upper limit , not dered ) & & & + & & & & & + sch+02 & 5 jun 2006 & @xmath14 mjy & ? & 0.76 & @xmath15 + & & & & & + do+08 & 2006 : may 3 , & @xmath16 mjy & + & jun 20 , 21 , jul 17 & & ( median flux , not dered ) & 1.06@xmath17 & - & 2.0 + & 2007 : may 18 , aug 12 & @xmath18 & 1.06 & - & @xmath19 + & & ( faintest flux , not dered ) & & & + & & & & & + sab+10 & 23 sep 2004 & 2.4 mjy & @xmath20 & 0.76 & 1.4 + & & ( upper limit , & & & + & & no stellar contam . ) & & & + & 23 sep 2004 & 0.9 mjy & & & 0.5 + & & ( upper limit , & & & + & & full stellar contam . ) & & & + in addition to this , an unbiased overview of the properties of the near - infrared emission from sgr a * can be difficult to obtain from the published literature because of publication bias ( bright events have individual interest and are often published alone ) . however , some studies have looked at the statistical properties . @xcite and @xcite presented lightcurves and flux distributions for sgr a * for about @xmath511 hours of 1.6@xmath21 m and @xmath532 hours of 1.7@xmath21 m data observed with nicmos on the hubble space telescope ( hst ) . with the resolution of the hst the close stellar sources are not as well separated from sgr a * as with the vlt or keck telescopes , and the stars s17 and s2 overlap with the sgr a * source in these observations . the flux distributions were fitted with a gaussian at low fluxes , which was attributed to the observational noise on constant sources ( the contribution from s2 , s17 and possible quiescent emission ) and a power - law at high fluxes , which was attributed to transient flares . the best fit models implied that sgr a * was active ( above the noise at low levels ) more than 40% of the time . @xcite presented an analysis of six nights of k-band ( and one l-band ) observations at the keck observatory , using an unbiased set of observations taken between 2005 and 2007 . a source at the position of sgr a * was always detected in this dataset , with an estimated maximum 35% contribution from stellar contamination . these authors reported that the source sgr a * was continuously variable , based on the larger variance of sgr a * compared to stars of similar brightness on five of the six k-band observation nights . this was the data set used to investigate timing properties of sgr a * in which it was claimed the data set was consistent with a featureless red noise power spectrum with no quasi - periodicity . however , with a sum duration for the k - band observations of about 12.1 hours , this data set did not sample well the higher fluxes of sgr a * , i.e. the source was relatively faint compared to publications where variable emission with suggestive quasi - periodic structure have been reported ( * ? ? ? * ; * ? ? ? * ; * ? ? ? * for a comparison of ks - band peak emission from the literature see table [ table2 ] in the appendix ) . although the studies of @xcite , @xcite and @xcite have gone some way towards understanding the statistical properties of sgr a * in the near - infrared , there has not yet been a study on a very large , unbiased dataset of the variability of sgr a * where the rare high fluxes are also well sampled . in this paper , we analyse the ks - band flux distribution of sgr a * for the years 2004 - 2009 from 117 observation nights carried out with the vlt in paranal , chile with the aim of seeking the flux - dependent characteristics of the variability of sgr a * at both high and low fluxes . we do this through investigation of the flux distribution of sgr a*. the dataset of this paper is @xmath512 times larger than the data set of @xcite . in order that our results might be compared with other publications , we give a summary in table [ table2 ] ( in the appendix ) of the brightest and/or notable ks / k-band variable emission reported in the literature , as well as the faintest values or upper limits . all are reported in the literature with different calibrations / extinction values , and we have done our best to determine the corrections to scale them to the calibration and extinction values used in this paper . in section [ section_dataset ] we present our observations and the results of using two different methods of photometry : a six year lightcurve ( aperture photometry ) , and the 2009 data set ( psf photometry ) . in section [ section_results ] we present the flux distribution of sgr a * and our results from various model fits to the flux distribution . in section [ section_discussion ] we discuss our results in the context of two variability states for sgr a * : a low - level lognormally varying _ quiescent state _ and sporadic high flux _ flares_. we summarize in section [ section_conclusions ] . since 2002 we have observed the galactic center with the near - infrared adaptive optics - assisted diffraction limited imager naco at the vlt @xcite . much of the observation time 2002 - 2009 was spent concentrated on the central few arcesconds , measuring the positions of the s - stars and monitoring sgr a*. by now we have amassed a large dataset with which we can investigate statistical properties of sgr a * s variability . while we utilised l ( 3.8@xmath21 m ) , ks ( 2.18@xmath21 m ) and h ( 1.66@xmath21 m ) bands , by far the largest proportion of our data is taken in ks - band , collected in either 13 mas pixel scale imaging , 13 mas pixel scale polarimetry , or 27 mas pixel scale imaging mode . the presence of many stars close to the central black hole complicates the attempt to acquire accurate photometry for the near - infrared sgr a * source . sgr a * is usually fainter than the surrounding s - stars , and the stars _ move_. a star can on occasion get so close to sgr a * in projection that the two sources become confused . for example , the @xmath516 year orbit star s2 @xcite was confused with sgr a * as it passed pericenter in 2002 . more recently , the @xmath22 mag star s17 was confused with sgr a * in 2006 - 2008 . we use two different methods in this paper : 1 . we first attempted to obtain as large a homogeneous , unbiased , dataset as possible , in order to obtain a best overview of the statistical properties of the variability of sgr a * , and to address in particular the variability at ( the rarer ) high fluxes . to do this we used aperture photometry because this allowed us to address the most important complication to the photometry of sgr a * in 2004 to 2009 the star s17 , confused with sgr a * in 2006 - 2008 . to deal with s17 we used a two - aperture photometry method to determine the combined flux of sgr a * and the star s17 in all years 2004 to 2009 with comparable accuracy . this is important because to understand the flux distribution we have to understand the photometric errors at low fluxes . if all years are measured with comparable accuracy the long - term errors can be well approximated with a gaussian ( with width dependent on flux ; see section [ section_obserrors ] ) . we did not include the ks - band data from 2002 - 2003 because the star s2 was so close to sgr a * during this time that it contributed to the flux measured with this method . since s2 is much brighter than s17 the flux of sgr a*+s17 could not be measured with an accuracy comparable to the other years . we secondly looked at a subset of the data in more detail in order to address the nature of the variability at low fluxes . determining the nature / existence of low level variability ( and in particular to distinguish it from observational errors ) requires more precise photometry than could be achieved with aperture photometry , in particular with the inclusion of s17 . we address the question of the nature of the low level variability by analyzing the ( high quality ) 2009 data , in which s17 is not confused with sgr a * , in greater detail with a psf - fitting photometric method starfinder , @xcite ) . the flux errors for this method are much smaller and allow us to distinguish with more certainty between true variability and flux errors at low fluxes ; this data set is not completely unbiased since sgr a * was only reliably detected in 87% of the selected images . by using these two methods in combination , we can overcome the individual difficulties of the methods and piece together a consistent picture of the near - infrared variability of sgr a*. our 2004 - 2009 ks - band data set consists of @xmath23 images . the data were reduced in the standard way by applying a sky subtraction , a flat field correction and a hot / dead pixel correction ( see e.g. , * ? ? ? * ) . we found it necessary to apply a quality cut to eliminate the worst data and ensure we obtained a homogeneous data set on which we could perform accurate photometry . this quality cut was carried out by eye , and the criteria for elimination included : * the two calibration stars were not in the image ( this happened rarely , and only in the polarimetric data ) * image ghosts close to sgr a * or psf artefacts * simply a bad quality image mostly corresponding to low strehl ratio data resulting from poor atmospheric conditions . the quality of images for this criterion was judged by the general visibility of s - stars , not by the visibility of sgr a * to avoid bias towards bright fluxes from sgr a*. we additionally eliminated 854 images from july in 2009 which were taken in a triggered mode , so that our dataset remains unbiased and representative of the overall variability of sgr a*. the remaining data set totaled 6774 images which were used to obtain a lightcurve for sgr a*. to extract fluxes for sgr a * as well as for several control stars , we carried out aperture photometry on each image . however , if we used a standard circular aperture centred on sgr a * , we would have a varying contribution from s17 ( the brightest star to be confused with sgr a * 2004 - 2009 ) to the lightcurve as the star moves through the aperture during 2006 - 2008 . a second star within the aperture , but not centered within the aperture also increases the error on our measurements of the flux of sgr a*. we would obtain more accurate results if s17 could somehow also be well - centered in the aperture at all times , as well as sgr a*. to solve the problem of s17 we thus used a two - aperture method with two circular sub - apertures , one centered on sgr a * and one centered on s17 and measure their combined flux , averaging the results where the two sub - apertures are each 40 , 53 and 66 mas in size . we used this method for all data 2004 to 2009 , so that we always measure the combined flux of s17 + sgr a*. while there may be additional effects due to confusion with other , fainter stars , at first order our method ensures that we measure the fainter fluxes of sgr a * with similar measurement errors from year to year than we would have if we neglected to include a sub - aperture about s17 . to further ensure the self - consistency of our dataset , we used the same set of calibrator stars for calibration of each image . this restricted us to only two suitable calibration stars , s30 and s65 , due to the small field of view of some ( especially polarimetric ) images . to measure the raw counts of control stars and the calibration stars we used the same aperture as for sgr a * and s17 , but centered the star in just one of the two sub - apertures . for each image , the raw counts of sgr a*/s17 and the control stars are then divided by the counts of the two calibrator stars and the calibrated counts are then flux calibrated by scaling relative to the median of s65 for the observation night , using @xmath24 mag for s65 ( e.g. * ? ? ? our photometric calibration is also consistent with @xcite ( s65 : @xmath25 mag ) . to convert magnitudes to fluxes ( mjy ) we used the zeropoint from @xcite ( @xmath26 mag corresponds to 667 jy ) . we computed the expected positions of sgr a * and of the control stars using the orbital ( polynomial ) fits of @xcite . for polarimetric data , we added the raw photon counts recorded in the apertures for all targets in both ordinary and extraordinary images first in order to recover the unpolarized intensities from the ordinary image ) . ] , before the flux calibration was carried out . we dereddened the final flux values using @xmath27 ( * ? ? ? * fritz 2010 in prep . ) . note that the absolute photometric calibration and extinction correction is not important for the analysis of relative fluxes presented in this paper , where we have focused on maximising the long - term relative accuracy of our photometric measurements . however , where we compare with previous publications , we additionally scale the reported fluxes to the photometric calibration ( as best as possible ) and extinction of this paper . the lightcurve we produced in this way for sgr a * is shown in figure [ fig_dataset ] . the data presented here is representative of the overall variability of sgr a * since it is not biased towards the presence of obvious ` flare events ' and the only data selection carried out concerned data quality and photometric consistency as explained above . it is by far the most extensive dataset for sgr a * that has been published : the observations we present here consist effectively a @xmath5184 hour long lightcurve ( if one subtracts from the total time all gaps larger than about 20 min , i.e. gaps not due to sky observations ) . the total amount of exposure time ( i.e. the time spent with the shutter open , excluding overheads ) is smaller , and totals @xmath272 hours , though 184 hours is a better indication of the amount of continuous coverage . . this flare is the brightest ks - band flare that has ever been observed ; the source reached an intrinsic peak flux of 27.5 mjy , a factor @xmath21.7 the flux of the star s2 . while the high flux excursion is preceded by what looks like a flatter , background level of emission , this is however , at@xmath57 mjy , several mjy brighter than the low flux levels from most other observation nights , and indicates there was increased source activity even at this time . the long - term trend for 2009 has not been subtracted from the lightcurve shown in this plot , and the last six datapoints did not make the data quality cut for the 2004 - 2009 flux distribution . , width=302 ] figure [ fig_dataset ] shows the 2004 - 2009 lightcurve of sgr a * and comparison star s7 . on top of the more rapid variability , there is a general trend for the lowest fluxes of the lightcurve to wander from year to year . it is at its lowest in 2006 . in 2004 the extra flux appears to be due to a combination of a faint star , a contribution from the halo of s2 , which was much closer to sgr a * during that year , and s19 , which was confused with s17 . the lightcurve also shows some increased flux in 2008 and 2009 ; and as we will show in section [ sec_stellarcontamination ] , there is at least one additional ( previously unidentified ) faint star which must also contribute to the increased flux in those years . since we can generally identify that stars are responsible there is good justification for subtracting these long ( i.e. year ) timescale trends from the lightcurve . for want of a better method of determining the stellar contribution to the lightcurves we subtracted the difference between the median of the data from each year and the minimum median value ( in 2006 ) this brings the offset in the lightcurve to roughly 3.5 - 4 mjy , much of which can be reasonably attributed to s17 ( between 2.9 and 3.3 mjy in the lightcurve can be attributed to s17 ; see section [ section_psfphot ] ) . it is apparent from figure [ fig_dataset ] that sgr a * is much more variable than the comparison source s7 . some of the flux excursions are much more dramatic than others , with fluxes above 8 mjy ( @xmath55 mjy intrinsic upon subtraction of s17 ) . many of these have been previously published for example , the second brightest peak of the dataset , in may 2006 , was published previously in @xcite and @xcite and has 16.7 mjy ( @xmath513.5 mjy intrinsic ; see table [ table2 ] in the appendix ) . on 5th august 2008 , we saw a particularly extreme event which can be seen as the most dramatic flux excursion in the lightcurve in figure [ fig_dataset ] . this event is also shown in higher time resolution in figure [ fig_superflare ] . on this particular night the source at the position of sgr a * brightened by a factor @xmath28 in a period of @xmath540 minutes , reaching a peak flux of 30.7 mjy ( intrinsic flux of @xmath29 mjy minus s17 , a factor increase over the upper limits on the lowest fluxes from sgr a * of @xmath227 ) . an increase in ks - band emission of this brightness is unparalleled in the literature for sgr a * : the second brightest that has been published is a flare from october 2003 @xcite which reached an intrinsic flux of @xmath520.1 mjy ( see table [ table2 ] in the appendix ) . 2 - 3 mas ; for the purposes of this plot the zero position of declination was fixed to the position for which the brightest flux from sgr a * was recorded ( the @xmath30mjy , @xmath3 mag , event from august 5th , 2008 ) . [ fig_contaminatingstar],title="fig:",width=302 ] + to create the 2004 - 2009 flux distribution of sgr a * we subtracted a trend from the data that we suspected to be due to faint stars . however the trend for higher fluxes in 2008 - 2009 is not explained by the presence of any known ( previously identified ) stars . here , however , we are able to present evidence that there was indeed one to two faint stars confused with sgr a * in the years 2007 to 2009 . in figure [ fig_contaminatingstar ] we show that there are deviations in the source position of sgr a * measured from imaging mosaics taken between 2007 and 2009 . the systematic deviations imply there was at least one , previously unidentified , faint star confused with sgr a*. in fact in new , very high quality observations of early 2010 , it is possible to identify two new faint stars very close to sgr a*. one or both of these stars may have undergone a close pericenter passage . from figure [ fig_contaminatingstar ] it appears that one of the stars was present in 2007 also , while our offset for 2007 does not argue for any extra star . however as we discuss in section [ section_previousmeasurements ] there appears to be a relatively steady ( on the order of @xmath50.5 mjy ) stellar contribution to the flux of sgr a * ( including the years 2006 - 2007 ) , which , together with the subtracted offsets , is probably the result of exactly such faint stars moving slowly in and out of confusion with sgr a * : probably one of the newly discovered stars does indeed already contribute to the flux in 2007 ( with the additional increase in flux in 2009 due to the second star ) . it is somewhat a mystery why these stars have not been identified previously . the stars responsible for the observed deviations in the source position have not yet been identified in data prior to 2007 when they should have been resolved separately . perhaps they have until now always been confused with other stellar sources . the star close to sgr a * in 2004 ( identified as s62 in * ? ? ? * though we disagree with this identification ) may be a candidate . + + + + we additionally carried out psf photometry on the ks - band data from 2009 ( 13 mas pixel scale imaging only ) using starfinder @xcite , which we use especially for investigating the question of whether sgr a * is continuously variable at low fluxes ( section [ sec_2009 ] ) . we use an automated program for running starfinder on many images developed by @xcite . the measured fluxes were again calibrated on the s - star s65 ( @xmath31 ; @xcite ) and the results are shown in figure [ fig_2009 ] . we note that due to the presence of the two previously unidentified faint stars ( section [ sec_stellarcontamination ] ) , we improve our chances of detecting a source in most images , while at the same time the faintness of this additional stellar contribution ensures our flux measurements have very small error , such that this data set is optimum for investigating the variability of sgr a * at low fluxes . to produce the lightcurve we first required that a faint s - star ( s21 , of @xmath51.3 mjy ) was detected in a given image as a basic data quality cut . from these images we then examined the detected positions of sources in the near neighbourhood ( @xmath5100 mas ) of the nominal position of sgr a * ( see figure [ fig_2009 ] ) and selected sources that were within 20 mas of the mean position of this detected source ( by this method a source was detected in 87% of the good quality selected images ) . due to this method of source selection , the dataset we present here is not completely unbiased , due to the 13% of images in which no source was detected , but the fraction in which sgr a * was not detected is small enough that the data set still serves well to assess whether sgr a * is in general more variable than stars of comparable flux . from the figure , sgr a * certainly appears most of the time more variable than the comparison stars of similar flux ( s21 and s60 in figure [ fig_2009 ] ) . s60 , in particular provides a very good comparison since it is also close to s31 , a star of similar brightness to s17 ; the two sources s60 and s31 also have a very similar separation to sgr a * and s17 during 2009 ( see figure [ fig_2009 ] ) . the flux distribution of s60 is fit by a gaussian with @xmath32 and @xmath33 which does not give any indication that the photometric accuracy is signficantly worse for sources of this separation and flux ratio ( the more isolated star s21 is fit by a gaussian with @xmath34 and @xmath35 ) . in general the starfinder and aperture photometry fluxes agree very well , with a constant offset of @xmath36 mjy . however , there is a systematic increase in the offset between the measured fluxes from the aperture photometry method and the starfinder method towards the end of 2009 , when the source(s ) confused with sgr a * has(have ) moved the furthest to the south ( see section [ sec_stellarcontamination ] ) . this is likely explained by starfinder s one - psf fit to the distorted psf of two sources ( which has the effect of decreasing the flux measured with the starfinder method ) ; the sources are even beginning to become separated at the end of the year ( figure [ fig_2009 ] ) . this method also provides us with an estimate for the flux contribution of s17 to the 2004 - 2009 flux distribution . the offset of @xmath36 mjy is slightly fainter than the flux of s17 ( @xmath37 mjy when separated from sgr a * in the 2009 data using starfinder ) . the lower total fluxes obtained with the aperture photometry method is probably a result of the higher stellar background surrounding sgr a * ( i.e. in the background aperture ) compared to the more isolated flux calibration star and/or a side effect of the double aperture method . 2.9 mjy is then a low estimate for the contribution of s17 to the combined sgr a*+s17 2004 - 2009 lightcurve , while 3.3 mjy from starfinder photometry is a high estimate . therefore we estimate the contribution of the flux of s17 to our 2004 - 2009 lightcurve produced via aperture photometry to be in the range @xmath38 mjy . for the flux distribution , we define the detection frequency in bin @xmath39 as @xmath40 where @xmath41 and @xmath42 are the exposure time and flux of the @xmath43th image , respectively , there are @xmath44 images and @xmath45 and @xmath46 denote the bin edges . the detection frequency in each bin is divided by the bin width so that the area under the measured flux distribution is equal to 1 . in the flux distribution each lightcurve data point was weighted by its exposure time so that the flux distribution is not biased towards observations with shorter time samplings . we chose a logarithmic binning with bins spaced at intervals separated by a factor of @xmath47 . the errors for each bin are computed as the square root of the exposure times in the bin added in quadrature ( with the same normalization as in equation [ equation_detfreq ] ) i.e. @xmath48 the flux distribution of sgr a * for the years 2004 - 2009 as derived from aperture photometry is shown in figure [ fig_fluxdist ] with various model fits ( described in the next section ) , as well as for a comparison star . the parameters and fit results for the model fits are given in table [ table1 ] . ( equation [ equation_sfobserror2009 ] ) , which are almost negligible ( compare to the intrinsic flux distribution shown in gray ) . for the same data , but analyzed with aperture photometry , the observational errors are important and have the effect of slightly widening and flattening the peak of the distribution . the red dashed line shown is not a fit to the flux distribution produced from the aperture photometry data , but rather , it is the best fit model for the starfinder photometry with a constant flux offset and convolved with the best fit error law _ determined from stars _ for 2009 aperture photometry data ( see footnote [ footnote_apobserror2009 ] ) . _ lower panel _ : comparison stars with fluxes close to the mode the flux distributions shown above , demonstrating the much greater variance in the flux distribution for sgr a * than that expected from observational noise in the photometric data set obtained with starfinder ( see section [ sec_2009 ] ) . [ fig_comparefluxdists],title="fig:",width=302 ] ( equation [ equation_sfobserror2009 ] ) , which are almost negligible ( compare to the intrinsic flux distribution shown in gray ) . for the same data , but analyzed with aperture photometry , the observational errors are important and have the effect of slightly widening and flattening the peak of the distribution . the red dashed line shown is not a fit to the flux distribution produced from the aperture photometry data , but rather , it is the best fit model for the starfinder photometry with a constant flux offset and convolved with the best fit error law _ determined from stars _ for 2009 aperture photometry data ( see footnote [ footnote_apobserror2009 ] ) . _ lower panel _ : comparison stars with fluxes close to the mode the flux distributions shown above , demonstrating the much greater variance in the flux distribution for sgr a * than that expected from observational noise in the photometric data set obtained with starfinder ( see section [ sec_2009 ] ) . [ fig_comparefluxdists],title="fig:",width=302 ] the main difficulty with fitting the distribution of fluxes is the influence of observational errors , which are important enough at low fluxes to widen the peak of the distribution from its intrinsic shape . we characterized the observational errors by fitting gaussian functions to the flux distributions of 22 nearby stars of fluxes between @xmath20.6 and 25 mjy . fitting a power law we obtain @xmath49 similar to that of @xcite who found a typical dependence of @xmath50 for their data . the @xmath20.5 power - law dependence of the errors is consistent with a photon noise origin @xcite . we do not find any flattening of the power law dependence of the noise towards low fluxes with statistical significance . the 13 mas pixel data from 2009 is of much higher quality and for the starfinder photometry has noise properties @xmath51 the noise dependence was determined in the same way as for the 2004 - 2009 dataset through comparison of 22 stars of fluxes 0.5 to 25 mjy . ] which is a significant improvement on the overall 2004 - 2009 aperture photometry accuracy , but still not as good as the accuracy obtained with starfinder for the same dataset . [ footnote_apobserror2009 ] ] we include the effect of observational errors in our model fits by convolving the intrinsic flux distribution with a gaussian of width @xmath52 , which has the dependence on flux of equation [ equation_apobserror ] : @xmath53 where @xmath54 is the intrinsic flux distribution ( without observational errors ) . the effect is only important at low fluxes @xmath55 mjy ( see figure [ fig_fluxdist ] ) and is responsible for broadening the low flux peak in the observed flux distribution for sgr a*. + + cccc|cccccc & + & + & & & & & & & & + @xmath56 & @xmath57 & @xmath58 & @xmath59 & @xmath60 & @xmath61 & @xmath62 & @xmath63 & @xmath64 & @xmath65 + & & & & & & & & + & + & + & & & & & & & & + @xmath66 & @xmath67 & @xmath68 & @xmath69 & @xmath70 & @xmath71 & @xmath72 & @xmath73 & @xmath74 & @xmath75 + & & & & & & & & a lognormal fit to the 2004 - 2009 flux distribution from aperture photometry is shown in figure [ fig_fluxdist ] , with the best fit parameters given in table [ table1 ] . this model has intrinsic probability distribution @xmath76 where @xmath77 where @xmath78 represents the observed flux ( measured in mjy here and elsewhere in this paper ) , and @xmath79 with @xmath80 a flux offset due to some constant contribution ( e.g. s17 + contaminating stars ) . the parameters @xmath81 and @xmath82 of the lognormal distribution have a natural analogy to the normal distribution when exponentiated : the source can be thought of as having a median flux of @xmath83 with a multiplicative standard deviation of @xmath84 ( i.e. the interval @xmath85 to @xmath86 contains @xmath268% of the probability ) . the residuals at low fluxes of the lognormal model are probably just due to the low flux wing of the error distribution which is not perfectly gaussian ( see star s7 in figure [ fig_fluxdist ] ) . the residuals for the lognormal model at high fluxes , on the other hand , can not arise from measurement error , and we obtain a much better fit to the flux distribution with a lognormal model which makes a transition to a flatter tail at high fluxes . the intrinsic probability distribution in this case is @xmath87 where @xmath88 is the lognormal distribution of equation [ equation_p_logn ] , @xmath89 is the flux at which the distribution makes the transition to the flatter tail , @xmath90 is the power - law slope of the tail , and @xmath39 is a renormalizing factor ] such that the total probability is 100% . the flattening of the distribution towards high fluxes in the 2004 - 2009 aperture photometry flux distribution is significant at @xmath91 . however , the fits are not formally ` good fits ' . this is to the most part due to residuals in the lowest flux bins , most likely caused by the deviation of the observational errors from the plain gaussian description used in our model . if we instead only fit only to fluxes @xmath92mjy ( ignoring the lowest three bins ) , we obtain a more reasonable @xmath93 for the lognormal plus tail model of 17.4/13 ( while the best fit lognormal model for the same has 37.6/15 ) . in this case the flatter tail of the distribution is still significant at @xmath94 . interestingly , in the 2009 starfinder photometric dataset the tail is also present with similar best fit parameters , although in this smaller dataset ( which only reaches fluxes of @xmath510 mjy ) the tail has a significance of only 1.4@xmath95 . what is not clear in the 2004 - 2009 data set is whether it is appropriate to fit only continuously emitting , continuously variable models to the flux distribution . a plausible alternative is a model in which the source of near - infrared emission emits only sporadically ( i.e. exhibits ` on ' and ` off ' periods ) . if this is the case observational errors alone ( on the measurement of a constant component to the flux ) should be responsible for observed variations in the flux level during ` off ' periods . the goal of this section is to determine whether there is too much variation at low levels for the data to be explained by observational errors in ` off periods ' of a sporadic model . we use the following prescription for a sporadic model for the flux distribution : @xmath96 where @xmath97 is the fraction of time the source spends in an ` on ' state . using @xmath98 ( equation [ equation_p_logn ] ) and fitting to both the 2004 - 2009 aperture photometry flux distribution and to the 2009 starfinder distribution with the measured noise laws of equations [ equation_apobserror ] and [ equation_sfobserror2009 ] , we find in both cases the best fits to the distributions require @xmath99 and @xmath100 ( at @xmath101 ) respectively , i.e. the measured noise laws can not account for the observed amount of variability at low fluxes . to look at the question from a different angle , we investigate what level of observational noise would be required to produce the observed variation at low fluxes . to do this we allow the normalization of the noise law to be a free parameter in the model fits , i.e. @xmath102 we find @xmath103 and @xmath104 for the 2004 - 2009 aperture photometric datset and the 2009 starfinder dataset respectively . we also refit the noise laws to the stars ( see equations [ equation_apobserror ] and [ equation_sfobserror2009 ] ) fixing the slope of the error law to 0.5 and obtain @xmath105 and @xmath106 for the 2004 - 2009 aperture photometric datset and the 2009 starfinder dataset respectively . the best fit noise law to the 2004 - 2009 flux distribution from aperture photometry allows @xmath107 but the normalization of the noise law is inconsistent with that of the stars at a level of 3.3@xmath95 . for the 2009 flux distribution from starfinder photometry the required noise law is even more unlikely , and is ruled out at a level of 4.5@xmath95 . we conclude that the observed behavior of sgr a * at low fluxes is best consistent with a continuously emitting , continuously varying source . we also detect longer timescale trends in the low flux level of sgr a * in the 2009 data ( figure [ fig_2009 ] ) , such as an @xmath50.8 mjy increase in the minimum level from the fourth to the fifth data sections , with a gap in time of only 12 days , and a similar size decrease from the second to the fourth data sections with a gap in time of only 11 days . it might be that a passing star ( such as the two new stars discovered in 2010 , see section [ sec_stellarcontamination ] ) is responsible for these trends , either passing in and out of confusion very quickly , or even just moving within the sgr a * psf and distorting the flux : the further apart the two sources the lower the fitted flux . however these stars can not move quickly enough for this : the change in flux is so large that in either case the star must move by at least @xmath550 mas within a period of 12 days to distort the flux as much as observed , which at the 8kpc distance of the gc requires an average speed of at least 0.1@xmath108 over a two week timescale . even assuming the most extreme case a star moving only in the plane of the sky and falling towards sgr a * in a parabolic orbit at the escape speed a star should take at least @xmath5110 days ( 0.02@xmath108 in average ) , to cover such a distance . a larger centroid shift between the datasets would also be expected if it were the case that a star were distorting the source psf ( @xmath520 mas instead of the observed @xmath109 mas ) . furthermore , even if this could explain the trend between the fourth and fifth datasets , the same explanation would have to be invoked to again explain the variation between the second and fourth datasets , also on a timescale of only @xmath511 days . we therefore conclude that the observed trends on timescales of a few weeks in the lightcurve are most likely intrinsic . though they can not be due to direct flux contamination from passing stars , the trends are possibly still related to the feeding of the accretion flow from stellar winds of the passing stars , which may trigger increased activity as the star passes orbital pericenter ( e.g. @xcite ) . we have shown in section [ section_results ] that the flux distribution of sgr a * is best described by a continuously emitting , continuously variable component with a lognormal flux distribution at low fluxes , but additionally that there is a significantly flatter tail above about 5 mjy , implying that _ there is something different about the high flux emission from sgr a*_. put together , it seems justified to identify * emission below 5 mjy as _ quiescent state _ emission * emission above 5 mjy as _ flaring _ emission . this is the ( phenomenological ) definition by which we hereafter refer to either ` flares ' or ` quiescent ' emission in sgr a*. we present how the two states may fit into a possible physical picture below . that the low fluxes of sgr a * are fit by a continuously present , variable component suggests that there is truly a _ _ quiescent state _ _ in sgr a * , i.e. a low - level , lognormally varying component ( factor @xmath52 in flux of the lognormal component corresponds to 1@xmath95 variability ) . our finding of continuously emitting , continuously variable component confirms the findings of @xcite who first reported continuous variability of sgr a * from the larger variance of the flux of sgr a * , as compared to stellar sources , in 5 out of 6 k-band observation nights . lognormal distributions of fluxes are seen in x - ray binaries , where they are interpreted as a sign that multiplicative processes are behind the variability ( e.g. @xcite ) . a good example of a multiplicative process is the model of @xcite where variability is produced through the inwards propagation of accretion rate fluctuations at different radii . these variations , produced in regions of the flow which themselves do not emit near - infrared emission , all combine multiplicatively as they propagate inwards . the end result of combined fluctuations is then imprinted on the variability produced by the ( say , near - infrared ) emitting region of the flow . a very similar idea may work with magnetic turbulence , which has been shown in grmhd / mhd simulations to be capable of producing the factor 40 - 50% millimeter variability @xcite . from where exactly the quiescent emission arises is however a difficult question . nonthermal electrons are required to emit in the near - infrared , and it s not clear how these should be related to the thermal electrons emitting at submm wavelengths , or how they should necessarily be arranged within the accretion inflow / outflow . * see also @xcite ) require a hybrid thermal / non - thermal electron distribution to explain the spectrum of sgr a * ( in particular the excess radio emission at low frequencies ) . the models predict that the same non - thermal electrons ( with @xmath51.5% of the thermal energy ) could produce emission in the near - infrared . thus it might be interesting to compare the flux distribution of the nir quiescent state emission ( @xmath110 mjy ) with that of the low - frequency radio emission , as well as correlations in timing properties , such as whether the medium - timescale trends ( @xmath52 weeks ) observed in the 2009 data ( figure [ fig_2009 ] ) correlate with any similar long - term trends in the radio regime . more detailed comparison of the low - level nir emission from sgr a * with other wavelengths ( e.g. submm ) could also shed light on how non - thermal electrons are related to the thermal population . it seems unlikely that the same variability process is responsible for both high and low flux emission from sgr a*. there is no obvious reason for the underlying process , if multiplicative at low fluxes , to deviate at high fluxes in order to explain the flatter tail above @xmath63 mjy . the flatter tail of the flux distribution in sgr a * requires at the very least some transition within the source ( to a _ flaring state _ ) , triggered around an intrinsic flux of 5 mjy , such that either large fluctuations or their emission undergo some kind of runaway amplification . on the other hand the physical mechanism behind the flares could be unrelated to ( though possibly still triggered by ) the mechanism producing the low level variability . the flare tail could arise from additional sporadic _ flare events _ which dominate the distribution of fluxes above 5 mjy . in this case 5 mjy is not a physically interesting flux outside the fact that it is the flux at which one is equally likely to observe either a flare event or a low level lognormal variation . spontaneous magnetic reconnection is a good candidate for a physical process that could give rise to sporadic flares in sgr a * ( e.g. * ? ? ? * ; * ? ? ? the decrease in magnetic field strength that would accompany the conversion of magnetic energy to high energy electron acceleration in a magnetic reconnection event can explain the non - one - to - one rise in the lightcurves of the so far brightest nir / x - ray flare from sgr a * @xcite . a number of other properties also indicate that there are two types of nir emission from sgr a * , with differences between high and low flux emission , which include : * _ spectral index_. there are indications that the spectral index at low fluxes is redder than at higher fluxes @xcite , although this has been disputed by other authors @xcite . * _ polarization_. changes in polarization in the rising / decaying phases of flares are seen @xcite , and low level emission appears to be generally more highly polarized ( @xmath111 ) than high flux emission ( @xmath112 ) @xcite . * _ association with x - ray flares_. the best fit model ( _ lognormal+tail+errors _ ) to the 2004 - 2009 flux distribution has 4.5% of the probability above the best fit transition flux of @xmath113 mjy , which , interestingly , is close to the x - ray flaring rate of @xmath114 ( for flares occurring once a day with a duration of 60 - 100 min ; @xcite ) . estimates of the nir flaring rate including emission below 5 mjy , on the other hand , typically put the nir flaring rate much higher at @xmath115 @xcite . perhaps the additional low - level component is even responsible for differences in the nir / x - ray peak flux ratios . there are a number of high flux ks / k-band events ( @xmath116 mjy ) , not part of the 2004 - 2009 dataset presented here but published elsewhere in the literature , which are also of @xmath1175 mjy intrinsic flux and can be identified as belonging to the flare tail of the flux distribution . to list some of the brightest ( see table [ table2 ] in the appendix for details ) : @xmath211 and 8.4 mjy ( 15 , 16 june 2003 ; * ? * ) ; 20.1 mjy ( 6 october 2003 ; * ? ? ? * ) ; 13.5 mjy ( 31 may 2006 ; @xcite , @xcite , and part of our 2004 - 2009 dataset ) ; 10.7 mjy ( 15 may 2007 ; * ? ? ? * ) ; and 14.8 mjy @xcite . our results are reasonably consistent with the median flux of 2.0 mjy over six separate observation nights from 2006 - 2007 found by @xcite ( see table [ table2 ] in the appendix for the scaling factors applied to scale the reported values to our calibration / extinction ) . we find a median flux of @xmath21.6 mjy for our 2004 - 2009 lightcurve with the long - timescale trend and s17 ( assuming 3.1 mjy ) removed ( note however that this still includes some constant contribution : the median flux of the lognormal component alone is 1.1 mjy ) . a number of previous measurements have put upper limits on any long - term steady quiescent state at near - infrared wavelengths which have been on the @xmath51 - 1.5 mjy level ( * ? ? ? * ; * ? ? ? * ; * ? ? ? * see table [ table2 ] in the appendix ) . these measurements are consistent with the picture we have put forward here for sgr a * at low levels , of a continuously emitting , continuously varying source . for a lognormally varying quiescent state with the properties of our best fit model to the 2004 - 2009 flux distribution , an upper limit of 1 - 1.4 mjy in selected observations is not surprising : the source is expected to be at @xmath1181 mjy roughly @xmath119 of the time . however , more likely the upper limits of 1 - 1.4 mjy include a stellar contribution to the flux . @xcite estimated an upper limit on the _ intrinsic _ flux from sgr a * of @xmath1200.5 mjy in the presence of a likely @xmath50.8 - 1 mjy stellar contribution . in the context of our best fit lognormal model , this low flux measurement is a rarer , but not unlikely occurrence , with a probability of @xmath121 . the 0.8 - 1.0 mjy diffuse component reported by @xcite might be associated with the @xmath50.3 - 0.7 mjy offset we find in our fits to the flux distribution of sgr a * , between the fitted constant component ( 3.6 mjy ) and the expected contribution of s17 ( 2.9 - 3.3 mjy ) . @xcite also estimated from the color of sgr a * at low fluxes , that they most likely had @xmath535% contribution from stellar contamination ( 0.7 mjy ) for their observations in 2006 . these results all seem to point towards an additional stellar component to the flux of sgr a * with a constant flux of @xmath50.5 mjy ( our data ) , though it does not necessarily always consist of the same stars from year to year . lognormal distributions of fluxes are also seen in other astrophysical objects , for example x - ray binaries ( prototype cyg x-1 in the low hard state , * ? ? ? * ) , implying a connection between sgr a * other low - accretion rate black holes @xcite . the physical picture of the low - hard state of x - ray binaries is that compared to higher luminosity flows the inner optically thick accretion disc disappears and is replaced by a hot inner flow @xcite . similar pictures , with hot inner flows , exist for sgr a * ( e.g. * ? ? ? sgr a * is , however , at the extreme low end of the accretion rate range of observable sources ( the ` quiescent ' state ) . connections between sgr a * and low - hard state x - ray binaries of higher accretion rate such as cygnus x-1 can shed light on whether or not the quiescent state is indeed a distinct state or whether there is simply a smooth continuation of the hard state down to such low accretion rates ( @xcite ) . if timescale scales with mass , then the flares in sgr a * of @xmath510 - 100 minute duration , correspond to @xmath2 millisecond timescales in a stellar mass black hole binary . it is also true that millisecond - timescale flares are seen in cyg x-1 , though it was shown by @xcite that the majority of these ( and all those in the low / hard state ) were not more frequent than expected in the context of the extension of the low - level lognormal distribution in this source to higher fluxes . there was one flare however , a 12.4@xmath95 event that occurred ( in fact when cyg x-1 was in the high / soft state ) that could not be accounted for in the context of the underlying variability and was posited by the authors to have a different physical origin . in this vein , it could be that the flares in sgr a * are due to the source s `` flickering attempts at outburst activity from out of quiescence '' , as suggested by @xcite . a connection between the near - infrared variability of sgr a * and the variability of x - ray binaries has also been made previously from a long timescale break in the psd of sgr a * which can be associated with a break timescale in the low - hard state of x - ray binaries ( meyer et al . 2009 ) , though the single dataset used to constrain the high frequency power spectrum in this case may not be representative . the lognormal distribution for low - level fluxes makes however an independent case for an analogy between the variability of sgr a * and low - hard state x - ray binaries . the flux distributions of @xcite and @xcite at 1.6@xmath21 m and 1.7@xmath21 m display a qualitatively similar shape to our ks - band distribution , although these datasets are still much smaller than ours , and the low - level activity appears to be dominated by the observational noise . nevertheless , with more data at 1.6 and 1.7 @xmath21 m and modeling of the observational errors , it might be possible to obtain constraints on the colours of the low level and high flux components . in future work we intend to use the same techniques as we have used in this paper at ks - band , in other bands ( l and h ) to investigate in detail the dependence of the flux distribution with wavelength . our work is not the first to point out that the flux distribution of sgr a * is not well - described by a gaussian : @xcite , @xcite and @xcite have all noted that the flux distribution has a high flux tail . however , the timing analyses which have been carried out to date @xcite in which sgr a * was compared to simulated red noise lightcurves have nevertheless used simulated lightcurves which have had , by construction , a gaussian flux distribution . sgr a * s intrinsic mean and variance are such that if one were to plot the simulated lightcurves scaled to sgr a * s mean and variance ( for the 2004 - 2009 dataset @xmath122 mjy subtracting 3.8 mjy for s17 plus other faint stars , and @xmath123 mjy ) , the model red noise lightcurves would have negative intrinsic fluxes much of the time which is rather unphysical . in @xcite the high flux tail was excluded when fitting the flux distribution , and only fluxes @xmath1183.2 mjy were fitted with a gaussian ( see table [ table2 ] in the appendix for scaling factors ; the reported value in @xcite was a reddened flux of 0.3 mjy ) . thus their model lightcurves best resemble the low level emission of sgr a*. indeed the entire dataset used by @xcite does not include much bright emission @xmath116 mjy , and thus their results really apply to the low level emission of sgr a*. that the low level emission from sgr a * is consistent with red noise fits together with our finding of the lognormal distribution of fluxes at low fluxes . both of these aspects of the variability are seen in x - ray binaries such as cyg x-1 @xcite . however , given that the flux distribution is not gaussian , it remains questionable that the power spectrum has yet been reliably constrained from the monte carlo simulations of previous timing studies . in particular , high and low flux states of sgr a * may require separate timing analysis . in this respect it is interesting that @xcite finds a quasi - periodic signal with false alarm probability of only @xmath124 ( 4.2@xmath95 significance in gaussian equivalent terms ) , if one considers just the window 385 - 445 minute subset from 30 - 31 july 2005 , though the signal was deemed insignificant when the entire lightcurve from the night was analyzed . we have determined the distribution of fluxes for the variable source sgr a * in the near - infrared and thereby investigated flux - dependent properties of the emission . we summarize our main results as follows : * sgr a * is continuously emitting and variable in the near - infrared . * at low ks - band fluxes the variability follows a lognormal distribution with a median flux of 1.1 mjy and a multiplicative standard deviation factor of 2.1 . we identify this continuously variable low - level state as the quiescent state of sgr a * in the near - infrared . * at least 0.5 mjy of the flux of sgr a * is due to a faint stellar component at all times during 2004 - 2009 . * there is variability on a @xmath2two - 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in this paper we examine properties of the variable source sgr a * in the near - infrared ( nir ) using a very extensive ks - band data set from naco / vlt observations taken 2004 to 2009 . we investigate the variability of sgr a * with two different photometric methods and analyze its flux distribution . we find sgr a * is continuously emitting and continuously variable in the near - infrared , with some variability occurring on timescales as long as weeks . the flux distribution can be described by a lognormal distribution at low intrinsic fluxes ( @xmath0 mjy , dereddened with @xmath1 ) . the lognormal distribution has a median flux of @xmath21.1 mjy , but above 5 mjy the flux distribution is significantly flatter ( high flux events are more common ) than expected for the extrapolation of the lognormal distribution to high fluxes . we make a general identification of the low level emission above 5 mjy as _ flaring _ emission and of the low level emission as the _ quiescent state_. we also report here the brightest ks - band flare ever observed ( from august 5th , 2008 ) which reached an intrinsic ks - band flux of 27.5 mjy ( @xmath3 ) . this flare was a factor 27 increase over the median flux of sgr a * , close to double the brightness of the star s2 , and 40% brighter than the next brightest flare ever observed from sgr a*.

The Godfather -- going as far as naming her youngest son Michael Corleone. See also: -- "Michael Corleone Blanco lives in the shadow of his cocaine-queen mother" -- "Jon Roberts, Smuggler in Cocaine Cowboys, Dies" Longtime Blanco family friend Cristian Rios confirmed reports by Colombian news outlets that Blanco died from her wounds after she was transported to a nearby hospital. "It's hard to comprehend right now," he tells Riptide. "I'm hoping the reprisals end here." Earlier today, a motorcycle-riding assassin pumped two bullets into the head of Griselda Blanco inside a Medellin, Colombia, butcher shop; ending the life of the queen of Miami's violent Cocaine Cowboys era. It was a bloody cinematic ending for the 69-year-old retired cocaine trafficker who was insatiably fond of the gangster epicgoing as far as naming her youngest son Michael Corleone.Longtime Blanco family friend Cristian Rios confirmed reports by Colombian news outlets that Blanco died from her wounds after she was transported to a nearby hospital. "It's hard to comprehend right now," he tells Riptide. "I'm hoping the reprisals end here." Two of her four sons were murdered while she was incarcerated in the 1980s and 1990s. She is survived by Michael, a 34-year-old Colombian American who is under house arrest in Miami while waiting for his trial on a cocaine trafficking charge from last year. "Michael is just beside himself," Rios says. "No matter what people think of Griselda, she was still his mom."According to the newspaper, a pair of suspects riding a motorcycle stopped at the open-air butcher shop, located in the Medellin neighborhood of Belen Parque. An unknown man riding on the back of the bike got off and walked toward Blanco. He fired two shots at her head from close range.The report states Blanco had been in the shop for about 30 minutes with a pregnant ex-daughter-in-law who was not identified. Whoever was behind the hit may have wanted to send an ironic final message since Blanco is the reputed originator of motorcycle assassinations.Known as, or the Godmother, Blanco was a pioneer in the coke trafficking industry during the 1970s and early 1980s. According to law enforcement, she oversaw a billion-dollar criminal organization that transported 3,400 pounds ofa month into the United States. She revolutionized smuggling by developing her own line of underwear with secret compartments to stuff drugs into. Blanco solidified her place in Colombian cartel lore as the mentor to Pablo Escobar. ||||| Griselda Blanco, the drug kingpin known for her blood-soaked style of street vengeance during Miami’s “cocaine cowboys” era of the ’70s and ’80s, was shot to death in Medellin by a motorcycle-riding assassin Monday. Blanco, 69, spent nearly two decades behind bars in the United States for drug trafficking and three murders, including the 1982 slaying of a 2-year-old boy in Miami. Called the “Godmother of Cocaine,” she was deported in 2004 to Colombia, where she maintained a low profile. Colombia’s national police confirmed her slaying late Monday. According to Colombian press reports, two gunmen on motorcycles pulled up to Blanco as she walked out of a butcher shop in Medellin, her hometown. One man pumped two bullets into her head, according to El Colombiano newspaper. It was the sort of death many had predicted for her: Blanco has been credited with inventing the idea of the “motorcycle assassin” who rode by victims and sprayed them with bullets. “It’s surprising to all of us that she had not been killed sooner because she made a lot of enemies,” former Miami homicide detective Nelson Andreu, who investigated her, said late Monday. “When you kill so many and hurt so many people like she did, it’s only a matter of time before they find you and try to even the score.” The former kingpin was with a pregnant daughter-in-law, who was uninjured. According to El Colombiano, the woman told police that Blanco was no longer involved in organized crime and that she was hoping to live off the sales of several properties she owned. Blanco came to epitomize the “cocaine cowboy” bloodshed of the 1980s, when rival drug dealers brazenly ambushed rivals in public. Raised in the slums of Medellin, she began her criminal career as a pickpocket, eventually commanding an empire that reportedly shipped 3,400 pounds of cocaine per month, by boat and plane. She was considered a Colombian pioneer in drug smuggling to the United States, a precursor to the larger cartels that dominated in the 1980s. She even had a Medellin lingerie shop custom design bras and girdles with special pockets to hold cocaine, a tool used by her drug mules flying to Miami. She ran the organization with her three of her four sons, two of whom were later assassinated in Colombia. Blanco was known for her flamboyant lifestyle — one of her sons was named Michael Corleone, an homage to The Godfather movies. Three of her husbands also died in drug-related violence. But it was her nasty temper and penchant for unyielding violence that drew the attention of law enforcement and the public. Investigators linked her to the daytime 1979 submachine gun attack at Dadeland Mall that shocked Miami. Detectives conservatively estimated that she was behind about 40 homicides. She was only convicted of three murders. Two of them: Blanco arranged the slayings drug dealers Alfredo and Grizel Lorenzo in their South Miami house, as their three children watched television in another room. They had failed to pay $250,000 for five kilos of cocaine that Blanco had allegedly delivered to them. She was also convicted of ordering a shooting that resulted in the death of 2-year-old Johnny Castro, shot twice in the head as he drove in a car with his father, Jesus “Chucho” Castro. Blanco was targeting Jesus Castro, a former enforcer for Blanco’s organization. Detectives learned the intimate details of the hit from Jorge Ayala, the charismatic hitman who later testified against Blanco. He told police that Blanco wanted Castro killed because he kicked her son in the buttocks. “At first she was real mad ’cause we missed the father,” Ayala told police. “But when she heard we had gotten the son by accident, she said she was glad, that they were even.” She had been arrested in 1985 in a cocaine trafficking case in New York. Ultimately, she served 13 years in federal custody before she was handed over to Florida authorities. Blanco seemed destined for Florida’s Death Row — but the prosecution’s murders case was dealt a severe blow. The reason: Ayala — the case’s chief witness — engaged in phone sex with secretaries from the Miami-Dade State Attorney’s Office. After an investigation, three secretaries were fired and a veteran prosecutor resigned. Special prosecutors from Orlando took over the case, and Blanco cut a plea deal in 1998. Blanco was sentenced to three concurrent 20-year sentences, of which she had to serve only about one-third because of guidelines in effect at the time of the murders. Even on her return to Colombia, she was believed to have held onto immense wealth. In recent years, younger Miamians were introduced to Blanco via two “Cocaine Cowboys” documentaries made by filmmakers Billy Corben and Alfred Spellman. “This is classic live-by-the-sword, die-by-the-sword,” Corben said Monday. “Or in this case, live-by-the-motorcycle-assassin, die-by-the-motorcycle assassin.” Miami Herald staff writer Jim Wyss contributed to this report.

– Griselda Blanco, the so-called "Godmother of Cocaine" who orchestrated a wave of horrific drug violence in the streets of Miami in the '70s and '80s, was gunned down in Colombia yesterday. Police say the 69-year-old was leaving a butcher shop when a pair of gunmen on motorcycles pulled up and put two bullets in her head—an ironic death given that Blanco herself is credited with inventing motorcycle assassinations, the Miami Herald reports. (She was also reportedly Pablo Escobar's mentor.) Her pregnant daughter-in-law was with her at the time but emerged unscathed. "It's surprising to all of us that she had not been killed sooner," one Miami homicide detective said. "She made a lot of enemies." Though Blanco was only ever convicted of three murders (including that of a 2-year-old boy), detectives believe she ordered at least 40. She spent almost 20 years in US prison before being deported to Colombia in 2004. She is survived by her son, Michael Corleone—yes, she named him after the Godfather character—who, according to the Miami New Times, is currently under house arrest in Miami.

the study of topological states of matter has become a major research focus of contemporary condensed matter physics @xcite . an early example is the two - dimensional ( 2d ) quantum hall effect based on the landau level quantization of electrons in the magnetic field , whose topological band structure is characterized by the first chern number @xcite . its chiral edge modes give rise to dissipationless charge transport and quantized hall conductance . in the past decade , tremendous progress has been made on the time - reversal invariant topological insulators in both 2d and 3d , whose band structure topology is described by the @xmath2 index @xcite . at the boundary , the 2d and 3d topological insulators exhibit 1d helical edge modes and 2d helical surface modes , respectively . various systems of the 2d and 3d topological insulators have been observed experimentally through various spectroscopic and transport measurements @xcite . another important development is based on high - dimensional generalizations of landau levels . landau level wave functions explicitly exhibit elegant analytic properties , which played an important role in the study of 2d fractional quantum hall effects @xcite . zhang and hu @xcite pioneered the study of landau levels on four- and higher - dimensional spheres and other compact manifolds by coupling fermions to gauge potentials of non - abelian monopoles @xcite . recently , landau levels ( lls ) in three- and higher dimensional flat continuum space have also been discussed @xcite . in 3d and 4d , their hamiltonians describe spin-@xmath3 fermions in an su(2 ) gauge potential , which were constructed from harmonic oscillators with certain spin - orbit coupling ( soc ) . the corresponding landau level wave functions are the same as those of harmonic oscillators , but they are reorganized by the soc term to exhibit non - trivial topology . in the symmetric - type @xmath0(@xmath1 ) gauge , the 3d and 4d rotational symmetries are explicitly maintained with exactly flat energy spectra and degenerate angular momenta . the lowest landau level wave functions exhibit interesting quaternion analyticity@xcite . in the landau - type gauge , they behave like spatially separated 2d helical dirac fermion modes or 3d chiral weyl fermion modes . modes with opposite helicities or chiralities are shifted along the third or fourth dimension in opposite directions , respectively @xcite . these lls have also been generalized to high dimensional dirac fermions and parity - breaking systems @xcite . one issue of the topological states based on high - dimensional landau levels is how to define their topological index . the non - trivial topology of filled landau levels was illustrated through the effective boundary hamiltonians , which exhibit helical fermi surfaces @xcite . however , unlike the 2d case , there was no full translation symmetry for the 3d landau level hamiltonians , and thus the @xmath2-index defined based on the bloch wave function structure could not be applied . a lattice construction of the hofstadter hamiltonian for the 3d ll problem will be helpful to directly calculate the topological index of that system with translation symmetry imposed . for the 2d case , the lattice version of the ll problem based on the @xmath4 vector field is well known as the hofstadter problem @xcite . in the landau gauge , the @xmath4 vector potential becomes a periodic scalar potential in the reduced 1d harper equation . the non - trivial chern number is interpreted as the linking number between fundamental loops on the complexified energy surface with the topology of a riemann surface @xcite . recently , this hofstadter hamiltonian was realized experimentally in optical lattices by laser - assisted tunneling @xcite . also , hofstadter problems have been theoretically generalized to systems with non - abelian gauge groups @xcite . in this article , we will consider the 3d lls of the landau - type su(2 ) gauge in which the system shows translation symmetry in the @xmath5 plane . for each pair of in plane momenta @xmath6 , the system can be reduced to one dimension , as described by the su(2 ) harper equation exhibiting the periodic configuration of spin - dependent potential . the bulk and surface spectra are explicitly calculated , and the non - trivial band topology are analyzed through the surface helical fermi surface and also from the analysis on the parity eigenvalues of the bulk wave functions . topological band structure transitions between the weak and strong 3d topological insulators are studied . the rest of this paper is organized as follows : in sect . [ sect : lattice ] , the lattice model for 3d lls in the su(2 ) landau gauge and the corresponding su(2 ) harper equation are constructed . in sect . [ sect : surface ] , the topological band structure is analyzed through the helical surface spectra and the @xmath2-index based on the parity eigenvalue analysis on the bulk wave function . in sect . [ sect : transition ] , the topological band structure transition in studied . discussions on the relationship with the previous work on the 3d hofstadter problem in the tilted magnetic field and experimental realizations are presented in sect . [ sect : disc ] . conclusions are summarized in sect . [ sect : conclusions ] . in this section , we construct the 3d @xmath7 landau level in lattices with full three - dimensional translation symmetry , and we show that it can be reduced into a family of generalized 1d @xmath0(@xmath1 ) harper equations . the 2d landau level in the magnetic field has been generalized into 3d continuum , which was defined as a spin-@xmath3 electron coupling to an external su(2 ) vector potential @xmath8 and a scalar potential @xmath9 @xcite as @xmath10 in the landau - type gauge , @xmath11 and @xmath12 only depend on the @xmath13-coordinate , which can be chosen as a_x(r)&=&g _ y z , a_y(r)= -g _ x z , a_z=0 ; + v(r)&=&-m ^2 z^2 , [ eq : landaugauge ] where @xmath14 is a coupling constant , @xmath15 are pauli matrices , and @xmath16 . equation ( [ eq : ham_cont ] ) describes a 3d topological insulator possessing the tr symmetry and translational symmetry along the @xmath17-@xmath18 plane . at an open boundary perpendicular to the @xmath13 axis , each filled landau level contributes a helical dirac fermi surface @xcite . the surface states carrying opposite helicities are spatially separated at @xmath19 and @xmath20 surfaces respectively . this can be shown explicitly by expanding eq . ( [ eq : ham_cont ] ) as @xmath21 ^ 2 $ ] , where @xmath22 and @xmath23 is the helicity operator defined as @xmath24 with @xmath25 . alternatively , eq . ( [ eq : ham_cont ] ) is also equivalent to an electron in a quantum - well with @xmath13-dependent spin - orbit coupling strength as h_3dll&= & + m ^2 z^2 -z ( p_x _ y - p_y _ x ) . [ eq : ham_cont2 ] gauge fields @xmath26 defined on the bonds of the cubic lattice , which has coordinate dependence only on @xmath27 . ] now let us construct the lattice version of the 3d ll hamiltonian eq . ( [ eq : ham_cont ] ) , or , eq . ( [ eq : ham_cont2 ] ) as a tight - binding model on a cubic lattice . the kinetic energy becomes the nearest - neighbor hopping term ; the so coupling is realized as the @xmath7 gauge potential defined on each bond of the cubic lattice , and the scalar quadratic potential is converted as a periodic potential along the @xmath13 axis on the lattice . the lattice hamiltonian reads h_latt&= & -_a , n , s , s^ t_a \{c^_n + e_a , s [ e^i a_n + e_a , n ] _ ss c_n , s + & + & h.c . } + _ n , s v(n ) c^_n , s c_n , s , [ eq:3dlattice ] where @xmath28 ( @xmath29 ) is the annihilation ( creation ) operator of electrons at site @xmath30 with spin @xmath31 . @xmath32 and @xmath33 ( @xmath34 ) are , respectively , the lattice unit vector and the hopping amplitude along the @xmath35-direction . the previous @xmath7 landau - type gauge of eq . ( [ eq : landaugauge ] ) defined in the continuum can now be defined on each bond of the cubic lattice as follows : a_n + x , n&= & _ y n_z , a_n + y , n= - _ x n_z , + a_n + z , n&=&0 , where @xmath36 is the flux quantum , whose value is taken as 1 in this paper . as illustrated in fig . [ fig : gauge ] , this gauge configuration can be obtained by rotating a 2d quantum spin - hall ( qsh ) @xcite hofstadter problem defined in the @xmath37 plane by 90@xmath38 around its @xmath13 axis , so that its @xmath39 plane forms another qsh problem . the qsh problem at each plane can be understood as two kramerss copies of the 2d u(1 ) hofstadter problem with opposite fluxes for opposite spins . further , because of the soc , the spin quantization axis along @xmath18 in the @xmath37 plane qsh problem is also rotated by 90@xmath38 , to be along @xmath17 , in the @xmath39 plane qsh problem , which imposes the 3d feature of the topological insulator and reflects the four - fold so coupled rotation symmetry in the lattice . for later convenience , we choose the @xmath27-dependent scalar potential as v(n_z)=2t_y ( 2 n_z ) . @xmath40 and @xmath41 are independent of @xmath42 and @xmath43 , hence , eq . ( [ eq:3dlattice ] ) explicitly maintains translational symmetry along the @xmath5 plane . in addition , it also possesses time - reversal and parity symmetries . next we transform the lattice hamiltonian eq . ( [ eq:3dlattice ] ) into the 1d harper equation . because of the translation symmetry in the @xmath5 plane , the in plane momenta @xmath44 and @xmath45 are good quantum numbers . for a given set of values of @xmath44 and @xmath45 , we introduce the partial fourier transform as c^_n_z , s(k_x , k_y)= _ n_x , n_y e^-i k_x n_x - i k_y n_y c^_n , s. then eq . [ eq:3dlattice ] is reduced to h_z(k_x , k_y)&=&-t_z _ n_z;s\{c^_n_z+1;s(k_x , k_y ) c_n_z;s(k_x , k_y ) + h.c . } + & -&2_n_z , s , s^ c^_n_z;s(k_x , k_y ) v_n_z;s , s c_n_z;s(k_x , k_y ) + [ eq : harper ] in which v_n_z;s , s & = & _ ss r(k_x , k_y ) ( 2 n_z ) + & + & [ -i_- _ + + i _ + _ -]_ss ( 2 n_z ) , [ eq : spin_incom ] and r(k_x , k_y)&=&t_x k_x + t_y(k_y -1 ) , + _ & = & t_x k_x i t_y k_y , + _ & = & ( _ x i _ y ) . ( [ eq : harper ] ) consists of the usual hopping along the @xmath13-direction and the periodic onsite spin - dependent potential eq . ( [ eq : spin_incom ] ) . in comparison , the harper equation for the 2d landau level problem in the landau gauge is a hopping hamiltonian in the presence of a periodic onsite scalar potential . as a result , ( [ eq : harper ] ) maintains time - reversal symmetry as h_z(k_x , k_y)=t h_z(-k_x ,- k_y ) t^-1 with @xmath46 and @xmath47 is the complex conjugation . , @xmath48 , @xmath49 , and @xmath50 . ] we consider the case of @xmath51 with @xmath52 and @xmath53 coprime integers , and then @xmath54 becomes periodical along the @xmath13-direction with an enlarged unit cell size of @xmath53 . below we also assume that the lattice size along the @xmath13-direction @xmath55 is an integer multiple of @xmath53 as @xmath56 . on a single particle basis with momenta @xmath44 and @xmath45 , | ( k_x , k_y)= _ n_z;s _ n_z;s(k_x , k_y ) c^_n_z;s(k_x , k_y ) |0 , the corresponding harper equation becomes & -&[_n_z+1;s(k_x , k_y ) + _ n_z-1;s(k_x , k_y ) ] + & - & _ s v_n_z;s , s _ n_z;s(k_x , k_y ) = _ n_z;s(k_x , k_y ) , [ eq : harper_2 ] where @xmath57 . in the form of transfer matrix , ( [ eq : harper_2 ] ) is represented as & = & t_n_z;ss^ ( , k_x , k_y ) + & & . the transfer matrix is defined as t_n_z;ss^ ( , k_x , k_y)&= & ( cc e_ss^ & -i_ss^ + i_ss^ & 0 + ) , [ eq : transfer_1 ] in which @xmath58 is the @xmath59 identity matrix ; and & = & -i - r(k_x , k_y ) ( 2 n_z ) + & - & ( 2n_z ) ( -i _ - _ + + i _ + _ - ) . noticing that the spin - dependence of the transfer matrix @xmath60 is @xmath27-independent , thus the harper equation ( eq . ( [ eq : harper_2 ] ) ) can be decoupled into two sets in the `` lattice helicty '' eigen - basis . the lattice helicty operator is defined as _ = t_x k_x _ y - t_y k_y _ x , which can be viewed as the lattice generalization of the helicity operator @xmath61 in the continuum . its eigenvalues are @xmath62 , corresponding to the in plane eigenstates _ ( k_x , k_y ) =( c i + 1 + ) . under the time - reversal transformation , @xmath63 as well as its eigenstates are invariant . in this representation , the transfer matrix @xmath60 is decomposed into two sets of @xmath64 with the @xmath59 form for @xmath63 positive and negative helicities , respectively , as t_n_z ; ( , k_x , k_y)&= & ( cc e _ & -1 + 1 & 0 + ) , [ eq : transfer_2 ] with & = & -- r(k_x , k_y ) ( 2 n_z ) + & & ( 2n_z ) . ) @xmath65-@xmath66-@xmath65 , ( @xmath67 ) @xmath68-@xmath66-@xmath68 , ( @xmath69 ) @xmath68-@xmath70-@xmath68 , respectively . the red and blue lines represent the surface states with positive and negative helicities , respectively . here , only surface modes localized at the lower boundary are plotted , and those of the upper surface are of the same values in the energy spectrum but with opposite lattice helicities . the following parameters are used : @xmath71 , @xmath72 , @xmath73 , and @xmath74 . , title="fig : " ] ) @xmath65-@xmath66-@xmath65 , ( @xmath67 ) @xmath68-@xmath66-@xmath68 , ( @xmath69 ) @xmath68-@xmath70-@xmath68 , respectively . the red and blue lines represent the surface states with positive and negative helicities , respectively . here , only surface modes localized at the lower boundary are plotted , and those of the upper surface are of the same values in the energy spectrum but with opposite lattice helicities . the following parameters are used : @xmath71 , @xmath72 , @xmath73 , and @xmath74 . , title="fig : " ] ) @xmath65-@xmath66-@xmath65 , ( @xmath67 ) @xmath68-@xmath66-@xmath68 , ( @xmath69 ) @xmath68-@xmath70-@xmath68 , respectively . the red and blue lines represent the surface states with positive and negative helicities , respectively . here , only surface modes localized at the lower boundary are plotted , and those of the upper surface are of the same values in the energy spectrum but with opposite lattice helicities . the following parameters are used : @xmath71 , @xmath72 , @xmath73 , and @xmath74 . , title="fig : " ] following the method introduced in ref . [ ] , we define the matrix @xmath75 as the product of @xmath76 for sites @xmath77 s in a unit cell with @xmath53-sites as m^(,k_x , k_y)&= & _ i=1^q t_i ; ( , k_x , k_y ) . [ eq : m_matrix ] for the open boundary condition , the energy of the surface states can be determined by the zeros of the matrix elements @xmath78 which are the roots of ( @xmath79)th - order polynomial equations . for each lattice helicity sector , the @xmath79 roots @xmath80 denote the surface states in the @xmath79 gaps between adjacent bands . lying in the 2nd gap . only one boundary helical fermi surface appears . ( b ) @xmath81 lying the 3rd gap . there are four boundary helical fermi surfaces . parameter values are @xmath71 , @xmath72 , @xmath73 , and @xmath74 . , title="fig : " ] lying in the 2nd gap . only one boundary helical fermi surface appears . ( b ) @xmath81 lying the 3rd gap . there are four boundary helical fermi surfaces . parameter values are @xmath71 , @xmath72 , @xmath73 , and @xmath74 . , title="fig : " ] in this section , we present the numeric results of the surface and bulk energy spectra of the 3d hofstadter problem , as well as the analysis of @xmath82 topological index from the parity eigenvalues of the bulk wave functions . we first consider the case with tetragonal symmetry in the @xmath5 plane . the harper equation ( eq . ( [ eq : harper ] ) ) is solved numerically with respect to @xmath44 and @xmath45 in the 2d brillouin zone as depicted in fig . [ fig : bz ] . a typical flux value of @xmath83 is used : each unit cell contains 7 sites , thus the spectra consist of 7 bands . to fully open band gaps , we choose an anisotropic ratio between @xmath84 and @xmath85 as @xmath86 . the bulk and surface spectra are plotted along different high symmetry lines connecting time - reversal invariant points in the brillouin zone in fig . [ fig : spectra ] ( @xmath35 ) , ( @xmath67 ) , and ( @xmath69 ) , respectively . in each gap between adjacent bands , helical surface states appear with their helicities marked with different colors in fig . [ fig : spectra ] . the states on the upper and lower surfaces can be distinguished by the values of @xmath87 where the @xmath88 is a surface state energy . if @xmath89 , then the corresponding eigenstates are localized on the lower @xmath90 or upper @xmath91 boundaries , respectively @xcite . if @xmath92 , it means that the corresponding states merge into bulk states , and they are no longer considered surface states . because of parity symmetry , the upper surface spectrum with momenta @xmath6 should be the same as that of the lower surface with @xmath93 . further , since the spin polarization is invariant under inversion operation , the corresponding surface states on the upper and lower surfaces are of opposite lattice helicity eigenvalues , thus only the surface states on the lower surface are depicted in fig . [ fig : spectra ] . the spectra are plotted in fig . [ fig : spectra ] along the high symmetry lines connecting time - reversal invariant points in the brillouin zone . in fig . [ fig : spectra ] ( @xmath35 ) , the spectra are presented along the cut of @xmath65-@xmath66-@xmath65 . the harper equation ( eq . ( [ eq : harper_2 ] ) ) along this cut is the same as that of the 2d hofstadter problem in the magnetic field @xcite but with kramers doubling because of the time - reversal symmetry . as a result , the surface modes appear in terms of kramers doublet pairs . for the band gap 1 to 6 counted from bottom to top , along the cut of @xmath65-@xmath66-@xmath65 , here are 3 , 1 , 2 , 2 , 1 , and 3 branches of kramers doublets across the gap , respectively . this pattern remains the same as along the cut from @xmath68-@xmath66-@xmath68 shown in fig . [ fig : spectra ] ( @xmath67 ) . along the path @xmath68-@xmath65-@xmath68 , the surface states do not run across the band gap . .the parity eigenvalues @xmath94 of the 3d bulk states at eight time - reversal invariant states . @xmath95 represents the @xmath77-th band counted from bottom to top , and @xmath96 is the index of states at the 8 time - reversal invariant momenta . the @xmath97 index @xmath98 or @xmath99 at the column of @xmath100 represents that the system is @xmath97-trivial or non - trivial when the lowest @xmath77 bands are filled . the parameter values are @xmath71 , @xmath72 , and @xmath73 . [ cols="^,^,^,^,^,^,^,^",options="header " , ] now , let us set @xmath101 but tune @xmath102 from small values to 1 . in the case of @xmath103 , eq . [ eq:3dlattice ] becomes decoupled @xmath37-layers . each @xmath37-layer is the kramers doubling of the 2d hofstadter problem with spin polarized along the @xmath104-direction . as @xmath102 increases , energy dispersion develops along the @xmath18-direction and the direction of spin polarization also twists . however , the band topology remains the same at small values of @xmath102 . in fig . [ fig : spectra_t02 ] ( @xmath35 ) , ( @xmath67 ) , and ( @xmath69 ) , the bulk and surface spectra at @xmath105 are presented along the cuts of @xmath65-@xmath66-@xmath65 , @xmath68-@xmath66-@xmath68 , and @xmath70-@xmath66-@xmath70 , respectively . along @xmath65-@xmath66-@xmath65 and @xmath68-@xmath66-@xmath68 , the bulk and surface spectra are qualitatively the same as those in fig . [ fig : spectra ] ( @xmath35 ) and ( @xmath67 ) , respectively . the numbers of branches of kramers doubles are @xmath106 , respectively , for the @xmath77-th band gap with @xmath107 . however , the @xmath5 plane is highly anisotropic . along the cut of @xmath45 axis , i.e. , @xmath70-@xmath66-@xmath70 , the spectra show no non - trivial mid - gap boundary modes across all gaps . in other words , this anisotropic case is a 3d weak topological insulator , which is topologically non - trivial only along the @xmath37 plane . this result can be confirmed from the calculation of the bulk @xmath2-index . similarly to table i , in table ii , we also present the corresponding parity eigenvalues @xmath108 for bulk wave functions at eight time - reversal invariant momenta ( @xmath96 ) of bands @xmath77 ( @xmath109 ) . the values of the strong @xmath2-index are all trivial for all the band gaps . nevertheless , the weak @xmath2-index in the @xmath37-direction exhibits a non - trivial pattern , which is non - trivial for the @xmath77-th band gap with @xmath110 and @xmath111 , and thus is consistent with the evenness of the branches of boundary kramers doublets presented in fig . [ fig : spectra_t02 ] ( @xmath35 ) . the weak @xmath2 indices for the @xmath5 and @xmath39-directions are all trivial . therefore , at @xmath105 , the system is qualitatively stacked by a 2d - like topological insulator in the @xmath37 plane , and it forms a 3d weak topological insulator . now let us study the case with a large value of @xmath112 . the bulk and boundary spectra are plotted in fig . [ fig : spectra_t08 ] ( @xmath35 ) , ( @xmath67 ) and ( @xmath69 ) along the same cuts as taken in fig . [ fig : spectra_t02 ] . in particular , along the @xmath18-direction cut @xmath70-@xmath66-@xmath70 in fig . [ fig : spectra_t08 ] ( @xmath69 ) , non - trivial boundary modes appear across the band gap , which exhibit a pattern similar to the spectra along the @xmath17-direction cut @xmath65-@xmath66-@xmath65 . although small anisotropy remains in the @xmath5 plane , the system has already become a 3d strong topological insulator . we have also calculated the parity eigenvalues of bulk wave functions at time - reversal invariant momenta , and the results are the same as that in table i , which also indicates that the strong @xmath2 index is non - trivial . the transition between weak and strong topological insulating states as @xmath102 varies must involve bulk band closing . it can be found that the transition point occurs at @xmath113 . in this case , the periodic spin - dependent potential characterizing the hofstadter problem @xmath114 defined in eq . ( [ eq : spin_incom ] ) vanishes at @xmath115 . as shown in fig . [ fig : spectra_t08 ] ( @xmath116 ) , all the band gaps closes at @xmath117 , which triggers this band topology transition . the above study of su(@xmath1 ) hofstadter problems in three - dimensions differs fundamentally from previously studied 3d hofstadter problems under a tilted magnetic field @xcite . firstly , the latter problem is u(@xmath118 ) in nature . there is only one fermion component on each lattice site ; the phase on each link and the flux penetrating each plaquette are u(1 ) . however , our case is a 3d non - abelian su(@xmath1 ) problem . here , the spin-1/2 spinor is located on each lattice site , and the gauge potentials defined on links are noncommutative su(2 ) phases . secondly , the bulk topological classes and surface spectra of these two problems are fundamentally different . our su(2 ) case maintains time - reversal symmetry , and hence it belongs to the aii class characterized by the @xmath2-indices calculated above @xcite . when the strong @xmath2-index is odd , it is a strong 3d @xmath2 topological insulator , and the surface spectra exhibit an odd number of dirac cones as shown in fig . [ fig : surfacecircle ] . in contrast , the 3d u(1 ) problem breaks time - reversal symmetry , and it is not a genuinely novel topological class . roughly speaking , it belongs to the ai class and can be understood the same as stacking layers of 2d quantum hall systems . in other words , it is a weak 3d topological state inheriting 2d features . the boundary fermi surfaces do not close form dirac cones but rather disconnect forming fermi arcs . finally , the reduced 1d hofstadter equations are also different in these two cases . [ eq : harper ] is in fact a matrix equation in spin space , and the associated transfer matrix eq . [ eq : transfer_1 ] is off - diagonal on spin - indices . the partially diagonalized transfer matrix eq . [ eq : transfer_2 ] is defined in the eigenbasis of the helicity operator @xmath63 . this set of helical eigenbasis render the non - trivial @xmath2 topological properties . recently , a paper@xcite considered the 3d hofstadter problem which corresponds to a tilted magnetic field in the cubic lattice with both the nearest and next nearest neighbor hopping . when the flux of each plaquette equals @xmath119 , time - reversal symmetry is restored . the reduced 1d aubry - andre - harper model belongs to the bdi class @xcite and the bulk spectra show weyl points . again the flux in this model is complex , and the realized time - reversal symmetry satisfies @xmath120 ; while , in our case the time - reversal symmetry satisfies @xmath121 because of the kramers degeneracy based on the su(2 ) structure . in other words , the time - reversal symmetry in our case is in in the symplectic class ; while , it is in the orthogonal class in ref . . next we discuss possible experimental realizations of the 3d su(2 ) hofstadter problem . in refs . , the 3d su(2 ) landau level problems in the continuum have been proposed to be realized in strained semiconductor systems . nevertheless , as in the case of the u(1 ) hofstadter problem , the characteristic length scale of landau level states is too long compared with the lattice constant and thus the lattice effect can be neglected . the recent development of ultra - cold atom physics provides a promising opportunity to realize the su(2 ) hofstadter problem . based on the available experimental techniques , such as laser assistant tunneling and shaken lattices , which realized the u(1 ) hofstadter problem @xcite , it is natural to expect that the 3d su(2 ) hofstadter problem can also be studied experimentally in the near future . basically , these techniques need to be extended to spin - dependent hopping or shaking . for a given direction , the associated spin eigenstates are addressed oppositely , such that they acquire opposite phases maintaining time - reversal symmetry . in principle , different spin eigenstates correspond to different internal states of atoms , which have different responses to external lasers , and thus the above spin - dependent manipulations can be realized . the key difficulty is that spin eigen - directions are orthogonal along @xmath17 and @xmath18-bonds due to their non - abelian nature . these could be realized by different sets of laser beams that control hoppings along the @xmath17 and @xmath18 directions separately , and their effects could be superposed together . along each direction , the spin eigenstates are chosen according to orthogonal pauli matrices , respectively . nevertheless careful designs are still needed to achieve the desired su(2 ) hofstadter hamiltonian . in summary , we have constructed the time - reversal invariant 3d hofstadter problem based on the 3d su(2 ) landau levels in the landau - type gauge . this lattice model provides an @xmath7 generalization of the usual 2d hofstadter problem in a magnetic field . for each pair of in plane momenta @xmath122 , this system is reduced to 1d described by a generalized @xmath7 harper equation with a helicity structure . different from its continuum version , this lattice system possesses 3d translation symmetry as characterized by the periodic spin - dependent potential in the @xmath7 harper equation . hence , quantitative analysis of the nontrivial @xmath2 band topology is performed . in the energy spectra studied in this paper , boundary states with opposite lattice helicity structures are spatially separated at different boundaries ; @xmath2 non - trivial helical boundary fermi surface are found and consistent with the @xmath2 bulk band topology analyzed based on the parity eigenvalues of the bulk wave functions . the transition of the band topology from a weak topological insulator to a strong one is also investigated . y. l. thanks d. arovas , t. l. ho , w. ketterle , and c. wu for helpful discussions . y. l. acknowledges the support at the princeton center for theoretical science . y. l. also thanks t. l. ho for his hospitality . 54ifxundefined [ 1 ] ifx#1 ifnum [ 1 ] # 1firstoftwo secondoftwo ifx [ 1 ] # 1firstoftwo secondoftwo `` `` # 1''''@noop [ 0]secondoftwosanitize@url [ 0 ] + 12$12 & 12#1212_12%12@startlink[1]@endlink[0]@bib@innerbibempty link:\doibase 10.1063/1.3293411 [ * * , ( ) ] link:\doibase 10.1103/revmodphys.83.1057 [ * * , ( ) ] link:\doibase 10.1103/revmodphys.82.3045 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevlett.49.405 [ * * , ( ) ] link:\doibase 10.1103/physrevb.25.2185 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1s103/physrevlett.61.2015 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.95.226801 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1103/physrevb.78.195424 [ * * , ( ) ] link:\doibase 10.1103/physrevb.76.045302 [ * * , ( ) ] link:\doibase 10.1103/physrevb.75.121306 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1038/nphys1274 [ * * , ( ) ] link:\doibase 10.1126/science.1173034 [ * * , ( ) ] , link:\doibase 10.1126/science.1189792 [ * * , ( ) ] , @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * ( ) link:\doibase 10.1103/physrevlett.109.135701 [ * * , ( ) ] link:\doibase 10.1016/j.nuclphysb.2014.07.011 [ * * , ( ) ] , link:\doibase 10.1016/j.nuclphysb.2014.07.005 [ * * , ( ) ] , link:\doibase 10.1103/physrevlett.110.216802 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.111.186803 [ * * , ( ) ] link:\doibase 10.1103/physreva.89.032105 [ * * , ( ) ] link:\doibase 10.1103/physrevb.85.085132 [ * * , ( ) ] link:\doibase 10.1103/physrevb.85.125122 [ * * , ( ) ] link:\doibase 10.1103/physrevb.14.2239 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1103/physrevlett.111.185302 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.111.185301 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.112.043001 [ * * , ( ) ] link:\doibase 10.1088/1367 - 2630/5/1/356 [ * * , ( ) ] , link:\doibase 10.1103/physrevlett.95.010403 [ * * , ( ) ] @noop ( ) , @noop ( ) @noop * * , ( ) http://iopscience.iop.org/1347-4065/26/s3-3/1913 [ * * , ( ) ] link:\doibase 10.1103/physrevb.41.11417 [ * * , ( ) ] link:\doibase 10.1103/physrevb.45.13488 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.86.1062 [ * * , ( ) ] link:\doibase 10.1103/physrevb.69.081303 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevb.91.125438 [ * * , ( ) ]

we formulate the three - dimensional @xmath0(@xmath1 ) landau level problem in cubic lattices with time - reversal invariance . by taking a landau - type @xmath0(@xmath1 ) gauge , the system can be reduced into one - dimension , as characterized by the @xmath0(@xmath1 ) generalization of the usual harper equations with a periodic spin - dependent gauge potential . the surface spectra indicate the spatial separation of helical states with opposite eigenvalues of a lattice helicity operator . the band topology is investigated from both the analysis of the boundary helical fermi surfaces and the calculation of the @xmath2-index based on the bulk wave functions . the transition between a three - dimensional weak topological insulator to a strong one is studied as varying the anisotropy of hopping parameters . = 1

it is a process through which an individual realizes moral problems or interprets an ethical position to make an appropriate decision . it is necessary for moral judgments , performing ethical behaviors , and other moral components . various studies have indicated the effects of ethical sensitivity on improving ethical performance of nurses and enhancing nurse patient relationships . previous research has shown that nurses , who are more sensitive to ethical issues , have greater ability to solve moral problems with less moral distress . on the other hand , individuals with no ethical sensitivity are more willing to learn issues related to their job . weaver and morse believed that working and being in clinical environment affects the level of moral sensitivity . they suggested that the level of moral sensitivity was related with age and individuals attitude toward their profession . a finnish study found a significant difference between moral judgment of nursing freshmen and seniors . it , therefore , concluded that education level can affect the level of moral sensitivity and accordingly moral judgment of nursing students . some other studies have been indicative of the effects of educational methods on moral sensitivity . in fact , education with more concrete facts , examples , case studies , and teaching aids will better enhance ethical sensitivity . using a combination of several teaching methods , instead of one method alone , will also increase the ethical sensitivity of students . clinical work experience and direct presence at patients bedside contrary to nursing students , medical students have been reported to have high ethical sensitivity during the first year of their presence in hospitals . various studies have reported several , and sometimes contrasting , factors to affect the level of ethical sensitivity . since sociocultural backgrounds of the workplace are known to have certain impacts on ethical sensitivity , greater numbers of studies in different communities will better determine the effective factors on this concept . despite the importance of ethical sensitivity in clinical practice , considered the findings of previous studies about ethical sensitivity to be limited , superficial , and mostly based on quantitative and objective analyses . as ethical sensitivity is apparently affected by different cultural conditions and working backgrounds , and its assessment requires a comprehensive and holistic approach which can be obtained by naturalistic methods . on the other hand since no previous iranian studies have reviewed ethical sensitivity and its determinants , this study evaluated nursing students understanding of factors influencing ethical sensitivity . in a qualitative study during 2009 in kerman ( iran ) , 8 female msc nursing students were included [ table 1 ] . polit and beck believed that this method is a valid method to obtain information from the participants in qualitative studies . open - ended questions were asked during individual interviews to let the subjects freely express their feelings and thoughts . in order to obtain better understanding and thorough information , the interviews were conducted at the department of nursing ( school of nursing and midwifery , kerman university of medical sciences ) or the dormitory based on the participants preferences . characteristics of individual interviewees in order to collect complementary information , two focus groups were also formed and a number of meetings were held to allow the participants to better describe their experiences and perceptions . the first focus group consisted of three female and five male students ( mean age : 27 years ) . they had a mean work experience of 3 years ( range : 0 - 10 years ) and were studying nursing education ( n = 2 ) , critical care nursing ( n = 3 ) , and neonatal critical care nursing ( n = 3 ) . the second focus group included two male critical care nursing students ( age : 28 and 30 years , work experience : 5 and 8 years ) . the subjects discussed the questions that the researchers had prepared in the focus groups . during discussions , the researchers tried to retain the participants attention on the main subject and to avoid distractions . this method of analysis focuses on human communications and allows the researcher to understand superficial and overt elements of the participants words . to perform manifest content analysis according to bernard 's theory , afterward , two research team members reviewed the texts separately to better understand their contents . they extracted the units of meaning and wrote them as comments on the original versions of texts . finally , five categories were obtained which indicated the students understanding of factors influencing ethical sensitivity . during this process the categories were also reviewed repeatedly to make sure that the results show the manifest content of the data . microsoft one note 2007 was used to organize the categories and classes . at the beginning of the study , the participants were explained about the confidentiality of data and their right to withdraw at any time . in addition , since the participants were nursing students and the interviews could interfere with their academic activities , the time and location of interviews were set according to their preferences . in order to increase the credibility of the study , long exposure to the data and maximum variation sampling were also beneficial to the credibility of the study . moreover , two faculty members who were familiar with qualitative research coded a number of interviews separately . better auditing of data was ensured by recording all stages of the study , e.g. interviews and methods of analysis , in detail . after all analyses , five main themes were found to indicate the students understanding of factors influencing ethical sensitivity . these themes included individual and spiritual characteristics , education , mutual understanding , internal and external controls , and experience of immoral acts . the participants believed that nurses are different from the whole society in terms of some individual characteristics such as morality . according to them , individual characteristics such as personality types ( law - oriented , decisive , reliable , accurate , able to say no ) , the relevance of individuals personality with their profession , emotions , empathy with patients , and interest in profession were mentioned as factors influencing ethical sensitivity . on the other hand , since all participants were muslim , religious beliefs were also reported to be effective . unfortunately , we will not go to patients bedside anymore when we are in charge of the shift . i always think that even if i do not give a vitamin pill to the patient , i ll owe him / her . i sometimes think about and feel really sad for people in some parts of africa . it is in my make - up and that is probably why i have learned these aspects of nursing better . most participants considered education as a major factor in ethical sensitivity . personal characteristics are , therefore , of high importance since they result from primary educations in an individual 's life . repeated education with reminders and warnings as nursing profession and treatment methods are progressing , constant and updated education on ethics seems indispensable . sometimes , someone really likes to do something but he / she has no information . an outsider would see the person as unscrupulous , but they do not know ! the participants emphasized that despite the absence of courses on ethics , they had received covert education from the behaviors of their instructors . there was a professor who used to take care of patients eyes and stroke them while we were suctioning them . we all liked and learned that , stated a participant . on the other hand , patients should be educated about their own rights . increased knowledge of patients may act as an external control to sensitize the community , and hence the nurses , to ethics . however , education to enhance nurses ethical sensitivity is not necessarily formal . in other words , any learning opportunity , like discussing everyday events , can be absolutely beneficial . according to the experiences of nursing students , ethical sensitivity requires relationships with at least one other person . nurses will be obliged to follow ethics if they understand the physical and emotional needs of patients through putting themselves in their situation . on the other hand , patients understanding of nurses situation and trusting how they prioritize the needs of all patients will lead to a calmer environment in which the nurse has enough time to think about more important issues such as ethics . now think they do not possess adequate knowledge and they had not been trained . but would we like such behaviors if we were patients ? if we were admitted in another hospital where no one knew us ? the feedback can be received from patients or their relatives , or even from other nurses and nursing managers . with a more holistic view maybe , again others feedback or things such as a mother 's gratitude have a positive effect which keeps us from feeling disappointed with everything we do . according to the participants , the whole society should also provide such an understanding . to be precise , as mutual understanding can positively affect ethical sensitivity , its absence will result in decreased ethical sensitivity . the subjects believed that in order to establish an appropriate mutual understanding , the society needs to accept nursing as a valuable profession . in their opinion , nurses should not be expected to be sensitive to important communicational aspects such as ethics unless the community has a correct understanding of nursing profession and transfers it to nursing volunteers and students . in such a situation , ethics and morality are no longer important . will someone who does not respect him / herself and whose job is not honored care about morality ? commented a participant . although rules and regulations can not entirely control the implementation of ethics , individuals will be more sensitive as long as measures of control exist . an example is the patients bill of rights which helps people know what is happening to them . they believed it can provide authorities with the required opportunity to permanently solve a problem . in addition , while laws should be enforced , individuals have to have law - oriented personalities as well . as the subjects in this study mentioned , external controls are only helpful in combination with internal controls which are more effective , stable , and valid . ethics can be implemented by the force of rules , but that does not make a moral person . he / she will follow ethics in only one aspect . you may be able to make someone who sits all his / her shift stand , but you can not wake their conscience . i mean as soon as you remove the law , they would sit again ! said a participant . the participants believed that nurses are different from the whole society in terms of some individual characteristics such as morality . according to them , individual characteristics such as personality types ( law - oriented , decisive , reliable , accurate , able to say no ) , the relevance of individuals personality with their profession , emotions , empathy with patients , and interest in profession were mentioned as factors influencing ethical sensitivity . on the other hand , since all participants were muslim , religious beliefs were also reported to be effective . unfortunately , we will not go to patients bedside anymore when we are in charge of the shift . i always think that even if i do not give a vitamin pill to the patient , i ll owe him / her . i sometimes think about and feel really sad for people in some parts of africa . it is in my make - up and that is probably why i have learned these aspects of nursing better . personal characteristics are , therefore , of high importance since they result from primary educations in an individual 's life . repeated education with reminders and warnings as nursing profession and treatment methods are progressing , constant and updated education on ethics seems indispensable . sometimes , someone really likes to do something but he / she has no information . an outsider would see the person as unscrupulous , but they do not know ! she said . the participants emphasized that despite the absence of courses on ethics , they had received covert education from the behaviors of their instructors . there was a professor who used to take care of patients eyes and stroke them while we were suctioning them . we all liked and learned that , stated a participant . on the other hand , patients should be educated about their own rights . increased knowledge of patients may act as an external control to sensitize the community , and hence the nurses , to ethics . however , education to enhance nurses ethical sensitivity is not necessarily formal . in other words , according to the experiences of nursing students , ethical sensitivity requires relationships with at least one other person . nurses will be obliged to follow ethics if they understand the physical and emotional needs of patients through putting themselves in their situation . on the other hand , patients understanding of nurses situation and trusting how they prioritize the needs of all patients will lead to a calmer environment in which the nurse has enough time to think about more important issues such as ethics . now think they do not possess adequate knowledge and they had not been trained . but would we like such behaviors if we were patients ? if we were admitted in another hospital where no one knew us ? the feedback can be received from patients or their relatives , or even from other nurses and nursing managers . with a more holistic view maybe , again others feedback or things such as a mother 's gratitude have a positive effect which keeps us from feeling disappointed with everything we do . according to the participants , the whole society should also provide such an understanding . to be precise , as mutual understanding can positively affect ethical sensitivity , its absence will result in decreased ethical sensitivity . the subjects believed that in order to establish an appropriate mutual understanding , the society needs to accept nursing as a valuable profession . in their opinion , nurses should not be expected to be sensitive to important communicational aspects such as ethics unless the community has a correct understanding of nursing profession and transfers it to nursing volunteers and students . in such a situation , ethics and morality are no longer important . will someone who does not respect him / herself and whose job is not honored care about morality ? commented a participant . although rules and regulations can not entirely control the implementation of ethics , individuals will be more sensitive as long as measures of control exist . an example is the patients bill of rights which helps people know what is happening to them . they believed it can provide authorities with the required opportunity to permanently solve a problem . in addition , while laws should be enforced , individuals have to have law - oriented personalities as well . as the subjects in this study mentioned , external controls are only helpful in combination with internal controls which are more effective , stable , and valid . ethics can be implemented by the force of rules , but that does not make a moral person . he / she will follow ethics in only one aspect . . you may be able to make someone who sits all his / her shift stand , but you can not wake their conscience . i mean as soon as you remove the law , they would sit again ! said a participant . caring is thus an entirely moral action . an immoral act will impose additional harm on a vulnerable person . since immoral acts put nurses in turmoil , they try to avoid such actions . therefore , not only education but also the experience of an immoral act will elevate nurses level of knowledge . well , previous experience is so important ! for example you might have been in a similar situation in the past . if you had made a wrong decision which caused a bad experience , you will try to decide more wisely this time , mentioned a participant . it not only paved the way for further studies , but also provided a list for planning measures to educate , promote , facilitate , and develop ethical sensitivity and ultimately develop moral performance of nurses . our findings indicated personal and spiritual characteristics , education , mutual understanding , internal and external controls , and experience of immoral acts as the factors affecting ethical sensitivity of nurses . the effects of religion , personal characteristics , communicational skills , and spirituality have been emphasized . such attitude may be formed as a result of various experiences throughout the life . since ethics have greater effects on spiritual aspects of life rather than its material dimensions , students who believe in spirituality are more sensitive to ethics . in other words , ethical sensitivity leads to moral acts which in turn facilitate moral development . kim et al . suggested that ethical sensitivity is influenced by upbringing , culture , religion , education , and life experiences . weaver and morse believed that personal characteristics and interpersonal relations are effective on ethical sensitivity . reported individual characteristics to be important in nursing students viewpoints about their profession . similarly , our participants considered the same factor as a determinant of ethical sensitivity . the subjects in the present study considered education , both on various aspects of professional skills and on ethics itself , as an important factor in enhancing ethical qualities and increasing individuals knowledge . likewise , kim et al . showed that students who had passed training courses in ethics had higher ethical sensitivity . weaver and morse announced that professional advancement and higher levels of knowledge and skills will increase ethical sensitivity . reported that moral judgment in senior students of nursing was significantly more than in freshmen . rahmani et al . found misunderstandings about patient rights , i.e. while nurses stated that they respected patients right to be independent and thus provided them with enough information to make decisions , patients thought the opposite . the importance of education in ethical sensitivity indicates the necessity of including this subject in nursing curriculum . students will only be sensitive to an ethical issue if they have an appropriate understanding of it . therefore , a direct relation between ethical awareness of students and their ethical sensitivity is expected . mutual understanding was another finding of this study which resulted in different codes . in nursing profession , an efficient ethical relation between nurses and patients requires both sides to understand each other . weaver and they , however , reported this perception to receive little attention from the organizations . on the other hand , family , coworkers , friends , and physicians had greater shares in supporting nurses . kim et al . suggested the impacts of individuals attitude toward their job on their ethical sensitivity . they stated that the public 's viewpoint on different majors will form a person 's point of view on his / her profession . having a positive viewpoint on one 's major will in turn increase their ethical sensitivity . however , each of them had a special experience of inadequate understanding on the part of different people of the community such as patients and their relatives . found the effects of personal characteristics on the attitudes of individuals toward their field of study . a mutual understanding between nurses and patients will ensure nurses that their decisions and actions are appreciated by the society . they will , therefore , be more sensitive to ethics . after the establishment of a mutual understanding she / he will instead fully attend to various physical , mental , and spiritual needs of the patient . on the other hand , when the patients and their relatives value the care provided by nurses and understand their problems and concerns , nurses will feel satisfied . the nursing students in this study believed that internal and external controls were effective on enhancing ethical sensitivity . the majority of participants in a previous research believed that standard policies will cause increased ethical sensitivity . weaver and morse emphasized that hospital criteria should not be in conflict with personal moral standards . however , the greater significance of internal controls over external controls was accentuated by our participants . while humans have both individual and collective dimensions , internal controls mostly affect the individual aspect of a person . since successful nursing requires the cooperation of a large number of individuals , external controls are also of high importance . however , a person 's conscience ( or internal control ) can compensate for the shortcomings of external controls . for instance , in situations when it is impossible to supervise a nurse ( such as times caring for a patient with reduced consciousness or working alone ) , the internal control will force the nurse follow ethics . despite the higher emphasis on internal controls in the present study , the two types of control are complementary to each other in forming ethical sensitivity . among the themes suggested by our participants were experiences of performing or witnessing immoral acts . kim et al . considered ethical sensitivity to be influenced by life experiences and clinical experience . according to ersoy and gndogmus , in the absence of education and adequate information , experience will play a major role in the establishment of ethical sensitivity . not only experience , but also direct or indirect confrontation with everyday situations ( holding positive or negative moral messages ) is effective on shaping a nurse 's cognitive organization . since experience is obtained through high costs for patients , nurses , and health systems , it should undoubtedly be considered as a chief factor in developing ethical sensitivity . a limitation of this study was evaluating nursing students experiences of the theoretical aspect of perception . obviously , experience of ethical sensitivity can affect other aspects of the students professional life which were not included in the present research . considering the specific geographic and cultural characteristics of the studied population , further research in other nursing education centers is recommended . moreover , as we only selected postgraduate students , future studies on perceptions of undergraduate and phd students are necessary . we found a combination of individual and spiritual characteristics , education , socialization , control , and experience to influence ethical sensitivity of nurses . this combination shapes a unique application to sensitize nurses in professional situations . in nursing human resource management , application of this combination in positive and negative reinforcement , education , educational objectives , and research can reveal the practicality of our findings . it is noteworthy that we did not introduce the above - mentioned factors in an isolated list . we actually provided an integrated and correlated collection . analyzing the systemic relationships of this collection these findings can be used not only in education and sensitization of nursing students , but also in increasing ethical sensitivity of clinical nurses . the latter , however , will require introducing favorable individual and spiritual characteristics , efforts in professional socialization , application of external controls , and reviewing the immoral experiences of nurses .

background : ethical sensitivity is considered as a component of professional competency of nurses . its effects on improvement of nurses ethical performance and the therapeutic relationship between nurses and patients have been reported . however , very limited studies have evaluated ethical sensitivity . since no previous iranian research has been conducted in this regard , the present study aimed to review nursing students understanding of effective factors on ethical sensitivity.materials and methods : this qualitative study was performed in kerman , iran , during 2009 . it used semi - structured individual interviews with eight msc nursing students to assess their viewpoints . it also included two focus groups . purposive sampling was continued until data saturation . data were analyzed using manifest content analysis.results:the students understanding of factors influencing ethical sensitivity were summarized in five main themes including individual and spiritual characteristics , education , mutual understanding , internal and external controls , and experience of an immoral act.conclusions:the findings of this study create a unique framework for sensitization of nurses in professional performance . the application of these factors in human resource management is reinforcement of positive aspects and decrease in negative aspects , in education can use for educational objectives setting , and in research can designing studies based on this framework and making related tools . it is noteworthy that presented classification was influenced by students themselves and mentioned to a kind of learning activity by them .

SECTION 1. SHORT TITLE. This Act may be cited as the ``EPA Science Advisory Board Reform Act of 2015''. SEC. 2. SCIENCE ADVISORY BOARD. (a) Independent Advice.--Section 8(a) of the Environmental Research, Development, and Demonstration Authorization Act of 1978 (42 U.S.C. 4365(a)) is amended by inserting ``independently'' after ``Advisory Board which shall''. (b) Membership.--Section 8(b) of the Environmental Research, Development, and Demonstration Authorization Act of 1978 (42 U.S.C. 4365(b)) is amended to read as follows: ``(b)(1) The Board shall be composed of at least nine members, one of whom shall be designated Chairman, and shall meet at such times and places as may be designated by the Chairman. ``(2) Each member of the Board shall be qualified by education, training, and experience to evaluate scientific and technical information on matters referred to the Board under this section. The Administrator shall ensure that-- ``(A) the scientific and technical points of view represented on and the functions to be performed by the Board are fairly balanced among the members of the Board; ``(B) at least ten percent of the membership of the Board are from State, local, or tribal governments; ``(C) persons with substantial and relevant expertise are not excluded from the Board due to affiliation with or representation of entities that may have a potential interest in the Board's advisory activities, so long as that interest is fully disclosed to the Administrator and the public and appointment to the Board complies with section 208 of title 18, United States Code; ``(D) in the case of a Board advisory activity on a particular matter involving, or for which the Board has evidence that it may involve, a specific party, no Board member having an interest in the specific party shall participate in that activity; ``(E) Board members may not participate in advisory activities that directly or indirectly involve review or evaluation of their own work, unless fully disclosed to the public and the work has been externally peer-reviewed; ``(F) Board members shall be designated as special Government employees; ``(G) no registered lobbyist is appointed to the Board; and ``(H) a Board member shall have no current grants or contracts from the Environmental Protection Agency and shall not apply for a grant or contract for 3 years following the end of that member's service on the Board. ``(3) The Administrator shall-- ``(A) solicit public nominations for the Board by publishing a notification in the Federal Register; ``(B) solicit nominations from relevant Federal agencies, including the Departments of Agriculture, Defense, Energy, the Interior, and Health and Human Services; ``(C) solicit nominations from-- ``(i) institutions of higher education (as defined in section 101(a) of the Higher Education Act of 1965 (20 U.S.C. 1001(a))); and ``(ii) scientific and research institutions based in work relevant to that of the Board; ``(D) make public the list of nominees, including the identity of the entities that nominated each, and shall accept public comment on the nominees; ``(E) require that, upon their provisional nomination, nominees shall file a written report disclosing financial relationships and interests, including Environmental Protection Agency grants, contracts, cooperative agreements, or other financial assistance, that are relevant to the Board's advisory activities for the three-year period prior to the date of their nomination, and relevant professional activities and public statements for the five-year period prior to the date of their nomination; and ``(F) make such reports public, with the exception of specific dollar amounts, for each member of the Board upon such member's selection. ``(4) Disclosure of relevant professional activities under paragraph (3)(E) shall include all representational work, expert testimony, and contract work as well as identifying the party for which the work was done. ``(5) Except when specifically prohibited by law, the Agency shall make all conflict of interest waivers granted to members of the Board, member committees, or investigative panels publicly available. ``(6) Any recusal agreement made by a member of the Board, a member committee, or an investigative panel, or any recusal known to the Agency that occurs during the course of a meeting or other work of the Board, member committee, or investigative panel shall promptly be made public by the Administrator. ``(7) The terms of the members of the Board shall be three years and shall be staggered so that the terms of no more than one-third of the total membership of the Board shall expire within a single fiscal year. No member shall serve more than two terms over a ten-year period.''. (c) Record.--Section 8(c) of such Act (42 U.S.C. 4365(c)) is amended-- (1) in paragraph (1)-- (A) by inserting ``or draft risk or hazard assessment,'' after ``at the time any proposed''; (B) by striking ``formal''; and (C) by inserting ``or draft risk or hazard assessment,'' after ``to the Board such proposed''; and (2) in paragraph (2)-- (A) by inserting ``or draft risk or hazard assessment,'' after ``the scientific and technical basis of the proposed''; and (B) by adding at the end the following: ``The Board's advice and comments, including dissenting views of Board members, and the response of the Administrator shall be included in the record with respect to any proposed risk or hazard assessment, criteria document, standard, limitation, or regulation and published in the Federal Register.''. (d) Member Committees and Investigative Panels.--Section 8(e)(1)(A) of such Act (42 U.S.C. 4365(e)(1)(A)) is amended by adding at the end the following: ``These member committees and investigative panels-- ``(i) shall be constituted and operate in accordance with the provisions set forth in paragraphs (2) and (3) of subsection (b), in subsection (h), and in subsection (i); ``(ii) do not have authority to make decisions on behalf of the Board; and ``(iii) may not report directly to the Environmental Protection Agency.''. (e) Public Participation.--Section 8 of such Act (42 U.S.C. 4365) is amended by amending subsection (h) to read as follows: ``(h)(1) To facilitate public participation in the advisory activities of the Board, the Administrator and the Board shall make public all reports and relevant scientific information and shall provide materials to the public at the same time as received by members of the Board. ``(2) Prior to conducting major advisory activities, the Board shall hold a public information-gathering session to discuss the state of the science related to the advisory activity. ``(3) Prior to convening a member committee or investigative panel under subsection (e) or requesting scientific advice from the Board, the Administrator shall accept, consider, and address public comments on questions to be asked of the Board. The Board, member committees, and investigative panels shall accept, consider, and address public comments on such questions and shall not accept a question that unduly narrows the scope of an advisory activity. ``(4) The Administrator and the Board shall encourage public comments, including oral comments and discussion during the proceedings, that shall not be limited by an insufficient or arbitrary time restriction. Public comments shall be provided to the Board when received. The Board's reports shall include written responses to significant comments offered by members of the public to the Board. ``(5) Following Board meetings, the public shall be given 15 calendar days to provide additional comments for consideration by the Board.''. (f) Operations.--Section 8 of such Act (42 U.S.C. 4365) is further amended by amending subsection (i) to read as follows: ``(i)(1) In carrying out its advisory activities, the Board shall strive to avoid making policy determinations or recommendations, and, in the event the Board feels compelled to offer policy advice, shall explicitly distinguish between scientific determinations and policy advice. ``(2) The Board shall clearly communicate uncertainties associated with the scientific advice provided to the Administrator or Congress. ``(3) The Board shall ensure that advice and comments reflect the views of the members and shall encourage dissenting members to make their views known to the public, the Administrator, and Congress. ``(4) The Board shall conduct periodic reviews to ensure that its advisory activities are addressing the most important scientific issues affecting the Environmental Protection Agency. ``(5) The Board shall be fully and timely responsive to Congress.''. SEC. 3. RELATION TO THE FEDERAL ADVISORY COMMITTEE ACT. Nothing in this Act or the amendments made by this Act shall be construed as supplanting the requirements of the Federal Advisory Committee Act (5 U.S.C. App.). SEC. 4. RELATION TO THE ETHICS IN GOVERNMENT ACT OF 1978. Nothing in this Act or the amendments made by this Act shall be construed as supplanting the requirements of the Ethics in Government Act of 1978 (5 U.S.C. App.). Passed the House of Representatives March 17, 2015. Attest: KAREN L. HAAS, Clerk.

EPA Science Advisory Board Reform Act of 2015 (Sec. 2) This bill amends the Environmental Research, Development, and Demonstration Authorization Act of 1978 to revise the process of selecting members of the Science Advisory Board, guidelines for participation in Board advisory activities, and terms of office. The Board provides scientific advice to the Environmental Protection Agency (EPA). This bill requires the Board to independently provide that advice. Among the revisions to requirements concerning the Board's membership are the following: a requirement to balance scientific and technical points of view; a set minimum level of representation from state, local, or tribal governments; allowance of affiliation with or representation of entities that may have a potential interest in the Board's advisory activities; conflict of interest restrictions; restrictions on participation in advisory activities involving review of a member's work; restrictions on appointment of registered lobbyists; and prohibitions on member receipt of current EPA grants or contracts. The EPA must make public a list of nominees to the Board and accept public comments on the nominees. Reports filed upon the provisional nomination of a member disclosing financial relationships and interests must also be made public. The EPA must provide draft risk or hazard assessments in its regulatory proposals and documents to the Board. The Board's advice and comments must be included in the record regarding any such proposal and published in the Federal Register. The Board's member committees and investigative panels must operate in accordance with the membership, participation, and policy requirements contained in this Act, including new requirements for public participation in advisory activities of the Board. The member committees and investigative panels do not have the authority to make decisions on behalf of the Board and may not report directly to the EPA. The bill imposes additional public participation requirements: The EPA and the Board must make public all reports and relevant scientific information at the same time they are received by the Board. The Board must hold public information-gathering sessions to discuss the state of the science related to a major advisory activity. Prior to convening a member committee or investigative panel, the EPA must accept and address public comments on questions asked of the Board. The Board, member committees, and investigative panels may not accept a question that unduly narrows the scope of an advisory activity. The Board must strive to avoid making policy determinations or recommendations, communicate uncertainties, encourage dissenting members to make their views known, conduct periodic reviews to ensure that its activities address the most important scientific issues affecting the EPA, and respond to Congress fully and in a timely manner.

in the redshift interval @xmath10 most ionizing photons in the universe are thought to originate in popii stars in normal ( @xmath11 ) galaxies @xcite . for reionization calculations at @xmath12 photons from lower mass halos should be taken into account @xcite , whereas at @xmath13 active galactic nuclei start to play a dominant role @xcite . the fact that the metagalactic uv field peaks at @xmath14 ( * ? ? ? * and ref . therein ) points to a peak in the galactic star formation ( sf ) rate at such redshifts ( see also * ? ? ? a major uncertainty in modeling the effect of this sf on the thermal state of the intergalactic medium ( igm ) is the value of the escape fraction @xmath1 of ionizing uv photons , which is a function of redshift , and galaxy type and mass . best observational estimates of @xmath1 come from the detailed multiwaveband studies of the local universe . @xcite find that less than @xmath15 of ionizing photons from low - redshift starburst galaxies escape into the igm . more recently , for several local starburst galaxies , @xcite estimate @xmath16 , noting that inclusion of dust will further reduce @xmath1 , and @xcite find @xmath17 for another local starburst . the situation is markedly different at @xmath18 , where the lyman continuum ( lyc ) detection points at much higher @xmath1 @xcite . by comparing the direct observations of the lyc from galaxies to the mean cosmic uvb intensity , @xcite conclude that the average @xmath1 increases from @xmath19 at @xmath20 to @xmath21 at @xmath22 . most theoretical estimates of @xmath1 to date have been based on models with a smooth distribution of gas @xcite or semi - analytical models with expanding shells and superbubbles in a disk galaxy @xcite . in this letter we present ab initio calculations of the energy - dependent @xmath1 of ionizing radiation from sf regions in proto - galaxies found in numerical simulations at five different redshifts from @xmath6 to 3.8 . we define @xmath23 simply as a fraction of photons of energy @xmath24 which reach a shell of radius @xmath25 around a given source ; by definition @xmath26 . we postprocess high - resolution simulation datasets with radiative transfer ( rt ) on nested grids , with the maximum grid resolution of @xmath27 . each galaxy contains from several hundred to several thousand distinct stellar sources representing individual , young sf regions . our interstellar gas distribution is extremely clumpy due to an array of physical processes including feedback from sf . we also estimate the effect of the dynamical expansion of hii regions on the escape of ionizing photons . to compute the escape of ionizing radiation from sf regions , we use an extension of the fully threaded transport engine ( ftte , * ? ? ? * ) to point sources . this new module was previously briefly introduced in the comparison study by @xcite . it extends the adaptive ray - splitting scheme of @xcite to a model with variable grid resolution . sources of radiation can be hosted by cells of any level of refinement , although usually in cosmological applications sources are sitting on the deepest level of refinement ( fig . [ radialgeometry ] ) . around each point source we build a system of @xmath28 radial rays which split either when we move further away from the source , or when we enter a refined cell , and @xmath29 is the angular resolution level . once a radial ray is refined it stays refined , even if we leave the high spatial resolution patch , until even further angular refinement is necessary . all ray segments are stored as elements of their host cells , and for actual transport we just follow these interconnected data structures accumulating photo - reaction number and energy rates in each cell . with multiple sources , we add the rates from all sources before updating the time - dependent rate network using the chemistry solver from @xcite , and the global timestep is chosen such that each species abundance does not change by more than @xmath30 . with a small ( @xmath31 ) number of star particles we can compute a full ray geometry separately for each source . for a large number of sources ( @xmath32 ) the algorithm allows construction of trees of sources in which individual tree nodes are treated as a single source far from their origin . our algorithm shares many common ideas with the recent rt module of the cosmological structure formation code enzo implemented by @xcite to study feedback from pop iii stars and , in fact , is a basis of an independently developed radiation hydrodynamics module of enzo which we will introduce elsewhere . we use results of high - resolution galaxy formation simulations in a standard @xmath0cdm cosmology done with a significantly improved version of the treesph code described by @xcite some detail is given in @xcite . the simulations invoke the formation of discrete star `` particles '' , which represent a population of stars born at the same time in accordance with a given initial mass function ( imf ) . for the purpose of this work we focus on two ( proto- ) galaxies , k15 and k33 , which at @xmath33=0 become typical disk galaxies of @xmath34= 245 and 180 @xmath35 , respectively . the rt calculation are performed at five different redshifts , @xmath2 , 3.6 , 3.4 , 2.95 , and 2.39 , for `` normal '' resolution simulations , and at the first three for `` high '' resolution ones ( 8 times higher mass resolution , twice better force resolution ) . for galaxy k15 we also vary the strength of supernova feedback ( table 1 ) . total particle numbers range from @xmath36 to @xmath37 ; star ( and sph ) particle masses are @xmath38 and @xmath39 @xmath40 , for normal and high resolution simulations , respectively . lccccccc simulation & resolution & feedback & z=3.8 & 3.6 & 3.4 & 2.95 & 2.39 + + k15 - 1 - 8 & normal & @xmath41normal & & 347 & & 1000 & 560 + k15 - 06 - 8 & normal & normal & 431 & 560 & 595 & 1161 & 596 + k15 - 06 - 64 & high & normal & 5061 & 5248 & 6005 & & + + k33 - 06 - 8 & normal & normal & 306 & 340 & 390 & 337 & 144 + k33 - 06 - 64 & high & normal & 2566 & 3122 & 3389 & & + radiative transfer is computed on top of a nested data structure containing 3d distributions of physical variables . to create such a structure from the sph simulation datasets , for each galaxy we cut out a @xmath42 box centered on the galaxy and projected this box onto a @xmath43 uniform grid . we then subdivided every base grid cell which contains more than @xmath44 sph particles , and continued this process of subdivision recursively so that no cell contains more than @xmath45 gas particles . in the ( normal resolution ) galaxy k15 - 1 - 8 at @xmath4 there are 347 stellar sources younger than @xmath46 ( fig . [ three ] ) . the birth times of particles are distributed almost uniformly over the span of @xmath47 , corresponding to a nearly constant star formation rate ( sfr ) of @xmath48 . to compute the stellar uv luminosity function for this and other galaxies , we use a population synthesis package starburst 1999 @xcite with continuous sf at a constant rate @xmath48 distributed among 347 stars . for other galaxies and at other redshifts the sfr per particle is adjusted to account for the actual number of stars produced in the past @xmath47 , and the specific ( per unit spectrum ) luminosity is distributed uniformly among all stars in the volume . we assume a triple - interval kroupa imf with indices ( 0.5,1.2,1.7 ) above the mass boundaries @xmath49 , respectively , a supernova cut - off at @xmath50 , a black hole cut - off @xmath51 , and solar metallicity . the resulting spectrum is shown in the lower right panel of fig . [ three ] . the treesph code assumes the uvb of haardt & madau ( 1996 ) with self - shielding in regions in which the mean free path of lyman - limit photons is less than 1 . in addition to radiative heating and cooling and the hydrodynamical @xmath52 term , some heating originates from shock dissipation which we include in the following way . after we project the 3d hydro fields onto the grids , in each cell we apply the uniform uvb with the self - shielding correction and compute the amount of additional heating needed to keep the temperature of that cell constant ( thermal equilibrium without sources ) . we then switch on the stellar sources retaining the extra heating term , and evolve simultaneously the equations of point source transfer and non - equilibrium chemistry to @xmath53 . with continuous sf and constant uv luminosities , all @xmath1 reach a plateau after the first few . in this paper all results are presented at @xmath54 at which point we assume convergence . direct momentum transfer from uv photons to the interstellar / intergalactic gas is negligible @xcite . however , heating and ionization by stellar photons creates pressure gradients that drive expansion of the hii regions into the surrounding gas . the physics of expansion has been studied in detail in 1d @xcite , 2d @xcite , and recently 3d @xcite radiation hydrodynamics simulations . without coupling rt to the hydro code , we can not model this expansion self - consistently . however , we can mimic its effect by lowering the density in the giant hii region around the starburst region which will ease the escape of uv photons . we use the results from section 3.1 of @xcite which lists the `` initial strmgren radius '' @xmath55 ( 1 myr after the burst ) and the `` final strmgren sphere '' @xmath56 ( 4 myr after the burst ; at this time the uv luminosity declines rapidly ) as a function of the local density and the ionizing source luminosity . for each source we use the initial gas density @xmath57 of the its host cell to find @xmath55 and @xmath56 and then modify the density of each cell inside @xmath56 by @xmath58 , provided that the initial density of that cell @xmath59 . for @xmath60 the expanding shell hits a denser region , and without a full hydrodynamical calculation one can not predict whether this will lead to expansion or compression of the denser region , which explains our condition . therefore , for a given source our density correction is anisotropic which seems entirely realistic for an hii front expansion in an inhomogeneous medium . for such large galaxies , we do not expect our results to change significantly if a fully self - consistent hydro / rt approach is used , as the energetic and momentum effects of ionization fronts are negligible compared to the effects of snii explosions , shocks etc . which are already included into our models , resulting in a very clumpy interstellar medium ( ism ) . however , the radiative feedback would also smooth some of the small - scale structure by raising the jeans mass which is especially important in lower mass galaxies , an effect which we plan to include in our future simulations . fig . [ escapefraction ] shows spectral dependence of @xmath1 at @xmath61 in each model , averaged over all sources . all @xmath1 have been corrected for the boundary of the volume . for individual sources the escape of photoionizing radiation is similar to a phase transition : it is very sensitive to conditions at the source and therefore can vary by a sizable factor for the same galaxy over the course of its evolution . we find that while there are variations among the models , the escape fractions tend to decrease with lower redshift , reflecting the fact that with time more gas cools into the higher density clouds , as well the declining sfr at @xmath62 . with normal feedback in both galaxies @xmath1 at the lyman edge drops from @xmath63 at @xmath2 to @xmath5 at @xmath6 . not surprisingly , in all our models @xmath1 of photons capable of doubly ionizing helium is very low , due to the softness of stellar radiation . the escape fraction of photons capable of single he ionization is comparable at all redshifts to that of h - ionizing photons . increasing sn feedback in k15 evacuates more gas from the vicinity of the sf regions leading to a threefold rise in @xmath1 at @xmath4 . lower local gas densities translate into a @xmath64 reduction in the sfr ( table 1 ) . at @xmath65 , a denser environment near the sources produces a much smaller difference in the sfr and @xmath1 , when we increase the strength of feedback , and , at @xmath6 , @xmath1 actually drops by @xmath66 as a larger fraction of gas swept - up by the shocks stays in the vicinity of the sf regions . next we compare our normal and high resolution results , at @xmath67 , and find a good agreement between the two . we see it as an additional test of our algorithm , since other properties of the two sets of simulations ( sfr , etc . ) also match . since our choice of distributing sf over the @xmath46 youngest stars is somewhat arbitrary , in galaxy k15 - 1 - 8 we also experimented with the same amount of sf distributed over all stars younger than @xmath68 and @xmath69 . ideally , these young stars would produce most of the ionizing uv photons . since we do not calculate transfer and hydro simultaneously , we feel that applying continuous sf with the constant rate is a better computational approach than assuming instantaneous sf which will have no lasting effect on the thermal state of the igm after few myrs . with continuous sf we expect our results to converge as we increase the number of star particles . the results at @xmath68 and @xmath47 are in fact very close to each other at all three redshifts ( fig . [ escapefraction ] ) , whereas the @xmath69 results are somewhat off , likely related to the small number of sources used to represent the sf in this latter case . the dashed lines in k15 - 06 - 8 in fig . [ escapefraction ] show the energy - dependent @xmath1 at @xmath61 corrected for the hii region expansion . at most redshifts expansion raises @xmath1 by @xmath70 , although at @xmath65 @xmath1 jumps by more than a factor of two . further analysis shows that most of this change can be attributed to removal of the gas from the highest refinement level cells which are hosting the sources , not the surrounding cells . in fig . [ radial ] we show how @xmath1 changes with distance from sources in galaxy k15 - 1 - 8 at @xmath4 . a large fraction of photons reaches the radius @xmath71 . as we do not have any reliable information on gas clumping on sub - resolution scales at these redshifts , the effective radius of absorption is not firmly established at this point . in our current models most absorption occurs within few hundreds pc of each star particle , well inside the virial radius of @xmath7245 kpc . at @xmath4 , the proto - galaxy consists of several star forming regions as well as a significant amount of the intergalactic hi , all of which account for some fractional absorption beyond @xmath73 . in this study we neglected the effect of dust extinction . @xcite point out that in the case of a smooth ism attenuation by dust can reduce @xmath1 by a factor of few . for a clumpy ism at high redshifts the magnitude of dust attenuation should be much lower , particularly that most ionizing photons are produced in star bursts , as opposed to a quiescent disk . in conclusion , our models with exact ionizing continuum rt around a large number of sf regions in young protogalaxies show a monotonic decline in @xmath1 of ionizing photons from higher to lower redshifts . with the normal feedback strength @xmath1 at the lyman edge drops from @xmath3 at @xmath4 to @xmath5 at @xmath6 . at higher redshifts sf on average occurs at slightly lower densities resulting in easier escape of uv photons into the igm . this result agrees well with the observational findings of @xcite on redshift evolution of @xmath1 . note that although the two galaxies in our study have a mass ratio of @xmath74 , their @xmath1 are very similar . one could suggest that perhaps , once star formation begins , it is the physical conditions in the clumpy gas clouds that determine the escape of uv photons , rather than the overall properties of their host galaxies . however , one would need a much larger statistical sample to test this speculation . in our next paper we will further examine the role of the fine structure of the clumpy ism in the escape of ionizing photons , as well as the importance of hydrodynamical effects . ar would like to thank mika juvela and eric lentz for valuable discussions on numerical methods , as well as the hospitality of the dark cosmology centre at the university of copenhagen . the treesph simulations were performed on the sgi itanium ii facility provided by dcsc . the dark cosmology centre is funded by the dnrf . , i. t. , ciardi , b. , alvarez , m. a. , maselli , a. , ferrara , a. , gnedin , n. y. , mellema , g. , nakamoto , t. , norman , m. l. , razoumov , a. o. , rijkhorst , e .- j . , ritzerveld , j. , shapiro , p. r. , susa , h. , umemura , m. , & whalen , d. j. 2006 , mnras , 873

using results from high - resolution galaxy formation simulations in a standard @xmath0cdm cosmology and a fully conservative multi - resolution radiative transfer code around point sources , we compute the energy - dependent escape fraction @xmath1 of ionizing photons from a large number of star forming regions in two galaxies at five different redshifts from @xmath2 to 2.39 . all escape fractions show a monotonic decline with time , from ( at the lyman - limit ) @xmath3 at @xmath4 to @xmath5 at @xmath6 , due to higher gas clumping at lower redshifts . it appears that increased feedback can lead to higher @xmath1 at @xmath7 via evacuation of gas from the vicinity of star forming regions and to lower @xmath1 at @xmath8 through accumulation of swept - up shells in denser environments . our results agree well with the observational findings of @xcite on redshift evolution of @xmath1 in the redshift interval @xmath9 .

I’m not sure if this has already been brought to everyone’s attention or not, but here is the deal: http://www.youtube.com/watch?v=l93wAqnPQwk&feature=player_embedded Above is a video of a 68-year-old bus monitor named Karen Klein being verbally harassed by a group of middle schoolers on their way home from Athena Middle School in Greece, New York. Throughout the ten minute video, you can hear the kids verbally berate the woman, calling her a bitch, fatass, poor, ugly, and various other words of the like. At one point in the video, you can hear one of the kids yell, “You’re so fuckin poor you fat ass,” in which Karen responds, “I try to live by some of these words, I try and it’s really hard,” referring to the words on her purse. Now, I don’t know about you, but that broke my heart. There’s even a point in the video where one of the kids touches Karen’s arm in an attempt to make fun of her. I’m not sure why these kids would want to bully a senior citizen to tears, but I feel we should do something, or at least try. She doesn't earn nearly enough ($15,506) to deal with some of the trash she is surrounded by. Lets give her something she will never forget, a vacation of a lifetime! Link to the school’s website: http://www.greece.k12.ny.us/athena-middle.cfm Bus number: #784 School’s fax number: (585) 966-4039 Staff E-mails & Other Links: http://www.greece.k12.ny.us/staff_directory.cfm http://www.greece.k12.ny.us/contact.cfm?school=7 https://maps.google.com/maps?q=Greeced=0CGoQ_AUoAg http://pastebin.com/mMvJ4ZP8 Links to the videos: http://www.youtube.com/watch?v=oipwaZos58E&feature=plcp http://www.youtube.com/watch?v=l93wAqnPQwk&feature=plcp http://www.youtube.com/watch?v=SBedTlo7BDs&feature=plcp Karen’s Facebook: https://www.facebook.com/kklein1944 ************ UPDATE 11:00 am est 6/21: This is Amanda (tammbg below). I am Karen's daughter and I just joined this campaign. I have spoken with Max and with Indiegogo and we just want to thank you so much for your support. I am at work now so can't put a picture up yet. We are completely overwhelmed with all the support, so thank you. ************* ||||| I’m not sure if this has already been brought to everyone’s attention or not, but here is the deal: http://www.youtube.com/watch?v=l93wAqnPQwk&feature=player_embedded Above is a video of a 68-year-old bus monitor named Karen Klein being verbally harassed by a group of middle schoolers on their way home from Athena Middle School in Greece, New York. Throughout the ten minute video, you can hear the kids verbally berate the woman, calling her a bitch, fatass, poor, ugly, and various other words of the like. At one point in the video, you can hear one of the kids yell, “You’re so fuckin poor you fat ass,” in which Karen responds, “I try to live by some of these words, I try and it’s really hard,” referring to the words on her purse. Now, I don’t know about you, but that broke my heart. There’s even a point in the video where one of the kids touches Karen’s arm in an attempt to make fun of her. I’m not sure why these kids would want to bully a senior citizen to tears, but I feel we should do something, or at least try. She doesn't earn nearly enough ($15,506) to deal with some of the trash she is surrounded by. Lets give her something she will never forget, a vacation of a lifetime! Link to the school’s website: http://www.greece.k12.ny.us/athena-middle.cfm Bus number: #784 School’s fax number: (585) 966-4039 Staff E-mails & Other Links: http://www.greece.k12.ny.us/staff_directory.cfm http://www.greece.k12.ny.us/contact.cfm?school=7 https://maps.google.com/maps?q=Greeced=0CGoQ_AUoAg http://pastebin.com/mMvJ4ZP8 Links to the videos: http://www.youtube.com/watch?v=oipwaZos58E&feature=plcp http://www.youtube.com/watch?v=l93wAqnPQwk&feature=plcp http://www.youtube.com/watch?v=SBedTlo7BDs&feature=plcp Karen’s Facebook: https://www.facebook.com/kklein1944 ************ UPDATE 11:00 am est 6/21: This is Amanda (tammbg below). I am Karen's daughter and I just joined this campaign. I have spoken with Max and with Indiegogo and we just want to thank you so much for your support. I am at work now so can't put a picture up yet. We are completely overwhelmed with all the support, so thank you. *************

– She may officially be $500,000 richer, but bullied school bus monitor Karen Klein is unimpressed with the apologies she's gotten so far from the foul-mouthed kids caught bullying her in a now-infamous video. "Of course he's going to say anything," Klein said of one apology to Anderson Cooper at CNN. "Josh, he always has a smirk on his face ... I don't think I would believe anything Josh has to say and I didn't want to talk to him today." While Klein said she "doesn't think" she'll press charges, she does want to see the kids involved punished. "I would like them to be kept off the bus for at least a year and forbidden to play any sports at least for a year. Someone mentioned community service and I thought that was a pretty good idea, too." Meanwhile, the indiegogo campaign to raise $5,000 to send Klein on vacation continues to surge, rocketing from $260,000 yesterday past the half-a-million mark (and growing and growing) today. "I still can't believe it," Klein said of the the support. And at the end of the CNN interview, Cooper told Klein that Southwest Airlines has offered to send her and nine others to Disney World in Florida for three nights. "Wow, that's too much," she said, amazed. "I don't feel like I've done anything, you know?"

FILE - In this Friday, Feb. 3, 2006 file photo, Italian Premier Silvio Berlusconi attends an Italian Republican party program conference in Rome. Pressure mounted on Premier Silvio Berlusconi to resign... (Associated Press) Italian Premier Silvio Berlusconi has won a much-watched vote in Parliament but it shows he can no longer count on an overall majority in the Chamber of Deputies. In parliament, 308 voted in favor, 321 abstained and no one voted against. The opposition immediately demanded that Berlusconi resign to calm financial markets, although he has always refused those calls. THIS IS A BREAKING NEWS UPDATE. Check back soon for further information. AP's earlier story is below. ROME (AP) _ Premier Silvio Berlusconi geared up for one of the most critical votes of his long political career Tuesday, as his main ally urged him to resign and Italy's political uncertainty rocked financial markets for yet another day. Berlusconi did not immediately respond to the demand, but he has repeatedly resisted all calls for his resignation before his term ends in 2013. Berlusconi's government is under intense pressure to enact quick reforms to shore up Italy's defenses against Europe's raging debt crisis. However, a weak coalition and doubts over Berlusconi's leadership have ignited market fears of a looming Italian financial disaster that could bring down the 17-nation eurozone and shock the global economy. "We asked him to step aside, take a step to the side," Northern League leader Umberto Bossi told reporters ahead of a key vote in Parliament that could force Berlusconi's resignation. Bossi is the volatile ally who also brought down Berlusconi's first conservative government in 1994. On the face of it, Tuesday's vote is just a routine measure to approve 2010 state finances, but it has now become a test of Berlusconi's political strength. Italy's center-left opposition said it would abstain in Tuesday's voting, to make it clear just how fragile Berlusconi's forces in Parliament are. If he is backed by fewer than 316 deputies _ or less than half of the 630-member chamber _ it would show the prime minister can no longer count on a majority in the lower house of Parliament, even though the government could still mathematically win the vote. Bossi said the man Berlusconi has already picked as his successor, former Justice Minister Angelino Alfano, should now lead the government. But it would be up to the Italian president, Giorgio Napolitano, to decide whether to appoint a new leader or dissolve parliament and call early elections. He would likely sound out political leaders before deciding. Added Bossi: "Today, nothing will happen." Italy is the eurozone's third-largest economy, with debts of around euro1.9 trillion ($2.6 trillion). Representing 17 percent of the eurozone's gross domestic product, it is considered too big for Europe to bail out like the continent already has done for Greece, Portugal and Ireland. Even worse, a substantial part of Italy's debt needs to be rolled over in the next few years _ the nation needs to raise euro300 billion ($412 billion) in 2012 alone _ just as interest rates for it to borrow have been soaring. Italy's borrowing rates spiked Tuesday to their highest level since the euro was established in 1999. By mid-afternoon, the yield on Italy's ten-year bonds was up 0.08 percentage point at 6.62 percent, down from an earlier high of 6.74 percent. A rate of over 7 percent is considered unsustainable and proved to be the trigger point that forced the other three eurozone nations into accepting financial bailouts. Even the business leaders who once enthusiastically backed the media mogul's leadership have been upset for months, saying Berlusconi's government has failed to revive Italy's stalled economy. "(Italy) cannot go forward" with the soaring spread. "The country cannot stay in these conditions," said Emma Marcegaglia, who leads a politically influential Italian business lobby. The opposition center-left has long demanded the 75-year-old leader's resignation, citing sex scandals, criminal prosecutions and legislative priorities it says are aimed at protecting his own business interests rather than those of the country. However, it has failed to come up with a leader who can unite the opposition. Berlusconi appeared to be frantically trying to line up vote after vote, with at least two party dissenters visiting his Rome residence Tuesday as parliament resumed debate ahead of the vote. One, lawmaker Isabella Bertolini, told reporters upon leaving she would vote in favor of the government. She said Berlusconi had laid out for her "all the possibilities and options that he's evaluating: Stay, step back, step aside." Finance Minister Giulio Tremonti hurriedly left a eurozone finance ministers meeting in Brussels to get back to Rome for the vote. But at least one deputy from Berlusconi's People of Freedom Party won't be there. Lawmaker Alfonso Papa, who is being investigated in a corruption scandal, is under house arrest. If he gets through Tuesday's hurdle, Berlusconi has indicated next week's vote on the austerity measures would be a confidence vote. If it loses that, he would have to resign. Antonio Di Pietro, a leader of a small center-left opposition party, told Sky TG24 TV that Berlusconi's "political adventure has been over for a while now." However, he doubted that Berlusconi would voluntarily leave. One of Berlusconi's closest allies, lawmaker Francesco Cicchitto, told reporters that coalition leaders will take stock immediately after the vote. "One thing at a time. First the vote, let's let it happen. Then we'll reflect," he said. International financial officials and the markets, meanwhile, fretted over how long it was going to take for Italian lawmakers to approve measures promised weeks ago by Berlusconi to rein in Italy's galloping public debt. "I'm not making any judgment on Mr. Berlusconi personally. But I think there is a problem of confidence," French Foreign Minister Alain Juppe told French radio RTL. During a G-20 summit last week, Berlusconi had to take the humiliating step of asking the International Monetary Fund to monitor the country's reform efforts. On Wednesday, a separate European Union monitoring mission is to begin work in Rome to review financial reforms taken so far. ___ Barry contributed from Milan. Angela Charlton reported from Paris. ||||| Dow Jones Reprints: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues, clients or customers, use the Order Reprints tool at the bottom of any article or visit www.djreprints.com ROME—Italian Prime Minister Silvio Berlusconi pledged to step down after Parliament approves austerity measures, as the euro-zone's third-largest economy tried to stave off the nightmare scenario of a bailout that would test the currency union. The promise to resign, which came after Mr. Berlusconi lost his parliamentary majority during a routine vote on budget matters, makes Italy's controversial leader—the nation's dominant political figure for nearly two decades—one of the highest-profile casualties of the financial crisis that has been ripping through Europe for the better part of two years. A growing investor exodus from Italian bonds, spurred by the political crises ...

– Silvio Berlusconi was holding on for dear life in advance of today's critical budget vote, and now it looks as if he's hanging by a quickly fraying thread. The Italian PM won the much-watched vote in Parliament, but lost his majority. He won just 308 of 630 possible votes; 321 abstained, and no one voted against, reports the AP. The opposition then immediately called for Berlusconi's resignation, and pressed him to start talks with President Giorgio Napolitano about a new government, reports the Wall Street Journal.

On July 7th, fire chief Chris Kocher at the Worland, Wyoming volunteer fire department received a phone call alerting him of a “blue glow” in a rural area off Highway 20 North. As soon as he arrived onsite and looked at the blazing area through binoculars, “I saw we had a sulfur fire,” Kocher tells The Verge. The fire looked like a carpet of sparkling blue blaze. In a video posted by the fire department on Facebook — which has been viewed almost 2 million times — you can see flames moving quickly across the surface, sometimes raising up into the air. It’s mesmerizingly beautiful — and also really dangerous. If you breathe the smoke, it can harm your lungs and even kill you. like a carpet of sparkling blue blaze When sulfur burns, it produces sulfur dioxide, a harmful gas that forms sulfurous acid when it comes in contact with water, including the moisture in your lungs. Sulfurous acid is related to acid rain, which can kill trees and fish. To keep safe, the firefighters at the scene were wearing a self-contained breathing apparatus, which is why in the video you can hear a Darth Vader-ish breathing noise (as The Washington Post points out). Putting down a sulfur fire isn’t the same as dealing with a regular fire: in fact, the crew used only a small amount of water from the fire truck plus firefighting foam. That way, the temperature of the sulfur could be cooled down below 309 degrees Fahrenheit — when it’s in a molten stage — so that a crust formed at the surface. “And then the fire’s out,” Kocher says. The whole thing took about 20 minutes. accidentally ignited by the exhaust of a motorcycle The sulfur mound is leftover from the Texas Gulf Sulfur Plant, which operated north of Worland in the 1950s. The sulfur is mixed heavily with soil, the Facebook post says. It’s not 100 percent sulfur concentrate, but it’s still highly flammable. The 10,000-square-foot area that went ablaze Friday night was accidentally ignited by the exhaust of a motorcycle, Kocher says. The area hadn’t seen a sulfur fire in about 12 years, but the crew was prepared because there are a lot of oil fields around Worland, so the firefighters know how to deal with sulfur dioxide. As for the viral video, Kocher says he was surprised to see all the media attention. You don’t see a bluish blazing field every day, and that’s probably what got people hooked. “It’s interesting to see how far the video has traveled,” he says. ||||| WORLAND, Wyo. (AP) — If you ever wondered what a burning pile of sulfur looks like, the answer is like a UFO crash site or maybe a scene on another planet. Firefighters in Worland, Wyoming, say it wasn't a UFO but the hot exhaust of an off-road motorcycle that ignited an old pile of sulfur Friday night. As seen in this video , the sulfur burned with bizarre effects: A blue carpet of flame topped by twisting orange columns of fire. The fire gave off sulfur dioxide gas and firefighters wore breathing equipment to stay safe. It happened at the former site of a sulfur plant. Worland Volunteer Fire Department Chief Chris Kocher says nobody was hurt or cited for causing the fire. Kocher says crews got the fire under control within 20 minutes.

– It's not often you hear firefighters describe a blaze as "beautiful," but that's exactly what happened following a fire in Worland, Wyo. In a Facebook post accompanying a video that has since gone viral, the Worland Volunteer Fire Department explains it was called to "an unknown type of fire" on Friday and was met with stunning blue and orange flames. But though beautiful, the blaze covering a 10,000-square-foot area resembling "a UFO crash site" was also highly dangerous, per the AP: A sulfur mound left over from a former sulfur plant had been ignited by the exhaust of a motorcycle, sending sulfur dioxide into the air. While water is usually a firefighter's primary line of defense, water combined with sulfur dioxide creates sulfurous acid. Fortunately, "the fire was burning in a 'bowl'-shaped area, allowing all runoff to be collected in the fire area. A minimal amount of water was used to cool the surface of the sulfur and reduce the temperature below the molten stage," the department says. A crust then formed on the surface of the sulfur, extinguishing the fire, reports the Verge. Firefighters, equipped with special breathing equipment, had the blaze under control in just 20 minutes. The fire chief adds no one was injured.

according to the previous publications , acute ischemic stroke ( ais ) could be mentioned as the most reason of events related to death and disability . in fact , acute focal cerebral ischemia and sequential dynamism disaster are convoyed by neuronal death in the parts of brain that cerebral blood flow was reduced . due to rising in the world 's prevalence and incidence of stroke , its global importance is increasing extremely . up - to - date epidemiological studies specified that 16.9 million people suffer from stroke each year , which indicates a global incidence of 258/100,000 in each year . however , the number of survivors almost doubled among 1990 and 2010 , but there are 5.9 million stroke - associated decreases globally each year . death related to stroke excessively affects blacks , and this inequality is established across all categories of stroke . poststroke complications include motor handicaps , dementia , depression , fatigue , and a high risk of early rehospitalization . the serine protease , tissue plasminogen activator ( tpa ) , as a key enzyme related to fibrinolytic pathway , is involved in disruption of blood clots . recombinant tpa ( rtpa ) is a form of tpa that is manufactured by the recombinant biotechnology methods . to achieve reperfusion , intravenous - rtpa ( iv - rtpa ) is given to the patients to cut the zymogen plasminogen peptide bond into the serine protease plasmin . in addition , tpa plays a role in cell migration and tissue remodeling . hyper- and hypo - fibrinolysis could be caused by increased or decreased activity which can result in excessive bleeding , thrombosis , or embolism . even though the prescription of tpa for ais has been increased in the current years regarding the accurate time for understanding iv - rtpa prescription , the precise records of the last known normal time are vital to confirm an optimum management for stroke patients . although publication in 2012 stated that iv - rtpa given within 6 h of stroke onset , another publication in 2013 recommended valuable early administration within 03 h , destructive later prescription of 34.5 h , and again beneficial of administration of 4.56 h. recent approaches mentioned that iv - rtpa therapy could be administered to cautiously nominated patients who can be treated within 4.5 h of ais onset . related to the populations that neurologic signs are revealed on awakening ( wake - up stroke ) , they usually are not given iv - rtpa because of the doubt about the time of stroke onset . previous studies have shown that iv - rtpa dosed at 0.9 mg / kg with a maximum of 90 mg seems to be safe and effective . because of the racial variances in blood coagulation - fibrinolysis features , asian patients might need lower dosage of drug . the current international guidelines by the american stroke association have established that iv - rtpa should only be given within 4.5 h of stroke onset , and door to needle time should be < 60 min , with a goal of 40 min . because of time - restriction - injection for iv - rtpa , up to now , there is not any proper guideline associated to the barriers in the iv - rtpa pharmacotherapy approach within the iranian population of patients with acute ischemic cerebral infarction . therefore , the aim of this study was to identify the barriers related to the use of iv - rtpa in such population . between 2014 and 2015 , patients with definitive diagnosis of acute cerebral infarction who attended the neurology ward located at the isfahan alzahra hospital ( n = 180 ) were studied . the investigation was approved by the research committee of isfahan university of medical sciences ( grant no of 393522 ) . approach for injection criteria was based on the international guidelines of stroke inclusion / exclusion criteria for injection of iv - rtpa . the barriers related to door to iv - rtpa needle time were noted into checklist that was divided into three parts . the first part was included age , sex , date of admission , and literacy for reading and writing . the second part was involved as prehospital information such as onset of symptoms , transfer to hospital ( private car / ambulance ) , arrival time , and the causes of delay to hospital ( unavailability of vehicles , ignorance of the symptoms , lack of correct diagnosis , far from hospital , and living alone ) . the third part was comprised stroke inclusion / exclusion criteria . [ flowchart 1 ] shows the barriers for iv - rtpa door to needle time taken for each individual patient that was filled by questioner . door to tpa needle time all statistical analyses were attempted using the spss statistical software package ( version 23.0 ; ibm , armonk , ny , usa ) . as shown in figure 1 , with a mean of 60 years , the minimum and maximum age of females was 29 and 70 years , respectively . age - related stroke in 75% of females was before the age of 70 , in which 31.4% of females ranged from 30 to 60 years . distribution of age - related stroke in females the mean age of males was 77.5 years ( ranged from 23 to 93 years ) . age - related stroke in 81% of males ranged from 70 to 90 years [ figure 2 ] . table 1 shows the frequency of patients with cerebrovascular accident ( cva ) , associated to the eligibility for intravenous tpa ( iv - tpa ) injection . related to transferring to hospital , 89.3% of patients were not transferred in proper time . distribution of age - related stroke in males distribution of patients eligibility for intravenous tissue plasminogen activator injection regarding eligibility for iv - tpa , 68.9% of total population has had criteria for such treatment . concerning to both items such as transferring to hospital in < 4.5 h after the onset of symptoms and eligibility for iv - tpa , only 6.6% of total population met the criteria for such management [ figure 3 ] . distribution of reasons for delay from prehospital to hospital table 2 shows distribution of inclusion / exclusion criteria items for iv - tpa injection . there was no evidence related to progressing or worsening of stroke symptoms in 92.2% ( n = 166 ) . related to other neurological deficit , 179 patients did not show any related signs or symptoms . in the beginning of cva symptoms onset , 22 out of 180 or 12.2% of patients presented seizures . there was history of intracranial hemorrhage , brain aneurysm , vascular malformation , brain tumor , and brain hemorrhage in 7.8% of patients . there was no sign or symptom related to subarachnoid hemorrhage in 179 patients ( 99.9% ) . only in 4 patients , 2.2% blood glucose was < 50 or more than 400 ( mg / dl ) . prothrombin time of > 15 or internal normalized ratio of prothrombin time of > 1.5 was noted in 22 of 180 patients ( 12.2% ) . the previous surgery or blood pressure of 185/10 mmhg was reported in 0.6% and 22% , respectively [ figure 4 ] . frequently distribution of inclusion / exclusion criteria items for iv - tpa injection co - incidents of reasons of delay from prehospital to hospital table 3 shows the mean of door to needle tpa the mean time associated to patients entry into hospital until to be visited by neurologist was with a mean of 195.92 6.65 min ( 182.8209.04 min ) . time taken for visiting by screen practitioner and emergency was 24.6 2 min ( 20.728.5 min ) . procedure related to computed tomography scan , clinical laboratory , and emergency visit was associated to the mean duration of 46.32 2.39 min ( 41.5951.06 min ) . figure 3 shows distribution of reasons for delay from prehospital to hospital . out of total population , there was lack of availability to car for transferring patients to hospital in 62 patients . there was difficulty related to long distance from patients home to hospital in 48 patients . there was a lack of information linked to emergency services and lack of familiarity with the service of 115 in 2 and 18 patients , respectively . there were reasons of delay due to ignorance or inattention to stroke symptoms because of literacy in 75% of patients population studied . mean of door to iv - tpa injection time taken for population studied ( n=180 ) the result of this study confirmed a minimum age of around 25 years of life for the event of stroke ( classified as acute ischemic cerebral infarction ) in both genders . this is in agreement with previous publications , in which noted that changes in ( 1 ) endothelial function , ( 2 ) alterations in the blood brain barrier , or ( 3 ) hormonal changes could be considered for such patients with young age - related stroke . linked to clinical care for patients with acute ischemic cerebral infarction , pharmacotherapy management , and device - induced reperfusion has established as optimistic management related to the both reperfusion effectiveness and 3 months functional results after ais . actually , iv - tpa was first approved in the united states in 1996 and shown to have a positive impact related to clinical outcome in recent years . in 2012 , the stroke academic industry roundtable suggested beneficial assessment of ( 1 ) neuroprotective agents , ( 2 ) iv - tpa , and ( 3 ) emerging treatments to decrease reperfusion damage . henninger and fisher reported that < 10% of all patients with ais receive intravenous thrombolysis and it has been expected that only around 7%15% of ais patients are qualified for acute endovascular intervention . investigation of barriers related to the use of iv - tpa in the treatment of patients with cva , from prehospital to hospital , showed inattention of patients to their symptoms at the time of symptoms onset , in which the reason in 30% was due to living lonely . unavailability for a car to transform patients to a proper hospital was noted in 30% . publication in 2015 confirmed that iv - tpa therapy could be prescribed to carefully selected patients and those could be administered within 4.5 h of ais onset . associated to populations that neurologic signs are exposed upon wake - up stroke typically , because of the uncertainty about the time of stroke onset , iv - rtpa should not be prescribed . there was a mean falling time of 3.3 h within hospital ( 95% confidence interval of 3.03.5 h ) . a previous publication by spokoyny et al . , in 2015 , highlighted the necessity for informative package associated to the determination and modification of the certain time of stroke onset , particularly at hospital without stroke expertise . finally , however , this study revealed barriers for door to iv - tpa injection , but its limitation could be mentioned as the lack of stroke data registry to generate standard model that could be adjustable to isfahan / iran health - care system . due to the ignorance of symptoms in 75% of patients , educative programs in television or other communicative media , by neurologist in terms of explaining stroke symptoms and its disaster disability consequences , should be more considered . it is also important for healthcare staff to understand the importance of protocol guidelines toward iv - tpa prescription in proper time . this study was supported by isfahan university of medical sciences ( grant no , 393522 ) . this study was supported by isfahan university of medical sciences ( grant no , 393522 ) . fkh contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work.fh contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work.ms contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work.ac contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work.zt contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work . fkh contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work . fh contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work . ms contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work . ac contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work . zt contributed to the conception of the work , conducting the study and revising the draft , approval of the final version of the manuscript and agreed for all aspects of the work .

background : according to previous publications , in patients with acute ischemic cerebral infarction , thrombolytic therapy using intravenous tissue plasminogen activator ( iv - tpa ) necessitates precise documentation of symptoms onset . the aim of this study was to identify major barriers related to the iv - tpa injection in such patients.materials and methods : between the year 2014 - 2015 , patients with definitive diagnosis of acute cerebral infarction ( n = 180 ) who attended the neurology ward located at the isfahan alzahra hospital were studied . to investigate barriers related to door to iv - tpa needle time , personal reasons , and criteria for inclusion or exclusion of patients , three questionnaire forms were designed based on the food and drug administration - approved indications or contraindications.results:the mean age of males versus females was 60 versus 77.5 years ( ranged 2393 vs. 2970 years ) , respectively . out of total population , only 10.7% transferred to hospital in < 4.5 h after the onset of symptoms . regarding to eligibility for iv - tpa , 68.9% of total population have had criteria for such treatment . concerning to both items such as transferring to hospital in < 4.5 h after the onset of symptoms and eligibility for iv - tpa , only 6.6% of total population met the criteria for such management . there was ignorance or inattention to symptoms in 75% of population studied . there was a mean of 195.92 6.65 min ( 182.8209.04 min ) for door to iv - tpa needle time.conclusion:despite the international guidelines for iv - tpa injection within 34.5 h of ischemic stroke symptoms onset , the results of this study revealed that falling time due to ignorance of symptoms , literacy , and living alone might need further attention . as a result , to decrease death and disability , educational programs related to the symptoms onset by consultant neurologist in isfahan / iran seem to be advantageous .

recently there has been significant effort directed towards understanding the wave dynamics in photonic lattices arranged in a honeycomb structure cf . @xcite . due to the extra symmetry of the honeycomb lattice , dirac points , or conical intersections between dispersion bands , exist . this is similar to what occurs in carbon - based graphene @xcite where the existence of dirac points is a key reason for many of its exceptional properties . because of the correspondence with carbon - based graphene , the optical analogue is often termed ` photonic graphene ' . in lattices without edges the wave dynamics exhibit conical , elliptic , and straight line diffraction cf . @xcite . however when edges and a ` pseudo - field ' are present , remarkable changes occur and long lived , persistent linear and nonlinear traveling edge waves with little backscatter appear . these localized waves exhibit the hallmarks of topologically protected states , thus indicating photonic graphene is a topological insulator @xcite . substantial attention has been paid to the understanding of edge modes in both condensed matter physics and optics . interest in such modes goes back to the first studies of the quantum hall effect ( qhe ) where it was found that the edge current was quantized @xcite . investigations related to the existence of edge states and the geometry of eigenspaces of schrdinger operators has also led to considerable interesting research @xcite . support for the possible existence of linear unidirectional modes in optical honeycomb lattices was provided in @xcite . these unidirectional modes were found to be related to symmetry breaking perturbations which separated the dirac points in the dispersion surface . the modes are a consequence of a nontrivial integer topological " charge associated with the separated bands . unidirectional electromagnetic edge modes were first found experimentally in the microwave regime @xcite . these modes were found on a square lattice which have no associated dirac points . recently though , for photonic graphene , it was shown in @xcite that by introducing edges and spatially varying waveguides that unidirectional edge wave propagation at optical frequencies occurs . the waveguides play the role of a pseudo - magnetic field , and in certain parameter regimes , the edge waves are found to be nearly immune to backscattering . the pseudo - magnetic fields used in the experiments @xcite are created by periodic changes in the index of refraction of the waveguides in the direction of propagation . the variation in the index of refraction has a well defined helicity and thus breaks ` time'-reversal symmetry ; here the direction of the wave propagation plays the role of time . the analytical description begins with the lattice nonlinear schrdinger ( nls ) equation @xcite with cubic kerr contribution @xmath0 where @xmath1 is the input wavenumber , @xmath2 is the ambient refractive index , @xmath3 , referred to as the potential , is the linear index change relative to @xmath2 , and @xmath4 represents the nonlinear index contribution . the scalar field @xmath5 is the complex envelope of the electric field , @xmath6 is the direction of propagation and takes on the role of time , @xmath7 is the transverse plane , and @xmath8 . below , in section [ sec : length - scale ] , concrete values are given for the parameters in eq . ( [ lnlsd ] ) . @xmath9 is taken to be a 2d lattice potential in the @xmath7-plane which has a prescribed path in the @xmath6-direction . this path is characterized by a function @xmath10 , such that after the coordinate transformation @xmath11 the transformed potential @xmath12 is independent of @xmath13 . experimentally , the path represented by @xmath14 can be written into the optical material ( fused silica ) @xcite via the femtosecond laser writing technique @xcite . since this technique enables waveguides to be written along general paths , we only require @xmath14 to be a smooth function . introducing a transformed field @xmath15,\ ] ] where @xmath16 is induced by the path function @xmath17 via the formula @xmath18 eq . is transformed to @xmath19 in eq . ( [ mlnlsd ] ) , @xmath16 appears in the same way as if one had added a magnetic field to eq . ; hence * a * is referred to as a pseudo - magnetic field . taking @xmath20 to be a typical lattice scale size , employing the dimensionless coordinates @xmath21 , @xmath22 , @xmath23 , @xmath24 , where @xmath25 is input peak power , defining @xmath26 with @xmath27 , rescaling @xmath16 accordingly , and dropping the primes , we get the following normalized lattice nls equation @xmath28 the potential @xmath29 is taken to be of honeycomb ( hc ) type . the dimensionless coefficient @xmath30 is the strength of the nonlinear change in the index of refraction . we also note that after dropping primes , the dimensionless variables @xmath31 are used ; these dimensionless variables should not be confused with the dimensional variables in eq . ( [ lnlsd ] ) . in contrast to @xcite , which in turn was motivated by the experiments in @xcite , this paper examines the case of periodic pseudo - fields which vary adiabatically , or slowly , throughout the photonic graphene lattice . we develop an asymptotic theory which leads to explicit formulas for isolated curves in the dispersion relation describing how the structure of edge modes depends on a given pseudo - field @xmath32 . therefore , we can theoretically predict for general pseudo - fields when unidirectional traveling waves exist and the speed with which they propagate . to exemplify the different classes of dispersion relations allowed in our problem , we take the pseudo - magnetic field to be the following function ( `` lissajous '' curves ) @xmath33 where @xmath34 , @xmath35 , @xmath36 , @xmath37 , @xmath38 , and @xmath39 are constant . below we will consider two cases in detail . in the first case we choose @xmath40 , @xmath41 , @xmath42 , and @xmath43 . this corresponds to the pseudo - field employed in @xcite , and in most parts of this paper . in this case the above function becomes a perfect circle given by @xmath44 where @xmath34 and @xmath36 are constant . in the second case we choose @xmath45 , @xmath41 , @xmath42 , and @xmath46 . in this case the above lissajous curve becomes a figure-8 curve given by @xmath47 where @xmath34 and @xmath36 are constant . for these classes of pseudo - fields , the numerically computed dispersion relations and the asymptotic prediction of the isolated curves agree very well . however the dispersion relations also exhibit sensitive behavior in which small gaps in the spectrum appear when the small parameter @xmath48 characterizing the slow evolution increases in size . further , we find that when edge modes exist there are two important cases . the first is the case where pure edge modes exist in the entire periodic interval . the second case is where quasi - edge modes persist only for part of the period . quasi - edge modes do not exist in the rapidly varying case studied in @xcite , and so we have shown adiabatic variation of the pseudo - field allows for new dynamics even at the linear level . we also present potential scaling regimes where these cases might be observed experimentally ; see section [ sec : length - scale ] . we are also able to analyze the effect of nonlinearity on these slowly varying traveling edge modes . a nonconstant coefficient ( ` time'-dependent ) one - dimensional nonlinear schrdinger ( nls ) equation governing the envelope of the edge modes is derived and is found to be an effective description of nonlinear traveling edge modes . in the rapidly varying case @xcite , the associated nls equation had constant coefficients , and so we see adiabatic variation introduces new dynamics into the nonlinear evolution of edge modes . using this new nls equation , in the focusing case , we find analytically , and confirm numerically , that unidirectionally propagating edge solitons are present in nonlinear photonic graphene lattices . computation of the nls equation is compared with direct simulation of the coupled discrete tight binding model with very good agreement obtained . as with the traditional , constant coefficient , focusing nls equation , nonlinearity balances dispersion to produce nonlinear edge solitons . depending on the choice of parameters , some of the nonlinear modes appear to be immune to backscattering and can propagate for long distances . we emphasize that these length scales are far beyond what might be expected from the scales defining the asymptotic theory . given this persistence , we argue that such cases are nonlinear analogues of topologically protected states in topological insulators . prior to the derivation of the ` time ' varying nls equation in this paper , and the constant coefficient version in @xcite , topological insulators have only been defined for linear systems . the results in this and previous papers show that nonlinear photonic graphene can also be thought of as a topological insulator . time - dependent nls equations also arise when dispersion varies along the propagation direction in an optical fiber @xcite , i.e. the case studied here would be an analogue of ` slow ' dispersion management . therefore , the results of this paper show that nonlinear , adiabatically varying photonic graphene lattices could provide useful new means for the control of light . this control results from the merging of nonlinear and symmetry - breaking effects . see also @xcite , where bulk nonlinear modes in photonic graphene have been found . further , the topologically protected nonlinear states " found here can potentially apply to other systems , recently introduced one dimensional domain walls @xcite . to begin the analysis , the substitution @xmath49 in @xmath50 gives @xmath51 the tight binding approximation for large @xmath52 assumes a bloch wave envelope of the form @xcite @xmath53 where @xmath54 , @xmath55 are the linearly independent orbitals associated with the two sites a and b where the honeycomb potential @xmath29 has minima in each fundamental cell , and @xmath56 is a vector in the brillouin zone . each @xmath57 , where the period vectors @xmath58 and @xmath59 are given by @xmath60 substituting the tight binding approximation ( [ eq : tb - ansatz ] ) into eq . ( [ eq:2d - nls - new ] ) , carrying out the requisite calculations ( see @xcite for more details ) , and after dropping small terms and renormalizing , we arrive at the following two dimensional discrete system @xmath61 where @xmath62 @xmath63 is the vector distance between the initial @xmath64 and @xmath65 sites ( see @xcite ) , @xmath66 is a lattice deformation parameter , @xmath67 , @xmath68 , and @xmath69 is a constant which depends on @xmath70 and the underlying orbitals . taking a discrete fourier transform in @xmath71 , i.e. letting @xmath72 and @xmath73 , yields the simplified system @xmath74 where @xmath75 @xmath76 and @xmath77 since @xmath78 , if @xmath79 is a solution of eqs . ( [ eq : abn - ori - a][eq : abn - ori - b ] ) at any given @xmath80 , then @xmath81 is a solution of eqs . ( [ eq : abn - ori - a][eq : abn - ori - b ] ) at @xmath82 . therefore , in the following @xmath80 is taken to be defined on a periodic interval of length @xmath83 . the value of @xmath56 is be taken to be zero ; we assume that @xmath32 has zero mean ( see @xcite ) . to analyze the equations ( [ eq : abn - ori - a]-[eq : abn - ori - b ] ) we will work on a zig - zag edge , which in the semi - infinite case means letting @xmath84 . we further assume that the pseudo - field @xmath16 evolves adiabatically , i.e. we take @xmath85 and @xmath86 . our goal is to find slowly evolving and decaying modes as @xmath87 . it is convenient to employ a multiple - scales ansatz @xmath88 where @xmath89 . from eq . ( [ eq : abn - ori - a]-[eq : abn - ori - b ] ) the basic perturbation equations are given by @xmath90 where @xmath91 . then expanding @xmath92 in powers of @xmath48 @xmath93 we have at leading order @xmath94 which has the following edge solution @xcite @xmath95 where @xmath96 with @xmath97 . this generalizes @xcite where purely stationary edge modes are obtained . the function @xmath98 is determined below . in the linear problem we take @xmath99 . we first return to investigate the properties of the edge solution ( [ envelope_eq]-[statsoln ] ) . in order to have decaying modes ( @xmath100 as @xmath87 ) we need @xmath101 , which then requires us to take @xmath102 where @xmath103 and @xmath104 . fixing the frequency @xmath80 , we define the time interval @xmath105 to be @xmath106 if @xmath107 $ ] , then the edge mode remains localized for the entire period for the given frequency @xmath80 . these edge modes will be referred to as pure edge modes . if @xmath108 $ ] , then the edge mode remains localized for only part of the period after which the mode disintegrates into the bulk . these edge modes are referred to as quasi - edge modes . in applications , pure edge modes are expected to be more relevant since they can in principle propagate over many periods . we define @xmath109 to be the frequencies @xmath80 for which pure edge modes exist , i.e. @xmath110 \right\}.\ ] ] in a single period , @xmath111 spans an interval denoted by @xmath112 $ ] . the frequency interval @xmath113 of pure edge modes then falls into one of the following three cases @xmath114 where @xmath115 and @xmath116 . we note that since no pure edge mode exists for any range of frequencies @xmath80 in case ( iii ) , this case will be omitted in the following discussion of pure edge modes . next we note that associated with the edge solution ( [ envelope_eq]-[statsoln ] ) , the fredholm condition ( [ fredholm ] ) , derived in appendix [ pert ] , implies that the envelope of the edge solution satisfies the equation @xmath117 where @xmath118 substituting ( [ statsoln ] ) into and manipulating terms , we find that @xmath119 as can be readily seen , this quantity is real , and thus since @xmath120 this term shows that the influence of the nontrivial pseudo - magnetic field @xmath16 on the nearly stationary edge modes is the introduction of a non - trivial phase . we know that the function @xmath121 is periodic in @xmath122 , and so we can write @xmath123 where the average term @xmath124 is given by @xmath125 therefore , to leading order , we have that the edge mode in the presence of a slowly varying pseudo - field @xmath126 is given by @xmath127 where the periodic function @xmath128 is given by @xmath129 since both @xmath128 and @xmath130 are periodic in @xmath122 , we see the floquet parameter for the periodic problem is given by @xmath124 , which then gives us the dispersion relation in the presence of a nontrivial pseudo - field @xmath16 . in general , one can not obtain floquet parameters in explicit form , though in this perturbative system we can do so . the dispersion relation @xmath131 can be classified according to a @xmath132 topological index @xmath133 where @xmath134 is the number of roots of @xmath135 @xcite . it can be readily seen that @xmath136 in case ( i ) , or when @xmath137 . in case ( ii ) , when @xmath138 , @xmath131 has the asymptotic behavior for @xmath139 ( see appendix [ app : alpha - asym ] ) @xmath140 where @xmath141 are positive constants , and @xmath142 are those times such that @xmath143 therefore the direction of blowup of @xmath131 as @xmath144 agrees with the sign of @xmath145 at @xmath146 . it follows that for a pseudo - field @xmath126 which is counterclockwise in the @xmath147-plane , @xmath131 goes from @xmath148 at @xmath149 to @xmath150 at @xmath151 , and vice - versa for a clockwise pseudo - field . thus for any pseudo - field @xmath126 that forms a simple closed curve in the @xmath147-plane , the topological index is always @xmath152 in case ( ii ) , and the sign of the overall group velocity depends only on the helicity of the pseudo - field . however , if the pseudo - field forms a self - intersecting closed curve , then @xmath124 may asymptote to @xmath148 or @xmath150 at both @xmath149 and @xmath153 , in which case the topological index is @xmath136 . in the case where the topological index is nontrivial , i.e. @xmath152 , the pure edge modes are expected to behave like topologically protected modes , i.e. there are no backward propagating modes to inhibit the evolution . below we show numerical examples of such long lasting edge states . a detailed discussion of the mechanism of topological protection is outside of the scope of this paper . to make the above analysis more concrete , we take the pseudo - field @xmath126 to be eq . ( [ eq : a - rechts ] ) with @xmath154 , unless otherwise stated . as shown in fig . [ fig : edge_slow_field](a ) for @xmath155 , @xmath126 forms a counterclockwise circle in the @xmath147-plane . in this case @xmath113 is always centered around @xmath156 since @xmath157 . figure [ fig : edge_slow_twopar ] shows the width @xmath158 of @xmath113 as a function of @xmath66 and @xmath34 . for @xmath159 , @xmath158 is always @xmath83 . as @xmath66 increases past @xmath160 , @xmath158 decreases discontinuously as a function of @xmath66 for @xmath161 with the discontinuity increasing as @xmath162 increases . for @xmath163 , @xmath158 decreases as @xmath66 or @xmath162 increases and becomes @xmath164 for sufficiently large @xmath66 or @xmath162 . of the existence interval @xmath113 of pure edge states as a function of the deformation parameter @xmath66 and the pseudo - field parameter @xmath34 . the color scale interpolates between white for @xmath164 and black for @xmath83 . the dispersion relations at the labeled points ( a)(b ) are shown in fig . [ fig : edge_disp_pure ] . , scaledwidth=28.0% ] figure [ fig : edge_disp_pure ] shows the unscaled dispersion relation @xmath165 of pure edge modes at the labeled points ( a)-(b ) on the @xmath166-plane in fig . [ fig : edge_slow_twopar ] . the blue curves show the dispersion relations computed directly using eqs . ( [ eq : abn - ori - a]-[eq : abn - ori - b ] ) . the computational domain has @xmath167 lattice sites for each vector @xmath168 and @xmath169 with zig - zag boundary conditions on both ends . the black curve shows the asymptotically predicted dispersion relation eq . ( [ eq : talpha - omega ] ) for pure edge modes localized on the left . in fig . [ fig : edge_disp_pure](a ) and fig . [ fig : edge_disp_pure](b ) , the small parameter is chosen to be @xmath170 . the asymptotic theory agrees well with the numerical computation . as @xmath48 decreases , the theory improves further . [ fig : edge_disp_pure](a ) shows a case ( i ) dispersion relation computed at @xmath171 and @xmath155 . in this case @xmath172 crosses the @xmath80 axis twice , so the topological index is @xmath136 . [ fig : edge_disp_pure](b ) shows a case ( ii ) dispersion relation computed at @xmath173 and @xmath155 . in this case , @xmath172 crosses the @xmath80 axis once , so the topological index is @xmath152 . interestingly , the dispersion relation of edge modes in fig . [ fig : edge_disp_pure](a ) breaks up into multiple segments near @xmath174 . also , in fig . [ fig : edge_disp_pure](b ) there are scattered eigenvalues near @xmath175 for @xmath80 immediately outside @xmath138 . these eigenvalues may result from the presence of quasi - edge modes at these values of @xmath80 . [ cols="^,^,^ " , ] in this paper , a method is developed which describes the propagation of edge modes in a semi - infinite honeycomb lattice in the presence of a periodically and relatively slowly varying pseudo - field with weak nonlinearity . two types of edge modes are found , referred to respectively as pure and quasi - edge modes . pure edge modes remain localized for the entire period , while quasi - edge modes remain localized for only part of the period . in the linear case , the dispersion relations of pure edge modes indicate that some modes may exhibit topological protection . with weak nonlinearity included , it is shown that in the narrow band approximation , a time - dependent nls equation is obtained . this nls equation admits solitons , and they are found to be part of the long time nonlinear evolution under suitable circumstances . these 1d nls solitons correspond to true edge solitons propagating on the edge of the semi - infinite honeycomb lattice . finally , over very long distances , with certain choices of parameters consistent with the notion of topological protection as indicated by the linear dispersion relation , localized nonlinear edge modes in the focusing case are found to also be immune from backscattering . on the other hand when the nls equation is defocusing significant dispersion occurs . this research was partially supported by the u.s . air force office of scientific research , under grant fa9550 - 12 - 1 - 0207 and by the nsf under grants dms-1310200 , che 1125935 . in section [ discrete eq ] , the basic multiple scales perturbation procedure was formulated , and the leading order solution was determined . in this appendix , we carry out the procedure from that point . at @xmath176 the perturbation equation is @xmath177 where @xmath178 in order for functions @xmath179 to have decaying solutions at infinity , the following fredholm condition must be satisfied @xmath180 the fredholm condition ( [ fredholm ] ) is obtained from the identity @xmath181 where @xmath182 , summing over the lattice points and using the boundary conditions on @xmath183 . we shall only use the condition ( [ fredholm ] ) to determine the evolution of the leading order function @xmath184 . in principle , one can solve for the decaying functions @xmath179 in order to obtain more accurate approximation , but going to higher order in the perturbation scheme is outside the scope of this paper . in this appendix we show the asymptotic behavior ( [ eq : alpha - asym - m][eq : alpha - asym - p ] ) of dispersion relations in case ( ii ) . to obtain eq . ( [ eq : alpha - asym - m ] ) , we first expand @xmath121 around @xmath185 and @xmath149 to yield at leading order @xmath186 where @xmath187 and @xmath188 . integration in @xmath122 then yields @xmath189 thus eq . ( [ eq : alpha - asym - m ] ) is obtained by noting that @xmath190 and @xmath191 . the derivation of eq . ( [ eq : alpha - asym - p ] ) is similar and omitted for brevity .

the propagation of localized edge modes in photonic honeycomb lattices , formed from an array of adiabatically varying periodic helical waveguides , is considered . asymptotic analysis leads to an explicit description of the underlying dynamics . depending on parameters , edge states can exist over an entire period or only part of a period ; in the latter case an edge mode can effectively disintegrate and scatter into the bulk . in the presence of nonlinearity , a ` time'-dependent one - dimensional nonlinear schrdinger ( nls ) equation describes the envelope dynamics of edge modes . when the average of the ` time varying ' coefficients yields a focusing nls equation , soliton propagation is exhibited . for both linear and nonlinear systems , certain long lived traveling modes with minimal backscattering are found ; they exhibit properties of topologically protected states .

SAN FRANCISCO (CBS 5) — Days before a San Francisco man was arrested on a US Airways flight over his saggy pants, the same airline allowed a man showing much more skin to fly. Jill Tarlow, who was on the June 9th flight from Fort Lauderdale to Phoenix, told CBS 5 the man wore a woman’s bathing suit, thigh high stockings and high heels. “I just kept thinking to myself. What if I was wearing that outfit?” Tarlow said. “Would US Airways not ask me to cover up? If a woman was in a stripper outfit they’d allow her to just board?” According to Tarlow, many passengers complained about the man’s attire to the gate staff. She telephoned US Airways after the plane landed in Phoenix. Tarlow said an airline spokesperson told her “…As long as he’s not harassing anyone or exposing himself, then we’re fine with it.” Six days later, Deshon Marman of San Francisco was removed from another US Airways flight after he allegedly refused to pull up his sagging pants. Upon hearing the news of Marman’s arrest, Tarlow then turned over the photos of the scantily clad man to Marman’s attorney Joe O’Sullivan. “I think the airline maybe has a market strategy toward drag queens and against young African Americans,” O’Sullivan told CBS 5. O’Sullivan is adamant that since the airline has no explicit dress code and allowed the scantily clad passenger to board suggest it’s not about clothing, but race. “It was racial because he is black. And he had dreadlocks and they jammed him,” O’Sullivan said. “Why would they have stopped him? No passenger complained about him. No police report says he showed he showed any flesh. YouTube and everything else is demonstrable. He was reverent, respectful. I almost felt it was obnoxious he said ‘Sir’ so many times.” A US Airways spokesperson told CBS 5 by phone Tuesday, as long as someone is not showing parts of their anatomy, they are permitted to fly. (Copyright 2011 by CBS San Francisco. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed.) ||||| Six days before a college football player was arrested at San Francisco International Airport in a dispute that began when a US Airways employee asked him to pull up his sagging pants, a man who was... Man flies US Airways in women's underwear (Photo) Man flies US Airways in women's underwear (Photo) Six days before a college football player was arrested at San Francisco International Airport in a dispute that began when a US Airways employee asked him to pull up his sagging pants, a man who was wearing little but women's undergarments was allowed to fly the airline, a US Airways spokeswoman conceded Tuesday. A photo of the scantily clad man was provided to The Chronicle by Jill Tarlow, a passenger on the June 9 flight from Fort Lauderdale, Fla., to Phoenix. Tarlow said other passengers had complained to airline workers before the plane boarded, but that employees had ignored those complaints. Jill Tarlow US Airways spokeswoman Valerie Wunder confirmed she'd received the photo before last week's incident in San Francisco and had spoken to Tarlow, but said employees had been correct not to ask the man to cover himself. "We don't have a dress code policy," Wunder said. "Obviously, if their private parts are exposed, that's not appropriate. ... So if they're not exposing their private parts, they're allowed to fly." So, does that mean Deshon Marman, the University of New Mexico player yanked from an Albuquerque-bound flight June 15 at SFO, was displaying his private parts when his pajama pants sagged to mid-thigh level? Wunder declined to comment on the incident directly. Police have said only that Marman's boxer shorts were exposed, and his attorney said surveillance video would prove Marman's skin had not been visible. Police arrested Marman, 20, who grew up in San Francisco, after he allegedly refused an US Airways employee's request to pull up his pants to keep his underwear from showing. Marman's later refusal to comply with the pilot's orders to get up from his seat led to his arrest on suspicion of trespassing, battery and resisting arrest, police said. The San Mateo County district attorney has not determined whether he will charge Marman. Marman's attorney, Joe O'Sullivan, said his client had been stereotyped by US Airways as a thug, and that the airline was guilty of racial discrimination for asking Marman to adjust his clothes. Marman is African American. "It just shows the hypocrisy involved," O'Sullivan said after he viewed the photo of the cross-dressing passenger. "They let a drag queen board a flight and welcomed him with open arms. Employees didn't ask him to cover up. He didn't have to talk to the pilot. They didn't try to remove him from the plane -- and many people would find his attire repugnant." O'Sullivan added, "A white man is allowed to fly in underwear without question, but my client was asked to pull up his pajama pants because they hung below his waist." Tarlow, 40, who was returning home to Phoenix after helping her mother move, said she had been shocked when she noticed the older man in blue underwear and black stockings standing in the Fort Lauderdale terminal. Tarlow said the man had obliged when she asked to take his photo. "No one would believe me if I didn't take his picture," Tarlow said. "It was unbelievable. ... And he loved it. He posed for me." Wunder reiterated the airline's stance that Marman had not been removed from the US Airways flight last week because of his clothing, but because he had failed to comply with an employee's request. "The root of the matter is, if you don't comply with the captain's requests," Wunder said, "the captain has the right to handle the issue because it's one of safety." Posted By: Justin Berton (Email, Twitter) |

– It's getting tough to figure out airline dress codes. One thing's clear, though: The tightest, tiniest "pants" apparently will fly. Days before a college football player was bounced—and busted—for wearing saggy pants, an older male passenger tarted out in women's bikini briefs and thigh-high black stockings was allowed to fly the same airline. The call was made even after other passengers on the Fort Lauderdale-to-Phoenix flight complained to US Airways workers. "We don't have a dress code policy," an airline spokeswoman told the San Francisco Chronicle. "Obviously, if private parts are exposed, that's not appropriate. But if they're not exposing their private parts, they're allowed to fly." Irritated passenger Jill Tarlow snapped a photo of the unidentified passenger. "I just kept thinking to myself, 'What if I was wearing that outfit?” Tarlow told CBS 5. “Would US Airways not ask me to cover up? If a woman was in a stripper outfit they’d allow her to board?" University of New Mexico football player Deshon Marman was yanked from a San Francisco flight bound for Albuquerque by the same airline earlier this month because his saggy pants exposed the top of his boxer shorts. Marman was arrested after he refused to pull up his pants. “I think the airline maybe has a market strategy toward drag queens and against young African Americans,” said Marman's attorney. "A white man is allowed to fly in underwear without question, but my client was asked to pull up his pants because they hung below his waist."

the management of undescended testes is one of the most controversial aspects in pediatric urology . the problem is not , in principle , the time to bring the testis down to the scrotum , but whether and when to perform imaging studies such as ultrasound ( us ) and why we still get the patients with undescended testis at a later age than global recommendations for orchidopexy . cryptorchidism is the most common congenital anomaly in boys and occurs in 3% to 9% of all full - term male neonates . the incidence of cryptorchidism decreases , due to spontaneous descent , to 1% to 2% by 6 months of age . although the recommended age for orchidopexy is around 6 months to 1 year of age , later orchidopexies have been reported in many studies . after the age of 2 years , the degenerative process in an undescended testis can be observed histologically . it may also have internal structure changed , but such findings , their incidences and methods of evaluation have not yet been described . some practitioners agree that to evaluate undescended testes , precise physical examination complemented with appropriate imaging studies is advised . in fact , we need such a diagnostic tool that would allow the evaluation of the testis before or after surgery , informing the physicians , as well as the parents and patients about testis development and changes that may suggest deterioration or even malignancy . the wide availability , high repeatability , low costs , and noninvasive nature of us have made it the imaging modality of choice for examining the scrotum . in many cases recent advances in us have improved the resolution of gray scale images of pediatric testis , which is especially important in the evaluation of the internal structure of undescended and mobile testis . the aim of this study was to evaluate the testicular volume and structure using us before and up to 3 years after orchidopexy in children with different age . from january 2007 to december 2012 , 128 patients between the ages of 2 and 10 years ( mean 6.3 years ) underwent orchidopexy for undescended testes . the patients in whom undescended testis was not visible during preoperative us and patients with retractile and abdominal testis were not included to the study . afterwards , patients were invited for annual follow - up and control scrotal us . among these patients , the total number of analyzed testes was 184 after orchidopexy and 72 scrotal testes in patients with unilateral cryptorchidisms . because of the broad age distribution , patients were divided according to age at the time of surgery into 3 groups : group i ( 24 years old , n = 56 testes ) , group ii ( 57 years old , n = 67 ) , and group iii ( 810 years old , n = 61 ) . the reference group was composed of 185 patients ( n = 370 testes ) between the ages of 2 and 13 years with normally descended testes with normal and homogeneous echogenicity of the testes . the institutional ethical committee approved our protocol and informed consent was received from all patients in this study . a phillips iu22 us scanner with an l17 - 5 mhz linear probe was used for the determination of testicular structure and volume . volume was calculated using the approximation for a prolate ellipsoid : v = 0.523 length thickness width . the testicular volume ratio was calculated by the equation of the operated testis volume to the scrotal ( control ) testis mean volume . the structure of the testis was assessed in gray scale with the same settings of the gain , focus , and depth . echogenicity was scored in 2 grades , normal ( homogeneous ) and abnormal ( inhomogeneous ) . all us scans were performed by 1 radiologist with 15 years experience in the field of clinical us . spss statistical software version 14.0 was used , with wilcoxon signed ranks test for the analysis of differences between ratios . the mean testicular volumes of operated and scrotal testes measured by us in various age groups before and 1 , 2 , and 3 years after surgery are shown in fig . 1 and table 1 . the age groups of patients from the reference group with normal testes are adjusted according to the increasing age of observed patients after orchidopexy . in patients with undescended testes from groups i iii , the testicular volume ratio of the operated testes on preoperative examination was 0.86 for group i , 0.82 for group ii , and 0.78 for group iii . on follow - up examination after 1 year of observation , the ratio in group i was still 0.86 and in groups ii and iii this increased to 0.87 and 0.86 . after 2 years the ratios changed to 0.89 , 0.88 , and 0.84 , respectively , and after 3 years of observation , the ratios showed an increase to 0.95 , 0.92 , and 0.90 . testicular volume , in milliliters , of the undescended testes in various age groups , before and 1 , 2 , 3 years after orchidopexy and mean volume of the scrotal and reference testes . patient age at treatment , number of testes ( n ) , and mean testicular volume measured by ultrasound of the undescended and scrotal testes in various age groups , before and 1 , 2 , 3 years after orchidopexy . testicular volume ratio of undescended testes and scrotal testes in patients with unilateral cryptorchidisms , at various age groups before and 1 , 2 , 3 years after orchidopexy and statistical significance of the ratios growth in relation to the ratio before orchidopexy ( p ) , 2 to 1 year after orchidopexy and 3 to 2 years after orchidopexy ( p ) the testicular volume ratio was also calculated in scrotal testes in patients with unilateral cryptorchidisms . in most cases , the ratio was close to one , except for the preoperative examination in all groups and 1 year after orchidopexy in group ii ( table 1 ) . the structure of the testis upon preoperative examination was inhomogeneous in 38 patients ( 21.7% ) ( group i n = 17 , group ii n = 15 , and group iii n = 6 ) . on follow - up exams , this type of structure remained in 13 ( 7.1% ) patients ( group i-9 , ii-3 , and iii-1 ) ( table 3 ) . the cryptorchid patients with inhomogeneous echo in the testis displayed a significant lower volume as compared to the testis with homogeneous echo ( table 3 ) . six testes ( 3.3% ; group i-3 , ii-2 , iii-1 ) with an initial ratio < 0.25 and the number and volume of testes with normal and abnormal testicular structure at various age groups before and 3 years after orchidopexy . microlithiasis was found in 9 patients with cryptorchidisms ( 4.9% ) , in 6 patients with inhomogeneous testis structure , and in 3 patients with homogeneous testis structure . there is a common consensus that cryptorchid testes should be brought down to the scrotum in early childhood to preserve function and mitigate cancer risk . however , in some pediatric centers , many of these procedures are performed later in life , even up to 10 years of age . this could be due to either lack of screening methods or unclear procedures in the case of undescended testes , as well as delayed diagnosis by medical practitioners . also , parental inattention and their unawareness of the necessity of this operation may affect the decision . other factors associated with the timing of orchidopexy include insurance status , and the hospital at which the surgery is performed . some authors suggest that us has no role in case of undescended testes , and a delayed urology consultation could be due to unnecessary us . although the possible consequences of cryptorchidism are well - known , there have been problems with the assessment of the influence of orchidopexy on the future function of the testis , as this requires a very long follow - up period from diagnosis and treatment in childhood until full testicular function in adulthood . to monitor testicular function , invasive testicular biopsies would be required , but such an invasive procedure in young boys would not be ethically acceptable . it has also been thought that repeated measurements of testicular volume could be translated to testicular function . another method of monitoring can be assessment of the serum hormone levels , like follicle - stimulating hormone , because of its role in spermatogenesis , but it does not give information about testis size and structure . in this study the use of us is emphasized , and indeed , abnormalities in the echostructure were seen in approximately 20% of patients in the present study ( table 3 ) . ultrasonography is known to be a reliable tool for the measurement of testicular volume with high reproducibility and is used to determine the volume of the cryptorchid testis before and after testis repositioning ( fig . 2 ) . in the case of unilaterally undescended testes , to compare the growth of the undescended testis to the scrotal testis , the testicular volume ratio can be calculated by using the operated to scrotal testis volume . this is an index of the degree of growth deficit of the cryptorchid testis and has been used in several studies concerning the growth of the undescended testis after surgery , as well as in this group of patients . in a study by kollin et al , there was an increase in the median ratio from 0.68 at 6 months to 0.81 at 4 years ( p < 0.001 ) in the early treatment group operated on at 9 months of age . in contrast , a decrease in the median ratio was noted in the late treatment group ( surgery at 3 years ) from 0.68 at 6 months to 0.56 at 4 years ( p < 0.001 ) . at ages 2 , 3 , and 4 years , there were significant differences in this ratio between the early and late treatment groups , again demonstrating the partial catch - up growth of testes that are treated early ( p < 0.001 ) . this means that only an early orchidopexy is likely to result in significant recovery of testicular size and appearance . also , in a study by kim et al at the follow - up examination 2 years after orchidopexy , the testicular volume percentage ( the ratio multiplied by 100 ) showed an increase : in the group of patients operated on before the 2nd year of life ( i ) from 46.6 to 90 ; in the group of patients operated between 2 and 5 years of life ( ii ) , from 68.1 to 78.2 ; and in the group operated after the 5th year of life ( iii ) , from 65.7 to 77.6 . only group i , which received orchidopexy within 2 years of birth , showed a significant recovery of testicular volume at follow - up compared with groups ii and iii . however , unilateral cryptorchidism may have some effect on scrotal testis , thus contralateral testis should not be assumed as a reference ( table 2 ) . that is why independent control group was introduced giving possibility to the combined assessment of the unilateral and bilateral undescended testes . the measurements of the scrotal testis ( rt ) and undescended one ( lt ) before orchidopexy ( upper images ) and 3 years after orchidopexy ( bottom images ) . lt = left testis , rt = right testis . in this study , there was an increase in the median ratio in all age groups ( table 2 ) , but the increase in the median ratio 3 years after surgery in group i ( from 0.86 to 0.95 ) was statistically significant ( p < 0.05 ) . that is way these or earlier age should be addressed for orchidopexy . significant growth occurred mostly in the 3rd year of observation , which confirms the need for long - term follow - up after orchidopexy . despite quite good catch up growth , some of the testes had significantly changed volume at the time of diagnosis . a large difference in testis volume could be recommendation for early orchidopexy as well as finding that testicular volume ratio in undescended testes decreased with age if the testes were left untreated ( from 0.86 in group i to 0.78 in group iii ) . this study also included patients who were elder at the time of orchidopexy than what is currently recommended ( group iii ) . those children and children from the eldest reference group could enter into puberty during observation , which restrict the value of the results of this group and suggest its exclusion from future research . some abnormalities , like hypoechoic and inhomogeneous patterns , were seen in 20% of patients with cryptorchidism . in 5% to 10% of undescended testes , what is more microlithiasis can occur more frequently in testes with abnormal structure . however , the combination of assessing testis echostructure and its volume could have the strongest prognostic importance , especially in a group of testes with a very low volume ratio ( < 0.25 ) and a hypoechoic , inhomogeneous structure , which was observed in 6 ( 3.3% ) patients . this is too small group of patients for statistical evaluation , but because these testes did not show any recovery during observation in these patients more advanced methods of evaluation should be considered , like hormones levels or even biopsy . the symptoms of deterioration of the testis structure may also appear in later age , but such findings were not observed in our patients . some of abnormalities , which quickly resolved after orchidopexy , could be due to the inguinal position of the testis and the need for deeper penetration of a us and , consequently , a weaker signal . this could give some limitations for the initial exam , before the surgery , but only in the assessment of the testis echostructure . other information , such as the location and the volume of the testis , could be still very valuable . in fact , undescended testis is a predisposing factor for malignancy , as well as microlithiasis . this also applies to the patients after orchidopexy . since in the case of microlithiasis , us is an established method of observation , why can not be used also in the case of undescended testes and testes after orchidopexy . authors realize that the subjectivity of the evaluation of the echostructure could also be some disadvantage , but additional us tools can be used in the assessment of the testis condition , such as color and spectral doppler . also to monitor the stiffness or vascularity of the testes , beyond 2d us , modern us techniques could be applied , such as elastography or 3d us , but this requires additional study . potentially these are the tools we are looking for . in summary , scrotal us can provide an accurate comparative assessment of the growth of testes before and after orchidopexy . in group of the patients 2 to 4 years old the growth of the ratio 3 years after surgery was statistically significant and these or earlier age should be recommended for orchidopexy . abnormalities in the structure of the testes do not accurately reflect the testicular function , but can be used for identifying testes requiring more advanced methods of evaluation , like hormones levels or even biopsy .

abstractthe aim of this study was to evaluate the testicular volume and structure using ultrasound ( us ) before and up to 3 years after orchidopexy in children with different age.a total of 128 patients underwent orchidopexy for undescended testes . afterwards , patients were invited for annual follow - up and control scrotal us . the total number of analyzed testes after orchidopexy was 184 . patients were divided according to age at the time of surgery : group i ( 24 years old ) , group ii ( 57 ) , and group iii ( 810 ) . in all patients , the testicular volume ratio was calculated as the operated testes volume versus the control testes mean volume.there was an increase in the median ratio in all age groups , from 0.86 to 0.95 in group i , 0.82 to 0.92 in group ii and 0.78 to 0.90 in group iii . in group of the patients 2 to 4 years old the growth of the ratio 3 years after surgery was statistically significant.abnormalities in the structure of the testes , which may indicate severe damage to the testis , were seen in approximately 20% of patients on initial exams . on follow - up exams , this type of structure remained in 7% of patients . testes with an initial ratio < 0.25 and inhomogeneous structure did not show any significant growth.scrotal us can be used for an accurate comparative assessment of the structure and growth of the testes before and after orchidopexy.abnormalities in the structure of the testes may identify testes requiring more advanced methods of evaluation .

dengue virus ( denv ) , which has 4 serotypes , is a mosquito - borne , enveloped , positive - stranded rna virus in the flaviviridae family . it is estimated that approximately 390 million dengue infections occur per year , of which 96 million manifest apparent symptoms . although most cases of denv infection are asymptomatic , a variable spectrum of symptoms can occur , ranging from a mild fever to fatal severe dengue hemorrhagic fever ( dhf ) and dengue shock syndrome ( dss ) . in dhf / dss cases , potentially lethal complications , including plasma leakage , severe hemorrhages , and organ failure , can develop . unfortunately , there is currently no effective vaccine or specific antiviral treatment . although the mechanisms of dhf / dss have not been fully clarified , it is believed that several proinflammatory mediators are involved in hemorrhage development , such as nitric oxide ( no ) and tumor necrosis factor- ( tnf- ) [ 3 , 4 ] . in monocytes collected from denv patients with acute fever , inducible no synthase ( inos ) , the major enzyme catalyzing no production , as seen in our previous studies , no can cause endothelial cell damage resulting in vascular leakage , which is induced by antibodies against denv nonstructural protein ( ns ) 1 [ 68 ] . in addition , yen et al . also observed increased macrophage infiltration and tnf- production in the endothelium of the hemorrhagic tissue and endothelial cell apoptosis in the tissues with enhanced expression of inos and nitrotyrosine in denv - infected mice . furthermore , tnf- has been reported to induce hemorrhage by causing endothelial cell death , which is associated with increased endothelial cell permeability , in an experimental dengue hemorrhage mouse model [ 9 , 10 ] . tnf receptor levels have also shown a highly positive correlation with the severity of dhf in patients . however , the underlying molecular mechanism of denv - induced inflammatory activation remains largely unknown . nuclear factor-b ( nf-b ) , which is a well - known transcription factor , participates in the regulation of proinflammatory mediators , including inos and tnf-. nf-b is a heterodimer consisting of p65 and p50 subunits , which associate with the inhibitor of nf-b ( ib ) family of inhibitory proteins . upon ib degradation , nf-b can be activated by several different signaling pathways , including the receptor - mediated signaling of pattern recognition receptors , such as toll - like receptors ( tlrs ) , retinoic - acid - inducible gene i , melanoma differentiation - associated gene 5 , and reactive oxygen species- ( ros- ) induced pathways . in denv infection , tsai et al . showed that tlr3 plays a major role in interleukin- ( il- ) 8 production and viral replication , compared with other tlrs . nf-b activation during denv infection has been reported since the 1990s , when several studies showed that denv can induce nf-b activation , leading to the induction of apoptosis in different cell types [ 1618 ] ; however , the underlying molecular mechanism remains undefined . recently , lin et al . clarified that the activation of nf-b , which leads to endothelium cell apoptosis and hemorrhage development , occurs through the interaction of the denv ns2b - ns3 ( ns2b3 ) protease complex with ib/. ns2b3 cleaves ib/ and activates ib kinase . however , whether nf-b is involved in denv - induced inos / no and tnf- production and which pathway mediates these events are still a mystery . because monocytic cells are the denv target cells , we used murine mononuclear phagocyte raw264.7 cells as a model [ 20 , 21 ] . in this study , we aimed to investigate the role of nf-b in denv - induced inos / no and tnf- production and to unveil the underlying molecular mechanism of nf-b activation . the reagents and antibodies used were translation inhibitor cycloheximide , transcription inhibitor actinomycin d , nf-b inhibitor caffeic acid phenethyl ester ( cape ) , antioxidant n - acetyl - cysteine ( nac ) , poly(i : c ) , tlr3 inhibitor , dimethyl sulfoxide ( dmso ) , and mouse monoclonal antibody ( ab ) specific for -actin ( sigma - aldrich , st . louis , mo ) ; abs against denv ns1 and envelope ( e ) ( genetex , san antonio , tx ) ; abs against inos and nf-b ( cell signaling technology , beverly , ma ) ; abs against isotype control igg ( millipore , billerica , ma ) ; donkey anti - goat igg conjugated with horseradish peroxidase ( hrp ) ( santa cruz biotechnology , santa cruz , ca ) and goat anti - rabbit igg conjugated with hrp ( chemicon international , temecula , ca ) ; rabbit anti - mouse igg conjugated with hrp ( abcam , cambridge , ma ) ; and alexa fluor 488- and alexa fluor 594-conjugated goat anti - mouse and goat anti - rabbit ( invitrogen , carlsbad , ca ) . inhibitors were then dissolved in dmso prior to dilution with sterile phosphate - buffered saline ( pbs ) for use in experiments . all drug treatments on cells were assessed for cytotoxic effects using cytotoxicity assays prior to experiments . raw264.7 mouse macrophage was purchased from american type culture collection ( atcc number tib-71 ) and were grown on plastic in dulbecco 's modified eagle 's medium ( dmem ) with 10% fetal bovine serum ( fbs ) ( sigma - aldrich , st . louis , mo ) , 100 units of penicillin , and 100 g / ml of streptomycin at 37c under 5% co2 . baby hamster kidney ( bhk ) cells and c6/36 cells were cultured in dmem ( invitrogen life technologies ) containing fbs . monolayers of c6/36 cells were incubated with denv at a multiplicity of infection ( moi ) of 0.01 and incubated at 28c in 5% co2 for 5 days . the virus supernatant was further filtered with 0.22 m filter and then stored at 80c until use . cells were resuspended at a concentration of 5 10 cells / ml in appropriate medium with denv and incubated for 90 min at 37c . then the cells were washed once with dmem medium , resuspended at a concentration of 5 10 cells / ml , and incubated at 37c with 5% co2 . bhk-21 cells were plated into 12-well plates ( 2 10 cells / well ) and cultured in dmem under co2-enriched conditions . after adsorption with a serially diluted virus solution for 1 h , the solution was replaced with fresh dmem containing 2% fbs and 0.5% methyl cellulose ( sigma - aldrich ) . five days after infection , the medium was removed , and the cells were fixed and stained with crystal violet solution containing of 1% crystal violet , 0.64% nacl , and 2% formalin . harvested cells were lysed in a buffer containing 1% triton x-100 , 50 mm tris ( ph 7.5 ) , 10 mm edta , 0.02% nan3 , and a protease inhibitor cocktail ( roche boehringer mannheim diagnostics , mannheim , germany ) . after a freeze - thaw cycle , cell lysates were centrifuged at 10,000 g at 4c for 20 min . proteins were then subjected to sds - page and transferred to pvdf membranes ( millipore , billerica , ma , usa ) using a semidry electroblotting system . after blocking with 5% skim milk in pbs , the membranes were incubated overnight with a 1 : 1,000 dilution of primary antibodies at 4c . the membranes were then washed with 0.05% pbs - tween 20 and incubated with a 1 : 5,000 dilution of hrp - conjugated secondary antibody at room temperature for 1 h. after washing , the membranes were soaked in ecl solution ( perkinelmer life and analytical sciences , inc . , boston , ma , usa ) for 1 min and exposed to an x - ray film ( biomax ; eastman kodak , rochester , ny , usa ) . the relative signal intensity was quantified using imagej software ( version 1.41o ; w. rasband , national institutes of health , bethesda , md , usa ) . the changes in the ratio of proteins compared with the normalized value of untreated cells ( indicated protein/-actin ) are also determined . one set of representative data obtained from three independent experiments is shown and the data shown as the mean sd values from three independent experiments . after treatment , we used a commercial enzyme - linked immunosorbent assay ( elisa ) kit ( r&d , mn , usa ) to detect the concentration of murine tnf- in cell - conditioned culture medium , according to the manufacturer 's instructions . production of no was assessed as the accumulation of nitrite ( no2 ) in the medium using a colorimetric reaction with the griess reagent . briefly , samples ( cell culture supernatants or murine ascites ) were mixed with an equal ( 1 : 1 ) volume of griess reagent ( 0.1% n-(1-naphthyl)ethylenediamine dihydrochloride , 1% sulfanilamide , and 2.5% h3po4 ) . the absorbance was measured at 540 nm using a 96-well microplate reader ( spectra max 340pc , molecular devices ) ; data were analyzed using softmax pro software . sodium nitrite was dissolved in double - distilled water and then used as standards ( from 1 to 50 m ) . to analyze nf-b promoter activity by a luciferase reporter assay , transient transfection was performed using the turbofect cell transfection reagent ( thermo , pa , usa ) . in short , cells were cotransfected with 0.2 g of an nf-b - promoter - driven firefly luciferase reporter and 0.01 g of a renilla luciferase - expressing plasmid ( prl - tk ; promega ) . twenty - four hours after the transfection , the cells were infected with denv for 24 h , lysed , and then harvested for luciferase and renilla measurement , using a luciferase assay system ( dual - glo ; promega ) . for each lysate , the firefly luciferase activity was normalized to the renilla luciferase activity to assess transfection efficiencies . to detect expression of nf-b and denv e protein , cells were fixed with 4% paraformaldehyde , permeabilized with 0.5% triton x-100 , and washed twice with ice - cold pbs . cells were stained with anti - nf-b and denv e abs and then with alexa 488-conjugated goat anti - mouse igg and alexa 594-conjugated goat anti - rabbit igg . cells were visualized under a laser - scanning immunofluorescence microscope ( ix71 ; olympus , pa , usa ) . transient transfection was performed using turbofect cell transfection reagent ( thermo , pa , usa ) according to the manufacturer 's instructions for optimization and usage . the plasmid expressing flag - tagged wild - type ( wt ) ns2b3 and a protease - dead mutant ns2b3 which has a single point mutation changing serine residue 135 of ns3 to alanine ( s135a ) and its control pcr3.1 were generated previously . cells were plated at 1 10/well in 96-well plates , cultured overnight , and washed twice with hank 's buffered salt solution ( hbss ) before experiments . cells were exposed to 20 m 5-(and-6)-chloromethyl-2,7-dichlorodihydrofluorescein diacetate , acetyl ester ( cm - h2dcfda ) ( invitrogen life technologies , carlsbad , ca , usa ) for 1 h. fluorescence was read immediately at wavelengths of 485 nm for excitation and 530 nm for emission on a fluorescence plate reader ( fluoroskan ascent , thermo electron corporation , milford , ma , usa ) . data obtained from three independent experiments are presented as the mean standard deviation ( sd ) . statistical analysis of data analyses were performed using prism version 5 ( graphpad software , san diego , ca ) . three or more sets of data were analyzed by one - way anova with tukey 's multiple - comparison posttest . we first examined whether murine mononuclear phagocyte raw264.7 cells could be efficiently infected by denv serotype 2 ( denv 2 ) strain pl046 in vitro . using western blotting and plaque assays , we confirmed the expression of viral ns1 and showed that viral titers were significantly increased at 24 h after infection with an moi of 50 ( figure 1(a ) ) . these results demonstrate that denv infects raw264.7 cells in vitro . to evaluate the expression of tnf- , no , and inos , we determined the multiple mois of denv infection and the kinetics of response to denv by elisa , griess reagent , and western blotting , respectively . the results showed that a relative increased response of tnf- production and inos expression in the multiple mois of denv infection ( figure 1(b ) ) . according to the results , we selected a high moi of denv infection for this study and all of these values increased in a time - dependent manner ( figure 1(c ) ) . to determine whether the upregulation of tnf- and inos / no occurred through new protein synthesis , raw264.7 cells were infected with denv in the presence or absence of the transcription inhibitor cycloheximide ( chx ) and the translation inhibitor actinomycin d ( acd ) for 24 h. treatment with chx and acd significantly suppressed the expression of tnf- , no , and inos ( figure 1(d ) ) . these results demonstrate that raw264.7 cells infected by denv induce tnf- production and inos / no biosynthesis through new protein synthesis . a luciferase reporter assay showed a significant increase of nf-b activation at the high mois of denv infection ( figure 2(a ) ) . to explore the activation of nf-b , we used immunocytochemical staining to detect the nuclear translocation of nf-b in the context of denv infection . in the infection group , the p65 subunit of nf-b translocated into the nucleus in e protein - positive cells ( figure 2(b ) ) at 6 h after infection . furthermore , a luciferase reporter assay showed that inhibiting nf-b with cape , an inhibitor of nf-b , blocked denv - induced nf-b activation ( figure 2(c ) ) . these results demonstrate that denv infection activates nf-b in raw264.7 cells . to further determine the essential role of nf-b in denv infection , we examined the effect of nf-b inhibition on tnf- , no , and inos expression . after treatment with cape , denv - induced tnf- production ( figure 3(a ) ) , no generation ( figure 3(b ) ) , and inos expression ( figure 3(c ) ) were dramatically downregulated . these results confirmed that nf-b plays a critical role in denv - induced tnf- , no , and inos expression . we examined the possibility of ros involvement in denv - induced nf-b activation followed by tnf- , no , and inos induction . dcfda staining followed by flow cytometry was used to detect changes in the ros level in a time - dependent manner . however , there was no significant difference after denv infection at the indicated time points ( figure 4(a ) ) . inhibiting ros using nac did not affect denv - induced nf-b activation ( figure 4(b ) ) . nac also had no influence on tnf- and inos expression ( figures 4(c ) and 4(e ) ) . however , inhibition of ros reduced no generation significantly during denv infection ( figure 4(d ) ) . these results indicate that ros is not responsible for the induction of nf-b activation followed by tnf- and inos upregulation but plays some role in the conversion of inos to no during denv infection . to investigate whether denv - induced nf-b activation followed by tnf- production and inos / no biosynthesis occurs in a protein - mediated manner , raw264.7 cells were inoculated with moi of 50 of heat - inactivated denv ( hi - denv ) . the results revealed that hi - denv was less efficient at inducing nf-b activity than live - denv ( figure 5(a ) ) . similarly , the levels of tnf- ( figure 5(b ) ) , no ( figure 5(c ) ) , and inos expression ( figure 5(d ) ) were lower in the hi - denv group compared with the live denv group . these experiments show that denv activates nf-b followed by tnf- and inos / no biosynthesis through viral proteins . according to tsai et al . , tlr3 plays a major role in cellular activation compared with other tlrs during denv infection . tlr3 is a well - defined receptor for viral rna , which can induce nf-b activation during viral infection . first , we used the tlr3 agonist polyinosinic - polycytidylic acid poly ( poly(i : c ) ) to determine whether tlr3 signaling can activate nf-b . the results revealed that poly(i : c ) activated luciferase activity of nf-b and that this activity was inhibited by cape ( figure 6(a ) ) . moreover , pharmacological inhibition of tlr3 suppressed nf-b activation ( figure 6(b ) ) . surprisingly , there was no difference in tnf- between the presence and absence of tlr3 inhibitor during denv infection ( figure 6(c ) ) . in contrast , denv - induced no ( figure 6(d ) ) and inos ( figure 6(e ) ) biosynthesis was significantly attenuated by tlr3 inhibition . these results demonstrate that tlr3-activated nf-b is required for inos / no biosynthesis , but not tnf- expression , during denv infection . a recent study showed that the denv protease ns2b3 activates nf-b by cleaving ib- and ib- . therefore , to investigate whether ns2b3-activated nf-b also participates in the induction of tnf- , no , and inos , we overexpressed a wild - type form of ns2b3 ( ns2b3-wt ) and a protease - dead mutant ns2b3 , which has a single point mutation changing serine residue 135 of ns3 to alanine ( s135a ) that abolished protease activity . western blotting confirmed that the overexpression of ns2b3-wt and ns2b3-s135a worked efficiently in raw264.7 cells . western blotting detected the proform and cleavage form of ns2b3 in ns2b3-wt cells but only one band in ns2b3-s135a cells , demonstrating the loss of ns2b3 autocleavage ability ( figure 7(a ) ) . nf-b activity was enhanced by overexpressing ns2b3-wt but decreased by overexpressing ns2b3-s135a ( figure 7(b ) ) . distinct from tlr3 signaling , ns2b3-s135a suppressed tnf- expression ( figure 7(c ) ) compared with the ns2b3-wt sample . in addition , neither ns2b3-wt nor ns2b3-s135a induced inos / no biosynthesis ( figures 7(d ) and 7(e ) ) . these results reveal that forced expression of denv protease ns2b3 induces nf-b activation followed by tnf- expression but not inos / no biosynthesis . in this study , we identified the distinct pathways of nf-b activation for regulating inos / no and tnf- expression during denv infection in raw264.7 cells . as summarized in figure 8 , the viral protein ns2b3 causes nf-b activation specifically for tnf- expression and , alternatively , tlr3 mediates nf-b activation for inos / no biosynthesis . ros is not involved in nf-b activation , as demonstrated in denv - infected raw264.7 cells . while this is not consistent with previous studies that have shown crosstalk between ros and nf-b activation , the presence of ros remains important for the generation of nitrite ( no2 ) . it may have a limitation on our findings that these results are demonstrated in murine macrophages . in the future , it has generally been suggested that tlrs are required for triggering nf-b - mediated expression of downstream target genes of proinflammatory mediators during the induction of inflammatory responses in denv infection . in addition to tlr3 , we confirmed an alternative activation of nf-b caused by viral protein ns2b3 . these results show the diverse effects of molecular regulation on nf-b during denv infection . in activated macrophages , the activation of nf-b usually induces inflammatory cytokine tnf- and inos / no generation by controlling the transcriptional activation of the genes . even under nf-b activation , the different upstream signaling pathways and coactivators may contribute considerably to inducing specific genes in response to different stimuli . the positive transcription elongation factor b , denv core , and nonstructural protein 5 may also synthetically regulate il-8 mrna transactivation [ 25 , 26 ] . for denv - induced expression of tnf- and inos in macrophages , other factors involved in the transcriptional activation of tnf- and inos need further investigation . during denv infection , the activation of nf-b has been widely reported to activate apoptosis in neuroblastoma , hepatoma , and endothelial cells [ 16 , 19 , 27 ] , accompanied by chemokine production in endothelial cells , il-8 production in monocytes , epithelial cells , and endothelial cells , mhc production in hepatoma cells , and type i ifn response in lung epithelial cells . however , the molecular mechanisms underlying the activation of nf-b caused by denv infection or viral proteins remain largely undefined . consistent with a study demonstrating that ns2b3 is required for denv - induced nf-b activation in endothelial cells , we showed an ns2b3-mediated nf-b activation of tnf- expression in denv - activated raw264.7 cells . interestingly , denv - infected raw264.7 cells also underwent apoptosis 48 h after infection ( data not shown ) . for ns2b3-mediated nf-b activation in endothelial cells , the endogenous nf-b inhibitors ib and ib protease - dead mutant ns2b3 s315a - transfected raw264.7 cells lost the ability to trigger nf-b activation and tnf- expression compared to wild - type ns2b3 . the nf-b - promoting effect of downregulating ib and ib may need to be confirmed in denv - infected macrophages . an increase in tnf- may contribute to the pathogenesis of dengue diseases by modulating cell death and survival , inflammation , and endothelial dysfunction . although tnf- may not contribute to viral replication directly , overproduction of tnf- may further cause nf-b activation , which has important consequences for nf-b - driven release of inflammatory cytokines during denv infection . according to our findings in addition to ns2b3 , we also showed a tlr3-mediated nf-b activation of inos / no biosynthesis . the induction of inos / no biosynthesis may contribute not only to inflammatory response but also to initiation of no - mediated antiviral activity . regarding the canonical pathway of tlr-3-mediated antiviral response , it is speculated that a tlr3-mediated inos / no induction may be increased for an antiviral purpose in denv - infected macrophages . in conclusion , this work identifies two different pathways for nf-b activation in denv - infected raw264.7 macrophages : through the viral protein ns2b3 and through the host pattern recognition receptor tlr3 . the viral protein ns2b3-regulated production of tnf- may represent an inflammatory response with a potential immunopathogenic role in denv infection . in contrast , tlr3-regulated inos / no biosynthesis may be a host response to confer antiviral activity . obviously , both tnf- and no may modulate inflammatory activation in denv - infected macrophages .

infection with dengue virus ( denv ) causes an increase in proinflammatory responses , such as nitric oxide ( no ) generation and tnf- expression ; however , the molecular mechanism underlying this inflammatory activation remains undefined , although the activation of the transcription factor nf-b is generally involved . in addition to tnf- production in denv - infected murine macrophage raw264.7 cells , inducible no synthase was transcriptionally and posttranslationally elevated and accompanied by no generation . nf-b is known to be activated by denv infection . pharmacologically inhibiting nf-b activation abolishes inos / no biosynthesis and tnf- production . with inhibition , the potential role of nf-b in oxidative signaling regulation was prevented during denv infection . heat - inactivated denv failed to cause the identified inflammatory responses . pharmacological inhibition of tlr3 partly decreased nf-b activation ; however , it effectively abolished inducible inos / no biosynthesis but did not inhibit tnf- production . in contrast to tlr3 , viral protein ns2b3 also independently contributed to nf-b activation to regulate tnf- production . these results show the distinct pathways for nf-b activation caused by denv infection individually for the regulation of inos / no and tnf- expression .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Corrosion Prevention Act of 2006''. SEC. 2. CREDIT FOR CORROSION PREVENTION AND MITIGATION MEASURES. (a) In General.--Subpart D of part IV of subchapter A of chapter 1 of the Internal Revenue Code of 1986 (relating to business-related credits) is amended by adding at the end the following new section: ``SEC. 45N. CORROSION PREVENTION AND MITIGATION MEASURES. ``(a) In General.--For purposes of section 38, the corrosion prevention and mitigation credit determined under this section for the taxable year is an amount equal to 50 percent of the excess of-- ``(1) qualified corrosion prevention and mitigation expenditures with respect to qualified property, over ``(2) the amount such expenditures would have been, taking into account amounts paid or incurred to satisfy Federal, State, or local requirements. ``(b) Qualified Corrosion Prevention and Mitigation Expenditures.-- For purposes of this section-- ``(1) In general.--The term `qualified corrosion prevention and mitigation expenditures' means amounts paid or incurred by the taxpayer during the taxable year for engineering design, materials, and application and installation of corrosion prevention and mitigation technology. ``(2) Certification may be required.--The Secretary shall require by regulation that no amount be taken into account under paragraph (1) for any design, material, application, or installation unless such design, material, application, or installation meets such certification requirements as the Secretary shall require. Such requirements shall provide for accreditation of certifying persons by an independent entity with expertise in corrosion prevention and mitigation technology. ``(3) Corrosion prevention and mitigation technology.-- Corrosion prevention and mitigation technology includes a system comprised of at least one of the following: a corrosion- protective coating or paint; chemical treatment; corrosion- resistant metals; and cathodic protection. The Secretary from time to time by regulations or other guidance modify the list contained in the predecing sentence to reflect changes in corrosion prevention and mitigation technology. ``(4) Qualified property.--The term `qualified property' means property which is-- ``(A) comprised primarily of a metal susceptible to corrosion, ``(B) of a character subject to the allowance for depreciation, ``(C) originally placed in service by the taxpayer, and ``(D) located in the United States. ``(c) Recapture of Credit.-- ``(1) In general.--If, as of the close of any taxable year, there is a recapture event with respect to any qualified property for which a credit was allowed under subsection (a), the tax of the taxpayer under this chapter for such taxable year shall be increased by an amount equal to the product of-- ``(A) the applicable recapture percentage, and ``(B) the aggregate decrease in the credits allowed under section 38 for all prior taxable years which would have resulted if the qualified corrosion prevention and mitigation expenditures of the taxpayer with respect to such property had been zero. ``(2) Applicable recapture percentage.-- ``(A) In general.--For purposes of this subsection, the applicable recapture percentage shall be determined from the following table: ``If the property ceases to be qualified property The recapture within: percentage is: (i) One full year after placed in service......... 100 (ii) One full year after the close of the period 80 described in clause (i).......................... (iii) One full year after the close of the period 60 described in clause (ii)......................... (iv) One full year after the close of the period 40 described in clause (iii)........................ (v) One full year after the close of the period 20. described in clause (iv)......................... ``(B) Recapture event defined.--For purposes of this subsection, the term `recapture event' means-- ``(i) Cessation of use.--The cessation of use of the qualified property. ``(ii) Change in ownership.-- ``(I) In general.--Except as provided in subclauses (II), the disposition of a taxpayer's interest in the qualified property with respect to which the credit described in subsection (a) was allowable. ``(II) Agreement to assume recapture liability.--Subclause (I) shall not apply if the person acquiring the qualified property agrees in writing to assume the recapture liability of the person disposing of the qualified property. In the event of such an assumption, the person acquiring the qualified property shall be treated as the taxpayer for purposes of assessing any recapture liability (computed as if there had been no change in ownership). ``(III) special rule for tax exempt entities.--Subclause (II) shall not apply to any tax exempt entity (as defined in section 168(h)(2)). ``(iii) Special rules.-- ``(I) Tax benefit rule.--The tax for the taxable year shall be increased under paragraph (1) only with respect to credits allowed by reason of this section which were used to reduce tax liability. In the case of credits not so used to reduce tax liability, the carryforwards and carrybacks under section 39 shall be appropriately adjusted. ``(II) No credits against tax.--Any increase in tax under this subsection shall not be treated as a tax imposed by this chapter for purposes of determining the amount of any credit under this chapter or for purposes of section 55. ``(III) No recapture by reason of casualty loss.--The increase in tax under this subsection shall not apply to a cessation of operation of the property as qualified property by reason of a casualty loss to the extent such loss is restored by reconstruction or replacement within a reasonable period established by the Secretary. ``(d) Denial of Double Benefit.--For purposes of this subtitle-- ``(1) Basis adjustments.-- ``(A) In general.--If a credit is determined under this section for any expenditure with respect to any property, the increase in the basis of such property which would (but for this subsection) result from such expenditure shall be reduced by the amount of the credit so allowed. ``(B) Certain dispositions.--If, during any taxable year, there is a recapture amount determined with respect to any property the basis of which was reduced under subparagraph (A), the basis of such property (immediately before the event resulting in such recapture) shall be increased by an amount equal to such recapture amount. For purposes of the preceding sentence, the term `recapture amount' means any increase in tax (or adjustment in carrybacks or carryovers) determined under subsection (c). ``(2) Other deductions and credits.--No deduction or credit shall be allowed under this chapter for any expense taken into account under this section. ``(e) Regulations.--The Secretary shall prescribe such regulations as may be appropriate to carry out this section.''. (b) Credit Made Part of General Business Credit.--Subsection (b) of section 38 of such Code (relating to current year business credit) is amended by striking ``plus'' at the end of paragraph (29), by striking the period at the end of paragraph (30) and inserting ``, plus'', and by adding at the end thereof the following new paragraph: ``(31) Corrosion prevention and mitigation credit determined under section 45N(a).''. (c) Clerical Amendment.--The table of sections for subpart D of part IV of subchapter A of chapter 1 of such Code is amended by inserting after the item relating to section 45M the following new item: ``Sec. 45N. Corrosion prevention and mitigation measures.''. (d) Effective Date.--The amendments made by this section shall apply to taxable years beginning after the date of the enactment of this Act.

Corrosion Prevention Act of 2006 - Amends the Internal Revenue Code to allow a business-related tax credit for 50% of net expenditures for engineering design, materials, and application and installation of corrosion prevention and mitigation technology for depreciable property comprised primarily of metals susceptible to corrosion.

seaweeds are key ecological factors in shallow marine areas forming the base of the trophic web and structuring ecosystems especially on consolidated substrata . hence , the pharmaceutical and the cosmetics industries have a special interest in algae as sources of specific molecules [ 14 ] . also , several works have investigated their value in human and animal nutrition [ 58 ] . among the algae - derived compounds , polyunsaturated fatty acids are especially important as they act as antioxidant agents involved in many physiological processes [ 9 , 10 ] . the studies to determine the fatty acids profiles started some years before and many of them focused on the use of these compounds as biomarkers for chemotaxonomy , though their concentration may be susceptible to environmental interference [ 1114 ] . some of the main important factors that influence the algae fatty acid concentration are the temperature , [ 15 , 16 ] , types of habitat [ 15 , 17 ] , and presence of metals and pollutants [ 12 , 13 , 18 ] . although less common , other approaches using fatty acids have explored the effects of industrial effluents and environmental variables on the amount and quality of fatty acids produced [ 19 , 20 ] and their role in food assimilation by herbivorous invertebrates . fernando de noronha archipelago is an isolated group of islands formed by relatively recent volcanic processes . the islands are located approximately 350 km off the northeastern brazilian coast and are part of pernambuco state . the archipelago was established as a marine protected area since 1988 , and its marine flora is composed of 128 taxa , including 44 species of chlorophyta , 62 of rhodophyta , and 22 of phaeophyta . the most abundant benthic algae groups found in the archipelago are represented by the families dictyotaceae and sargassaceae . other seaweeds also commonly found are the green algae caulerpa verticillata and red algae galaxaura spp . [ 23 , 24 ] . as part of a broader research project aimed to study chemical compounds of seaweeds from fernando de noronha , herein is provided baseline information on the fatty acids produced by eleven species commonly found in the archipelago . samples were collected between february and march 2006 at two sites of the main island , caieiras beach ( 35018.8s , 322357.3w ) and sueste bay ( 3521.2s , 322519.7w ) . research permit from the brazilian environmental agency ( ibama ) to collect algae was registered under number 050/2006 . seaweeds were randomly collected by hand by uprooting the whole plant , which were placed in labeled plastic bags , frozen , and sent to the laboratory . the algae were identified , cleaned from epiphytes , animals , and sediment , washed with distilled water , and in an oven at 40c dried for seven days . ten milliliters ( 10 ml ) of dichloromethane ( j. t. baker , phillipsburg , nj , usa ) were added to 1 g ( dried weight ) of each species of algae and submitted to ultrasonic bath for 30 minutes . this procedure was repeated three times and the total extract was concentrated on nitrogen gas . subsequently , 2.0 ml of 1.0 m sodium methoxide were added to the extract and shaken occasionally during five minutes at 65c . after cooling the extract , 1.0 ml of water and three samples of 1.0 ml of chloroform ( j. t. baker , phillipsburg , nj , usa ) was added to each sample , shaken for one minute , and centrifuged at 3000 rpm , or 1612.8 g , to extract methyl esters of the fatty acids . the chloroform phase ( 3.0 ml ) , was removed and nitrogen gas was used to evaporate the solvent . samples were suspended in 1.0 ml ethyl acetate ( j. t. baker , phillipsburg , nj , usa ) , and sodium sulphate anhydrous ( sigma inc . , st . samples were analyzed through gc - ms ( gas chromatography coupled to mass spectrometer detector ) in a shimadzu qp2010 with ionization source of 70 ev and fragmentation by electronic ionization ( ei ) . the volume of 1.0 l for each sample was injected at 220c in a dbwax column ( 30 m 0.25 mm 0.25 m ) . the analysis occurred with 1-minute sample time in the splitless mode , a column flow of 1.3 ml min , a linear velocity of 41.4 cm s , and scan between m / z 40 and m / z 500 . oven 's temperature started with 50c , increasing to 20c min until 200c , kept in this temperature for 5 minutes , then increased to 5c min until 230c and kept in this temperature for 30 minutes . for identification of compounds , the peaks were compared with some standards and always consulting the libraries wiley version no . 7 and nist version nos . the gc - ms analysis had excellent resolution , and the characteristics of the detected unsaturated and saturated fatty acids are given in tables 2 and 3 . the eleven species have myristic acid ( 14 : 0 ) , pentadecanoic acid ( 15 : 0 ) , palmitic acid ( 16 : 0 ) , stearic acid ( 18 : 0 ) , oleic acid ( 18 : 1 , n ) , linoleic acid ( 18 : 2 ) , arachidonic acid ( 20 : 4 ) , and eicosapentaenoic acid ( 20 : 5 ) . the major compounds were hexadecanoic acid methyl ester and phytol , which were detected in all samples analyzed . other apolar compounds , mainly alcohols , were also identified and are provided in table 4 . the only seaweed in which 20 : 0 fatty acid was absent was the green algae , c. verticillata , and the acid 17 : 0 was absent in only one red algae . there were problems in isomer identification while conducting tentative taxonomic analysis , especially in double and triple bonds of c16 and c18 fatty acids , due to great similarity in retention time and in the molecular fragmentation in mass spectrum . few differences were observed in the production of fatty acids by brown , green , and red algae . also , as only one species of green seaweed was analyzed , this prevents further taxonomic comparisons with brown and red algae . in spite of the fact that gc - ms is a highly efficient and sensitive method of analysis , it was unable to precisely determine which of the polyunsaturated fatty acids with 16 or 18 atoms of carbon was present in each species . other apolar compounds detected had a more restrict distribution among species , and although most of them were detected in only one species , it was not possible to use them as chemotaxonomy markers , that is , phytol or loliolide . moreover , the fatty acids referred to as chemotaxonomic agents in previous investigations [ 14 , 17 ] did not allow discerning brown , green , and red algae in the present study . fernando de noronha is an area subjected to low levels of pollution because it is a marine protected area where anthropic activities are controlled . hence , it would be interesting to compare the fatty acid profiles obtained in this study with the ones from coastal areas of the main land near of the archipelago region that has different degrees of pollution . fatty acid profiles or other algae species , which are widely distributed and resistant to environmental changes , might be compared to the profiles of specimens collected in areas subjected to agrotoxics , solvents , and metals , as already done by tewari et al . with mercury . in addition , the baseline information obtained may also be applicable to a long - term ongoing research focusing on the sea urchins , which are important grazers in the archipelago , in order to determine possible relationships between the algae species consumed and their assimilation efficiency by those invertebrates . the methodology used allowed determining the fatty acid profile of eleven seaweed species from fernando de noronha archipelago . as no specificity was found in the presence of a particular set of fatty acids , these compounds could not be used as taxonomic indicators in this case .

hyphenated techniques of gas chromatography coupled to mass spectrometer were used to determine fatty acids in eleven species of seaweeds from fernando de noronha archipelago . the main compounds detected in all studied species were the alcohol phytol and the fatty acids 14 : 0 ; 15 : 0 ; 16 : 0 ; 18 : 0 ; 18 : 1 n9 ; 18 : 2 9,12 ; 20 : 4 ; 20 : 5 . these fatty acids are commonly found in seaweeds present in warm regions . thus , we found no specificity in the presence of a particular set of fatty acids and the studied species indicating that they are not useful as taxonomic indicators . however , they could be used in a comparative study with algae found in polluted area because many of the studied seaweeds are widespread and fernando de noronha has low human influence .

Things are heating up for America's favorite dad, who is in the midst of a firestorm over allegations of sexual assault. (USA NOW, USA TODAY) Entertainer Bill Cosby gestures during an interview about the upcoming exhibit, Conversations: African and African-American Artworks in Dialogue, at the Smithsonian's National Museum of African Art. (Photo: Evan Vucci, AP) NPR Weekend Edition host Scott Simon spoke out on Twitter Sunday night to address his recent interview with Bill Cosby in which the 77-year-old comedian refused to answer questions about multiple sexual assault allegations that have recently become public again. In the interview, Simon asked Cosby about the "serious allegations raised" against him, and in response, Cosby remained silent, shaking his head "no." When asked if he wanted to address allegations, Cosby again shook his head. Simon's tweets explain his reasoning in addressing the allegations, and clarify the conditions over which he held the interview. Following the Weekend Edition segment, Cosby's publicist, David Brokow, announced he would not appear on the Nov. 19 episode of The Late Show With David Letterman. Cosby also postponed a visit to The Queen Latifah Show scheduled for Oct. 30, after comedian Hannibal Buress brought attention to the allegations when he called Cosby a rapist during a stand-up routine earlier that month. In a statement to the Associated Press Sunday, Cosby's attorney said he would not dignify "decade-old, discredited" claims of sexual abuse. Here are Simons tweets: Pls let me try to answer some of the questions I've gotten on the @BillCosby interview. http://t.co/A0NNdk5REI #'s follow — Scott Simon (@nprscottsimon) November 17, 2014 1) I did not see Camille Cosby's reaction because I looked directly at Mr. Cosby. That question was for him alone, not her. — Scott Simon (@nprscottsimon) November 17, 2014 2a) I have never interviewed @billclinton But yes, I would ask him such questions if fact warranted. This being noted- — Scott Simon (@nprscottsimon) November 17, 2014 2b) few public figures have already had to answer questions about sexual conduct in public as @billclinton already has. — Scott Simon (@nprscottsimon) November 17, 2014 3a) The charges against Mr. Cosby have not been "discredited" as his atty suggests. There were out of court settlements- — Scott Simon (@nprscottsimon) November 17, 2014 3b)-this noted, Barbara Bowman & Tamara Green have been outspoken, & not in settlement. Mr. Cosby free to talk. — Scott Simon (@nprscottsimon) November 17, 2014 3c) & charges are worth reading. Not just personal philandering. Serious physical assault of many women over time. — Scott Simon (@nprscottsimon) November 17, 2014 4a) Mr. Cosby's ppl approached us for interview on occasion of lending art to Smithsonian. & we talked about it. But- — Scott Simon (@nprscottsimon) November 17, 2014 4B)-once charges publicized, we could not duck asking. We even felt he might welcome the chance to say, "It's not true." — Scott Simon (@nprscottsimon) November 17, 2014 A last thought now: Mr. Cosby was w/ his famous Hollywood PR man. He could not have been "ambushed" by my question. — Scott Simon (@nprscottsimon) November 17, 2014 Bill Cosby meme fail on Twitter is just latest in social media campaigns gone wrong. (USA NOW, USA TODAY) Contributing: Jayme Deerwester Follow @lindsdee on Twitter. Read or Share this story: http://usat.ly/1qNG9iH ||||| Sexual assault accusations have been raining down on Bill Cosby over the last week or two, above and beyond a 2006 out-of-court payoff to alleged victim Andrea Constand. 13 women have reportedly accused the comedian of intimate transgressions of one kind or another. Last Thursday the Washington Post published a piece by alleged Cosby victim Barbara Bowman. In response to which Cosby cancelled an appearance on Late Night with David Letterman and refused to discuss the issue with NPR’s Scott Simon in an audio interview posted on 11.15. I’m recapping the basics because an old friend, former actress, music industry publicist and journalist Joan Tarshis, has decided to share her own, heretofore private story about her unfortunate encounter with Cosby back in 1969. She had opportunities to spill to the tabloids a few years back but she didn’t want to go that route. The flood of recent Cosby coverage has changed her mind. She got in touch this morning and sent me the following: “I was 19 years old in autumn of 1969. I had flown to Los Angeles from New York to work on a monologue with Godfrey Cambridge. Two women I was staying with were friends of Bill Cosby, and they took me to have lunch with him in his cottage at Universal Studios, where he was shooting The Bill Cosby Show. He was always generous with his food and drinks, though he never drank alcohol. But he always topped my Bloody Mary’s with beer, which he called a ‘redeye.’ “Cosby seemed to take a liking to me, and so I was invited back a few times. I was naturally flattered. I visited the set on my own and he once introduced me to Sidney Poitier as ‘Midget,’ his pet name for me because I was 5’3″. “One day he asked me to stay after the shooting and work on some material with him. I was even more flattered and thought this would help move my writing career along. In his bungalow he made me a redeye, and I began to tell him about the earthquake Los Angeles had just had and the sound it made. He liked my ideas for an earthquake bit. “The next thing I remember was coming to on his couch while being undressed. Through the haze I thought I was being clever when I told him I had an infection and he would catch it and his wife would know he had sex with someone. But he just found another orifice to use. I was sickened by what was happening to me and shocked that this man I had idolized was now raping me. Of course I told no one. “Back home with my parents, my mother kept bringing his name up as a source of pride. Cosby was very hot then with his first sitcom, The Bill Cosby Show, and she was proud that her daughter had written with him. So the day that he called, she answered the phone and he told her he was inviting me to The Westbury Music Theater. I was repulsed by the thought of seeing him again, but I saw no way out. I couldn’t tell my mother what he had done. Or what I had let happen, feeling the guilt that rape victims often feel. “He sent a limo to pick me up and I was dropped off at the Sherry Netherland Hotel and went up to his suite. I remember noticing that his leather shaving kit was filled with bottles of pills, and thinking that this seemed odd. He was, of course, very friendly and I, of course, was very uncomfortable. He made me a redeye, and I, being nervous and dealing at the time with an alcohol problem (I’ve been in recovery since 1988), drank it. In the car I had something else to drink, but was already beginning to feel a bit stoned. “When we got to Westbury and he went on, there was no seat for me. I stood in the back of the theater with his chauffeur, feeling insulted that I wasn’t respected enough to be given a reserved seat. But soon after, I remember feeling very, very stoned and asking his chauffeur to take me back to the car. I was having trouble standing up. The next thing I remember was waking up in his bed back at the Sherry, naked. I remember thinking ‘You old shit, I guess you got me this time, but it’s the last time you’ll ever see me.’ “It took me about 20 years to admit this to anyone. My girlfriend, who was a cartoonist, told me she had heard rumors about Cosby, and believed them. She always thought where there’s smoke there’s fire. “But during those years as I grew into adulthood, I watched Cosby be praised by everyone from Presidents to Oprah to the Jello Corporation. It all made me ill, knowing first-hand there was something unbalanced about him. I had heard and/or strongly suspected I was not the only white girl he had drugged and raped but I never had any proof. No one began talking until 2004. And though I knew I should say something, I still felt ashamed. Ashamed that I didn’t earlier. “In any event now, as more and more of his rape victims have come forward, all telling similar stories, the time is right to join them.”

– The sex assault accusations against Bill Cosby keep snowballing. After a week in which one of his more vocal accusers, Barbara Bowman, hit the media circuit, a new accuser has come forward. Jeffrey Wells at Hollywood Elsewhere says "old friend [and] journalist" Joan Tarshis has now revealed her own alleged experiences with Cosby in 1969, when she was just 19 years old. She tells Wells that the comedian drugged and sexually assaulted her on two separate occasions and that even though Cosby didn't drink himself, he always made her a "redeye" (a Bloody Mary topped with beer); in one instance after she drank one, she says she woke up naked in his hotel bed; another time she says she woke up as she was being undressed and was subsequently raped. "Through the haze I thought I was being clever when I told him I had an infection and he would catch it and his wife would know he had sex with someone," she says. "But he just found another orifice to use. I was sickened by what was happening to me and shocked that this man I had idolized was now raping me. Of course I told no one." Cosby appeared on NPR's Weekend Edition on Saturday, where Scott Simon pressed him about the "serious allegations raised"; Cosby said nothing and his lawyer yesterday dismissed the "decade-old, discredited allegations. In a follow-up tweet, Simon notes, "The charges against Mr. Cosby have not been 'discredited' as his atty suggests. There were out of court settlements"; more from Simon on the interview here.

nucleoli are non - membrane - bound structures within the nucleus where ribosomal rna ( rrna ) genes are transcribed . these atypical cellular organelles consist of three major compartments with specific functions : ( 1 ) fibrillar centers ( fc , pre - rrna synthesis ) , ( 2 ) dense fibrillar components ( dfc , pre - rna processing ) , and ( 3 ) granular components ( gc , ribosome assembly ) . their organization allows hosting a number of proteins and rnas with an important role in various cellular processes . thus the perturbation of nucleolar dynamic assembly exerts profound effects on several cellular functions . a detailed description of nucleolar morphology and organization has been provided elsewhere [ 1 , 2 ] . here we focus on the mechanisms by which nucleolar activity may regulate neuronal function and survival and contribute especially to neurodegenerative diseases . one intriguing mechanism to control embryonic development , differentiation , and survival is the nucleolar shuttling of cell cycle regulators and transcription factors dictating cell lineage to the nucleoplasm . for example , during the embryonic development , transcription of rrna genes is repressed by lineage - commitment transcription factors turning off the pluripotency genes . during neural lineage commitment there is no direct evidence that rrna transcription is inhibited ; it is likely , however , that mechanisms involving nucleolar dynamics could be in play . for example in brain and retina the levels of the nucleolar protein nucleostemin , a controller of pre - rrna processing , are rapidly reduced before cell cycle exit and neural differentiation [ 4 , 5 ] , suggesting that rrna biosynthesis may have a regulatory effect on neurogenesis . however , the major regulatory function associated with altered dynamics of nucleolar proteins is connected to the stress response and involves among others the release of ribosomal proteins ( rps ) to the nucleoplasm . in response to adverse growth conditions , metabolic deficits , and oxidative stress , rrna synthesis disruption of ribosome biogenesis releases rps such as l5 , l11 , l23 , and s7 into the nucleoplasm where they interfere with the activity of the e3 ubiquitin ligase mdm2 . normally , this enzyme promotes proteasomal degradation of the transcription factor p53 , but this function is impaired by rps leading to accumulation of p53 , which in turn initiates transcriptional and non - transcriptional programs . by sensing cellular stress signals and transmitting them to the p53 stabilization system the nucleolar protein nucleophosmin is dowregulated upon excitotoxic stimuli in neurons and alters p53 levels . nevertheless , nucleophosmin - induced cell death appears to be p53 independent , suggesting that other yet unknown pathways control the stress response . more regulatory functions can be postulated based on the observation that the nucleoli are also composed of rnas , which are involved in the processing and maturation of cellular rnas . for example , small nuclear rnas are modified in the nucleolus , suggesting a possible link between nucleolar activity and splicing regulation . in mature neurons changes in protein synthesis during synaptic activity are linked to increased number of nucleoli , by the postsynaptic protein aida-1d that regulates the generation of functional nucleoli by enhancing the release of small nuclear ribonucleoproteins ( snrnps ) to the nucleoli . more recently , a significant number of small non - coding rnas ( ncrnas ) regulating mrna translation have been located in the gc of the nucleolus . although the role of this nucleolar transit is not understood , it is tempting to speculate that the regulation of micrornas ( mirnas ) processing and location is an additional mechanism linking nucleolar activity to protein synthesis regulation . recently , it has been demonstrated that also specific stress stimuli such as acidosis and heat shock induce immobilization of proteins by long ncrnas in the nucleolus . in turn , reduced levels of ribosomal proteins may alleviate mirna - mediated repression of translation initiation , highlighting the finely tuned cross - talk of the translational components that have their epicenter in the nucleolus . these premises and the increasing evidence of the role of ncrnas in neuronal development and plasticity support the unexplored functional link between nucleolus and ncrnas in neuronal survival and activity . in summary , by sequestering regulatory proteins and rnas , and by influencing their dynamics upon specific stimuli , the nucleolus can finely tune distinct cellular functions beyond protein synthesis under physiological conditions . it is well known that nucleolar malfunction contributes to the pathology of several rare human genetic disorders , such as werner syndrome , dyskeratosis congenita , treacher collins syndrome and predisposes to certain forms of cancer [ 17 , 18 ] . moreover , decline in rrna synthesis and nucleolar size occur during aging , which is the principal risk factor for neurodegenerative diseases [ 19 , 20 ] . one of the major problems in neurodegenerative diseases is that the majority of cases are sporadic and , even when an inherited basis is ascertained , there is a high inter - individual variability . current treatments only help to ameliorate the symptoms but treatments that stop or reverse the pathology are still missing . the interest on nucleolar stress is gaining momentum and the number of studies is rapidly growing over the last years ( fig . 1 ) . a focus on the role of nucleolar stress for neuronal activity and survival offers a basic and yet transformative perspective to the field of research on neurodegeneration . for example , silencing of rdna may occur during early stages of alzheimers disease ( ad ) pathology and play a role in ad - related ribosomal deficits and , ultimately , in dementia . in line with this speculation , differential methylation activity of the human rdna has been proposed as a mechanism to decrease rrna gene expression in ad patients . thus , rdna specific methylation pattern could be used as a marker of the disease or of its progression .fig . 1diagram showing the increasing number of publications and citations related to nucleolar stress . a number of publications found in pubmed database searching for nucleolar + stress . only four out of 39 publications have been published before the year 2005 . b number of times the publications in ( a ) have been cited ; asterisk , last updated on aug 31 , 2012 diagram showing the increasing number of publications and citations related to nucleolar stress . a number of publications found in pubmed database searching for nucleolar + stress . only four out of 39 publications have been published before the year 2005 . b number of times the publications in ( a ) have been cited ; asterisk , last updated on aug 31 , 2012 nucleolar integrity is disrupted in dopaminergic neurons of parkinsons disease ( pd ) patients in human post - mortem brain samples . treatment of mice with the neurotoxin mptp ( widely used in pharmacological models of pd to inhibit complex i activity in dopaminergic neurons ) , decreases rrna synthesis causing early nucleolar disruption . the findings demonstrating that impaired mitochondrial activity affects nucleolar function support the concept that nucleolar stress may occur at early disease stages and that contributes to the pathogenesis . although the molecular basis of this control is still not understood , regulators of rrna transcription might be involved . in fact , previous studies identified nucleolin as a protein - regulating rrna synthesis and ribosome biogenesis [ 24 , 25 ] and interacting with alpha - synuclein and dj-1 , two major proteins involved in familial pd pathogenesis . strikingly , the expression levels of nucleolin are dramatically reduced in the substantia nigra pars compacta of human pd patients . more recently , misfolded dj-1 protein caused by l166p mutation has been shown to alter rrna biogenesis in cellular models of pd , further supporting the association of impaired nucleolar activity with pd pathogenesis . these neurodegenerative diseases are associated with expansion of trinucleotide in repeats transcribed or untranscribed region of different genes . huntington s disease ( hd ) , for instances , is associated with an expansion in exon 1 of the huntingtin gene , which leads to an aberrant polyglutamine tract in the huntingtin protein . rrs1 ( regulator of ribosome synthesis ) , a protein inhibiting transcription of both rrna and ribosomal protein genes , is highly expressed in a presymptomatic hd mouse model . the levels of the basal rna polymerase i factor ubf1 are decreased in cellular and animal hd models . in post - mortem specimens of human hd cases , insoluble aggregates of huntingtin a hallmark of this disorder are found in the nucleolus . the presence of insoluble protein aggregates is not limited to hd and is a rather common feature of neurodegenerative diseases . for instances , aggregates are found in the nucleolus of spinocerebellar ataxia patients , an inherited disorder caused by cag or ctg expansion [ 30 , 31 ] . in these neurodegenerative diseases nucleolin appears to play a role because cag rnas deprive rrna promoter of this histone chaperone , downregulating rrna transcription . abnormal interaction with nucleolin also accounts for the neurological disorder ataxia with oculomotor apraxia type 1 , due to mutated aprataxin . in several human cancers the angiogenic ribonuclease angiogenin ( ang ) is upregulated and acts as a transcription factor , binding to rrna promoters and stimulating rrna transcription . moreover , nucleolar activity may be repressed by inhibition of the proteasomal machinery , another hallmark of neurodegenerative diseases . dysfunction of snrnp biogenesis involves protein relocalization to the nucleolus in type i spinal muscular atrophy , an autosomal recessive disorder leading to degeneration and death of motor neurons caused by loss or mutations of the survival motor neuron 1 gene . mutant rna molecules downregulating rrna transcription in polyglutamine diseases and mutant proteins altering the localization of nucleolar proteins in pd show an active role of mutant gene products to cause rrna transcription failure , supporting similar mechanistic studies in other neurodegenerative disorders . the association of nucleolar stress with neurodegenerative diseases raises the question of what cellular and molecular alterations depend on it . recently developed mouse models in which nucleolar function is specifically impaired have provided the first mechanistic insights into nucleolar stress in the nervous system . these models are based on the genetic ablation of tif - ia , an evolutionary conserved transcription factor essential for the recruitment of rna polymerase i to rrna promoters . since its identification , it was evident that tif - ia activity is strongly dependent on external signals . by now , it is known that tif - ia is regulated by a variety of protein kinases at distinct serine residues : erk and rsk in response to mitogenic signals , s6k in response to growth stimuli [ 39 , 40 ] , jnk2 in response to oxidative stress , ampk in response to cellular energy status , perk - dependent phosphorylation in response to endoplasmic reticulum stress ( fig . 2 ) . in addition , proteasome activity is required for pre - rrna synthesis and tif - ia may represent a potential link by which proteasomes are recruited to rrna genes .fig . 2schematic of the rna polymerase i machinery at the rdna promoters with the different signals and pathways regulating tif - ia activity and exerting positive or negative control on nucleolar activity and integrity schematic of the rna polymerase i machinery at the rdna promoters with the different signals and pathways regulating tif - ia activity and exerting positive or negative control on nucleolar activity and integrity tif - ia global knock - out in mice results in early embryonic lethality . specific loss of tif - ia in neural progenitors leads to rrna synthesis inhibition , nucleolar disruption , rapid apoptotic death of developing neurons , and consequent anencephalia . the conditional ablation of tif - ia in mice offers the major advantage of allowing focused investigation on the impact of nucleolar stress not only on cell cycle and growth regulation of neural progenitors , but also on quiescent postmitotic neurons in living organisms . inactivation of the tif - ia gene in adult dopaminergic neurons by a drug - inducible approach leads to a phenotype closely resembling pd , characterized by depletion of dopamine in the striatum , oxidative stress , mitochondrial impairment , progressive and differential loss of dopaminergic neurons in the substantia nigra pars compacta , as well as marked deficiencies in motor performance . at the mechanistic level , mtor activity is downregulated by tif - ia ablation in dopaminergic neurons , underscoring a negative feedback that co - regulate and coordinate the translational process . in addition , the p53-dependent apoptosis in proliferating cells appears to be conserved in dopaminergic neurons under nucleolar stress , as shown by increased neuronal survival in absence of p53 . the importance of p53 for the pathogenesis of neurodegenerative diseases has been clearly shown for hd , and further confirmed also for ad and pd . it is suggested that p53 could also serve as a convergence point in the molecular pathways for different neurodegenerative diseases . p53 induces cell cycle arrest , senescence , and apoptosis in response to different stress signals such as dna damage , hypoxia , nutrient deprivation , and nucleolar stress . however , identifying the key elements that define a particular p53-mediated stress response outcome remains a central , yet unresolved , question . the identification of such downstream effectors is crucial to manipulate the deleterious consequences of cellular stress mediated by nucleolar disruption . nucleolar stress may start a progressive series of events affecting protein translation , which can be deregulated in consequence of altered distribution of nucleolar proteins and/or biogenesis of mirnas , as well as of other cellular mechanisms . because ribosomes seem to be specialized for the synthesis of specific mrna , nucleolar stress by regulating ribosomal composition could specifically affect the translation of particular sets of mrna in developing and adult neurons . the activation of p53 and the negative feedback on mtor call in play metabolic and survival pathways executing cell fate decision , by inhibiting mitochondrial function and protein synthesis ( fig . non - traditional nucleolar roles are depicted as concentric circles with the early events closer to the nucleolus and intersecting with the traditional nucleolar role in protein synthesis summary of the cellular and molecular alterations derived from nucleolar stress . the non - traditional nucleolar roles are depicted as concentric circles with the early events closer to the nucleolus and intersecting with the traditional nucleolar role in protein synthesis the tif - ia - based models will allow exploring initial adaptive mechanisms to stress conditions and by indirectly interfering with p53 turnover in specific cells can be used to gain understanding of context - dependent p53 functions . some attempts have been reported to overexpress p53 in a constitutive and/or inducible way by the generation of transgenic mice , but engineered mice having high p53 activity in specific cell types are not available because of the difficulty to generate mutant mice which reproduce the natural levels of proteins . ultimately , tif - ia mutant mice can be used to develop and validate therapeutic intervention and identify biomarkers associated with a specific degenerative pattern ( table 1 ) . modulation of the pol i transcriptional machinery is already proposed for anticancer therapies either by targeting specific components or the upstream pathways . inhibition of pol i in cancer cells has been shown to induce their apoptotic death . intriguingly , the tif - ia mutant mice have been already useful for testing the neuroprotective role of the phosphatase pten in dopaminergic neurons , supporting their possible use for evaluating new therapeutic approaches .table 1potential applications of the different types of tif - ia mutant mice for the investigation of features linked to nucleolar stresstype of mutationphenotypeapplicationglobal knock out embryonic lethality ( e8.5 ) ; growth deficitsstudy of early embryonic compensatory mechanismsembryonic neural progenitors anencephalia at birth ; impaired neurogenesis ( e13.5)study of effects on early neuronal differentiationadult hippocampal neurons progressive but differential degeneration of adult hippocampal neuronsanalysis of changes of neuronal activity and protein synthesis before neuronal deathembryonic or adult dopaminergic neurons [ 23 , 51]parkinsonism ; early mitochondrial dysfunction and mtor downregulationsearch for biomarkers ; neurorestorative / neuroprotective strategiesother neuronsunpublished observationsanalysis of context - specific responses to nucleolar stressoverexpression ; heterozygositynot determined yetrole of nucleolar stress as a disease modifier potential applications of the different types of tif - ia mutant mice for the investigation of features linked to nucleolar stress increasing evidence point to a multifactorial basis of neurodegenerative disease onset and progression . perhaps there is time to bridge the gap between the reductionist approach focused on particular molecules involved in the pathology of a particular disease . the research for identifying common molecular checkpoints as possible new targets for pharmacotherapy seems necessary . despite the total market of 2.2 billion usd estimated for anti - pd drugs major pharmaceutical companies discouraged by the relatively little progresses announced cuts to brain disorder research in favor of sequencing projects to identify genetic risk factors . investing more efforts in defining the toxic species causing rrna transcription failure and the molecular alterations of nucleolar stress in specific cellular contexts will shed new light onto the mechanisms underlying differential vulnerability to stress conditions and indicate potential targets to manipulate them . otherwise there will always be a missing piece in our understanding of neurological disorders and in our way to cure them .

nucleoli are the sites where synthesis of rrna and ribosomal assembly take place . along with these traditional roles , the nucleolus controls cellular physiology and homeostasis . the cellular and molecular alterations associated with impaired nucleolar activity ( nucleolar stress ) have just started to be systematically explored in the nervous system taking advantage of newly available animal models lacking rrna synthesis in specific neurons . these studies showed that nucleolar function is necessary for neuronal survival and that its modality of action differs between and within cell types . nucleolar function is also crucial in pathology as it controls mitochondrial activity and critical stress signaling pathways mimicking hallmarks of human neurodegenerative diseases . this mini - review will focus on the modes of action of nucleolar stress and discuss how the manipulation of nucleolar activity might underscore novel strategies to extend neuronal function and survival .

obesity is defined as an excess accumulation of adipose tissue that results when calorie intake exceeds energy expenditure . obesity can be assessed in a number of ways , including anthropometrically , using body mass index ( bmi ) ( weight ( kg)/height ( m ) ) , waist circumference , or waist : hip ratio ( waist circumference ( cm ) divided by hip circumference ( cm ) ) , or by using techniques that directly measure body fat , such as dual energy x - ray absorptiometry ( dxa ) , bioelectrical impedance analysis , computed tomography , and magnetic resonance imaging [ 2 , 3 ] . anthropometric approaches are usually used in epidemiologic studies of the association between obesity and disease risk because they are relatively inexpensive and easy to implement . using anthropometric approaches , and in particular bmi , many epidemiologic studies have shown that obesity is associated with increased risk of breast cancer in postmenopausal women [ 46 ] . however , a major limitation of bmi as an index of obesity is that the numerator ( i.e. , weight ) fails to differentiate between lean and fat mass , so that two individuals with the same bmi may differ considerably with respect to percent body fat . differences between individuals in terms of age , sex , and/or ethnicity further complicate the interpretation of bmi . other anthropometric indices such as waist circumference and waist : hip ratio are indirect measures of central adiposity rather than of whole body fat distribution . for these reasons , associations between bmi and other anthropometric indices and breast cancer risk may fail to capture the true nature of the relationship between excess body fat and risk . given the limitations of anthropometric indices , studies that employ direct measures of body fat may yield more accurate estimates of the association between adiposity / obesity and breast cancer risk . dxa directly assesses bone mineral content and the soft tissue surrounding the bone by measuring the amounts of fat and lean tissue , and it can be used to both characterize body composition and provide precise estimates of fat , bone , and bone - free lean mass . therefore , we used dxa - derived measures of body fat obtained in the women 's health initiative ( whi ) to examine the association between body fat and risk of incident , invasive breast cancer . additionally , we compared these risk estimates with those obtained using conventional anthropometric measurements . the whi is a large , multicenter study designed to foster understanding of the determinants of major chronic diseases in postmenopausal women . women between the ages of 50 and 79 and representing major racial / ethnic groups were recruited from the general population at 40 clinical centers throughout the united states between 1993 and 1998 into either the clinical trial ( ct ) component ( n = 68,132 ) or the observational study ( os ) component ( n = 93,676 ) . the ct component included several randomized controlled interventions : the hormone therapy ( ht ) trials of estrogen alone and of estrogen plus progestin , the low - fat dietary modification ( dm ) trial , and the calcium - vitamin d supplementation ( cad ) trial , none of which was designed to promote change in body weight . details of the design and reliability of the baseline measures have been published elsewhere [ 12 , 13 ] . written informed consent was obtained from all participants and the whi was approved by the institutional review boards of all participating institutions . the analyses reported here were based on the cohort of 11,393 women who had body fat assessed using dxa . self - administered questionnaires , completed at study entry , were used to collect information on demographics , medical , reproductive , and family history , and on dietary and lifestyle factors , including smoking history , alcohol consumption , and recreational physical activity . in addition , all participants had their weight , height , and waist and hip circumferences measured at baseline by trained staff using standardized protocols ; during followup , the majority had measurements taken at years three and six , and small proportions had measurements taken at years one and nine . weight was measured to the nearest 0.1 kg , and height to the nearest 0.1 cm . waist circumference at the natural waist or narrowest part of the torso and hip circumference at the maximal circumference were recorded to the nearest 0.1 cm . bmi was computed as weight ( kilograms ( kg ) ) divided by the square of height ( meters ( m ) ) . in the whi , 11,393 women in three designated centers ( birmingham , tucson / phoenix , and pittsburgh ) had body fat measured by whole body dxa scans performed in fan - beam mode and obtained from hologic qdr scanners ( qdr 2000 , 2000 + , or 4500 ) ( hologic , inc . , measurements were made at baseline and again at years one , three , six , and nine of followup . a standardized procedure for participant positioning and scan analysis was executed for all scans in the three centers . all dxa operators attended a central training session and were certified on the basis of an evaluation of scanning and analysis technique . quality control entailed having technicians at the dxa coordinating center ( university of california , san francisco ) review unacceptable scans , outliers , and a random sample of all scans . when two qdr2000 scanners were retired , in vivo cross - calibration was performed at two sites to convert qdr4500 to qdr2000-equivalent values . these correction factors and adjustments for longitudinal changes in scanner performance clinical outcomes ( including new cancer diagnoses ) were updated semiannually in the ct and annually in the os using in - person , mailed , or telephone questionnaires . self - reports of breast cancer were verified by centralized review of medical records and pathology reports by trained physician adjudicators . as of march 31 , 2011 , after a median of 12.9 years of followup , a total of 537 incident cases of breast cancer had been diagnosed among the 11,393 subjects with dxa measurements . a total of 11,393 women had dxa measurements performed during the course of the study . of these , we excluded 108 women ( 8 cases and 100 noncases ) who were missing baseline dxa measurements and 325 women ( 26 cases and 299 noncases ) with a previous history of breast cancer . this left 10,960 women available for analysis ( 503 cases and 10,457 noncases ) , of whom 380 ( 76.5% ) cases and 7628 ( 72.9% ) noncases were not in any intervention group ( os , control , placebo ) , 6 ( 1.2% ) cases and 289 ( 2.8% ) noncases were in the estrogen - alone trial intervention group and not in any other , 19 ( 3.8% ) cases and 314 ( 3.0% ) noncases were in the estrogen plus progestin trial intervention group and not in any other , 50 ( 9.9% ) cases and 943 ( 9.0% ) noncases were in the dietary modification trial intervention group and not in any other , 26 ( 5.2% ) cases and 644 ( 6.2% ) noncases were in the calcium plus vitamin d supplementation trial intervention group and not in any other , 22 ( 4.4% ) cases and 612 ( 5.9% ) noncases were in the intervention groups of 2 trials , and 0 cases and 27 ( 0.3% ) noncases were in the intervention groups of 3 trials . cox proportional hazards models were used to estimate hazard ratios ( hrs ) and 95% confidence intervals ( ci ) for the associations between various measures of body fat ( see below ) and risk of breast cancer . cases contributed person - time to the study from their date of enrollment until the date of diagnosis of their breast cancer , and noncases contributed person - time from their date of enrollment and were censored as of the end of followup ( march 31 , 2011 ) , the date of death , or the date of withdrawal from the study , whichever came first . in the first stage of the analysis , baseline body fat measures ( whole body fat mass ( g ) , whole body percent fat , fat mass of trunk ( g ) , fat mass of right leg ( g ) , fat mass of left leg ( g ) , and ratio of fat mass of trunk to average of fat mass of right and left legs ( as an estimate of upper abdominal fat versus hip fat ) ) and anthropometric indices of obesity ( bmi ( kg / m ) , waist circumference ( cm ) , and waist : hip ratio ) were used as the exposure variables , and they were categorized by quintiles . in multivariate analyses , adjustment was made for established risk factors for breast cancer and for randomization assignment in the ct . specifically , we adjusted for age ( years ) at baseline ( continuous ) , family history of breast cancer ( yes , no ) , age ( years ) at menarche ( < 12 , 12 , 13 , > 13 ) , age ( years ) at first full - term pregnancy ( < 20 , 2029 , 30 , missing ) , parity ( 0 , 1 , 2 , 3 , 4 , 5 ) , age ( years ) at menopause ( < 45 years , 4554 , 55 , missing ) , metabolic equivalents ( mets ) from physical activity ( met hours / week , continuous calculated as described elsewhere ) , history of breast biopsy ( yes , no ) , oral contraceptive use ( ever , never ) , hormone therapy ( type and duration ) , alcohol intake ( servings per week continuous ) , pack - years of smoking ( continuous ) , education ( less than high school graduate , high school graduate / some college , college graduate , postcollege ) , ethnicity ( white , black , other ) , randomization assignment in the ct , and total caloric intake ( kcal / day continuous ) . trial assignment was taken into account by including dummy variables for each arm of each trial ( i.e. , intervention , placebo , control ) in the multivariable model . tests for interaction ( with ht use ) were based on likelihood ratio tests comparing models with and without product terms representing the variables of interest , and tests for trend were performed by assigning the median value to each category of the exposure variable of interest and modeling this variable as a continuous variable . the proportional hazards assumption evaluated by testing the correlation of schoenfeld residuals of predictors with ranked survival times and by testing the interaction between the predictors of interest and log - survival times was not violated . all p values were two sided ; p values < 0.05 were considered statistically significant . in the second stage of the analysis , we analyzed the repeated body fat measurements and anthropometric indices as time - dependent covariates in cox proportional hazards models to account for fluctuations in the measurements over time . with this approach , the predictive significance of various aspects of these measures was evaluated , including time - lagged values ( 13 years , 24 years , and 35 years prior to diagnosis of breast cancer ) and the average of all measurements . the relevant time - dependent covariate for subjects at risk at time t was a function of measurements obtained only until the time of diagnosis in the index case . among cases , measurements made within 1 year of diagnosis ( n = 35 for dxa - derived body fat measurements ; n = 28 for anthropometric variables ) were excluded from all analyses since these values may have been influenced by the presence of subclinical disease . finally , in order to assess the predictive power of whole body fat mass and percent body fat versus bmi , of fat mass of the trunk versus waist circumference , and of the trunk : leg fat mass ratio versus waist : hip ratio , we computed c - indices ( the c - index is a measure of the discriminatory ability of a given survival model ) by applying a sas macro developed by the mayo clinic biostatistics group . to test for differences between the c - indices from the different models we applied an ad hoc asymptotic z - test statistic assuming that the correlations between the c - indices are 0.5 . the z scores were computed as ( c1-c2)/sqrt(se(c1 ) + se(c2 ) se(c1)*se(c2 ) ) , where c1 and c2 are estimated c - indices and se(c1 ) and se(c2 ) are their corresponding standard errors . the baseline dxa - derived body fat measurements and the anthropometric measurements were mostly moderately to strongly positively correlated with each other ( table 1 ) . however , the correlations with waist : hip ratio were generally weaker than those with the other variables , and there were inverse associations between fat mass of the right and left legs with the ratio of trunk fat mass to the average of the fat mass of the right and left legs . dxa - derived whole body fat mass was positively associated with a history of diabetes , a relatively early menarche , intake of energy , and carbohydrate , and with black race and ( to a lesser extent ) hispanic ethnicity , and was inversely associated with ever use of hormone therapy ( ht ) , and with alcohol intake and physical activity ( table 2 ) . for bmi , the patterns of associations with these variables were similar to those for dxa - derived whole body fat mass ( data not shown ) . all baseline dxa - derived body fat measures showed strong positive associations with breast cancer risk ( table 3 ) . the multivariable - adjusted hr for the uppermost quintile level ranged from 1.53 ( 95% ci 1.142.07 ) for fat mass of the right leg to 2.05 ( 95% ci 1.502.79 ) for fat mass of the trunk . these results changed little when we additionally adjusted for scanner type , a personal history of diabetes , height , carbohydrate intake , and fat intake ( data not shown ) . data on estrogen receptor ( er ) status were available for 437 cases ( 353 er+ , 84 er ) . the dxa - derived body fat variables were all strongly positively associated with risk of er+ breast cancer , but were not associated with risk of er breast cancer , and these estimates differed significantly from each other ( data not shown ) . there were too few cases to allow meaningful analyses by combined er / progesterone receptor status . when we stratified by ever use of ht , strong positive associations , of similar magnitude to those presented in table 3 , were evident in both ever and never users ( data not shown ) . the hrs for whole body fat mass , whole body percent fat , and fat mass of the right and left legs were slightly higher in never users than in ever users , whereas the reverse was observed for trunk fat . in contrast , the hrs for the ratio of trunk fat mass : leg fat mass were substantially higher in never users than in ever users : hr ( 95%ci)quintile 5 versus quintile 1 = 2.55 ( 1.534.25 ) in never users and 1.37 ( 0.902.10 ) in ever users . however , on formal testing , there was no evidence of effect modification by ht use . in sensitivity analyses , the patterns shown in table 3 were similar after exclusion of those in the intervention group of the dietary modification trial ( these subjects experienced slight weight loss during the followup period ) ; after exclusion of those in the intervention groups of the ht trials ( ht may attenuate changes in body composition with age ( e.g. , gain in percent fat mass and upper body fat ) ) ; after excluding the nine cases who were diagnosed with ductal carcinoma in situ of the breast prior to the development of invasive breast cancer ; and after excluding the first three years of followup ( to address the possibility of reverse causality ) ( data not shown ) . however , the results were somewhat attenuated after exclusion of the 83 cases and 1264 noncases who were very obese ( bmi > 35 kg / m ) ( accurate measurement of body composition is difficult in obese women [ 21 , 22 ] ) . specifically , although the hr estimates for the second to fifth quintile levels were all greater than one , they were generally lower than the comparable estimates for the entire study population , and the trends for whole body percent fat ( p = 0.12 ) , and for fat mass of the right ( p = 0.12 ) and left ( p = 0.08 ) legs , were no longer statistically significant . the hrs ( 95% cis ) for the fifth versus the first quintile level were 1.47 ( 0.992.17 ) for whole body fat mass , 1.29 ( 0.891.87 ) for whole body percent fat , 1.69 ( 1.152.47 ) for trunk fat mass , 1.24 ( 0.861.78 ) for fat mass of the right leg , 1.40 ( 0.981.99 ) for fat mass of the left leg , and 1.75 ( 1.252.44 ) for the ratio of trunk fat mass : average of right and left leg fat mass . all three anthropometric measures ( bmi , waist circumference , waist : hip ratio ) were strongly , positively associated with breast cancer risk ( table 4 ) . the multivariable - adjusted hrs ( 95% cis ) for the highest versus the lowest quintile levels were 1.97 ( 1.452.68 ) for bmi , 1.97 ( 1.462.65 ) for waist circumference , and 1.91 ( 1.412.58 ) for waist : hip ratio , and the associated trends in risk were statistically significant . these associations were evident in both ever and never users of ht and there was no evidence of effect modification by ht use ( data not shown ) . when both waist : hip ratio and bmi were included in the same model ( together with other variables included in the multivariate models ) , there was some attenuation of the associations , but both remained significant : the hrs ( 95% ci ) for the 2nd to 5th quintile levels for waist : hip ratio were 1.31 ( 0.971.78 ) , 1.34 ( 0.981.83 ) , 1.12 ( 0.801.56 ) , and 1.59 ( 1.152.19 ) , respectively , with p ( trend ) = 0.01 , and those for bmi were 1.09 ( 0.791.49 ) , 1.30 ( 0.951.78 ) , 1.26 ( 0.911.75 ) , and 1.73 ( 1.242.40 ) , respectively , with p ( trend ) = 0.0003 . of the 10,960 women who had baseline dxa measurements , 4,360 ( 40% ) had measurements at year one ( os participants were not required to have dxa measurements at this time point ) , 8,906 ( 81% ) at year three , 7,822 ( 71% ) at year six , and 3,972 ( 36% ) at year nine . table 5 shows the results of the time - dependent covariate analyses . for the average of all measurements , the results were similar to those obtained using the baseline measurements , with those for trunk fat showing the strongest association , followed by those for whole body fat mass . the association of body fat measured in different time windows was also strongest for fat mass of the trunk and for whole body fat mass , both of which showed statistically significant positive associations and trends in all time windows . the magnitude of the associations was similar for measurements made 13 years and 24 years prior to diagnosis and was somewhat stronger for those made 35 years prior to diagnosis . time - dependent covariate analyses of the anthropometric measures of obesity yielded strong , positive associations with breast cancer risk ( table 6 ) . however , the point estimates were slightly attenuated compared with those obtained using the baseline measurements only . as with the time - dependent analyses of the dxa - derived measures , the magnitude of the associations was strongest for the measurements made 35 years prior to diagnosis ( data not shown ) . the c - indices for the dxa and anthropometric variables of interest were all very similar , ranging from 0.630 for bmi to 0.645 for waist circumference ( table 7 ) . furthermore , none of the pairwise comparisons , including whole body fat mass and percent body fat versus bmi , fat mass of the trunk versus waist circumference , and the trunk : leg fat mass ratio versus waist : hip ratio , was statistically significant . additionally , the c - index for a model with both whr and bmi was 0.647 , which did not significantly improve on the c - index for a model with bmi alone ( 0.641 ) or that for a model with whr alone ( c = 0.640 ) . similarly , fitting a model with whr and total leg fat mass yielded a c - statistic of 0.649 , which did not represent a significant improvement over those for whr alone or total leg fat mass alone ( 0.636 ) . similar results were observed when we modeled whr and fat mass of the right leg and whr and fat mass of the left leg ( data not shown ) . the results of the present study provide strong support for a positive association between body fat and breast cancer risk in postmenopausal women . the dxa - derived measures of body fat and fat distribution were associated with 1.5- to 2-fold increases in breast cancer risk ( for the highest versus the lowest quintile level ) . the point estimates were strongest for fat mass of the trunk and for whole body fat mass , but the confidence intervals for these associations overlapped with those for all other body fat measures . there was no evidence of effect modification by ever use of ht , and the results were generally robust to various sensitivity analyses . however , the results were attenuated somewhat after exclusion of the very obese ( bmi > 35 kg / m ) . the results of the repeated measures analyses generally supported the findings from the analysis of the baseline measures . finally , anthropometric indices of obesity were also strongly associated with increased breast cancer risk and they predicted risk as well as the dxa - derived measures of body fat . dxa provides highly reproducible and accurate measures of body fat , and therefore it is now used extensively for estimating body composition . it allows regional analysis of fat distribution , and although it does not differentiate visceral fat from subcutaneous fat in the abdominal region , there is a strong correlation between trunk fat measured by dxa and abdominal visceral fat measured by single slice computerized tomography . variability in dxa measurements can arise because of differences between scanner models and between different versions of software from the same manufacturer [ 8 , 23 ] . in this regard ( as indicated earlier ) , in the present study , when two qdr2000 scanners were retired , in vivo cross - calibration was performed to convert qdr4500 to qdr2000-equivalent values , and these correction factors and adjustments for longitudinal changes in scanner performance were applied to participant scan results . we are not aware of any previous studies of dxa - derived measures of body fat and risk of breast cancer . nevertheless , several previous case - control and cohort studies [ 2629 ] have shown direct measures of body fat , obtained using methods other than dxa , to be positively associated with breast cancer risk . in two of these studies the association was observed with upper body fat or central adiposity , while in the remaining studies , the associations were observed with body fat overall [ 2729 ] . however , these studies were based on fewer cases ( 106 to 357 ) than the present report , did not have repeated measures of body fat , and used either skinfold thickness [ 25 , 26 ] or bioelectrical impedance analysis ( bia ) [ 2729 ] to measure body fat . both of these approaches to measuring body fat have limitations : skinfold thicknesses are measured with greater error than other anthropometric measures and are unreliable measures of central adiposity , while bia , in comparison with dxa , overestimates percent body fat in lean subjects and underestimates it in obese subjects . the associations between the dxa measures of body fat and breast cancer risk appeared to be confined largely to er+ tumors . however , given the relatively small number of er cases , this finding warrants cautious interpretation . nevertheless , it is in accord with previous observations [ 31 , 32 ] , and it has been suggested that this may result from an obesity - induced increase in circulating free estrogen levels which induce progesterone receptor expression and hence stimulation of er+/pr+ tumors . the present study also showed that anthropometric indices of obesity , namely , bmi , waist circumference , and waist : hip ratio , were all strongly , positively associated with breast cancer risk . these findings are essentially in accord with those of previous studies conducted elsewhere [ 46 ] . previous investigations in whi have also shown positive associations with bmi [ 3335 ] , although in two of these [ 33 , 35 ] the association was confined largely to those who had never used ht , and in one there was no association with waist : hip ratio . the present whi study showed further that these indices did not differ in their ability to predict risk when compared with dxa - derived measures of whole body fat mass / percent body fat , fat mass of the trunk , and trunk : leg fat mass ratio , respectively . in this regard , as in the present study , bmi has been shown in previous studies to have a relatively strong positive correlation with measures of percent body fat obtained using dxa [ 7 , 36 , 37 ] or bia [ 38 , 39 ] , while waist circumference and waist : hip ratio , which are used as indirect measures of abdominal / central obesity , have been shown to have relatively strong positive correlations with total abdominal fat and abdominal visceral fat measured using computerized tomography or magnetic resonance imaging ; waist circumference , but not waist : hip ratio , has also been shown to have strong positive correlations with percent body fat and total fat mass measured using dxa . however , bmi , the most widely used anthropometric index of obesity , has been shown to have low sensitivity for diagnosing obesity defined according to percent body fat measured using body composition measurement techniques such as dxa , bia , and air displacement plethysmography , such that substantial proportions of individuals classified as lean or overweight by bmi are classified as obese according to their percent body fat [ 3 , 43 ] . consistent with this observation , such individuals have a higher prevalence of dysregulation of metabolic factors ( e.g. , glucose , insulin , insulin resistance , c - reactive protein , etc . ) and of the associated metabolic syndrome compared to lean individuals with normal body fat amounts [ 43 , 44 ] . recent evidence from whi provides some support for an association between the metabolic syndrome and its component parts and breast cancer risk . these observations suggest that while use of bmi may allow reasonably accurate prediction of breast cancer risk for groups of individuals , it provides potentially misleading information about the risk for a given individual , with implications for clinical management , particularly of those with normal weight obesity ( i.e. , normal body weight based on bmi but relatively high body fat content ) . there is now a substantial body of epidemiologic evidence supporting a positive association between obesity in postmenopausal women and breast cancer risk . in general terms , it has been suggested that the association of obesity with increased cancer risk may result from alterations in adipocyte biology or through alterations in the stromal - vascular fraction of adipose tissue . hence , many possible mechanisms for the increase in risk have been proposed , including increased circulating levels of leptin and inflammatory cytokines ( e.g. , tnf , il-6 , pai1 ) and decreased adiponectin levels , as well as increased insulin / igf signaling , elevated lipid levels , and , particularly in relation to breast cancer in postmenopausal women , an increase in aromatase expression in adipose tissue and a decrease in circulating sex hormone - binding globulin resulting ( as mentioned earlier ) in elevated bioavailable estradiol levels [ 1 , 46 , 47 ] . however , these mechanisms may not fully explain the relationship between obesity and cancer risk , and other mechanisms , including obesity - induced hypoxia , shared genetic susceptibility between obesity and cancer , and migration of adipose stromal cells might also be relevant . the present study has several strengths including its prospective design , long - term followup , large number of breast cancer cases , essentially complete ascertainment of cases and centralized pathology review , standardized protocols administered by trained staff for measurement of anthropometric variables and of body fat using dxa , repeated measures of the variables of interest over time , and the availability of information on a wide range of potential confounding factors . limitations of the study include the fact that it was restricted to postmenopausal women , so that there were no dxa measures of body fat from earlier in life , and the limitations of dxa itself , including between - model variability in dxa measurements , although the latter issue was addressed by in vivo cross - calibration . in conclusion , the results of the present study provide strong support for a positive association between dxa - derived measures of body fat ( whole body fat mass , percent body fat , fat mass of the trunk and legs , and the ratio of trunk to leg fat mass ) and breast cancer risk in postmenopausal women . they suggest further that anthropometric indices of obesity ( bmi , waist circumference , and waist : hip ratio ) predict breast cancer risk as well as dxa - derived measures of body fat .

associations between anthropometric indices of obesity and breast cancer risk may fail to capture the true relationship between excess body fat and risk . we used dual - energy - x - ray - absorptiometry- ( dxa- ) derived measures of body fat obtained in the women 's health initiative to examine the association between body fat and breast cancer risk ; we compared these risk estimates with those for conventional anthropometric measurements . the study included 10,960 postmenopausal women aged 5079 years at recruitment , with baseline dxa measurements and no history of breast cancer . during followup ( median : 12.9 years ) , 503 incident breast cancer cases were diagnosed . hazard ratios ( hr ) and 95% confidence intervals ( ci ) were estimated using cox proportional hazards models . all baseline dxa - derived body fat measures showed strong positive associations with breast cancer risk . the multivariable - adjusted hr for the uppermost quintile level ( versus lowest ) ranged from 1.53 ( 95% ci 1.142.07 ) for fat mass of the right leg to 2.05 ( 1.502.79 ) for fat mass of the trunk . anthropometric indices ( categorized by quintiles ) of obesity ( bmi ( 1.97 , 1.452.68 ) , waist circumference ( 1.97 , 1.462.65 ) , and waist : hip ratio ( 1.91 , 1.412.58 ) ) were all strongly , positively associated with risk and did not differ from dxa - derived measures in prediction of risk .

in recent years , an increasing number of location - based services ( lbss ) have been released , mostly because of the rapid expansion of the mobile device market . lbss take advantage of geographic location to provide users with accurate and targeted information for locating friends on a map , discovering nearby social events , crowdsensing applications such as generating alerts about traffic jams along a route , and more . to ensure that such services work properly , it is necessary that geographic locations claimed by users are factual . for example , lbss with location - based access control that allow users to obtain a discount coupon , require that users can not cheat on their position , to avoid delivering coupons to those who really did not deserve them . similarly , social networks that enable users to discover where their friends are , work correctly only if geographic locations are certified . the term _ proof - of - location _ refers to a method by which a system can confirm the geographic locations of users . in literature , different approaches to this topic have been investigated and proposed . @xcite presented a trusted computing module that ensures gps data generated and transmitted by mobile devices . this solution is not acceptable inasmuch the trusted computer module would be expensive and difficult to adopt . saroiu and wolman @xcite proposed a solution where users prove their geographic locations through a wi - fi infrastructure . not even this approach is affordable , as it relies on a complex pki infrastructure that needs to be deployed and maintained . another solution introduced by zhu and cao @xcite envisages a network infrastructure that provides proof - of - location of mobile devices equipped with bluetooth . although this solution appears effective and robust , its centralized architecture eases tracking of pseudonym - identified users by malicious administrators , whereas it might hinder the deployment of user - created location - based services . with the objective of achieving a system that , at the same time , provides verification of geographic location of its users and ensures a high level of privacy to them , we have designed a completely decentralized proof - of - location mechanism for location - based peer - to - peer overlay schemes , such as overdrive by heep _ @xcite or adgt by brambilla _ _ @xcite . the decentralized nature of peer - to - peer systems guarantees higher privacy levels , as it removes the central authority knowing both the geographic location of users and the information they exchange . to endow location - based peer - to - peer overlay schemes with proof - of - location , while preserving the decentralized approach , our protocol is based on the _ block chain _ @xcite , which is mostly known for being bitcoin s core technology . in the following , peer - to - peer network , overlay network , peer - to - peer overlay and network are equivalent expressions we use with reference to the same concept . the block chain technology is a novel peer - to - peer approach , which allows to maintain a continuously - growing list of data records , linked in a way that makes them immutable . in general , a block is a set of one or more data records , prefaced by a block header and protected by a proof of some type . the initial and most widely known application of this technology is bitcoin s public transaction ledger , a digital asset and a payment system invented by satoshi nakamoto @xcite . the main feature that differentiates the block chain from all other distributed databases is its completely decentralized nature , which escapes the presence of a trusted central authority . indeed , block chain maintenance is performed by a network of communicating nodes , which store their own copy of the block chain , validate transactions , add them to their copy of the block chain , and then broadcast block additions to other nodes . all these operations are performed in such a way that _ consensus _ emerges among network nodes , about the information stored in the block chain . we have adopted the block chain technology to endow networked nodes with the capability to verify and store geographic locations , not requiring a centralized super - node that oversees sensitive data of other nodes . in our approach , recent valid proofs - of - location are recorded into blocks , which are then added to the end of the chain and , once confirmed by consensus , they can not be changed . in particular , each peer @xmath0 of the network is described by a unique i d @xmath1 , which is also its _ public key_. moreover , every peer @xmath2 is able to digitally sign messages with the _ private key _ @xmath3 associated with its i d . similarly to the solution proposed by zhu and cao @xcite , peers can communicate with near nodes through any short - range communication technology , such as bluetooth , bluetooth smart or zigbee , and they periodically use these interfaces to broadcast proof - of - location requests and responses to their neighbors . supposing next block to be confirmed is @xmath4 , a proof - of - location request contains the identifier of the peer that has produced it ( _ i.e. _ , @xmath5 ) , the geographic location of the peer , and a hash of the preceding block in the block chain @xmath6 . the request is signed with the requester s private key , so that anyone can verify that it has not been tampered with , as depicted in figure [ fig : request ] . @xmath7 the peer that receives the proof - of - location request verifies its validity , according to the following rules : 1 . the request has to come from a peer that , beyond being in touch through the short - range communication technology , is a known contact in the location - based peer - to - peer overlay scheme ; 2 . the request is digitally signed by the peer that has produced it ; 3 . the request contains an admissible geographic location , _ i.e. _ , not further than the adopted maximum distance reachable with the short - range communication technology ; 4 . the request refers to the end block of the block chain ; otherwise , peers start a synchronization process via the peer - to - peer network to align their block chains . once all checks have been fulfilled , a proof - of - location response is produced . the responding peer wraps the received request in a new message , together with its geographic location and identifier ( _ i.e. _ , its public key @xmath8 ) . the proof - of - location response is also signed with the private key of the responding peer , as illustrated in figure [ fig : response ] . @xmath9 the response is verified in a similar way to the request : 1 . the response comes from one of the peers to whom the request was sent ; 2 . the response is digitally signed by the peer that produced it ; 3 . the response contains an admissible geographic location , _ i.e. _ , not further than the maximum distance that is reachable with the adopted short - range communication technology . in case the response is correctly verified , it corresponds to a proof - of - location , attesting that two peers are geographically close to each other and specifying their geographic locations . proofs - of - location are then broadcast to the network , which records them in the public record of all proofs - of - location , namely the block chain , after validating them . when a peer receives proofs - of - location related to peers that should be located nearby , it checks for their presence in the list of contacts provided by the peer - to - peer overlay . it is expected that geographic locations specified in proofs - of - location are reasonably close to each other , within the limits of the adopted short - range communication technology . if these constraints are not fulfilled , proofs - of - location are discarded and not disseminated within the network . every peer in the network puts all known valid unacknowledged proofs - of - location into a block , together with a reference to the previous valid block known to that peer . in addition to proofs - of - location and the reference to the preceding block , the block contains the identifier of the peer that generated it . moreover , the block is signed with the private key of the peer that generated it , as shown in figure [ fig : block ] . @xmath10 afterwards , the newly created block is broadcast to the peers of the network , which decide whether to add the block to the end of the block chain or not . if the majority of peers adds the block to the block chain then consensus is achieved , therefore proofs - of - location are made persistent . otherwise , the block is discarded and not attached to the block chain . whereupon , it is verified that the hash of the referenced block matches the end block in the chain , otherwise a _ fork _ in the block chain occurs . which one branch will become part of the main block chain depends on the distributed consensus algorithm explained below . afterwards , the peer makes sure that proofs - of - location specified in the block are not already present in previous blocks of the block chain . in case a proof - of - location concerns the geographic location of the peer itself , it is checked that signatory peers of the proof - of - location are known ( _ i.e. _ , they belong to the contact list provided by the peer - to - peer overlay ) . if these conditions are not respected , the block is discarded , instead of being propagated into the network . unlike bitcoin , where distributed consensus is achieved by means of a proof - of - work technique , in our approach , a _ proof - of - stake _ mechanism is adopted , whereby next valid block in the block chain is the one produced ( _ mined _ ) by the peer that owns the majority of proofs - of - location in the latest @xmath11 blocks of the block chain . in bitcoin , peers are encouraged by the reward they earn to repeatedly run hashing algorithms to validate transactions . conversely , our protocol does not require such an extremely time - consuming work , thus there is no reward for mined blocks , albeit it can be provided at the application layer . therefore , in case a peer receives more than one valid block from its neighbors , it will add to the end of its block chain the one produced by the peer that has received the largest number of proofs - of - location , in the latest @xmath11 blocks . moreover , to prevent the monopoly problem , _ i.e. _ , a peer that keeps out proofs - of - location that concern other peers from the block it produces with the purpose to remain the peer that owns the majority of proofs - of - location and , therefore , that takes control of the block chain , the protocol prevents that the same peer generates more than one block in the latest @xmath11 blocks of the chain . remarkably , as distributed consensus is obtained according to information contained in the latest @xmath11 blocks of the chain ( @xmath12 to handle forks of the block chain ) , it is not necessary that every peer of the network handle all blocks of the block chain . the protocol works properly even if peers do not consider proofs - of - location contained in the blocks that precede the latest @xmath12 , but only the identifier of the peer that has produced it and the reference to the previous block . the value of @xmath11 depends on the application layer . when it is important to store many past geographic locations , such as in applications for tracking and monitor vehicle fleets , @xmath11 has a higher value , compared to applications that localize nearby friends . forensic applications may be interested to store the whole block chain , in order to provide effective and trusted alibis for people under investigation . on the other hand , the lower is the value of @xmath11 , the smaller is also the space occupied in memory . therefore , the protocol is independent from the application layer and even versatile for the realization of different lbs types . we have analyzed the behavior of the proposed protocol , in case it is exposed to attacks that affect proof - of - location mechanisms , thus resulting to be particularly dangerous for lbss @xcite . 1 . * cheating on own geographic location . * a peer could attempt to fake its geographic location , specified in a proof - of - location request or response , in order to obtain a proof - of - location attesting that its geographic location is different from the actual one . our protocol prevents this kind of attack , since each peer that receives a proof location request or response , verifies that the specified geographic location is not further than the maximum distance reachable with the adopted short - range communication technology . * cheating on another peer s geographic location . * another possible attack could hail from a peer that produces false claims about other peers geographic locations . the protocol precludes such an attack , thanks to the asymmetric cryptography mechanism , whereby all the declarations concerning geographic locations stated by peers are digitally signed with their private keys and easily verifiable using their public keys that correspond to their identifiers . * replaying proofs - of - location . * proofs - of - location could be rebroadcast in the network by a malicious peer , with the purpose to forge its geographic location or that of other peers . since every peer of the network checks that the proof - of - location is not already contained inside the block chain before retransmitting it , it is not possible to successfully complete this attack . moreover , inasmuch every proof - of - location contains a reference to a block of the block chain , it is immediately discarded in case the referenced block is older that the latest @xmath11 blocks of the block chain . 4 . * colluding with other peers . * another threat exists when two or more peers collude with each other to generate fake proofs - of - location . in literature , this kind of attack is denoted as _ sybil attack _ and it happens when a malicious peer tries to prove itself in a geographic location that is not the actual one , with the help of another peer . indeed , two peers could agree upon producing a proof - of - location attesting that their geographic locations are different from real ones , and broadcast it in the network . + since our protocol relies on a location - based peer - to - peer protocol where peers expect to be directly connected , in the overlay network , with their geographic neighbors , colluding peers can be easily identified by means of the short - range communication technology . moreover , it is unlikely that the whole list of neighbors provided by the peer - to - peer protocol is made of colluding peers . for the sake of precision , there are four possible situations : 1 . * proof - of - location and location declared in the peer - to - peer overlay are equal and both fake . * if a peer receives a proof - of - location concerning two other peers that claim to be close to it , it verifies that at least one of the two peers can be contacted with the short - range communication technology ; if not , the proof - of - location is discarded . * proof - of - location and location declared in the peer - to - peer overlay are different and both fake . * if a peer receives from another peer a proof - of - location concerning the latter peer and related to a geographic location that is different from the one provided by the peer - to - peer overlay , such a proof - of - location is immediately discarded . proof - of - location is fake ; the location declared in the peer - to - peer overlay is real . * this situation is addressed in the same way of the previous one . proof - of - location is real ; the location declared in the peer - to - peer overlay is fake . * also this case , which is probably the most intuitive , is resolved like the second one . + hence , collusion is hindered by information provided by peers belonging to the location - based peer - to - peer overlay . determining real identity of peers . * an attacker could attempt to determine the real identity of peers through full observation of proofs - of - location in the block chain . actually , in our protocol there is no limit on the number of identifiers : in the same way as bitcoin protocol allows the use of more than one receiving address , users of our protocol can freely decide to change their peer identifiers . as proved by zhu and cao @xcite , if a peer has the possibility to periodically change its identifier according to a poisson distribution , it gains unobservability and an attacker can not determine the real identity of the peer by observing location proof records . thus , our protocol is shown to be robust against all major lbs - related attacks . in this paper , we have illustrated a novel approach for the realization of lbss , where the certification of user geographic location ( proof - of - location ) is important for service reliability and correctness . our approach adopts the block chain technology for the persistence of proof - of - location in the network and a proof - of - stake method as a distributed consensus mechanism . the novel peer - to - peer protocol we have designed , in addition to providing proof - of - location , stands out from other solutions not relying on a centralized server , therefore paying specific attention to privacy of users . moreover , the proposed protocol is able to resist against all major lbs - related attacks . v. lenders , e. koukoumidis , p. zhang , m. martonosi , _ location - based trust for mobile user - generated content : applications , challenges and implementations _ , proc . of the 9th workshop on mobile computing systems and applications ( hotmobile ) , napa , ca , usa , february 2008 . b. heep , m. florian , j. volz , i. baumgart , _ overdrive an overlay - based geocast service for smart traffic applications _ , proc . of the 10th annual conference on wireless on - demand network systems and services ( wons ) , banff , alberta , canada , march 2013 . g. brambilla , m. picone , m. amoretti , f. zanichelli , _ an adaptive peer - to - peer overlay scheme for location - based services _ , proc . of the ieee 13th international symposium on network computing and applications ( nca ) , cambridge , ma , usa , august 2014 . r. khan , s. zawoad , m. haque , r. hasan , _ ` who , when , and where ? ' location proof assertion for mobile devices _ , proc . of the 28th annual ifip wg 11.3 working conference on data and applications security and privacy , vienna , austria , july 2014 .

location - based services ( lbss ) build upon geographic information to provide users with location - dependent functionalities . in such a context , it is particularly important that geographic locations claimed by users are the actual ones . verification approaches proposed in the last few years are not satisfactory , as they depend on a centralized infrastructure that entails a high risk to the privacy of users . in this paper , we present a novel approach for producing proofs - of - location , _ i.e. _ , digital certificates that attest someone s presence at a certain geographic location , at some point in time , whereby lbss can validate user locations . in particular , our approach relies on the block chain mostly known for being bitcoin s core technology to design a completely decentralized peer - to - peer architecture that guarantees location trustworthiness and preserves user privacy , at the same time .

weak decays of @xmath3 mesons encode valuable information about the quark - flavour sector of the standard model ( sm ) of particle physics . the conceptually simplest observables are branching ratios , which describe the probability for the considered decay to occur . measurements of @xmath0-decay branching ratios at hadron colliders would require precise knowledge of the @xmath0 production cross section , which is not available , and rely therefore on experimental control channels and the ratio of the @xmath4 fragmentation functions ( for a detailed discussion , see ref . @xcite ) . at the @xmath5 @xmath6 factories operating at the @xmath7 resonance , @xmath0-decay branching ratios can be extracted since the total number of produced @xmath0 mesons can be determined separately @xcite . the neutral @xmath0 mesons exhibit @xmath3@xmath8 mixing . measuring the time - dependent angular distribution of the @xmath9 decay products @xcite , lhcb has recently established a non - vanishing difference @xmath10 between the decay widths of the @xmath0 mass eigenstates @xcite : @xmath11 where @xmath12 is the inverse of the average @xmath0 lifetime @xmath13 . since a discrete ambiguity could also be resolved @xcite , we are left with the sign in ( [ ys ] ) , which agrees with the sm expectation . a sizable value of @xmath10 was theoretically expected since decades @xcite . in view of the sizable @xmath10 , special care has to be taken when dealing with the concept of a branching ratio , and the question of how to convert measured experimental " @xmath0-decay branching ratios into theoretical " @xmath0 branching ratios arises . this issue is the central topic of this writeup , summarizing the results of refs . a special emphasis will be put on the rare decay @xmath1 . the untagged rate of a @xmath0 decay , were no distinction between initially present @xmath3 or @xmath8 mesons is made , is a sum of two exponentials : @xmath14 which can be rewritten as @xmath15.\label{untagged-2}\end{aligned}\ ] ] here the parameter @xmath16 was introduced in ( [ ys ] ) , and @xmath17 is an observable depending on the final state @xmath18 . the branching ratios given by experiments are extracted from total event yields , without taking time information into account , and can be defined as follows @xcite : @xmath19 @xmath20 = \frac{\tau_{b_s}}{2}\left(r^f_{\rm h } + r^f_{\rm l}\right ) \left[\frac{1 + { \cal a}^f_{\delta\gamma}\ , y_s}{1-y_s^2 } \right].\ ] ] on the other hand , theorists usually consider and calculate the following cp - averaged branching ratios : @xmath21 where the @xmath3@xmath8 oscillations are switched off " by choosing @xmath22 . it should be noted that this @xmath0 branching ratio concept allows a straightforward comparison with branching ratios of decays of @xmath23 or @xmath24 mesons through the @xmath25 flavour symmetry of strong interactions . the experimental branching ratios defined in ( [ br - exp ] ) can be converted into the theoretical branching ratios defined in ( [ br - theo ] ) by means of @xmath26 { \rm br}\left(b_s \to f\right)_{\rm exp},\label{brratio-1}\end{aligned}\ ] ] where the term in square brackets would equal one for a vanishing @xmath0 decay width difference . however , for the experimental value of @xmath16 in ( [ ys ] ) , the theoretical @xmath27 branching ratios can differ from their experimental counterparts by up to @xmath28 , depending on the the final state @xmath18 . using theoretical input , in particular the @xmath25 flavour symmetry , the @xmath29 observables can be estimated for specific decays ( for examples of recent analyses , see refs . @xcite ) , as compiled in ref . @xcite . once time information for the untagged @xmath0 decay data sample becomes available , the theoretical input for determining @xmath30 can be avoided in the extraction of the theoretical branching ratio ( [ br - theo ] ) @xcite . using the effective @xmath0 decay lifetime @xmath31 , \label{taueff}\end{aligned}\ ] ] we obtain @xmath32{\rm br}\left(b_s \to f\right)_{\rm exp } , \label{brratiot}\end{aligned}\ ] ] where only measurable quantities appear on the right - hand side . the measurement of effective @xmath0 decay lifetimes is hence an integral part of the extraction of the theoretical branching ratios ( [ br - theo ] ) from the data and not only an interesting topic to constrain the @xmath3@xmath8 mixing parameters @xcite . the use of the theoretically clean relation in ( [ brratiot ] ) is advocated for the compilation of @xmath0 decay properties in particle listings . for a discussion of experimental subtleties related to the measurement of @xmath0 decay branching ratios and effective lifetimes , the reader is referred to ref . @xcite . the branching ratio measurements of @xmath33 decays into two vector mesons , such as @xmath34 , @xmath35 and @xmath36 , are also affected by the sizable width difference @xmath10 @xcite . here an angular analysis of the decay products of the vector mesons has to be performed in order to disentangle the cp - even ( @xmath37 ) and cp - odd ( @xmath38 ) final states , with @xmath39 the experimental branching ratios can then be converted into the theoretical branching ratios through @xmath40 \mbox{br}_{\rm exp}^{vv}\ ] ] with the help of theoretical information on the @xmath41 observables , or by means of the relation @xmath42 f_{vv , k}^{\rm exp}\ ] ] utilizing effective lifetime measurements @xcite . a key probe of new physics ( np ) is the rare decay @xmath43 , which receives only loop contributions from box and penguin topologies in the sm . here the ( theoretical ) branching ratio is predicted as follows @xcite : @xmath44 in the presence of np , the branching ratio may be affected by new particles in the loops or new contributions at the tree level @xcite . the error of ( [ br - sm ] ) is dominated by lattice qcd input for non - perturbative physics @xcite . the limiting factor for the @xmath1 branching ratio measurement at hadron colliders is the ratio @xmath45 , where the fragmentation functions @xmath46 describe the probability that a @xmath47 quark fragments in a @xmath48 meson . a new method for determining @xmath45 using nonleptonic @xmath49 , @xmath50 , @xmath51 decays @xcite was recently implemented at lhcb @xcite , with a result in good agreement with measurements using semileptonic decays @xcite . the @xmath52-breaking form - factor ratio entering the non - leptonic method has recently been calculated with lattice qcd @xcite . searches for the @xmath1 decay were performed by the cdf @xcite , d0 @xcite , atlas @xcite , cms @xcite and lhcb collaborations . the latter experiment has recently reported the currently most stringent upper bound on the branching ratio , which corresponds to @xmath53 at the 95% confidence level @xcite , and is approaching the sm prediction ( [ br - sm ] ) . for a recent review of the experimental studies , see ref . @xcite . in the analyses of the @xmath1 decay , the impact of @xmath10 was not taken into account . in view of the discussion in the previous section , the question arises how the sizable value of @xmath10 affects the theoretical interpretation of the @xmath1 data and whether we can actually take advantage of this decay width difference @xcite . in order to address this issue , we use the general low - energy effective hamiltonian describing the decay @xmath54 as the starting point . using a notation similar to ref . @xcite , where a model - independent np analysis was performed , it can be written as @xmath55,\label{heff}\end{aligned}\ ] ] where @xmath56 and @xmath57 are the fermi and qed fine - structure constants , respectively , and the @xmath58 are elements of the cabibbo kobayashi maskawa ( ckm ) matrix . the short - distance physics is encoded in the wilson coefficients @xmath59 , @xmath60 of the four - fermion operators @xmath61 where @xmath62 denotes the @xmath47-quark mass , @xmath63 , and the @xmath64 are obtained from the @xmath65 through the replacements @xmath66 . it should be noted that only operators with non - vanishing contributions to @xmath54 are included in ( [ heff ] ) ; in particular the matrix elements of operators involving the @xmath67 vector current vanish . the hadronic structure of the leptonic @xmath54 decay is very simple and can be expressed in terms of a single , non - perturbative parameter , which is the @xmath0-meson decay constant @xmath68 @xcite . in the sm , only the @xmath69 operator contributes with a real wilson coefficient @xmath70 , leading to the prediction in ( [ br - sm ] ) . the sensitivity to ( pseudo-)scalar lepton densities entering the @xmath71 and @xmath72 operators is an outstanding feature of the @xmath54 channel . the corresponding wilson coefficients are still largely unconstrained , thereby leaving ample space for np @xcite . for the calculation of the @xmath73 observables , it is convenient to go to the rest frame of the decaying @xmath8 meson and to use the notation @xmath74 to distinguish between the left - handed ( @xmath75 ) and right - handed ( @xmath76 ) muon helicity configurations . in this setting , the @xmath77 and @xmath78 states are simply related to each other through cp transformations . thanks to @xmath3@xmath8 mixing , we get interference effects between the @xmath79 and @xmath80 decay processes that are described by the observable @xmath81.\ ] ] here @xmath82 is the @xmath3@xmath8 mixing phase , whereas @xmath83 denotes a convention - dependent phase which is associated with cp transformations @xcite . expressing the @xmath84 decay amplitude as @xmath85 and performing appropriate cp transformation results eventually in the following expression @xcite : @xmath86,\ ] ] where all convention - dependent quantities ( such as the @xmath83 phases ) cancel , @xmath87 , and @xmath88 @xmath89 these combinations of wilson coefficient functions have been introduced in such a way that we simply have @xmath90 and @xmath91 in the sm , whereas @xmath92 and @xmath93 carry , in general , non - trivial cp - violating phases @xmath94 and @xmath95 ( see also ref . it should be noted that the non - perturbative @xmath0-meson decay constant @xmath96 , which arises in the parametrization of ( [ ampl ] ) and affects the sm prediction ( [ br - sm ] ) , cancels in the observable ( [ xi - obs ] ) . before having a closer look at the branching ratio , it is interesting to consider the following time - dependent rate asymmetries , which require tagging information and knowledge of the muon helicity @xmath97 : @xmath98 @xmath99 here @xmath100 denotes the mass difference between the heavy and light @xmath0 mass eigenstates while @xmath16 is given in ( [ ys ] ) . neglecting the impact of @xmath10 , such cp asymmetries were considered for @xmath101 decays within various np scenarios in the previous literature @xcite . the observables entering ( [ asym-1 ] ) are governed by @xmath102 in ( [ xi - obs ] ) and take the following expressions @xcite : @xmath103\ ] ] @xmath104 @xmath105 which are theoretically clean . note that @xmath106 and @xmath107 do not depend on the muon helicity @xmath97 . in the discussion given above , it was assumed that np enters only through the wilson coefficients governing the @xmath54 decay and that the @xmath3@xmath8 mixing phase @xmath108 takes its sm value @xmath109 , which is cancelled in ( [ xi - def ] ) through the ckm factors of the ratio of decay amplitudes . in ( [ s - lam ] ) and ( [ adg - lam ] ) , np in @xmath3@xmath8 mixing can straightforwardly be included through the replacements @xmath110 . the lhcb data for cp violation in @xmath111 decays already constrain @xmath112 to the few - degree level @xcite . consequently , this effect is negligible from the practical point of view for the following considerations . it is difficult to measure the muon helicity . in order to circumvent this problem , we consider the @xmath113 rate and its counterpart for initially present @xmath8 mesons , which can be combined into the cp asymmetry @xmath114 since a non - zero value would immediately signal new cp - violating phases , it would be most interesting to measure this asymmetry . this feature was recently highlighted in ref . @xcite for minimal @xmath115 models @xcite . unfortunately , despite the independence on the muon helicity , this is still challenging from the practical point of view as tagging and time information are required . an analogous expression holds for the rare @xmath116 decays , where @xmath117 is negligibly small . from the practical point of view , the branching ratio extracted from untagged data samples , ignoring the decay - time information , is the first measurement : @xmath118 here the untagged @xmath119 rate is given in general terms in ( [ untagged-1 ] ) and ( [ untagged-2 ] ) . since @xmath120 in ( [ adg - lam ] ) does actually not depend on the muon helicity , i.e. @xmath107 , we can apply ( [ brratio-1 ] ) to extract the theoretical branching ratio from the experimental branching ratio ( [ defbrexp ] ) : @xmath121 { \rm br}(b_s \to \mu^+\mu^-)_{\rm exp}.\label{brratio}\end{aligned}\ ] ] the former is considered and calculated by the theoretical community ( see , e.g. , refs . @xcite ) , and satisfies @xmath122 ) , @xmath30 depends sensitively on np entering through the wilson coefficients which govern the @xmath1 channel . consequently , this observable is currently unknown . varying @xmath123 $ ] yields @xmath124 which has to be added to the experimental error of ( [ defbrexp ] ) . on the other hand , within the sm , we have the theoretically clean prediction @xmath125 . if we rescale the theoretical sm branching ratio in ( [ br - sm ] ) correspondingly by a factor of @xmath126 and use ( [ ys ] ) , we obtain @xmath127 this is the sm branching ratio reference value for the comparison with the experimental branching ratio ( [ defbrexp ] ) . once the @xmath43 decay has been observed and more experimental data become available , it is possible to include also the decay time information in the analysis so that the effective @xmath43 lifetime @xmath128 , which is defined as in ( [ taueff ] ) , can be measured . since @xmath30 in ( [ adg - lam ] ) does not depend on the muon helicity , this observable can be extracted from the effective lifetime with the help of the relation @xmath129,\ ] ] and results in @xmath130 { \rm br}\left(b_s \to \mu^+\mu^-\right)_{\rm exp}.\label{brmumu - correct}\end{aligned}\ ] ] this expression takes the same form as ( [ brratiot ] ) and allows the conversion of the experimental @xmath131 branching ratio into its theoretical counterpart , irrespective of whether there are np contributions present or not . consequently , the error in ( [ br - error ] ) can then be eliminated . the effective @xmath43 lifetime and the extraction of @xmath30 from untagged data samples is an important new measurement for the high - luminosity upgrade of the lhc . extrapolating from the currently available analyses of the effective @xmath132 and @xmath133 lifetimes performed by the cdf and lhcb collaborations , a precision of @xmath134 or better appears feasible @xcite . detailed experimental studies of this exciting new feature of the @xmath43 channel are strongly encouraged . looking at the expression for @xmath135 in ( [ adg - lam ] ) , it is obvious that this observable and the effective lifetime @xmath128 may well be affected by np . the @xmath10 effects propagate also into the constraints on np parameters that can be obtained from the comparison of the experimental information on the @xmath131 branching ratio with the sm branching ratio , where it is useful to introduce @xcite @xmath136[r - def ] using ( [ adg - lam ] ) and ( [ brratio ] ) , the ratio @xmath137 takes the form @xmath138 \left ( |p|^2 + |s|^2\right)}\nonumber\\ & & \hspace*{-0.9truecm}=\left[\frac{1+y_s\cos2\varphi_p}{1-y_s^2 } \right ] |p|^2 + \left[\frac{1-y_s\cos2\varphi_s}{1-y_s^2 } \right ] |s|^2.\label{r - expr}\end{aligned}\ ] ] combining ( [ br - sm ] ) and ( [ lhcb - bound ] ) yields the bound @xmath139 , where the theoretical uncertainty of the sm prediction of the @xmath1 branching ratio was neglected . the ratio @xmath137 would fix a circle in the @xmath140@xmath141 plane for @xmath142 , i.e. for a vanishing @xmath0 decay width difference . on the other hand , for non - zero values of @xmath16 , @xmath137 can be converted into ellipses which depend on the cp - violating phases @xmath143 . as the latter quantities are in general unknown , @xmath137 results in a circular band , with the upper bounds @xmath144 . since the @xmath145 and @xmath146 contributions can not be separated through experimental information on @xmath137 , as can be seen in ( [ r - expr ] ) , there may still significant np contributions be present in @xmath43 , even if the branching ratio should eventually be measured close to the sm expectation . as was pointed out in ref . @xcite , the measurement of the effective lifetime @xmath128 and the associated untagged @xmath30 observable allows a resolution of this situation . the point is that @xmath147 fixes a straight line through the origin in the @xmath140@xmath141 plane . for illustrations , the reader is referred to the figures shown in ref . @xcite . in the most recent analyses of the constraints on np parameter space that are implied by the experimental upper bound on the @xmath131 branching ratio for various extensions of the sm , authors have now started to take the effect of @xmath10 into account ( see , for instance , the papers listed in refs . the non - vanishing width difference of the @xmath0-meson system , which has recently been established by lhcb , leads to subtleties in the extraction of @xmath0 branching ratio information from the data but offers also new observables . the differences between the experimental and theoretical branching ratios can be as large as @xmath28 , depending on the final state . both branching ratios can be converted into each other either through theoretical considerations or through the measurement of the effective @xmath27 decay lifetimes . as the latter involves only experimental data , it is generally the preferred avenue . the rare decay @xmath43 is also affected by @xmath10 , where the theoretical branching ratio in ( [ br - sm ] ) has to be rescaled by @xmath126 for the comparison with the experimental branching ratio , resulting in the sm reference value of @xmath148 . thanks to @xmath10 , the @xmath1 decay offers a new observable , which is the effective lifetime @xmath128 . it allows the inclusion of the @xmath10 effects in the conversion of the experimental into the theoretical branching ratio . moreover , it offers also a new , theoretically clean np probe that may still show large np effects , in particular those originating from the ( pseudo-)scalar @xmath149 densities entering the four - fermion operators . this observable may even show np should the @xmath1 branching ratio be found close to the sm prediction . the measurement of @xmath128 and the associated @xmath30 observable is an exciting new topic for the high - luminosity upgrade of the lhc . detailed feasibility studies are strongly encouraged . i am grateful to the organizers , in particular giulia ricciardi , for hosting and inviting me to another excellent meeting of the capri flavour physics workshop series , and would like to thank my phd students and colleagues for the enjoyable collaboration on the topics discussed above . r. fleischer , n. serra and n. tuning , phys . d * 82 * ( 2010 ) 034038 [ arxiv:1004.3982 [ hep - ph ] ] . a. drutskoy _ et al . _ ( belle collaboration ) , phys . rev . d * 76 * ( 2007 ) 012002 [ hep - ex/0610003 ] . m. pepe altarelli , these proceedings . r. aaij _ et al . _ [ lhcb collaboration ] , phys . * 108 * ( 2012 ) 241801 [ arxiv:1202.4717 [ hep - ex ] ] . for a recent review , see a. lenz , arxiv:1205.1444 [ hep - 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the lhcb experiment has recently established a sizable width difference between the mass eigenstates of the @xmath0-meson system . this phenomenon leads to a subtle difference at the 10% level between the experimental branching ratios of @xmath0 decays extracted from time - integrated , untagged data samples and their theoretical counterparts . measuring the corresponding effective @xmath0-decay lifetimes , both branching ratio concepts can be converted into each other . the rare decay @xmath1 and the search for new physics through this channel is also affected by this effect , which enhances the standard - model reference value of the branching ratio by @xmath2 , while the effective lifetime offers a new observable to search for physics beyond the standard model that is complementary to the branching ratio . @xmath0 decays , branching ratios , effective lifetimes , new physics

in this paper i consider the problem of detecting neutrinos from active galactic nuclei ( agn ) . recent predictions ( see for example @xcite ) of the diffuse background of neutrinos from the sum of all agn are high enough that water and ice cerenkov detectors under construction such as dumand @xcite , amanda @xcite , lake baikal @xcite and nestor @xcite should be sensitive to muons from the interactions of the neutrinos in the earth @xcite . most recently , protheroe @xcite has used a new model to calculate the rate of gamma ray and neutrino production in agn jets . the resulting diffuse neutrino background varies over many orders of magnitude depending upon assumptions made about the relative contributions of various production mechanisms in the agn system . the minimum estimated flux may be beyond the reach of the current generation of neutrino detectors mentioned above . i have reassessed the detectability of a wide range of flux predictions using calculations of the neutrino cross sections based on nucleon structure function parameterizations @xcite ( parton distributions ) derived from recent accelerator experiments @xcite . use of the new parton distributions leads to higher cross sections and a corresponding increased probability of a detectable muon being produced in the rock surrounding a detector . however , increased neutrino absorption in the earth is an important effect and offsets some of the gains for the longest neutrino paths through the earth . i present the rates and angular distributions of muons for different agn spectra and for the flux of atmospheric neutrinos @xcite produced when cosmic rays interact with the earth s atmosphere , including neutrinos from charmed meson decay @xcite . the outline of the paper is as follows . a brief review of the quark parton model and how it is used to calculate neutrino cross sections using accelerator structure function data ( parton distributions ) is presented . i then examine two of the most recent sets of parton distributions and look at the implications for the total cross sections . finally , i discuss the use of these cross sections to estimate the rates and angular distributions of neutrino induced muons in large detectors , using a monte carlo simulation of the passage of neutrinos through the earth . this has the advantage of allowing a precise treatment of the effects of neutral current scattering , which reduces the neutrino energies before they finally interact to produce muons . the prospects for detection of the agn fluxes above the atmospheric backgrounds are then examined . upon completion of these calculations , i learned of similar work by gandhi , quigg , reno and sarcevic @xcite , using another recent set of parton distributions @xcite , which yield muon rates consistent with the results presented in this work . the interaction of a neutrino with a nucleon may be described @xcite in terms of the quark - parton model . the nucleon is considered to be a collection of quasi - free partons ( quarks and gluons ) which share the nucleon momentum . a proton consists of three valence quarks ( up , up and down ) surrounded by a sea of quark / antiquark pairs of all flavours . the description of a weak interaction of a neutrino ( energy @xmath2 ) with a nucleon ( mass @xmath3 ) in the quark - parton model is described in terms of an interaction of the neutrino with any one of the individual quarks ( which carries a fraction @xmath4 of the nucleon momentum ) . in a charged current process a @xmath5 boson is exchanged from a muon - neutrino to the quark with the neutrino turning into a muon ( energy @xmath6 ) . a neutral current process involves the exchange of a @xmath7 boson , with the neutrino remaining a neutrino . the square of the 4-momentum transfer is denoted @xmath8 and the variable @xmath9 ( @xmath10 ) describes the fractional energy transfer . the cross section for the inclusive processes @xmath11 and @xmath12 can be written in terms of the variables @xmath13 and @xmath14 ( referred to as bjorken scaling variables ) where @xmath4,@xmath15 and @xmath16 are related to the square of the centre of mass energy @xmath17 , by @xmath18 . the cross section for the _ charged current _ interaction @xmath11 is written in terms of three structure functions @xmath19 and @xmath20 , but if the transverse momentum carried by the quarks in the nucleon is negligible then the relation @xmath21 @xcite reduces this dependence to two structure functions @xcite : @xmath22^{2 } \nonumber \\ & & \;\;\;\;\;\;\;\;\;\;\;\;\;\ ; \times \left\{(1-y+\frac{y^{2}}{2 } ) f^{\nu n , \bar{\nu}n}_{2}(x , q^{2 } ) \pm ( y-\frac{y^{2}}{2})xf^{\nu n , \bar{\nu}n}_{3}(x , q^{2 } ) \right\ } \label{eq : sigma_cc}\end{aligned}\ ] ] the @xmath23 sign corresponds to the @xmath24 cross sections . @xmath25 is the mass of the w - boson and @xmath26 is the fermi constant @xcite . the cross section in equation [ eq : sigma_cc ] is expressed in natural units where @xmath27 yielding a result in units of gev@xmath28 , to convert to a cross section in @xmath29 we multiply by @xmath30 @xmath31 @xcite . equation [ eq : sigma_cc ] also holds for @xmath32 . the structure functions @xmath33 and @xmath34 are defined in terms of quark distributions @xcite : @xmath35 and @xmath36 + [ b - t]\}\end{aligned}\ ] ] where @xmath37 are the sums of the quark / antiquark distributions ( @xmath38 etc ) . each quark distribution is a function of @xmath4 and @xmath8 describing the number of quarks of that flavour having a fractional momentum in the range @xmath39 , at momentum scale @xmath8 . note that the @xmath23 sign again corresponds to the @xmath24 cross sections . the _ neutral current _ cross sections @xmath12 are expressed in the same form as equation [ eq : sigma_cc ] , but with @xmath40 replaced by @xmath41 and the structure functions @xmath42 and @xmath43 written as @xcite @xmath44 \nonumber \\ & + & 2x[(c - s)+(t - b)][\delta^2_1 + \delta^2_3 - \delta^2_2 - \delta^2_4 ] \end{aligned}\ ] ] and @xmath45\ ] ] the @xmath46 factors are the chiral couplings , defined in terms of the weak mixing parameter @xmath47 @xcite @xmath48 for this work the cross sections have been calculated using sets of parton distributions @xcite fitted to the latest hera deep inelastic scattering data @xcite . the h1 and zeus collaborations have extracted the electromagnetic structure function @xmath49 from collisions of 26.7 gev electrons with 820 gev protons . @xmath49 is the sum of the individual parton distributions weighted by the squares of their electric charges : @xmath50 from the @xmath49 measurement the individual quark distributions can be calculated and used to form the structure functions @xmath51 and @xmath52 needed for the neutrino nucleon cross section calculation . however , to calculate the cross section in the energy range @xmath53 gev , we need to know the parton distributions at higher @xmath8 than the hera measurements . qcd theory @xcite describes the evolution of the parton distributions to higher @xmath8 . i consider two different solutions of the evolution equations , which predict sufficiently different behaviour in the unknown regions of @xmath8 and @xmath4 to give neutrino cross sections up to a factor of two bigger than previous calculations @xcite in the energy range of interest . martin , roberts and stirling have presented several sets of parton distributions @xcite based on the increasing amount of accelerator data . their latest parton set ( mrs g " ) @xcite is a parameterisation that includes the recent hera @xmath42 data . the mrs fits supply individual parton distributions @xmath54 which can be used to form @xmath42 and @xmath43 . in their recent work @xcite frichter , mckay and ralston have effectively fitted a two parameter ( @xmath55 ) solution of the structure function evolution equations to the hera @xmath56 data : @xmath57 @xmath58 is the qcd scale parameter ( taken as @xmath59 in the fmr result ) and @xmath60 and @xmath61 are the @xmath62 moments of the quark - gluon and gluon - gluon splitting functions , evaluated at next to leading order @xcite . in order to obtain @xmath63 , fmr make the assumption that the quark ( @xmath64 ) and anti - quark ( @xmath65 ) distributions of the @xmath66 flavour are equal , and that @xmath67 substituting into @xmath49 and @xmath63 yields @xmath68 and @xmath69 from which we obtain : @xmath70 a least squares minimization to the 1992 and 1993 hera @xmath71 data yields best fit parameters @xmath72 and @xmath73 . to obtain the total cross sections i have integrated equation [ eq : sigma_cc ] using the mrs g and fmr parton distributions , for both the charged and neutral current forms of @xmath42 and @xmath43 . the mrs g distributions cover the full range @xmath74 required , but the fmr result applies only at @xmath75 or less . in order to evaluate the fmr cross section over the full @xmath13 range , i have used the fmr result for @xmath76 and the mrs g result for @xmath77 . the mrs g parton distributions are valid down to @xmath78 , which is adequate for the calculation of the cross sections in the energy range considered in this work ( @xmath79 gev ) . ( note that the double - logarithmic approximation @xcite may be used to extrapolate the parton distributions to lower @xmath4 for cross section calculations @xcite where @xmath80gev . ) note also that i have combined a set of _ next - to - leading order _ ( nlo ) parton distributions ( mrs g ) calculated in the @xmath81 renormalization convention with the _ leading order _ ( lo ) form of the structure functions @xmath82 and @xmath83 . the nlo expressions for @xmath82 and @xmath83 ( obtained by convolving the quark and gluon distributions with the wilson coefficients @xcite ) will differ from the lo expressions by terms with coefficients @xmath84 , where @xmath85 is the qcd coupling constant , which decreases as @xmath8 increases . in the regions of high @xmath8 ( @xmath86 ) important for the neutrino energies considered in this work @xmath84 has a value of @xmath87 and the resulting differences between the lo and nlo structure functions , and hence the difference in the resulting cross sections , will be small ( @xmath88 a few percent ) . given the very large uncertainties in the astrophysical assumptions in this work , this is an acceptable approximation . the total neutrino / anti - neutrino charged / neutral current cross sections obtained by using the fmr and mrs g parton distributions are shown in figure [ crossfinal ] , along with the @xmath89 neutrino charged current estimate by reno @xcite . above @xmath90 gev neutrino and anti - neutrino cross sections are equal and the fmr cross sections are roughly 1.5 times bigger than the mrs g predictions and 2 times bigger than the reno @xmath89 prediction . the recent calculations of gandhi _ et al _ @xcite , using the cteq3 parton distributions @xcite , yield a neutrino charged current cross section lower than using mrs g by about 7% at 10@xmath91 gev , with difference rising to 23% at 10@xmath92 gev . the cteq3 cross section is bigger than the reno @xmath89 cross section by 1 - 10% in the same energy range . the reported observations @xcite of uhe @xmath93rays from binary x - ray systems in the early 1980s led to predictions of neutrino fluxes from such objects . the assumption was that protons accelerated in the vicinity of the compact object would interact with other matter in the system to give both neutral and charged pions , the neutral pions decaying to produce the observed @xmath93rays and the charged pions producing a neutrino flux . calculations were made @xcite of the expected neutrino flux by scaling the models to the observed @xmath93ray flux . however the non - confirmation of the @xmath93ray observations by much larger and more sensitive air shower arrays such as casa @xcite has led to upper limits on the @xmath93ray fluxes that are orders of magnitude lower than the original detection claims , dampening expectation of observable neutrino fluxes from binary x - ray systems . attention in recent times has focussed on the production of neutrinos in active galactic nuclei , where particle acceleration may be occuring at accretion shocks in the vicinity of massive black holes . stecker , done , salamon and sommers ( sdss ) @xcite calculated the neutrino flux resulting from interactions of protons with energy above the threshold energy for photoproduction on uv photons ( @xmath94 ) . szabo and protheroe ( sp ) @xcite included all the subsequent interactions of the protons after the initial photoproduction . luminosity functions @xcite ( derived from x - ray and gamma - ray measurements - describing the luminosity of agn as a function of redshift ) and the relationship between the neutrino and x - ray and gamma - ray outputs in a given agn model were used to calculate the neutrino output from the sum of all agn in the universe . more recently stecker and salamon @xcite revised their original model and calculated diffuse neutrino backgrounds for quasar cores and blazar jets . protheroe @xcite has calculated the neutrino and gamma - ray fluxes from proton acceleration in blobs of matter in agn jets . two major production mechanisms were considered . accelerated protons may leave the blob and interact with the radiation field of the accretion disk ( @xmath95 interactions ) , or interact with each other or with other matter in the vicinity ( @xmath96 interactions ) . the observed time variability of gamma - rays from agn such as mkr421 place constraints on the relative contribution of each mechanism . the @xmath96 interactions have a long characteristic time scale and therefore can not produce variability of the order of a day . the @xmath97 contribution , however , can vary rapidly and must be responsible for the time variation . to produce an intensity change of a factor of 2 over a short time scale , the @xmath96 interaction can contribute no more than about 50% to the total output . the @xmath96 interactions produce the most neutrinos , so the maximum allowable neutrino flux comes from equal contributions of @xmath96 and @xmath97 and the minimum flux from 100% @xmath97 . the luminosity function @xcite derived from the egret survey and the results from the sas-2 experiment @xcite have been used to produce a diffuse neutrino background estimate . figure [ agnspec ] shows the resulting neutrino fluxes from a number of different models . note that the fluxes are multiplied by @xmath98 to reduce the range of the plot . curves labelled sp ( dot - dashed lines ) are predictions from the earlier szabo and protheroe models . sdss92 is the stecker _ et al _ @xmath97 flux , while ss95 is the sum of the quasar core and blazar jet contributions in the stecker and salamon model ( dashed lines ) . the new protheroe model is shown in solid lines for the limiting cases , the minimum expectation coming from @xmath97 interactions only and the maximum from equal contributions from @xmath96 and @xmath97 interactions . the major backgrounds to searches for agn fluxes come from the decay of kaons , pions and muons produced from the interactions of cosmic rays in the earth s atmosphere . these fluxes show an angular dependence ; in the horizontal direction the fluxes at the surface are greatest as the kaons , pions and muons traverse more atmosphere and have more time to decay . the results of lipari @xcite are shown . another potential background comes from the prompt decay of charmed particles produced in cosmic ray interactions in the atmosphere . the expected neutrino fluxes should have a flatter energy spectrum and not show an angular dependence as the particles mostly decay before they can interact . zas , halzen and vzquez @xcite have calculated the expected neutrino fluxes from charmed meson decay under various assumptions of the charm production cross section and have computed muon rates in downward looking detectors . gaisser , halzen and stanev @xcite conclude that model b is an upper limit to the neutrino fluxes in the region @xmath99 tev . however , model d predicts higher fluxes at lower neutrino energies and gives overall the highest muon rates in downward looking detectors of the two cases . i therefore use model d to predict the upper limit on the muon rate from charm production . as a lower limit , i take the prediction of thunman , ingelman and gondolo @xcite which gives neutrino fluxes nearly 100 times smaller than the zhv model d. it is clear that there is a large uncertainty in the potential contribution of charmed meson decay to the neutrino induced muon fluxes . the implications of this on the detectability of the agn fluxes will be addressed in the next section . cerenkov detectors ( dumand , amanda , nestor , lake baikal ) detect upward going muons from charged current interactions of neutrinos in the earth . the muons can be produced many kilometres from the detector and still survive to be detected via their cerenkov emissions in water or ice . calculations of the expected muon fluxes from agn @xcite have been made using various parton distributions and muon energy loss assumptions . in their original cross section paper @xcite , frichter , mckay and ralston calculated the rates of charged lepton production in a cubic kilometre volume of ice and noted that despite the increased attenuation with their new cross section , the increased interaction probability more than compensated for this , resulting in increased lepton production . in later work @xcite , they calculated the specific rate expectations for a radio receiver in antarctic ice , detecting radio cerenkov radiation from electrons . the highest of the szabo and protheroe fluxes @xcite and the stecker _ et al _ flux @xcite were used , the results suggesting these fluxes would be readily detectable with a single antenna buried at a depth of 600 metres . zas , halzen and vzquez @xcite calculated the detection rates of neutrino induced horizontal air showers and underground muons , again for sdss and sp fluxes . these calculations included the expected rates from charm induced neutrinos . the cross sections were calculated with the kmrsb-5 @xcite parton distributions which give total cross sections of about the size of the reno @xmath89 estimate . most recently , gandhi , quigg , reno and sarcevic @xcite ( gqrs ) , have evaluated the cross sections for a variety of parton distributions and have then used the cteq3 parton distributions @xcite to estimate muon rates from astrophysical sources . due to the relative differences in the final cross sections , the cteq3 partons will yield muon rates closer to those using reno @xmath89 than mrs g. the calculation of muon fluxes induced by neutrino interactions in the earth is complicated by neutrinos undergoing neutral current interactions in the earth ( which reduce their energies but do not remove them from the beam ) before they finally interact to produce a muon . the final number of neutrinos in a given energy bin after passage through the earth is reduced by both charged and neutral current interactions , but some of the total loss is offset by originally higher energy neutrinos having moved down in energy due to neutral current interactions . an effective total cross section can be calculated , which is dependent on the original source spectrum . this approach was followed by berezinsky _ et al _ @xcite where the total cross section was taken as the sum of neutral and charged current cross sections , with a correction term included to account for the source dependent neutral current neutrino regeneration effect . as an alternative approach to the neutral current effect , i have developed a monte carlo simulation @xcite to model the passage of the neutrinos through the earth , taking into account the relative likelihood of neutral and charged current interactions , and selecting the final neutrino or muon energy from the energy dependent @xmath15 distributions . a simple weighting system was devised ( and generalized to account for neutrinos that undergo none , one , two or more neutral current scatters before a charged current interaction ) to keep the computing time reasonable . neutrinos and anti - neutrinos were treated separately using the appropriate cross sections . the column density of nucleons to be traversed by a neutrino as a function of nadir angle is calculated using the preliminary reference earth model @xcite , which describes how the density of the earth varies with distance from the centre . the final energy of a muon reaching the detector is determined using the muon propagation code of lipari and stanev @xcite . the muon energy losses due to bremsstrahlung @xcite , @xmath100 pair production @xcite and photonuclear interactions @xcite are treated stochastically in order to give the correct final fluctuations in muon ranges . ionization losses are also taken into account . only muons which are produced within the final tens of kilometres from the detector will actually survive to the detector , so for these calculations i use standard rock ( @xmath101 g @xmath102 ) for the propagation . i have calculated the expected muon rates using the cross sections reno @xmath89 , fmr and mrs g resulting from the parton distributions described in section [ partons ] which are derived from the latest accelerator structure function data . the higher cross sections result in greater attenuation of neutrinos within the earth , but this effect is offset by a greater probability of muon production by the surviving neutrinos in the final kilometres of rock before a detector , leading to greater expected muon rates . it is important to remember that the effective area of a detector will have an energy and arrival angle dependence and that the overall detection rate will depend upon the energy and angular spectrum of muons incident upon the detector . for example , the effective area for muon detection ( averaged over arrival direction ) @xcite by the dumand - ii detector ( @xmath103m@xmath104 geometric area ) varies from about @xmath105m@xmath104 at 10 gev ( the array does not trigger on all muons ) up to @xmath103m@xmath104 at 5 tev and goes up to @xmath106m@xmath104 at @xmath107 gev ( the array triggers on muons that pass outside the detector volume ) . the muon rates calculated here assuming a spherical detector with a constant 20000m@xmath104 effective area for all arrival directions and all muon energies will therefore be approximate lower bounds on the numbers of muons detected for muons above about 1 tev ( near the energy at which the effective area equals the geometric area ) . due to the increase in effective area at higher energies , the muon rates for flatter spectra will be enhanced over those of steeper spectra compared to the numbers presented here which are calculated for an energy independent effective area . keeping this in mind , we examine the predicted muon rates induced by agn neutrinos . the integral muon rates expected in a downward looking detector ( @xmath108 field of view ) are shown in figure [ intmuonrates ] for the three different cross sections and nine different neutrino spectra of figure [ agnspec ] . the predicted muon fluxes span several orders of magnitude . the sp94 flux exceeds the atmospheric background for a muon energy cut of a few gev . at the other extreme , the p96p@xmath93 does not exceed the atmospheric background until an energy of around 10 tev . the wide variation in the expected number of muons from charm induced neutrinos is evident . the tig neutrino flux induces a very low rate of muons , around 1/10 of the lowest agn flux ( p96p@xmath93 ) , and should not pose a background problem at any muon energy cut . however , the zhv d neutrino flux results in a muon rate exceeding that of the sdds92 flux for muon energies up to @xmath88400 gev , and roughly equal to that of the conventional atmospheric and p96p@xmath93 fluxes at a muon energy cut of 10 tev . this great uncertainty suggests that there would be difficulties in identifying the origins of any observed muons should the lowest agn flux be correct . the results presented here are not directly comparable to those of gandhi _ et al _ @xcite , as the neutrino source spectra used in both cases are not identical . gqrs made a broken power law approximation to the sp94 ( b=1 ) neutrino flux ; this yields muon rates less than the sp94 curve in figure [ intmuonrates ] , which comes from using the highest of the sp94 fluxes . gqrs also calculated muon rates for the ss95 neutrino flux , but only for the quasar core component , whereas i have used the sum of quasar core and blazar jet components . also , gqrs treat neutral currents by taking two cross sections : the first the sum of charged and neutral current cross sections , which gives a lower limit to the muon rate ; the second the charged current cross section alone , which will give an upper limit to the muon rate . to check the consistency of the two sets of results , i have used the forms of the neutrino fluxes as implemented by gqrs with the mrs g and reno @xmath89 cross sections and find that the muon rates obtained are consistent with the differences in cross sections in the two sets of work . the sp94 and sp92max fluxes have already been excluded by an analysis of the energy distribution of horizontal neutrino - induced muons in the frjus experiment @xcite . the frjus detector was a fine grain tracking calorimeter operated deep underground , with the ability to accurately determine the energy of the through going muons from the energy deposited from electromagnetic showering . at near horizontal angles the background atmospheric muon flux is sufficiently suppressed by the rock overburden to allow a measurement of the rate of atmospheric and agn induced muons . the number of muons ( producing an observed energy loss in the detector greater than the maximum observed energy loss ) expected from each agn spectrum has been calculated @xcite taking into account the rock thickness , muon propagation and the increasing efficiency of the detector with increasing muon energy . the high fluxes sp94 and sp92max predict more muons than the 90% confidence level upper limit of 2.3 muons and are therefore excluded by this experiment . all the other fluxes considered predict less than 2.3 muons and are therefore not excluded by the frjus result . the angular distributions of the muon fluxes for muon energies above @xmath109 gev and @xmath110 gev are shown in figure [ muonang103 ] for a collecting area of 20000 m@xmath104 , which corresponds to that of the proposed nine string dumand - ii array . the increases in the overall muon rates predicted by the fmr cross section are not uniform over arrival direction . it is clear that most of the increases come from the highest nadir angles ( muons coming from angles 0 to @xmath8830 degrees down from the horizon ) where the thickness of the earth traversed by the neutrinos is smaller and attenuation less important while the likelihood of muon production near the detector is greater . the rate of directly upgoing muons is very similar for all three cross sections considered - the increased rate of muon production in the final kilometres of rock is balanced by increased neutrino attenuation in the earth . the increase in muon rates comes from arrival directions where surface or shallow detectors are most susceptible to noise contamination from downward going atmospheric muons mis - reconstructed as horizontal or upward going . however , deep underwater detectors which are better shielded from atmospheric muons will be sensitive to these increased near horizontal fluxes . for example , the dumand - ii detector is expected to be sensitive to muons from downgoing neutrinos up to @xmath8820 degrees above the horizon . .[ratetable]integral muon rates in a @xmath103m@xmath104 downward looking detector for nadir angles @xmath111 ( most upgoing ) and @xmath112 ( nearer horizontal ) for various neutrino spectra , cross sections and minimum muon energies . [ cols="^,^,^,^,^,^,^,^ " , ] here we consider only those neutrino predictions that have not been ruled out by the frjus experiment . the total muons expected for nadir angles greater and less than 60 degrees as a function of muon energy cut and cross section for each neutrino source are summarized in table [ ratetable ] . it is evident that the highest of these fluxes may be observable over the atmospheric background for a 100 gev muon energy cut ( @xmath88300 - 500 events per year above @xmath882000 background ) but that the smaller fluxes ( 10 - 100 events per year ) would not . for a muon energy cut of 1 tev , the atmospheric background is significantly reduced and the fluxes p96@xmath113 , sp92min and ss95 q+b are now greater than the background and should be observable . the lower sdss92 flux would produce @xmath8855 - 70 events per year above a 225 background and should be observable over several years but an uncertain contribution from charm induced neutrinos ( @xmath881 - 50 muons ) would complicate matters . however figure [ muonang103 ] shows that the charm induced muons have a flat angular distribution and this might aid in identification . the p96@xmath97 is well below the background and given the charm uncertainty , would seem not to be detectable . moving to a 10 tev cut reduces the atmospheric background to @xmath885 per year , making all the fluxes readily observable , except for the lower bound of p96@xmath97 . this latter flux , the atmospheric background and the highest charm decay estimate ( zhv d ) produce roughly equal numbers of muons . given that the charm induced muon rate could actually be practically zero ( as table [ ratetable ] shows ) , this would make a differentiation between charm induced and agn induced muon fluxes difficult , if only a small excess above the expected conventional atmospheric rate was seen . one could not simply do a counting experiment as the excess above the conventional atmospheric background could come from either of two sources . an examination of the angular distributions or differential energy spectra of the detected muons would be needed . the p96@xmath97 , charm d and conventional atmospheric fluxes produce different angular distributions , shown in figure [ 10tevblow ] . the shape of the atmospheric neutrino induced muon curve reflects primarily the angular distribution of the source neutrinos . the isotropic charm - induced neutrinos produce a flatter angular distribution ; but with muons resulting from higher energy neutrinos the angular shape shows evidence of some neutrino absorption . the muons induced by the isotropic p96@xmath97 flux show a strong angular dependence due to contributions from much higher neutrino energies . the three angular distributions are quite different for nadir angles greater than @xmath114 ( @xmath115 ) . a detector located deep enough such that atmospheric muons are not a problem should be sensitive to these differences , provided enough muons were measured to reveal the angular shape ( requiring many years exposure for a 20000 m@xmath104 detector or a much larger detector ) . surface or shallow detectors are affected by misreconstruction of downward muons , which restricts their acceptance aperture . figure [ 10tevblow ] shows that for nadir angles less than @xmath114 ( @xmath116 ) the angular distributions of all three spectra are the same shape ( fairly flat ) . thus , even using a very large detector / long exposure time but with restricted aperture , the angular distribution alone is not sufficient to determine how much of a small excess of muons was due to agn , because of the large uncertainty in the charm induced neutrino flux . measuring the energy spectrum of the observed muons may allow a differentiation between source spectra . the p96@xmath97 and charm d fluxes give equal numbers of muons above 10 tev ; however @xmath8895% of the charm d muons are in the energy range 10 - 100 tev . the p96@xmath97 muons are split roughly equally between the range 10 - 100 tev and the region above 100 tev . a comparison of the excesses in each of these energy regions may aid identification . however , we are dealing with very low count rates where statistical fluctuations and the uncertainty in the conventional atmospheric neutrino flux will also play a role . as we have just seen , determining the origin of a small excess of muons above the conventional atmospheric expectation relies on looking for angular or energy distribution characteristics . the p96@xmath97 and charm d spectra produce sufficiently different muon distributions to allow them to be distinguished . the integral muon energy spectrum ( figure [ intmuonrates ] ) for the p96@xmath117 flux is similar to the charm d muon spectrum , although it produces an absolute level of muons about a factor of 10 bigger . also the angular distributions for the p96@xmath117 flux have near the same slopes as the charm d angular distributions . this shows that the higher the contribution from @xmath96 interactions to the diffuse agn flux , the more the muon energy and angular distributions become similar to those from the charm induced neutrinos . an agn spectrum made up of only 10% @xmath96 and 90% @xmath97 contributions produces a differential muon spectrum with @xmath8885% of the muons ( above 10 tev ) in the energy range 10 - 100 tev , and an absolute level only a few times bigger than the charm d muon spectrum . this shows that a small observed muon excess showing angular and energy distribution characteristics typical of the charm induced muon spectra could actually be due to a combination of an agn spectrum with a modest @xmath96 contribution with a low overall flux level ( of order of the p96@xmath97 flux given here ) and a charm spectrum lower than the charm d spectrum considered here . in this discussion i have considered models which produce low numbers of muons in large detectors . clearly , there will be unambiguous signatures of agn fluxes if the more optimistic fluxes are correct . excesses well above those predicted by the charm d flux will be clear evidence of an extra terrestrial origin . the p96@xmath97 flux , although of the same level as the charm d flux , has distinctive characteristics ( flatter muon energy spectrum and steeper angular distribution ) that set it apart from the charm induced muons . however , agn spectra with only modest @xmath96 contributions produce muon distributions with similar characteristics to the charm induced muons . interpreting a small observed excess of muons above the conventional atmospheric expectation will require a better understanding of the production of neutrinos from the prompt decay of charmed particles in the atmosphere . in this work i have calculated the expected agn neutrino induced muon rates in large detectors and have compared them to the backgrounds expected from atmospheric neutrinos ( produced by the decay of pions , kaons , muons and the prompt decay of charmed mesons ) . a monte carlo simulation has been used which correctly accounts for the effects of neutral current scattering and uses cross sections calculated with the fmr and mrs g parton distributions , which were derived from recent accelerator data . these higher cross sections result in greater muon rates due to a greater probability of muon production in the final kilometres before a detector , but for incident neutrino directions in the 120 degree aperture about the nadir this effect is largely offset by increased neutrino absorption . the increases in muon rates come from nadir angles greater than 60 degrees , the region where surface or shallow detectors are most susceptible to atmospheric muon contamination . the very deepest detectors will be able to observe these increased fluxes . the lowest neutrino flux considered , due to @xmath97 interactions only in the protheroe agn model , would produce roughly 6 muons per year above 10 tev in a 20000 m@xmath104 detector , which is about the same as that expected from the conventional atmospheric sources and the same as expected from the highest estimates from charmed meson decay . the lowest neutrino induced muon flux due to charmed meson decay gives practically negligible muon rates , which suggests that telling these sources apart may be difficult . however , the p96@xmath97 agn flux produces muons with angular and energy characteristics that would allow it to be distinguished from the charm and conventional atmospheric backgrounds . on the other hand , an agn flux with around 10% or more contribution from @xmath96 interactions produces muon angular and energy distributions similar to those of the charm induced muons . an observation of muons seemingly consistent with the level of the charm d flux could actually be due to an agn spectrum with a modest @xmath96 contribution and an overall flux level around 1/10 th of the p96@xmath117 flux , in combination with a charm induced flux consistent with the tig model . a better understanding of the charm production mechanism in the atmosphere will then be required to interpret such an observation of a small number of muons above the conventional atmospheric background . this discussion has centred around a possible worst case scenario ( low agn fluxes and uncertain charm fluxes ) . the larger fluxes considered in this work would be readily observable in a 20000 m@xmath104 detector , using energy cuts of around 1 - 10 tev . the planned deployments or extensions of the dumand , amanda , nestor and lake baikal experiments should herald the birth of observational extra - terrestrial neutrino astronomy , if the more optimistic agn models and neutrino fluxes considered in this work are near to correct . i thank f. steffens , w. melnitchouk , a. thomas and g. frichter for useful discussions on qcd and neutrino cross sections and r. protheroe for clarifying aspects of agn and atmospheric neutrino production . i thank b. dawson and r. clay for useful discussions , encouragement and careful reading of manuscripts and m. roberts , t. porter and j. reid for their advice throughout the course of this work . an anonymous referee is also thanked for helpful comments on the original manuscript .

new information on the structure of the nucleon from the hera @xmath0 collider leads to higher neutrino cross sections for the processes @xmath1 needed to calculate the expected rates of astrophysical neutrino induced muons in large detectors either under construction , or in the design stage . these higher cross sections lead to higher muon rates for arrival angles where neutrino attenuation in the earth is less important . on the other hand , new estimates of agn neutrino fluxes suggest that the expected muon rates in these detectors may be much lower than previously calculated . i use the new cross sections to calculate the expected muon rates and angular distributions in large detectors for a variety of agn models and compare these rates with the atmospheric neutrino backrounds ( from both conventional decay channels and the prompt charmed meson decay channels ) . if the lowest flux estimates are correct , there may be diffculties in determining the origin of a small excess of muons , due to the large uncertainty in the rate of the charmed meson neutrino production channel . however , the more optimistic agn neutrino fluxes should be detectable in proposed detectors , such as dumand - ii , amanda , nestor and lake baikal .

however , some types of femoral fractures , such as an atypical femoral fracture ( aff ) , a periprosthetic femoral fracture ( ppff ) , and a subtrochanteric fractures are recalcitrant challenges for orthopedic surgeons123 ) . even after displaced aff is treated with standard method , the results are not so satisfactory . reportedly , up to 46% of affs treated with intramedullary nail ( imn ) required reoperation for delayed union or nonunion4 ) . high risk of complication has been reported with ppff such as nonunion , aseptic loosening , infection , and death3 ) . femoral nonunion ( fnu ) is also surgically demanding since the failure rate after surgical treatment for fnu is reportedly high ( 0 - 53%)25 ) and their successful treatment may be prolonged and exploit numerous resources . ppff is expected to occur in 1.0% to 3.5% of primary total hip arthroplasty ( tha)7 ) , and the number of annual tha implantation was estimated around 1,000,000/year . fnu was reported to occur up to 20% of femoral fractures , depending on the type of fracture and on the technique used5 ) . the most well - known cause of aff is long term use of bisphosphonate , which induces over - suppression of bone turnover . in normal bone , bone turnover repairs micro - damages which occur during normal daily activities , and micro - damage accumulates and leads to aff without the repair process6 ) . nonunion is often a consequence of inadequate fixation or poor biology for bone forming cells after fracture treatment . for treating these problems , skeletal stabilization and provision of an environment conducive to bone healing teriparatide ( tptd ) is a synthetic / recombinant human parathyroid hormone consisting of a 1 - 34 n - terminal amino acid sequence of the intact parathyroid hormone molecule , which is approved for osteoporosis . though accurate mechanism of tptd 's anabolic effect on bone is not completely understood yet , tptd clearly have osteogenic effect8 ) . given anabolic action of tptd and pathophysiology of aff and fnu together previous preclinical studies revealed tptd improved fracture healing with or without surgery , and some clinical case series also introduced tptd as potential agent which can promote union in incomplete aff or fnu patients who was treated without surgery9 ) . however , in clinical settings , question remains whether adjuvant tptd expedites bone healing process of surgically challenging femoral fractures , such as aff , ppff , and fnu , or not . the present authors postulated that adjuvant tptd could enhance surgical union rate and abundant callus formation without safety concerns even used at perioperative period . therefore , we determined the following : ( 1 ) whether the adjuvant tptd could achieve satisfactory union rate of surgically challenging cases such as displaced aff , ppff , and fnu ; ( 2 ) whether the adjuvant tptd could promote development of abundant callus after surgical fixation ; ( 3 ) whether the adjuvant tptd had medically serious adverse effects . from august 2010 to september 2014 , all the patients who used tptd after surgery for aff , ppff , and fnu ( 13 patients ) were followed up more than a year after tptd medication and included in this retrospective case series study , which was approved by the institutional review board of seoul national university college of medicine ( irb no . , postoperative adjuvant tptd had been offered to all the patients who had gone through a surgery for osteosynthesis of aff , ppff , or fnu except for the patients with abnormality of serum laboratory test or history of bony malignancy . relatively high prevalence of complication and treatment failure of aff , ppff , and fnu , the mechanism of tptd , expected effects on fracture healing and the currently approved indications of tptd were explained . tptd was prescribed at the approved dose for the treatment of osteoporosis ( 20 g / day ) only to the patients who consented to an empirical , off - label therapy . in all cases except for one ( case 8) , this was the first time to use tptd . patients started injection median 13 days ( interquartile range [ iqr ] , 20.3 days ) after the index surgery . medication was stopped if the patient refused to continue the medication for any causes including intolerable adverse reaction and financial burden . on radiologic evaluation , we classified fracture pattern ( subtrochanteric or femur shaft fractures ) . the femur shaft fracture was defined as extending from below the subtrochanteric region to supracondylar metaphyseal flare . six were acute affs , one was acute ppff , and the other six were fnus . among 13 cases , none was smoker , three had been receiving nonsteroidal anti - inflammatory drugs as painkillers for less than one month , and two had diabetes mellitus10 ) . the severity of osteoporosis was estimated on the basis of a bone mineral density measurement by dual - energy x - ray absorptiometry ( dexa ) in eight patients . six of the fractures affected the femoral shaft , and seven affected the subtrochanteric area ( table 1 ) . eight were aff or fnu after aff with all the major features of affs highlighted in the task force report of the american society for bone and mineral research11 ) . after aff , all the patients were counseled to stop bisphosphonate . with difference of potential impairment for bone healing , seven of acute fracture cases were designated as acute fracture group and six of fnu cases as fnu group . among all acute fractures , which were closed injury , six were affs , and the other was ppff . among six of affs , four fractures occurred without trauma and two with minor trauma such as all the original injuries were closed femoral fractures , due in two cases to motor vehicle collisions and in four to slip downs including a case of vancouver b1 periprosthetic fracture of bipolar hemi - arthroplasty12 ) . the median time from initial injury to index operation with adjuvant tptd was 8.4 months ( iqr , 29.9 months ) , with a median of 1.5 operations before the index operation ( iqr , 2.5 operations ) in fnu group . imn , plate or both were utilized for fixation depending on the surgeon 's decision . bone graft was done depending on the surgeon 's decision as well . in acute fracture group , two open reduction and internal fixation ( orif ) with plate , five imns to subtrochanteric affs were applied with adjuvant tptd . autogenic bone graft was performed in two cases ( case 1 and 2 ) . in fnu group , tptd supplemented two imns ( one exchange nailing and one dynamization with nail ) , four orifs ( two with plate , two with plate and nail ) . structural allogeneic bone graft was performed in three cases ( case 8 , 12 and 13 ) . at the time of surgery , all nonunions were aseptic according to intraoperative microbiology samples and the overall clinical profile of each case ( fig . patients were followed up every month to assess adverse response and necessity of tptd continuation . after medication , visiting interval was individualized depending on progression to union , usually two to three months . evidence of union was assessed with radiographs on every visit . without consensus of the assessment of fracture union , the pain - free ambulation was regarded as clinical union14 ) . and cortical continuity of more than three cortices on anteroposterior and lateral plain radiographs was considered as complete radiologic union15 ) . the intervals between medication and appearance of each sign of union were recorded . for evaluating the amount of callus , we evaluated fracture healing response , which was calculated by dividing largest diameter of the callus by the bone diameter at that level on the same radiograph16 ) . however , the largest diameter of even the most amorphous tube - like structure is substantially the most important determinant of volume in the absence of massive variations in length . a numerical value for fracture healing response was therefore calculated by dividing the largest diameter of callus by that of bone diameter at or adjacent to the fracture site on the same radiograph . with variations of medication start after surgery and chronicity of lesion , fracture responses of both before tptd start and after union were measured and ratio of both was calculated as a reflection of tptd effect on callus formation . all seven acute fractures were united and five of six fnus were healed ( fig . 1 , 2 , table 2 ) . one patient ( case 10 ) who went through three operations before index operation did not progress to successful healing even after nail dynamization with three months of adjuvant tptd . the median time to clinical union was recorded as 5.7 months ( iqr , 7.5 months ) , and the median time to radiological union was recorded as 5.4 months ( iqr , 3.9 months ) . median ratio of fracture healing responses before and after tptd start was 1.2 ( iqr , 0.3 ) . with the difference of chronicity of lesion , acute fractures showed higher ratio of fracture healing response ( median , 1.4 ; iqr , 0.1 ) , whereas fnus showed relatively lower ratios ( median , 1.1 ; iqr , 0.2 ) ( table 2 ) . we harvested callus tissue for the microscopic examination from a patient who required revision surgery after two months of tptd use ( case 8) . the patient with bipolar hemiarthroplasty which was done four years before suffered from displaced periprosthetic fracture of vancouver b1 type . noncompliance to surgeon 's instruction led to failure of orif after adjuvant tptd of two months . while the patient had gone through revision with plate and structural allogeneic bone graft , callus tissue was harvested for histologic evaluation . abundant bone , cartilage , and fibrous tissue were observed in the harvested tissue under the microscopic examination ( fig . one was 74-year old female ( case 1 ) with femoral shaft fracture who complained about nausea and leg cramps . tptd was used for 12 weeks as scheduled and union completed 12 weeks after medication without any other adverse reactions . the other was 69-year old female ( case 2 ) with subtrochanteric fracture who suffered from pruritus and rash around injection site . she stopped medication after four - week use and union completed 48 weeks after medication without recurrence of discomfort . the current study reviewed 13 patients who were treated with adjuvant tptd after surgical treatment for aff , ppff , or fnu . abundant calluses were pronounced and successful union could be achieved in 12 patients without medically severe adverse reaction . as some of biological factors unfavorable for fracture union are already known , such as aff , nonunion , advanced age , medical comorbidities , smoking , nonsteroidal anti - inflammatory drug use etc.10 ) , novel methods which can stimulate biology of bone healing process may be much help to the fracture patients with the unfavorable factors . both aff and fnu have poor biologic environment for fracture healing even after surgical treatment12 ) . however , considerable morbidity is associated with this established procedure , including blood loss , nerve and muscle injury , chronic pain at the donor site and local infection17 ) . bone morphogenic protein also has been tried , but frequent adverse effects were reported with safety concerns19 ) . compared to other methods , adjuvant tptd has certain advantages as a systemically administered agent which can stimulate bone healing process for a prolonged period without invasive procedure18 ) . tptd was tried to reverse the unfavorable condition in several preclinical studies in conditions with , osteoporosis20 ) , long term use of steroid21 ) , diabetes22 ) , stress fracture23 ) , and surgically made nonunion20 ) . tptd alone was tried for delayed union or nonunion and reported anecdotally24 ) . in the most of reports , tptd was applied to delayed union over 6 months after surgery . a preclinical study for unfavorable condition with surgical fixation27 ) showed positive results of adjuvant tptd . while most of clinical reports for adjuvant tptd were anecdotal25 ) , miyakoshi et al.26 ) reported 16 patients were treated with surgical fixation and adjuvant tptd . tptd treatment significantly shortened the postoperative time for fracture healing and reduced rates of delayed healing or non - union after bisphosphonate - associated aff . clinical reports about adjuvant tptd with surgery are still only one in aff and none in nonunion . to our knowledge , the current study is the first case series which reports that adjuvant tptd is effective to stimulate biology disrupted with surgical intervention . this case series will be the basis for further study . among 13 patients in the current study , he had gone through three operations before the index operation , which was dynamization with three months of adjuvant tptd . the dynamization 23 months after initial injury might be a risk factor for the failure . dynamization is a simple method to stimulate osteogenesis by controlled axial instability28 ) . despite the theoretic basis , the success rate of dynamization for nonunion is reported around 50% and to be decreased when it is performed late after established nonunion28 ) . moreover , repeated operations around the fracture site may have aggravated the damage of local vascularity , which in turn diminishes biologic property of bone healing . as a result , the current case series showed tptd stimulate formation of abundant callus with median increase of 22% in diameter of callus . according to the difference of chronicity of lesion , the fracture healing responses increased in a various extent . acute fractures had shown more increase in healing response than nonunions . however , taking it into consideration that the volume is proportional to the cube of its length , the increment of diameter does not fully reflect the increment of volume . as nonunions already had a certain amount of callus at the time of tptd start , callus diameter of nonunions can not be directly compared to those of acute fractures . spencer16 ) reported femoral fracture healing response of control group up to 1.5 . according to the study , as lack of stability also leads to abundant formation of callus as well , the fracture healing responses can not be compared directly to the results of the different studies and further prospective study with standard measurement of callus volume might reveal the comparison . clinical union was delayed more than radiographic union in five patients in the present study . we assumed that the major cause of the difference between clinical and radiographic union resulted from the retrospective nature of the present study . the retrospective review of medical records has certain limits on evaluating pain nature which determines whether the clinical union was achieved . to avoid a subjective interpretation of medical records , we evaluated clinical union in the most conservative way . as the method for determining union is still controversial , the further studies may have to adopt the prospective evaluation in the authorized methods29 ) . according to the report based on a telephone survey , intolerable adverse reaction was the major cause of tptd discontinuation30 ) . therefore , adverse reactions of tptd had been one of the major interests of previously published studies30 ) . previous reports about safety concerns of tptd were studied in the postmenopausal women who were not in perioperative period . around operative treatment , patients are exposed to various medical substances which cause or aggravate adverse effects which overlap to the ones of tptd . still none of reports were regarding the safety concerns of tptd around perioperative period . two adverse reactions of the current study were within the limits of the reports already published . the similar adverse reaction in patients of postoperative period provide us the impression that adverse reactions of adjuvant tptd are not quite discordant with previously reported ones and encourage us to proceed to further study . as the purpose of the current case series was to review all the patients with adjuvant tptd in our center and to plan the further study based on this review , further prospective study would be possible after more encouraging results are published including the current study . second , the small sample size in our study gives little power to detect any relationships . as high cost and application to unapproved indication of tptd make patients hesitate to use it , the reports for adjuvant tptd for surgically treated patients are still anecdotal . further studies are expected to reveal whether adjuvant tptd is effective for the surgically challenging cases . comparing the results of this study with the ones of literature can lead to a hasty conclusion because of the small sample size and inconsistent methods to measure outcomes . we thought it is reasonable to understand the high union rate and the tendency of abundant callus formation in the current study as the potential effect of adjuvant tptd . the various treatments for complex problems made hard for us to control variables . as the purpose of the present study was to review all the patients with adjuvant tptd in our center and to find a positive role of adjuvant tptd , the current case series fulfilled the purpose with suggesting the potential effect of adjuvant tptd . three patients started tptd more than a month after index surgery , and three patients stopped the medication before 12 weeks . although this heterogeneity attenuates the strength of the evidence for adjuvant tptd , 92% of the present case series with challenging fracture achieved union , revealing the clue for the positive role of adjuvant tptd . adjuvant tptd was tried to 13 challenging cases including aff , ppff , and fnu . abundant calluses were pronounced in all the patients and successful union could be achieved in 12 patients . no medically serious adverse reaction was observed in our series . the present review of 13 cases warrants further studies for the positive role of adjuvant tptd on the bone healing of patients with defective bone healing potential .

purposeatypical femoral fracture ( aff ) , periprosthetic femoral fracture ( ppff ) and femoral nonunion ( fnu ) are recalcitrant challenges for orthopedic surgeons . teriparatide ( tptd ) had been demonstrated to have anabolic effects on bone in various studies . we postulated that adjuvant tptd after operation would enhance biologic stimulation for bone formation . we investigated ( 1 ) whether the adjuvant tptd could achieve satisfactory union rate of surgically challenging cases such as displaced aff , ppff and fnu ; ( 2 ) whether the adjuvant tptd could promote development of abundant callus after surgical fixation ; ( 3 ) whether the adjuvant tptd had medically serious adverse effects.materials and methodsthirteen patients who agreed to off label use of tptd in combination of operation were included in this retrospective case series . median patients ' age was 68.7 years , and there were three male and ten female patients . their diagnoses were nonunion in six patients and acute fracture in seven . medical records and radiographic images were reviewed.resultstwelve of thirteen fractures were united both clinically and radiologically within a year after adjuvant tptd . union completed radiologically median 5.4 months and clinically 5.7 months after the medication , respectively . callus appeared abundantly showing median 1.4 of fracture healing response postoperatively . there was no serious adverse reaction of medication other than itching , muscle cramp , or nausea.conclusioneven appropriate surgical treatment is a mainstay of treatment for aff , ppff , and fnu , the current report suggested that adjuvant tptd combined with stable fixation results in satisfactory outcome for the challenging fractures of femur .

the aim of donor nephrectomy is to achieve an adequate graft with the lowest morbidity to the donor . during recent decades , the best approach has been a large flank incision with a rib resection . although this is a safe procedure , it is associated with high morbidity due to incision pain and abdominal asymmetry.1 sub - costal abdominal incision may produce less pain , because it causes less damage to the muscles and nerves of the abdominal wall and can potentially prevent abdominal wall weakness . the laparoscopic approach offers less postoperative pain and a more rapid return to daily activities . although effective , the learning curve for the laparoscopic approach is steep and requires a trained team along with proper equipment . in this study , a prospective analysis of the flank incision ( fi ) , extra - peritoneal sub - costal incision ( sc ) , and transperitoneal video - laparoscopic ( vl ) methods for donor nephrectomy two patients refused to enroll , and a total of 107 pairs of donors and recipients were studied in three groups : 38 vl , 32 sc , and 37 fi . the vl approach was used in all left nephrectomies because of the larger extension of the left renal vein . for the right kidney , either the fi or sc approach was performed , allowing for use of the entire extension of the right vein with the aid of a vascular clamp on the inferior vena cava . a single surgical team performed all open nephrectomies , while a team experienced with the minimally invasive approach executed the laparoscopic procedures . fi nephrectomies were performed with the patient in lateral decubitus with partial resection of the 12th rib . in the sc approach , the patient was positioned in a 30 oblique supine position and the incision made from the tip of the 12th rib to the rectus abdominis muscle . in the laparoscopic approach , the patient was also positioned in a 3045 lateral decubitus using a maximum intracavitary pressure of 15 mmhg . the renal vessels were controlled with a hem - o - lok ( weck closure systems , research triangle park , nc , usa ) device . the kidney was extracted in an adequate retrieval bag through a transverse supra - pubic incision . warm ischemia time was measured from renal arterial occlusion to immersion of the organ in the cold perfusion solution . all donors underwent the same follow - up protocol regardless of surgical approach . in order to evaluate the postoperative pain and analgesic intake , donors that did not undergo a pre - established form of anesthesia ( epidural block associated with general anesthesia ) as well as those who underwent surgical re - exploration postoperative analgesia consisted of metamizole sodium , which was administered either intravenously ( 1 g ) or orally ( 0.75 g ) upon the patient s request . when metamizole sodium was insufficient , meperidine ( 20 mg ) after discharge , oral metamizole sodium was prescribed at the same dosage given during the hospital stay . surgical re - intervention , blood transfusion , and abdominal wall infection were analyzed on the 90th day after surgery . late postoperative complications were categorized as incisional problems , chronic pain , hypoesthesia , and abdominal wall asymmetries . in the recipients , data regarding the terminal chronic renal insufficiency etiology , time of dialysis , level of immunological match between donor and recipient , and length of hospital stay were collected . the immunosuppression protocol was based on administration of cyclosporine , prednisone , and azathioprine or mycophenolate mofetil . recipient surgical complications were analyzed in first- and second - time transplant recipients due to the fact that the iliac fossa was not previously manipulated . regardless of condition , all recipients were considered for determination of the post - transplant graft and patient survival rates . serum creatinine was measured on the 1st , 3rd , 5th , 10th , 30th , and 90th postoperative days , and when possible it was also measured one and two years after the transplant . for the analysis of creatinine levels , patients who underwent postoperative dialysis were not included in the measurements for the following ten days . postoperative complications were categorized as vascular and ureteral abnormalities , lymphocele , hematoma , and need for another surgical intervention . univariate analysis was performed using the student s t - test for continuous parametric data , wilcoxon rank sum test for continuous non - parametric data , pearson s chi - square test for categorical data , or fisher exact test where appropriate . within group comparisons the mean warm ischemia time in the vl group was 2.71.3 min , which was significantly longer than that for the sc and fi groups ( valor sc and valor fi , respectively ) . there was one pleural opening each in the sc ( 3.1% ) and fi ( 2.7% ) groups . two patients , both from the vl group ( 1.9% ) , required re - operation . one patient underwent an exploratory laparotomy showing no abnormal findings on the second day after transplantation , whereas the second patient presented with hypotension and tachycardia associated with abdominal pain two hours after nephrectomy . in surgery , this patient was the only one in this pool of donors ( 0.9% ) to receive a blood transfusion . there was a higher frequency of late incisional problems on the 90th postoperative day , where these were most frequently categorized as pain in the fi group and paresthesia and abdominal asymmetry in the fi and sc groups ( table 1 ) . data regarding the demographics of the 107 transplant recipients , duration of dialysis before the transplant , and post - transplant hospital stay length are shown in tables 2 and 3 . data regarding pain intensity and analgesic consumption were collected for 103 of the 107 donors . four patients ( all from the vl group ) were excluded from this evaluation ; two of the patients were excluded because they did not receive epidural anesthesia , and two were excluded because they underwent re - operation during the postoperative period . data regarding the need for dialysis during the first week , delayed renal function , and immediate renal function are presented in table 2 . no statistically significant difference was noted among the three groups with regard to the immediate function of the transplanted organ ( p=0.785 ) . the mean creatinine levels of the 87 evaluated recipients are shown in figure 1 . nine patients were excluded from this dataset due to the need for dialysis during the first week after transplantation . there was no statistically significant difference in the creatinine levels at any time during the postoperative period , frequency of vascular ( p=0.834 ) or ureteral complications ( p=1.0 ) , or total complication rate ( p=0.570 ) between groups . of the 107 transplant recipients , the 9 patient deaths ( 8.4% ) were equally distributed among all three groups ( p=0.516 , figure 2 ) . four patients died during their initial hospital stay , two secondary to sepsis , and two due to cardiovascular complications . the other five deaths occurred during the late postoperative period , four of which were due to cardiovascular complications . in the last decade , approaches with lower morbidity have been proposed for living kidney donors . approximately over a similar period vl approaches to renal surgery have been developed and tested in brazil.2,3 during in this study , we compared three approaches with respect to their benefits for donors and graft function . because the vl and sc approaches were new at our institution , the first 15 nephrectomies for each procedure were not included in this study to eliminate effects due to the learning curve.47 initially , we found no evidence indicating that the vl approach was safe for kidneys with multiple arteries ; when we faced such a condition , the right kidney was harvested.8,9 in recent years , however , arterial multiplicity is no longer considered an exclusion criterion for laparoscopic donor nephrectomy.10 pain intensity on an analog scale differed in all three groups , and a significant decline was noted on various postoperative days . the fi group presented the highest pain intensity during the follow - up period . a statistically significant difference in the first three postoperative days was observed in comparison to the vl group . the sc group presented lower pain intensity in comparison to the fi group , but higher pain intensity than the vl group ; however , these differences were not statistically significant . the difference in postoperative pain had a direct relationship with the amount of consumed analgesic . in the fi group , a greater number of patients required metamizole and meperidine during the hospital stay or after discharge . the hospital stay was longer in the fi group , but no difference in length was observed between the vl and sc groups . other studies in the literature have noted similar results , with longer convalescence and longer times away from daily activities.11 in all groups , some late complications were related to the operative wound . in the vl group , four donors ( 10.5% ) presented pain or paresthesia around the supra - pubic scar ( pfannestiel incision ) used for organ extraction . as expected , there was no complaint or abdominal asymmetry 90 days after nephrectomy in this group . pain , paresthesia , and/or abdominal asymmetry were observed in 19 ( 59.4% ) and 24 ( 64.9% ) donors from the sc and fi groups , respectively . these rates are higher than the average of 48% reported in the literature , 14 . such a high complaint and asymmetry rates are undesirable in a group of healthy kidney donor volunteers . in the recipient group , there was no relationship between the approach used to harvest the kidney and its function in the recipient . as reported in previously published studies , this correlation shows that the longest surgical and warm ischemia times remain within a safe and reasonable range without impairment post - transplant renal function.12,13 our data showed a higher rate of delayed graft function than did previous studies . we believe that this higher rate is related to intra - operative hypo - hydration . with strict adherence to a new protocol for donor hydration , this incidence this data is supported by existing literature , which describe complication rates of up to 31% for the vl approach and 19% for open surgery.14,15 finally , there was no difference in the graft or recipient survival rates that could be attributed to the effect of warm ischemia time or manipulation of the kidney pedicle . donor nephrectomy performed with the laparoscopic and anterior sub - costal approaches is just as safe as that performed via the standard flank oblique incision . the former techniques offer advantages with regard to postoperative pain , hospital stay , and late morbidity from the incision . the lower morbidity in the laparoscopic and subcostal approaches did not compromise the harvesting of an adequate organ , since graft function , surgical complications , and survival rates were similar in all groups .

purpose : living donor nephrectomy is usually performed by a retroperitoneal flank incision . due to the significant morbidity and long recovery time for a flank incision , anterior extra peritoneal sub - costal and transperitoneal video - laparoscopic methods have been described for donor nephrectomy . we prospectively compare the long - term results of donors as well as functional recipients submitted to these three approaches . materials and methods : a total of 107 live donor renal transplantations were prospectively evaluated from may 2001 to january 2004 . donors were compared with regard to operative and warm ischemia time , postoperative pain , analgesic requirements , and complications . recipients were compared with regard to graft function , acute cellular rejection , surgical complications , and graft and recipient survival . results : the mean operative and warm ischemia times were longer in the video - laparoscopic group ( p<0.001 ) , whereas patients of the flank incision group presented more postoperative pain ( p=0.035 ) , required more analgesics ( p<0.001 ) , had longer hospital stays ( p<0.001 ) , and suffered more pain on the 90th day after surgery ( p=0.006 ) . in the sub - costal and flank incision groups , there was a larger number of paraesthesias and abdominal wall asymmetries ( p<0.001 ) . recipient groups were demographically comparable and presented similar acute tubular necrosis incidence and delayed graft function . the incidence of acute cellular rejection was higher in the video - laparoscopic and flank incision groups ( p=0.013 ) . there was no difference in serum creatinine levels , surgical complications , or recipient or graft survival between groups . conclusions : the video - laparoscopic and sub - costal approaches proved to be safe , and to provide donor advantages relative to the flank incision approach . among recipients , the complication rate , graft survival , and recipient survival were similar in all groups .

a superconductor in contact with a normal metal induces cooper correlations between electrons in the normal region , the phenomenon known as the proximity effect . its microscopic origin lies in andreev reflection @xcite of an electron into a hole at the normal - metal superconducting ( n - s ) interface . the probability of andreev reflection and thus the strength of the proximity effect is determined by the transparency of the n - s interface and the nature of electron propagation in the n part of the structure . disorder in the normal conductor near the n - s contact was shown theoretically @xcite to increase considerably the effective probability of andreev reflection ( see ref . @xcite for a recent review from the experimental viewpoint ) . the standard semiclassical theory of n - s conductivity @xcite , based either on the traditional nonequilibrium superconductivity approach @xcite or on the scattering formalism @xcite , usually neglects interaction effects in the n part of the structure . however , in low - dimensional structures , coulomb interaction in the normal diffusive region gets enhanced @xcite , which may affect strongly the andreev conductance and noise . in this paper we address the effect of interaction between electrons in the normal part of an n - s structure on the charge transport through the system . to study a system with interaction a novel theoretical method should be developed since neither of the above - mentioned approaches can handle interaction corrections . indeed , the scattering matrix formalism relying on the linear relation between the outgoing and incoming states is _ a priori _ a one - particle description . on the other hand , larkin - ovchinnikov kinetic equation @xcite can be generalized to allow for ( at least some part of ) interaction corrections , but its practical solution seems hardly possible beyond the first order of perturbation theory in interaction strength @xcite . an appropriate formalism had been developed in ref . @xcite in the framework of the keldysh action for disordered superonductors @xcite . we start from the fully microscopic lagrangian describing interacting electrons in the diffusive conductor . then , successively integrating over electronic degrees of freedom in the normal conductor we end up with the _ proximity action _ , @xmath0 $ ] , which is a functional of two matrices , @xmath1 and @xmath2 , describing the states of the superconductive and external normal terminals of the n - s structure ( cf . fig . [ f : nsisland ] ) . once the form of the proximity action is known , one can easily calculate the conductivity of the system , current noise , and , in principle , higher correlators of current and even the full statistics of transmitted charge @xcite . the proximity action approach bears an obvious analogy with the scattering matrix approach @xcite as both describe transport properties in terms of the characteristics of the terminals ( stationary - state green functions of the terminals @xmath3 in the former versus asymptotic scattering states in the latter approach ) . in this respect , the proximity action method also shares the logic of nazarov s circuit theory of andreev conductance @xcite . on the other hand , the keldysh action approach is a natural generalization of the kinetic equation for dirty superconductors for the case of fluctuating fields . the larkin - ovchinnikov kinetic equation then emerges as a saddle point equation for the keldysh action @xcite . [ f : nsisland ] fig . . a small superconductive island ( s ) of size @xmath4 connected to a reservoir ( r ) through a tunnel barrier ( i ) and a dirty normal film ( n ) of size @xmath5 . as an application of the formalism , we will study charge transport in two - dimensional ( 2d ) n - i - s structures shown in fig . [ f : nsisland ] at low ( compared to the s gap @xmath6 ) temperature and voltages , and arbitrary ratio @xmath7 , where @xmath8 and @xmath9 are the resistances of the diffusive normal conductor , and of the tunnel barrier in the normal state , correspondingly . we will calculate the andreev conductance and noise of such systems in the presence of cooper interaction in the normal conductor modified by the coulomb interaction @xcite , as a function of the decoherence time " of an electron and the andreev - reflected hole , @xmath10 , where @xmath11 . we will show that the cooper interaction effects in 2d are substantially different from those in the 1d case considered in ref . in particular , the lowest - order relative correction @xmath12 scales as @xmath13 and grows with the size of the system @xmath14 , provided that @xmath15 . we will sum up the main logarithmic terms of the order of @xmath16^n$ ] and find that cooper repulsion may lead to a nonmonotonuos dependence of @xmath17 on @xmath18 and on the decoherence energy scale @xmath19 . in this paper we will not consider the weak localization @xcite and interaction - induced corrections @xcite to the sheet conductance , @xmath20 , of the normal metal assuming that it is relatively large , @xmath21 . we will also not take into account the effect of the coulomb zero - bias anomaly ( zba ) @xcite on the andreev conductance . this effect was considered in @xcite within the lowest - order tunneling approximation . it was shown , similar to the coulomb zba problem for normal conductors ( cf . , e. g. , ref . @xcite ) , that it can be strongly suppressed if the bare long - range coulomb potential is screened , e. g. , by placing a nearby metal gate . this is the situation we assume in the present paper . another limitation of the present discussion is that we will consider the case of a 2d geometry of the current flow between the superconductive and normal electrodes of the structure , as shown in fig . [ f : nsisland ] . this will make possible to construct a unified functional renormalization group treatment that takes into account modifications of the proximity effect strength both due to multiple andreev reflections and due to cooper - channel repulsion . note that the sample geometry should not necessarily be symmetric as shown in fig . [ f : nsisland ] : the only important feature of the geometry chosen is the 2d spreading of the current flow . here we present a brief overview of the proximity action approach to charge transport in n - i - s systems elaborated in ref . @xcite . eliminating all dynamic degrees of freedom in the normal diffusive conductor , one reduces the total action of the system to the form @xmath0 $ ] , with the matrices @xmath1 and @xmath2 having the meaning of the steady - state keldysh green function of the s island and external normal terminal labeled by r in fig . [ f : nsisland ] , respectively . in the low frequency limit , @xmath22 , when diffusive electron motion spreads over the whole conducting region during one circle of the external voltage , the resulting proximity action has the form s_prox[q_s , q_n ] = -i ^2 g _ n=1^_n ( q_s q_n)^n . [ prox ] the action is known once the infinite set of parameters ( `` charges '' ) @xmath23 is specified . remarkably , for noninteracting systems , knowledge of @xmath24 is equivalent to knowledge of the whole distribution function @xmath25 of transmission coefficients of the system . to formulate this analogy , it is convenient to make a fourier transform from @xmath24 to a @xmath26-periodic function @xmath27 of an auxiliary continuous variable @xmath28 : u(x ) = _ n=1^n _ n nx . [ u - def ] the relation between the function @xmath27 and the generating function of transmission coefficients introduced by nazarov @xcite ( cf . also ref . @xcite ) was established in ref . @xcite by direct comparison : 4 g u(x ) = _ 0 ^ 1 p(t ) dt . [ equiv ] for interacting systems and systems with fluctuations @xcite , eq . ( [ equiv ] ) may be interpreted as a generalization of the notion of transmission coefficients . determination of @xmath24 is a separate task related with elimination of fast modes in the normal conductor . we will discussed it later , while now we will explain how to obtain transport properties from the proximity action ( [ prox ] ) . in order to study conducting properties of the system , we apply a bias voltage @xmath29 to the superconducting and normal terminals of the structure and study its current response . the resulting expressions for the andreev conductance ( in units of @xmath30 ) and noise power take the form @xcite g_a = 4 g u_x ( 2 ) , [ gs ] and i_i_- & = & \ { ( 3-p_s ) ( ) + & + & 12 p_s [ ( -2ev ) + ( + 2ev ) ] } , [ iis ] where @xmath31 , and the superconductive noise function @xmath32 is given by p_s = 1 - . [ ps ] the quantity @xmath33 gives the reduction of the shot noise between the normal and superconducting terminals , @xmath34 , compared to its poissonian value for a single electron tunneling , and can be identified with the fano factor @xcite . for an n - s system , all quantities are expressed in terms of derivatives of @xmath27 at @xmath35 . the counterparts of eqs . ( [ gs])([ps ] ) for the case when the s island is in the normal state can also be expressed in terms of the same function @xmath27 , but with derivatives taken at @xmath36 . the conductance of the system @xmath37 , while the current - current correlator is given by eq . ( [ iis ] ) with the replacements @xmath38 , @xmath39 , and @xmath40 . in principle , one can go further and calculate the full charge transfer statistics in terms of the function @xmath27 following the derivation @xcite in the scattering matrix technique . we have seen that the set @xmath24 or , equivalently , the function @xmath27 encodes all information about charge transmission through the system . now we will discuss how to determine the charges @xmath23 for the system shown in fig . [ f : nsisland ] . the starting point is the microscopic keldysh action for a s island in contact with a disordered metal , derived in ref . it can be represented as a sum of the bulk and boundary contributions . the bulk action , @xmath41 , is a functional of three fluctuating fields : the matter field @xmath42 in the film , the electromagnetic potential , and the order parameter field used to decouple the quartic interaction vertex in the cooper channel . @xmath42 is a matrix in the direct @xmath43-dimensional product @xmath44 of the keldysh and nambu - gorkov spaces , its average value giving the electron green function in the keldysh form , @xmath45 . in the tunneling hamiltonian approximation , the boundary action , s_tun[q_s , q]= - q_s q(d ) , [ tun ] describes an elementary tunneling process between the s island and the n metal . here @xmath46 is the dimensionless tunneling conductance of the interface , and @xmath47 is taken at the metal side of the n - s boundary . the next step is to eliminate degrees of freedom in the n film . 2d geometry of the system suggests that this procedure can be realized with the help of the renormalization group ( rg ) approach by successive integrating over fast modes in the bulk . as a result , the boundary action ( [ tun ] ) which initially described single andreev reflection process gets modified by multiple andreev reflections and acquires the form s_bound = -i ^2 g _ n=1^_n ( ) [ q_sq(r)]^n . [ sg ] where the logarithmic variable @xmath48 , @xmath49 is the high - frequency cutoff , and @xmath50 is the energy associated with the current scale @xmath51 . at the energy scale @xmath52 , the multicharge action ( [ sg ] ) reduces to eq . ( [ tun ] ) : @xmath53 , and @xmath54 , and , consequently , @xmath55 . under the action of the rg , the charges @xmath56 are changing . in the zero - energy limit , when the cooperon decoherence energy @xmath19 is smaller than the current rg energy scale @xmath57 , both diffusons and cooperons contribute to the rg equation which , written in terms of the function @xmath58 , reads @xcite u_+ u u_x = - ( ) u(2 , ) x. [ urg ] the r.h.s . of the functional rg equation ( [ urg ] ) is due to the cooper channel interaction with the scale - dependent constant @xmath59 given by @xcite [ lambda - res ] ( ) = , where @xmath60 is defined at the energy scale @xmath52 . at @xmath61 , coulomb repulsion in 2d drives @xmath59 toward the fikelstein s fixed point @xmath62 . in deriving eq . ( [ urg ] ) we neglected the weak localization and interaction corrections to the film conductance @xmath63 , making use of the small parameter @xmath64 . in the absence of cooper channel interaction , eq . ( [ urg ] ) acquires the form of the euler equation . in this case it is convenient to rewrite it in terms of the new variable @xmath65 and the function @xmath66 as @xmath67 , with the initial condition @xmath68 . in this representation , all information about geometry of the system had gone , and the euler equation for @xmath69 describes evolution of @xmath24 for any ( not only 2d ) system consisting of a tunnel barrier and a diffusive conductor in the zero - energy limit @xcite . if the decoherence energy scale @xmath70 then cooperons become inoperative at the latest stage of renormalization procedure , where @xmath71 . in this case the functional rg equation reduces to u_+ u u_x = 0 , [ turg ] where @xmath72/2 $ ] . the function @xmath73 bears the knowledge of the decoherence scale @xmath19 through the initial condition @xmath74/2 $ ] , where @xmath75 is the solution of eq . ( [ urg ] ) at the upper border of its applicability , @xmath76 . note , however , that crossover from the @xmath77 to @xmath78 regimes is described by eqs . ( [ urg ] ) , ( [ turg ] ) with the logarithmic accuracy only . the rg equations ( [ urg ] ) and ( [ turg ] ) should be integrated until we reach the perfect boundary between the n film and the reservoir . then , substituting @xmath79 into the effective boundary action ( [ sg ] ) , we arrive at the proximity action ( [ prox ] ) with @xmath80 , where @xmath81 . now we proceed with the analysis of the functional rg equations derived in the previous section . we start from the zero - energy limit , @xmath82 , described by eq . ( [ urg ] ) . in the absence of interaction one readily reproduces the known result @xcite for the andreev conductance : g_a^(0 ) = g_t = g_d , [ ga ] where @xmath83 , @xmath84 , and the function @xmath85 satisfies @xmath86 . it is often convenient to characterize the system with the help of the _ effective interface resistance _ @xmath87 defined formally through @xmath88 . for a noninteracting system , the ratio @xmath89 as a function of @xmath7 is shown in fig . [ f : r / r1 ] by the dashed line . it behaves as @xmath90 for @xmath91 and saturates at @xmath92 for @xmath93 . correspondingly , @xmath94 for @xmath91 , and @xmath95 for @xmath93 . at relatively small scales , the effect of cooper interaction described by the r.h.s . of eq . ( [ urg ] ) can be considered perturbatively . the magnitude of the first - order interaction correction to the quasiclassical conductance ( [ ga ] ) , @xmath96 , _ grows _ @xcite with the system size @xmath14 and eventually becomes of the order of @xmath97 at @xmath98 . comparing this scale to the scale @xmath99 , corresponding to the crossover from the tunneling ( @xmath91 ) to diffusive ( @xmath93 ) limits , one can distinguish between the regimes of strong , @xmath100 , and weak , @xmath101 , repulsion ( still , in both cases @xmath102 ) . [ f : r / r1 ] fig . . dependence of the effective interface resistance @xmath103 vs. @xmath7 for different values of @xmath104 obtained by numerical solution of eq . ( [ urg ] ) for @xmath105 . the dashed line corresponds to the noninteracting case , @xmath106 . in general , the functional rg equation ( [ urg ] ) does not allow an analytical solution , and should be solved numerically . for clarity , we will assume hereafter that the interaction constant had reached the finkelstein s fixed point @xmath107 , so that strong repulsion corresponds to a relatively weak tunneling conductance @xmath108 , and vice versa . the effective interface resistance @xmath87 normalized to the tunneling resistance @xmath9 as a function of @xmath7 is plotted in fig . [ f : r / r1 ] for different values of the ratio @xmath109 . for the case of strong repulsion , @xmath110 , @xmath111 very quickly ( at @xmath112 ) reaches its asymptotic value and saturates at @xmath113 . the limiting value @xmath114 decreases with the decrease of @xmath109 up to @xmath115 . at smaller @xmath109 , corresponding to the case of weak repulsion , @xmath114 starts to grow again , and reaches an asymptotic behavior @xmath116 at @xmath117 . in this limit @xmath111 reaches its asymptotic value at large scale @xmath118 . the data of fig . [ f : r / r1 ] demonstrate that in a 2d system the limits @xmath119 and @xmath120 _ do not commute _ : for any small but finite @xmath121 , @xmath103 will eventually ( though , at very large @xmath122 ) deviate from the noninteracting dependence ( dashed line in fig . [ f : r / r1 ] ) and become large . [ f : ga_t_int ] fig . . dependence of the andreev conductance @xmath123 ( normalized to the zero - energy value ) on the ratio @xmath124 for different values of @xmath122 . for all plots , @xmath125 , @xmath126 , and @xmath127 . at large enough temperature , voltage , or magnetic field , @xmath128 , the resistance of the structure is given by @xcite r_a(t , t _ * ) = r_d + r_t , eff(t _ * ) , [ ra * ] where @xmath129 . therefore , a nonmonotonous behavior of @xmath130 will manifest itself in a nonmonotonous temperature , voltage and magnetic field dependence of the subgap conductance . the unusual enhancement of conductivity with the increase of the decoherence energy scale @xmath19 is most pronounced in the limit of weak repulsion , @xmath131 . since the total resistance is the sum of @xmath87 and @xmath8 , cf . ( [ ra * ] ) , the magnitude of the effect is determined by the ratio @xmath132 which has a maximum at @xmath133 . an example of such a nonmonotonous dependence of @xmath123 is shown in fig . [ f : ga_t_int ] . the curves differ by the ratio @xmath7 and correspond to @xmath127 ( i. e. , @xmath134 ) . we emphasize that the described nonmonotonous behavior has nothing to do with usual finite - bias " conductance anomaly in n - s structures with good interfaces @xcite , which occur at @xmath135 even in the absense of interaction in the n region . in simple terms the origin of this new effect can be understood as follows : repulsion in the normal metal produces a superconductive `` gap function '' in the normal conductor , @xmath136 , with the negative ( compared to @xmath137 in a superconductor ) sign . due to its opposite sign , @xmath138 decreases the conductance of the structure , therefore any decoherence that reduces @xmath136 leads to the increase of the conductance . now we turn to the analysis of the noise function @xmath32 . for a noninteracting system in the zero - energy limit it is given by @xcite p_s^(0)(t ) = 1 + . [ ps ] eq . ( [ ps ] ) describes a crossover from the poissonian ( @xmath139 ) to the sub - poissonian ( @xmath140 ) @xcite character of the noise as the system evolves from the tunnel ( @xmath91 ) to the diffusive ( @xmath93 ) limits . in the presence of interaction , @xmath32 can be estimated , qualitatively , by comparing the effective tunneling resistance , @xmath87 , with the diffusive resistance , @xmath8 . for @xmath141 , @xmath142 , while in the opposite case @xmath143 . if we again assume that @xmath144 , then @xmath32 will become a function of two parameters : @xmath7 and @xmath145 . the boundaries between the regions with @xmath139 and @xmath140 on the plane ( @xmath146 , @xmath147 ) are sketched in fig . [ f : diagram ] . in the case of strong repulsion , @xmath148 , @xmath87 very quickly ( at @xmath149 ) saturates at @xmath150 . then one obtains @xcite @xmath151 $ ] , where @xmath152 is the noise function @xcite for the system with the n island . thus , in the limit @xmath148 , the crossover between the tunnel and diffusive character of noise is shifted to @xmath153 , see fig . [ f : diagram ] . [ f : diagram ] fig . . schematic map of the noise coefficient @xmath32 as a function of the tunnel and diffusive resistances in the presence of cooper repulsion @xmath126 . dark area refers to the tunnel limit @xmath154 , whereas light regions correspond to the diffusive regime with @xmath143 . in the limit of weak repulsion , @xmath155 , the situation is more interesting . for @xmath156 , interaction corrections can be neglected and @xmath32 is given by the noninteracting expression ( [ ps ] ) . so , at @xmath156 , @xmath32 decreases from 3 to 1 , the corresponding boundary being shown in fig . [ f : diagram ] . later , at @xmath157 ( when @xmath158 ) interaction corrections become relevant . in this region , @xmath87 is of the order of @xmath8 , and one may anticipate that @xmath32 will deviate from 1 . for even larger @xmath122 when resistance is dominated by the diffusive conductor , @xmath32 will eventually reduce down to 1 . this crossover region is marked in fig . [ f : diagram ] by the dashed lines . the function @xmath32 in the crossover region @xmath157 obtained by numerical solution of eq . ( [ urg ] ) is plotted in fig . [ f : lam_shot ] as a function of @xmath159 . it has a minimum @xmath160 at @xmath161 and a maximum @xmath162 at @xmath163 . [ f : lam_shot ] fig . . noise function @xmath164 vs. @xmath165 for the case of weak interaction , @xmath155 . finally , we consider the @xmath19 dependence of the noise power . in the case of weak interaction , @xmath32 decreases ( at @xmath166 ) with the increase of the cooperon decoherence energy scale @xmath19 , as if the system is becoming more diffusive . this trend is opposite to what one has in the noninteracting case when the increase of @xmath19 drives the system toward the tunnel limit , thus , increasing @xmath32 . in the limit of strong repulsion , @xmath148 , the zero - energy noise function @xmath167 exhibits a crossover from the tunnel to diffusive regimes at @xmath168 . nevertheless , upon increase of @xmath19 the function @xmath169 remains @xmath170 independent down to much smaller values of @xmath171 which correspond to the energy scales @xmath172 . we developed the proximity action functional method able to describe quantum charge transport in mesoscopic superconductive structures in the presence of interaction in the normal metal . new method is applied to the study of the effect of repulsion in the cooper channel upon andreev conductance and noise in 2d n - s structures . interaction corrections scale as @xmath173 and lead to nonmonotonous dependence of both the conductance and the fano factor upon temperature , voltage and magnetic field . we are grateful to g. b. lesovik and yu . v. nazarov for useful discussions . this research was supported by the nsf grant dmr-9812340 ( a. i. l. ) , rfbr grant 98 - 02 - 16252 , nwo - russia collaboration grant , swiss nsf - russia collaboration grant 7supj062253.00 , and by the russian ministry of science via the project mesoscopic electron systems for quantum computing " ( m. v. f. and m. a. s. ) .

we review a novel approach to the superconductive proximity effect in disordered normal superconducting ( n - s ) structures . the method is based on the multicharge keldysh action and is suitable for the treatment of interaction and fluctuation effects . as an application of the formalism , we study the subgap conductance and noise in two - dimensional n - s systems in the presence of the electron - electron interaction in the cooper channel . it is shown that singular nature of the interaction correction at large scales leads to a nonmonotonuos temperature , voltage and magnetic field dependence of the andreev conductance . 2

complications during percutaneous coronary intervention ( pci ) include coronary artery complications ( perforation , distal embolization , side branch occlusion , and stent thrombosis ) and vascular complications ( puncture site hematoma , retroperitoneal bleeding , and atheroembolism ) . among them , stent entrapment with resulting stent deployment failure is rare but can cause fatal conditions such as stent thrombosis or myocardial infarction . although many methods have been used for stent retrieval , there are few reports of the use of a snare via a contralateral femoral approach . here we report one case of half - degloved stent entrapment that occurred during pci and that was successfully treated by a snare via a contralateral approach . an 80-year - old male was admitted owing to recurrent chest pain for elective pci of a chronic total occlusion ( cto ) in a left circumflex ( lcx ) lesion . six months previously , the patient had undergone emergent pci in the left anterior descending artery ( lad ) owing to unstable angina . follow - up coronary angiography revealed no significant in - stent restenosis in the lad and cto in the lcx ( fig . a 7-fr jl4 guiding catheter was engaged and predilation with a 2.020-mm balloon was done . after ballooning , we attempted to insert the 2.530-mm resolute - integrity ( medtronic , minneapolis , mn , usa ) stent into the lcx , but the stent failed to cross the cto lesion in the lcx . we used the deep intubation technique , but the stent could not cross the lesion entirely because the lesion was severely calcified and angulated . while attempting to push the stent , we noticed that the stent was stuck within the lesion . after a struggle , the guiding catheter was taken out but we observed that the stent was half - degloved off the balloon ( fig . because of the risk of stent loss and embolization , we decided to pull out the catheter and stent strut by use of an amplatz gooseneck snare ( ev3 , plymouth , mn , usa ) . we pushed down the guiding catheter and stent strut together to the iliac bifurcation level . the left femoral artery was punctured and we used a 6fr balkin sheath to grab the stent with the snare and both the stent strut and the balloon catheter were removed successfully by the snare ( fig . we completed the procedure and decided on medical therapy instead of pci for the lcx lesion . two days later , the patient was discharged and there have been no adverse events during 3 months of clinical follow - up . entrapment of coronary angioplasty devices , especially the stent strut , is rare but is a serious complication of pci for which cardiac surgery is sometimes required . calcified , long lesions and angulated lesions may predispose to entrapment of the stent strut . the incidence of stent dislodgement or migration ranges from 1.4% to 8%.1 - 4 to prevent stent dislodgement or migration , predilatation with a balloon catheter or use of stents with a smaller profile and good tractability are recommended in case of severe angulated or calcified lesions , as in this patient.5 a variety of stent retrieval methods have been described in the literature , such as using a snare device , a multipurpose basket , a variety of forceps , an angioguard ( a distal protection device ) , a simple balloon and just crushing of the stent into the vessel wall by a balloon.6 - 10 however , using a balloon or a snare to rescue an entrapped stent in a half - degloved state may contribute to stent loss ; to prevent stent loss , it would be safer to approach both sides by inserting the snare via another vascular route . in this case , we pushed down the stent strut and guiding catheter together to the iliac bifurcation level . after that , the contralateral femoral artery was punctured and both stent strut and balloon catheter were removed successfully by a snare with the aid of a 6fr balkin sheath . we think that this technique is safer than other methods in this situation to prevent stent loss and embolization . however , to avoid serious complications , interventional cardiologists should keep in mind the various complications during pci and should understand the lesion anatomy and characteristics in their daily practice .

although stent entrapment is a rare event during percutaneous coronary intervention , stent entrapment can cause stent breakage or loss , which results in fatal complications such as stent embolism or acute myocardial infarction . we report one case of stent entrapment that was successfully treated by a snare via a contralateral transfemoral approach .

gauginos in weak scale supersymmetry could acquire dominantly dirac masses instead of majorana masses . dirac gaugino masses have been considered long ago @xcite and have inspired more recent model building @xcite and phenomenology @xcite . dirac masses for gauginos of the mssm requires the model to be extended to include a chiral superfields in the adjoint representation of each gauge group . some or all of the gauginos could be dirac , majorana , or mixed states depending on the model and the mediation of supersymmetry breaking . among the dramatic consequences that have been studied include : gaugino contributions to scalar masses that are `` supersoft '' ( not log - divergent ) @xcite ; substantial relief from the supersymmetric flavor problem when the low energy model includes an approximate @xmath12-symmetry @xcite ; suppressed edms @xcite ; heavier dirac gauginos that are just as naturalness as lighter majorana gauginos @xcite ; the ( suppressed ) production cross sections of colored superpartners at lhc @xcite ; and the absence of some of the historically characteristic signals of supersymmetry ( same sign lepton searches ) . there are many other interesting consequences of dirac ( or partially dirac ) gauginos that we do not have time or space to review , but can be found in papers cited above . for this snowmass white paper , we delineate some ideas for searches involving dirac gauginos that provide benchmarks to understand the impact of lhc searches thus far , the gaps in the searches that persist , and the opportunities for future searches . one of the important consequences of a dirac gluino is that it can be several times heavier than a majorana gluino with the same degree of naturalness with respect to the electroweak symmetry breaking scale @xcite . once a dirac gluino mass is above roughly @xmath13-@xmath14 tev , gluino pair production as well as associated squark - gluino production cross sections are negligible at the 8 tev lhc . for a dirac gluino of any mass , several squark production channels vanish due to the absence of a `` chirality flipping '' majorana mass in @xmath15-channel exchange , namely @xmath16 , @xmath17 , etc . other squark production channels that involve the gluino in @xmath15-channel exchange , such as @xmath18 , are suppressed by @xmath19 in the amplitude , where @xmath20 is the momentum in the propagator . this suggests the dominant production mode of colored superpartners is @xmath21 for first ( and second , third ) generation squarks is through @xmath22-channel gluon exchange . the total colored superpartner production cross section is therefore reduced by roughly two orders of magnitude compared with what is typical in the mssm a majorana gluino roughly equal in mass to the squarks . there are no dedicated searches for supersymmetric models with a gluino that acquires a dirac ( or `` mixed '' dirac and majorana ) mass . since a dirac gluino can be a factor of several times heavier than a majorana gluino without additional fine - tuning , one interesting scenario to consider is when the squark masses are generated dominantly from the finite contributions from the dirac gluino . in this case , @xmath23 . for squark masses larger than @xmath24 gev , the dirac gluino is sufficiently heavy @xmath25 tev , and with sufficiently suppressed effects at the 8 tev lhc , that it is effectively decoupled from the spectrum . note that this is _ not true _ of a majorana gluino of the same mass , due to the structure of the interactions , in particular , the lower dimension operator for squark production with a majorana mass insertion ( that leads to @xmath26-suppressed effective interactions ) . we can therefore map a modestly heavy dirac gluino into the existing `` decoupled gluino '' simplified model searches performed by the atlas and cms collaborations . squark production with a decoupled gluino is a specific simplified model in which the atlas and cms collaborations have placed bounds on the cross sections within the @xmath27 space . here we mention only the results from the latest analyses , namely a jets plus missing energy search strategy at atlas using @xmath28 fb@xmath29 of 8 tev data at atlas @xcite and cms @xcite . the simplified model used for each search assumed the first and second generation squarks have a common mass @xmath30 , there is a single lsp with mass @xmath31 , and the squarks are assumed to decay @xmath32 of the time via @xmath33 . for a nearly massless lsp , the current atlas results rule out @xmath34 gev while the cms results rule out @xmath35 gev . if the lsp mass were @xmath1 gev , the atlas and cms analyses @xcite find _ no bound _ on the squark mass . these results can be contrasted with , for example , the current bound on the mssm simplified where a majorana gluino is also present in the spectrum . consider the case where @xmath36 : the latest atlas result constrains @xmath37-@xmath38 tev for an lsp up to @xmath39 gev in mass @xcite . regarding the search for first and second generation squarks with a decoupled gluino , the atlas note stated @xcite : `` the expected limits for [ the decoupled gluino case ] do not extend substantially beyond those obtained from the previous published atlas analysis because the events closely resemble the predominant @xmath40/@xmath41-jet background , leading the background uncertainties to be dominated by systematics . '' this implies the need for innovative search strategies to uncover squark production with suppressed production cross sections . clearly , if the first and second generation squarks are much lighter than the standard mssm analyses suggest , it is worthwhile to consider what future collider studies can say about this scenario . following our earlier analysis from 2012 @xcite , we consider the following scenarios : `` dirac5 '' , `` mssm5 '' , `` mssmequal '' detailed in table [ scenarios - table ] . these are _ not _ meant to represent to full spectrum of possibilities or phenomenology associated with suppressed colored sparticle production . instead , we are interested to provide a few benchmark examples of the differences between gluinos having a dirac mass versus a majorana mass as it pertains to searches for ( highly ) suppressed colored sparticle production . .simplified models considered in this writeup . all masses are in tev . sparticles not listed are decoupled . [ cols="^,^,^,^",options="header " , ] in fig . [ fig : crosssections1 ] , we show the production cross sections for three quantities : the total colored sparticle production ( squark and gluino production ) , the cross section of @xmath42 , and the cross section of @xmath43 . all allowed combinations of the first two generations of squarks are summed together . in all results we used madgraph4 @xcite at leading order , for lhc operating at @xmath3 and @xmath4 tev . and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] + and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] + and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] and @xmath4 tev.,title="fig:",scaledwidth=50.0% ] the figures clearly show the suppression in cross sections persist at lhc collider energies of @xmath44 and @xmath4 tev . notice that @xmath43 production is always subdominant to @xmath42 production for a scenario with a @xmath45 tev dirac gluino , throughout the squark mass range shown , @xmath46 tev . by contrast , @xmath43 production is comparable or dominates the production cross section of squarks for either scenario involving a majorana gluino . in the spirit of the irvine `` storyboards '' @xcite for discovery of new physics in the next run of the lhc , we consider the possibility that the lhc has discovered a jets plus missing energy signal consistent with first and second generation squark production with squark mass @xmath47 tev , but with a highly suppressed cross section relative to the expectations from mssm . there are several investigations one would like to apply to the signal . the first obvious one is to try to pin down the mass scale of the squarks and obtain an upper bound on the lsp mass . this requires careful examination of the signal kinematic distributions , e.g. @xcite . searching for accompanying signals , namely in the @xmath50-jet categories could uncover evidence for , or absence of , an accompanying gluino production signal . even if there is no accompanying signals consistent with a kinematically accessible gluino , we saw above that the squark production rates are nevertheless sensitive to a kinematically inaccessible majorana gluino . this can be seen by contrasting the squark production rates for the mssm5 scenario against the dirac5 scenario . if the experimental data on the the squark production rate appears to be consistent with just @xmath42 production , the signal can be probed for consistency with this hypothesis . for example , by measuring the angular distributions of the final state decay products should allow the experiments to verify the signal is consistent with @xmath22-channel gluon production of @xmath42 ( versus a @xmath15-channel gluino - mediated production of @xmath43 with a rate that happened to match the `` observed '' squark anti - squark rate ) . if the rate is slightly larger than what is expected from just @xmath42 production , there are several possible culprits . one is that the gluino is not completely decoupled , and its effects on @xmath15-channel exchange are being ( slightly ) felt . another is that the first and second generation squarks are not precisely degenerate in mass , but these kinematic differences are not readily observable . the central goal in this scenario would be to discover the heavy gluino state . this is where a dirac gluino becomes much more advantageous compared with a majorana gluino ( holding the squark production cross sections roughly the same ) . because the dirac gluino can be much lighter without affecting squark production channels , this suggests associated @xmath51 production can be probed by 33 tev lhc . the leading order rates for @xmath51 production in dirac5 scenario , with @xmath47 tev and @xmath52 tev , are @xmath53 clearly , the cross section at the lhc operating at @xmath44 tev is much too small to be seen at any conceivable integrated luminosity . however , at the higher center - of - mass energy of @xmath4 tev , it is at least conceivable to obtain evidence for a heavy gluino given that the cross section is nearly @xmath14 orders of magnitude larger . at even higher energy machines ( @xmath54 tev ) , there should be no difficulty measuring and studying both associated and gluino pair production . we have focused on the narrow issue of first and second generation squark production in the presence of a heavy dirac gluino . the highly suppressed cross section of lighter squarks is an incredibly important signal to find or rule out , to determine if supersymmetry is realized in this interesting but non - standard way . our quick - and - dirty preliminary investigation suggests that high energy is more important that high luminosity , since kinematics may well limit the ability to probe the dirac gluino directly . this are many more interesting issues that could be explored , and thus far , have few if any experimental analyses completed : * what happens when there is a heavy dirac gluino and lighter majorana electroweak gauginos ? this is an interesting scenario where the electroweak @xmath55-term is not suppressed ( giving the ordinary tree - level higgs mass contribution familiar from the mssm ) , and does not appear to significantly affect squark production @xcite . how much of the same - sign dilepton signal remains when the gluino is dirac while the electroweakinos are majorana ? * what happens when the first and second generation , or even up - type and down - type squarks are not degenerate in mass ? a few interesting recent examples that contains a light second generation can be found in ref . @xcite . * what happens if there is substantial squark mixing , e.g. , following the @xmath12-symmetric supersymmetric model @xcite . squark decays to heavy flavor ( tops , bottoms , and @xmath56s ) become generic . are the bounds better in the case of third generation squarks ( given multitude of dedicated analyses for this `` natural '' region ) ? how effective ( or ineffective ) are the standard jets plus missing energy strategy ? * how is @xmath57 gev realized in this scenario ? in scenarios with dirac electroweak gauginos , there are methods to raise the tree - level contribution mass ( for example , @xcite ) , that typically also require moderately heavy stops ( @xmath58-@xmath14 tev ) . how easily can the stops be probed with colliders ? this is a common but important issue in this and most other supersymmetric scenarios . * ilc implications ? if dirac electroweak gauginos are present , the sleptons and higgs scalars acquire weak - coupling suppressed contributions to their masses , and thus are generically light . in addition , in models with an approximate @xmath12-symmetry @xcite , there are more `` higgs - like '' states to uncover , since each higgs supermultiplet ( @xmath59 ) is paired up with an @xmath12-supermultiplet partner ( @xmath60 ) giving many more scalars and fermions with electroweak interactions with the standard model . finally , we should emphasize that in complete models involving dirac gauginos , there are a host of indirect methods to probe the model . these rely on intensity frontier experiments , adding to the motivation that a diverse array of experiments in particle physics _ that can probe new mass scales _ are an essential complement to the energy frontier experiments . for example , if the low energy theory contains large squark or slepton mixing , there is the possibility to observe a flavor - 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we consider the modifications to squark production in the presence of a naturally heavier dirac gluino . first generation squark production is highly suppressed , providing an interesting but challenging signal find or rule out . no dedicated searches for supersymmetry with a dirac gluino have been performed , however a reinterpretation of a `` decoupled gluino '' simplified model suggests the bounds on a common first and second generation squark mass is much smaller than in the mssm : @xmath0 gev for a massless lsp , and _ no bound _ for an lsp heavier than about @xmath1 gev . we compare and contrast the squark production cross sections between a model with a dirac gluino and one with a majorana gluino , updating earlier results in the literature to a @xmath2 collider operating at @xmath3 and @xmath4 tev . associated production of squark+gluino is likely very small at @xmath3 tev , while is a challenging but important signal at even higher energy @xmath2 colliders . several other salient implications of dirac gauginos are mentioned , with some thought - provoking discussion as it regards the importance of the various experiments planned or proposed . * dirac gauginos in supersymmetry suppressed jets @xmath5 met signals : + a snowmass whitepaper * + graham d. kribs@xmath6 and adam martin@xmath7 + @xmath8__school of natural sciences , institute for advanced study , princeton , nj 08540 _ _ + @xmath9__department of physics , university of oregon , eugene , or 97403 _ _ + @xmath10__ph - th department , cern , ch-1211 geneva 23 , switzerland _ _ + @xmath11__department of physics , university of notre dame , notre dame , in 46556 _ _ +

percolation is a phenomenon in which a cluster formed by given objects becomes infinite , i.e. , in real systems it extends from one border of the system to another . in general , one of the common theoretical procedures is to determine the percolation threshold , i.e. , the minimum concentration of objects at which the percolations too place . it has all features of the phase transition and thus , from many years it has been an object of theoretical interest . the percolation theory has a lot of applications in physics , especially in disordered systems and porous media . computer simulation of this process can usually be realized by random sequential adsorption ( rsa ) [ 24 ] . rsa can model the adsorption of atoms and small molecules , binding of large ligands to polymer chains or protein to solid surfaces , polymers or biological membranes . the lattice approximation is commonly used for the consideration of the percolation in many systems in order to suppress the degree of freedom and for computational purposes . the objects or their parts ( beads ) are located in vertices of a quasi - crystalline lattice in such a case a cluster is formed when an object has neighbors , i.e. , the distance between objects ( or parts of objects ) is equal to the lattice unit . usually , the percolation problem is classified as site percolation where sites are blocked and bond percolation where bonds joining the sites are blocked . one has to remember that the percolation of the polymer chain is a special case of bond - site percolation where bonds are correlated because the chains are integral objects . the most popular large objects studied using the rsa method were stiff elongated rods ( needles ) [ 510 ] . the percolation in such a system was found to be quite different from that for other large objects : the percolation threshold does not change monotonically with the length of the object because needles tend to form locally ordered clusters . in spite of rather extensive studies there are still some inconsistencies in the description of the scaling behavior of percolation and jamming thresholds with aspect ratios of these objects . systems containing other elongated objects ( ellipsoids , rectangles ) were also studied and it was shown that the aspect ratio was a crucial parameter that determined the percolation threshold [ 1113 ] . the consideration of the percolation phenomenon in systems containing other large and irregular objects like polymer chains requires some studies to evaluate calculation methods for this purpose . short flexible chains ( oligomers ) were studied up to date mainly by means of the rsa method by [ 1418 ] . studied the percolation and jamming ( the maximum coverage ) in such systems but it is difficult to refer to their results because of quite different determination of the thresholds [ 14 , 15 ] . nieto et al . performed a detailed and a solid study in which they concentrated on the universality of the percolation process and the influence of the lattice representation on it [ 16 , 17 ] . recent studies of two - dimensional polymer systems performed by zia et al . have shown interesting behavior of the bond percolation threshold [ 1922 ] , however , this model was different from others as polymer chains can cross themselves . the percolation of semi - flexible chains was recently studied by the rsa method showing the temperature dependencies of percolation threshold and a non monotonic behavior of these threshold at some conditions . mixtures of small objects ( oligomers ) of a different shape were also studied by means of the rsa method while mixtures of stiff rods and flexible chains appeared to be tractable by a theory ( a connectedness ornstein - zernike formalism ) . long flexible chains were recently studied by means of the rsa and the cma ( the cooperative motion algorithm ) [ 2629 ] simulation methods . the influence of the presence of explicit solvent molecules , the analysis of the clusters formed by macromolecules and the confirmation of the universal critical behavior of these systems were the main results discussed in these works . in this paper we studied the structure of two - dimensional systems consisting of flexible linear polymer chains near the percolation threshold . the representation of polymer chains was very simple : macromolecules were represented by the sequences of identical beads and positions of these beads were restricted to vertices of a square lattice . the main question addressed was to compare and evaluate methods used for studies of the percolation in systems containing long flexible chains . the paper is organized in the following way : in section the model and the algorithms we describe in detail the idealized representation of polymer chains and both simulation methods used ( rsa and a metropolis - like algorithm ) . in section results and discussion we present the results , mainly percolation thresholds and discuss the comparison of simulation methods and their evaluation . the section conclusions contains the most important conclusions concerning comparison of results and validating of both simulation methods . flexible linear polymer chains were approximated by sequences of beads without any atomic details and single bead represented some chemical mers . each chain in the system consisted of n beads and the number of chains was n. in order to make the calculations more efficient a lattice approximation was introduced : the positions of polymer beads were limited to vertices of a square lattice . the excluded volume was the only potential introduced into the model and , therefore , the chains could not cross themselves . other long - distance interactions were assumed to be identical , i.e. , the system was athermal and corresponded to good solvent conditions . the system was studied in a large two - dimensional monte carlo box and the edge of this box l was chosen to be large enough when compared to the chain s diameter in order to avoid the chain interacting with its image and in order to minimize the influence of the system s size on the percolation threshold . the problem concerning the finite size of the monte carlo box in our studies will be discussed below in the next section . the structure of the polymer system was determined by means of two different simulation methods . the properties of the systems under consideration were calculated by means of the monte carlo simulation employing an algorithm based on local changes of chain s conformation ( fig . the set of these local moves consisted of : 1-bead motion , 2-bead motion , 1-bead end modification and 2-bead end modifications . additionally we used wave motions , where fragments of chain ( three consecutive segments ) were transferred randomly along the chain and exchanged with a single bond and the reptation motion . these last two micromodifications are essential for the ergodicity of the process and make the relaxation of the system considerably faster [ 3032 ] . a polymer bead was picked randomly and an attempt of a motion was performed and accepted / rejected due to excluded volume and geometrical constraints . a monte carlo cycle was defined as one attempt of each local motion applied in average to one bead . an initial polymer s conformation was constructed in a process of the simultaneous growing and the equilibration procedure : a system containing n chains each containing n beads was eventually built . for each system under consideration 1015 independent monte carlo simulation runs were performed . each simulation run consisted of 1010 cycles and at the start of each simulation run the equilibration run was performed , which lasted 1010 cycles . the criterion of the equilibration of the system was the stability of some time - mean parameters of the system , such as the end - to - end distance and the radius of gyration.fig . all two - dimensional chains are present on the surface ( in blue ) and they undergo local changes of conformation ( old conformation is marked in red and the new ones in blue ) ( a ) . random sequential adsorption where a two - dimensional chain ( in red ) is put on a surface and accepted ( in green ) when it does not cross with chains already present on the surfaces ( in blue ) schemes of algorithms used in simulations . all two - dimensional chains are present on the surface ( in blue ) and they undergo local changes of conformation ( old conformation is marked in red and the new ones in blue ) ( a ) . random sequential adsorption where a two - dimensional chain ( in red ) is put on a surface and accepted ( in green ) when it does not cross with chains already present on the surfaces ( in blue ) in this method polymer chains were subsequently adsorbed on a substrate . a two - dimensional chain was randomly selected from an earlier prepared library of conformations and put on the substrate . the adsorbed macromolecules could not overlap and this was realized by the forbidding of the double occupancy of lattice points by polymer beads . all chains were immobilized , e.g. , no conformational changes were allowed and the diffusion process was forbidden ( fig . simulation started with an empty substrate and for each chain at first we randomly selected the position of the chain s beginning . if all these sites were empty , the new chain was added to the system , otherwise the entire procedure was repeated . if any element of the added chain was at the distance of one lattice unit from an already deposited chain ( or a cluster of chains ) the newly added chain formed one cluster with them . before the rsa process we prepared libraries containing a collection of polymers conformations for a given chain length n. for shorter chains the libraries were filled with all possible conformations . for longer chains the libraries were created using the modifications of chain conformations by the algorithm described in section the polymer representation . libraries contained up to 10 different conformations and these conformations were independent one from the other , i.e. , each of the chains was recorded after a large time step . we used the libraries to avoid creating non - overlapping polymer chains during the simulations ( and problem with biased statistics when generating self - avoiding walks ) and thus to speed up the rsa process significantly . when neighboring chains formed continuous path from one system edge to the opposite , this was called a percolation . in order to recognize the moment of percolation a hoshen & kopelman - like algorithm was applied . in this cluster identification algorithm one travels over all lattice points row - wise and identifies clusters consisting of neighboring beads . the tree of labels indicates the connections between the identified clusters [ 1 , 33 ] . flexible linear polymer chains were approximated by sequences of beads without any atomic details and single bead represented some chemical mers . each chain in the system consisted of n beads and the number of chains was n. in order to make the calculations more efficient a lattice approximation was introduced : the positions of polymer beads were limited to vertices of a square lattice . the excluded volume was the only potential introduced into the model and , therefore , the chains could not cross themselves . other long - distance interactions were assumed to be identical , i.e. , the system was athermal and corresponded to good solvent conditions . the system was studied in a large two - dimensional monte carlo box and the edge of this box l was chosen to be large enough when compared to the chain s diameter in order to avoid the chain interacting with its image and in order to minimize the influence of the system s size on the percolation threshold . the problem concerning the finite size of the monte carlo box in our studies will be discussed below in the next section . the structure of the polymer system was determined by means of two different simulation methods . the properties of the systems under consideration were calculated by means of the monte carlo simulation employing an algorithm based on local changes of chain s conformation ( fig . the set of these local moves consisted of : 1-bead motion , 2-bead motion , 1-bead end modification and 2-bead end modifications . additionally we used wave motions , where fragments of chain ( three consecutive segments ) were transferred randomly along the chain and exchanged with a single bond and the reptation motion . these last two micromodifications are essential for the ergodicity of the process and make the relaxation of the system considerably faster [ 3032 ] . a polymer bead was picked randomly and an attempt of a motion was performed and accepted / rejected due to excluded volume and geometrical constraints . a monte carlo cycle was defined as one attempt of each local motion applied in average to one bead . an initial polymer s conformation was constructed in a process of the simultaneous growing and the equilibration procedure : a system containing n chains each containing n beads was eventually built . for each system under consideration 1015 independent monte carlo simulation runs were performed . each simulation run consisted of 1010 cycles and at the start of each simulation run the equilibration run was performed , which lasted 1010 cycles . the criterion of the equilibration of the system was the stability of some time - mean parameters of the system , such as the end - to - end distance and the radius of gyration.fig . all two - dimensional chains are present on the surface ( in blue ) and they undergo local changes of conformation ( old conformation is marked in red and the new ones in blue ) ( a ) . random sequential adsorption where a two - dimensional chain ( in red ) is put on a surface and accepted ( in green ) when it does not cross with chains already present on the surfaces ( in blue ) schemes of algorithms used in simulations . all two - dimensional chains are present on the surface ( in blue ) and they undergo local changes of conformation ( old conformation is marked in red and the new ones in blue ) ( a ) . random sequential adsorption where a two - dimensional chain ( in red ) is put on a surface and accepted ( in green ) when it does not cross with chains already present on the surfaces ( in blue ) a two - dimensional chain was randomly selected from an earlier prepared library of conformations and put on the substrate . the adsorbed macromolecules could not overlap and this was realized by the forbidding of the double occupancy of lattice points by polymer beads . all chains were immobilized , e.g. , no conformational changes were allowed and the diffusion process was forbidden ( fig . simulation started with an empty substrate and for each chain at first we randomly selected the position of the chain s beginning . if all these sites were empty , the new chain was added to the system , otherwise the entire procedure was repeated . if any element of the added chain was at the distance of one lattice unit from an already deposited chain ( or a cluster of chains ) the newly added chain formed one cluster with them . before the rsa process we prepared libraries containing a collection of polymers conformations for a given chain length n. for shorter chains the libraries were filled with all possible conformations . for longer chains the libraries were created using the modifications of chain conformations by the algorithm described in section the polymer representation . libraries contained up to 10 different conformations and these conformations were independent one from the other , i.e. , each of the chains was recorded after a large time step . we used the libraries to avoid creating non - overlapping polymer chains during the simulations ( and problem with biased statistics when generating self - avoiding walks ) and thus to speed up the rsa process significantly . when neighboring chains formed continuous path from one system edge to the opposite , this was called a percolation . in order to recognize the moment of percolation a hoshen & kopelman - like algorithm was applied . in this cluster identification algorithm one travels over all lattice points row - wise and identifies clusters consisting of neighboring beads . the tree of labels indicates the connections between the identified clusters [ 1 , 33 ] . simulations were performed for a chain length n from 3 to 500 ( the metropolis - like algorithm ) and for n from 1 to 500 ( the rsa method ) . in order to determine the influence of the size of the system on the percolation threshold the simulations were performed in the monte carlo box with the edge l = 50 , 100 , 200 , 1000 and 2000 . the polymer concentration was defined as a fraction of lattice sites occupied by chains , i.e. , the number of polymer beads to the total number of sites in the system : = nn / l . the structure of the adsorbed polymer layer was frequently a subject of theoretical and simulation studies . the metropolis - like algorithm one has to detect if a given configuration of the system contains a percolated polymer cluster or not . therefore , we can determine the percolation probability calculated as the ratio of the number of percolated systems to the total number of configurations generated for a given set of parameters . figure 2 presents the percolation probability p as a function of the polymer concentration . all p( ) curves are typical , i.e. , s - shaped and the increase of the chain length shifts the curve toward lower polymer concentrations . qualitatively the same behavior was found for other two - dimensional polymer chains : for short chains on the square lattice , long linear chains with explicit solvent molecules on the triangular lattice and the square lattice and for off - lattice hard ellipsoids . one can also observe that the slope of curves decreases with the chains length which is caused by the finite size of the system.fig . 2plot of the percolation probability p obtained in the mc method as a function of the polymer concentration . the case of the monte carlo box l = 1000 . chain lengths are given in the inset plot of the percolation probability p obtained in the mc method as a function of the polymer concentration . the case of the monte carlo box l = 1000 . chain lengths are given in the inset the percolation threshold can be determined from the s - shaped probability curves as an inflection point . in order to calculate the value of the thresholds for infinitely large system two procedures were proposed . the first one finds the inflection point on a p( ) curve using the following fitting [ 17 , 35]:1\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ p\left(\phi \right)=1-{\left(1 + \exp \left(\frac{\phi -{c}_p}{a}\right)\right)}^{-1 } $ $ \end{document}where a is a constant that determines the slope of the curve and with a 0 the curve reduces to the step function ( for an infinitely long chain ) . the extrapolation of the percolation threshold to the thermodynamic limit was done by fitting to the scaling relation:2\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ \left|{c}_p(l)-{c}_p\left(\infty \right)\right|\sim { l}^{-1/\nu } , $ $ \end{document}where cp(l ) and cp( ) are percolation thresholds for the monte carlo box ll and for an infinite system respectively , and is a critical exponent ( theoretical predictions give = 4/3 ) . in fig . all curves are linear , i.e. , the extrapolation of the percolation thresholds toward an infinite system can be made according to eq . one can also notice from this figure that the corrections to the thresholds obtained from simulations in a large mc box ( 2000 2000 ) are on the order of 10 , which is below the standard error.fig . 3log - log plot of the percolation thresholds c p obtained in the mc method as a function of the ( l / n ) for some chain lengths log - log plot of the percolation thresholds c p obtained in the mc method as a function of the ( l / n ) for some chain lengths the second method of the determination of the percolation threshold for an infinite system is based on the finding that percolation probability curves p( ) for systems of different size intersect in one point [ 11 , 21 , 36 ] . figure 4 shows the percolation probabilities p as functions of the polymer concentrations for the chain n = 10 calculated for some sizes of the monte carlo box l. the increase of the system makes the probability curve steeper ( for the infinite system one expects the step function ) . all curves intersect in one point which can give the value of the percolation threshold for the infinitely large box . the values obtained using this methodology are exactly the same as those obtained in the first method . 4plot of the percolation probability p obtained via the mc method as a function of the polymer concentration . the case of chain n = 10 . the sizes of the monte carlo box l are given in the insettable 1the percolation thresholds obtained by the rsa and mc methods . the values of thresholds are extrapolated toward infinite system ( see text for details).nrsamc10.592(2)20.562(2)30.549(2)0.550(2)50.523(2)0.521(3)100.480(3)0.484(3)200.428(5)0.439(4)300.398(5)0.411(4)400.375(8)0.387(6)500.354(6)0.375(8)750.325(8)0.354(10)1000.315(11)0.345(9)2000.282(12)0.320(11)3000.261(14)0.305(12)3000.244(15)0.291(11)4000.230(17)0.278(14 ) plot of the percolation probability p obtained via the mc method as a function of the polymer concentration . the case of chain n = 10 . the sizes of the monte carlo box l are given in the inset the percolation thresholds obtained by the rsa and mc methods . the values of thresholds are extrapolated toward infinite system ( see text for details ) . the percolation thresholds calculated via both simulation techniques are presented in fig . 5 and plotted against the chain length n. one can observe that the threshold decreases with increase of the length of the macromolecule ( the number of beads comprising the chain ) regardless of the simulation method used . there is one more interesting observation concerning the behavior of the percolation thresholds : the values obtained in the mc method are always higher than those from the rsa method and this difference increases with the chain length ( at least for the chain lengths studied ) . 5plot of percolation thresholds c p for as a function of chain length n obtained via both methods studied plot of percolation thresholds c p for as a function of chain length n obtained via both methods studied the question arises what would be the percolation threshold for infinitely long flexible chains ? to answer this question one should consider the polymer local density , i.e. , the number of polymer segments within an equivalent ellipse defined as < n / s>. for a single chain < s > increases faster than the number of segments because < s > scales as n for two - dimensional systems . the percolation threshold corresponds to the system near the crossover from dilute to semidilute solution [ 37 , 38 ] . thus , the polymer density in the entire system near this crossover should approach zero as within a single chain . on the other hand , the number of chains in an infinite monte carlo box would also be infinite . therefore , it is difficult to state if the percolation threshold , which decreases with the length of chain that was observed in our simulations , will eventually approach zero or other non - zero value . a formula describing the influence of the chain length on the percolation threshold was proposed by nieto et al . . it was based on the galam and maugier equation formulated for a site and bond percolation:3\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ { c}_p={p}_o{\left[\left(d-1\right)\left(c-1\right)\right]}^{-a } , $ $ \end{document}where d is the dimension of the system , c is lattice coordination number while po and a are fitting parameters . nieto and al . extended this formula for chains consisting of n elements giving the following expressions for both parameters a and po:4\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ a(n)={a}_a \exp \left(-n/{b}_a\right),\kern2em { p}_o(n)={a}_{p_o } \exp \left(-n/{b}_{p_o}\right ) . $ $ \end{document } aa , ba , apo and bpo are new fitting parameters . it has to be stressed that in this formula cp approaches zero when the chain length becomes infinite . unfortunately , the fitting parameters a and b have no physical meaning . on the other hand , the next publication of nieto at al . suggests non - zero value of the percolation threshold for infinitely long chain . in order to describe the dependency of the percolation threshold on the chain length they proposed a different formula:5\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$ { c}_p={c}_p^{*}+\varomega exp\left(-\frac{\kappa } { n}\right ) , $ $ \end{document}where cp * , and are fitting parameters and the parameter cp * corresponds to the percolation threshold for the infinitely long chain . the fitting of their data gave cp * = 0.461 0.001 but it has to be stressed that nieto et al . studied very short chains only ( n 15 ) . fitting of our data gives a similar result for short chains ( cp * = 0.447 ) while quite a different one for the entire range of the chain lengths ( cp * = 0.261 ) . one has to remember that the percolation threshold depends on the chain s fractal dimension , which is characteristic for the entire class of objects . this hypothesis was already validated for a slightly different model of two - dimensional linear and cyclic chains on triangular lattice with explicit solvent molecules introduced [ 26 , 27 ] . this suggests that the main factor , which determines the percolation threshold of a complex object , is its structure . it was shown that the rsa method gave lower percolation threshold when compared to those obtained by mc simulations . the size of a single chain can be expressed by means of the radius of gyration < s > , i.e. , the mean - squared distance between polymer beads belonged to the same chains and its center of mass . in the mc method all chains have size that is characteristic for a given polymer density and in average each chain has the same dimension . in the rsa method figure 6 presents the values of the chains reduced mean - squared radius of gyration < s > /n as a function of the pseudo - time . pseudo - time is a number of a chain put successfully on the substrate divided by the number of chains that had been approached after reaching the percolation threshold . these reduced values are necessary in order to study size s changes for chains of different length . for short ( n = 5 and 10 ) chains their size along with the rsa procedure almost does not change for these chains the dependency of the polymer size on the density of the system is rather small . the size of long chains ( n = 100 ) considerably decreases during the adsorption process . it should be expected as each next chain meets smaller space to be fit in . this behavior was implicitly confirmed by wang and pandey who had found that the radius of gyration of deposited chains ( in the rsa method ) was less sensitive to the polymer density and that chains featured memory of time of deposition . the differences in the average structure of a single chain in both methods used can be studied by the analysis of the spatial distribution of polymer beads in a chain . figure 7 presents the distributions of polymer beads around the chain s center of mass . one can observe that the shape of both curves is similar while the distribution of beads of the chain used in the mc method is slightly broader . this distribution of segments confirms that the only difference between average chains in both methods is their size.fig . 6the reduced mean - squared radius of gyration < s > /n of a chain successfully put on the substrate as a function of the pseudo - time in the rsa method ( see text for details ) . n = 80 obtained via both methods studied the reduced mean - squared radius of gyration < s > /n of a chain successfully put on the substrate as a function of the pseudo - time in the rsa method ( see text for details ) . the chain lengths are given in the inset the distribution of polymer beads around the chain s center of mass for the chain n = 80 obtained via both methods studied it is possible to obtain the same percolation threshold in both methods . for this purpose one has to prepare a different library of chains conformation from which chains are randomly picked up and put on the substrate . this library should contain conformation typical for a polymer solution at the density near the percolation threshold determined via the rsa method . then , the next library containing conformations typical for the density equal to the new percolation threshold should be prepared and the next rsa procedure should be performed . the differences in the structure of the surface covered by a film formed of short and long flexible linear macromolecules can also be visualized . figure 8 presents typical snapshots of some polymer systems under consideration taken at the percolation threshold . the decreasing density of the system is clearly visible as the percolation threshold changes here from 0.521 to 0.345 . the percolation clusters are the largest among other clusters and their size increases when the chain length increases . the number of polymer beads in percolation clusters considerably decreases when going from short to long chains . one can also observe the presence of non - percolated islands inside the percolation cluster and the decreasing number of these non - percolating islands when going from short to long chains.fig . 8snapshots of the system at the percolation threshold for systems consisted of chains n = 5 ( a ) , n = 10 ( b ) , n = 50 ( c ) and n = 100 ( d ) snapshots of the system at the percolation threshold for systems consisted of chains n = 5 ( a ) , n = 10 ( b ) , n = 50 ( c ) and n = 100 ( d ) an idealized polymer model was developed in order to study the percolation in systems containing long linear flexible macromolecules . in this model the polymer chains were represented as sequences of identical beads and the positions of these beads were restricted to vertices of a square lattice . the model systems were athermal , i.e. , the excluded volume was the only potential introduced . two different computer simulations techniques were used to determine the properties of the polymer systems : random sequential adsorption and monte carlo simulations with a metropolis - like algorithm . it was shown that the usage of the random sequential adsorption method led to lower percolation thresholds in the entire range of the chain lengths studied . the percolation threshold decreases in the entire range of lengths studied while for shorter chains ( n 50 ) this decrease is rather rapid . because of these differences in prediction of the percolation threshold , the question of validity of the rsa method for long flexible chain systems arises . one can argue that the rsa method simulates the systems where the macromolecules precipitate from a diluted solution at good solvent conditions and are firmly bound by the surface ( the adsorption is irreversible , for instance because of chemical bonds ) . on the other hand , in the metropolis method adsorbed objects can move along the surface and their conformations are typical for polymer systems near the crossover between the diluted and semidiluted solution . in other words , the average size of a polymer chain in the metropolis method is smaller than that of an isolated chain used in the rsa method which enables better packing and results in lower percolation thresholds .

the structure of a two - dimensional film formed by adsorbed polymer chains was studied by means of monte carlo simulations . the polymer chains were represented by linear sequences of lattice beads and positions of these beads were restricted to vertices of a two - dimensional square lattice . two different monte carlo methods were employed to determine the properties of the model system . the first was the random sequential adsorption ( rsa ) and the second one was based on monte carlo simulations with a verdier - stockmayer sampling algorithm . the methodology concerning the determination of the percolation thresholds for an infinite chain system was discussed . the influence of the chain length on both thresholds was presented and discussed . it was shown that the rsa method gave considerably lower thresholds for longer chains . this behavior can be explained by a different pool of chain conformations used in the calculations in both methods under consideration.figurethe percolation cluster ( in red ) in the system consisting of long flexible chains

this article uses data from a retrospective cohort study , exploring perinatal outcomes among children ( epoch ) , which was conducted in colorado . participants were 613 years of age ; the multiethnic offspring of singleton pregnancies ; born at a single hospital in denver , colorado , between 1992 and 2002 ; whose biological mothers were members of the kaiser permanente of colorado health plan ( kpco ) ; and who were still kpco members and living in colorado over the study period ( 20062009 ) . for this analysis , eligible participants were children exposed to diabetes in utero ( exposed group ) and a random sample of children not exposed to diabetes in utero without intrauterine growth restriction ( defined as birth weight for gestational age score < the 10th percentile ) ( unexposed group ) . children and their biological mothers were invited for a research visit between january 2006 and october 2009 . the study was approved both by the colorado multiple institutional review board and human participant protection program . physician - diagnosed maternal diabetes status was ascertained from the kpco perinatal database , an electronic database linking the neonatal and perinatal medical records , as described previously . gestational diabetes mellitus ( gdm ) is coded as present if diagnosed through the standard kpco screening protocol ( described below ) and absent if screening was negative . at 2428 weeks , all pregnant women are offered screening with a 1-h 50-g oral glucose tolerance test ( ogtt ) . a value 140 mg / dl identifies patients who undergo a 3-h 100-g diagnostic ogtt . gdm is diagnosed when two or more glucose values during the diagnostic ogtt meet or exceed the criteria for a positive test as recommended by the national diabetes data group ( 11 ) . exposure to diabetes in utero was defined as the presence of preexistent diabetes or gdm diagnosed during the index pregnancy . in addition , birth weight , gestational age , and maternal prepregnancy weight were also obtained from the database . at the study visits , mothers were queried about breast- and formula - feeding , timing , and the introduction of other solid foods and beverages . because of for exclusively breast - fed infants , duration was equal to the age of the child ( months ) when breastfeeding was stopped . for infants that were ever fed formula , mothers were asked to classify their infant feeding as formula only , more formula than breast milk , equal breast milk and formula , or more breast milk than formula . breastfeeding exclusivity was quantified using weights from 0 to 1 , with exclusive breastfeeding having a weight of 1 and exclusive formula - feeding having a weight of 0 . for infants fed both breast milk and formula , exclusivity was equal to 0.25 for more formula than breast milk ; 0.50 for formula and breast milk equally ; and 0.75 for more breast milk than formula . the breast milk months measure incorporated duration and exclusivity to estimate an overall breast milk dose equivalent in months . it was the sum of months of exclusive breastfeeding and the weighted months of mixed breast milk and formula ( duration of exclusive breastfeeding [ months ] + duration of mixed breast- and formula - feeding [ months ] exclusivity weight ) . breastfeeding status was categorized as low ( < 6 breast milk months ) and adequate ( 6 breast milk months ) based on american academy of pediatrics recommendations ( 12 ) . maternal recall of breastfeeding after periods of time spanning between 9 and 20 years has been found to correlate well with infant feeding data obtained from medical records ( r = 0.86 ) ( 13 ) or collected prospectively ( r = 0.95 ) ( 14 ) . waist circumference was measured to the nearest 1 mm at the midpoint between the lower ribs and the pelvic bone with a metal or fiberglass nonspring - loaded tape measure . skinfolds were measured in triplicate using holtain calipers ( average : subscapular , 20 mm below the tip of the scapula ; triceps , halfway between the acromion process and the olecranon process ) . the subscapular - to - triceps skinfold ratio ( str ) was calculated to assess regional differences in subcutaneous fat distribution . magnetic resonance imaging of the abdominal region was used to quantify visceral adipose tissue ( vat ) and subcutaneous adipose tissue ( sat ) with a 3 t hdx imager ( general electric , waukashau , wi ) by a trained technician . each study participant was placed supine and a series of t1-weighted coronal images were taken to locate the l4/l5 plane . one axial , 10-mm , t1-weighted image at the umbilicus or l4/l5 vertebra was analyzed to determine sat and vat content . the analysis technique used was a modification of the technique of engelson , where adipose tissue regions were differentiated by their signal intensity and location ( i.e. , not internal contents of bowel ) . census - based questions and categorized as hispanic ( any race ) , non - hispanic white , or non - hispanic african american . pubertal development was assessed by child self - report with a diagrammatic representation of tanner staging adapted from marshall and tanner ( 15 ) . youth were categorized as tanner < 2 ( prepubertal ) and 2 ( pubertal ) . maternal level of education and total household income were self - reported during the research office visit . all analyses were conducted using sas v.9.2 ( sas institute , cary , nc ) . multiple linear regression was conducted to examine the association between exposure to maternal diabetes in utero and measures of offspring adiposity ( bmi , waist circumference , vat , sat , and str ) , controlling for potential confounders . in determining the best model for the relationship between adiposity outcomes and in utero diabetes exposure , a significant interaction between age and tanner stage on vat was noted ( p = 0.0008 ) , suggesting that the effect of age on childhood adiposity depends on pubertal development . because such an effect was reported previously in the literature ( 16,17 ) , an interaction term between age and tanner stage was included in our model for all outcomes of interest . stratified analyses were conducted to explore the association between exposure to diabetes in utero and childhood adiposity outcomes in offspring with low versus adequate breastfeeding . this article uses data from a retrospective cohort study , exploring perinatal outcomes among children ( epoch ) , which was conducted in colorado . participants were 613 years of age ; the multiethnic offspring of singleton pregnancies ; born at a single hospital in denver , colorado , between 1992 and 2002 ; whose biological mothers were members of the kaiser permanente of colorado health plan ( kpco ) ; and who were still kpco members and living in colorado over the study period ( 20062009 ) . for this analysis , eligible participants were children exposed to diabetes in utero ( exposed group ) and a random sample of children not exposed to diabetes in utero without intrauterine growth restriction ( defined as birth weight for gestational age score < the 10th percentile ) ( unexposed group ) . children and their biological mothers were invited for a research visit between january 2006 and october 2009 . the study was approved both by the colorado multiple institutional review board and human participant protection program . physician - diagnosed maternal diabetes status was ascertained from the kpco perinatal database , an electronic database linking the neonatal and perinatal medical records , as described previously . gestational diabetes mellitus ( gdm ) is coded as present if diagnosed through the standard kpco screening protocol ( described below ) and absent if screening was negative . at 2428 weeks , all pregnant women are offered screening with a 1-h 50-g oral glucose tolerance test ( ogtt ) . a value 140 mg / dl identifies patients who undergo a 3-h 100-g diagnostic ogtt . gdm is diagnosed when two or more glucose values during the diagnostic ogtt meet or exceed the criteria for a positive test as recommended by the national diabetes data group ( 11 ) . exposure to diabetes in utero was defined as the presence of preexistent diabetes or gdm diagnosed during the index pregnancy . in addition , birth weight , gestational age , and maternal prepregnancy weight were also obtained from the database . at the study visits , mothers were queried about breast- and formula - feeding , timing , and the introduction of other solid foods and beverages . because of for exclusively breast - fed infants , duration was equal to the age of the child ( months ) when breastfeeding was stopped . for infants that were ever fed formula , mothers were asked to classify their infant feeding as formula only , more formula than breast milk , equal breast milk and formula , or more breast milk than formula . breastfeeding exclusivity was quantified using weights from 0 to 1 , with exclusive breastfeeding having a weight of 1 and exclusive formula - feeding having a weight of 0 . for infants fed both breast milk and formula , exclusivity was equal to 0.25 for more formula than breast milk ; 0.50 for formula and breast milk equally ; and 0.75 for more breast milk than formula . the breast milk months measure incorporated duration and exclusivity to estimate an overall breast milk dose equivalent in months . it was the sum of months of exclusive breastfeeding and the weighted months of mixed breast milk and formula ( duration of exclusive breastfeeding [ months ] + duration of mixed breast- and formula - feeding [ months ] exclusivity weight ) . breastfeeding status was categorized as low ( < 6 breast milk months ) and adequate ( 6 breast milk months ) based on american academy of pediatrics recommendations ( 12 ) . maternal recall of breastfeeding after periods of time spanning between 9 and 20 years has been found to correlate well with infant feeding data obtained from medical records ( r = 0.86 ) ( 13 ) or collected prospectively ( r = 0.95 ) ( 14 ) . waist circumference was measured to the nearest 1 mm at the midpoint between the lower ribs and the pelvic bone with a metal or fiberglass nonspring - loaded tape measure . skinfolds were measured in triplicate using holtain calipers ( average : subscapular , 20 mm below the tip of the scapula ; triceps , halfway between the acromion process and the olecranon process ) . the subscapular - to - triceps skinfold ratio ( str ) magnetic resonance imaging of the abdominal region was used to quantify visceral adipose tissue ( vat ) and subcutaneous adipose tissue ( sat ) with a 3 t hdx imager ( general electric , waukashau , wi ) by a trained technician . each study participant was placed supine and a series of t1-weighted coronal images were taken to locate the l4/l5 plane . one axial , 10-mm , t1-weighted image at the umbilicus or l4/l5 vertebra was analyzed to determine sat and vat content . the analysis technique used was a modification of the technique of engelson , where adipose tissue regions were differentiated by their signal intensity and location ( i.e. , not internal contents of bowel ) . census - based questions and categorized as hispanic ( any race ) , non - hispanic white , or non - hispanic african american . pubertal development was assessed by child self - report with a diagrammatic representation of tanner staging adapted from marshall and tanner ( 15 ) . youth were categorized as tanner < 2 ( prepubertal ) and 2 ( pubertal ) . maternal level of education and total household income were self - reported during the research office visit . all analyses were conducted using sas v.9.2 ( sas institute , cary , nc ) . multiple linear regression was conducted to examine the association between exposure to maternal diabetes in utero and measures of offspring adiposity ( bmi , waist circumference , vat , sat , and str ) , controlling for potential confounders . in determining the best model for the relationship between adiposity outcomes and in utero diabetes exposure , a significant interaction between age and tanner stage on vat was noted ( p = 0.0008 ) , suggesting that the effect of age on childhood adiposity depends on pubertal development . because such an effect was reported previously in the literature ( 16,17 ) , an interaction term between age and tanner stage was included in our model for all outcomes of interest . stratified analyses were conducted to explore the association between exposure to diabetes in utero and childhood adiposity outcomes in offspring with low versus adequate breastfeeding . a total of 89 youth exposed to diabetes in utero ( 91% with gdm ) and 379 unexposed youth participated in the study and had complete data on variables of interest . the mean sd age of exposed youth was 9.6 1.7 years and 10.6 1.3 for unexposed youth ( p < 0.0001 ) at the study visit . exposed youth were more likely to be non - hispanic white or hispanic ( p = 0.04 ) , and a larger proportion of exposed youth self - reported a tanner stage < 2 , indicating they were prepubertal ( 71.1 vs. 50.8% , p = 0.0005 ) . mothers with diabetes during pregnancy were , on average , older ( p < 0.0001 ) than mothers whose pregnancies were not complicated by diabetes . exposed and unexposed offspring were not significantly different in terms of intrauterine growth and socio - economic factors or infant feeding practices ( table 1 ) . infant feeding and characteristics of epoch subjects according to exposure to maternal diabetes in utero data are n ( % ) or means sd unless otherwise indicated . weighted months of mixed breast milk and formula ( duration of exclusive breastfeeding [ months ] + duration mixed breast- and formula - feeding [ months ] exclusivity weight ) . table 2 shows the association between breastfeeding status ( low vs. adequate ) and adiposity outcomes among offspring exposed and unexposed to diabetes in utero . both exposed and unexposed youth who had adequate breastfeeding ( 6 breast milk months ) had significantly lower bmi , waist circumference , sat , and vat at ages 613 years than those with < 6 breast milk months . the only adiposity parameter that did not show a statistically significant relationship with breastfeeding was str ( p = 0.26 and p = 0.72 , respectively , in exposed and unexposed participants ) , though the pattern was similar . association between breast milk months ( < 6 and 6 breast milk months ) and adiposity parameters at age 613 years for youth exposed and not exposed to maternal diabetes in utero means from multiple linear regression model adjusted for age , sex , race / ethnicity , tanner stage , and age tanner stage interaction . figure 1 shows the associations between exposure to diabetes in utero and adiposity outcomes stratified by breastfeeding status and adjusted for age , sex , tanner stage , and tanner by age interaction . among adolescents with low breastfeeding status ( < 6 breast milk months ) , exposure to diabetes in utero was associated with a 1.7 kg / m higher bmi ( p = 0.03 ) ; 5.8 cm higher waist circumference ( p = 0.008 ) ; 6.1 cm higher vat ( p = 0.06 ) ; 44.6 cm higher sat ( p = 0.03 ) ; and 0.11 higher str ( p = 0.008 ) . the association between exposure to diabetes in utero and the adiposity parameters was substantially reduced and not significant for adolescents with adequate breastfeeding in infancy ( 6 breast milk months ) with a 0.7 kg / m lower bmi ( p = 0.4 ) ; 2.7 cm higher waist circumference ( p = 0.1 ) ; 2.1 cm higher vat ( p = 0.4 ) ; 23.4 cm higher sat ( p = 0.11 ) ; and 0.05 higher str ( p = 0.14 ) among exposed versus unexposed children . a e : effect of exposure to diabetes in utero on mean levels of childhood adiposity parameters . stratified by breastfeeding ( bf ) status , data are adjusted for age , sex , race / ethnicity , tanner stage , and age tanner stage interaction . a : bmi : p = 0.03 for youth with low breastfeeding ; p = 0.4 for youth with adequate breastfeeding . b : waist circumference ( wc ) : p = 0.008 for youth with low breastfeeding ; p = 0.10 for youth with adequate breastfeeding . c : vat : p = 0.06 for youth with low breastfeeding ; p = 0.40 for youth with adequate breastfeeding . d : sat : p = 0.03 for youth with low breastfeeding ; p = 0.11 for youth with adequate breastfeeding . e : str : p = 0.008 for youth with low breastfeeding ; p = 0.14 for youth with adequate breastfeeding . we found that adequate breastfeeding ( 6 breast milk months ) was associated with lower bmi , waist circumference , and sat levels in a multiethnic population of youth 613 years of age from colorado . moreover , our study provides novel evidence that the effect of exposure to diabetes in utero on childhood adiposity parameters is substantially attenuated by breastfeeding , such that the obesity outcomes in exposed youth who were adequately breast - fed were similar to those of unexposed youth . our data suggest that breastfeeding promotion may be an effective strategy for reducing the increased risk of childhood obesity in the offspring of mothers with diabetes during pregnancy . the current literature on the impact of breastfeeding for the offspring of diabetic women is inconclusive . ( 18 ) suggested an adverse effect of breastfeeding during the first 7 days of life on relative weight at 2 years of age among offspring of women with type 1 diabetes and gdm . however , a follow - up of this study was conducted by rodekamp et al . ( 19 ) with an extended assessment of breastfeeding exposure beyond the first week of life . the researchers found that neither dose of breast milk nor duration of breastfeeding among offspring of type 1 diabetic women was associated with increased risk of overweight or impaired glucose tolerance at 2 years of age . in another study , kerssen et al . ( 20 ) showed no effect of breast milk , formula , or mixed feeding on the weight or bmi of offspring exposed to type 1 diabetes during pregnancy at 1 year of age . in contrast , among 15,253 offspring of the 1989 nurses health study ii , mayer - davis et al . ( 21 ) reported a protective or of 0.63 ( 95% ci 0.500.78 ) for overweight at 12 years of age for breastfeeding duration of 9 versus < 9 months . or for overweight among offspring exposed to gdm in utero who were exclusively breast - fed compared with those exclusively formula - fed was 0.62 ( 0.241.60 ) . among pima indians , pettitt and knowler ( 22 ) found a substantial reduction ( 30.1 vs. 43.6% ) in type 2 diabetes among the offspring exposed to diabetes in utero if they were breast - fed for at least 2 months compared with those who were bottle - fed . a similar reduction was observed among pima offspring not exposed to in utero diabetes ( 6.9 and 11.9% among offspring of nondiabetic women who were breast - fed and bottle - fed , respectively ) . the early postnatal period may represent a critical period for the future obesity risk in childhood ( 23 ) and adult life ( 6 ) . the macronutrient composition of breast milk ( i.e. , protein , fat , carbohydrate ) and bioactive substances not present in formula may influence metabolic programming and regulation of body fatness and growth rate . higher insulin levels ( 24 ) and lower leptin levels ( 25 ) have been reported in formula - fed infants compared with breast - fed babies . the effect of breastfeeding on infant growth may be an important determinant of early life programming for future obesity and chronic disease , especially for the offspring of diabetic pregnancies . our study adds to the limited body of evidence by suggesting that breastfeeding attenuates the unfavorable effects on childhood adiposity parameters conferred by exposure to maternal diabetes . importantly , all measures of adiposity were influenced including the more sensitive vat and sat . the mechanisms that trigger adipose tissue deposition in specific locations at different periods of fetal development or in childhood remain unclear . identification of strategies to alter the long - term development of fat deposition and accumulation are necessary to minimize the significant increased morbidity risk associated with childhood obesity . fetal life and early infancy both represent critical periods when obesity begins and may be effectively minimized by targeted prevention strategies . an a priori power calculation suggested that , with 100 exposed individuals , our study had 80% power to detect a difference in the effect of exposure to diabetes in utero on childhood bmi according to breastfeeding status ( an interaction ) of 0.4 bmi units . the observed difference in our study was 0.5 bmi units ; however , the difference was not statistically significant , possibly because of the slightly smaller achieved sample of exposed individuals . this suggests that we had limited power to detect a statistically significant effect of breastfeeding in modifying the association between exposure to diabetes in utero and childhood adiposity . nevertheless , our findings of an attenuation of the effect of in utero exposure on childhood adiposity by breastfeeding was robust and consistent across various measures of adiposity including bmi , waist circumference , sat , vat , and fat distribution . similar effects were noted regardless of how our breastfeeding variable was defined ( i.e. , breastfeeding yes / no , duration in months , etc . ; data not shown ) . moreover , our study had several important strengths including state - of - the - art assessment of childhood adiposity and fat distribution , a validated exposure assessment , and an assessment of breast milk dose that incorporated breastfeeding exclusivity and duration . in conclusion , our study found no deleterious effects of breastfeeding among a diverse group of children exposed to diabetes in utero . in contrast , we suggest that breastfeeding may be protective against the increased childhood adiposity associated with intrauterine diabetes exposure . further work is needed to confirm this finding in larger populations , and to determine if the reductions in adiposity continue into adulthood .

objectiveto evaluate whether breastfeeding attenuates increased childhood adiposity associated with exposure to diabetes in utero.research design and methodsretrospective cohort study of 89 children exposed to diabetes in utero and 379 unexposed youth with measured bmi , waist circumference , skinfolds , visceral ( vat ) and subcutaneous ( sat ) abdominal fat . a measure of breast milk months was derived from maternal self - report and used to categorize breastfeeding status as low ( < 6 ) and adequate ( 6 breast milk months ) . multiple linear regression was used to model the relationship between exposure to diabetes in utero and offspring adiposity outcomes among youth stratified according to breastfeeding status.resultsadequate ( vs. low ) breastfeeding status was associated with significantly lower bmi , waist circumference , sat , and vat at ages 613 years . among youth in the low breastfeeding category , exposure to diabetes in utero was associated with a 1.7 kg / m2 higher bmi ( p = 0.03 ) , 5.8 cm higher waist circumference ( p = 0.008 ) , 6.1 cm2 higher vat ( p = 0.06 ) , 44.6 cm2 higher sat ( p = 0.03 ) , and 0.11 higher ratio of subscapular - to - triceps skinfold ratio ( p = 0.008 ) . among those with adequate breastfeeding in infancy , the effect of prenatal exposure to diabetes on childhood adiposity outcomes was not significant.conclusionsadequate breastfeeding protects against childhood adiposity and reduces the increased adiposity levels associated with exposure to diabetes in utero . these data provide support for mothers with diabetes during pregnancy to breastfeed their infants in order to reduce the risk of childhood obesity .

the earth magnetopause is the outer boundary of the terrestrial magnetosphere . outside of this boundary , the magnetosheath plasma is the shocked solar wind plasma , @xmath0 cold and dense , with a magnetic field direction essentially determined by the solar wind one . inside of it , the magnetospheric plasma is comparatively hot and tenuous , with a magnetic field direction essentially determined by the planetary one . experimentally , investigating the magnetopause structure by spacecraft measurements is made difficult by the fact that the boundary is not steady : it can be shaken by the variations of the solar wind pressure , and perturbed by different kinds of waves , incident body waves as well as surface waves . it can also be locally and temporarily the place of different surface instabilities , implying or not magnetic reconnection , such as kelvin - helmholtz , rayleigh taylor or tearing instabilities ( _ hasegawa et al _ , 2012 ) . two informations are crucial to investigate the magnetopause nature : 1 ) accurately determine the direction of its normal with respect to the magnetic field ( in a strictly stationary configuration , having the normal magnetic field @xmath1 null or not have quite different consequences on the physical nature of the layer , even if the non null @xmath1 is small ) and 2 ) determine an approximate spatial coordinate along the normal , to be able to draw the spatial profiles of the different relevant parameters , in the boundary frame , @xmath2 independently of the velocity at which these profiles are traversed by the spacecraft . several methods have been developed for both of these two purposes . to study the large scale shape of the boundary , its motion and its orientation , multi - spacecraft methods have been developed , particularly for the esa cluster mission ( _ paschmann and daly _ , 1998 and 2008 ) . these methods are essentially based on timing differences between spacecraft and all rely on strong assumptions on the boundary : its form ( plane or slightly curved at the scale of the spacecraft tetrahedron ) , its stationarity ( constant profile and width , hereafter cta for `` constant thickness approach '' , ( _ haaland et al _ , 2004 ) , or its velocity with respect to the spacecraft ( hereafter cva for `` constant velocity approach '' , _ russell et al _ 1983 ) . others are single spacecraft : they also rely on assumptions on the boundary properties such as planarity and stationarity , but they use in addition theoretical knowledge on the measured physical quantities , such as conservation laws . when using in particular the magnetic field data , the mvab method ( minimum variance analysis on the magnetic field @xmath3 , _ sonnerup and scheible _ , 1998 ) takes advantage that div@xmath4 , which draws @xmath5 in the 1-d case . its variant mvabc ( c for corrected ) adds the constraint @xmath6 , using the additional information that the magnetopause normal component @xmath1 is generally close to zero , if not strictly zero . this allows to handle cases when two components are nearly constant and not a single one ( @xmath0 when two eigenvalues of the variance - covariance matrix are small ) . when the magnetopause can be supposed 1-d and stationary but when its thickness is small , making the kinetic effects non negligible with respect to the mhd ones , the experimental profiles have to be compared with the kinetic models of the tangential layers that can be found in the literature ( see _ de keyser and roth _ , 1998 , for a review of the first models of this kind , and _ belmont et al . _ , 2012 , for the most recent one ) . the experimental method developed in this paper should enable to perform such comparisons . when the magnetopause layer can not be supposed 1-d , other methods are needed . some have been developed to reconstruct the magnetopause structure , supposing it is 2-d and stationary , and that it respects mhd equations : these are the grad - shafranov reconstruction methods ( see _ hasegawa et al _ , 2004 , for long - duration reconstruction ) . a review and discussion of short- and long- duration methods is made in _ de keyser _ ( 2006 ) . experimentally , it is often difficult to decide whether the 1-d or the stationary hypothesis has to be questioned first . future comparison between the results of the reconstruction methods and those of the method proposed in this paper should be interesting in this respect . to find an approximate normal coordinate allowing to investigate the internal structure of the layer and to determine profiles across it , other methods have been developed independently , introducing the notion of `` transition parameter '' ( _ lockwood and hapgood _ , 1997 ) . these methods can be used with single - spacecraft data . they also rely on assumed magnetopause properties , and they have been based hitherto on the variations in density and temperature of the electron population . this of course limits the temporal resolution of the method -and consequently its spatial one- to the electron experiment resolution . we propose here a new single spacecraft method , referred hereafter as `` bv '' to show that the magnetic field and the flow velocity data are used simultaneously , to analyze magnetopause - like interfaces . it combines the two previous types in such a way that it allows to determine in the same operation the magnetopause normal with an improved accuracy and a transition parameter with an improved time resolution and expectingly closer to a real spatial coordinate . fitting the magnetic field hodogram with a prescribed form , which is here an elliptical arc , allows to determine the normal direction with a fairly good accuracy . in addition , the angle @xmath7 characterizing the position on the elliptical arc provides a reliable transition parameter inside the current layer , which can be viewed as a proxy for a normalized coordinate in the normal direction . on the other hand , as soon as the normal direction is known , the velocity measurements give a non - normalized normal coordinate , which is just the integral of the normal flow velocity @xmath8 . it can give , in particular , a fairly good estimate of the physical width of the layer whenever the measured velocity should be in most cases dominated by the motion of the boundary . using simultaneously the magnetic and velocity measurements just consists in imposing that the normal coordinate determined by the only velocity measurements is proportional to the transition parameter coming from the only magnetic measurements . since the integral of @xmath8 is very sensitive to the normal direction , this enables to improve the determination of this direction with respect to the only magnetic one , while the time resolution of @xmath9 remains approximately the magnetic one , which is much better than the velocity resolution . section 2 presents the principles of the bv technique , and section 3 the different validation tests performed . the method allows to draw spatial profiles of any physical parameter across the magnetopause boundary . examples of such profiles are presented in section 4 , before discussing the interest and the limitations of the bv method and concluding in section 5 . as the previous equivalent methods , the basic assumption of the bv technique is that , apart from oscillating perturbations , the boundary is sufficiently one dimensional and stationary at the scale of the spacecraft crossing . to explain the principles of this method , we use here a set of cluster data on march , 3rd , 2008 , when cluster c3 encounters the magnetopause around 23:16 , as it can be seen on fig . [ caa profiles at the crossing ] from the transition in the energy composition of the plasma , the density gradient and the rotation of magnetic field observed . the method uses principally the magnetic field data ( _ balogh et al . _ , 1997 ) . in subsection 2.1 we describe how we obtain an initial guess with only magnetic field data . subsection 2.2 then explains the bv method itself , which combines magnetic field and ion velocity data . in order to correctly initialize the minimization process of the complete bv method , involving magnetic field and ion velocity data , it is necessary to perform first an initialization stage , which provides an approximated frame and a first elliptical fit . this stage uses only the magnetic field data . it is done itself in several steps . the first step consists in finding a first approximation of the normal direction via a mvabc technique ( _ sonnerup and scheible _ , 1998 ) . ( [ hodogram lmn ] ) shows the tangential hodogram derived by this method . in this example as in many other observations ( _ panov et al _ , 2011 ) , we observe a c - shaped hodogram , which can be fitted by an elliptical model . although the general concept of the bv method is valid for any 1d layer , its present implementation is conceived for such kind of hodograms . further generalization to more complicated hodograms ( in particular for the s - shaped hodograms described in _ panov et al _ , 2011 ) is of course always possible . the second step consists in selecting the `` magnetic ramp '' , @xmath0 the interval of data where the gradient of @xmath10 is located . we then further select the data points by choosing only a sample of `` representative points '' among them . this step has a double purpose : eliminate the perturbations that can be considered as `` noise '' , and make the different parts of the crossing equally represented in the statistics , even if the spacecraft does not spend the same time in these different parts . first we roughly eliminate the perturbations by discarding all points too far from the mean trajectory of the hodogram , and we represent each too close packet of points by only one single point . an elliptic fit and a new reference frame are derived from these points , using a powell algorithm . the points selected in this way and the correspondent fit in the new frame are shown in fig . ( [ first fit ] ) . then , the second goal is achieved by keeping a constant number of points in each @xmath7 slice , which corresponds to the hypothesis ( to be justified in next section ) that @xmath7 varies linearly with @xmath11 . a new elliptic fit and approximated frame are then obtained , which provides a fine initialization for the bv method itself . the above stage has given an initial guess for the bv method regarding 1 ) the normal direction , and 2 ) the parameters describing the elliptic hodogram . the main part of the method then consists in using the temporal information @xmath12 , together with the velocity measurements from the hot ion analyser experiment ( _ rme et al _ , 1997 ) . going back to the totality of the @xmath3 data points , one minimizes the distance between them and the elliptical model @xmath13 , the function @xmath9 being the integral of the normal velocity @xmath8 . we therefore assume that this velocity is dominated by the layer velocity , @xmath0 that the normal velocity in the layer frame is zero or negligible . the minimization is done with respect to the three angles that characterize the rotation of the ellipse proper frame and to the parameters of the elliptic hodogram , initialized previously , using the same powell algorithm as above . the distance to be minimized is : @xmath14 where @xmath15 represents the data points and @xmath16 represents the model . this model is given by : @xmath17 with : @xmath18 @xmath11 being the position deduced from the normal velocity integral . the magnetic field data and velocity data are obtained from prepared data by a rotation of m(@xmath19 ) . the parameters of the fit are @xmath20 and @xmath21 . this final stage provides all the needed outputs : the normal direction , the spatial position @xmath9 along this normal ( measured directly in physical units , providing in particular the layer thickness in km ) , and the fit of magnetic field , as illustrated , for example , on fig . ( [ fitcomponents ] ) . here the computed magnetopause thickness is 1800 km and the linear pearson correlation coefficients of the fit of @xmath22 and @xmath23 are 0.99 and 0.95 . the spatial position @xmath11 is then extrapolated linearly outside the boundary , in order to plot approximated profiles of any plasma parameter on scales larger than the ramp region if necessary . having presented how the bv method works in the previous section , we will now explain what led us to this way of proceeding and what are the different validation tests we have performed . we will discuss first the validity and the limitations of the hypotheses done , and discuss afterward the consistency of the obtained results . we used three different tools to develop and validate the method : - a simple code to generate artificial magnetic field data , - a hybrid simulation of an asymmetric reconnection layer ( _ aunai et al _ , 2013b ) , - and real data from the cluster mission , especially a 2008 low latitude crossings list compiled by n. cornilleau - wehrlin . the first new assumption of the method , with respect to previous single spacecraft data analysis methods , is the elliptic shape of the tangential magnetic field hodogram , the simplest model geometry to describe c - shaped hodograms . this elliptical shape is indeed consistent with a simple generalization of the circular model @xmath24 proposed by ( _ panov et al _ , 2011 ) : @xmath25 these formulas imply in particular that @xmath26 , which can be a test of the elliptical shape . the efficiency of the method can be tested first on a numerical simulation of reconnection ( _ aunai et al _ , 2013b ) , far from the x point . its applicability is not obvious in this case , since , before the development of the reconnection pattern , the initial condition is purely tangential , without any rotation . nevertheless , the hall effect creates a self - consistent out - of - plane magnetic component during the reconnection process , which , in the considered asymmetric configuration ( asymmetric in density and temperature and coplanar and antisymmetric in magnetic field ) , results in a c - shaped hodogram if looked between the separatrices . ( [ fitaunai ] ) shows the magnetic field in the interval that corresponds to the gradient of @xmath27 . the error is here less than 2 percent . we have checked that this good accuracy is kept as long as the crossing considered is not too close to the x - point , which is generally the case for crossings of reconnected magnetopause or to the limits of the simulation . concerning the analytical form of @xmath28 , we also checked the validity of the linear hypothesis in the same simulation study . ( [ alpha(y)aunai ] ) shows how @xmath7 varies as a function of the normal coordinate @xmath29 of the simulation . we observe that , apart from weak periodic variations , the linear form is well satisfied . it is worth explaining that the weak periodic departures from the linear variations ( which can be well described by the three of four first terms of a fourier transform ) can indeed be accounted for in the minimization procedure , but it would increase the number of free parameters and drastically affect the convergence of the minimization process . regarding the consistency of the results , the first test consists in running the first part of the method ( identification of the ellipse and of its proper frame ) on a magnetic field that is artificially generated with an elliptic hodogram . such artificial data have thus been constructed with the same analytical formulas as those of the program , then turned on a random frame , and added with a random gaussian noise centered on the signal , with a relative amplitude up to 50% . the result is that the method always allows to find the good initial normal direction with at least 5 significant numbers , as well as the right ellipse parameters , whenever the noise does not exceed 30% . the second test consists in using the above numerical simulation ( _ aunai et al _ , 2013b ) to mimic a real magnetopause crossing . in order to make the method work , we must modify the simulation results in a way that makes it likely closer to most real magnetopause crossing : we multiply the tangential velocities by a large factor ( @xmath30 ) . thanks to this change , the tangential velocities get a much larger contrast than the normal ones , which is necessary for the program convergence . it must be noted that such a contrast of the tangential velocities does generally exist at the magnetopause , since the tangential velocity change is generally of the order of a few 100 km / s , while the normal one ( in the spacecraft frame ) is generally about ten times smaller and varies very little . in order to focus on the reconnection process freely of any kh instability , the simulation did not include such a velocity shear . furthermore , the normal velocity of the virtual spacecraft considered with respect to the boundary , has to be chosen large enough with respect to the normal velocities in the boundary frame . this is also , as already mentioned , a reasonable hypothesis for a real magnetopause crossing . under these assumptions , we get normals with an angular precision oscillating between 0 and 5 degrees ( with the corresponding errors on the shape of the tangential hodogram ) and 0 - 5% errors on the @xmath11 parameter ( and derivative ) , which corresponds to the internal velocity and the approximations on @xmath31 . the result is not changing as long as the virtual spacecraft crosses the simulation far enough ( several @xmath32 ) from the x point , where the 2d effects are not dominant . in these cases , the precision of the mvabc method is of the same order , ( slightly better or worse , depending on the cases ) , because @xmath1 is actually very close to 0 . regarding real cluster data , the measurements show more perturbations , but the variations of the field value around the mean ellipse are still around 5 percent for most c - shaped hodograms . a good test for the elliptical shape is to plot @xmath33 , that should be linear for a tangential ellipse . fig . ( [ champscarreslmn ] ) shows this plot for two magnetopause crossings on 03/03/2008 and 04/01/2008 . it shows that the elliptical shape is a good approximation . it is clear , from the the tests on the numerical simulation , that the bv method has limitations related to the necessary contrast between the normal and tangential component profiles . when applied to real cluster data , these limitations may have , in some occasions , consequences on the results obtained . we will discuss these limitations in the conclusion section . it is to be noted however that these limitations are based on assumptions which are different -and generally weaker- than those of the other single - spacecraft methods such as mvab or mvabc . we will present a detailed study on a case ( _ dorville et al , 2013 _ ) , where the bv method leads to a better understanding and more precise results than mvab(c ) . when all the methods are confidently applicable , the results seem to be consistent with each other and with the theoretical knowledge . we show on fig . ( [ eye])``oeil '' a reproduction of a figure from ( _ haaland et al _ , 2004 ) corresponding to a benchmark case where different methods have been used . the center of the figure is the mean mvabc normal and other single and multi - spacecraft methods are represented in a polar plot in the plane perpendicular to this normal . the result of the bv method on c1 spacecraft is indicated by a star . the figure shows that , if the result is different from other methods , it is inside the dispersion range of the points . the thickness of the layer always stands between a few hundreds of kilometers and a few thousands , which is consistent with literature , the tangential velocities being generally one order of magnitude larger than the normal one ( in the spacecraft frame ) . the normal magnetic fields always stand between 0 and 20 nt , the non null values being reliable and quantitative indications of a connected boundary , which could hardly be obtained previously . as explained above , the first main direct product of the method is an accurate determination of the direction normal to the boundary , leading to reliable values of the small components @xmath1 and @xmath8 of the magnetic field and the flow velocity across the boundary . the second direct product is the determination of a spatial coordinate @xmath9 allowing to draw any plasma parameter profile against the spatial position @xmath11 from their temporal measurement . the magnetopause layer thickness is also an interesting by - product deriving directly from the two preceding ones . examples of @xmath11 profiles are presented in fig . ( [ cis ] ) for the crossing of 03/03/08 . here we see the characteristic jump of density at the magnetopause , but no temperature jump , the pressure evolving like the density . for the different crossings that we investigated , we could often observe clear differences concerning the locations of the particle gradients with respect to the magnetic field rotation . in a companion paper , we will present an interesting case study where the bv method can bring new information about the nature of the magnetopause . + in fig . ( [ efield ] ) the normal electric field obtained with the efw experiment ( _ gustafsson et al_,(2001 ) ) and the tangential components are shown for the same 03/03/2008 crossing . we see that the maximum variance is on the normal electric field , as expected by theory , and quite constant tangential electric fields , which confirms that the normal direction found is a good one . ( [ staffdata ] ) shows the profiles of magnetic field spectral power density obtained with the staff experiment ( _ cornilleau - wehrlin et al _ , 2003)for different frequency ranges . one can observe that the source of waves lies in the magnetosheath and that the depth of penetration depends on the frequency , the lowest frequencies penetrating deeper toward the magnetospheric side . this ability to get spatial profiles of all the quantities in the boundary is a key to a better understanding of the physical nature of the magnetopause . we have presented the new bv method to analyze the structure of the magnetopause boundary layer , using spacecraft data . it combines the magnetic field and velocity measurements of one single spacecraft and permits to find the normal direction and a good resolution on a spatial coordinate to resolve small scale variations inside the layer . using it , we are able to study the internal structure of the layer , for any of the physical quantities measured on board . the method works on simulation and generated data , and its assumptions can be verified on cluster crossings . it is worth observing the conditions of validity of the bv method are not the same as the other single spacecraft methods such as mvab , and that they are in general less restrictive . in mvab , one needs to discriminate @xmath34 and @xmath35 , which fails systematically in structures as shocks , and often at the magnetopause since this one is often quasi - coplanar . mvabc has the same condition of validity , with the additional problem that it can not be used for determining @xmath1 since this component is supposed null . in the bv method , one needs to discriminate the two couples of data sets : ( @xmath36 ) and ( @xmath37 ) . this is clearly a weaker condition since , even if @xmath34 and @xmath35 are nearly constant , the differences between @xmath38 and @xmath39 , ( profiles and/or orders of magnitude ) are generally sufficient to guarantee a correct operation . the difficulties can only arise when not only @xmath34 and @xmath35 are indistinguishable ( mean jump much smaller than noise ) , but also @xmath38 and @xmath39 . contrary to the multi - spacecraft timing methods , the bv method can also handle cases when the boundary is shaken with a non trivial normal velocity evolution ( which seems frequent ) . when this evolution is non negligible between two spacecraft crossings , the timing methods obviously fail . the bv method however brings a new limitation : although one works essentially with magnetic field data , a sufficiently long crossing is needed ( at least three or four velocity measurement points inside the crossing)to make efficient the contribution of the velocity data . we are therefore not able to analyze as many crossings as the other methods . with the proposed method , the structure of the magnetopause should be now open to more detailed investigations . some examples of spatial profiles have been given in section 4 . the method is used in a companion article , for an atypical magnetopause case study giving new insight on this structure . the authors would like to thank n cornilleau - wehrlin for fruitful discussion and her help to work with cluster data and detect magnetopause crossings , and the caa and all cluster instruments teams for their work on cluster data . aunai , n. , g. belmont , and r. smets ( 2011 ) , proton acceleration in antiparallel collisionless magnetic reconnection : kinetic mechanisms behind the fluid dynamics , j. geophys . res . , 116 , a09232 , doi:10.1029/2011ja016688 . aunai , n. , et al . comparison between hybrid and fully kinetic models of asymmetric magnetic reconnection : coplanar and guide field configurations . physics of plasmas 2013 ; 20 : 022902 . balogh , a. , dunlop , m. w. , cowley , s. w. h. , southwood , d. j. , thomlinson , j. g. , and the cluster magnetometer team : the cluster magnetic field investigation , space sci . , 79 , 65 , 1997 cornilleau - wehrlin , n. , chanteur , g. , perraut , s. , rezeau , l. , robert , p. , roux , a. , de villedary , c. , canu , p. , maksimovic , m. , de conchy , y. , hubert , d. , lacombe , c. , lefeuvre , f. , parrot , m. , pinon , j. l. , dcrau , p. m. e. , harvey , c. c. , louarn , ph . , santolik , o. , alleyne , h. st . c. , roth , m. , chust , t. , le contel , o. , and staff team : first results obtained by the cluster staff experiment , ann . geophys . , 21 , 437 - 456 , doi:10.5194/angeo-21 - 437 - 2003 , 2003 . de keyser , j. 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to investigate the internal structure of the magnetopause with spacecraft data , it is crucial to be able to determine its normal direction and to convert the measured time series into spatial profiles . we propose here a new single - spacecraft method , called the bv method , to reach these two objectives . its name indicates that the method uses a combination of the magnetic field ( b ) and velocity ( v ) data . the method is tested on simulation and cluster data , and a short overview of the possible products is given . we discuss its assumptions and show that it can bring a valuable improvement with respect to previous methods .

persons living with hd who participated in this study were a subset of a larger validation sample for the hdqol . all were recruited through a mail - out via the huntington s disease association ( hda ) in the uk and provided their consent prior to their inclusion in the study . from this sample , 105 persons living with hd chose to provide proxy data in addition to their own ( at risk , n = 10 ; pre - symptomatic gene positive , n = 17 ; stage 1 , n = 9 ; stage 2 , n = 8 ; stage 3 , n = 10 ; stage 4 , n = 35 and stage 5 , n = 15 ) . the study was approved by university of reading research ethics committee and has been performed in accordance with 1964 declaration of helsinki . research questionnaires were sent to persons living with hd , referred to generically as patients although this includes people who were not yet clinically symptomatic . those who volunteered to participate were invited to give the accompanying proxy report questionnaires to someone they felt knew them well . patients were instructed that they might get assistance in completing the questionnaire , from the proxy or another helper , if they found this difficult ; however the questionnaire responses should be solely their own . proxies were instructed to complete the questionnaires independently of the patient , and were asked to focus on how they think the quality of life of the patient has been affected , drawing upon their perceptions and thoughts as a companion / carer . patients and proxies were requested to return the questionnaires using the pre - paid reply envelope provided within a fortnight . patients and proxies were asked to provide demographic details and information regarding patient s functional ability as an indication of disease stage . they were asked to complete three questionnaires as follows.self- or proxy - report version , respectively , of the hdqol . this is a disease - specific patient reported outcome measure developed from hd patient interviews , where each item comprises a relevant aspect of health - related quality of life on which hd participants provide a self - reported response on a likert scale . the proxy - report version is identical to the self - reported patient version , except that proxies are asked their own opinion of the patient for each item . following exploratory factor analysis and rasch analysis of data from a larger sample , reported elsewhere , several scales can be identified . in the present paper , we report the summary scale and the six specific scales ( i.e. specific cognitive , specific hopes and worries , specific services , specific physical and functional , specific mood state , specific self and vitality ) in order that proxy each specific scale total , and the summary scale , ranges from 0 ( worst hrqol ) to 100 ( best hrqol).self - report version of the eq-5d : note that proxies were here reporting their own health status , not the patient s . this generic hrqol measure comprises five questions on mobility , self - care , pain , usual activities and psychological status using three - point scales , and generates a summary scale ( 1 = best health state ) and visual analogue scale to indicate general health status ( 100 = best health status ) .self - report version of the sf-12v2 : again , proxies reported their own status . this generic measure includes twelve items , measures eight domains of health on five - point scales , and is used to calculate two component scores the physical component summary score ( pcs ) and the mental component summary score ( mcs ) . pcs and mcs scales are transformed to 0100 scale ( 0 = worst , 100 = best ) . this is a disease - specific patient reported outcome measure developed from hd patient interviews , where each item comprises a relevant aspect of health - related quality of life on which hd participants provide a self - reported response on a likert scale . the proxy - report version is identical to the self - reported patient version , except that proxies are asked their own opinion of the patient for each item . following exploratory factor analysis and rasch analysis of data from a larger sample , reported elsewhere , several scales can be identified . in the present paper , we report the summary scale and the six specific scales ( i.e. specific cognitive , specific hopes and worries , specific services , specific physical and functional , specific mood state , specific self and vitality ) in order that proxy each specific scale total , and the summary scale , ranges from 0 ( worst hrqol ) to 100 ( best hrqol ) . self - report version of the eq-5d : note that proxies were here reporting their own health status , not the patient s . this generic hrqol measure comprises five questions on mobility , self - care , pain , usual activities and psychological status using three - point scales , and generates a summary scale ( 1 = best health state ) and visual analogue scale to indicate general health status ( 100 = best health status ) . self - report version of the sf-12v2 : again , proxies reported their own status . this generic measure includes twelve items , measures eight domains of health on five - point scales , and is used to calculate two component scores the physical component summary score ( pcs ) and the mental component summary score ( mcs ) . pcs and mcs scales are transformed to 0100 scale ( 0 = worst , 100 = best ) . all statistical tests are designated significant at p < 0.05 , two - tailed . self and proxy agreement on the level of specific and summary scale scores was examined by computing mean scores , mean differences and their 95% confidence intervals . means were computed for the whole study sample , and for three subgroups according to the disease stage of persons living with hd ( early hd = at risk , pre - symptomatic gene carriers and stage 1 ; moderate hd = stages 2 and 3 ; advanced hd = stages 4 and 5 ) . two - way mixed - design analyses of variance were used to compare the effect of the patient s hd stage subgroup and the type of rater ( self or proxy ) as independent variables on pairs of self- and proxy - rated specific and summary scale scores ( dependent variables ) . multivariate and univariate analyses of covariance were used to examine whether proxy mean scores were accounted for by other potential determinants in addition to patients hd stage , including the proxy s own hrqol as reflected in eq-5d and sf12v2 scores , the patient s eq-5d and sfv12 scores , and measures of patient proxy contact . to explore agreement in terms of correlation , we examined scatterplots of patient ratings against proxy ratings . linear regression was used to assess the relationship between self and proxy ratings across the whole sample . chi - square , fisher exact and t tests were used to explore associations between regression standardised residuals ( residuals above 1.96 being defined as outliers ) and other variables such as hd stage , gender of patients or proxies . intraclass correlation coefficients ( iccs ) with a one - way random effects model and their respective confidence intervals were calculated to quantify correlation between self and proxy scores . the criteria used were the following : icc 0.80 indicates excellent agreement ; 0.80 > icc 0.60 substantial agreement ; 0.60 > icc 0.40 moderate and icc < 0.40 poor agreement [ 16 , 24 ] . iccs were also calculated separately for patient hd stage subgroups and for cases with advanced hd who did not receive any assistance in completing the questionnaires . persons living with hd who participated in this study were a subset of a larger validation sample for the hdqol . all were recruited through a mail - out via the huntington s disease association ( hda ) in the uk and provided their consent prior to their inclusion in the study . from this sample , 105 persons living with hd chose to provide proxy data in addition to their own ( at risk , n = 10 ; pre - symptomatic gene positive , n = 17 ; stage 1 , n = 9 ; stage 2 , n = 8 ; stage 3 , n = 10 ; stage 4 , n = 35 and stage 5 , n = 15 ) . the study was approved by university of reading research ethics committee and has been performed in accordance with 1964 declaration of helsinki . research questionnaires were sent to persons living with hd , referred to generically as patients although this includes people who were not yet clinically symptomatic . those who volunteered to participate were invited to give the accompanying proxy report questionnaires to someone they felt knew them well . patients were instructed that they might get assistance in completing the questionnaire , from the proxy or another helper , if they found this difficult ; however the questionnaire responses should be solely their own . proxies were instructed to complete the questionnaires independently of the patient , and were asked to focus on how they think the quality of life of the patient has been affected , drawing upon their perceptions and thoughts as a companion / carer . patients and proxies were requested to return the questionnaires using the pre - paid reply envelope provided within a fortnight . patients and proxies were asked to provide demographic details and information regarding patient s functional ability as an indication of disease stage . they were asked to complete three questionnaires as follows.self- or proxy - report version , respectively , of the hdqol . this is a disease - specific patient reported outcome measure developed from hd patient interviews , where each item comprises a relevant aspect of health - related quality of life on which hd participants provide a self - reported response on a likert scale . the proxy - report version is identical to the self - reported patient version , except that proxies are asked their own opinion of the patient for each item . following exploratory factor analysis and rasch analysis of data from a larger sample , reported elsewhere , several scales can be identified . in the present paper , we report the summary scale and the six specific scales ( i.e. specific cognitive , specific hopes and worries , specific services , specific physical and functional , specific mood state , specific self and vitality ) in order that proxy each specific scale total , and the summary scale , ranges from 0 ( worst hrqol ) to 100 ( best hrqol).self - report version of the eq-5d : note that proxies were here reporting their own health status , not the patient s . this generic hrqol measure comprises five questions on mobility , self - care , pain , usual activities and psychological status using three - point scales , and generates a summary scale ( 1 = best health state ) and visual analogue scale to indicate general health status ( 100 = best health status ) .self - report version of the sf-12v2 : again , proxies reported their own status . this generic measure includes twelve items , measures eight domains of health on five - point scales , and is used to calculate two component scores the physical component summary score ( pcs ) and the mental component summary score ( mcs ) . pcs and mcs scales are transformed to 0100 scale ( 0 = worst , 100 = best ) . this is a disease - specific patient reported outcome measure developed from hd patient interviews , where each item comprises a relevant aspect of health - related quality of life on which hd participants provide a self - reported response on a likert scale . the proxy - report version is identical to the self - reported patient version , except that proxies are asked their own opinion of the patient for each item . following exploratory factor analysis and rasch analysis of data from a larger sample , reported elsewhere we report the summary scale and the six specific scales ( i.e. specific cognitive , specific hopes and worries , specific services , specific physical and functional , specific mood state , specific self and vitality ) in order that proxy each specific scale total , and the summary scale , ranges from 0 ( worst hrqol ) to 100 ( best hrqol ) . self - report version of the eq-5d : note that proxies were here reporting their own health status , not the patient s . this generic hrqol measure comprises five questions on mobility , self - care , pain , usual activities and psychological status using three - point scales , and generates a summary scale ( 1 = best health state ) and visual analogue scale to indicate general health status ( 100 = best health status ) . self - report version of the sf-12v2 : again , proxies reported their own status . this generic measure includes twelve items , measures eight domains of health on five - point scales , and is used to calculate two component scores the physical component summary score ( pcs ) and the mental component summary score ( mcs ) . pcs and mcs scales are transformed to 0100 scale ( 0 = worst , 100 = best ) . all statistical tests are designated significant at p < 0.05 , two - tailed . self and proxy agreement on the level of specific and summary scale scores was examined by computing mean scores , mean differences and their 95% confidence intervals . means were computed for the whole study sample , and for three subgroups according to the disease stage of persons living with hd ( early hd = at risk , pre - symptomatic gene carriers and stage 1 ; moderate hd = stages 2 and 3 ; advanced hd = stages 4 and 5 ) . two - way mixed - design analyses of variance were used to compare the effect of the patient s hd stage subgroup and the type of rater ( self or proxy ) as independent variables on pairs of self- and proxy - rated specific and summary scale scores ( dependent variables ) . multivariate and univariate analyses of covariance were used to examine whether proxy mean scores were accounted for by other potential determinants in addition to patients hd stage , including the proxy s own hrqol as reflected in eq-5d and sf12v2 scores , the patient s eq-5d and sfv12 scores , and measures of patient proxy contact . to explore agreement in terms of correlation , we examined scatterplots of patient ratings against proxy ratings . linear regression was used to assess the relationship between self and proxy ratings across the whole sample . chi - square , fisher exact and t tests were used to explore associations between regression standardised residuals ( residuals above 1.96 being defined as outliers ) and other variables such as hd stage , gender of patients or proxies . intraclass correlation coefficients ( iccs ) with a one - way random effects model and their respective confidence intervals were calculated to quantify correlation between self and proxy scores . the criteria used were the following : icc 0.80 indicates excellent agreement ; 0.80 > icc 0.60 substantial agreement ; 0.60 > icc 0.40 moderate and icc < 0.40 poor agreement [ 16 , 24 ] . iccs were also calculated separately for patient hd stage subgroups and for cases with advanced hd who did not receive any assistance in completing the questionnaires . characteristics of the persons living with hd and their proxies are summarised in table 1 . most of the participants with hd ( 87% ) had confirmed positive gene status and 67% had received a clinical diagnosis . almost all of the proxies were spouses or partners ( 83% ) ; 10% were parents ; 5% were children of hd individuals and for 2% of proxies this information was missing . proxies spent a lot of time per day or night caring for the person living with hd ( mean 12.44 h , sd 9.59 , range 0:24 ) and most of them ( 87% ) had contact on a daily basis . the average time the proxies had known the person living with hd was 30.94 years ( sd 15.49 , range 1:60 ) . one patient did not report their hd stage , so this patient and proxy were omitted from analyses involving hd stage , giving sample sizes of 36 for early hd , 18 for moderate hd and 50 for advanced hd . the pair was included in whole - sample analyses ( n = 105 ) . the self - reported eq-5d and sf-12v2 measures show that , as expected , patients scored worse than proxies on all indices of hrqol . proxies physical health ( sf-12v2 pcs ) was near the average of available normative data but their mental health ( mcs ) fell below the population norm [ 25 , 26].table 1participant demographics and self - reported hrqol scores , with mean sd and rangepersons with hdproxiesnumber of subjects105105female / male61/4455/50age56.42 12.82 ( 17:90)56.55 12.89 ( 17:90)full - time education ( years)13.77 4.50 ( 4:35)13.25 4.07 ( 0:25)full or part - time employment / retired or unemployed20/8549/56eq-5d visual analogue scale ( vas)58.38 23.20 ( 0:100)75.31 20.31 ( 0:100)eq-5d index score0.56 sd = 0.35 ( 0.33:1)0.78 0.22 ( 0.04:1)sf-12v2 physical component score ( pcs)41.52 12.78 ( 16.33:66.20)50.67 8.94 ( 30.05:64.73)sf-12v2 mental component score ( mcs)39.95 11.50 ( 13.89:67.34)43.85 11.25 ( 11.83:70.29)eq-5d euroqol questionnaire , sf-12v2 short - form health questionnaire , 12-item version 2 participant demographics and self - reported hrqol scores , with mean sd and range eq-5d euroqol questionnaire , sf-12v2 short - form health questionnaire , 12-item version 2 figure 1 shows the patient and proxy ratings separated by patient s hd stage subgroup ( early , moderate or advanced).fig . 1mean ratings by patients ( white bars ) and proxies ( dark bars ) se , on the six specific scales and summary score of the hdqol . means are shown separately for early stage hd ( n = 36 ) , moderate stage hd ( n = 18 ) and advanced stage hd patients ( n = 50 ) mean ratings by patients ( white bars ) and proxies ( dark bars ) se , on the six specific scales and summary score of the hdqol . means are shown separately for early stage hd ( n = 36 ) , moderate stage hd ( n = 18 ) and advanced stage hd patients ( n = 50 ) two - way mixed - design anovas , rater ( self vs. proxy ) hd stage , yielded strong effects of hd stage on every measure ; fs(2,101 ) ranged from 7.47 ( hopes and worries ) to 72.8 ( physical and functional ) , ps 0.001 , with hrqol ratings becoming progressively poorer across the three groups . there were no significant rater hd stage interactions , fs(2,101 ) 2.71 , suggesting that patterns of self and proxy hrqol scores were broadly consistent across stages . these were again nonsignificant on the summary scale and on all specific scales except the specific hopes and worries scale , where proxy ratings were significantly better than patients own , and there was a trend for both the specific cognitive and the specific physical and functional scales proxy ratings to be poorer than self-ratings.table 2mean hdqol specific and summary scale scores by raterhdqolself - rated ( n = 105)proxy - rated ( n = 105)anova rater effectmean ( sd)mean ( sd)mean diff95% cif(1,101)pspecific scales cognitive51.34 ( 32.24)46.52 ( 33.98)4.820.74 to 8.903.450.07 hopes and worries50.98 ( 27.93)56.89 ( 30.57)5.909.90 to 1.9111.320.001 services69.71 ( 34.57)72.37 ( 33.97)2.657.74 to 2.431.75ns physical and functional62.05 ( 33.56)59.97 ( 34.80)2.081.08 to 5.252.900.09 mood state58.66 ( 28.08)57.42 ( 28.12)1.242.77 to 5.24<1ns self and vitality57.39 ( 25.78)53.60 ( 26.75)3.780.21 to 7.352.22nssummary scale57.71 ( 25.03 ) 56.2 ( 26.46)1.501.21 to 4.21<1nsci confidence interval , hdqol huntington s disease health - related quality of life questionnairehdqol scales are scored on a 0 ( worst hrqol ) 100 ( best hrqol ) scalea positive mean difference indicates that self - rated scale score is higher than proxy - rated scale scoreeffect of rater ( self vs. proxy ) in 2-way mixed anova , rater hd stage mean hdqol specific and summary scale scores by rater ci confidence interval , hdqol huntington s disease health - related quality of life questionnaire hdqol scales are scored on a 0 ( worst hrqol ) 100 ( best hrqol ) scale a positive mean difference indicates that self - rated scale score is higher than proxy - rated scale score effect of rater ( self vs. proxy ) in 2-way mixed anova , rater hd stage to explore what factors other than patient s hd stage might affect proxies hdqol scores , a multivariate analysis of covariance tested the effect of hd stage along with potential covariates on the six specific scales and summary scale . the covariates were indices obtained from patients and proxies eq-5d and sf-12v2 self - ratings , plus proxy estimates of how long they had known the patient and how much they were in contact . over and above the expected strong effect of hd stage , the only variable which significantly affected proxy scores ( wilks lamda = 0.64 , p = 0.006 ) was the patient s mental state ( as measured by sf-12v2 mcs ) . univariate analyses showed that the proxy - rated scales which were affected by patient s mcs were specific hopes and worries , specific mood state , specific self and vitality and the summary scale all slope parameters were positive ( 0.621.72 ) , i.e. the proxy rating of hrqol improved as the patient s mcs score improved . the correlation between proxy and patient hdqol summary score ratings is illustrated in fig . 2 overall there is a strong linear relationship ( = 0.81 , r = 0.73 , f(1,103 ) = 276 , p < 0.001 ) . however outliers ( where a proxy s score is greatly discrepant from the patient s own ) are evident , commonly in the mid - range of hrqol and especially among patients with moderate hd . one outlier pair ( patient score of 27 and proxy score of 59 ) was the one whose patient did not report their hd stage ( and is therefore missing from the plot ) . among the remaining seven outlier pairs , two patients were early stage , four moderate and one advanced . thus , outliers were significantly more likely to come from the moderate hd subgroup than the other subgroups , fisher exact p = 0.016 . information supplied by the proxy implies that the patient in the eighth pair , missing from the analysis , also probably had moderate hd.fig . 2plot of patient - rated versus proxy - rated summary scale scores , with regression line and 95% cis based on all data . symbols represent patient s stage of hd : bullet early , shadowed white circle moderate , filled diamond advanced plot of patient - rated versus proxy - rated summary scale scores , with regression line and 95% cis based on all data . symbols represent patient s stage of hd : bullet early , shadowed white circle moderate , filled diamond advanced we explored other potential associates , including gender of patient and proxy , nature of proxy patient relationship , proxy s own hrqol and frequency of contact . none were significant , and there was only a trend for proxy gender , fisher exact p = 0.061 ; seven out of eight outlier proxies were male compared to 43 out of 97 others . this effect is independent from the preceding one , because moderate subgroup proxies were not more likely to be male than those in other subgroups , the excess of male proxies among outliers is not simply an extreme case of generally poor prediction of patient hrqol by males ; after removing all outliers , the absolute standardised residuals of male proxies were similar to those of females ( male m = 0.68 , female m = 0.65 , t(95 ) < 1 ) . scatterplots of other subscales ( not shown ) show the same pattern of lower proxy patient agreement and more outliers in the moderate hd group . icc values for the whole sample reflected excellent ( > 0.80 ) or substantial ( > 0.60 ) agreement on all scales , as did virtually all values for the early and advanced hd subgroups separately . in the moderate hd subgroup , agreement was moderate ( < 0.60 ) to poor ( < 0.40).table 3intraclass correlation coefficients between self and proxy scores for the hdqol specific and summary scales : whole sample and hd stage subgroupshdqolwhole sample ( n = 105)early hd ( n = 36)moderate hd ( n = 18)advanced hd ( n = 50)icc(95% ci)icc(95% ci)icc(95% ci)icc(95% ci)specific scales cognitive0.79(0.710.85)0.78(0.610.88)0.03(0.47 to 0.42)0.61(0.400.76 ) hopes and worries0.74(0.630.81)0.83(0.690.91)0.49(0.05 to 0.77)0.77(0.630.86 ) services0.71(0.600.79)0.76(0.580.87)0.48(0.04 to 0.76)0.74(0.590.85 ) physical and functional0.88(0.840.92)0.87(0.770.93)0.24(0.23 to 0.63)0.81(0.690.89 ) mood state0.73(0.630.81)0.56(0.290.75)0.46(0.02 to 0.76)0.76(0.610.85 ) self and vitality0.75(0.650.82)0.63(0.390.79)0.65(0.28 to 0.85)0.59(0.370.74)summary scale0.85(0.790.90)0.81(0.650.90)0.37(0.09 to 0.70)0.81(0.690.89)hd huntington s disease , icc intraclass correlation coefficient , ci confidence interval , hdqol huntington s disease health - related quality of life questionnaire intraclass correlation coefficients between self and proxy scores for the hdqol specific and summary scales : whole sample and hd stage subgroups hd huntington s disease , icc intraclass correlation coefficient , ci confidence interval , hdqol huntington s disease health - related quality of life questionnaire agreement in the advanced hd subgroup might have been inflated because advanced hd patients were more likely than others to have reported that they received assistance from proxies in completing the questionnaires , ( (2,n = 104 ) = 15.56 , p < 0.001 ) . therefore , iccs were recomputed for the advanced hd subgroup after removing the 16 cases ( out of a total of 50 ) who received assistance . iccs for this subset were slightly lower than for the whole advanced subgroup e.g . but agreement remained substantial on all scales except for cognitive , and self and vitality , where it was moderate though still highly significant . previous reports on the carers of patients with hd have examined their reports of their own hrqol and compared it to that of patients [ 2729 ] . however , the current study using the proxy version of the hdqol is the first in which carers or others act as proxies , providing their own perceptions of the hrqol of persons living with hd , maintaining a proxy proxy perspective . proxy agreement was substantial to excellent for the summary scale score of the hdqol , and also for most of its specific scales . on the specific hopes and worries scale , proxies rated patients hrqol as better than patients own ratings , while on both the specific cognitive scale and specific physical and functional scale the reverse was true . the literature shows that for chronically ill patients including those with neurological disorders such as stroke , brain cancer and parkinson s disease [ 15 , 16 ] , patient proxy agreement on validated disease - specific questionnaires are generally moderate to high , and when discrepant , proxies often provide poorer qol ratings than patients . our data are consistent with the literature , but it is notable that proxies rated patients specific hope and worries scale score as better rather than worse than patients own ratings . this dimension may be particularly difficult for proxies to gauge as it is perhaps even more internal than other psychosocial dimensions , which can garner lower agreement than more objective physical dimensions . when patient proxy agreement is examined across disease severity , the early and advanced subgroups showed substantial to excellent agreement on the summary score as well as for the specific scale scores . in both subgroups , the highest icc values emerged on the most objective , observable scale specific physical and functional as has often been reported elsewhere . yet subjective scales such as specific hopes and worries , or specific mood state , yielded substantial iccs . this may reflect the fact that proxies were long - term companions or close family members who typically show better agreement than unrelated healthcare providers [ 17 , 34 ] . proxy agreement , not only with early hd patients who could validly assess their own hrqol , but also with advanced hd patients who usually have physical or cognitive barriers to self - reporting . patient agreement in the advanced group was not merely an artefact of proxies assisting with questionnaire completion , because agreement remained substantial even after excluding patients who received assistance . this is in contrast to poorer agreement reported for more advanced stage alzheimer s and parkinson s disease patients [ 1517 ] . to confirm these postal study results , further investigation where questionnaire completion is fully monitored would be useful . for moderate stage 2 and 3 patients , patient the qol cancer severity literature reports a similar pattern of results where larger patient proxy discrepancies were more frequent for patients who were slightly and moderately affected , rather than at extreme ends of the spectrum . this may be due to greater scope for variability in ratings of patients and proxies at an intermediate level of disease manifestation . progression of hd is suggested to be fastest , more variable and diverse in the moderate stages , compared to early or advanced stages of the disease . therefore , patients with moderate hd might be the most heterogeneous group and most changeable over time , making it hard for proxies to form stable judgements . furthermore , the moderate stages may be particularly complex for patients , who are beginning to experience a physical and psychological decline which both they and their family have long dreaded . they may be anxious about other people s attitudes , or wrongly believe that transient difficulties are signs of hd , as we have previously found . some proxies may find it hard to communicate with patients and understand their subtle and fluctuating symptoms at this stage , and our analysis hints that this may be particularly true of male proxies . by comparison , advanced - stage patients state and relations with carers are more stable , perhaps making it easier for proxies to evaluate hrqol . it is also worth noting that the proxy proxy perspective adopted here where proxies were encouraged to use their own viewpoint , rather than explicitly trying to simulate the patient s feelings can lead to genuine differences between proxy and patient views of hrqol . we examined factors that might influence proxies tendency to over- or under - rate hrqol . previous studies have suggested that proxies level of burden , psychosocial stress and amount of time they spend with patients could moderate their assessment [ 1 , 3739 ] . in the present case , neither proxies own physical or psychosocial hrqol ( as putative measures of carer burden ) , nor however , the patient s own psychological state ( sf-12v2 mental component score ) influenced proxy scores on the more subjective specific scales of the hdqol specific hopes and worries , specific mood state , specific self and vitality even after the patient s disease stage was taken into account . therefore , proxies ratings of psychosocial aspects of hrqol were sensitive to patients psychological state , as well as symptom severity . in summary , this cross - sectional study addressed parameters of patient proxy agreement on hrqol for the first time in hd , by comparing proxy assessment with patient self - report , using the disease - specific hdqol . there was substantial agreement for the summary scale and also the specific scales and this suggests that the hdqol proxy version yields generally similar scores to patients own , particularly on physical and functional aspects but also on more scale , proxies on average rated hrqol as better than patients self - ratings , while on both the specific cognitive and specific physical and functional scales proxies tended to rate hrqol more poorly than patients themselves . as more modest patient proxy agreement was found for moderate - stage patients , proxy report should not be used as a substitute for patient - reported rating for these patients . as there was good patient proxy agreement for advanced - stage patients , proxy evaluation using this questionnaire could be a particularly useful complementary tool to self - report in advanced hd .

huntington s disease ( hd ) is a fatal , neurodegenerative disease for which there is no known cure . proxy evaluation is relevant for hd as its manifestation might limit the ability of persons to report their health - related quality of life ( hrqol ) . this study explored patient proxy ratings of hrqol of persons at different stages of hd , and examined factors that may affect proxy ratings . a total of 105 patient proxy pairs completed the huntington s disease health - related quality of life questionnaire ( hdqol ) and other established hrqol measures ( eq-5d and sf-12v2 ) . proxy patient agreement was assessed in terms of absolute level ( mean ratings ) and intraclass correlation . proxies ratings were at a similar level to patients self - ratings on an overall summary score and on most of the six specific scales of the hdqol . on the specific hopes and worries scale , proxies on average rated hrqol as better than patients self - ratings , while on both the specific cognitive scale and specific physical and functional scale proxies tended to rate hrqol more poorly than patients themselves . the patient s disease stage and mental wellbeing ( sf-12 mental component scale ) were the two factors that primarily affected proxy assessment . proxy scores were strongly correlated with patients self - ratings of hrqol , on the summary scale and all specific scales . the patient proxy correlation was lower for patients at moderate stages of hd compared to patients at early and advanced stages . the proxy report version of the hdqol is a useful complementary tool to self - assessment , and a promising alternative when individual patients with advanced hd are unable to self - report .

consider the one - dimensional gas of spin @xmath0 fermions interacting via the @xmath2-potential . the hamiltonian of this model is @xmath3 . \label{h}\ ] ] the fermionic fields @xmath4 ( @xmath5 is a spin index , @xmath6 ) satisfy canonical equal - time anti - commutational relations @xmath7 the operators @xmath8 are the density operators for spin - up ( spin - down ) fermions and @xmath9 is the total fermion density operator . in this paper we will consider the infinite @xmath10 limit of one - particle correlation functions @xmath11 and @xmath12 where the average @xmath13 is taken over the thermal ensemble at a given temperature @xmath14 and chemical potential @xmath15 we will calculate the large @xmath16 and @xmath17 asymptotics of the correlation functions and assuming that ( a ) the limit of infinite repulsion @xmath18 is taken at finite positive chemical potential @xmath19 and ( b ) , the zero temperature limit is taken afterwards . the ground state of the system is infinitely degenerate at infinite @xmath20 this degeneracy leads to a non - trivial ( non - conformal ) behaviour of the correlation functions and at zero temperature . the physics of this phenomenon were presented earlier @xcite , here we present a detailed derivation of these results . our starting point is the determinant representation for @xmath21 and @xmath22 recently derived by izergin and pronko @xcite . we relate the objects entering this representation to the solution of the corresponding matrix riemann - hilbert problem ( rh problem ) @xcite . we perform the asymptotic analysis of this rh problem making use of previous work @xcite . the large @xmath16 asymptotics of the correlation functions at @xmath23 are given in subsection [ answer0 ] . the asymptotics of the time - dependent correlation functions in the space - like region are given in subsection [ answerx ] . the asymptotics in the time - like region for @xmath24 are given in subsection [ answert ] . the large @xmath17 asymptotics of the correlation functions for @xmath25 are given in section [ ks=0 ] . this section is introductory . in subsection [ elrel ] we recall some elementary relations for the correlation functions and . in subsection [ detrep ] we recall the results of @xcite on the determinant representation for these correlation functions . in subsection [ residue ] we examine the analytic properties of the functions entering this determinant representation . in subsection [ rhsection ] , following @xcite , we formulate the matrix rh problem related to the determinant representation of the correlation functions and . in this subsection we recall some elementary relations for the correlation functions and . due to the parity and the time reversal symmetry of the hamiltonian the functions and obey the following symmetry properties @xmath26 and @xmath27 here the asterisk stands for the complex conjugation . furthermore , the following relation between @xmath28 and @xmath29 can be written @xmath30 where @xmath31 stands for the anticommutator . at @xmath23 this relation becomes @xmath32 which is obvious from equation . note also the scaling relation @xmath33 where @xmath34 is the correlation function taken at a given chemical potential @xmath15 in the following we will assume that @xmath35 @xmath36 and @xmath37 the correlation functions for all other cases will follow from the relations , and . in this subsection , following @xcite , we write down the determinant representation for the correlation functions and . we use the notations of @xcite . in paper @xcite the following representation of the correlation functions and was derived @xmath38 and @xmath39 to shorten notations we will henceforth omit @xmath40 @xmath17 and @xmath41 in the arguments of all functions unless they are necessary . the objects entering the representations and are defined as follows . the function @xmath42 is @xmath43 the determinant @xmath44 is the fredholm determinant of a linear integral operator @xmath45 with the kernel @xmath46 defined on @xmath47\times[-1,1].$ ] the functions entering this kernel are defined as follows : @xmath48\\ e_-(k)=\frac{1}{\sqrt{\pi}}\rme^{\tau(k)/2}\\ \tau(k)=\rmi k^2 t - \rmi k x\\ e_0(k)={\rm p.v . } \int_{-\infty}^\infty \rmd p \frac{\rme^{-\tau(p)}}{\pi(p - k ) } } \label{edefs}\ ] ] note that @xmath49 is symmetric , @xmath50 and nonsingular at @xmath51 to define @xmath52 and @xmath53 introduce the resolvent operator @xmath54 @xmath55 due to the specific form of the kernel @xmath56 the resolvent kernel @xmath57 may be written as @xmath58 where functions @xmath59 are the solutions to the integral equations @xmath60 for the pairs @xmath61 and @xmath62 we will often use the vector notation : @xmath63 now define the functions @xmath64 and @xmath65 @xmath66 where @xmath67 and @xmath68 run through two values : @xmath69 . in particular , @xmath70 the function @xmath53 in is @xmath71 where @xmath72 is the vacuum green function @xmath73 in this subsection we examine the analytic properties of the functions entering the representations and . using these properties we transform the integrals in equations and to the form convenient for the asymptotical analysis . let us change the integration variable @xmath41 in and to @xmath74 then @xmath75 @xmath76 where @xmath77 the integration contour , @xmath78 is oriented counterclockwise . introduce the function @xmath79 and denote by @xmath80 and @xmath81 its analytic branches in the upper and lower half - planes , respectively . the analytic continuations of @xmath80 and @xmath81 to the real axis satisfy @xmath82 using the kernel @xmath83 can be rewritten as @xmath84 \label{vepm}\end{aligned}\ ] ] where @xmath85 \frac{e_{+}(k)-e_{+}(p)}{k - p } \label{v1}\\ w_{2}(k , p)=\frac1{2\pi}\exp\left[\frac{\tau(k)+\tau(p)}2\right ] \frac{e_{-}(k)-e_{-}(p)}{k - p}. \label{v2}\end{aligned}\ ] ] by using the fredholm theory of linear integral equations ( see , _ e.g. _ , @xcite , chapter 3 , section 7 ) the following two facts may be shown : ( a ) the fredholm determinant @xmath86 with the kernel @xmath87 defined by - is analytic in the complex @xmath88-plane except at most at @xmath89 and @xmath90 ( b ) the corresponding resolvent kernel @xmath91 may be represented as @xmath92 where the function @xmath93 is analytic in the complex @xmath88-plane except at most at @xmath89 and @xmath90 the explicit form of @xmath93 is given in the reference cited above . we will not use it in our calculations . consider equation . the function @xmath94 entering this equation , is defined by equation . inverting @xmath95 and substituting the resulting expression in , one gets @xmath96 combining equations and one sees that @xmath97 is analytic in the complex @xmath88-plane except at most at @xmath89 and @xmath90 keeping this in mind , deform the integration contour in to a contour @xmath98 shown in figure [ fig : zintegral ] . shows the integration contour @xmath98 in equations and . both contours are oriented counterclockwise . the cross indicates the pole of the function @xmath99 at @xmath100,scaledwidth=35.0% ] since the function @xmath99 has a simple pole at the point @xmath101 , one gets @xmath102 next consider equation . like the function @xmath103 the function @xmath104 is analytic in the complex @xmath88-plane except at most at @xmath89 and @xmath90 note that despite the singular factor @xmath105 the integrand does not have a singularity at @xmath106 due to the second order zero of @xmath107 at this point . indeed , one can see from that @xmath108 for @xmath109 therefore , @xmath110 for @xmath111 which is seen from equation . using the definitions , and one can see that @xmath112 for @xmath113 . deforming the integration contour in to the contour @xmath98 shown in figure [ fig : zintegral ] , one gets @xmath114 consider a special case of @xmath115 the kernel becomes equal to zero since @xmath116 hence , the kernel becomes a linear function of @xmath117 this implies that ( see , _ e.g. _ , @xcite , chapter 3 , section 7 ) ( a ) the determinant @xmath118 becomes an analytic function of @xmath88 for all @xmath119 ( b ) the function @xmath93 in equation also becomes an analytic function of @xmath88 for all @xmath120 thus , by virtue of the function @xmath121 is analytic in the complex @xmath88-plane and the second term in the right hand side of vanishes : @xmath122 the function @xmath123 can be obtained from equation using equation . in this subsection we write differential equations for the fredholm determinant @xmath124 entering the representations and . first , we obtain the differential equation with respect to @xmath125 as follows from and - the @xmath41 derivative of the kernel is given by @xmath126 differentiating the identity @xmath127 we immediately get @xmath128 + \frac{1-\rme^{-\rmi\eta}}{\rmi } \tr[(\hat i+\hat v)^{-1}\hat w_2 ] . \label{diffetalndet}\ ] ] transform the right hand side of employing , and . the result for the first term is @xmath129=\tr\hat r= -\rmi \int_{-1}^{1 } \rmd k [ \vec f(k)]^{t } \sigma_2 \partial _ k \vec f(k ) \label{detavect}\ ] ] where @xmath130 is the second pauli matrix @xmath131 the second term in the right hand side of is more complicated : @xmath132&=\tr[(\hat i-\hat r ) \hat w_2]\nonumber\\ & = \int_{-1}^{1}\rmd k w_2(k , k ) - \int_{-1}^{1}\rmd k \int_{-1}^{1}\rmd p r(k , p)w_2(p , k ) . \label{w}\end{aligned}\ ] ] the differential equations for @xmath133 with respect to @xmath16 and @xmath17 can be obtained in a similar way . they read @xmath134 . \label{tderiv}\end{aligned}\ ] ] finally , the following initial conditions for the differential equations follow from and : @xmath135 and @xmath136 the differential equations , and will be used in the subsequent asymptotical calculation of @xmath137 in this subsection we briefly recall the notion of the riemann - hilbert problem ( rh problem ) and its relation to the objects entering the representations and . the standard formulation of the riemann - hilbert problem is as follows @xcite : for a given oriented contour @xmath138 in the complex @xmath139-plane and for a given matrix @xmath140 defined on this contour , seek a matrix @xmath141 such that @xmath142 the contour @xmath138 is called ` conjugation contour ' or ` jump contour ' ; the matrix @xmath140 is called ` conjugation matrix ' or ` jump matrix ' . the matrices @xmath143 are the boundary values of @xmath141 as @xmath139 approaches @xmath144 @xmath145 by convention , the @xmath146 side ( respectively , @xmath147 side ) of @xmath138 lies to the left ( respectively , right ) as one traverses the contour in the direction of the orientation . an example of such an oriented contour is shown in figure [ fig : firstcontour ] . by using the cauchy transform one can see that the rh problem is equivalent to the matrix - valued integral equation ( @xcite , chapter xv ) @xmath148 . \label{singeq}\ ] ] ( the functions @xmath149 @xmath150 and @xmath151 are supposed to be integrable along the contour @xmath152 we will impose this condition for all rh problems appearing below ) . suppose the jump matrix @xmath140 depends on the external parameter , @xmath40 and @xmath153 uniformly for @xmath154 . then , it can be shown solving perturbatively that @xmath155 uniformly outside an arbitrarily small vicinity of the contour @xmath152 we will use the estimate in the subsequent asymptotical analysis . next we relate the rh problem to the objects entering the determinant representations and . consider the following conjugation matrix @xmath156 or in the vector notation @xmath157^{t}\sigma_2 \label{nu0vec}.\ ] ] choose the conjugation contour to be the interval @xmath47 $ ] oriented as shown in figure [ fig : firstcontour ] and denote this contour as @xmath158 . the thick line connecting the points @xmath159 and @xmath160 shows the conjugation contour @xmath161 for the rh problem . the arrow shows the direction of the orientation of this contour.,scaledwidth=50.0% ] let @xmath162 be a solution to the rh problem @xmath163 then the components @xmath164 and @xmath165 of the vector @xmath166 satisfy equations . indeed , consider equation where the conjugation matrix @xmath167 is chosen to be the matrix @xmath168 given in equation . multiply equation by the vector @xmath169 from the right . equations follow immediately . combining equations and where the matrix @xmath167 is chosen to be @xmath168 write @xmath170 comparing equations and one sees that the functions @xmath64 and @xmath65 can be found from the large @xmath139 expansion of @xmath141 @xmath171 consider an arbitrary compact domain @xmath172 in the complex plane of the parameter @xmath88 , not containing the point @xmath89 . since the fredholm determinant in equations and is analytic in @xmath173 it only has a finite set of zeroes @xmath174 in @xmath175 the integral equations are solved uniquely for any @xmath176 in @xmath175 the solutions @xmath177 of the integral equations can be found from a solution @xmath141 of the rh problem by using equation . the functions @xmath64 and @xmath65 can be found from the expansion . the fredholm determinant @xmath178 is completely defined by the differential equations and with the initial condition or , alternatively , by the differential equation with the initial condition . since the functions @xmath97 in and @xmath104 in are analytic in @xmath179 their values at the points @xmath180 can be found by analytic continuation . in this section we solve the rh problem asymptotically for @xmath181 and @xmath115 as it is obvious from , to calculate @xmath182 it is sufficient to solve this rh problem at a specific value @xmath101 of the parameter @xmath117 nevertheless , we will construct the solution for all complex @xmath88 outside an arbitrarily small vicinity of the point @xmath89 . this general result will prove useful in the subsequent analysis of the @xmath183 case . in subsection [ rhp0 ] we formulate explicitly the rh problem for @xmath184 see equation . in subsections [ deformed1 ] and [ deformed2 ] , following along the lines of @xcite , we transform the rh problem so as to make it convenient for the large @xmath16 analysis . in subsection [ explicit ] we give an explicit solution to the jump relation ( [ rhpx].b ) in a vicinity of the end points @xmath185 of the contour @xmath158 in subsection [ perturthe ] we construct the solution to the rh problem in the large @xmath16 limit by matching the solution given in subsection [ explicit ] with the condition ( [ rhpx].c ) . in subsection [ approx ] we summarize the results of this section . in this subsection we give an explicit formulation of the rh problem at @xmath23 . by taking the limit @xmath186 and assuming that @xmath187 in we get for @xmath188 @xmath189 the conjugation matrix becomes @xmath190 the oriented contour @xmath161 shown in figure [ fig : firstcontour ] remains unchanged . thus , we have defined the rh problem for @xmath23 @xmath191 introduce a matrix @xmath192 note that @xmath193 . the jump matrix and the functions satisfy the involutions @xmath194^{-1 } \label{involution}\ ] ] and ( note ) @xmath195 respectively . as a consequence , we have the involution @xmath196 for the solution @xmath141 of the rh problem and , by virtue of , the involution @xmath197 for @xmath198 in this subsection an rh problem equivalent to the rh problem is formulated on the lens - shaped conjugation contour shown in figure [ fig : lens ] . represent @xmath141 as a product of two matrices @xmath199 and define @xmath200 by the formula @xmath201^{-1 } & \qquad k\in\omega_{d } \end{array } \right .. \label{ldef}\ ] ] a lens - shaped contour @xmath202 dividing the complex @xmath139-plane into the regions @xmath203 , @xmath204 and @xmath205 is displayed in figure [ fig : lens ] . . the thick lines show the lens - shaped contour @xmath206=@xmath207 it is the conjugation contour for the rh problem . this contour divides the complex @xmath139-plane into three regions : @xmath208 @xmath204 and @xmath209 , scaledwidth=50.0% ] the matrices @xmath210 and @xmath211 are defined as @xmath212 introducing a matrix @xmath213 by the formula @xmath214 one can see that the following representation for the conjugation matrix can be written @xmath215 note that @xmath216^{-1 } \qquad p\nu_2p^{-1}=\nu_2^{-1 } \label{inv123}\ ] ] where the matrix @xmath217 is defined by . it follows from equations , , and that @xmath218 solves the following rh problem @xmath219 we will calculate the large @xmath16 asymptotics of @xmath220 the asymptotics of @xmath141 will then follow from . the advantage of the rh problem from the point of view of the large @xmath16 analysis will be clear from the next subsection . in this subsection we present the scheme of the analysis of the rh problem in the large @xmath16 limit . the @xmath16-dependent entry of the jump matrix @xmath210 ( respectively , @xmath211 ) entering decays exponentially as @xmath181 everywhere on the jump contour @xmath221 ( respectively , @xmath222 ) except at the points @xmath223 the jump matrix @xmath213 is a constant matrix . for the rh problems with such a behaviour of the jump matrices , the following scheme of the large @xmath16 analysis can be employed @xcite . denote by @xmath224 a vicinity of the points @xmath225 split @xmath218 in a product of three matrices @xmath226 the matrix @xmath227 satisfies the jump relation @xmath228 everywhere on the contour @xmath229 and the jump relation ( [ rhpxdeformed].b ) on the part of contour @xmath206 lying in @xmath230 the matrix @xmath231 represents the corrections to @xmath227 due to the mismatch between the analytic branches of @xmath227 in and outside @xmath230 the matrix @xmath232 represents the corrections to @xmath233 due to the discontinuities , exponentially small as @xmath234 across the parts of the contours @xmath221 and @xmath222 lying outside @xmath230 below we give the precise sense to @xmath235 , @xmath236 and @xmath237 let @xmath224 consist of two discs @xmath238 and @xmath239 shown in figure [ fig : contourxlr ] . let the radii of these disks be equal and less than one . denote the domain @xmath240 as @xmath241 and @xmath242 are shaded in gray ; their boundaries @xmath243 and @xmath244 are oriented clockwise.,scaledwidth=50.0% ] introduce a matrix @xmath227 by @xmath245 where the matrices @xmath246 @xmath247 and @xmath248 are defined as follows . the matrix @xmath249 is analytic everywhere in @xmath250 except the contour @xmath251 on this contour it satisfies the jump relation with the jump matrix @xmath252_{+}=[q_{\infty}(k)]_{-}\nu_2 \qquad k\in \sigma_2 \cap \mathcal d_\infty \label{qinfjump}\ ] ] and is normalized at infinity : @xmath253 we choose the following ( obviously , not unique ) solution to and : @xmath254 note that it satisfies the involution @xmath255 the matrix @xmath256 is analytic everywhere in @xmath238 except the contour @xmath257 on this contour it satisfies the jump relation with the jump matrices - @xmath258_{+}=\left[q_r(k)\right]_{- } \nu_i(k ) \qquad k \in \sigma_i\cap \mathcal d_r \qquad i=1,2,3 . \label{qrjump}\ ] ] a solution to the jump relation is given in subsection [ explicit ] . the matrix @xmath259 is analytic everywhere in @xmath260 except the contour @xmath261 on this contour it satisfies the jump relation similar to @xmath262_{+}=\left[q_l(k)\right]_{- } \nu_i(k ) \qquad k \in \sigma_i\cap \mathcal d_l \qquad i=1,2,3 . \label{qljump}\ ] ] a solution to the jump relation is given in subsection [ explicit ] . it should be stressed that any solution to the jump relation ( respectively , ) multiplied from the left by an arbitrary matrix with the entries being entire functions of @xmath139 in @xmath238 ( respectively , @xmath242 ) , still remains a solution to ( respectively , ) . in subsequent calculations we will employ this property to simplify the form of the conjugation matrices @xmath263 and @xmath264 defined by equation below . next define the matrix @xmath236 entering the decomposition as a solution to the following rh problem : @xmath265 with the clockwise oriented conjugation contours @xmath266 shown in figure [ fig : contourxlr ] . the jump matrices @xmath267 are chosen to ensure the continuity of @xmath268 across @xmath269 @xmath270 this implies @xmath271^{-1 } \qquad k\in\partial \mathcal d_{r , l}. \label{thetarldef}\ ] ] we solve the rh problem in the large @xmath16 limit in subsection [ perturthe ] . with the matrices @xmath235 and @xmath236 defined above one can easily see that the matrix @xmath272 in the decomposition solves the following rh problem @xmath273\nu_{i}(k)[s(k)q(k)]^{-1 } \qquad k \in\sigma_i\cap\mathcal d_\infty \qquad i=1,3\\ \mbox{(c)}\quad & k(k)\to i \mbox { as } k\to \infty } \label{k}\end{aligned}\ ] ] we solve the rh problem in the large @xmath16 limit in subsection [ approx ] . in this subsection we explicitly construct matrices @xmath247 and @xmath248 satisfying the jump relations and , respectively . since the conjugation matrix is @xmath274-periodic in @xmath275 we will restrict our considerations to the interval @xmath276 to shorten notations , introduce the parameter @xmath277 consider the part of the contour @xmath206 lying in the disk @xmath278 for the convenience of presentation we choose @xmath221 and @xmath222 to be perpendicular to @xmath279 as shown in figure [ fig : contourr ] . is shaded in gray . the segments of the contours @xmath221 and @xmath222 lying in @xmath238 are straight and perpendicular to @xmath280 , scaledwidth=30.0% ] consider a matrix @xmath281 with the entries @xmath282 \\ \phi^r_{21}(k;x ) & = - x^{\frac{\eta}{2\pi } } \frac { \pi\varsigma_1(k-1 ) \rme^{-\frac{\rmi \eta}{4}}\rme^{-\rmi x } } { \gamma^2\left(\frac{\eta}{2\pi}\right ) \sin^2\frac{\eta}{2 } } \psi\left[1-\frac{\eta}{2\pi } , 1 ; -\rmi x(k-1)\right ] \\ \phi^r_{12}(k;x)&= x^{-\frac{\eta}{2 \pi } } \frac { \pi \varsigma_2(k-1)\rme^{\frac{3 \rmi \eta}{4}}\rme^{\rmi x } } { \gamma^2\left(-\frac{\eta}{2 \pi}\right ) } \psi\left[1+\frac{\eta}{2\pi},1;\rmi x(k-1)\right ] \\ \phi^r_{22}(k;x)&= x^{\frac{\eta}{2 \pi } } \varsigma_2(k-1)\rme^{\frac{\rmi \eta}{4 } } \psi\left[\frac{\eta}{2\pi},1;\rmi x(k-1)\right ] } \label{phientries}\ ] ] here @xmath283 is the tricomi @xmath284 function , which has a branch cut discontinuity across the negative real axis @xcite @xmath285\psi(a,1 , w- \rmi 0 ) \nonumber \\ \lo= \frac{2\pi \rmi \rme^{- \rmi a \pi}}{\gamma^2(a ) } e^w\psi(1-a , 1 , -w ) \qquad w\in \mathbb{r}_{- } \label{tricomi}\end{aligned}\ ] ] and @xmath286 are piecewise - constant functions defined by @xmath287 and @xmath288 using it is easy to check that @xmath281 satisfies the jump relation on the contour @xmath289 shown in figure [ fig : contourr ] @xmath290_{+}=[\phi_r(k;x)]_{-}\nu_i(k;x ) \qquad k\in\sigma_{i}\cup\mathcal d_r \qquad i=1,2,3 . \label{phirjump}\ ] ] it follows from the involution that a solution @xmath291 to the jump relation may be obtained from @xmath292 via the involution @xmath293 as was mentioned in the paragraph following equation , any matrix @xmath247 of the form @xmath294 with @xmath295 being an arbitrary analytic in @xmath238 matrix , satisfies . choosing @xmath296 one ensures that @xmath256 goes to @xmath297 as @xmath234 for any @xmath298 see . this will facilitate the asymptotic solution of the rh problem . taking into account and define @xmath259 in @xmath242 by the formula @xmath299 to calculate the large @xmath16 asymptotics of @xmath256 we use the asymptotic formula for the tricomi @xmath284 function ( @xcite , section 6.13.1 ) @xmath300 \qquad \mbox{as } \qquad w\to \infty . \label{tricomias}\ ] ] applying to one gets from : @xmath301 where @xmath302 the large @xmath16 asymptotics of @xmath303 follows from and . note that the terms in asymptotic expansions of @xmath304 explicitly written down in do not have jumps across the contours @xmath221 and @xmath222 . this reflects the fact that the @xmath16-dependent entries in the jump matrices @xmath210 and @xmath211 are exponentially small on @xmath221 and @xmath305 respectively . in this subsection we solve the rh problem in the large @xmath16 limit . consider the conjugation matrices @xmath263 and @xmath264 of the rh problem . they are defined by the formula and satisfy the involution @xmath306 as can be shown using the involutions and . substituting the asymptotic expression into one gets the approximation of the matrix @xmath263 by a matrix @xmath307 @xmath308 \label{thetar}\ ] ] uniform for @xmath309 here @xmath310 and @xmath311^{-\frac\eta\pi } \\ b_r [ x(k+1)]^{\frac\eta\pi } & \rmi\left(\frac{\eta}{2\pi}\right)^2 \end{array}\right ) . \label{upsilonr}\ ] ] it follows from the involution that the matrix @xmath264 is approximated by a matrix @xmath312 @xmath313 \label{thetal}\ ] ] uniformly for @xmath314 where @xmath315 consider the rh problem @xmath316 with the matrices @xmath317 and @xmath318 defined by equations and , respectively . comparing and with and we conclude that the solution @xmath319 of the rh problem approximates the solution @xmath231 of the rh problem @xmath320 \label{stilde}\ ] ] uniformly outside a vicinity of the conjugation contours @xmath243 and @xmath321 due to a simple analytical structure of the conjugation matrices and the rh problem can be solved exactly . to begin with , introduce the following notation for the analytic branches of @xmath319 @xmath322 the matrix @xmath323 analytically continued from @xmath324 into @xmath238 has a simple pole at @xmath325 as follows from the representation . the matrix @xmath326 is analytic in @xmath278 therefore , the jump relation ( [ rhpsl].b ) @xmath327 implies that the analytic continuation of @xmath328 into @xmath238 has a simple pole at @xmath329 similarly , the analytic continuation of @xmath328 into @xmath239 has a simple pole at @xmath330 finally , taking into account the condition given in equation ( [ rhpsl].c ) , @xmath331 , we see that the most general form of @xmath328 is @xmath332 with the matrices @xmath333 and @xmath334 being independent of @xmath139 . the involution @xmath335 which follows from the involution , provides a simple relation between @xmath333 and @xmath336 @xmath337 so we only need to calculate one of the matrices , say , @xmath333 . for this , invert : @xmath338^{-1 } \qquad k\in \partial \mathcal d_r . \label{jrrinverse}\ ] ] using and the right hand side of equation can be analytically continued into @xmath278 in the following , equation will be understood to be such a continuation . the matrix @xmath339^{-1}$ ] has the form @xmath340^{-1 } = [ \det\tilde\theta_{r}(k)]^{-1 } \left[i-\frac{\upsilon_{r}(k)}{x(k-1)}\right]\ ] ] where @xmath341 and @xmath342 is a @xmath139-independent number @xmath343 the right hand side of must be analytic in @xmath344 since the left hand side is . the matrix @xmath339^{-1}$ ] goes to zero as @xmath345 cancelling the pole of @xmath328 at this point . however , @xmath346^{-1}$ ] is singular at the points where @xmath347 equation is quadratic in @xmath139 . its solutions , @xmath348 lie inside the disk @xmath238 for sufficiently large @xmath16 . therefore , to cancel the singularities in the matrix @xmath333 has to satisfy the pair of matrix equations @xmath349=0 . \label{eqa}\ ] ] the determinant of the matrix in square brackets in is equal to @xmath350 and , therefore , is equal to zero . employing this fact one gets ( after some algebra ) the matrix @xmath351 the large @xmath16 asymptotics of @xmath352 is @xmath353 where @xmath354 and @xmath355 applying the involution to one gets the large @xmath16 asymptotics of @xmath356 @xmath357 in this subsection we show that the the matrix @xmath272 in the decomposition does not contribute to the asymptotic solution of the rh problem to the order we are interested in . this will conclude the asymptotic solution of the rh problem . consider the decomposition . in subsection [ perturthe ] we constructed explicitly the approximation @xmath358 to @xmath236 up to the order of @xmath359 this approximation is uniform outside an arbitrarily small vicinity of the conjugation contours @xmath243 and @xmath321 the matrix @xmath235 was constructed explicitly in subsections [ deformed2 ] and [ explicit ] . using these results , solve asymptotically the rh problem for the matrix @xmath237 the matrices @xmath210 and @xmath360 entering ( [ k].b ) , converge as @xmath181 to the identity matrix uniformly and exponentially fast on the contours @xmath361 and @xmath362 , respectively . one can prove that @xmath363 uniformly outside a vicinity of the contours @xmath364 . the basic idea in obtaining is the same as in obtaining : to use . one should take into account , though , that we have now , contrary to , no uniform estimate for the jump matrix in ( [ k].b ) in a vicinity of the contours @xmath365 since we have no uniform estimate for @xmath231 entering this matrix , in this vicinity . for further details we refer the reader to reference @xcite . substituting and into the decomposition one gets the estimate @xmath366 \label{schi}\ ] ] uniform outside an arbitrarily small vicinity of the contours @xmath365 and @xmath367 using one gets the approximation to @xmath141 up to the order of @xmath368 , uniform outside this vicinity . this completes the solution to the rh problem in the large @xmath16 limit . in this section we calculate the equal - time correlation functions @xmath182 and @xmath123 in the large @xmath16 limit . the asymptotic expressions for these functions were obtained in papers @xcite . the main purpose of this section is a to give a detailed illustration of our method on this known example . the procedures of this section will be extensively used in the subsequent analysis of the time - dependent correlation functions . in subsection [ basympt ] we calculate the functions @xmath64 from the large @xmath139 expansion of @xmath369 from thus obtained @xmath370 we calculate the fredholm determinant @xmath371 in the large @xmath16 limit , see equation . the constant @xmath372 entering is calculated in subsection [ casy ] . we give the answer for @xmath373 and @xmath374 in subsection [ answer0 ] . in this subsection we use the results of section [ section : rhp0 ] on the asymptotic solution of the rh problem to calculate the functions @xmath64 and the fredholm determinant @xmath371 in the large @xmath16 limit . it follows from , , and that in the vicinity of @xmath376 the following uniform approximation is valid : @xmath377 recall that the matrix @xmath249 is given by the formula , the matrix @xmath378 by the formulas , and . the approximation being uniform , the functions @xmath64 can be calculated from the large @xmath139 expansion of equation . expanding and in inverse powers of @xmath139 and comparing with one gets @xmath379 where @xmath380 is the third pauli matrix . substituting equations and into one gets for @xmath370 and @xmath52 @xmath381 + \mathcal o \left(x^{-1-\epsilon}\right ) \label{bpmas } \\ b_{--}&=2 \rmi\rme^{-\frac{\rmi\eta}2 } \csc\frac{\eta}2 ( \varkappa_l- \varkappa_r)[1 + \mathcal o \left(x^{-\epsilon}\right ) ] \label{bmmas}\end{aligned}\ ] ] where @xmath382 and @xmath383 are defined by and @xmath384 is defined by . to calculate the fredholm determinant @xmath371 we integrate taking into account the boundary condition : @xmath385 substituting equation into and calculating the integral in the large @xmath16 limit , one obtains @xmath386 we calculate the integration constant @xmath372 in subsection [ casy ] . in this subsection we calculate the constant @xmath372 in using the differential equation . consider equation . for @xmath23 the kernel @xmath387 vanishes and , therefore , the second term in the right hand side of vanishes . the remaining term is given by equation . with the help of the involution and the identity @xmath388 the integral in can be reduced to the integral over positive @xmath389 yielding @xmath390^{t } \sigma_2 \partial _ k \vec f(k ) . \label{detaposik}\ ] ] the large @xmath16 asymptotics of the function @xmath391 in equation is calculated as follows . use equation @xmath392 and replace @xmath141 by its large @xmath16 asymptotics obtained in section [ section : rhp0 ] . it follows from that @xmath393 where @xmath218 solves the rh problem . the formula gives the approximation to @xmath218 uniform outside an arbitrarily small vicinity of the contours @xmath365 and @xmath367 since the radius of @xmath238 was chosen initially to be less than one , the contour @xmath243 crosses the interval @xmath394.$ ] the integration variable @xmath139 in lies in this interval and , therefore , the estimate can not be applied everywhere on the integration contour . this problem is circumvented by the analytic continuation of equation from the disk @xmath238 into a bigger region @xmath395 containing the interval @xmath394,$ ] as shown in figure [ fig : omegarcontinuation ] . into the region @xmath395 containing the interval @xmath394.$],scaledwidth=50.0% ] the matrices @xmath396 and @xmath397 are given in @xmath395 by the same formulas as in @xmath398 the matrix @xmath247 by , and ; the matrix @xmath399 by . using and one gets the approximation to @xmath391 @xmath400 \label{f = sg}\ ] ] uniform for @xmath401.$ ] the function @xmath402 is defined by the equation @xmath403_+\nu_1(k ) \vec e(k ) \qquad k\in[0,1 ] . \label{g = phirnue}\ ] ] the matrix @xmath210 entering is given by equation , the function @xmath404 by and , the matrix @xmath256 by , and . with the help of the identity @xcite @xmath405 where @xmath406 one gets for @xmath407 \\ g_{-}(k)=\frac{\sqrt{\pi } \rme^{-\frac{\rmi \eta}{4}}}{\gamma\left(\frac{\eta}{2\pi}\right)\sin\frac{\eta}{2 } } \rme^{- \frac{\rmi k x}{2 } } x^{\frac{\eta}{2\pi } } ( k+1)^{\frac \eta { 2 \pi } } { } _ 1f_1\left[\frac{\eta}{2\pi } , 1 ; \rmi x ( k-1 ) \right ] . } \label{gexplicit}\ ] ] using the uniform estimate and the formulas one can derive the following estimate for @xmath408^{t } \sigma_2 \partial_k \vec g(k)[1+\mathcal{o}(x^{-1-\epsilon } ) ] . \label{detagdkg}\ ] ] performing the integral in asymptotically one gets @xmath409 where @xmath410 \label{c1}\ ] ] and @xmath411 is the digamma function , @xmath412 integrating equation over @xmath413 taking into account the initial condition and comparing the resulting expression with one gets @xmath414 - \frac{\eta^2}{2 \pi^2 } ( \ln 2 + 1 ) - \frac{1}{\pi } \int_0^{\eta } \rmd \lambda \ln\left [ \frac{\gamma\left(1+\frac{\lambda}{2\pi}\right ) } { \gamma\left(1- \frac{\lambda}{2\pi}\right ) } \right ] . \label{cdef}\ ] ] in this subsection we give the answer for the correlation functions @xmath182 and @xmath123 in the large @xmath16 limit . the correlation function @xmath182 is given by the formula . the asymptotics of @xmath52 is given by ; the asymptotics of @xmath371 by with the constant @xmath372 given by . recall that @xmath415 therefore the point @xmath101 corresponds to @xmath416 the final answer for @xmath182 is @xmath417 where the anomalous exponent @xmath5 is given by @xmath418 the phase shift @xmath419 by @xmath420 \label{x0def}\ ] ] and the constant @xmath421 by @xmath422 \right\ } \label{xidef}\ ] ] where @xmath372 is defined by equation . the relative correction to is of the order of @xmath423 note that equations and were first derived in paper @xcite . the phase shift and the constant were calculated in paper @xcite . the asymptotics of the function @xmath123 is obtained from equation by using equation . recall that in the derivation of equation we assumed that @xmath16 is positive . the result for negative @xmath16 follows from equation . in this section we find the asymptotic solution of the riemann - hilbert problem for @xmath424 we assume that @xmath187 and @xmath425 we will consider the large @xmath16 asymptotics for a fixed value of @xmath426 in subsection [ reformulation ] we reformulate the rh problem so as to make it similar to the rh problem . in subsections [ lenstsl ] and [ lenstsl2 ] we repeat the construction made for the @xmath23 case in subsections [ deformed1 ] and [ deformed2 ] , respectively . in subsection [ qrlt ] we give an explicit solution to the jump relation ( [ rhptz].b ) in a vicinity of the end points @xmath185 of the contour @xmath158 in subsection [ sast ] we perform the matching procedure analogous to that of subsection [ perturthe ] . in subsection [ approxt ] we summarize the results of this section . in this subsection we reformulate the rh problem so as to make it similar to the rh problem . represent @xmath141 as a product of two matrices @xmath427 and define @xmath428 by @xmath429 \\ 0 & 1 \end{array } \right ) \label{v}\ ] ] with @xmath295 given by equation and @xmath430 being a piecewise - constant function @xmath431 the sectors @xmath432 and @xmath433 are shown in figure [ fig : tcontour ] . for the rh problem . the sectors @xmath434 and @xmath435 are shaded in gray.,scaledwidth=50.0% ] the oriented contour @xmath436 separating the sector @xmath437 from @xmath438 and the sector @xmath439 from @xmath440 is chosen so that ( a ) it passes through the point @xmath441 ( b ) the real part of @xmath442 is positive for all @xmath443 except @xmath444 @xmath445 and @xmath446 it is easy to see that @xmath428 is analytic everywhere in the complex @xmath139-plane except the contour @xmath447 where it satisfies the jump relation @xmath448^{-1}v_{-}(k ) \qquad k\in \sigma_s \label{museq}\ ] ] with @xmath449 note that the condition implies @xmath450 with @xmath428 and @xmath436 defined above , one gets the following rh problem for @xmath451 @xmath452 where the contours @xmath161 and @xmath436 are shown in figure [ fig : tcontour ] . since @xmath141 is analytic across @xmath447 the matrix @xmath453 should satisfy and , therefore , is given by . the matrix @xmath454 can be obtained comparing the jump relations ( [ rhptime].b ) and ( [ rhptz].b ) @xmath455^{-1 } \qquad k\in\sigma_0 . \label{muv}\ ] ] representing in the form @xmath456 with @xmath457 given by and one gets @xmath458 we see that the matrix @xmath454 is different from the matrix @xmath459 defined by , only in that @xmath460 in the latter is replaced by @xmath461 in the former . the matrix @xmath454 obeys the involution @xmath462^{-1 } \label{mu0involution}\ ] ] with the matrix @xmath217 defined by equation . this involution is a natural generalization of the involution . in this subsection an rh problem equivalent to the rh problem is formulated on the conjugation contour @xmath464 the procedure will resemble that of subsection [ deformed1 ] . represent @xmath451 as a product of two matrices @xmath465 and define @xmath200 by the formula @xmath466^{-1 } & \qquad k\in\omega_{d } \end{array } \right . .\label{ldeft}\ ] ] the lens - shaped contour @xmath202 is the same as in subsection [ deformed1 ] . it is shown in figure [ fig : tlens ] . and the contour @xmath467,scaledwidth=50.0% ] the matrices @xmath468 and @xmath469 are defined as @xmath470 for the conjugation matrix the following representation can be written @xmath471 where the matrix @xmath472 coincides with the matrix @xmath213 defined by equation . note that @xmath473^{-1}\qquad p\mu_2p^{-1}=\mu_2^{-1 } \label{mu13inv}\ ] ] where the matrix @xmath217 is defined by . it follows from equations , , and that @xmath218 solves the following rh problem @xmath474 where the contours @xmath475 are shown in figure [ fig : tlens ] . we will calculate the large @xmath16 asymptotics of @xmath220 the asymptotics of @xmath451 will then follow from . in this subsection we present the scheme of the analysis of the rh problem in the large @xmath16 limit . the scheme is similar to the one given in subsection [ deformed2 ] . like the @xmath23 case , the jump matrix @xmath468 ( respectively , @xmath469 ) goes to the identity matrix , as @xmath234 everywhere on the contour @xmath221 ( respectively , @xmath222 ) except at the points @xmath223 the jump matrix @xmath453 goes to the identity matrix everywhere on @xmath436 except at the point @xmath476 therefore , to construct a uniform approximation to @xmath218 we use the same scheme as in subsection [ deformed2 ] . introduce three disks @xmath344 @xmath242 and @xmath477 as shown in figure [ fig : tsplit ] . @xmath242 and @xmath477 are shaded in gray.,scaledwidth=50.0% ] denote the domain @xmath478 as @xmath241 represent the solution @xmath218 of the rh problem as a product of three matrices @xmath479 the matrix @xmath227 is given by the formula @xmath480 the matrix @xmath481 is given by equation . the matrix @xmath482 is defined in @xmath477 and satisfies @xmath483_+= \left[q_s(k)\right]_{-}\mu_s(k ) \qquad k \in \sigma_s\cap\mathcal d_s .\label{qjumpts}\ ] ] we choose the following solution of the jump relation : @xmath484 where the integral runs along the contour @xmath436 shown in figure [ fig : tsplit ] . the matrices @xmath247 and @xmath248 are defined in the disks @xmath238 and @xmath260 respectively , and satisfy there the jump relations @xmath258_+= \left[q_r(k)\right]_{-}\mu_i(k ) \qquad k \in \sigma_i\cap\mathcal d_r \qquad i=1,2,3 \label{qjumptr}\ ] ] and @xmath262_+= \left[q_l(k)\right]_{-}\mu_i(k ) \qquad k \in \sigma_i\cap\mathcal d_l \qquad i=1,2,3 . \label{qjumptl}\ ] ] we give solutions to the jump relations and in subsection [ qrlt ] . the matrix @xmath236 is defined as a solution of the rh problem @xmath485 with the clockwise oriented conjugation contours @xmath486 shown in figure [ fig : tsplit ] and the conjugation matrices @xmath487 defined by @xmath488^{-1 } \qquad k\in \partial \mathcal d_\alpha \qquad \alpha = r , l , s . \label{thetarlsdef}\ ] ] we solve the rh problem in the large @xmath16 limit in subsection [ sast ] . the matrix @xmath272 in the decomposition is constructed in complete analogy with the matrix @xmath272 considered in subsection [ deformed2 ] . in this subsection we solve explicitly the jump relations and by mapping them on the jump relations and , solved in subsection [ explicit ] . introduce the ` light cone ' variables @xmath489 and @xmath490 @xmath491 consider the jump relation and make the following conformal map @xmath492 of the disk @xmath238 in the complex @xmath139-plane onto a vicinity @xmath493 of the point @xmath494 in the @xmath495-plane , as shown in figure [ fig : cmap ] . the disk @xmath238 and its image @xmath496 are shaded in gray . the conjugation contours @xmath221 and @xmath222 are chosen so that their images @xmath497 and @xmath498 are parallel to the imaginary axis.,scaledwidth=60.0% ] introducing a @xmath139-independent matrix @xmath14 by the formula @xmath499 one can easily check that @xmath500 t \qquad k\in\mathcal d_r \qquad i=1,2,3 . \label{tmut}\ ] ] here the matrices @xmath501 @xmath469 and @xmath502 are defined by the formulas , and , respectively ; the matrices @xmath503 @xmath211 and @xmath213 are defined by the formulas , and , respectively . choose the shape of the contours @xmath221 and @xmath222 in the @xmath139-plane so that their images @xmath504 and @xmath505 in the @xmath495-plane are parallel to the imaginary axis , as shown in figure [ fig : cmap ] . write equation with @xmath139 replaced by @xmath495 and @xmath16 replaced by @xmath506 @xmath507_{+}=\left[\phi_r(\lambda_r;x_r)\right]_{- } \nu_i(\lambda_r;x_r ) \qquad \lambda_r\in \sigma^\prime_i \qquad i=1,2,3 \label{phijumpt}\ ] ] where @xmath508 is defined by . by virtue of the jump relation is equivalent to @xmath509t\right\}_{+}= \left\{\phi_r[\lambda_r(k);x_r]t\right\}_{-}\mu_i(k ) \qquad k\in\sigma_i \qquad i=1,2,3.\ ] ] one sees that the matrix @xmath510t$ ] solves the jump relation in the disk @xmath278 now we are in a position to write down an ansatz for @xmath511 @xmath512 t \label{qrt}\ ] ] where @xmath513^{-\frac\eta{2\pi } } & 0 \\ 0 & [ \lambda_r(k)-1]^{\frac\eta{2\pi } } \end{array } \right ) t^{-1}. \label{ertdef}\ ] ] with this choice of @xmath514 the matrix @xmath256 goes to @xmath515 as @xmath234 for any @xmath516 taking into account the involution choose the following solution to the jump relation @xmath517 where @xmath247 is given by formulas and . in this subsection we solve the rh problem in the large @xmath16 limit . the procedure will resemble that of subsection [ perturthe ] . consider the conjugation matrices @xmath263 and @xmath264 defined by equation . they satisfy the involution @xmath518 as can be shown using the involutions and . substituting equations and into equation and using the results of subsection [ explicit ] one gets the following approximation of the matrix @xmath263 by a matrix @xmath519 @xmath520 \label{thetarassl}\ ] ] uniform for @xmath309 here @xmath521 the matrix @xmath522 is given by @xmath523^{-\frac{\eta}{\pi } } \left(\frac{2 k_s } { 2 k_s - k-1}\right)^{1+\frac{\eta}{\pi } } \\ b_r \left[x(k+1 ) \right]^{\frac{\eta}{\pi}}\left(\frac{2 k_s } { 2k_s - k-1}\right)^{1-\frac{\eta}{\pi } } & \rmi \left(\frac{\eta } { 2\pi}\right)^2 \frac{2 k_s}{2 k_s - k-1 } \end{array } \right ) \label{upsilonrt}\ ] ] where @xmath524 it follows from the involution that the matrix @xmath264 is approximated by a matrix @xmath312 @xmath525 \label{thetalassl}\ ] ] uniformly for @xmath314 where @xmath526 and @xmath527 the explicit expression for @xmath528 reads @xmath529^{\frac{\eta}{\pi } } \left(\frac{2 k_s } { 2k_s - k+1}\right)^{1-\frac{\eta}{\pi } } \\ b_l \left[x ( 1-k ) \right]^{-\frac{\eta}{\pi } } \left(\frac{2 k_s } { 2 k_s - k+1}\right)^{1+\frac{\eta}{\pi } } & \rmi \left(\frac{\eta } { 2\pi}\right)^2 \frac{2 k_s}{2 k_s - k+1 } \end{array } \right ) \label{upsilonlt}\end{aligned}\ ] ] where @xmath530 to calculate the conjugation matrix @xmath531 in the large @xmath16 limit use the large @xmath16 asymptotics of the integral in @xmath532 where @xmath533 is defined by equation . note that the leading term in is of the order of @xmath534 substituting equation into equation and using equation one gets @xmath535 \label{thetastilde}\ ] ] uniformly for @xmath536 where @xmath537 and @xmath538 consider the rh problem @xmath539 with the jump matrices @xmath540 @xmath312 and @xmath541 defined by , and , respectively . in complete analogy with equation the solution @xmath319 of the rh problem approximates the solution @xmath231 of the rh problem @xmath542 \label{ststilde}\ ] ] uniformly outside a vicinity of the conjugation contours @xmath543 @xmath244 and @xmath544 to solve the rh problem represent @xmath319 as a product of two matrices @xmath545 where the matrix @xmath546 is the solution to the rh problem @xmath547 with the jump matrices @xmath307 and @xmath312 given by and , respectively . comparing and one sees that the matrix @xmath548 solves the following rh problem @xmath549 where the jump matrix @xmath541 is defined by equation . let us solve the rh problem first . since the jump matrices and have the same analytic properties in the complex @xmath139-plane as the matrices and , the rh problem can be solved similarly to the rh problem . introduce the following notation for the analytic branches of @xmath546 : @xmath550 using the same arguments as in deriving equation from one gets @xmath551 where the matrices @xmath352 and @xmath334 do not depend on @xmath552 dropping terms of order @xmath368 and higher , we find @xmath553 and @xmath554 here @xmath555 and @xmath384 is defined by equation . the matrices @xmath556 and @xmath557 are found from ( [ rhpnt].b ) @xmath558^{-1}\qquad n_l(k)=n_{\infty}(k)[\tilde\theta_l(k)]^{-1}. \label{nrl}\ ] ] next , solve the rh problem . use the same method as was exploited in solving the rh problems and . denote the analytic branches of @xmath548 by @xmath559 the jump matrix @xmath560 in ( [ rhpmt].b ) has a simple pole at @xmath476 therefore @xmath561 where the matrix @xmath562 does not depend on @xmath552 choosing @xmath563^{-1 } \label{ast}\ ] ] one solves . this can be checked directly . like the @xmath23 case , the matrix @xmath272 in the decomposition does not contribute to the asymptotic solution of the rh problem to the order we are interested in . substituting into the decomposition one gets the estimate @xmath366 \label{schit}\ ] ] uniform outside an arbitrarily small vicinity of the contours @xmath564 and @xmath565 using and one gets the approximation to @xmath141 up to the order of @xmath566 uniform outside this vicinity . this completes the solution to the rh problem in the large @xmath16 limit . in this section we derive the asymptotic expressions for the correlation functions @xmath21 and @xmath567 in the space - like region @xmath568 the asymptotic expressions are derived assuming that @xmath569 at a fixed value of the parameter @xmath441 defined in . the explicit expressions are written assuming @xmath187 and @xmath570 all other cases follow from the relations and . all the calculations will be similar to those for the @xmath23 case . in subsection [ basymptt ] we calculate the functions @xmath64 and @xmath65 from the large @xmath139 expansion of @xmath369 having these functions we calculate the fredholm determinant @xmath371 in the large @xmath16 limit , see equation . the constant @xmath372 entering is calculated in subsection [ casyt ] . this constant is found to be the same as in the @xmath23 case . we give the answer for the correlation functions @xmath21 and @xmath567 in subsection [ answerx ] . in this subsection we use the results of section [ section : rhptime ] on the asymptotic solution of the rh problem to calculate the functions @xmath571 @xmath65 and the fredholm determinant @xmath371 in the large @xmath16 limit . it follows from , , , , , and that in the vicinity of @xmath376 the following uniform approximation is valid : @xmath572 recall that the matrix @xmath573 is given by equation , the matrix @xmath574 by equation , the matrix @xmath481 by , the matrix @xmath575 by . the approximation being uniform , the functions @xmath64 and @xmath65 can be calculated in the large @xmath16 limit from the large @xmath139 expansion of equation . in particular , @xmath576\left[1+\mathcal o(x^{-\epsilon})\right ] . \label{bmmt}\ ] ] the function @xmath577 entering has the form @xmath578\right . \nonumber\\ \lo-\left.2\sin^2\frac\eta2\left(\frac{k_s-1}{k_s+1}\right)^{\frac\eta\pi}g_0 \right\}\left [ 1+\mathcal o(x^{-\epsilon})\right].\end{aligned}\ ] ] the expressions for the other potentials are quite bulky , so we write down the differential equations and in the large @xmath16 limit omitting intermediate calculations @xmath579 and @xmath580 where @xmath581 and @xmath384 is given by equation . integrating equations and asymptotically one gets @xmath582 + c(\eta ) + \mathcal o\left(x^{-\epsilon}\right ) . \label{logdett}\ ] ] note that @xmath583 we calculate the integration constant @xmath372 in subsection [ casyt ] . it will be the same as for the @xmath23 case . in this subsection we calculate the constant @xmath372 in using the differential equation . the calculation will resemble that of subsection [ casy ] . consider the first term in the right hand side of equation . split the integral in equation in two parts and define @xmath584^{t } \sigma_2\partial_k \vec f(k ) \label{jrdef } \\ j_l=\frac{1}{1-\rme^{-\rmi \eta}}\int_{-1}^{0 } \rmd k [ \vec f(k)]^t \sigma_2\partial_k \vec f(k ) . \label{jldef}\end{aligned}\ ] ] consider @xmath585 first . the large @xmath16 asymptotics of the function @xmath391 in equation is calculated as follows . use equation @xmath586 substituting and into and using and one gets @xmath587 where @xmath588 the matrix @xmath451 solves the rh problem and the functions @xmath589 and @xmath442 are defined by equation . it follows from and that @xmath590 where @xmath218 solves the rh problem . substituting equation into and performing the analytic continuation of the formula in complete analogy with the analytic continuation of the formula discussed in subsection [ casy ] and shown in figure [ fig : omegarcontinuation ] we obtain the approximation to @xmath591 @xmath592 \label{fas}\ ] ] uniform for @xmath401.$ ] the matrices @xmath573 and @xmath593 are defined in subsection [ sast ] , the function @xmath402 is given by the formula @xmath594_{+}\mu_1(k)\vec e_0(k)\qquad k\in [ 0,1 ] . \label{grdef}\ ] ] substituting into the expression for @xmath595 defined by equations , and , and using the identity one gets @xmath596 } { \left[x_r ( k+1)\right]^{\frac{\eta } { 2 \pi } } } \left(\frac{k-1}{\lambda_r-1 } \right)^\frac{\eta}{2 \pi } \\ g_{-}^r(k;x , t)= \frac{\sqrt{\pi}\rme^{-\frac{\rmi \eta}{4 } } \rme^{{\tau(k)}/{2 } } } { \gamma\left(\frac{\eta}{2\pi}\right)\sin\frac{\eta}{2 } } \frac { { } _ 1f_1\left[\frac{\eta}{2\pi } , 1 ; \rmi x_r ( \lambda_r-1 ) \right]}{\left [ x_r ( k+1)\right]^{-\frac \eta { 2 \pi } } } \left(\frac{k-1}{\lambda_r-1 } \right)^{-\frac{\eta}{2 \pi } } } \label{gexplicitt}\ ] ] where @xmath597 is defined by equation . using the uniform estimate and equations , - one can derive the following estimate for @xmath598^t \sigma_2 \partial_k \vec g_r(k)[1 + \mathcal o ( x^{-1-\epsilon } ) ] . \label{jras}\ ] ] performing the integral in asymptotically one gets @xmath599 where @xmath600 is defined by equation . the large @xmath16 asymptotics of @xmath601 is calculated similarly , yielding @xmath602 we have calculated the large @xmath16 asymptotics of the first term in the right hand side of equation . by analysis of equation one can show that the second term in the right hand side of equation is of the order of @xmath603 therefore , the large @xmath16 asymptotics of is @xmath604 integrating equation over @xmath413 taking into account the initial condition and comparing the resulting expression with one finds that @xmath372 is given by the same expression as in the @xmath23 case . in this subsection we write down the asymptotic expressions for the correlation functions @xmath21 and @xmath567 in the space - like region @xmath568 the asymptotic expressions are given assuming that @xmath569 at a fixed value of the parameter @xmath441 defined in . the explicit expressions are written assuming @xmath187 and @xmath570 all other cases follow from the relations and . the correlation function @xmath21 is given by the formula . the asymptotics of @xmath52 is given by ; the asymptotics of @xmath371 by with the constant @xmath372 given by . recall that @xmath415 therefore the point @xmath101 corresponds to @xmath416 the leading contribution to the asymptotics of @xmath21 comes from the first term in the right hand side of equation , yielding @xmath605 \nonumber \\ \lo- \frac{\xi}{2\rmi}\frac{\rme^{-x\ln2/\pi } } { ( x-2t)^{2\delta}(x+2t)^{2\bar\delta } } \exp\left[-\rmi(x - x_0)+\frac{\rmi\ln2}{\pi}\ln(x-2 t ) \right ] \label{gholespacelike}\end{aligned}\ ] ] where the normalization constant @xmath421 is defined by equation and the phase shift @xmath419 by equation . the anomalous exponents are given by @xmath606 the relative correction to is of the order of @xmath423 show that the second term in the right hand side of equation does not contribute to the asymptotics . by virtue of , the determinant @xmath371 is of the order of @xmath607 on the integration contour @xmath608 where @xmath98 is the circle @xmath609 figure [ fig : zintegral ] . therefore , for @xmath610 and for sufficiently large @xmath16 the contribution of the second term is negligible . the correlation function @xmath567 is calculated similarly , yielding @xmath611 where @xmath21 is given by equation , the function @xmath612 is defined by equation and @xmath613 defined by . compare the result with the general relation . one can see that the last term in the right hand side of equation corresponds to the averaged anticommutator of fermion fields in equation . it contains a rapidly oscillating factor @xmath614 this means that although formally present in the long distance expansion of the correlation function @xmath29 this term is irrelevant at energies smaller than the chemical potential . in this section we find the asymptotic solution of the riemann - hilbert problem for @xmath616 we assume that @xmath187 and @xmath425 we will consider the large @xmath17 asymptotics at a fixed value of the parameter @xmath441 defined in . in subsection [ reformulationtl ] we reformulate the rh problem so as to make it similar to the rh problem . in subsection 7.2 we repeat the construction made for the @xmath23 case in subsections [ deformed1 ] and [ deformed2 ] . in subsection 7.3 we give an explicit solution to the jump relation ( 7.7.b ) in a vicinity of the points @xmath617 and @xmath476 in subsection 7.4 we perform the matching procedure analogous to the one of subsection [ perturthe ] . in this subsection we reformulate the rh problem so as to make use of the results of subsections [ lenstsl2 ] and [ qrlt ] . consider a contour shown in figure [ fig : tlikecontour ] . for the rh problem . the contour @xmath221 consists of two semi - infinite lines parallel to the imaginary axis.,scaledwidth=40.0% ] this contour divides the complex @xmath139-plane into four regions , denoted as @xmath432 through @xmath618 represent the solution @xmath141 of the rh problem as a product of two matrices @xmath619 where @xmath620 \\ 0&1 \end{array } \right ) . \label{tlvdef}\ ] ] the piecewise constant functions @xmath621 and @xmath622 are defined by @xmath623 and @xmath624 the contour @xmath221 is chosen so that the real part of @xmath442 is positive for all @xmath625 except @xmath185 and @xmath626 note that the condition implies @xmath627 using equations , and , and the property one gets the following rh problem for @xmath451 @xmath628 where the jump matrices @xmath501 @xmath502 and @xmath469 are given by equations , and , respectively . the matrix @xmath629 is defined as @xmath630 in this subsection we sketch the scheme of the analysis of the rh problem in the large @xmath17 limit . this scheme is similar to the one given in subsection [ lenstsl2 ] . the matrices @xmath501 @xmath469 and @xmath629 converge to the identity matrix , as @xmath631 everywhere on their conjugation contours except at the points @xmath617 and @xmath476 introduce three disks @xmath260 @xmath238 and @xmath477 as shown in figure [ fig : tlksplit ] . @xmath242 and @xmath477 are shaded in gray.,scaledwidth=50.0% ] denote the domain @xmath632 as @xmath633 represent the solution @xmath451 of the rh problem as a product of three matrices @xmath634 here the matrix @xmath227 is defined by @xmath635 the matrix @xmath636 is given by equation . the matrices @xmath247 and @xmath248 are defined in @xmath238 and @xmath260 respectively , and satisfy there the jump relations @xmath258_{+}=\left[q_r(k)\right]_{- } \mu_i(k ) \qquad k\in \sigma_i\cap \mathcal d_r \qquad i = 1 , 2 , 4 \label{qrttl}\ ] ] and @xmath262_{+}=\left[q_l(k)\right]_{- } \mu_i(k ) \qquad k\in \sigma_i\cap \mathcal d_l \qquad i= 1 , 2 , 3 \label{qlttl}.\ ] ] the matrix @xmath637 is defined in @xmath477 and satisfies @xmath483_{+}=\left[q_s(k)\right]_{- } \mu_i(k ) \qquad k\in \sigma_i\cap \mathcal d_s \qquad i = 2 , 3 , 4 . \label{qalphatl}\ ] ] we give solutions to the jump relations , and in subsection [ exacttl ] . the matrix @xmath231 in the decomposition is the solution to the rh problem with the conjugation matrices @xmath487 defined by equation . the matrices @xmath638 @xmath248 and @xmath482 in solve the jump relations , and , respectively . like the spacelike case , the matrix @xmath272 can be replaced by the identity matrix . in this subsection we solve explicitly the jump relations , and . we use the results of subsection [ qrlt ] . the jump relation coincides with the jump relation . therefore one can use the solution to this relation . to obtain a solution to the jump relation consider the conjugation matrices @xmath501 @xmath502 and @xmath629 defined on the contours @xmath639 @xmath229 and @xmath640 shown in figure [ fig : tlksplit ] . these matrices satisfy the following involutions @xmath641 where @xmath642 is a @xmath139-independent matrix defined by @xmath643 denote the solution to the jump relation by @xmath644 comparing the conjugation contours in the disks @xmath238 shown in figures [ fig : tsplit ] and [ fig : tlksplit ] and using the involutions a solution @xmath247 to the jump relation can be found from @xmath645 @xmath646 finally , write down a solution to the jump relation : @xmath647 where @xmath648 and the integral runs along the contour @xmath436 which consists of the part of the contour @xmath222 lying outside @xmath242 and the part of the contour @xmath649 lying outside @xmath650 see figure [ fig : tlksplit ] . in this subsection we solve the rh problem in the large @xmath17 limit . the procedure will resemble that of subsection [ sast ] . the conjugation matrix @xmath651 is approximated by a matrix @xmath652 @xmath653 uniformly for @xmath654 where @xmath655 is defined by equations and . the conjugation matrix @xmath263 is approximated by a matrix @xmath519 @xmath656 uniformly for @xmath657 where the matrix @xmath519 is given by equation and @xmath658 is defined as @xmath659 here we use the notation @xmath660 for the matrix given by equation . the matrix @xmath642 is defined by equation . the conjugation matrix @xmath531 is approximated by a matrix @xmath541 @xmath661\ ] ] uniformly for @xmath662 the matrix @xmath541 is given by equation where @xmath663 is calculated using , and @xmath664 the asymptotic estimate for the matrix @xmath236 is given by equation where the matrix @xmath358 is the solution of the rh problem with the matrices @xmath665 defined in the paragraph above . like the spacelike case , solve the rh problem using the decomposition . the matrix @xmath574 entering the definition is given by equation with matrices @xmath352 and @xmath334 given by @xmath666 and @xmath667 here @xmath668 and @xmath384 is defined by equation . the matrix @xmath669 in the decomposition is given by equation with @xmath562 defined by equation . in this section we derive the asymptotics of the correlation functions @xmath567 and @xmath21 in the time - like region @xmath616 the asymptotic expressions will be given assuming that @xmath671 at a fixed value of the parameter @xmath441 defined in equation . it will also be assumed that @xmath187 and @xmath672 ; all other cases follow from the relations and . the calculations in this section are similar to those given in sections [ zerotimeg ] and [ spacelikeg ] . we will therefore omit most technical details already explained in those sections and focus on the particulars of the time - like case . in subsection [ basympttimelike ] we give the the large @xmath17 asymptotics of @xmath94 @xmath53 and @xmath673 in subsection [ answert ] we perform the contour integral entering representations and and obtain the asymptotic expressions for the correlation functions @xmath567 and @xmath674 the asymptotic expressions for the functions @xmath52 and @xmath53 are calculated similarly to subsection [ basymptt ] yielding @xmath676\right\}\left[1+\mathcal o(t^{-\epsilon})\right ] \label{bmmtl}\end{aligned}\ ] ] and @xmath677\left[1 + \mathcal o(t^{-\epsilon})\right ] \label{bpptl}\ ] ] where @xmath678 and @xmath679 are given by equaiton . the large @xmath17 asymptotics of the fredholm determinant @xmath680 is @xmath681 + \tilde c(\eta ) + \mathcal o\left(t^{-\epsilon}\right ) . \label{logdett2 } \label{logdettl}\ ] ] the constant @xmath682 can , in principle , be calculated in the same manner as the constant @xmath372 for the space - like region . there is , however , a difference which did not allow us to obtain a closed analytical expression for @xmath682 so far . unlike the space - like case , the second term in the right hand side of equation is not small as a function of the asymptotic parameter @xmath17 . therefore , the calculation of @xmath682 requires the asymptotic analysis of the expression , which is straightforward but cumbersome . this is in contrast with the high temperature case , where the calculation of such a constant was done using an additional differential equation involving the functions @xmath64 and @xmath65 only @xcite . such an equation does not exist in the zero temperature case , considered here . in this subsection we write down the asymptotic expressions for the correlation functions @xmath21 and @xmath567 in the time - like region @xmath616 the asymptotic expressions are given assuming that @xmath569 at a fixed value of the parameter @xmath441 defined in . the explicit expressions are written assuming @xmath187 and @xmath570 all other cases follow from the relations and . consider the representations and . applying the same arguments as given in subsection one can show that the contributions from the integrals along the contour @xmath98 in and can be neglected in the large @xmath17 limit . substituting the results , and in equations and we find @xmath684 \nonumber \\ \lo+ \frac{\tilde \xi}{4\rmi}\frac{\rme^{-x\ln2/\pi } } { ( 2t - x)^{2\delta}(2t+x)^{2\bar\delta } } \exp\left[-\rmi(x - x_0)+\frac{\rmi\ln2}{\pi}\ln(2t - x ) \right ] \nonumber \\ \lo+ \frac{\rme^{-\rmi t}}{2}g_0^*(x , t ) \frac{\rme^{-x\ln2/\pi}\rme^{c(\rmi\ln2 ) } } { ( 4t^2-x^2)^{2\bar\delta } } \left(\frac{2t - x}{2t+x}\right)^{-\rmi\ln2/\pi } \label{gholetimelike}\end{aligned}\ ] ] and @xmath685 \nonumber \\ \lo- \frac{\tilde \xi}{2\rmi}\frac{\rme^{-x\ln2/\pi } } { ( 2t+x)^{2\delta}(2t - x)^{2\bar\delta } } \exp\left[-\rmi(x - x_0)+\frac{\rmi\ln2}{\pi}\ln(2t+x ) \right ] , \label{gelectrontimelike}\end{aligned}\ ] ] where the dimensions @xmath686 and @xmath687 are given by equation , the phase shift @xmath419 by equation . the normalization constant @xmath688 can be obtained from the constant @xmath421 given in equation by replacing the constant @xmath372 with @xmath689 in this section we consider the special case of @xmath690 the large @xmath17 asymptotics of the correlation functions @xmath691 and @xmath692 are given assuming that @xmath672 ; the case of negative @xmath17 follows from the relation . in the derivation of the asymptotical expressions we the use the results of section [ answertl ] . for @xmath25 it is convenient to calculate the large @xmath17 asymptotics of the integrals ( 2.6 ) and ( 2.7 ) without the deformation of the integration contour leading to ( 2.32 ) and ( 2.33 ) . substituting asymptotic formulae ( 8.2 ) and ( 8.3 ) in equation ( 2.7 ) we arrive at the expression @xmath693\ln t \right \ } \nonumber \\ \lo+ \int_{-\pi}^{\pi } \rmd \eta \frac{f(\eta)}{1-\cos\eta } \frac{\rmi 4^{-1-\frac{\eta}{\pi}-\left(\frac\eta{2\pi}\right)^2}\rme^{\tilde c(\eta ) } } { \gamma^2(-\frac{\eta}{2 \pi } ) \rme^{\rmi \frac\eta2 } } \exp \left \{\left[-1-\frac{\eta}{\pi}-2 \left(\frac{\eta}{2\pi}\right)^2\right]\ln t \right\}. \label{electronsaddlepoit}\end{aligned}\ ] ] for large @xmath17 the integrals on the right hand side of ( 9.1 ) can be evaluated in the saddle point approximation with @xmath694 playing the role of the asymptotic parameter . the relative correction to the integrands in equation ( 9.1 ) is of the order of @xmath695 at the saddle points , @xmath696 one has @xmath697 leading to an unknown constant factor . this factor can , in principle , be calculated using the approach presented in this paper . the resulting expression for @xmath29 reads @xmath698.\ ] ] the integral ( 2.6 ) is evaluated similarly , yielding @xmath699 with the relative correction of the order of @xmath700 m.b . zvonarev s work was supported by the danish technical research council via the framework programme on superconductivity . a partial support from the russian foundation for basic research under grant no . 01 - 01 - 01045 and from the programme `` mathematical methods in nonlinear dynamics '' of russian academy of sciences are also acknowledged . 999 cheianov vadim v and zvonarev m b 2003 non - unitary spin - charge separation in one - dimensional fermion gas _ preprint _ cond - mat/0308470

we calculate the long time and distance asymptotics of the one - particle correlation functions in the model of impenetrable spin @xmath0 fermions in 1 + 1 dimensions . we consider the spin disordered zero temperature regime , which occurs when the limit @xmath1 is taken at a positive chemical potential . the asymptotic expressions are found from the asymptotic solution of the matrix riemann - hilbert problem related to the determinant representation of the correlation functions .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Free and Independent Cuba Assistance Act of 1993''. SEC. 2. FINDINGS. The Congress makes the following findings: (1) The economy of Cuba has experienced a decline of approximately 45 percent in the last 3 years, on account of the end of its subsidization by the former Soviet Union, the extreme decline in trade between Cuba and the countries of the former Soviet Bloc, and the policy of the Russian Government and the countries of the former Soviet Bloc to conduct economic relations with Cuba on strictly commercial terms. (2) At the same time, the welfare and health of the Cuban people has substantially deteriorated, and continues to deteriorate, as a result of this economic decline and the refusal of the Castro regime to adopt any economic or political reforms that would lead to democracy, a market economy, or an economic recovery. (3) As long as no such economic or political reforms are adopted by the Cuban Government, the economic condition of the country and the welfare of the Cuban people will not improve in any significant way. (4) The Castro regime has made it abundantly clear that it will not engage in any substantive economic or political reforms that would lead to democracy, a market economy, or an economic recovery. SEC. 3. POLICY TOWARD A TRANSITION GOVERNMENT AND A DEMOCRATIC GOVERNMENT IN CUBA. It is the policy of the United States-- (1) to support the self-determination of the Cuban people; (2) to recognize that the self-determination of the Cuban people is a sovereign and national right of the citizens of Cuba which must be exercised free of interference by the government of any other country; (3) to encourage the Cuban people to empower themselves with a government which reflects the self-determination of the Cuban people; (4) to recognize the potential for a difficult transition from the current regime in Cuba that may result from the initiatives taken by the Cuban people for self-determination in response to the intransigence of the Castro regime in not allowing any substantive political or economic reforms, and to be prepared to provide the Cuban people with humanitarian, developmental, and other economic assistance; (5) in solidarity with the Cuban people, to provide emergency relief assistance to a transition government in Cuba, and long term assistance to a democratic government in Cuba, governments that result from an expression of the self- determination of the Cuban people; (6) that such assistance is intended to facilitate a peaceful transition to democracy in Cuba and the consolidation of democracy in Cuba; (7) that such assistance be delivered to the Cuban people through a transition government in Cuba, through a democratic government in Cuba, or through United States, international, or indigenous nongovernmental organizations; (8) to encourage other countries to provide similar assistance, and work cooperatively with such countries to coordinate such assistance; (9) to ensure that emergency relief is rapidly implemented and distributed to the people of Cuba upon the institution of a transition government in Cuba; (10) not to provide favorable treatment or influence on behalf of any individual or entity in the promotion of the choice by the Cuban people of their future government; (11) to assist a transition government in Cuba and a democratic government in Cuba to prepare the Cuban military forces for a new role in a democracy; (12) to be prepared to enter into negotiations with a democratic government in Cuba either to return the United States Naval Base at Guantanamo to Cuba or to renegotiate the present agreement under mutually agreeable terms; (13) to lift the economic embargo on Cuba when the President determines that there exists a democratic government in Cuba; and (14) to assist a democratic government in Cuba to strengthen and stabilize its national currency. SEC. 4. AUTHORIZATION OF ASSISTANCE TO THE CUBAN PEOPLE. (a) Plan for Assistance.-- (1) Development of plan.--The President shall develop a plan for providing, at such time as the President determines that a transition government in Cuba is in power, economic assistance to the people of Cuba while such government, and a democratic government in Cuba, are in power. (2) Types of assistance.--Assistance under the plan developed under paragraph (1) shall include the following: (A) Assistance under the plan to a transition government in Cuba shall be limited to-- (i) such food, medicine, medical supplies and equipment, and assistance to meet emergency energy needs, as is necessary to meet the basic human needs of the Cuban people; and (ii) assistance described in subparagraph (C). (B) Assistance under the plan to a democratic government in Cuba shall consist of additional economic assistance and assistance described in subparagraph (C). Such economic assistance may include-- (i) assistance under chapter 1 of part I (relating to development assistance), and chapter 4 of part II (relating to the economic support fund), of the Foreign Assistance Act of 1961; (ii) assistance under the Agricultural Trade Development and Assistance Act of 1954; (iii) financing, guarantees, and other forms of assistance provided by the Export- Import Bank of the United States; (iv) financial support provided by the Overseas Private Investment Corporation for investment projects in Cuba; (v) assistance provided by the Trade and Development Agency; (vi) Peace Corps programs; (vii) relief of Cuba's external debt; and (viii) other appropriate assistance to carry out the purposes of this Act. (C) Assistance under the plan to a transition government in Cuba and to a democratic government in Cuba shall also include assistance in preparing the Cuban military forces to adjust to a new role in a democracy and civilian life, which may include assistance for housing, educational, and training programs. (b) Strategy for Distribution.--The plan developed under subsection (a) shall include a strategy for distributing assistance under the plan. (c) Distribution.--The plan developed under subsection (a) shall authorize assistance under the plan to be provided through United States, international, and indigenous nongovernmental organizations and private voluntary organizations, including humanitarian, educational, and labor organizations. (d) International Efforts.--The President shall take the necessary steps to obtain the agreement of other countries and of international financial institutions to provide to a transition government in Cuba, and to a democratic government in Cuba, assistance comparable to that provided by the United States under this Act, and to work with such countries and institutions to coordinate all such assistance programs. (e) Caribbean Basin Initiative.--The President shall determine, as part of the assistance plan developed under subsection (a), whether or not to designate Cuba as a beneficiary country under section 212 of the Caribbean Basin Economic Recovery Act. (f) Trade Agreements.--Upon the enactment of legislation implementing a free trade agreement between the United States and any other country or countries (except Cuba) in the Western Hemisphere, the President-- (1) shall take the necessary steps to enter into a framework agreement with a transition government in Cuba providing for trade with and investment in Cuba; and (2) may thereafter enter into negotiations with a democratic government in Cuba to conclude a free trade agreement between the United States and Cuba. (g) Communication With the Cuban People.--The President shall take the necessary steps to communicate to the Cuban people the plan for assistance developed under this section. (h) Report to Congress.--The President shall transmit to the Congress, not later than 180 days after the date of the enactment of this Act, a report describing in detail the plan developed under this section. SEC. 5. COORDINATION OF ASSISTANCE PROGRAM; IMPLEMENTATION AND REPORTS TO CONGRESS; REPROGRAMMING. (a) Coordinating Official.--The Assistant Secretary of State for Inter-American Affairs shall be responsible for-- (1) implementing the strategy for distributing assistance under the plan developed under section 4(a); (2) ensuring the speedy and efficient distribution of such assistance; and (3) ensuring coordination among, and appropriate oversight by, the agencies of the United States that provide assistance under the plan, including resolving any disputes among such agencies. (b) Implementation of Plan; Reports to Congress.-- (1) Implementation with respect to transition government.-- Upon making a determination that a transition government in Cuba is in power, the President shall transmit that determination to the Congress and shall commence the delivery and distribution of assistance to such transition government under the plan developed under section 4(a). (2) Reports to congress.--Not later than 15 days after making the determination referred to in paragraph (1), and not later 90 days after making that determination, the President shall transmit to the Congress a report setting forth the strategy for providing assistance described in section 4(a)(2)(A) and (C) to the transition government in Cuba under the plan of assistance developed under section 4(a), the types of such assistance, and the extent to which such assistance has been distributed in accordance with the plan. (3) Implementation with respect to democratic government.-- The President shall, upon determining that a democratic government in Cuba is in power, submit that determination to the Congress and shall commence the delivery and distribution of assistance to such democratic government under the plan developed under section 4(a). (4) Annual reports to congress.--Not later than 60 days after the end of each fiscal year, the President shall transmit to the Congress a report on the assistance provided under the plan developed under section 4(a), including a description of each type of assistance, the amounts expended for such assistance, and a description of the assistance to be provided under the plan in the current fiscal year. (c) Reprogramming.--Any changes in the assistance to be provided under the plan developed under section 4(a) may not be made unless the President notifies the Congress at least 15 days in advance in accordance with the procedures applicable to reprogramming notifications under section 634A of the Foreign Assistance Act of 1961. (d) Effect on other laws.--Assistance may be provided under the plan developed under section 4(a) notwithstanding any other provision of law. SEC. 6. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated to the President such sums as may be necessary to carry out this Act. SEC. 7. TERMINATION OF EMBARGO. Upon submitting a determination to the Congress under section 5(b)(3) that a democratic government in Cuba is in power, the President shall terminate the embargo on trade with Cuba. SEC. 8. REQUIREMENTS FOR TRANSITION GOVERNMENT. For purposes of this Act, a transition government in Cuba is a government in Cuba which-- (1) is demonstrably in transition from communist totalitarian dictatorship to democracy; (2) makes public commitments to and is making demonstrable progress in-- (A) releasing all political prisoners and allowing for investigations of Cuban prisons by appropriate international human rights organizations; (B) establishing an independent judiciary; (C) respecting internationally recognized human rights and basic freedoms in accordance with the Universal Declaration of Human Rights, to which Cuba is a signatory nation; (D) dissolving the present Department of State Security in the Cuban Ministry of the Interior, including but not limited to, the Committees for the Defense of the Revolution and the Rapid Response Brigades; (E) organizing free and fair elections for a new government-- (i) to be held within 1 year after the transition government assumes power; (ii) with the participation of multiple independent political parties that have full access to the media on an equal basis, including (in the case of radio, television, or other telecommunications media) in terms of allotments of time for such access and the times of day such allotments are given; and (iii) to be conducted under the supervision of internationally recognized observers, such as the United Nations, the Organization of American States, and other elections monitors; (F) granting permits to privately owned indigenous telecommunications companies to operate in Cuba; and (G) allowing the establishment of an independent labor movement and of independent social, economic, and political associations; (3) does not include Fidel Castro or Raul Castro, or any person appointed by either such individual in a position of authority; and (4) allows the speedy and efficient distribution of assistance to the Cuban people. SEC. 9. REQUIREMENTS FOR DEMOCRATIC GOVERNMENT. For purposes of this Act, a democratic government in Cuba is a government in Cuba which-- (1) results from free and fair elections conducted under internationally recognized observers; (2) has permitted opposition parties ample time to organize and campaign for such elections, and has permitted full access to the media to all candidates in the elections; (3) is showing respect for the basic civil liberties and human rights of the citizens of Cuba; (4) has made demonstrable progress in establishing an independent judiciary; (5) is moving toward establishing a market-oriented economic system; and (6) has made or is committed to making constitutional changes that would ensure regular free and fair elections that meet the requirements of paragraph (2). SEC. 10. AMENDMENT TO CARIBBEAN BASIN ECONOMIC RECOVERY ACT. The table contained in section 212(b) of the Caribbean Basin Economic Recovery Act (19 U.S.C. 2702(b)) is amended by inserting ``Cuba'' between ``Costa Rica'' and ``Dominica''.

Free and Independent Cuba Assistance Act of 1993 - Requires the President, at such time as a transition government is in power in Cuba, to develop a plan for providing economic assistance to the Cuban people while such government and a democratic government are in power. Limits such assistance to humanitarian assistance while a transition government is in power. Expands such assistance to include development and agricultural assistance and export financing (as well as other specified assistance) when a democratic government is in power. Requires the President to take steps to obtain the agreement of other countries and international financial institutions to provide comparable assistance to Cuba. Directs the President to determine whether to designate Cuba as a beneficiary country pursuant to the Caribbean Basin Economic Recovery Act. Requires the President, upon enactment of legislation implementing a free trade agreement between the United States and another country in the Western Hemisphere, to: (1) take steps to enter into a framework agreement with the transition government in Cuba providing for trade and investment in Cuba; and (2) enter into negotiations with a democratic government in Cuba to conclude a free trade agreement. Directs the President to communicate the plan for assistance to the Cuban people. Authorizes appropriations. Requires the President to terminate the trade embargo on Cuba upon submitting a determination that a democratic government is in power in Cuba to the Congress. Sets forth conditions under which a government in Cuba will be considered transitional or democratic.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Government Shutdown Prevention Act''. SEC. 2. AMENDMENT TO TITLE 31. (a) In General.--Chapter 13 of title 31, United States Code, is amended by inserting after section 1310 the following new section: ``Sec. 1311. Continuing appropriations ``(a)(1) If any regular appropriation bill for a fiscal year does not become law prior to the beginning of such fiscal year or a joint resolution making continuing appropriations is not in effect, there is appropriated, out of any moneys in the Treasury not otherwise appropriated, and out of applicable corporate or other revenues, receipts, and funds, such sums as may be necessary to continue any project or activity for which funds were provided in the preceding fiscal year-- ``(A) in the corresponding regular appropriation Act for such preceding fiscal year; or ``(B) if the corresponding regular appropriation bill for such preceding fiscal year did not become law, then in a joint resolution making continuing appropriations for such preceding fiscal year. ``(2) Appropriations and funds made available, and authority granted, for a project or activity for any fiscal year pursuant to this section shall be at a rate of operations not in excess of 75 percent of the lower of-- ``(A) the rate of operations provided for in the regular appropriation Act providing for such project or activity for the preceding fiscal year, ``(B) in the absence of such an Act, the rate of operations provided for such project or activity pursuant to a joint resolution making continuing appropriations for such preceding fiscal year, ``(C) the rate of operations provided for in the House or Senate passed appropriation bill for the fiscal year in question, except that the lower of these two versions shall be ignored for any project or activity for which there is a budget request if no funding is provided for that project or activity in either version, ``(D) the rate provided in the budget submission of the President under section 1105(a) of title 31, United States Code, for the fiscal year in question, or ``(E) the annualized rate of operations provided for in the most recently enacted joint resolution making continuing appropriations for part of that fiscal year or any funding levels established under the provisions of this Act. ``(3) Appropriations and funds made available, and authority granted, for any fiscal year pursuant to this section for a project or activity shall be available for the period beginning with the first day of a lapse in appropriations and ending with the earlier of-- ``(A) the date on which the applicable regular appropriation bill for such fiscal year becomes law (whether or not such law provides for such project or activity) or a continuing resolution making appropriations becomes law, as the case may be, or ``(B) the last day of such fiscal year. ``(b) An appropriation or funds made available, or authority granted, for a project or activity for any fiscal year pursuant to this section shall be subject to the terms and conditions imposed with respect to the appropriation made or funds made available for the preceding fiscal year, or authority granted for such project or activity under current law. ``(c) Appropriations and funds made available, and authority granted, for any project or activity for any fiscal year pursuant to this section shall cover all obligations or expenditures incurred for such project or activity during the portion of such fiscal year for which this section applies to such project or activity. ``(d) Expenditures made for a project or activity for any fiscal year pursuant to this section shall be charged to the applicable appropriation, fund, or authorization whenever a regular appropriation bill or a joint resolution making continuing appropriations until the end of a fiscal year providing for such project or activity for such period becomes law. ``(e) This section shall not apply to a project or activity during a fiscal year if any other provision of law (other than an authorization of appropriations)-- ``(1) makes an appropriation, makes funds available, or grants authority for such project or activity to continue for such period, or ``(2) specifically provides that no appropriation shall be made, no funds shall be made available, or no authority shall be granted for such project or activity to continue for such period. ``(f) For purposes of this section, the term `regular appropriation bill' means any annual appropriation bill making appropriations, otherwise making funds available, or granting authority, for any of the following categories of projects and activities: ``(1) Agriculture, rural development, and related agencies programs. ``(2) The Departments of Commerce, Justice, and State, the judiciary, and related agencies. ``(3) The Department of Defense. ``(4) The government of the District of Columbia and other activities chargeable in whole or in part against the revenues of the District. ``(5) The Departments of Labor, Health and Human Services, and Education, and related agencies. ``(6) The Department of Housing and Urban Development, and sundry independent agencies, boards, commissions, corporations, and offices. ``(7) Energy and water development. ``(8) Foreign assistance and related programs. ``(9) The Department of the Interior and related agencies. ``(10) Military construction. ``(11) The Department of Transportation and related agencies. ``(12) The Treasury Department, the U.S. Postal Service, the Executive Office of the President, and certain independent agencies. ``(13) The legislative branch.''. (b) Clerical Amendment.--The analysis of chapter 13 of title 31, United States Code, is amended by inserting after the item relating to section 1310 the following new item: ``1311. Continuing appropriations.''. (c) Protection of Other Obligations.--Nothing in the amendments made by this section shall be construed to effect Government obligations mandated by other law, including obligations with respect to Social Security, Medicare, and Medicaid. SEC. 3. EFFECTIVE DATE AND SUNSET. (a) Effective Date.--The amendments made by this Act shall apply with respect to fiscal years beginning with fiscal year 2003. (b) Sunset.--The amendments made by this Act shall sunset and have no force or effect 3 years after the date of enactment of this Act.

Government Shutdown Prevention Act - Provides for continuing appropriations for a fiscal year in the absence of regular appropriations, at a level not exceeding 75 percent of the lowest of possible rates of operations found in: (1) the previous fiscal year's appropriations or continuing appropriations acts; (2) the House or Senate passed appropriation bill for the fiscal year in question (except for a project or activity not funded in one such version); (3) the presidential budget submission; or (4) the annualized rate of operations provided for in the most recently enacted joint resolution making continuing appropriations for part of that fiscal year or any funding levels established under this Act.Charges expenditures made under this Act to the applicable appropriation, fund, or authorization when it becomes law.

SECTION. 1. PURPOSE. The purpose of this Act is to make improvements in the codification of title 46, United States Code, as enacted by H.R. 1442 (109th Congress), based on-- (1) public comments submitted too late to be incorporated in the codification; and (2) amendments to laws, made after the cutoff date specified in section 18(a) of that bill, which were repealed and replaced by the codification. SEC. 2. PERSONAL INJURY TO OR DEATH OF SEAMEN. Section 30104 of title 46, United States Code, is amended by striking subsections (a) and (b) and inserting the following: ``(a) Cause of Action.--A seaman injured in the course of employment or, if the seaman dies from the injury, the personal representative of the seaman may bring an action relying on the laws of the United States regulating recovery for personal injury to, or death of, a railway employee. Such an action may be maintained in admiralty or, at the plaintiff's election, as an action at law, with the right of trial by jury. ``(b) Venue.--When the plaintiff elects to maintain an action at law, venue shall be in the judicial district in which the employer resides or the employer's principal office is located.''. SEC. 3. AMENDMENTS TO CHAPTER 537. (1) Section 53701 of title 46, United States Code, is amended by-- (A) redesignating paragraphs (2)-(13) as paragraphs (3)-(14), respectively; (B) inserting after paragraph (1) the following: ``(2) Administrator.--The term `Administrator' means the Administrator of the Maritime Administration.''; and (C) amending paragraph (13) (as redesignated) to read as follows: ``(13) Secretary.--The term `Secretary' means the Secretary of Commerce with respect to fishing vessels and fishery facilities.''. (2) Section 53706(c) of title 46, United States Code, is amended to read as follows: ``(c) Priorities for Certain Vessels.-- ``(1) Vessels.--In guaranteeing or making a commitment to guarantee an obligation under this chapter, the Administrator shall give priority to-- ``(A) a vessel that is otherwise eligible for a guarantee and is constructed with assistance under subtitle D of the Maritime Security Act of 2003 (46 U.S.C. 53101 note); and ``(B) after applying subparagraph (A), a vessel that is otherwise eligible for a guarantee and that the Secretary of Defense determines-- ``(i) is suitable for service as a naval auxiliary in time of war or national emergency; and ``(ii) meets a shortfall in sealift capacity or capability. ``(2) Time for determination.--The Secretary of Defense shall determine whether a vessel satisfies paragraph (1)(B) not later than 30 days after receipt of a request from the Administrator for such a determination.''. (3) Section 53707 of title 46, United States Code, is amended in-- (A) subsections (a) and (d), by inserting ``or Administrator'' after ``Secretary'' each place it appears; (B) subsection (b), by striking ``Secretary of Transportation'' and inserting ``Administrator''; (C) subsection (c), by striking ``of Commerce''; and (D) subsection (d)(2), by-- (i) inserting ``if the Secretary or Administrator considers necessary,'' before ``the waiver''; and (ii) striking ``the increased'' and inserting ``any significant increase in''. (4) Section 53708 of title 46, United States Code, is amended in-- (A) subsection (a), by striking ``Secretary'' and ``Secretary of Transportation'' each place they appear in the heading and in text and inserting ``Administrator''; (B) subsections (b) and (c), by striking ``of Commerce'' each place it appears in a heading and in text; (C) subsection (d), by-- (i) inserting ``or Administrator'' after ``Secretary'' the first place it appears; and (ii) striking ``financial structures, or other risk factors identified by the Secretary. Any independent analysis conducted under this subsection shall be performed by a party chosen by the Secretary.'' and inserting ``or financial structures. A third party independent analysis conducted under this subsection shall be performed by a private sector expert in assessing such risk factors who is selected by the Secretary or Administrator.''; and (D) subsection (e), by-- (i) inserting ``or Administrator'' after ``Secretary'' the first place it appears; and (ii) striking ``financial structures, or other risk factors identified by the Secretary'' and inserting ``or financial structures''. (5) Section 53712(b) of title 46, United States Code, is amended by striking the last sentence and inserting ``If the Secretary or Administrator has waived a requirement under section 53707(d) of this title, the loan agreement shall include requirements for additional payments, collateral, or equity contributions to meet the waived requirement upon the occurrence of verifiable conditions indicating that the obligor's financial condition enables the obligor to meet the waived requirement.''. (6) Subsections (c) and (d) of section 53717 of title 46, United States Code, are amended by striking ``of Commerce'' each place it appears in a heading and in text. (7) Section 53732(e)(2) of title 46, United States Code, is amended by inserting ``of Defense'' after ``Secretary'' the second time it appears. (8) The following provisions of title 46, United States Code, are amended by striking ``Secretary'' and ``Secretary of Transportation'' and inserting ``Administrator'': (A) Section 53710(b)(2)(A)(i). (B) Section 53717(b) each place it appears in a heading and in text. (C) Section 53718. (D) Section 53731 each place it appears, except when ``Secretary'' is followed by ``of Energy''. (E) Section 53732 each place it appears, except when ``Secretary'' is followed by ``of the Treasury'', ``of State'', or ``of Defense''. (F) Section 53733 each place it appears. (9) Section 53710(b)(1) of title 46, United States Code, is amended by striking ``Secretary's'' and inserting ``Administrator's''. (10) The following provisions of title 46, United States Code, are amended by inserting ``or Administrator'' after ``Secretary'' each place it appears in headings and text, except when ``Secretary'' is followed by ``of Transportation'' or ``of the Treasury'': (A) The items relating to sections 53722 and 53723 in the table of sections at the beginning of chapter 537. (B) Sections 53701(1), (4), and (9) (as redesignated by paragraph (1)(A)), 53702(a), 53703, 53704, 53706(a)(3)(B)(iii), 53709(a)(1), (b)(1) and (2)(A), and (d), 53710(a) and (c), 53711, 53712 (except the last place it appears, as amended by paragraph (5)), 53713 to 53716, 53721 to 53725, and 53734. (11) Sections 53715(d)(1), 53716(d)(3), 53721(c), 53722(a)(1) and (b)(1)(B), and 53724(b) of title 46, United States Code, are amended by inserting ``or Administrator's'' after ``Secretary's''. SEC. 4. MISCELLANEOUS AMENDMENTS. Title 46, United States Code, is amended as follows: (1) Chapters 513 and 515 are amended by striking ``Naval Reserve'' each place it appears in analyses, headings, and text and inserting ``Navy Reserve''. (2) Section 51504(f) is amended to read as follows: ``(f) Fuel Costs.-- ``(1) In general.--Subject to the availability of appropriations, the Secretary shall pay to each State maritime academy the costs of fuel used by a vessel provided under this section while used for training. ``(2) Maximum amounts.--The amount of the payment to a State maritime academy under paragraph (1) may not exceed-- ``(A) $100,000 for fiscal year 2006; ``(B) $200,000 for fiscal year 2007; and ``(C) $300,000 for fiscal year 2008 and each fiscal year thereafter.'' (3) Section 51505(b)(2)(B) is amended by striking ``$200,000'' and inserting ``$300,000 for fiscal year 2006, $400,000 for fiscal year 2007, and $500,000 for fiscal year 2008 and each fiscal year thereafter''. (4) Section 51701(a) is amended by inserting before the period at the end ``and to perform functions to assist the United States merchant marine, as determined necessary by the Secretary''. (5)(A) Section 51907 is amended to read as follows: ``Sec. 51907. Provision of decorations, medals, and replacements ``The Secretary of Transportation may provide-- ``(1) the decorations and medals authorized by this chapter and replacements for those decorations and medals; and ``(2) replacements for decorations and medals issued under a prior law.''. (B) In the table of sections of chapter 519, the item relating to section 51907 is amended to read as follows: ``51907. Provision of decorations, medals, and replacements.''. (6)(A) The following new chapter is inserted after chapter 539: ``CHAPTER 541--MISCELLANEOUS ``Sec. ``54101. Assistance for small shipyards and maritime communities.''. (B) Section 3506 of the National Defense Authorization Act for Fiscal Year 2006 (46 App. U.S.C. 1249) is transferred to and redesignated as section 54101 of title 46, United States Code, to appear at the end of chapter 541 of title 46, as enacted by subparagraph (A). (C) The heading of section 54101 is amended to read as follows: ``Sec. 54101. Assistance for small shipyards and maritime communities''. (D) The table of chapters at the beginning of subtitle V is amended by inserting after the item relating to chapter 539 the following new item: Miscellaneous...................................................54101''. (7) Section 55101(b) is amended by-- (A) inserting ``or'' after the semicolon at the end of paragraph (2); (B) striking paragraph (3); and (C) redesignating paragraph (4) as paragraph (3). (8) Section 60301 is amended in-- (A) subsection (a), by striking ``2 cents per ton (but not more than a total of 10 cents per ton per year)'' and inserting ``4.5 cents per ton, not to exceed a total of 22.5 cents per ton per year, for fiscal years 2006 through 2010, and 2 cents per ton, not to exceed a total of 10 cents per ton per year, for each fiscal year thereafter,''; and (B) subsection (b), by striking ``6 cents per ton (but not more than a total of 30 cents per ton per year)'' and inserting ``13.5 cents per ton, not to exceed a total of 67.5 cents per ton per year, for fiscal years 2006 through 2010, and 6 cents per ton, not to exceed a total of 30 cents per ton per year, for each fiscal year thereafter,''. SEC. 5. REPEALS. The following provisions are repealed, except with respect to rights and duties that matured, penalties that were incurred, or proceedings that were begun before the date of enactment of this Act: Statutes at Large ---------------------------------------------------------------------------------------------------------------- Statutes at Large Date Public Law Section -------------------------- U.S. Code (46 Volume Page App.) ---------------------------------------------------------------------------------------------------------------- 1936 June 29 858 1113.................. ...... ................ 1279f ............ 1114.................. ...... ................ 1279g 2006 Jan. 6 109-163 515(g)(2)............. 119 3236............ 1131, 1295b, 1295c ............ 3502.................. 119 3547............ 1295c ............ 3507(a)-(c)(3), (d)... 119 3555, 3557...... 1271-1280, 1280b ............ 3509.................. 119 3557............ 1295e ............ 3510.................. 119 3557............ 2004 Feb. 8 109-171 4001.................. 120 27.............. 121, 132 ---------------------------------------------------------------------------------------------------------------- SEC. 6. EFFECTIVE DATE. This Act shall be effective only if H.R. 1442 in the 109th Congress is enacted. If such bill is enacted, this Act shall be effective on the date of, and immediately after, enactment of such bill.

Makes revisions to the codification of title 46 ("Shipping") of the United States Code, as proposed by H.R. 1442.

the multi - nucleon systems with an antikaon draw significant attention in hadron and nuclear physics . it is considered that the strong attraction in the @xmath0 channel leads to various interesting phenomena . the simplest example is the @xmath2 resonance as a @xmath0 quasi - bound state @xcite . the difficulty of the description of @xmath2 by the three - quark picture in the constituent quark model @xcite is compatible with the interpretation as the quasi - bound state of the @xmath0 system slightly below the threshold . in the early days , @xmath2 in the @xmath0 scattering amplitude was analyzed with @xmath3-matrix approaches and dispersion relations @xcite . later , coupled - channel approaches with chiral su(3 ) symmetry @xcite have been applied , and confirmed the @xmath0 quasi - bound picture of @xmath2 . in addition , a recent lattice qcd analysis supports this picture based on the vanishing of the strange magnetic form factor @xcite . the @xmath0 molecule picture indicates that the spacial structure of @xmath2 is relatively larger than the usual hadronic scale , which is shown by several approaches @xcite . experimentally , the @xmath2 signal in the @xmath4 spectrum has been studied with various reactions @xcite . another interesting example is the antikaon bound states in nuclei , the @xmath1-nuclei @xcite . because of the strong @xmath0 attraction , the @xmath1-nuclei may exhibit the qualitatively different structure from the normal nuclei . experimentally , there have been some claims for the evidence of the @xmath5 state @xcite . for instance , j - parc e27 experiment has reported a broad enhancement in the proton coincidence missing mass spectra in the @xmath6 reaction at 1.69 gev/@xmath7 @xcite . however , we have to note that quantitative results of these experiments are not consistent with each other . furthermore there are experiments which have found no such quasi - bound structure @xcite . to draw a definite conclusion , further studies are needed . theoretically , the rigorous three - body calculations of the @xmath5 system have recently been performed @xcite . all calculations have obtained the qualitatively consistent result that the @xmath5 system is bound between the @xmath5 and @xmath8 thresholds . however , the quantitative predictions of the mass and the width are substantially different from each other and are not consistent with the experimentally reported values . in this way , the quantitatively conclusive result of the @xmath5 system has not been achieved . it is the @xmath0 interaction below the threshold that is essential for the calculations of @xmath1-nuclear systems . however , the subthreshold region can not be directly accessible by experiments , so we have to extrapolate the scattering amplitude constrained by the experimental data above the @xmath0 threshold . previous studies of the @xmath1-nuclei have suffered from the large uncertainty , mainly because the experimental data has not been sufficient to constrain the subthreshold amplitude . recently , the siddharta collaboration has measured the precise energy - level shift of the kaonic hydrogen @xcite . this data is related to the @xmath9 scattering length @xcite , which quantitatively constrains the scattering amplitude at the @xmath0 threshold . this reduces the uncertainty of the amplitude below the @xmath0 threshold significantly @xcite . for a reliable prediction of @xmath2 and the @xmath1-nuclei , the constraint from the siddharta data should be taken into account . the base for the few - body calculations is the two - body hadron interaction . historically , the hadron interaction has been constructed phenomenologically . in the case of the nuclear force , phenomenological interactions are quite successful in reproducing the experimental data with the precision of @xmath10 @xcite . though the phenomenological interactions have been successfully applied to various few - body systems , the direct connection to qcd is not obvious . the first principle calculation of qcd is the lattice simulation which provides the promising approach to the hadron potentials @xcite . however , the nuclear force in the realistic set - up is yet to be constructed . another approach is based on chiral perturbation theory which is the effective field theory of qcd with chiral symmetry being the guiding principle @xcite . in this approach , the potential can be systematically improved with the higher order contributions . in the state - of - the - art calculations , it is possible to construct the nuclear force as precise as the phenomenological ones . in this work , we construct the @xmath0 potential using chiral unitary approach which is based on chiral perturbation theory and unitarity of the scattering amplitude . thanks to the systematic improvement , the low energy @xmath11 total cross sections , threshold branching ratios , and the siddharta data are well reproduced with an accuracy of @xmath10 @xcite . the potential is constructed in the local form in the coordinate space for the convenience of the applications to few - body calculations . in contrast to the nuclear force , the @xmath0 potential can not be directly obtained in chiral perturbation theory which does not contain the long range meson exchange processes . we therefore construct the potential so as to reproduce the scattering amplitude from chiral unitary approach on the real energy axis following ref . given that the uncertainty of the subthreshold amplitude is reduced by the siddharta constraint , we have to establish the construction procedure with the high precision in the wide energy region . moreover , to analyze the structure of @xmath2 , the precision in the complex energy plane is necessary . in this way , we construct the reliable @xmath0 potential applicable for the quantitative calculations . in sec . [ sec : formulation ] , we briefly introduce chiral unitary approach for the @xmath0 scattering , and the framework to construct the hadron local potential from this approach . in sec . [ sec : precisepot ] , we examine the construction procedure to reproduce the original amplitude even in the complex energy plane with a simple model as an example . the new construction procedure of the hadron potential is applied to the @xmath0 amplitude with the siddharta constraint in sec . [ sec : application ] , leading to the reliable @xmath0 potential . using this new @xmath0 potential , we investigate the spatial structure of @xmath2 . the last section is devoted to the summary of this work . to describe the @xmath0 scattering , it is mandatory to consider the channel coupling with the lower energy @xmath4 state and the existence of the @xmath2 resonance below the threshold . here we utilize the nonperturbative coupled - channel framework called chiral unitary approach @xcite which is based on the resummation of the interaction terms derived from chiral perturbation theory . the @xmath12-wave meson - baryon scattering amplitude @xmath13 at the total center of mass energy @xmath14 is @xmath15_{ij } , \notag\end{aligned}\ ] ] where @xmath16 and @xmath17 represent the meson - baryon interaction kernel derived from chiral perturbation theory and the loop function , respectively with the meson - baryon channel indices being denoted by @xmath18 . there are four meson - baryon channels with isospin @xmath19 , @xmath0 , @xmath4 , @xmath20 and @xmath21 corresponding to @xmath22 and 4 , respectively . the interaction kernel @xmath16 is systematically obtained in chiral perturbation theory , where the leading contribution is given by the weinberg - tomozawa term . systematic improvement with higher order correction has been discussed in ref . recently , the refined calculations for the @xmath23 sector including the next - to - leading order terms @xcite are being available with the constraint from the siddharta data . the dimensional regularization is applied to the loop function @xmath24 with the finite part being specified by the subtraction constant . adjusting the subtraction constant adequately , the experimental data such as scattering cross sections , threshold branching ratios and the scattering length can be reproduced well . although there are other regularization schemes constrained by the crossing symmetry @xcite and the su(3 ) symmetry @xcite , the present phenomenological regularization scheme is sufficient to consider the @xmath0 scattering near the threshold . the @xmath0 forward scattering amplitude @xmath25 is related to the amplitude @xmath26 as @xmath27 where @xmath28 represents the nucleon mass . in the isospin @xmath19 channel , there are two resonance poles in the @xmath2 energy region , induced by the attractive interactions of the @xmath0 channel and the @xmath4 channel @xcite . in this paper , we refer to the higher ( lower ) energy pole near the @xmath0 ( @xmath4 ) threshold as @xmath0 pole ( @xmath4 pole ) . our aim is to construct the @xmath0 single - channel interaction for the application to few - body calculations as well as the @xmath2 analysis . in this work , we construct a single - channel local potential which produces the amplitude equivalent to the chiral coupled - channel approach . the coordinate space wave function calculated by the potential is useful to study the spatial structure of @xmath2 . in addition , the local potential is easily implemented in the variational calculations of the few - body systems @xcite . to this end , we first extract the single - channel @xmath0 interaction from the coupled - channel scattering equation . we define the effective interaction @xmath29 as @xmath30^{-1},\ \ m , l=2,3, ... ,n . \notag\end{aligned}\ ] ] the quantities with the superscript ( @xmath31 ) are the @xmath32 matrices . using this single - channel scattering equation @xmath33^{-1}$ ] , the original amplitude is exactly reproduced . because of the elimination of the lower energy @xmath4 channel , the effective @xmath0 interaction @xmath29 has an imaginary part . next , we define the energy dependent local potential @xmath34 where @xmath35 , @xmath36 and @xmath37 are the nonrelativistic energy , the energy of the nucleon and the energy of the anti - kaon , @xmath38 with the mass of the antikaon @xmath39 . the spatial distribution of the potential is governed by @xmath40 which is normalized as @xmath41 . the flux factor @xmath42 is determined by the matching with the original amplitude at the @xmath0 threshold in the born approximation @xcite . in this work , we choose a gaussian for @xmath40 @xmath43 where the parameter @xmath44 determines the range of the potential . using the local potential , we can calculate the wave function from the schrdinger equation , @xmath45 where @xmath46 is the reduced mass and @xmath47 is the @xmath12-wave part of the two - body radial wave function . from the behavior of the wave function at @xmath48 , the scattering amplitude @xmath25 can be obtained . in ref . @xcite , the parameter @xmath44 was determined to match the amplitude @xmath25 with the original amplitude in the @xmath2 resonance region . in this work , we determine the parameter @xmath44 by the matching of the full amplitude at the @xmath0 threshold . this prescription is along the same line with the determination of the flux factor @xmath42 . the potential well reproduces the original amplitude near the @xmath0 threshold , while the deviation increases in the energy region far below the threshold . to enlarge the applicability of the potential , we add the correction @xmath49 to the strength of the potential , @xmath50 . \label{eq : equivpot1 } \ ] ] for the analytic continuation of the amplitude in the complex energy plane , it is useful to parameterize the strength of the potential by a polynomial in the energy , @xmath51 . \label{eq : fit } \ ] ] we refer to the energy range where the potential is parameterized as parameterized range , which will be specified for each potential . we comment on the analytic behavior of the amplitude calculated from the potential . because the potential is constructed to reproduce the original amplitude , the correct analytic behavior is guaranteed within the parametrized range on the real axis . on the other hand , the extrapolation of this potential to other energy regions should be carefully performed , since some unphysical singularities can in general be developed . this will be discussed in detail in the next section . in this section , we study how the original amplitude is reproduced by the @xmath0 local potential . examining the previous method in ref . @xcite in detail , we improve the construction procedure to reproduce the original amplitude even in the complex energy plane . here , we mainly employ the amplitude of the hnjh model @xcite for the comparison with ref . inclusion of the siddharta constraint will be discussed in the next section to construct a realistic @xmath0 potential . a resonance state is represented by a pole of the scattering amplitude in the complex energy plane . the pole structure of the @xmath0 amplitude is therefore important for the study of the spacial structure of @xmath2 . it is considered that the pole structure of the @xmath0 system may affect the result of the @xmath5 system @xcite . we thus focus on the scattering amplitude from the previous potential in the complex plane . in fig . [ fig : vequiv ] , we compare the @xmath52 scattering amplitude from the local potential @xmath25 in ref . @xcite with the corresponding original amplitude in the chiral unitary approach @xmath53 for the models orb @xcite , hnjh @xcite , bnw @xcite and bmn @xcite on the real axis . the @xmath0 amplitudes on the real axis are reasonably well reproduced by the potentials in ref . @xcite . on the other hand , we find a large deviation of the amplitude in the complex energy plane . in table [ tab : pole_fkn_fknch ] , we list the pole positions of the scattering amplitudes . while chiral unitary approaches generate two poles in the @xmath2 energy region , the local potentials give only one pole . in addition , the position of the pole does not agree with neither of the original poles . hence , the potential construction procedure should be improved by paying attention to the amplitude in the complex energy plane . ( thick lines ) and the amplitudes directly from chiral unitary approach @xmath54 ( thin lines ) with models orb @xcite , hnjh @xcite , bnw @xcite and bmn @xcite . the real ( imaginary ) parts are shown by the solid ( dotted ) lines.,width=302 ] .pole positions of the original scattering amplitudes from chiral unitary approach @xmath54 and the amplitudes from the local potentials @xmath25 . all poles are found in the @xmath4 unphysical and @xmath0 physical riemann sheet . the pole at @xmath55 in the bmn model is above the @xmath0 threshold , and hence is not in the most adjacent sheet to the real axis . [ cols= " < , < , < " , ] in all cases , the values of @xmath56 remain larger than the typical hadron size . we find the qualitative picture of the molecular state is valid irrespective of the potential range . we have constructed the new @xmath0 local potential ( siddharta potential ) which reproduces the scattering amplitude from the chiral su(3 ) dynamics . in the construction procedure , we have paid attention to the two steps : the precision in the complex energy plane and the constraint from the recent siddharta data . this new potential is useful for the quantitative calculation of the interesting systems such as @xmath1 few - body systems and the @xmath2 . we first establish the procedure of potential construction by improving the previous work @xcite . the previous potential almost reproduced the original amplitude on the real energy axis , while we have found that there is a substantial deviation in the complex energy plane , including the poles of @xmath2 . therefore we need to improve the potential construction procedure to reproduce the original amplitude even in the complex energy plane . we find that the reduction of the deviation on the real energy axis @xmath57 in the wide parametrized range is important , based on the uniqueness of the analytic continuation in the complex energy plane . thanks to these improvements , we have succeeded in reproducing the original amplitude in the drastically large region in the complex plane including the two poles of @xmath2 . next , we have applied the new procedure to the amplitude with the siddharta constraint to construct the realistic @xmath0 potential . here we produce the @xmath0 amplitude with isospin symmetry from the coupled - channel chiral model in refs . @xcite . based on these amplitudes , we have constructed the realistic @xmath0 local potentials for the @xmath19 and @xmath58 channels . the @xmath19 local potential reproduces the original amplitude in the complex energy plane including the poles of @xmath2 . at the present time , this is the most reliable local @xmath0 potential for the quantitative calculations . applying this new potential to @xmath2 , we have estimated the spacial structure of @xmath2 . the mean distance of @xmath1 and @xmath59 is found to be 1.44 fm . this result shows the meson - baryon molecular nature of @xmath2 . as a future perspective , the calculation of the @xmath5 system with the new reliable potential is of particular importance . we hope that this result will bring new insight in the theoretical and experimental studies of the @xmath5 system . the authors thank yoshiko kanada - enyo for useful discussion on the mean squared radius of the quasi - bound state . this work is supported in part by jsps kakenhi grants no . 24740152 and by the yukawa international program for quark - hadron sciences ( yipqs ) . in this appendix , we consider the mean squared radius of a quasi - bound state in comparison with a bound state in the zero range limit . when the spatial extent of the wave function is much larger than the potential range , we can treat the potential in the zero range approximation . in this case , the mean squared radius @xmath60 is determined only by the eigenmomentum @xmath61 , where @xmath62 for the bound state and @xmath63 for the quasi - bound state . in the zero range limit , the radial wave function of the ( quasi-)bound state in @xmath12 wave is written as @xmath64 where @xmath47 is related to the wave function as @xmath65 . the normalization condition determines the factor @xmath66 . we consider the following two normalization conditions , @xmath67 where the former is the standard normalization whereas the latter uses the gamow vector labeled by @xmath68 . in the zero range limit , these conditions are expressed as @xmath69 r } = \frac{|a|^2}{2{\rm im}[k]}=1 , \notag \\ _ g\langle \psi|\psi\rangle_g & \to a^2\int_0^\infty dr\ e^{2ik r}=\frac{a^2}{2ik}=1 . \notag\end{aligned}\ ] ] these integrals converge for the bound state or the quasi - bound state because @xmath70>0$].]@xmath71 ) can be normalized only by eq . with appropriate prescription @xcite . ] the normalized wave functions are written as @xmath72}{2\pi}}\frac{e^{ikr}}{r } \equiv e^{i\theta } \sqrt{\frac{{\rm im}[k]}{2\pi}}\frac{e^{ikr}}{r } , \label{eq : wavefcn_nor_usual } \\ \psi_g(r ) & \to \sqrt{\frac{-ik}{2\pi}}\frac{e^{ikr}}{r } , \label{eq : wavefcn_nor_gamow } \ ] ] where @xmath73 is an arbitrary real constant . in the standard normalization , physical observables are independent of the phase of the wave function , so @xmath73 is an irrelevant phase . in the case of the bound state @xmath74 , eq . and eq . are equivalent . on the other hand , these wave functions of the quasi - bound state are in general different , @xmath75 . with these wave functions , we can calculate the mean squared radius , @xmath76 r } \notag \\ & = \frac{1}{2{(\rm im}[k])^2 } , \label{eq : r2_usual } \\ \langle r^2 \rangle_g & = \int d\bm{r}\ r^2\psi_g(r)^2 \notag \\ & \to \frac{-ik}{2\pi}4\pi\int_0^\infty dr\ r^2e^{2ik r } \notag \\ & = \frac{1}{2(-ik)^2}. \label{eq : r2_gamow } \ ] ] in the case of the bound state @xmath77 , both the normalizations give the same result , @xmath78 for the quasi - bound state , eq . and eq . are different : @xmath79 eq . gives a real number for the mean squared radius , while eq . gives a complex number . it is common to use the gamow vector @xcite for unstable states . because the radial wave function of the quasi - bound state asymptotically behaves as @xmath80 , eq . is the natural extension of the bound state . we therefore use the normalization with the gamow vector in fig . [ fig : psi ] and table [ tab : r^2 ] . on the other hand , it is difficult to extract the spacial information from the complex @xmath81 in eq . . we note that the dumping of the wave function of the quasi - bound state is expressed by @xmath82r}$ ] in the asymptotic behavior @xmath80 . in this sense , we consider that the real @xmath83 with the standard normalization , which is determined by @xmath70 $ ] , can be interpreted as the spacial extent of the quasi - bound state . hence , in this paper , we use @xmath83 to estimate the spacial extent of the @xmath0 quasi - bound state , @xmath2 . as explained in refs . @xcite , the careful treatment is necessary for the system with the energy - dependent potential . here , we explain the treatment in the cases of real potential and complex one . first , we summarize the case of the energy - dependent real potential , following ref . @xcite . we consider the schrdinger equation with a time - dependent wave function @xmath84 with @xmath85 , @xmath86\psi({\bm r},t ) . \label{eq : tdepschro } \ ] ] for an eigenfunction of the hamiltonian , @xmath87 , the time - independent schrdinger equation becomes @xmath88 \psi_e({\bm r } ) = e\psi_e({\bm r } ) . \label{eq : tindepschro } \ ] ] with eq . , the continuity equation for energy - dependent potential can be calculated as follows , @xmath89^*\psi_e \notag \\ & \phantom{aaaaa}+ \psi_{e^\prime}^*\left[-i\left\ { -\frac{1}{2}\nabla^2+v({\bm r},e)\right\ } \psi_e \right ] \notag \\ & = -\nabla\cdot { \bm j } + i\psi_{e^\prime}^ * \big[v({\bm r},e^\prime)-v({\bm r},e)\big ] \psi_e , \label{eq : cont } \ ] ] where @xmath90 . \notag\end{aligned}\ ] ] for the energy - independent potential , the second term of the last line in eq . disappears and the usual continuity equation @xmath91 can be hold . however , for the energy - dependent potential , the additional term have to be included . using the schrdinger equation , @xmath92 , we obtain the relation , @xmath93\psi_e \right\ } \notag \\ & = \frac{\partial \psi_{e^\prime}^*}{\partial t } \left[\frac{v(e^\prime)-v(e)}{e^\prime - e } \right]\psi_e \notag \\ & \phantom{aaaaa}+ \psi_{e^\prime}^*\left[\frac{v(e^\prime)-v(e)}{e^\prime - e } \right]\frac{\partial \psi_e}{\partial t } \notag \\ & = \left\{-ie^\prime \psi_{e^\prime } \right\}^ * \left [ \frac{v(e^\prime)-v(e)}{e^\prime - e } \right ] \psi_e \notag \\ & \phantom{aaaaa}+ \psi_{e^\prime}^ * \left [ \frac{v(e^\prime)-v(e)}{e^\prime - e } \right ] \left\{-ie^\prime \psi_e \right\ } \notag \\ & = i\psi_{e^\prime}^*\left [ v(e^\prime)-v(e ) \right ] \psi_e , \label{eq : addterm } \ ] ] and the continuity equation for the energy - dependent potential can be modified as @xmath94 where @xmath95\psi_e({\bm r},t ) . \notag\end{aligned}\ ] ] therefore , taking the limit of @xmath96 , the norm @xmath59 can be modified as @xmath97 \psi_e({\bm r},t ) \notag \\ & = \int d{\bm r}\ \psi_e^*({\bm r } ) \left[1-\frac{\partial v({\bm r},e)}{\partial e } \right ] \psi_e({\bm r } ) . \label{eq : norm } \ ] ] furthermore , the orthogonality relation can be modified as @xmath98 & \psi_e({\bm r } ) = 0 , \label{eq : ortho } \\ & ( e^\prime \ne e ) . \notag\end{aligned}\ ] ] actually , the usual orthogonality relation is not satisfied because the term with @xmath99 remains nonzero after integrating eq . with respect to @xmath100 . the above method can not be directly applied to the case of the complex potential . in this case , following the same procedure , @xmath99 is obtained as @xmath101\psi_e({\bm r},t ) . \notag\end{aligned}\ ] ] because @xmath102 for the complex potential , taking the limit of @xmath96 , this term diverges and does not become the derivative of the potential . when we treat the complex potential problem , it is common to use the adjoint wave function @xmath103 @xcite , which satisfies the schrdinger equation @xmath104 under the adequate boundary condition @xcite , the time - independent eigenfunction @xmath105 have the following properties , @xmath106 with this adjoint wave function , we consider the continuity equation again , labeling the quantities with the adjoint function by the index @xmath68 " . @xmath107^*\psi_e \notag \\ & \phantom{aaaaa}+ \psi_{e^\prime}^{\dag * } \left[-i\left\ { -\frac{1}{2}\nabla^2+v(e)\right\ } \psi_e \right ] \notag \\ & = -\nabla\cdot{\bm j}^g + i\psi_{e^\prime}^{\dag * } \left(v(e^\prime)-v(e)\right ) \psi_e , \label{eq : contgamow } \ ] ] where @xmath108 . \notag\end{aligned}\ ] ] following the same procedure as in eq . , the continuity equation for the complex energy - dependent potential can be satisfied . @xmath109 where @xmath110\psi_e({\bm r},t ) . \notag\end{aligned}\ ] ] therefore , we should modify the norm and the orthogonality relation as @xmath111 \psi_e({\bm r},t ) \notag \\ & = \int d{\bm r}\ \psi_e({\bm r } ) \left[1-\frac{\partial v({\bm r},e)}{\partial e } \right ] \psi_e({\bm r } ) , \label{eq : norm } \ ] ] @xmath112 & \psi_e({\bm r } ) = 0 , \label{eq : ortho } \\ & ( e^\prime \ne e ) . \notag\end{aligned}\ ] ] r. dalitz and s. tuan , phys . rev . lett . * 2 * , 425 ( 1959 ) . r. dalitz and s. tuan , annals phys . * 10 * , 307 ( 1960 ) . n. isgur and g. karl , phys . rev . * d18 * , 4187 ( 1978 ) . j. k. kim , phys . * 14 * , 29 ( 1965 ) . j. k. kim , phys . * 19 * , 1074 ( 1967 ) . b. r. martin , phys . rev . * 175 * , 2034 ( 1968 ) . b. r. martin and m. sakitt , phys . rev . * 183 * , 1345 ( 1969 ) . b. r. martin and m. sakitt , phys . rev . * 183 * , 1352 ( 1969 ) . a. d. martin , phys . b65 * , 346 ( 1976 ) . a. d. martin , nucl . phys . * b179 * , 33 ( 1981 ) . n. kaiser , p. siegel and w. weise , nucl . a594 * , 325 ( 1995 ) . e. oset and a. ramos , nucl a635 * , 99 ( 1998 ) . j. oller and u. g. meissner , phys . lett . * b500 * , 263 ( 2001 ) . m. f. m. lutz and e. e. kolomeitsev , nucl . * a700 * , 193 ( 2002 ) . t. hyodo and d. jido , prog . . phys . * 67 * , 55 ( 2012 ) . j. m. m. hall _ lett . * 114 * , 132002 ( 2015 ) . t. yamazaki and y. akaishi , phys . rev . * c76 * , 045201 ( 2007 ) . t. sekihara , t. hyodo and d. jido , phys . lett . * b669 * , 133 ( 2008 ) . t. sekihara , t. hyodo and d. jido , phys . rev . * c83 * , 055202 ( 2011 ) . t. sekihara and t. hyodo , phys . rev . * c87 * , 045202 ( 2013 ) . a. dote and t. myo , nucl a930 * , 86 ( 2014 ) . m. niiyama _ et al . _ , phys . rev . * c78 * , 035202 ( 2008 ) . hades , g. agakishiev _ et al . _ , phys . rev . * c87 * , 025201 ( 2013 ) . clas , k. moriya _ _ , phys . rev . * c87 * , 035206 ( 2013 ) . clas collaboration , k. moriya _ et al . _ , phys . rev . * c88 * , 045201 ( 2013 ) . clas , k. moriya _ et al . _ , 112 * , 082004 ( 2014 ) . y. nogami , phys . * 7 * , 288 ( 1963 ) . y. akaishi and t. yamazaki , phys . rev . * c65 * , 044005 ( 2002 ) . t. yamazaki and y. akaishi , phys . lett . * b535 * , 70 ( 2002 ) . finuda collaboration , m. agnello _ et al . * 94 * , 212303 ( 2005 ) . g. bendiscioli _ et al . _ , nucl . phys . a789 * , 222 ( 2007 ) . t. yamazaki _ et al . lett . * 104 * , 132502 ( 2010 ) . y. ichikawa _ et al . _ , ptep * 2015 * , 021d01 ( 2014 ) . leps , a. tokiyasu _ et al . _ , lett . * b728 * , 616 ( 2014 ) . j - 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we develop the single - channel local potential for the @xmath0 system , which is applicable to quantitative studies of @xmath1 bound states in nuclei . because the high precision measurement of the kaonic hydrogen by siddharta reduces the uncertainty of the @xmath0 amplitude below the @xmath0 threshold , the local potential should be calibrated in a wide energy region . we establish a new method to construct the local potential focusing on the behavior of the scattering amplitude in the complex energy plane . applying this method , we construct the @xmath0 potential based on the chiral coupled - channel approach with the siddharta constraint . the wave function from the new potential indicates the @xmath0 molecular structure of @xmath2 .

SECTION 1. SHORT TITLE. This Act may be cited as the ``World War II War Crimes Accountability Act of 2008''. SEC. 2. FINDINGS. Congress finds the following: (1) Surviving Nazi war criminals are becoming increasingly rare. (2) The identities of many of the remaining criminals were made known only after the end of the Cold War and the collapse of Communist governments throughout eastern Europe. (3) In most of these formerly communist countries, the volume of available information is enormous, and the available resources to study it and identify war crimes suspects is comparatively small. (4) In the United States, the Office of Special Investigations (OSI) of the Department of Justice is responsible for detecting, investigating and taking legal action to denaturalize or deport persons who took part in Nazi- sponsored acts of persecution committed abroad between 1933 and 1945. (5) As of April 2008, OSI had successfully prosecuted more than 100 people involved in Nazi war crimes who were residing in the United States. (6) As a government office with limited resources, OSI is under enormous strain to identify and prosecute those criminals identified by newly-released records before it is too late. (7) Some foreign governments hinder the efforts of OSI, Congress, and the United States Government to extradite or deport convicted Nazi war criminals from the United States to their country of origin or other relevant jurisdiction. (8) Certain nongovernmental organizations have been instrumental in the search for wanted Nazi war crimes suspects for over 60 years. (9) In 2002, the Simon Wiesenthal Center launched Operation: Last Chance to maximize the identification and help facilitate the prosecution of the remaining unprosecuted Nazi war criminals, helping to achieve justice for the victims of the Holocaust. (10) Simon Wiesenthal, a survivor of the Nazi death camps whose work stands as a reminder and a warning for future generations, dedicated his life to-- (A) documenting the crimes of the Holocaust; and (B) hunting down the perpetrators still at large. (11) As founder and head of the Jewish Documentation Center in Vienna, Simon Wiesenthal successfully brought to justice wanted Nazi war criminals, including-- (A) Franz Stangl, the commandant of the Treblinka death camp; (B) Franz Murer, ``The Butcher of Wilno''; and (C) Erich Rajakowitsch, who was in charge of the ``death transports'' in Holland. (12) Mr. Wiesenthal's work, which contributed enormously to the modern understanding of justice, war crimes, and crimes against humanity, should be continued. (13) Of the most guilty Nazis and Nazi collaborators still at large, Operation: Last Chance has identified the following suspects: (A) Dr. Aribert Heim, who served as a medical doctor at the Sachsenhausen, Buchenwald, and Mauthausen concentration camps, is the most wanted ex-Nazi still at large. His most terrible crimes were committed at Mauthausen, where he murdered hundreds of inmates by administering lethal injections of phenol to their hearts or by other torturous killing methods during the fall of 1941. His whereabouts are unknown. (B) Dr. Sandor Kepiro, who served as an officer in the Hungarian gendarmerie, was 1 of several Hungarian officers convicted in 1944 for the mass murder of several thousand civilians (mostly Jews) in the city of Novi Sad on January 23, 1942. In the wake of the occupation of Hungary in March 1944, he was pardoned, promoted, and returned to active service. He escaped to Austria in 1945, fled to Argentina in 1948, and returned to Hungary in 1996. (C) Milivoj Asner, who served as the police chief of the city of Slavonska Pozega. During 1941 and 1942, Mr. Asner orchestrated the robbery, persecution and destruction of the local Serb, Jewish and Gypsy communities, which culminated in the deportation of hundreds of civilians to Ustasha concentration camps, where most of the deportees were murdered. After his exposure in Operation: Last Chance, the former police chief later escaped once again to Klagenfurt, Austria where he currently resides. (D) Charles Zentai is accused of murdering 18-year- old Peter Balazs, a Jewish boy he caught riding a Budapest tram without the requisite yellow star on November 8, 1944. After Hungarian requests for his extradition went unanswered, Zentai was able to immigrate to Australia in February 1950, where he currently lives. SEC. 3. SENSE OF THE SENATE. It is the sense of the Senate that-- (1) the United States should actively encourage extradition and prosecution of the remaining Nazi war criminals (as described by 8 U.S.C. 1182 (a)(3)(e)); (2) the Simon Wiesenthal Center should be commended for its historic work in bringing to light the atrocities of the Holocaust and in advancing justice for Nazi war criminals through Operation: Last Chance; and (3) the Office of Special Investigation of the Department of Justice is advancing the declared foreign policy of the United States by bringing wanted World War II criminals to justice and should be commended for its actions. SEC. 4. DESIGNATION OF VISA WAIVER PROGRAM COUNTRIES. (a) Cooperation.--After a country is initially designated as a visa waiver program country under section 217(c) of the Immigration and Nationality Act (8 U.S.C. 1187(c)), the Attorney General, in evaluating the effect that such designation would have on the law enforcement and security interests of the United States under paragraph (2)(C) of such section, shall consider the extent to which such country is cooperating in-- (1) extraditing or prosecuting wanted or indicted Nazi war criminals to the relevant jurisdiction; and (2) admitting into their territory aliens described in section 212(a)(3)(E)(i) and ordered removed from the United States by a United States immigration judge, the Board of Immigration Appeals, or a Federal court. (b) Presidential Discretion.-- (1) In general.--If the President determines that it would not be in the national interest of the United States to terminate a country's designation as a visa waiver program country based on the evaluation under subsection (a), the President may decline to terminate such designation after providing advance written notification to-- (A) the Committee on Foreign Relations of the Senate; (B) the Committee on the Judiciary of the Senate; (C) the Committee on Foreign Affairs of the House of Representatives; and (D) the Committee on the Judiciary of the House of Representatives. (2) Contents.--In providing notification under paragraph (1), the President shall-- (A) identify each crime suspect described in subsection (a)(2) whose admission has not been effected; and (B) submit copies of all decisions rendered by United States immigration judges, the Board of Immigration Appeals, and Federal courts that relate to such crime suspects. SEC. 5. ANNUAL REPORT. In each of the fiscal years 2009 through 2013, the President shall submit an annual report to the committees listed in section 4(b)(1), which describes, for each country that has a pending application for entry into or renewal of the visa waiver program, whether such country is-- (1) cooperating satisfactorily in extraditing or deporting wanted Nazi war crimes suspects to the jurisdiction in which they have been indicted or convicted; (2) prosecuting wanted Nazi war crimes suspects effectively within such country's jurisdiction; and (3) cooperating satisfactorily in admitting to the territory of such country aliens described in section 212(a)(3)(E)(i) and ordered removed from the United States territory by a United States immigration judge, the Board of Immigration Appeals, or a Federal court.

World War II War Crimes Accountability Act of 2008 - Expresses the sense of the Senate that: (1) the United States should encourage extradition and prosecution of the remaining Nazi war criminals; (2) the Simon Wiesenthal Center should be commended for its historic work in bringing to light the atrocities of the Holocaust and in advancing justice for Nazi war criminals through Operation: Last Chance; and (3) the Office of Special Investigation of the Department of Justice is advancing U.S. foreign policy by bringing wanted World War II criminals to justice and should be commended for its actions. Directs the Attorney General, in evaluating the effect on U.S. law enforcement and security interests for purposes of a country's eligibility for visa waiver program designation, to consider the extent to which such country is: (1) cooperating in extraditing or prosecuting Nazi war criminals; and (2) admitting into its territory aliens ordered removed from the United States because of participation in Nazi persecution, genocide, torture, or extrajudicial killing. Authorizes the President, after congressional notification, to not terminate a country's designation based upon such evaluation if in the national interest.

medication adherence is a growing concern to healthcare systems as nonadherence to pharmacotherapy has been associated with adverse outcomes and higher costs of care . medication nonadherence is likely to grow as the population ages and as patients need to take more medications to treat chronic conditions . several studies highlighted that the levels of adherence to treatment in patients with chronic diseases are inadequate showing rates that do not exceed 50% . adherence and persistence to drug treatment represent the key factors necessary to gain a significant reduction in morbidity and mortality and to optimize the use of financial resources , but these aspects are widely underestimated in clinical practice and by patients [ 15 ] . the world health organization ( who ) estimates that the cost of nonadherence to drug therapy amounts to 125 million euros per year in europe . indirect methods include patient interviews , pill counts , refill records , and measurement of health outcomes . however , the most practical approach to apply in clinical practice is patient self - report . the advantages of assessing medication adherence by self - report included simplicity , speed , and viability of use . the morisky medication adherence scale ( mmas-8 ) is one of the most commonly used self - reporting methods [ 8 , 9 ] . in addition , the mmas-8 provides information on behaviors associated with low adherence that may be unintentional ( e.g. , forgetfulness ) or intentional ( e.g. , stopped taking medication(s ) without telling the doctor , because they felt worse when they took it ) . identification of these behaviors can facilitate tailoring of interventions to specific patient issues and is strongly related to concordance [ 7 , 10 ] . currently there are many studies evaluating the degree of adherence to treatment in patients with specific diseases [ 7 , 1113 ] , while there seems to be a lack in the literature related to adherence to treatment in the general population . the purpose of the current analysis was to evaluate adherence to medication in the general population during a prevention - related event held in campania region ( southern italy ) . the prevention - related event was organized by the health campus , a nonprofit organization . it was established to carry out a continuous activity of dissemination and promotion of prevention through specific clinical screening and educational initiatives . the study is part of a larger activity that started in 2010 to assess the health status of the general population of the campania region , by providing free consultation , visits , and diagnostics for people coming to the outdoor hospital held in different public squares of campania region during popular events . the health campus focuses its energy and resources primarily on two major objectives : first , to provide specialist visits for disease prevention and early detection of risks to the health of campania citizens ; second , to promote dissemination of a culture of prevention that encourages a change in lifestyle for healthy living . field clinic , where early diagnosis tests are offered to the general public free of charge . thus the public is encouraged to undergo specialist examinations and is informed about health risks and good practice habits to adopt for early diagnosis and screening . the health campus is typically set up during large , popular events or at the request of public and/or private organizations . a cross sectional assisted interview survey was conducted by pharmacists on a population group selected during the health campus event held in naples in april 2013 during the america 's cup . people who were attending the event and were interested to undergo clinical evaluation and/or to take the opportunity of the available screening services , upon arrival , were selected as eligible if they were 18 years or older and taking at least one medication for at least one chronic condition . while waiting to receive a medical checkup , they were invited to the assessment of medication adherence and were interviewed by pharmacists . all participants provided their written informed consent to the study that was conducted in line with the helsinki declaration for human studies . the information collected included demographic data ( i.e. , age and gender ) , level of education ( referred to italian education system ) , smoking habit , number of drugs taken , and type of chronic disease present such as hypertension , diabetes , heart failure , copd , renal failure , and osteoporosis . self - reported adherence was assessed using the italian validated version of the morisky medication adherence scale ( mmas-8 ) . permission for use is required . this scale has been validated and used in many languages [ 12 , 15 , 16 ] . it consists of eight items that address specific behavior regarding medication assumption and both intentional and unintentional adherence ( questionnaire used for interview is reported as supplementary material available online at http://dx.doi.org/10.1155/2015/682503 , table s1 ) . scores on the morisky medication adherence scale can range from 0 to 8 , scores < 6 reflecting low adherence , scores 6 < 8 reflecting medium adherence , and scores = 8 reflecting high adherence . in this study , none of the interviewed participants reported high adherence on the morisky scale , so the dependent variable of patient adherence was dichotomized into 2 groups : low adherence ( scores < 6 ) versus medium adherence ( scores 6 ) . the mmas provides information on behaviors associated with low adherence that may be unintentional ( e.g. , forgetfulness ) or intentional ( e.g. , stopped taking medication(s ) without telling the doctor , because they felt worse when they took it ) . the mmas-8 is divided into 4 items that assess intentional nonadherence and 4 items that assess unintentional nonadherence . we divided participants with low adherence into two categories : intentional nonadherent when majority of answers provided indicate a behavior that is not related to forgetfulness and unintentional nonadherent when majority of answers provided indicate a behavior that is related to forgetfulness . baseline characteristics of the study population were analyzed using descriptive statistics and their degree of adherence , chi square test , and student 's t - test were used where appropriate . pearson 's correlation was used to assess bivariate association between adherence score and participant characteristic . additionally , associations between adherence and covariates were evaluated after accounting for other variables and predictors using logistic regression . factors were then sequentially eliminated from the multivariate model until only factors significant at the level of p < 0.05 remained in the final model . the characteristics of the analyzed population and the results of univariate association between low adherence on the morisky scale and patient - reported factors are reported in table 1 . 18.9% of patients have a degree graduation , 35.3% of patients had high school graduation whereas 29.8% of patients attended secondary school graduation , and 16.0% finished the primary schools . more specifically , patients with hypertension were 169 ( 54.2% ) ; 37 ( 11.9% ) had type ii diabetes ; 29 ( 9.3% ) had heart failure ; 26 ( 8.3% ) had osteoporosis ; 22 ( 7.1% ) had gastritis ; 5 ( 1.6% ) had copd ; and 4 ( 1.3% ) had renal failure . a total of 37.5% of patients took from 2 to 3 drugs and 59.9% of patients have at least one disease . a total of 76.9% of patients were nonsmoking . in the overall population , 59.9% of participants demonstrated low adherence and 40.1% medium adherence . table 1 shows the characteristics of the population and the significant results ( p < 0.05 ) of the univariate analyses examining the associations between scores on the morisky scale and patient - reported factors . considering the frequency distribution of the mmas-8 items , 42.6% of patients answered that they forgot to take their medicines , 47.1% of patients had problems taking their medicines in the last two weeks , 21.8% of patients have stopped taking their medicines without telling their doctor , 55.4% of patients stated that when they travel they forgot to bring along their medication , 20.2% of patients stated that when they feel like their condition is under control , they stop taking their medication , and 18.3% of patients felt hassled about sticking to their treatment plan . in conclusion , a total of 60.9% of nonadherent participants were intentional , 13.4% of nonadherent subjects were unintentional , and 25.7% of nonadherent participants did not fall within either category . the number of medications prescribed , age , and number of diseases are not significant . however , educational level , smoking habit , and gender were statistically significant ( p = 0.01 ; 0.03 ; 0.03 , resp . ) ( table 1 ) . univariate analysis showed that males have a higher risk of being low adherent than women ( odds ratio ( or ) 1.67 , 95% confidence interval ( ci ) , 1.052.66 ) ; the risk of being nonadherent to treatment for smokers is about double compared to nonsmokers ( odds ratio ( or ) 0.54 , 95% confidence interval ( ci ) 0.300.95 ) . only 2 factors remained as significant independent predictors of high adherence after logistic regression adjustment : level of education ( p = 0.03 ) and smoking habit ( p = 0.03 ) ( table 2 ) . people with high school graduation ( odds ratio ( or ) , 2.21 , 95% confidence interval ( ci ) , 1.084.52 ) and nonsmokers ( odds ratio ( or ) 1.87 , 95% confidence interval ( ci ) , 1.043.35 ) are more adherent to treatment than those with lower education and smokers ( table 2 ) . to the best of our knowledge , this is the first survey about adherence to medication that was carried out during a prevention event , among a population selected at the community level . previous studies on adherence have mostly been restricted to specific clinical populations , a specific disease , and/or a single treatment and the relevance of the outcomes to prescription drug users in general has been unclear . patient compliance to drug therapy is one of the most relevant issues in clinical practice as the success of a therapeutic intervention depends on the actual patient adherence to therapy . the noncompliance to treatment has direct consequences such as the distortion of the effectiveness of the treatment . furthermore , several observational studies raised many concerns about undertreatment in current clinical practice , because it leads to an increase in the number of hospitalizations and consequently an increase of the cost for the health system . in industrialized countries , adherence to treatment by patients with chronic diseases is about 50% . the main causes of poor adherence are the lack of motivation of the patients as well as low average education level , limited awareness about health , and the lack of perception of risk arising from treatment discontinuation . this is in line with our results that showed that low level of education is a predictor of low adherence . moreover different studies indicate that 30% of the interviewed participants claim forgetfulness as the reason for their nonadherence , thus making it a prominent reason for nonadherence . using the mmas-8 about 42.6% of respondents say they do not take their medication regularly due to forgetfulness and 21.8% stop their treatment without speaking to their doctor . intentional nonadherence indicates a lack of understanding and misconceptions regarding the chronicity of a health condition . this behavior can be related to lack of concordance , intended as the fact that the prescriber and patient should come to an agreement about the regimen that the patient will take . taking medications continuously and according to the instructions of the physician is an important aspect of drug treatment . this aspect , however , does not seem to be considered by the patients : our analysis showed that no more than 40.1% of patients have a medium level of adherence . several studies showed that interventions by pharmacists , often as a part of the care team , jointly with clinicians , have been found to be effective in improving medication adherence [ 24 , 25 ] . however in italy pharmacists are not sufficiently involved in adherence - related activities , despite the fact that pharmacists are the last point of contact with the patient before beginning the use of the medications . for this reason we chose to involve the pharmacist in the administration of the questionnaire as a way to improve awareness about adherence - related issues among pharmacists as well . the european innovation partnership a1 action group on active and healthy ageing , in 2012 , has implemented joint initiatives between various european countries to improve the quality of the prescription and adherence to treatment . many intervention strategies that are currently being discussed among partners are aimed to promote coordinated and multidisciplinary intervention by involving all major stakeholders ( general practitioners and specialists , pharmacists , nurses , family , health authorities , and pharmaceutical industry ) . the present initiative is part of the strategy carried out by the eip - aha a1 action group and provides preliminary data that might be useful for the further focused interventions . participation in this study was voluntary and , as a result , there may have been a selection bias . population has not been selected on the basis of specific diseases or according to the number of medications prescribed . nevertheless we assume that to be a minor limitation as the study was not aimed to assess adherence in specific conditions . our results give a first overview about level of adherence and predictive factors . a larger population could provide more robust results . questionnaires are a self - reporting tool that is relatively simple and economical to use , but it could overestimate the rate of medication adherence [ 29 , 30 ] . in conclusion , we provided information about adherence levels in a population selected among participants to a prevention - related event . we found that a factor that could be associated with low levels of adherence was level of education which in turn is related to inadequate health literacy . initiatives to raise awareness of the issue are needed as well as dissemination of the fundamental principles underlying control strategies of nonadherence to therapy . performing such initiatives requires a collective , joint effort that involves different categories of stakeholders , from patient to health care providers and policy makers , whose role may be different depending upon the kind of initiative and health system organization .

objectives . the aim of the study was to assess self - reported medication adherence measure in patients selected during a health education and health promotion focused event held in the campania region . the study also assessed sociodemographic determinants of adherence . methods . an interviewer assisted survey was conducted to assess adherence using the italian version of the 8-item morisky medication adherence scale ( mmas-8 ) . participants older than 18 years were interviewed by pharmacists while waiting for free - medical checkup . results . a total of 312 participants were interviewed during the health campus event . a total of 187 ( 59.9% ) had low adherence to medications . pearson 's bivariate correlation showed positive association between the mmas-8 score and gender , educational level and smoking ( p < 0.05 ) . a multivariable analysis showed that the level of education and smoking were independent predictors of adherence . individuals with an average level of education ( odds ratio ( or ) , 2.21 , 95% confidence interval ( ci ) , 1.084.52 ) and nonsmoker ( odds ratio ( or ) 1.87 , 95% confidence interval ( ci ) , 1.043.35 ) were found to be more adherent to medication than those with a lower level of education and smoking . conclusion . the analysis showed very low prescription adherence levels in the interviewed population . the level of education was a relevant predictor associated with that result .

the typical " jupiter - family comet ( jfc ) loses mass through a relatively slow process of volatile sublimation and dust entrainment . common mass loss rates when a jfc is near perihelion are roughly @xmath0 kg / s @xcite , depending on the size of the nucleus s active area . " this indicates that nominally the cometary nucleus could disintegrate away probably only after thousands of orbits around the sun . this end - state of a jfc has never been directly observed , although such very tiny comets ( meters in diameter ) that are about to disintegrate would be difficult to discover . in any case current thinking ( e.g. * ? ? ? * ) holds that most jfcs end their lives either by plunging into the sun , colliding with a planet , simply turning off and becoming asteroid - like , or by catastrophic fragmentation . this review will focus on this last option and its attendant large mass loss rate . the primary motivation for studying split comets is that they are laboratories for understanding cometary structure and bulk mechanical properties . since this can give us clues about how comets are put together , split comets can be an important window for investigating the details of planetary formation and specifically the accretion of solids into icy planetesimals . as mentioned above , split comets also represent an aspect of cometary evolution . since split comets expose previously buried material to the space environment and thus to our telescopes , they give us a way to probe chemical and thermophysical changes in cometary nuclei . in this paper , recent developments in our understanding of split comets will be discussed . an excellent recent review of this topic is provided by @xcite , and there have been several likewise good reviews before that ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? the goal of this paper is to not duplicate that earlier work but rather to provide updates on work occuring in the interim . conceptually , the question of how do you know when a comet has split ? " is easy to answer . the observational manifestation of a splitting is a condensation that appears away from the head of the comet but moving with very nearly the same proper motion . however not all near - nuclear condensations are actually indicative of a split ; the condensation may or may not hold a solid body and may be simply ( e.g. ) a trick of perspective on jet features in the coma , or a clump of dust from an outburst . the overall dust production rate and the complexity of coma morphology can make the actual identification of a real splitting problematic . in particular , a splitting is often associated with an outburst or a brightening , potentially making it even more difficult to identify a fragment . interestingly , a fragment may not appear even when a comet brightens dramatically . for example comet 29p / schwassmann - wachmann 1 has frequent outbursts ( see , e.g. , * ? ? ? * ) , yet no fragment has ever been seen . on the other hand a comet that appears perfectly typical " could have had a recent splitting , but the fragments may be more than a few arcminutes from the head , i.e. beyond the field - of - view of a typical ccd camera . due to sporadic monitoring of most comets , a fragment will not always be seen in the near - nuclear region ; it may not be discovered until well after the split , as was the case for fragment b of 57p / du toit - neujmin - delporte @xcite , which was found 0.2@xmath1 away from fragment a , the comet s main head . the even more extreme case is the paternity of comets 42p / neujmin 3 ( discovered in 1929 ) and 53p / van biesbroeck ( discovered in 1954 ) , which were found @xcite to be pieces of one comet that split after a close approach to jupiter in 1850 . another problem in determining whether a split has happened is simply faintness . a 50-meter radius bare nucleus that is 2.0 au from the sun and 1.0 au from earth all reasonable numbers for a cometary fragment will have an r - band magnitude of about 25 ( for a geometric albedo of 0.04 ) , which is beyond the reach of many facilities . even when such a fragment is actively outgassing and thus brighter , the observation itself may not be done in such a way as to detect the fragment . all this makes determining the frequency of fragmentation among jfcs relatively difficult to measure . a list of published instances of jfc fragmentation is give in table 1 , but since many comets have long intervals ( months or years ) where no observations are obtained by either professionals or amateurs , this is naturally a lower limit of the true roster . @xcite estimated that a jfc has 0.3% chance of splitting per perihelion passage , based on the historical record of observed fragmentations . @xcite observed a sample of 34 jfcs with ccds in the late 1980s and early 1990s , and found 2 had split , corresponding to a @xmath21% chance of a jfc splitting per year . if these are accurate estimates of the splitting rate , one remarkable consequence is that over the course of the @xmath3 orbits that a typical jfc will be active @xcite , it can expect to split perhaps dozens to hundreds of times . as noted by @xcite , while jfc splittings may be perceived as being rarer than splittings by near - isotropic comets , a given jfc will shed fragments many times during its active life . this finding suggests that the shape and rotation state of a jfc is intimately tied to the specific fragmentation events it has suffered , since the amount of mass coming off in a fragment can be significant compared to the total mass lost by normal outgassing in the course of an orbit . suppose a jfc with perihelion at 1 au and aphelion at 5.2 au ( jupiter s distance ) has a mass loss that is 200 kg / s at perihelion and is proportional to the inverse - square of heliocentric distance . this comet will lose about @xmath4 kg in one orbit . if the effective radius of the nucleus is 2 km , and the density is about 400 kg / m@xmath5 , that is just 0.03% of the comet s total mass . if the comet is active " over 10% of its surface , the mass loss from those active areas erodes about 2 m deep . if an equivalent mass were to come off as a spherical fragment , however , the fragment would be 130 m in radius . this is a reasonable size for a typical " fragment of a jfc @xcite . such a splitting would represent a significant change in gravitational field , angular momentum , and topography . as mentioned earlier , we have not discovered a population of very tiny comets . we do not have observational evidence of a population of deka- or hectometer sized jfcs that could be made up of fragments . the discovery biases almost certainly play a role in this , although , as @xcite showed , if one accounts for the biases it seems that the jfc size distribution really does fall off below @xmath21 km . in other words if the jfc size distribution were a power - law , we should have discovered more comets smaller than 1 km than we actually have . this suggests that most deka- or hectometer sized jfc fragments will not stay as coherent bodies for long ( years to decades ) but eventually disintegrate . in any case , directed , deep searches for smaller jfcs would be useful so that we could directly address this problem with as little observational bias as possible . in particular , a search that covers the projected orbits of several jfcs would put constraints on the lifetimes of the fragments . for example , in fig . 1 we show a spitzer space telescope mosaic of the vicinity of comet 73p / schwassmann - wachmann 3 in may 2006 . approximately three dozen fragments can be seen ; how many will survive to the comet s next perihelion in 2011 ? ( we discuss this comet further in 4.2 . ) while tidal disruption as a mechanism for splitting comets is well understood , it is responsible for only a small fraction of observed splits . briefly , a comet passing close enough to a planet ( usually jupiter ) or the sun will feel different gravitational forces on one end of its nucleus compared to the other . the difference in forces can be strong enough to overcome the body s cohesion . the extremely low tensile strength and high porosity of cometary nuclei , as suggested most recently by the deep impact visit to comet 9p / tempel 1 @xcite , indicate that a tidal force need not be that strong to successfully rip a comet apart . however , in only one case comet d/1993 f2 ( shoemaker - levy 9) are we very sure that tidal disruption is the cause of the fragmentation . comet 16p / brooks 2 probably also suffered this fate but it was not discovered until a few years after the purported close - approach . for all the other comets in table 1 , tidal disruption could not have been the cause of the split . in these cases , we are no closer to understanding why a particular comet splits when it does than we were when @xcite wrote his review . he gives four other methods that could cause splitting : by fast rotation , by thermal stress , by internal gas pressure , and by impacts . since that review was written , our understanding of the thermal properties of cometary nuclei has improved as a result of the deep impact experiment . for example there is stronger evidence now that the thermal conductivity of cometary nuclei is extremely low @xcite , so low that the thermal pulse can penetrate only a few centimeters due to diurnal heating . this means that on diurnal time scales thermal energy may not be transported effectively into the comet s interior any faster than the surface can itself be excavated by normal cometary activity . the existence of abundant co@xmath6 with its low sublimation temperature in p / tempel 1 s coma @xcite also indicates that the comet could not have been entirely baked out . of course these are results for just one comet , but if they are indicative of the average " thermal properties of a jfc , then perhaps it may be less likely for jfcs to split as a result of thermal stress . on the other hand , the low strength of a jfc means that one can conceive of localized structures ( e.g. sheer cliffs in depressions or concentrations of less porous rock ) where thermal stress in just a small volume could cause a much bigger volume to break off . this relates to more fundamental questions of nucleus structure about which we do not yet have much data . how well are the volatiles and refractories mixed within the nucleus ? is the high porosity manifest in micro- or macro- scales ? how common is significant topography ? fragment b was discovered in july 2002 well away from the main part of the comet . soon after , we @xcite discovered eighteen more fragments ( named c " through t " ) along the line of variation ( the projected orbital path ) and extending out 27 arcminutes from the comet s head . a montage of these individual fragments as seen on ut july 17 is shown in fig . 2 , along with a plot of the fragments positions . the fragments had varying brightnesses ranging from 20 to 23.5 mag in r - band . they also had widely varying degrees of condensation ; some fragments were nothing more than blobs of dust with no central source , such as i and p. all fragments seemed to be actively outgassing , though with apparently varying production rates . interestingly , there was no outburst in 2002 associated with this shedding of mass . there was a significant outburst at the previous apparition , in 1996 , when the comet was observed to be about 5 mag brighter than expected . however dynamical analysis of the largest fragments by @xcite suggests that they could not have broken off six years earlier . the fragments must represent a significant fraction of the comet s total mass . how much mass , and what fraction is it ? the size of the nucleus before fragmentation is unknown , but @xcite derived an upper limit to the radius of 1.1 km . so for an assumed density of 400 kg / m@xmath5 , the upper limit to total mass would be approximately @xmath7 kg . the activity of the fragments makes their size estimation problematic , so a mass estimate is even more difficult . however we can make an order - of - magnitude analysis . for example , fragment g had an r - band magnitude of about 22.5 , which at the distance of 57p at the time , would correspond to a solid body with effective radius of about 130 meters . such a body alone would be @xmath20.1% of 57p s total mass . this is an overestimate for this particular fragment since cometary dust contributes to the magnitude , but there are a few fragments that are likely much bigger than g , so this is a reasonable order - of - magnitude estimate of 57p s mass loss . a slightly more sophisticated analysis would be to navely convert all 19 fragment magnitudes to sizes , and thus create a cumulative size distribution ( csd ) . one finds that such a distribution is fairly shallow , with @xmath8 , the number of objects with radius bigger than @xmath9 , proportional to only @xmath10 . while this totally ignores the obvious activity of the fragments , if activity scales roughly with the fragment s surface area , the power - law slope of the size distribution will be unaffected . this slope means that the total mass @xmath11 contained in fragments up to some size cutoff @xmath12 is proportional to @xmath13 . this suggests that much of the fragmented mass is in the largest pieces such as b , e , and f. interestingly , the csd slope is shallower than that of large dust grains found in jfc trails , as measured by @xcite . they found @xmath14 for grains over 0.25 mm . whether this is a clue as to the physical mechanism behind fragmentation remains to be studied . the real significance of the discovery of the train behind 57p is that it was the first time so many fragments had been observed around a , comet . other comets have had as many fragments but only while being completely broken apart or after passage by jupiter or the sun ( e.g. , comet c/1999 s4 ( linear ) , comet d/1993 f2 ( shoemaker - levy 9 ) , and the kreutz sungrazers ) . it motivates the question of whether shedding events happen more frequently than thought and are just being missed due to the extreme faintness of the fragments . indeed , the sheer length of 57p s train suggests that there were several fragmentation episodes in the past . if a jfc loses only fragments of magnitude 23 , 24 , or fainter , only deep imaging of the comet during the course of monitoring will reveal them . the case of 57p also raises questions about the endurance of the smallest fragments . @xcite state that fragment f would have left the primary nucleus i.e. fragment a about 14 months before the discovery observation ; at discovery , f was 6 arcmin from fragment a. they predicted the future motion of fragment f based on this model , but unfortunately apparently little if any data could be obtained by observers to corroborate or refute the hypothesis . however , if true , it suggests that large fragments farther down the train could have been released at even earlier times . fragment t is 27 arcminutes from fragment a 4.5 times farther than fragment f. t could have left the main nucleus ( on its own or as part of another fragment ) years in the past . this would not necessarily be unprecedented , since as @xcite notes jfc fragments can have long endurance ( hundreds of days ) , and there is indication that jfcs can split most anywhere along their orbit . the estimation of the endurance of fragment t would also depend on at what relative speed it left the nucleus . in any case , fragment t is a fairly small fragment : could it have survived for years , and are we just now seeing the end of its life ? is it really persistent despite its small size ? it is also possible that fragment t is a subfragment of a brighter fragment , say fragment s. even so , the distance between s and t is appreciable ( 3.2 arcmin ) and suggests an endurance for t of several months despite its small apparent size . @xcite have modeled the survival times of fragments and show that small , clean icy fragments can survive for months after separation , although whether or not fragment t can be clean enough , " is uncertain . the images in fig . 2 show cometary dust , not gas , and so there must be some dirtiness " to the fragments , which would shorten their lives @xcite . the faintness of the fragments , and then later the fact that the comet was post perihelion and at unfavorable elongation , prevented detailed follow up . the endurance of the the fragments was not directly measured . therefore further observations of the fragments and of the main comet itself at future apparitions would be extremely useful to understand how this comet is evolving . one of the most - widely observed split comets since d / shoemaker - levy 9 has been 73p / schwassmann - wachmann 3 , which first split in 1995 and approached to within 0.07 au of earth in may 2006 . this recent visit was a monumentally important apparition scientifically since it would allow us detailed studies of bright and relatively - fresh fragments fragments whose ices had formerly been deeply embedded within the comet s nucleus but were now exposed to sunlight . in a way , it was similar to the deep impact experiment in that 73p provided us with a close - up view of subsurface pristine cometary material . a review of this comet s behavior was given by @xcite and by @xcite , which we briefly summarize here . this comet split into several fragments in 1995 , some of which deactivated or disintegrated before the apparition was over . at the comet s next apparition in 2000 and 2001 , two of the 1995 fragments , b and c ( the primary part of the comet ) , were recovered , and two new fragments , e and f , were confirmed ( although apparently e broke off from c during the previous orbit ) . f disappeared later in the apparition but the stage was thus set for the 2006 apparition : would b and c survive another perihelion passage ? would e have survived ? would there be a train of even more fragments ? the result was that in april and may 2006 over 60 fragments were found including b and c but not e. the proximity to earth certainly helped ; a fragment of the same size as 57p - g ( mentioned in the last subsection ) would be about 3 mag brighter at 73p s geocentric distance . in any case some of the fragments were very short - lived , lasting for only a few days . amateur astronomers contributed greatly to the census of fragments , in fact even finding fragments that disappeared within a day and so could not be followed up and formally named . lists of the fragments and relevant info have been compiled by @xcite and @xcite , and the former also discusses some preliminary work on describing the cascading fragmentation . one of the many spectacular images from this apparition is shown in fig . 3 , which comes from the hubble space telescope . fragment b was a dynamic and rapidly changing fragment for much of the apparition , and this image epitomizes this . it shows several subfragments ( a.k.a . mini - comets " ) tailward of fragment b itself . these pieces are probably dekameter in scale , and a sequence of images from hst show these fragments moving down the tail , outgassing until they disintegrate away in timescales of only hours or days . the image field - of - view is only about 25 arcseconds . a wider scale picture is shown in fig . 1 , covering almost 5 degrees of sky along the comet s orbital path . the dynamics of the small fragments in figs . 1 and 3 have been analyzed by @xcite , who found that the hst fragments are strongly affected by the non - gravitational reaction force due to outgassing suggesting a high volatile content . on the other hand , the meteoroids " in the spitzer image are moving as would be expected simply from radiation pressure and solar gravity suggesting a low volatile content . this perhaps could be explained as an evolutionary effect , where the hst fragments dry out to become the spitzer fragments . this does require that the hst fragments would have to have sufficient size and sufficiently low rock - to - ice ratio to be able to survive for the several days that they are seen in the hst data . unfortunately , identifying the fragments seen by hst on april 18 with some part of the extended emission seen in the spitzer mosaic on may 4 would be problematic since the spatial resolutions are so different and the time gap is so large . the variability of fragment b is in stark contrast to fragment c , the primary fragment @xcite . that fragment remained relatively stable , with only slowly varying activity , nowhere near the frequency and amplitude of changes seen from night - to - night ( and sometimes within a night ) in fragment b. the two fragments must be roughly comparable in size , yet the specifics of b s shape and the location of its volatiles has made apparently a huge difference in the evolution . many observations of comet 73p were obtained during its apparition , and analysis on these rich datasets continue . we summarize here some of the exciting results and apologize for oversights . arguably some of the most important findings involve the composition . overall , 73p seems to be depleted in ch@xmath15oh , c@xmath6h@xmath16 , and c@xmath6h@xmath6 , but has typical " abundance of hcn @xcite . this means that this ecliptic comet that came from the trans - neptunian region is compositionally similar to c/1999 s4 ( linear ) , a carbon - chain depleted oort cloud comet @xcite . furthermore it is unlike its fellow ecliptic comet 9p / tempel 1 @xcite . this matching of compositions across dynamical classes hints that there was sufficient mixing in the protoplanetary disk to allow individual icy planetesimals to accrete material from various regions . in other words perhaps there is not necessarily a compositional distinction that exactly matches the dynamical distinction of ecliptic comets forming beyond neptune and oort cloud comets forming among the giant planets . alternately , there could simply be interlopers polluting the dynamical groups . in particular , we are only now starting to build up a statistically significant sample of the parent - molecule composition of jfcs @xcite to build upon the daughter - species work by ( e.g. ) @xcite and @xcite . we can note that 73p is a depleted " comet in the @xcite taxonomy and 9p is typical ; " as the parent species of more jfcs are observed , 73p and 9p can be placed into better context . several people compared the two main fragments , b and c , to each other ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? the consensus result is that b and c have similar composition . this is an important finding since both fragments are relatively large fractions of the original comet and so show us fresh material that formerly was very deep inside the nucleus . they should be excellent laboratories for determining heterogeneity i.e. , whether large blocks of the comet have different compositions . no such effect was found , and this is in stark contrast to comet 9p , where the heterogeneity was quite obvious after the deep impact flyby ( e.g. * ? ? ? the fact that 73p seems to be both ( a ) homogeneous and ( b ) different from what may be currently considered typical " composition suggests that this comet had an atypical formation history . however this is speculative and , again , we are suffering somewhat from a small jfc sample . in any case we clearly see the vital need for more surveys of jfc composition . one important additional result regarding composition was presented by @xcite . they showed that the b and c fragments both have the same depleted " abundance of cn , c@xmath6 , and c@xmath15 relative to water . as mentioned , since the fragments were outgassing relatively pristine material , this suggests that this depletion seen in many jfcs could not be an evolutionary effect , but rather is primordial . it may be indicative of the chemistry happening in the protoplanetary disk at the location where at least some of the jfcs formed . the proximity of 73p motivated many observers to investigate the physical properties of the fragments . of primary concern were the fragments sizes and masses . @xcite observed the comet in 1994 , before breakup , and estimated an upper limit of 1.1 km for the radius . some of the most exciting data on the nuclei after break - up were obtained by @xcite , who used radar to obtain delay - doppler maps of fragments b and c in may 2006 . 73p was at the time only the second comet so imaged . the data show that fragment b is at least 0.2 km in radius and that fragment c is about 0.5 to 1 km in radius . these results are consistent with earlier estimates of those two fragments sizes @xcite . while fragment c is the primary remnant of the comet , fragment b took a significant fraction of the mass with it . knowing the rotational states of the larger fragments could potentially give insight into the fragmentation process , the dekameter - scale structure of the comet , and/or the cometary mass . so far , there have been reports only for fragment c ( e.g. * ? ? * ; * ? ? ? fragment b was so active and changing on such short timescales that obtaining either a photometrically- or morphologically - derived period may be challenging . coma structures were seen however ( e.g. * ? ? ? * ) so a sufficient baseline of observations could prove fruitful . rotation periods for the other relatively bright fragments , such as g and h , have not been reported to our knowledge . images such as figs . 1 and 3 make it clear that there is a continuum of sizes among the fragments . an analysis of the size distribution of all fragments has yet to be presented , but @xcite have studied a group of fragments that at the time had all just recently broken off fragment b. their processed image is shown in fig . 4 , and was obtained a few weeks after the hst image in fig . they identify 54 fragments in their data , all of which were active , and measured the luminosity of each . assuming that the activity is proportional to the fragment surface area , they then derive a csd power - law slope " the csd power - law slope but it is actually the differential size distribution s slope ; their @xmath17 is the csd slope . ] based on their 54 fragments : @xmath18 . this is tantalizingly similar to the rough csd slope for 57p as discussed in 4.1 . both csd slopes are much shallower than the overall jfc csd slope as derived by @xcite , suggesting that the process of splitting has an underlying physical mechanism that is different from the primary evolutionary processes ( such as collisions and erosion ) that affect kilometer - scale jfcs . it is important to note however that there is a size mismatch , so such a conclusion is tentative ; there are no independent jfcs known to have nuclei as small as the fragments seen in 73p and 57p . interestingly , both @xcite and @xcite have used simulations to suggest that the jfc csd becomes shallower at sub - kilometer sizes due to a real dearth of such comets in the inner solar system . the centaur 174p / echeclus = ( 60558 ) 2000 ec@xmath19 was discovered by spacewatch in march 2000 @xcite , and it orbits between 5.9 and 15.6 au from the sun . its current orbital intersection distance with jupiter is 0.9 au and with saturn is just 0.2 au ; as a centaur it is likely to be significantly perturbed on @xmath210@xmath20 year timescales @xcite and may become a jfc . no cometary activity was reported for several years after its discovery , and physical properties of the bare object were obtained by several groups @xcite . activity was first noticed in december 2005 by @xcite and continued through may 2006 @xcite , while the comet was about 13 au from the sun . @xcite present an analysis of contemporaneous ground - based visible and spitzer infrared imaging of the comet from february 2006 . their images are shown in fig . 5 , and demonstrate why this comet should be counted as one that has split . the center of brightness of the cometary activity is not on the nucleus itself , but offset ( by six arcseconds at the time the images were taken ) . furthermore there is a condensation embedded in the coma . however , imaging obtained in march 2006 ( i.e. the following month ) by @xcite shows a more diffuse coma , and they state that the surface brightness profiles of the coma suggest that the dust is no longer coming from a central source but rather from a diffuse source . one hypothesis to explain the observations is : echeclus itself was mostly inactive , but perhaps active enough in one locale for a fragment to break off . this fragment stayed active , while the remainder of echeclus continued to have no activity . after a few months , the fragment itself began to disintegrate into smaller pieces or subfragments . the subfragments remained active and so at the spatial resolution obtainable from earth the coma appeared to emanate from a distributed source . the problem with this scenario is explaining why there would not be activity from the hole " on the primary created by the departing fragment . an alternate hypothesis is that we are seeing a satellite of echeclus that just happens to be active . however , the motion of the fragment over the course of several months suggests that it is moving hyperbolically @xcite . the apparent motion is too great for a bound orbit , given the expected mass of echeclus . also , echeclus s hill sphere radius at the time was roughly only @xmath21 km , i.e. about 6 arcsec on the sky . further evidence against the satellite hypothesis is that a search in earlier deep imaging ( when no activity was seen ) yielded no such object @xcite . the fragment itself could be a few kilometers in radius @xcite compared to the @xmath240 km of the primary and so a large impulse would be needed for that much mass to be accelerated up to the @xmath215 to 30 m / s required to reach escape velocity . while typical separation speeds are an order of magnitude smaller @xcite , we note that a fragment that is flung off the surface of echeclus due to the primary s rotation could be given such a speed , since in that case the fragment s speed would be proportional to the primary s radius . on the other hand , current evidence suggests that echeclus has a relatively long rotation period of 27 hours @xcite . while a fragment remains the best explanation for 174p , further study of this enigmatic comet is certainly warranted . the main science goals would be to ( a ) ascertain the nature of echeclus s activity so as to explain how such a large mass could have left the primary ; ( b ) explain why activity is so tightly localized ; ( c ) determine what the source of the activity is ( co ? crystallization of amorphous h@xmath6o ice ? ) and whether this plays a role in making fragmentation more likely ; ( d ) monitor the rest of the centaur population to determine whether any other objects suffer these events , and what the frequency is ; and ( e ) infer what centaur fragmentation implies for the bulk structure and strength of the jfcs that the centaurs become . the soho spacecraft has discovered over 1500 comets , almost all of which are sungrazers " ( comets with perihelia less than about 0.06 au ) . a large fraction of the soho comets are part of the kreutz family , whose comets pass only about 0.005 au from the center of the sun . since the sun s radius is 0.00465 au , many kreutz comets ( and almost all the ones discovered by soho , which are faint ) disintegrate to dust very near perihelion if not earlier . the kreutz comets are all presumably fragments of a long - period comet that broke apart thousands of years ago ; see @xcite for a recent review . since the kreutz comets are of long - period , we do not consider them here . however soho has discovered four other families of sungrazer comets , some of which may be of short - period . while the meyer group @xcite comets have orbital inclinations of about 72@xmath1 , well out of the ecliptic , the marsden group @xcite , the kracht group @xcite , and the kracht ii group @xcite have members with inclinations of 27@xmath1 , 13@xmath1 , and 13@xmath1 , respectively , perfectly normal for short - period comets . as with the kreutz family , the members of each group have similar orbits and thus imply a single progenitor in the past . the perihelia of these comets are at about 0.05 au , so , while not currently passing within the sun s roche limit , perhaps stress due to tidal forces or due to energy transport facilitated fragmentation at higher heliocentric distances . such distant fragmentation has been suggested by @xcite for the kreutz comets . recent work incorporating the 12-year database of cometary astrometry from soho has revealed possible linkages between some of the comets in these three groups , as well as between some comets not belonging to any known group . this information is collected in table 2 . it is worth noting that the linking of apparitions with short - arc orbits can be difficult , especially when independent comets move on similar orbits anyway . there are several other possible links among comets within the three groups that have been reported ( e.g. * ? ? ? * ; * ? ? ? @xcite present a detailed analysis of some of the marsden and kracht group linkages . detailed physical studies of the sungrazing short - period comets are currently limited to observations by sun - staring spacecraft . these often provide magnitudes and thus some secular light curve . in many cases , the comets are sufficiently faint that neither a tail nor an extended coma is visible , limiting the amount of available information on gas and dust . the nuclei are probably of order dekameters in radius @xcite ; this means that even with an improved orbit , it would be feasible to observe such a comet well away from the sun only when it is near earth . for example , a 10-meter radius nucleus at opposition 0.1 au from earth still only achieves an r - band magnitude of 22.5 . so even in a very favorable apparition ( which would not happen very often to begin with ) , it will not be easy to make detailed studies of such comets . the detailed study of a wide sample of sungrazing short - period comets will probably have to wait for very deep and wide sky surveys , or for classically - scheduled time at the largest telescopes . as comet 73p shows , comet fragments have a distribution of sizes . indeed , fig . 1 demonstrates that such a comet gives off fragments that are decimeter sized and larger fragments that are larger than what can be typically lifted off a comet s surface simply by gas drag @xcite . these fragments remain in a trail in the orbit plane since radiation pressure acts slowly on them . the deep infrared observations by iras brought to light the existence of cometary debris trails @xcite , consisting mainly of millimeter and centimeter sized grains that are the largest solid bodies that come off the comet during normal " activity . such grains have often been found to contain most of the mass that is contained in dust . the grains in the trails represent an intermediate size scale between the visible - wavelength dust that is typically micron sized and smaller , and observed fragments that are dekameter sized and larger . an infrared survey of debris trails has been performed by spitzer . @xcite present 24 @xmath22 m imaging of 34 jfcs in which a trail is unambiguously seen in 27 of them about 80% . most of these comets were observed while 2 to 4 au from the sun , and months away from perihelion . examples of the observations presented by @xcite are shown in fig . most of the comets in their survey had not suffered splitting events in the traditional sense ; the particles were liberated by regular cometary activity . one could call these millimeter and centimeter sized particles fragments " only in a liberal definition . nonetheless , the high frequency of trails , coupled with the fact that often the trail was seen all the way out to the edge of the field of view , indicates that jfcs are prodigious producers of millimeter and centimeter sized fragments into the interplanetary dust environment . as @xcite point out , the total mass of these large grains is larger than the total mass of grains seen at visible wavelengths . usually fragments are found serendipitously , but a few pointed searches for fragments have been performed . the survey of @xcite , mentioned earlier , focussed on finding fragments near ( i.e. a few arcminutes away from ) the primary comet . the faint meter and dekameter scale objects could have been missed , however . @xcite did a telescopic search for meter - sized ( and larger ) perseid meteoroids while earth was passing through the meteor stream ; this would have detected fragments of the halley - family comet 109p / swift - tuttle . they sought to find objects a few arcminutes away from the radiant before they collided with earth s atmosphere . the search found no objects , thus constraining the space density of meter - scale objects within the stream . another survey has made use of the proliferation of ccd cameras with very wide fields - of - view . @xcite have used the megacam instrument on the cfh telescope atop mauna kea to search for fragments up to half a degree away from a comet s head . they have observed about 12 jfcs so far with no fragments seen to a limiting magnitude of about 24 . for these comets this limit corresponds to fragments of size about 100 m in radius . with such a large field - of - view , the search is not just a snapshot in time , but actually tests whether these comets have had any splitting event in the previous several months . this kind of survey gives a more complete view of the fragmentation history and so should provide a good new measurement of the frequency of jfc splittings . the interested reader is encouraged to study the recent review of split comets given by @xcite . we have tried here to provide a summary of recent developments on the topic of split comets . but what does the future hold for our understanding of this phenomenon ? while splittings caused by tides can be predicted if the comet s orbit is known , the large majority of jfc splittings instead happen stochastically . classically - scheduled observing runs will often fail to catch these events . synoptic observations of comets however will in general be more fruitful for understanding the full evolution of a comet before , during , and after a fragmentation event ; unbiassed and well - sampled datasets will be important . it is possible that all - sky survey projects in the coming decade will indeed provide us with a great deal of such data . for example , pan - starrs and lsst will likely discover several hundred comets each in their first year of operation in addition to the thousands of new trojans , centaurs , and trans - neptunian objects they will find @xcite . in addition , the temporal coverage ( scanning the sky on week - long timescales ) , depth ( reaching approximately 23rd magnitude ) , and angular resolution will ensure that moderate - sized fragments of jfcs will be found more reliably . furthermore , we will be able to follow the photometric and dynamic evolution of the fragments for months and possibly years at a time . the datasets will revolutionize our picture of fragment behavior and endurance ( in addition to revolutionizing many questions about comets ) . since the review by @xcite was published , the most important event with regard to split jfcs was the apparition of comet 73p / schwassmann - wachmann 3 in 2006 . following up other known split comets in the future would be worthwhile as well but 73p represents a unique case that is crucial to study . observations of 73p in forthcoming years can give us new details about its fragments and its continuing evolution . if fragments b and c survive , we will be able to watch their new surfaces age as they continue to be exposed to the space environment . will the resulting chemistry change the apparent production rates we measure in their comae ? if so , how ? observations of other jfcs at multiple apparitions have shown a constancy in relative coma abundances from orbit to orbit @xcite , but likely none of those comets have had such a recent fragmentation event that produced a secondary of comparable size to the primary . physical observations of the continued unraveling of fragment b and perhaps the eventual unraveling of fragment c would also give us more insight into cometary structure . unfortunately , three of the next five apparitions of 73p are unfavorable only the visits in 2022 and 2033 are good but even limited data on each fragment at each orbit would be useful . more generally , wide - field observations of all jfcs that will make close approaches to earth would be useful for understanding the frequency of fragmentation and the endurance of the fragments , since the proximity will make searches for meter - scale fragments feasible . for example , comet 103p / hartley 2 approaches to 0.12 au in 2010 , and comet 45p / honda - mrkos - pajduakov comes to 0.06 au in 2011 . bauer , j.m . , choi , y .- j . , weissman , p.r . , stansberry , j.a . , fernandez , y.r . , roe , h.g . , buratti , b.j . , sung , h .- i . , 2008 . the large - grained dust coma of 174p / echeclus astron . soc . 120 , 393404 . biver , n. , bockele - morvan , d. , boissier , j. , colom , p. , crovisier , j. , lecacheux , a. , lis , d. c. , parise , b. , menten , k. , and the odin team , 2006 . comparison of the chemical composition of fragments b and c of comet 73p / schwassmann - wachmann 3 from radio observations . boehnhardt , h. , 2002 . comet splitting observations and model scenarios . earth moon & plan . 89 , 91115 . bonev , t. , boehnhardt , h. , and borisov , g. , 2008 . broadband imaging and narrowband polarimetry of comet 73p / schwassmann - wachmann 3 , components b and c , on 3 , 4 , 8 , and 9 may 2006 . astron . & astrophys . 480 , 277287 . carusi , a. , perozzi , e. , valsecchi , g.b . , kresak , l. , 1985 . first results of the integration of motion of short - period comets over 800 years . in : carusi , a. , valsecchi , g.b . ( eds . ) , dynamics of comets : their origin and evolution , pp . 319340 . d. reidel publishing co. dello russo , n. , vervack , r.j . , weaver , h.a . , biver , n. , bockele - morvan , d. , croivisier , j. , lisse , c.m . , 2007 . compositional homogeneity in the fragmented comet 73p / schwassmann - wachmann 3 . nature 448 , 172175 . disanti , m. a. , anderson , w.m . , villanueva , g.l . , bonev , b.p . , magee - sauer , k. , gibb , e.l . , mumma , m.j . , 2007 . depleted carbon monoxide in fragment c of the jupiter - family comet 73p / schwassmann - wachmann 3 . j. 661 , l101-l104 . feaga , l. m. , ahearn , m.f . , sunshine , j.m . , groussin , o. , farnham , t.l . , 2007 . asymmetries in the distribution of h@xmath6o and co@xmath6 in the inner coma of comet 9p / tempel 1 as observed by deep impact . icarus 190 , 345356 . fuse , t. , yamamoto , n. , kinoshita , d. , furusawa , h. , watanabe , j. , 2007 . observations of fragments split from nucleus b of comet 73p / schwassmann - wachamnn 3 with subaru telescope . japan 59 , 381386 . groussin , o. , ahearn , m.f . , li , j .- y . , thomas , p.c . , sunshine , j.m . , lisse , c.m . , meech , k.j . , farnham , t.l . , feaga , l.m . , delamere , w.a . , 2007 . surface temperature of the nucleus of comet 9p / tempel 1 . icarus 187 , 1625 . howell , e. s. , nolan , m.c . , harmon , j.k . , lovell , a.j . , benner , l.a . , ostro , s.j . , campbell , d.b . , margot , j. , 2007 . radar and radio observations of the fragmented comet 73p / schwassmann - wachmann 3 . bull . hughes , d. w. , mcbride , n. , 1992 . short - period comet splitting . 102 , 265268 . kobayashi , h. , kawakita , h. , mumma , m.j . , bonev , b.p . , watanabe , j. , fuse , t. , 2007 . organic volatiles in comet 73p - b / schwassmann - wachmann 3 observed during its outburst : a clue to the formation region of the jupiter - family comets . j. 668 , l75l78 . lorin , o. , rousselot , p. , 2007 . search for cometary activity in three centaurs [ ( 60558 ) echeclus , 2000 fz@xmath23 and 2000 gm137 ] and two trans - neptunian objects [ ( 29981 ) 1999 td@xmath24 and ( 28978 ) ixion ] . mon . not . 376 , 881889 . meech , k. j. , svore , j. , 2004 . using cometary activity to trace the physical and chemical evolution of cometary nuclei . in : festou , m. c. , keller , h. u. , weaver , h. a. ( eds . ) , comets ii , pp . university of arizona press . mumma , m. j. , 2008 . chemical diversity of organic volatiles among comets : an emerging taxonomy and implications for processes in the proto - planetary disk . in : kwok , s. , sandford , s. a. ( eds . ) , proceedings iau symposium no . 251 : organic matter in space , pp . 309 - 310 . cambridge university press . reach , w. t. , lisse , c. m. , kelley , m. s. , vaubaillon j. , 2007 . rocket effect for fragments and meteoroids of the split comet 73p / schwassmann - wachmann 3 . rousselot , p. , 2008 . 174p / echeclus : a strange case of outburst . astron . & astrophys . 480 , 543550 . rousselot , p. , petit , j .- m . , poulet , f. , sergeev , a. , 2005 . photometric study of centaur ( 60558 ) 2000 ec@xmath19 and trans - neptunian object ( 55637 ) 2002 ux@xmath25 at different phase angles . icarus 176 , 478491 . schleicher , d. g. , birch , p. v. , bair , a. n. , 2006 . the composition of the interior of comet 73p / schwassmann - wachmann 3 : results from narrowband photometry of multiple components . schleicher , d. g. , bair , a. n. , 2008 . compositional taxonomy of comets and the unique cases of 96p / machholz 1 and 73p / schwassmann - wachmann 3 . in : lpi editorial board ( eds . ) , lpi contribution no . 1405 : asteroids , comets , meteors 2008 ( cd - rom ) , paper i d 8174 . sekanina , z. , 2007 . earth s 2006 encounter with comet 73p / schwassmann - wachmann : products of nucleus fragmentation seen in closeup . in : valsecchi , g.b . , vokrouhlicky , d. ( eds . ) , near earth objects , our celestial neighbors : opportunity and risk , pp . 211220 . cambridge university press . sekanina , z. , chodas , p. w. , 2005 . origin of the marsden and kracht groups of sunskirting comets . i. association with comet 96p / machholz and its interplanetary complex . 161 , 551586 . stansberry , j. , grundy , w. , brown , m. , cruikshank , d. , spencer , j. , trilling , d. , margot , j .- l . , 2008 . physical properties of kuiper belt and centaur objects : constraints from the spitzer space telescope . in : barucci , m. a. , boehnhardt , h. , cruikshank , d.p . , morbidelli , a. ( eds . ) , the solar system beyond neptune , pp . university of arizona press . storm , s. , samarasinha , n. , mueller , b. , farnham , t. , fernandez , y. , kidder , a. , snowden , d. , ahearn , m. , harris , w. , knight , m. , morgenthaler , j. , lisse , c. , roesler , f. , 2006 . time variability of component c of the fragmented comet 73p / schwassmann - wachmann 3 . sykes , m. v. , walker , r. g. , 1992 . cometary dust trails . i - survey . icarus 95 , 180210 . toth , i. , lamy , p. l. , weaver , h. a. , 2003 . hubble space telescope observations of the nucleus fragment 73p / schwassmann - wachmann 3-b . toth , i. , lamy , p. , weaver , h. a. , 2005 . hubble space telescope observations of the nucleus fragment 73p / schwassmann - wachmann 3-c . icarus 178 , 235247 . toth , i. , lamy , p. , weaver , h. , ahearn , m. , kaasalainen , m. , lowry , s. , 2006 . villanueva , g. l. , bonev , b.p . , mumma , m.j . , magee - sauer , k. , disanti , m. a. , salyk , c. , blake , g. a. , 2006 . the volatile composition of the split ecliptic comet 73p / schwassmann - wachmann 3 : a comparison of fragments c and b. astrophys . j. 650 , l87l90 . weaver , h. a. , lisse , c. m. , mutchler , m. j. , lamy , p. , toth , i. , reach , w. t. , 2006 . hubble space telescope investigation of the disintegration of 73p / schwassmann - wachmann 3 . weissman , p. r. , chesley , s. r. , choi , y. j. , bauer , j. m. , tegler , s.c . , romanishin , w.j . , consolmagno , g. , stansberry , j. a. , 2006 . motion of the activity source associated with active centaur 174p / echeclus ( 60558 ) . 38 , 551 . ll comet & when + 3d / biela & 1840 + 16p / brooks 2 & 1889 , 1995 + 51p / harrington & 1994 , 2001 + 57p / du toit - neujmin - delporte & 2002 + 69p / taylor & 1915 + 73p / schwassmann - wachmann 3 & 1995 , 2001 , 2006 + 79p / du toit - hartley & 1982 + 101p / chernykh & 1991 , 2005 + 108p / ciffreo & 1985 + 120p / shoemaker - holt 1 & 1996 + 141p / machholz 2 & 1987 , 1989 + 174p / echeclus & 2006 + 205p / giacobini & 1896 , 2008 + d/1993 f2 shoemaker - levy 9 & 1992 + p/2004 v5 ( linear - hill ) & 2004 + 2list adapted from work by @xcite . + 2note that 174p is also a centaur . + m. about three dozen fragments of this split comet are visible here , and almost every one has its own cometary tail . the fragments themselves all lie on the comet s projected orbit . courtesy w. t. reach of caltech . to 1 cm , width=528 ] m image from the spitzer space telescope . in each panel , the two arrows indicate the main body of echeclus itself and the condensation of the coma . note that the orientations are slightly different ; in the tmo image , equatorial north is up , while in the sst image , north is 21@xmath1 to the right of up . to 1 cm , width=528 ]

our current understanding of split , jupiter - family comets is reviewed . the focus is on what recent studies of comets have told us about the nature of the splitting phenomenon . the goal is to not repeat the information given in recent reviews of split comets , but to build upon it . in particular , we discuss comets that have suffered splitting or fragmentation events in the past few years . these include comets ( a ) 57p / du toit - neujmin - delporte , observed with a long train of fragments in 2002 ; ( b ) 73p / schwassmann - wachmann 3 , which split in 1995 and was extensively studied during its relatively close passage to earth in 2006 , during which dozens of fragments were discovered and studied ; and ( c ) 174p / echeclus , a centaur and potentially future jfc , which split in late 2005 and was the first such centaur observed to do so . we also discuss recent observations by soho of split comets that are likely of short - period . the spitzer space telescope has observed many jfcs and provided us with unprecedented detailed views of cometary debris trails , which may be thought of as a middle ground between normal " ejection of micron - sized dust grains and the cleaving off of meter - to - kilometer sized fragments . we will also discuss potential breakthroughs in studying splitting jfcs that may come from future surveys . comets splitting , comets individual ( 57p , 73p , 174p ) , comets evolution 96.30.cw , 96.30.c-

SECTION 1. SHORT TITLE. This Act may be cited as the ``Recapture Excess Profits and Invest in Relief (REPAIR) Act of 2005''. SEC. 2. TEMPORARY WINDFALL PROFITS TAX. (a) In General.--Subtitle E of the Internal Revenue Code of 1986 (relating to alcohol, tobacco, and certain other excise taxes) is amended by adding at the end thereof the following new chapter: ``CHAPTER 56--TEMPORARY WINDFALL PROFITS ON CRUDE OIL ``Sec. 5896. Imposition of tax. ``Sec. 5897. Windfall profit; etc. ``Sec. 5898. Special rules and definitions. ``SEC. 5896. IMPOSITION OF TAX. ``(a) In General.--In addition to any other tax imposed under this title, there is hereby imposed on any applicable taxpayer an excise tax in an amount equal to 50 percent of the windfall profit of such taxpayer for any taxable year beginning during 2005 or 2006. ``(b) Applicable Taxpayer.--For purposes of this chapter, the term `applicable taxpayer' means, with respect to operations in the United States-- ``(1) any integrated oil company (as defined in section 291(b)(4)), and ``(2) any other producer or refiner of crude oil with gross receipts from the sale of such crude oil or refined oil products for the taxable year exceeding $100,000,000. ``SEC. 5897. WINDFALL PROFIT; ETC. ``(a) General Rule.--For purposes of this chapter, the term `windfall profit' means the excess of the adjusted taxable income of the applicable taxpayer for the taxable year over the reasonably inflated average profit for such taxable year. ``(b) Adjusted Taxable Income.--For purposes of this chapter, with respect to any applicable taxpayer, the adjusted taxable income for any taxable year is equal to the taxable income for such taxable year (within the meaning of section 63 and determined without regard to this subsection)-- ``(1) increased by any interest expense deduction, charitable contribution deduction, and any net operating loss deduction carried forward from any prior taxable year, and ``(2) reduced by any interest income, dividend income, and net operating losses to the extent such losses exceed taxable income for the taxable year. In the case of any applicable taxpayer which is a foreign corporation, the adjusted taxable income shall be determined with respect to such income which is effectively connected with the conduct of a trade or business in the United States. ``(c) Reasonably Inflated Average Profit.--For purposes of this chapter, with respect to any applicable taxpayer, the reasonably inflated average profit for any taxable year is an amount equal to the average of the adjusted taxable income of such taxpayer for taxable years beginning during the 2000-2004 taxable year period (determined without regard to the taxable year with the highest adjusted taxable income in such period) plus 10 percent of such average. ``SEC. 5898. SPECIAL RULES AND DEFINITIONS. ``(a) Withholding and Deposit of Tax.--The Secretary shall provide such rules as are necessary for the withholding and deposit of the tax imposed under section 5896. ``(b) Records and Information.--Each taxpayer liable for tax under section 5896 shall keep such records, make such returns, and furnish such information as the Secretary may by regulations prescribe. ``(c) Return of Windfall Profit Tax.--The Secretary shall provide for the filing and the time of such filing of the return of the tax imposed under section 5896. ``(d) Crude Oil.--The term `crude oil' includes crude oil condensates and natural gasoline. ``(e) Businesses Under Common Control.--For purposes of this chapter, all members of the same controlled group of corporations (within the meaning of section 267(f)) and all persons under common control (within the meaning of section 52(b) but determined by treating an interest of more than 50 percent as a controlling interest) shall be treated as 1 person. ``(f) Regulations.--The Secretary shall prescribe such regulations as may be necessary or appropriate to carry out the purposes of this chapter.''. (b) Clerical Amendment.--The table of chapters for subtitle E of the Internal Revenue Code of 1986 is amended by adding at the end the following new item: ``Chapter 56. Temporary Windfall Profit on Crude Oil.''. (c) Deductibility of Windfall Profit Tax.--The first sentence of section 164(a) of the Internal Revenue Code of 1986 (relating to deduction for taxes) is amended by inserting after paragraph (5) the following new paragraph: ``(6) The windfall profit tax imposed by section 5896.''. (d) Hurricane Relief Trust Fund.-- (1) In general.--Subchapter A of chapter 98 of the Internal Revenue Code of 1986 (relating to trust fund code) is amended by adding at the end the following new section: ``SEC. 9511. HURRICANE RELIEF TRUST FUND. ``(a) Establishment.--There is established in the Treasury of the United States a trust fund to be known as the `Hurricane Relief Trust Fund', consisting of such amounts as may be appropriated or credited to such Fund as provided in this section or section 9602(b). ``(b) Transfers to Fund.--There are hereby appropriated to the Hurricane Relief Trust Fund amounts equivalent to the taxes received in the Treasury under section 5896. ``(c) Expenditures.--Amounts in the Hurricane Relief Trust Fund shall be available, without further appropriation, to offset the supplemental spending bills that are targeted to aid victims of Hurricanes Katrina and Rita enacted after the date of the enactment of this section and before January 1, 2008. Any funds that have not been expended by December 31, 2008, shall be credited back to the General Fund as regular tax receipts.''. (2) Clerical amendment.--The table of sections for such subchapter is amended by adding at the end the following new item: ``Sec. 9511. Hurricane Relief Trust Fund.''. (e) Effective Dates.-- (1) In general.--Except as provided in paragraph (2), the amendments made by this section shall apply to taxable years beginning in 2005 and 2006. (2) Subsection (c).--The amendments made by subsection (d) shall take effect on the date of the enactment of this Act.

Recapture Excess Profits and Invest in Relief (REPAIR) Act of 2005 - Amends the Internal Revenue Code to: (1) impose on certain oil companies, for taxable years beginning in 2005 or 2006, an excise tax on 50 percent of their windfall profit from the sale of crude oil; (2) allow a tax deduction for the payment of such windfall profit tax; and (3) establish in the Treasury the Hurricane Relief Trust Fund to which windfall tax revenues will be paid to offset the cost of supplemental spending legislation enacted to aid Hurricane Katrina and Rita victims.

absorptive targets and light traps find widespread use in flux calibration , termination of residual reflections in optical systems , and establishing the zero point in reflectance spectrometry . @xcite approximating a near - ideal absorber in a finite volume presents a challenge for such applications the absence of reflected light or how black " an object appears is not a unique material property or treatable as a boundary condition within the framework of electromagnetic theory @xcite but an object s reflectance and absorptance are intimately tied to the surface s material properties and the underlying geometry of the structure . @xcite thus to implement a low reflectance calibrator design , the absorber material s dielectric and magnetic properties need to be either known or experimentally determined in order to suitably tailor the target s geometry . at microwave through sub - millimeter wavelengths , precision absorptive standards find use in radiometric flux calibration and low reflectance targets for remote sensing , @xcite astrophysics , @xcite and other metrology applications . @xcite elements of the design techniques used in these microwave structures can be applied to realize compact , light - weight , and low - reflectance absorbers while maintaining the overall manufacturability for far infrared use at cryogenic temperatures . in this work , a calibration target for cryogenic applications is explored and its performance is described in detail . the design , manufacture and optical characterization of the target structure and selected coatings of potential interest are summarized in sections [ sec : design ] , [ sec : fabrication ] , and [ sec : characterization ] respectively . low reflectance targets have been realized from individual geometric structures @xcite or tilings @xcite of absorbing dielectric cones or pyramids . wedges , rulings @xcite and brewster angle light traps @xcite have also been employed in instrumentation settings where only a single polarization state is of interest . through the microwave waveband , the absorptive coating s finish is typically smooth compared to the freespace wavelength , @xmath7 , and the resulting reflections from surfaces making up the target s facets are largely specular . in this limit , the effective reflectance for a pyramidal wedge with vertex angle , @xmath8 , can be estimated from geometric optics considerations , @xmath9 . here the single bounce reflection at the angle of incidence , @xmath10 , is estimated from the fresnel coefficients . @xcite in effect , the geometry can be used to limit the impact of imperfect _ a priori _ knowledge of the coating properties on the final target absorptance at cryogenic temperatures . @xcite as a result , the key geometric parameters that control the reflectance in this limit are the details of the pyramid s points , grooves at the structure base , and the number of reflections within the structure . @xcite ideally these features would be perfectly sharp ; however , in practice a finite length scale is achievable and set by fabrication tolerances and the coating morphology . in the limit where the freespace wavelength , @xmath7 , is less than twice the tiling period , @xmath11 , the target s response can be computed by treating the structure as an artificial dielectric adiabatic impedance taper . @xcite as the wavelength is further increased beyond the length scale of the taper , @xmath12 , the target s surface appears smooth and incident fields evanescently propagate into the structure . @xcite as a result , the radiation is largely specularly reflected from the structure . more generally , these arguments can be extended to treat the diffuse reflectance from the surface roughness in the design process if sufficient details are available . @xcite here the experimentally observed diffuse reflectance is taken as a property of the coating that in turn determines acceptable substrate geometry and the short wavelength limit of the structure s response . the use of an appropriate coating with a controlled and sufficient thickness to absorb the incident radiation is also an important consideration . here the material is assumed to be non - magnetic and characterized as a function of frequency by a complex dielectric function , @xmath13 , relative to the permittivity of freespace . the thickness of the target s lossy dielectric layer employed must be greater than the material s field penetration length scale , @xmath14 , to suitably attenuate signals before reflection from the underlying substrate . @xcite by design , the substrate is optically thick and the absorptance is related to the reflectance by , @xmath15 . consideration of the fresnel coefficient magnitude at the surface of the lossy dielectric reveals that a lower index coating leads to lower insertion loss per bounce and thus has greater absorptance from the overall structure in the long wavelength limit . in the infrared , a reduction in coating thickness is desirable as long as the coating maintains structural integrity and minimal thermal gradients . with appropriate attention to detail a variety of coatings could potentially be employed in this application @xcite to achieve the desired response . the service temperature of epoxies , paints , and deposited films are typically limited by the material s adhesion and thermal match to the substrate material over the temperature range of interest . for high temperature applications , chemical breakdown and aging may also require more careful consideration . at cryogenic temperatures typical anodized coating ( thermal conductivity , @xmath16w / m / k ) with thickness , @xmath17 m , produces a thermal gradient across the absorber , @xmath18k / mw per unit incident flux , @xmath19 . for our application this consideration is subdominant to the @xmath20k thermometry calibration uncertainty at 4k . cooling or achieving precise knowledge of the target temperature becomes a greater concern in going from bulk to low - volume - filling - fraction metal or semiconducting foams @xcite and semi - metallic nanotubes @xcite in the long wavelength limit due to such coatings lower thermal conductivity . additional considerations for space qualification and other low - outgassing applications can be found in the literature . @xcite based upon prior experience for the target implementation described here we use a custom specified thickness of acktar fractal black @xcite ( acktar fb ) amenable to a variation on the vendor s standard ( @xmath21 m thickness coating ) process for the absorptive coating . . representative geometric ray traces are indicated with dashed lines . the minimal number of bounces occur when rays go through the focus formed by the slot s radius ( black dots , right ) . for a simple slot , the single bounce observation angle is controlled by the slot width and depth ( shaded region , upper right ) . the overall absorptance can be improved through the addition of a dog leg " in the slot as shown ( lower right ) . , width=3 ] in implementing the absorptive calibrator design we concentrate on the use of simple manufacturing approaches to achieve the desired response in the infrared . the underlying approach adopted was to use a lossy dielectric on a highly conductive substrate to achieve high absorptance . see figure [ fig1_disk_crossection ] for target geometry and ray - trace summary . an aluminum alloy , 6061-t6 , is chosen as the target s substrate material . it is durable , easy to machine , and its high thermal conductance minimizes thermal gradients and enables knowledge of the device temperature . the design described is driven by a need for the target to have a total thickness @xmath22 mm . a total calibrator diameter , @xmath23 mm , was chosen for compatibility with our existing integrating sphere configuration and for use as a low - reflectance reference in a cryogenic filter wheel assembly . a pyramidal tiling of the surface is used to limit the total required thickness of the target relative to a single pyramid . the tips of the pyramids ( radius @xmath24 m ) used in the tiling were readily achievable by wire electrostatic discharge milling ( edm ) with a full apex angle , @xmath25 , and are comparable to the surface roughness features of the coatings employed . a finite width slot was substituted for the sharp groove found at the base of the pyramid in a traditional microwave target design . slots @xmath26 m in width , @xmath27 m deep , on a pitch @xmath28 m were defined by the edm wire diameter . the finite slot width relative to the pitch limits the achievable reduction in the pyramidal tiling thickness by a factor of @xmath29 . the resulting patterned features in the aluminum substrate are less than half of the component s thickness and the remainder of the substrate is used to provide low lateral thermal conduction , mounting points for cooling , and thermometry . a cross - section of the fabricated pyramidal target s pyramidal tiles are shown in the upper panel of figure [ fig1_disk_crossection ] . in the specular limit , this geometry has @xmath30 reflections for @xmath31 of rays incident on the pyramidal structure . the ratio of the slot width over the depth limits number of rays with a single bounce and sets the target reflectance in this structure . by tipping the target to @xmath32 from the normal the specular reflectance contribution from the bottom of the slot can be reduced . alternatively , a dog leg " at the bottom of the channel as shown in the lower panel of figure [ fig1_disk_crossection ] can be used to improve the absorptance by increasing the number of bounces ( @xmath33 ) in the slot region and effectively reduces the angular extent of the caustic arising from the slot s finite radius . if greater volume for the target is available , the influence of the finite slot width can be further reduced by using an adiabatically curved path for the slot to geometrically hide its termination from view . the pyramidally tiled absorber structures and optical witness flats were subsequently coated with acktar fb @xcite via physical vapor deposition ( pvd ) for spectral characterization . two coating thicknesses , @xmath34 m and @xmath35 m , were specified in order to insure sufficient coating absorption . see figure [ fig2_disk_photo_sem ] for detailed digital images and a summary of the samples optically characterized in this study . m steelcast ( stycast 2850 ft epoxy loaded with @xmath36 stainless steel powder by volume ) sample on aluminum flat ; ( top - center ) @xmath37 m aeroglaze z306 black paint on steelcast sample for enhanced long and short wavelength response ; ( top - right ) detail of acktar fb coated calibrator on a substrate roughened with a pyramidal tiling viewed approximately @xmath38 from vertical ; ( middle - left ) @xmath39 m acktar fb witness coating on aluminum flat ; ( middle - center ) @xmath39 m acktar fb calibrator roughened with a pyramidal tiling ; ( middle - right ) sem image of @xmath39 m acktar fb coating ; ( lower - left ) @xmath40 m acktar fb witness coating on aluminum flat ; ( lower - center ) @xmath40 m acktar fb calibrator roughened with a pyramidal tiling ; and ( lower - right ) sem image of @xmath40 m acktar fb coating . the images of the flat " and rough " samples ( i.e. , left- and center - columns ) were taken as a single exposure under an intense visible light source from approximately normal incidence . the logarithmic brightness scale has been uniformly adjusted in all digital images of the samples to convey the full range of the intensity recorded . the grey scale in the scanning electron microscope images ( i.e. , middle- and lower - right panels of figures ) are uncorrected and convey the typical morphology of the acktar fb samples investigated.,width=3 ] in addition , a flat sample was coated with `` steelcast '' , a dielectric mixture comprised of emerson cumming 2850 ft epoxy with a @xmath36 volume filing fraction of @xmath41 m stainless steel powder . @xcite the sample was then hand lapped to @xmath42 m thickness with 600grit sand paper . the relative dielectric permittivity and magnetic permeability of this dielectric mixture are @xmath43 and @xmath44 , respectively . these properties were verified for the mixture employed by using a witness coupon as a waveguide fabry - perot resonator @xcite at @xmath45 . to explore improving the steelcast low frequency reflectance , a sample was coated with an anti - reflection layer realized from a @xmath46 m thick layer of aeroglaze z306 paint @xcite with an rms surface roughness , @xmath47 m . in modeling this multi - layer dielectric coating @xcite an effective relative permittivity , @xmath48 , is estimated for the paint on the epoxy substrate using the measured sample parameters and the specular reflectance @xmath49 ( e.g. , see the spectrum in fig . [ fig3_reflectance_specular ] labeled ag : z306 " ) . this combination of materials finds use in targets and baffles in cryogenic applications below @xmath50 and provides an informative point of reference to the microwave structures motivating the calibrator design presented . loaded epoxy structures are typically fabricated by building up the absorber in layers via spraying , molding , or with great difficultly direct machining on a textured substrate . the achievable tolerances with these approaches have higher variability than is observed with pvd coating on an identical patterned substrate in the design s critical tip and slot regions . as a result , a significantly greater calibrator volume is required to insure identical optical performance in practice and the structure s thermal time constant and gradients are correspondingly increased . while relatively high index loaded epoxies provide a path in the microwave to minimize the coating thickness and mass , in going to the infrared , lower index lossy thin films and conversion coatings more naturally serve this purpose . realizing the desired substrate geometry presents the primary challenge to be address in this path to calibrator volume reduction . infrared and sub - millimeter spectra were obtained using a bruker ifs125hr fourier transform spectrometer ( fts ) . this instrument is equipped with internal dtgs ( deuterated triglycine sulfate ) detectors for use in the near- through far - infrared and an external lhe - cooled bolometer with two interchangeable filters for far - infrared and sub - millimeter wavelengths ( @xmath51 and @xmath52 , respectively ) . an array of beamsplitters is used for the different spectral regions ; the following were used here : si on caf2 ( near - ir ) , ge on kbr ( mid - ir ) , @xmath53 m multi - layer mylar ( bruker t222/2 ) , and @xmath54 m mylar ( far - infrared and sub - millimeter ) . the fts is equipped with three internal light sources : tungsten ( near - ir ) , sic globar ( mid - ir ) , and a mercury arc lamp ( far - ir ) . reflectance spectra for the samples were measured in each band and then merged together to form a composite spectrum . spectra are recorded _ in vacuo _ ( @xmath55 mbar ) . m ( gray ) and @xmath40 m ( black ) coatings ; and the bold lines are the acktar fb @xmath39 m ( gray ) and @xmath40 m ( black ) coatings on substrates roughened with a pyramidal tiling . the coatings are deposited on aluminum substrates . , width=3 ] m ( gray ) and @xmath40 m ( black ) coatings ; and the bold lines are the acktar fb @xmath39 m ( gray ) and @xmath40 m ( black ) coatings on substrates roughened with a pyramidal tiling . all coatings are deposited on aluminum substrate disks . the room temperature bruker integrating sphere ( 300k , @xmath56 ) and the opasi - t cryogenic reflectometer ( 4.2k , @xmath57 ) data were calibrated with a polished aluminum reference . the measured data from the two instrument configurations are in agreement in the region of shared spectral overlap.,width=3 ] specular reflectance data were recorded over the frequency range of @xmath58 at a @xmath59 resolution using a pike technologies accessory ( part no . sku2084 ) . light from the spectrometer takes a `` w''-path through the accessory , which has collimating optics and a fixed @xmath60 angle of incidence on the sample . in this set - up , the sample s reflectance spectrum is obtained by taking the ratio of the light intensity detected from the sample being measured to the intensity of an gold coated flat provided with the pike accessory . see figure [ fig3_reflectance_specular ] for the observed specular reflectance spectra . diffuse reflectance spectra were recorded using a bruker integrating sphere accessory ( part no . a562g / q ) over a frequency range of @xmath61 . this accessory is equipped with a side - mounted dtgs detector used primarily for mid- and near- infrared wavelengths and is supplied with a diffusely reflecting gold reference . internal absorptive baffles are used to shield the detector from receiving light reflected directly from the samples . in order to mitigate the typical noise of measurements with the integrating sphere apparatus , and to help enhance the broad structure of the features ( e.g. , see the acktar fb @xmath39 m flat coating between @xmath62 ) , spectra were recorded using spectral resolutions of 8 and @xmath63 . in addition to the bruker integrating sphere accessory , diffuse reflectance was measured for the roughened acktar fb @xmath40 m coating using a custom cryogenic integrating sphere . @xcite this apparatus is equipped with a si bolometer element ( 4.2k ) and an internal temperature - controlled sample wheel . far infrared spectra between @xmath64 with @xmath65 resolution were measured using this apparatus mounted to a bruker ifs 113v fts equipped with an internal sic globar source and 3.5 and @xmath66 m mylar beamsplitters . see figure [ fig4_reflectance_diffuse ] for observed diffuse reflectance spectra . from the observed diffuse reflectance of the witness samples in figure [ fig4_reflectance_diffuse ] one notes both acktar fb coatings have a slightly lower reflection than aeroglaze z306 paint in the spectral range of interest . the calibrator constructed with @xmath40 m of acktar fb was noted to have the best overall optical performance of the structures tested with an observed diffuse reflectance of @xmath67 between @xmath1 ( @xmath68 m ) . the minimum in the diffuse reflectance , @xmath69 , occurs at @xmath70 ( @xmath71 m ) . this represents a reduction in the diffuse reflectance by a factor of @xmath72 over a simple flat with an identical coating . the low frequency response of the calibrator samples is set by the pyramidal tiling s pitch and finite coating thickness . at greater than @xmath32 from normal incidence the grey lines seen in figure [ fig2_disk_photo_sem ] that originate from spectral reflectance off the bottom of the calibrator s slots are no longer discernible . this artifact can be further mitigated by gradually turning the slot and removing its endpoint from view as indicated in figure [ fig1_disk_crossection ] . incorporation of this fabrication detail is recommended to improve the overall emittance . the calibrator is broadband , mechanically robust , and has survived multiple cool downs to @xmath6k . due to the structure s low reflectance it has been adopted as the preferred absorptive light trap for general laboratory use . the authors gratefully acknowledge financial support from the nasa roses / apra program and thank e. sharp and c. wheeler for their contributions to preparation and fabrication of the structures presented here . r. kinzer was supported by an appointment to the nasa postdoctoral program at gsfc , administered by the oak ridge associated universities . 33ifxundefined [ 1 ] ifx#1 ifnum [ 1 ] # 1firstoftwo secondoftwo ifx [ 1 ] # 1firstoftwo secondoftwo `` `` # 1''''@noop [ 0]secondoftwosanitize@url [ 0 ] + 12$12 & 12#1212_12%12@startlink[1]@endlink[0]@bib@innerbibempty @noop * * , ( ) @noop _ _ ( , , ) pp . @noop _ _ ( , , ) p. link:\doibase 10.1117/12.370182 [ * * , ( ) ] link:\doibase 10.1063/1.1142534 [ * * , ( ) ] link:\doibase 10.1086/306805 [ * * , ( ) ] link:\doibase 10.1007/bf01010634 [ * * , ( ) ] link:\doibase 10.1063/1.2209960 [ * * , ( ) ] link:\doibase 10.1063/1.1821622 [ * * , ( ) ] link:\doibase 10.1364/ao.16.002352 [ * * , ( ) ] link:\doibase 10.1364/ao.20.001118 [ * * , ( ) ] link:\doibase 10.1002/col.5080110406 [ * * , ( ) ] @noop _ _ , edited by and ( , , ) chap . , pp . @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1109/15.328859 [ * * , ( ) ] link:\doibase 10.1109/15.809815 [ * * , ( ) ] link:\doibase 10.1364/josa.64.000339 [ * * , ( ) ] link:\doibase 10.1364/ao.23.002311 [ * * , ( ) ] http://stacks.iop.org/0022-3735/18/i=8/a=010 [ * * , ( ) ] link:\doibase 10.1063/1.1149739 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) in link:\doibase 10.1117/12.894601 [ _ _ ] , , vol . ( ) @noop `` , '' ( , ) in link:\doibase 10.1117/12.819277 [ _ _ ] , , vol . ( ) in @noop _ _ ( ) @noop link:\doibase 10.1007/s10762 - 007 - 9299 - 4 [ * * , ( ) ] @noop @noop _ _ ( , , ) chap . . link:\doibase 10.1364/ao.50.004115 [ * * , ( ) ]

a compact cryogenic calibration target is presented that has a peak diffuse reflectance , @xmath0 , from @xmath1 @xmath2 m ) . upon expanding the spectral range under consideration to @xmath3 @xmath4 m ) the observed performance gracefully degrades to @xmath5 at the band edges . in the implementation described , a high - thermal - conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target . the resulting target assembly is lightweight , has a low - geometric profile , and has survived repeated thermal cycling from room temperature to @xmath6k . basic design considerations , governing equations , and test data for realizing the structure described are provided . the optical properties of selected absorptive materials acktar fractal black , aeroglaze z306 , and stycast 2850 ft epoxy loaded with stainless steel powder are characterized and presented .

SECTION 1. SHORT TITLE. This Act may be cited as the ``China Human Rights and Democracy Act of 1997''. SEC. 2. UNITED STATES INTERNATIONAL BROADCASTING TO CHINA. (a) Authorization of Appropriations for International Broadcasting to China.--In addition to such sums as are otherwise authorized to be appropriated for ``International Broadcasting Activities'' for fiscal years 1998 and 1999, there are authorized to be appropriated for ``International Broadcasting Activities'' $40,000,000 for fiscal year 1998 and $30,000,000 for fiscal year 1999, which shall be available only for broadcasting to China. Of the funds authorized to be appropriated for fiscal year 1998, $10,000,000 is authorized to be appropriated for capital expenditures for the purchase and construction of transmission facilities. Of the funds authorized to be appropriated for fiscal year 1998 and fiscal year 1999, $20,000,000 is authorized to be appropriated for Radio Free Asia. (b) Sense of Congress.--It is the sense of the Congress that United States international broadcasting through Radio Free Asia and Voice of America should be increased to provide continuous 24-hour broadcasting in multiple languages and dialects which shall include Mandarin, Cantonese, Tibetan, and Uighur. SEC. 3. DEMOCRACY BUILDING IN CHINA. (a) Authorization of Appropriations for NED.--In addition to such sums as are otherwise authorized to be appropriated for the ``National Endowment for Democracy'' for fiscal years 1998 and 1999, there are authorized to be appropriated for the ``National Endowment for Democracy'' $5,000,000 for fiscal year 1998 and $5,000,000 for fiscal year 1999, which shall be available to promote democracy, civil society, and the development of the rule of law in China. (b) East Asia-Pacific Regional Democracy Fund.--The Secretary of State shall use funds available in the East Asia-Pacific Regional Democracy Fund to provide grants to nongovernmental organizations to promote democracy, civil society, and the development of the rule of law in China. SEC. 4. HUMAN RIGHTS IN CHINA. (a) Reports.--Not later than March 30, 1998, and each subsequent year thereafter, the Secretary of State shall submit to the International Relations Committee of the House of Representatives and the Foreign Relations Committee of the Senate an annual report on human rights in China, including religious persecution, the development of democratic institutions, and the rule of law. Reports shall provide information on each region of China. (b) Prisoner Information Registry.--The Secretary of State shall establish a Prisoner Information Registry for China which shall provide information on all political prisoners, prisoners of conscience, and prisoners of faith in China. Such information shall include the charges, judicial processes, administrative actions, use of forced labor, incidences of torture, length of imprisonment, physical and health conditions, and other matters related to the incarceration of such prisoners in China. The Secretary of State is authorized to make funds available to nongovernmental organizations presently engaged in monitoring activities regarding Chinese political prisoners to assist in the creation and maintenance of the registry. (c) Human Rights Officers in China.--The Secretary of State shall designate or assign not less than 6 foreign service officers to the United States Embassy and consular offices in China with the principal assignment of monitoring and reporting on human rights matters in China. In addition, the number of officers assigned to the United States diplomatic missions in China whose principal assignment is commerce or trade may not exceed the number of officers in China whose principal assignment is human rights matters. SEC. 5. REPORTS TO CONGRESS ON CHINESE MILITARY AND INTELLIGENCE ACTIVITIES. (a) Report Concerning Chinese Intelligence Activities Directed Against United States Interests.--No later than March 30 of each calendar year, the President shall report in both classified and unclassified form on all Chinese intelligence collection activities directed against United States interests to the Committees on National Security, International Relations, and Intelligence of the House of Representatives and the Committees on Armed Services, Foreign Relations, and Intelligence of the Senate. (b) Information Concerning Commercial Enterprises Affiliated With the Chinese Military.--The Secretary of Commerce, in consultation with the Secretaries of State, Defense and Treasury and the Director of the Central Intelligence Agency, shall compile and make available to the public through all appropriate means, including internet technology, information concerning Chinese commercial enterprises or joint ventures in which the Chinese Ministry of Defense, the Peoples Liberation Army, affiliated commercial entities, or senior officials of such entities and their immediate family, have an ownership interest. SEC. 6. PRINCIPLES THAT SHOULD BE ADHERED TO BY ANY UNITED STATES NATIONAL CONDUCTING AN INDUSTRIAL COOPERATION PROJECT IN THE PEOPLE'S REPUBLIC OF CHINA. (a) Purpose.--It is the purpose of this section to create principles governing the conduct of industrial cooperation projects of United States nationals in the People's Republic of China. (b) Statement of Principles.--It is the sense of the Congress that any United States national conducting an industrial cooperation project in the People's Republic of China should: (1) Suspend the use of any goods, wares, articles, or merchandise that the United States national has reason to believe were mined, produced, or manufactured, in whole or in part, by convict labor or forced labor, and refuse to use forced labor in the industrial cooperation project. (2) Seek to ensure that political or religious views, sex, ethnic or national background, involvement in political activities or nonviolent demonstrations, or association with suspected or known dissidents will not prohibit hiring, lead to harassment, demotion, or dismissal, or in any way affect the status or terms of employment in the industrial cooperation project. The United States national should not discriminate in terms or conditions of employment in the industrial cooperation project against persons with past records of arrest or internal exile for nonviolent protest or membership in unofficial organizations committed to nonviolence. (3) Ensure that methods of production used in the industrial cooperation project do not pose an unnecessary physical danger to workers and neighboring populations or property, and that the industrial cooperation project does not unnecessarily risk harm to the surrounding environment; and consult with community leaders regarding environmental protection with respect to the industrial cooperation project. (4) Strive to establish a private business enterprise when involved in an industrial cooperation project with the Government of the People's Republic of China or other state entity. (5) Discourage any Chinese military presence on the premises of any industrial cooperation projects which involve dual-use technologies. (6) Undertake to promote freedom of association and assembly among the employees of the United States national. The United States national should protest any infringement by the Government of the People's Republic of China of these freedoms to the International Labor Organization's office in Beijing. (7) Provide the Department of State with information relevant to the Department's efforts to collect information on prisoners for the purposes of the Prisoner Information Registry, and for other reporting purposes. (8) Discourage or undertake to prevent compulsory political indoctrination programs from taking place on the premises of the industrial cooperation project. (9) Promote freedom of expression, including the freedom to seek, receive, and impart information and ideas of all kinds, regardless of frontiers, either orally, in writing or in print, in the form of art, or through any media. To this end, the United States national should raise with appropriate authorities of the Government of the People's Republic of China concerns about restrictions on the free flow of information. (10) Undertake to prevent harassment of workers who, consistent with the United Nations World Population Plan of Action, decide freely and responsibly the number and spacing of their children; and prohibit compulsory population control activities on the premises of the industrial cooperation project. (c) Promotion of Principles by Other Nations.--The Secretary of State shall forward a copy of the principles set forth in subsection (b) to the member nations of the Organization for Economic Cooperation and Development and encourage them to promote principles similar to these principles. (d) Registration Requirement.-- (1) In general.--Each United States national conducting an industrial cooperation project in the People's Republic of China shall register with the Secretary of State and indicate whether the United States national agrees to implement the principles set forth in subsection (b). No fee shall be required for registration under this subsection. (2) Preference for participation in trade missions.--The Secretary of Commerce shall consult the register prior to the selection of private sector participants in any form of trade mission to China, and undertake to involve those United States nationals that have registered their adoption of the principles set forth above. (e) Definitions.--As used in this section-- (1) the term ``industrial cooperation project'' refers to a for-profit activity the business operations of which employ more than 25 individuals or have assets greater than $25,000; and (2) the term ``United States national'' means-- (A) a citizen or national of the United States or a permanent resident of the United States; and (B) a corporation, partnership, or other business association organized under the laws of the United States, any State or territory thereof, the District of Columbia, the Commonwealth of Puerto Rico, or the Commonwealth of the Northern Mariana Islands. SEC. 7. PROMOTION OF EDUCATIONAL, CULTURAL, SCIENTIFIC, AGRICULTURAL, MILITARY, LEGAL, POLITICAL, AND ARTISTIC EXCHANGES BETWEEN THE UNITED STATES AND CHINA. (a) Exchanges Between the United States and China.--Agencies of the United States Government which engage in educational, cultural, scientific, agricultural, military, legal, political, and artistic exchanges shall endeavor to initiate or expand such exchange programs with regard to China. (b) Legislative Exchange Program.--It is the sense of the Congress, that the Speaker of the House and the Majority Leader of the Senate should establish a legislative exchange program with the National Peoples Congress of China. (c) Sense of Congress.--It is the sense of the Congress that a federally chartered not-for-profit organization should be established to fund exchanges between the United States and China through private donations. SEC. 8. DENIAL OF ENTRY INTO THE UNITED STATES OF CERTAIN CHINESE GOVERNMENT APPLICANTS. (a) Denial of Entry.--Except as provided in subsection (b), the Secretary of State may not issue any visa to, and the Attorney General may not admit to the United States, any national of the People's Republic of China where a consular officer or the Attorney General knows or has reasonable grounds to believe-- (1) the applicant has been materially involved in the commission of human rights violations, as defined in subsection (c), within the People's Republic of China; or (2) the applicant has been materially involved in the proliferation of conventional or nuclear weapons technology, or other sensitive or dual-use technologies, in contravention of United States interests. (b) Waiver.-- (1) In general.--Subject to paragraph (2), the President may waive the applicability of subsection (a) with respect to any applicant otherwise covered by that paragraph if the President determines that the waiver with respect to the applicant is in the national interest of the United States. (2) Notice.-- (A) Requirement.--The President may not exercise the authority provided in paragraph (1) with respect to an applicant unless the President submits to Congress a written notification of the exercise of the authority. (B) Contents.--Notices of the exercise of waiver authority shall include-- (i) a statement of the activities of the applicant which triggered the application of this statute; and (ii) an explicit statement detailing the policy reasons and factual bases for the finding that the issuance of a visa to the applicant at issue is in the national interest of the United States. (C) Other reports.--The Secretary of State, in consultation with the Attorney General, shall provide to the Congress, not later than March 1 of each calendar year following the enactment of this statute, a report concerning the application of this provision. This report should include information on all instances in which this statute was triggered by an applicant and the subsequent disposition of the application. (c) Definitions.--For the purposes of this Act, the term ``human rights violations'' means actions which are in contravention of the Universal Declaration of Human Rights or the International Covenant on Civil and Political Rights, including, but not limited to, material involvement in the suppression of the free practice of religion, the creation and implementation of coercive family planning policies or the massacre of nonviolent demonstrators in Tiananmen Square on June 4, 1989. SEC. 9. SENSE OF CONGRESS CONCERNING ESTABLISHMENT OF A COMMISSION ON SECURITY AND COOPERATION IN ASIA. It is the sense of the Congress that Congress, the President, and the Secretary of State should work with the governments of other countries to establish a Commission on Security and Cooperation in Asia which would be modeled after the Commission on Security and Cooperation in Europe.

China Human Rights and Democracy Act of 1997 - Authorizes appropriations for International Broadcasting Activities only for broadcasting to China. Earmarks funds for: (1) capital expenditures for the purchase and construction of transmission facilities; and (2) Radio Free Asia. (Sec. 2) Expresses the sense of the Congress that U.S. international broadcasting through Radio Free Asia and Voice of America should be increased to provide continuous 24-hour broadcasting in multiple languages and dialects, including Mandarin, Cantonese, Tibetan, and Uighur. (Sec. 3) Authorizes appropriations to the National Endowment for Democracy, and directs the Secretary of State to use funds available in the East Asia-Pacific Regional Democracy Fund, to promote democracy, civil society, and the development of the rule of law in China. (Sec. 4) Directs the Secretary to report annually to specified congressional committees on human rights in China, including religious persecution, the development of democratic institutions, and the rule of law. Directs the Secretary to: (1) establish a Prisoner Information Registry for China; and (2) assign not less than six foreign service officers to the U.S. Embassy and consular offices in China to monitor and report on human rights matters in China. (Sec. 5) Requires specified reports to the Congress on Chinese intelligence activities against U.S. interests and on commercial enterprises affiliated with the Chinese military. (Sec. 6) Expresses the sense of the Congress that U.S. nationals conducting industrial cooperation projects in China should adhere to certain principles. Declares that such nationals should: (1) suspend the use of any merchandise that they have reason to believe was produced by convict or forced labor, and refuse to use forced labor in their projects; (2) seek to ensure that political or religious views, sex, ethnic or national background, or association with dissidents will not prohibit hiring, lead to harassment, demotion, or dismissal of an individual employed in the industrial cooperation project; (3) ensure that methods of production used in the projects do not pose unnecessary danger to workers and the surrounding neighborhoods and environment; (4) strive to establish a private business enterprise when involved in an industrial cooperation project with China or other state entity; (5) discourage any military presence on the premises of projects which involve dual-use technologies; (6) promote freedom of association and assembly among the U.S. national's employees; (7) provide the Department of State with information relevant to its efforts to collect information on prisoners for purposes of the Prisoner Information Registry; (8) discourage or prevent compulsory political indoctrination programs from taking place on project premises; (9) promote freedom of expression of all kinds; and (10) prevent harassment of workers who decide freely the number and spacing of their children, and prohibit compulsory population control activities on the premises of the project. Directs the Secretary to forward a copy of these principles to the member nations of the Organization for Economic Cooperation and Development, and encourage them to promote similar principles. Directs each U.S. national conducting an industrial cooperation project in China to register with the Secretary and indicate whether they agree to implement such principles. Requires the Secretary of Commerce to give preference to U.S. nationals that have adopted such principles when selecting participants for trade missions in China. (Sec. 7) Requires the promotion of cultural, educational, scientific, agricultural, military, legal, political, and artistic exchanges between the United States and China. Expresses the sense of the Congress that: (1) the Speaker of the House and the Majority Leader of the Senate should establish a legislative exchange program with China; and (2) a federally chartered not-for-profit organization should be established to fund exchanges between the United States and China through private donations. (Sec. 8) Prohibits the Secretary from issuing any visa to, and the Attorney General from admitting to the United States, any Chinese national that has been materially involved in: (1) the commission of human rights violations; or (2) the proliferation of conventional or nuclear weapons technology, or other sensitive or dual-use technologies, in contravention of U.S. interests. Provides for waiver of such requirements in the U.S. national interest. (Sec. 9) Expresses the sense of the Congress that the Congress, the President, and the Secretary should work with the governments of other countries to establish a Commission on Security and Cooperation in Asia which would be modeled after the Commission on Security and Cooperation in Europe.

from fungi to mammals , the stress - activated mapk pathway is evolutionarily conserved and plays a crucial role in responding to a plethora of environmental cues ( bahn , 2008 ) . for example , a two - component - like phosphorelay system is found to be a major signaling cascade upstream of the stress - activated mapk pathway in fungi , but not in mammals ( bahn , 2008 ) . s. cerevisiae contains a stress - activated mapk , named hog1 , a protein involved in sensing , responding , and adapting to diverse environmental cues including pheromone sensing and initiation of sporulation during mating , filamentous growth under nitrogen starvation , and the response to osmotic and cell wall stresses ( chen and thorner , 2007 ) . the hog pathway is one of the key sas pathways in c. neoformans and consists of multiple signaling components ( fig . 1 ) . the signaling cascade upstream of the hog1 mapk module is the multi - component phosphorelay system , comprised of a hybrid sensor histidine kinase ( hk ) , including tco1 and tco2 ( bahn et al . , 2006 ) , a histidine - containing phosphotransfer protein ( hpt ) ypd1 , and response regulators ( rr ) , ssk1 and skn7 . the hog1 mapk module consists of ssk2 mapk kinase kinase ( mapkkk ) , pbs2 mapk kinase ( mapkk ) , and hog1 mapk . downstream of the hog1 mapk , multiple stress defense and protein kinase genes have been identified recently ( ko et al . after exposure to certain external cues , a hybrid sensor hk in the phosphorelay system autophosphorylates a his residue in its hk domain and transfers the phosphate group to an asp residue in the rr domain in the same hybrid sensor hk . subsequently , the phosphate in the rr domain is delivered to a his residue in the hpt and then transferred to an asp residue in a response regulator ( bahn , 2008 ) . next , the activated response regulator interacts with the autoinhibitory domain of the ssk2-like mapkkk and induces the autophosphorylation of a thr residue in the ser / thr kinase domain . in turn , the activated mapkkk phosphorylates the ser and thr residues of the pbs2-like mapkk , which then dually phosphorylates the thr and tyr residues of the hog1-like mapk ( bahn , 2008 ) . in c. neoformans , tco1 and tco2 hks act redundantly and independently for either positive or negative regulation of the hog1 mapk . however , the ssk1 response regulator appears to positively regulate the hog1 mapk module since phenotypes of the ssk1 mutant are mostly identical to those of the hog1 mutant ( bahn et al . , 2006 ) . another c. neoformans response regulator , skn7 , is also involved in stress responses to high salt conditions , oxidative damages ( e.g. tert - butyl hydroperoxide ) , and the antifungal drug fludioxonil . skn7 , however , appears to act independently from the hog1 mapk module ( fig . 1 ) ( bahn et al . , 2006 ) . the hog1 mapk is found in both c. neoformans serotype a and serotype d. the role of hog1 in c. neoformans , and its regulatory mechanism , however , varies between different clinical and environmental c. neoformans strains ( hoang et al . , most notably , the hog1 mapks in a majority of c. neoformans are uniquely regulated in response to environmental stresses . in most other fungi and in mammals , the hog1 mapk is unphosphorylated and localizes to the cytosol under unstressed condition , but is rapidly phosphorylated for translocation into the nucleus and activation of target genes . by contrast , in a number of c. neoformans strains , including the serotype a h99 strain , hog1 is constitutively phosphorylated , found in both the cytosol and nucleus even under unstressed conditions , and rapidly dephosphorylated for activation by stress ( bahn , 2008 ) . this type of hog1 regulation is not observed in all c. neoformans strains . in a minority of c. neoformans strains , such as the serotype d jec21 stain , hog1 is regulated in a conventional manner similar to other fungi ( bahn , 2008 ) . this difference appears to account for the different roles of the hog pathway between c. neoformans strains . for instance , the hog1 mutant generated in the h99 strain background , but not the hog1 mutant generated in the jec21 background , shows an increased sensitivity to high temperature ( 39~40 ) and hydrogen peroxide . in addition , the mating capability is enhanced in the hog1 mutant of the h99 strain , but not of the jec21 strain . in the h99 strain background , mutation of genes in the hog pathway induces pheromone production and cell - cell fusion in the early stage of mating ( bahn et al . , 2005 ) . the major benefit of having constitutively phosphorylated hog1 appears to be increased stress - resistance . notably , the c. neoformans strains with constitutively phosphorylated hog1 are more stress - resistant than those having unphosphorylated hog1 under unstressed condition . the hog pathway in c. neoformans not only responds to osmotic stress , but also controls diverse environmental stress responses against uv irradiation , oxidative stress , heavy metal stress , antifungal drugs , toxic metabolites , and high temperature ( bahn et al . , 2005 , 2006 , 2007 ; moreover , the hog pathway is involved in controlling production of two major c. neoformans virulence factors , capsule and melanin , which are also regulated by the camp signaling pathway ( alspaugh et al . , 1997 , 2002 ; d'souza et al . , 2001 ; bahn et al . , finding , dna microarray analyses have shown that genes required for production of capsule , such as cap10 , cap59 , cap60 and cap64 , and melanin , such as lac1 , were found to be induced following inactivation of the hog pathway ( ko et al . , 2009 ) . recently , a genome - wide transcriptome analysis of the hog pathway has led to the discovery of a number of hog downstream target genes . in response to osmotic stress , the ena1 gene , encoding a putative p - type atpase sodium pump , , ena1 is required for long - term adaptation to osmotic shock and is also activated by hog1 ( proft and struhl , 2004 ) . the c. neoformans ena1 mutant is hypersensitive to osmotic shock under glucose starvation and low ph conditions ( ko et al . , 2009 ; idnurm et al . , interestingly , idnurm and co - workers reported that ena1 is required for full virulence of c. neoformans ( idnurm et al . a number of genes are regulated in a hog1-dependent manner ( ko et al . , 2009 ) . these include sch9 , encoding a protein kinase , and ubc6 - 2 and ubc8 , two genes that appear to be involved in the ubiquitin proteasome system . in s. cerevisiae , sch9 kinase regulates transcription factors , such as sko1 , that respond to osmotic shock ( pascual - ahuir and proft , 2007 ) . the c. neoformans sch9 mutant shows hypersensitivity to osmotic shock and fludioxonil , phenotypes that are distinguished from those of the hog1 mutant , indicating that sch9 appears to be governed by both hog and other pathways ( ko et al . , 2009 ) . the protein degradation pathway , including the ubiquitin proteasome system , is also commonly activated by oxidative stress in other eukaryotic organisms ( vandenbroucke et al . , 2008 ) . the most notable observation of the hog pathway transcriptome analysis is that it regulates genes involved in ergosterol biosynthesis . inhibition of the hog pathway , such as mutation of the ssk1 and hog1 genes , increases the expression levels of a number of genes , such as erg11 , a gene involved in ergosterol biosynthesis . supporting this finding , it was observed that cellular ergosterol contents increase by inhibiting the hog pathway . confirming this , the hog1 mutant was found to be resistant to azole drugs , such as fluconazole , but is hypersusceptible to amphotericin b ( ko et al . , 2009 ) . this provides an important combination antifungal therapeutic method , one which will increase efficacy but decrease toxicity of amphotericin b , a drug that is currently the most widely used for treatment of cryptococcosis . in c. neoformans , the pkc ( protein kinase c)/mpk1 signaling pathway is involved in responding to a variety of environmental stresses , including osmotic stress , oxidative stress , nitrosative stress , and breaches of cell wall integrity . moreover , deletion of the pkc1 gene induces an increase in capsule size and reduces the ability to synthesize melanin when compared to the wild - type . this pathway comprises several signaling components , including the small gtp - binding protein rho1 , pkc , bck1 mapkkk , mkk1/mkk2 mapkk , and mpk1 mapk , a gene which is homologous to slt2 in s. cerevisiae ( levin , 2005 ) . it has been reported that dag ( diacylglycerol ) functions as a second messenger activating mammalian protein kinase c. the production of dag is regulated by ipc1 ( inositol - phosphorylceramide synthase-1 ) ( heung et al . , 2004 ) . the pkc / mpk1 mapk pathway in s. cerevisiae regulates the organization of the actin cytoskeleton and cell wall integrity ( delley and hall , 1999 ) . pkc1 plays a more crucial role in sensing and responding to environmental cues ( levin et al . , 1990 ) . in response to an oxidative stress , such as hydrogen peroxide and diamide , this activation results in the formation of disulfide bonds in cytoskeletal proteins and induces disruption of the cell wall . in c. neoformans , the pkc / mpk1 pathway is also involved in responding to a diversity of stresses , including oxidative stress , and breaches of cell wall integrity ( fig . 2 ) ( gerik et al . , 2008 ) . following exposure to reactive oxygen or nitrogen species ( ros and rns , respectively ) , the mpk1 mapk is activated by phosphorylation downstream of the pkc pathway in c. neoformans . activation of the mpk1 mapk is not observed in the pkc1 mutant following exposure to nitrosative stress ( e.g. nano2 ) , oxidative stress ( e.g. hydrogen peroxide ) , or a cell wall damaging agent ( e.g. calcoflour white ) , clearly indicating that phosphorylation of mpk1 is governed by pkc1 ( gerik et al . , recently , it has been shown that the bck1 , mkk1 and mpk1 mutants exhibited hypersensitivity to fludioxonil , methylglyoxal , hydrogen peroxide , and high temperature , but not osmotic stress ( bahn et al . , 2007 ) . furthermore , the pkc1 mutant is hypersensitive to cell wall destabilizers such as sds , calcoflour and congo red ( berridge et al . , 2003 ) , indicating that pkc1 plays an essential role in maintaining cell wall integrity . these characteristics may be related to the hyper - susceptibility of the pkc1 mutant to high temperature ( gerik et al . , 2008 ) . deletion of the pkc1 gene induces an increase in capsule size , a phenotype not observed in the bck1 , mkk2 and mpk1 mutants ( gerik et al . , 2008 ) . in addition , the pkc1 and mkk2 mutants show a reduction in melanin synthesis ( gerik et al . , 2005 , 2008 ) . for regulation of melanin formation , the pkc pathway is activated by the sphingolipid pathway . the role of the pkc pathway in capsule and melanin biosynthesis could be related to the ability to maintain cell wall integrity since the capsule is deposited into the cell wall and a laccase , an essential enzyme for the production of melanin , is located in the cell wall ( zhu et al . , 2001 ca is an important secondary messenger governing a variety of stress responses in eukaryotic organisms . in c. neoformans , the ca - mediated signaling pathway also plays a critical role in adaptation to certain environmental stresses , such as high temperature and cell wall stress ( fig . 3 ) ( fox and heitman , 2002 ; kraus and heitman , 2003 ) . in response to certain external cues , the concentration of cytosolic ca is changed , an event which results in the transmission of signals from the membrane to the nucleus . for example , a rise in concentration of cytosolic ca leads to the activation of pkc , an enzyme which functions in a variety of cellular responses including cellular growth and activation of transcription factors ( berridge et al . , 2003 ) . the ca signaling pathway is well conserved from fungi to mammals ( kraus et al . , 2005 ) . in this pathway , calmodulin and calcineurin play essential roles in the stress response of fungi ( kraus et al . , 2005 ) . calmodulin is a small cytosolic protein that binds four ca ions via the ef hand motifs forming a ca / calmodulin complex that acts as a ca sensor ( kraus and heitman , 2003 ) . the bound ca induces a conformational change of the calmodulin , resulting in the release of free energy ( ikura , 1996 ) . in s. cerevisiae , the ca signaling pathway is also involved in cellular mechanisms , such as mitosis ( by regulation of nuflp / spc110p , stress responses ) , and cytoskeleton rearrangement ( chin and means , 2000 ; cyert , 2001 ) . calcineurin , a ser / thr specific phosphatase , is the target of ca bound calmodulin and its function is well conserved among eukaryotic cells ( aramburu et al . , 2000 ) . the calmodulin - mediated activation of calcineurin is inhibited by chemical compounds such as cyclosporine a ( csa ) and tacrolimus ( fk506 ) , two well known immunosuppressive drugs ( hemenway and heitman , 1999 ) . in the cell , csa and fk506 form complexes with cyclophilin a and fk506-binding protein ( fkbp12 ) , respectively , and these complexes inhibit the action of calcineurin ( liu et al . , 1991 ) . calcineurin is a heterodimer composed of catalytic subunit a ( cna1 ) , containing autoinhibitory and calmodulin binding domains , and ca binding regulatory b subunit ( cnb1 ) ( watanabe et al . , 1996 ) . the ca / calcineurin pathway is also involved in a variety of stress responses in c. neoformans ( fig . 3 ) . the csa does not affect the viability of c. neoformans at low temperature , but does at 37. this indicates that calcineurin is not essential at low temperature , but indispensable during infection of the host ( odom et al . , 1997 ) . furthermore , the cna1 mutant is hypersensitive to high co2 concentration and ph 7.3 , conditions which are essential for the cells to infect the host . as a result , the mutant lacking calcineurin is sensitive to li and provides resistance for mn , which is the opposite phenotype observed in s. cerevisiae . calcineurin b ( subunit b ) in c. neoformans is also indispensable for growth at 37. the cnb1 has defects in haploid fruiting and mating response , phenotypes not seen in cna1 mutants ( fox et al . , 2001 ) . the ras - signaling pathway is another important sas pathway that governs thermotolerance of c. neoformans . ras is a monomeric gtpase activated by replacement of bound gdp with gtp , an event mediated by a guanine nucleotide - exchange factor ( gef ) , or inactivated by a gtpase - activating protein ( gap ) ( bourne et al . , 1990 ; bourne et al . , the ras - signaling pathway has been implicated in growth , differentiation , and stress response of eukaryotic organisms . in mammals , ras regulates cell proliferation via the erk mapk and a mutation in the ras gene is regarded as one of the main causes of human cancers ( barbacid , 1987 ) . in fungi , ras is also involved in a variety of cellular responses , including cell cycle regulation and camp production ( thevelein , 1994 ; jiang et al . , 1998 ) . although ras is conserved from fungi to mammals , the role of ras in cells varies among species . s. cerevisiae , for example , has two ras proteins , ras1 and ras2 that control a variety of cellular responses , including the production of camp , regulation of mapk signaling , diploid and haploid growth , and polarization of actin cytoskeleton ( toda et al . , 1985 ; , 1999 ; ho and bretscher , 2001 ) . in schizosaccharomyces pombe , ras also controls the mapk pathway in the pheromone response during mating , but is not involved in the production of camp ( nielsen et al . the ras - signaling pathway is involved in camp signaling , environmental stress response , and pheromone response during mating in c. neoformans ( fig . c. neoformans also expresses ras1 and ras2 , and these two proteins not only have distinct roles in stress response , such as thermotolerance , but also share some functions ( waugh et al . , 2002 ) . although mutating both ras1 and ras2 in s. cerevisiae causes lethality , c. neoformans ras1 ras2 double mutants are viable but with growth defects under normal conditions ( kataoka et al . ras1 , but not ras2 , is required for growth at high temperature , mating response , and virulence ( alspaugh et al . , 2000 ; waugh et al . , 2003 ) . overexpression of ras2 , however , partly restores the growth of the ras1 mutant at high temperature and completely suppresses its mating defect , indicating that these ras proteins share some functions . unlike other sas pathways , however , the ras - signaling pathway is not involved in production of virulence factors , such as melanin and capsule ( waugh et al . , 2002 ) . the guanine nucleotide exchange factor cdc24 was found to be the downstream effector of ras1 ( nichols et al . , 2007 ) . the cdc24 mutant shows the same phenotype as the ras1 mutant in response to high temperature and actin polarization . the cdc24 ras1 double mutant shows no synergistic defect of growth at 37 compared to the cdc24 and ras1 , clearly indicating that ras1 and cdc24 share a common signal transduction pathway . recently , cdc42 was found to be the target of the ras1-cdc24 signaling complex in c. neoformans ( nichols et al . , 2007 ) . c. neoformans is armed with various stress - activated signaling ( sas ) pathways that promote survival of the pathogen in the harsh host environment . the sas pathways of c. neoformans include the hog , ca / calcineurin , pkc / mpk1 mapk , and ras - signaling pathways . perturbation of the sas pathways not only impairs the capability of c. neoformans to resist a variety of environmental stresses during host infection , but also affects production of virulence factors , such as capsule and melanin . a drug(s ) targeted to signaling components of the sas pathway will be effective for treatment of cryptococcosis . first , most of the central signaling components of the sas pathways are evolutionarily conserved and therefore their inhibitors could have side - toxicity . exceptions include components of the two - component system , which are fungal - specific . further identification and characterization of the downstream targets of the sas pathways by dna microarray or proteomics approaches will likely provide more ideal targets for development of antifungal therapies . for example , fluconazole and fludioxonil are known to have synergistic antifungal activity with the calcineurin inhibitor fk506 ( del poeta et al . , 2000 ; furthermore , it has been shown that inhibition of the hog pathway renders cells hypersensitive to amphotericin b ( ko et al . , 2009 ) . in conclusion , complete understanding of sas pathways will provide unprecedented opportunities to develop novel antifungal therapy against c. neoformans .

cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals . the ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host . four major stress - activated signaling ( sas ) pathways have been characterized in c. neoformans , including the hog ( high osmolarity glycerol response ) , pkc / mpk1 mapk ( mitogen - activated protein kinase ) , calcium - dependent calcineurin , and ras signaling pathways . the hog pathway in c. neoformans not only controls responses to diverse environmental stresses , including osmotic shock , uv irradiation , oxidative stress , heavy metal stress , antifungal drugs , toxic metabolites , and high temperature , but also regulates ergosterol biosynthesis . the pkc ( protein kinase c)/mpk1 pathway in c. neoformans is involved in a variety of stress responses , including osmotic , oxidative , and nitrosative stresses and breaches of cell wall integrity . the ca2+/calmodulin- and ras - signaling pathways also play critical roles in adaptation to certain environmental stresses , such as high temperature and sexual differentiation . perturbation of the sas pathways not only impairs the ability of c. neoformans to resist a variety of environmental stresses during host infection , but also affects production of virulence factors , such as capsule and melanin . a drug(s ) capable of targeting signaling components of the sas pathway will be effective for treatment of cryptococcosis .

the thesis of j .- p . serre , at the beginning of the fifties , introduced the idea of using the cohomology of loop spaces in topology . topologists have quickly studied the cohomology of iterated loop spaces @xmath4 which are spaces of maps @xmath5 on spheres @xmath6 . the computation of the cohomology of @xmath4 would make possible the determination of homotopy classes of these maps @xmath5 but , for the moment , this computation is well understood only when @xmath7 is the @xmath0-fold suspension of a space @xmath8 . besides , we have a comprehensive knowledge of the homotopy classes of finite cell complexes in a few particular cases only ( which do not include spheres ) for which the homotopy vanishes in dimension @xmath9 . our works @xcite give an algebraic device to model iterated loop spaces @xmath4 on all spaces @xmath7 and for every value of @xmath0 . the goal of this paper is to explain how to make explicit a structured complex computing the cohomology of a profinite completion of the iterated loop spaces @xmath10 from this model , by putting together results of @xcite and of another article @xcite . the obtained complex is defined purely algebraically , in terms of the internal structure of certain operads , and inherits nice operadic structures from which we hope to get information of new nature on the topology of @xmath10 . the @xmath2-operads give the core structures of our construction . for our purpose , we consider @xmath2-operads in the category of differential graded modules ( dg - modules for short ) and we use the noun @xmath2-algebra to refer to any category of algebras associated to an @xmath2-operad in that ambient category . in that context , the @xmath2-operads refer to the homotopy type of operads which are weakly equivalent to the chain operad of boardman - vogt little @xmath0-cubes . most models of @xmath2-operads come in nested sequences @xmath11 such that @xmath12 is an @xmath13 operad , an operad weakly equivalent to the operad @xmath14 of associative and commutative algebras . the @xmath15-operads , which form the initial terms of nested sequences of the form ( * ) , are weakly equivalent to the operad @xmath16 of associative non - commutative algebras . intuitively , an @xmath15-algebra structure is interpreted as a structure which is homotopy associative in the strong sense but non - commutative , while an @xmath17-algebra is fully homotopy ( associative and ) commutative . the @xmath2-algebra structures , which are intermediate between @xmath15 and @xmath17 , are interpreted as structures which are homotopy associative in the strong sense and homotopy commutative up to some degree . a commutative algebra naturally inherits an @xmath2-algebra structure , for all @xmath18 . throughout this paper , a space means a simplicial set and we associate to a simplicial set @xmath7 the standard normalized complex @xmath19 with coefficients in the ground ring @xmath20 of our base category of dg - modules . as we deal with pointed spaces , we use the reduced complex @xmath21 in our constructions rather than the whole complex @xmath19 . to handle structures without unit ( like these reduced complexes @xmath22 ) , we also remove @xmath23-ary operations from our operads . the cochain algebras @xmath22 inherit an @xmath17-algebra structure by @xcite , for which we have an explicit construction ( see @xcite ) giving an action of certain @xmath17-operads equipped with a filtration of the form ( * ) on @xmath22 . in that context , we immediately see that the @xmath17-algebra @xmath22 inherits an @xmath2-algebra structure for all @xmath0 . now a natural homology theory @xmath24 is associated to any category of algebras over an @xmath2-operad . for a cochain algebra @xmath25 , the theorems of @xcite , put together , imply that the homology @xmath26 determines the cohomology of a profinite completion of the @xmath0-fold loop space @xmath4 . but we observe in @xcite that @xmath2-operads are in a sense koszul and we prove , using a good @xmath2-operad @xmath27 , that a cofibrant model of @xmath2-operad is yielded by an operadic cobar construction @xmath28 , where @xmath29 is an operadic desuspension of the dual cooperad of @xmath27 in dg - modules . this result implies that the homology @xmath24 of any @xmath27-algebra can be computed by a nice structured complex of the form @xmath30 , where @xmath31 is the connected @xmath32-cofree coalgebra on @xmath33 and @xmath34 is a twisting coderivation determined by the @xmath2-algebra structure of @xmath33 ( this construction is reviewed in [ koszuldualityreview ] ) . the goal of this paper is to determine the differential of this complex @xmath35 for the cochain algebra of a sphere @xmath36 , where @xmath37 . in @xcite , we observe that the action of @xmath28 on @xmath38 , by way of the morphism @xmath39 , is determined by a composite of : 1 . [ corestructures : embedding ] the image under the cobar construction @xmath40 of a morphism @xmath41 dual in dg - modules to the embedding @xmath42 ; 2 . [ corestructures : twist ] the operadic suspension of an augmentation morphism @xmath43 which , by operadic bar duality , is equivalent to a morphism @xmath44 on the suspension of the operad @xmath45 associated to the standard category of @xmath3-algebras , the classical version of homotopy lie algebra structure . the existence of a morphism @xmath44 reflects the existence of a restriction functor from @xmath46-algebras to @xmath3-algebras and has been used in the literature in the case @xmath47 , in conjunction with the deligne conjecture , to determine the homotopy type of certain deformation complexes ( see for instance @xcite ) . in @xcite , we prove that these morphisms @xmath48 are unique up to a right homotopy in the category of operads , and hence , are characteristic of the structure of an @xmath46-operad . we give a conceptual definition of the complex @xmath49 in terms of the embedding @xmath42 , of the morphism @xmath44 and of the composition structure of the operad @xmath27 . we will obtain a result of a particularly simple form also because the reduced normalized complex @xmath38 is a free @xmath20-module of rank one . we give all details in [ spherekoszulduality ] . for this introduction , we are simply going to state the final outcome of our construction : the application of our result to iterated loop space cohomology as it arises from @xcite . we dualize the construction to ease the formulation of our result . we form , for any @xmath50 , the free complete @xmath27-algebra @xmath51 on one generator @xmath52 of degree @xmath53 . the elements of this algebra @xmath54 are just formal power series @xmath55 where @xmath56 is an @xmath57-ary operation of the operad @xmath58 . our result makes appear a composition product @xmath59 , borrowed to @xcite , defined termwise by sums of operadic substitution operations @xmath60 running over all entries of @xmath61 . we observe that the existence of a morphism @xmath62 is formally equivalent to the existence of an element @xmath63 , of degree @xmath64 , satisfying the relation @xmath65 , where @xmath66 refers to the canonical differential of @xmath54 . we embed this element @xmath67 into @xmath51 , for any @xmath50 . we have then : we consider the twisted complex @xmath68 defined by adding the map @xmath69 to the natural differential of the free complete @xmath27-algebra @xmath51 . when the ground ring is @xmath70 , we have an identity @xmath71 between the continuous cohomology of the profinite completion of @xmath10 and the homology of the dual complex of @xmath68 in @xmath70-modules ( we take the continuous dual with respect to the topology of power series ) . the profinite completion of the theorem is defined by the limit of a diagram @xmath72 where @xmath73 ranges over homotopy finite approximations of @xmath74 ( see @xcite ) . this formulation is slightly abusive because the profinite completion of @xmath10 would be the limit of a diagram of homotopy finite approximations of the space @xmath10 itself . nevertheless results of @xcite imply that these limits coincide . the theorem has an @xmath75-version where the profinite completion of @xmath10 is replaced by a @xmath76-profinite approximation , the limit of a diagram @xmath72 where @xmath73 now ranges over homotopy @xmath76-finite approximations of @xmath74 ( see again @xcite ) . the topological results of @xcite are stated in the @xmath75-setting , but the arguments work same over @xmath70 . the above theorem is not intended for computational purposes and we should not undertake any computation with it the iterated bar complexes of @xcite , which are equipped with nice filtrations , seem better suited for such an undertaking . the actual goal of this article , with this theorem , is to make explicit the connection between the cohomology of iterated loop spaces of spheres and the homotopical structures of @xmath2-operads . in subsequent work , we plan to apply the theorem to gain qualitative information on the structure of iterated loop space cohomology by using connections , explained in @xcite , between @xmath2-operads and quantum field theory . in [ koszuldualityreview ] , we briefly review the definition of the homology @xmath77 associated to an operad @xmath78 , the applications of the bar duality of operads to the definition of complexes @xmath79 computing @xmath77 , and we explain how to apply this construction to @xmath2-operads with the result of @xcite . in [ freecompletealgebras ] , we explain the definition of the free complete algebras of the form @xmath51 and their duality connection with cofree coalgebras @xmath80 on a dg - module @xmath81 of rank one . in [ spherekoszulduality ] , we study the applications of operadic bar duality to the cochain algebra of spheres @xmath38 and we determine the form of the complex @xmath49 from which we obtain the outcome of our theorem . in [ koszuldualityreview ] and [ spherekoszulduality ] , we deal with a particular @xmath2-operad , already used in the proof of @xcite , which arises from a certain filtration of an @xmath17-operad introduced by barratt - eccles in @xcite . in [ homotopyinvariance ] , we explain that the homotopy type of the complex @xmath82 which occurs in our main theorem does not depend on the choice of the @xmath2-operad @xmath27 and of the element @xmath83 associated to a morphism @xmath84 . to begin with , we review the background of our constructions . we are only going to give a brief survey of this background since our main purpose is to explain our conventions . we refer to @xcite for a more detailed account with the same overall conventions as in the present article . to begin with , we explicitly specify which base category of dg - modules is considered throughout the article . the ground ring , fixed once and for all , is denoted by @xmath20 . for us a dg - module refers to a @xmath70-graded @xmath20-module @xmath81 equipped with an internal differential @xmath85 that decreases the degree by one , and we take this category of dg - modules as base category @xmath86 . the category of dg - modules is equipped with its standard tensor product @xmath87 together with the symmetry isomorphism @xmath88 involving a sign . this sign is determined by the standard sign convention of differential graded algebra , which we follow . the notation @xmath89 is used to represent any sign arising from an application of this convention . the ground ring @xmath20 , viewed as a dg - module of rank @xmath90 concentrated in degree @xmath23 , defines the unit object for the tensor product of dg - modules . the morphism sets of any category @xmath91 are denoted by @xmath92 . the morphisms of dg - modules are the degree and differential preserving morphisms of @xmath20-modules @xmath93 . the category of dg - modules comes also equipped with internal hom - objects @xmath94 characterized by the adjunction relation @xmath95 with respect to the tensor product @xmath87 . recall briefly that a homogeneous element of @xmath94 is just a morphism of @xmath20-modules @xmath93 raising degrees by @xmath96 . the differential of a homomorphism @xmath97 is defined by the ( graded ) commutator @xmath98 , where we consider the internal differentials of @xmath81 and @xmath99 . the elements of the dg - hom @xmath94 are called homomorphisms to be distinguished from the actual morphisms of dg - modules , the elements of the morphism set @xmath100 . the dual of a dg - module @xmath81 is the dg - module such that @xmath101 , where we again view the ground ring @xmath20 as a dg - module of rank @xmath90 concentrated in degree @xmath23 . we always consider operads ( and cooperads ) in the category of dg - modules . we adopt the notation @xmath102 for the whole category of operads in dg - modules . we use the notation @xmath103 for the initial object of the category of operads which reduces to the ground ring @xmath104 in arity @xmath90 and is trivial otherwise . in general , we tacitely assume that an operad @xmath78 satisfies @xmath105 ( we say that @xmath78 is non - unitary ) . in some cases , we may assume that an operad satisfies @xmath106 too . we say in this situation that @xmath78 is a connected operad . cooperads @xmath107 are always assumed to satisfy the connectedness assumptions @xmath108 and @xmath109 in order to avoid difficulties with infinite sums in coproducts . we use the notation @xmath110 ( respectively @xmath111 ) for the category of non - unitary ( respectively connected ) operads in dg - modules . we call @xmath112-object the structure , underlying an operad , formed by a collection @xmath113 where @xmath114 is a dg - modules equipped with an action of the symmetric group on @xmath57 letters @xmath115 . a connected operad inherits a canonical augmentation @xmath116 which is the identity in arity @xmath117 and is trivial otherwise . we adopt the notation @xmath118 for the augmentation ideal of any operad @xmath78 equipped with an augmentation @xmath116 . we have in the connected case @xmath119 and @xmath120 for all @xmath121 . any connected cooperad @xmath107 has a coaugmentation @xmath122 and a coaugmentation coideal @xmath123 defined like the augmentation and the augmentation ideal of a connected operad . the suspension of a dg - module @xmath81 is the dg - module @xmath124 defined by the tensor product @xmath125\otimes c$ ] where , for all @xmath126 , we adopt the notation @xmath127 $ ] for the free graded @xmath20-module of rank @xmath90 concentrated in degree @xmath128 . the operadic suspension of an operad @xmath78 , is an operad @xmath129 characterized by the commutation relation @xmath130 at the level of free algebras . basically , the operad @xmath129 is defined arity - wise by the tensor products @xmath131\otimes\operatorname{\mathsf{p}}(n)^{\pm}$ ] where the notation @xmath89 refers to a twist of the natural @xmath132-action on @xmath133 by the signature of permutations . we have an operadic suspension operation defined in the same way on cooperads . note that we can apply the suspension of dg - modules arity - wise to any operad @xmath78 ( or cooperad ) to produce a @xmath112-object @xmath134 such that @xmath135\otimes\operatorname{\mathsf{p}}(r)$ ] , but this suspended @xmath112-object does not inherit an operad structure . the category of algebras in dg - modules associated to an operad @xmath78 is denoted by @xmath136 . the free @xmath78-algebra associated to a dg - module @xmath81 is denoted by @xmath137 . recall simply that this free @xmath78-algebra is defined by the dg - module of generalized symmetric tensors @xmath138 , where the @xmath115-quotient identifies tensor permutations with the action of permutations on @xmath139 . note that we can remove the @xmath23 term of this expansion since we assume @xmath105 . we use the notation @xmath140 where @xmath141 , @xmath142 , to represent the element of @xmath137 defined by the tensor @xmath143 . we may also use the graphical representation @xmath144\ar@{.}[r ] & \cdots\ar@{.}[r]\ar@{}[d]|{\displaystyle{\cdots } } & x_r\ar[dl ] \\ \ar@{.}[r ] & * + < 8pt>[f]{p}\ar[d]\ar@{.}[r ] & \\ \ar@{.}[r ] & 0\ar@{.}[r ] & } } \ ] ] for these elements @xmath145 . in the case of a cooperad @xmath107 , we use the notation @xmath80 for the connected cofree @xmath107-coalgebra such that @xmath146 . in this definition , we take the same generalized symmetric tensor expansion as a free algebra over an operad for the underlying functor of a cofree coalgebra over a cooperad and therefore , we can safely adopt the functional and graphical representation of elements of free algebras of operads to denote the elements of @xmath80 . note that @xmath80 does not agree with the standard cofree connected coalgebras of the literature in usual cases ( like cocommutative coalgebras ) precisely because we take coinvariants instead of invariants , but we generally apply the definition of @xmath80 to cooperads @xmath107 equipped with a free @xmath112-module structure so that the result is the same if we replace coinvariants by invariants in the definition of @xmath80 . the coaugmentation morphism of a cooperad yields an embedding @xmath147 which identifies the dg - module @xmath81 with a summand of @xmath80 . similarly , if @xmath78 is an augmented operad , then we have a split embedding @xmath148 , yielded by the operad unit of @xmath78 . the morphism @xmath149 induced by the augmentation of @xmath78 gives a canonical retraction of @xmath148 so that @xmath81 is canonically identified with a summand of @xmath137 . the category of dg - modules @xmath86 is equipped with its standard model structure in which the weak - equivalences are the morphisms which induce an isomorphism in homology , the fibrations are the degreewise surjections ( see @xcite ) . the category of non - unitary operads @xmath110 inherits a full model structure from dg - modules so that a morphism @xmath150 is a weak - equivalence ( respectively , a fibration ) if @xmath151 forms a weak - equivalence ( respectively , fibration ) of dg - modules @xmath152 in each arity @xmath153 . the cofibrations are characterized by the right - lifting - property with respect to acyclic fibrations . the category of @xmath112-objects in dg - modules also inherits a full model structure with the same definition for the class of weak - equivalences ( respectively , fibrations ) . any operad cofibration with a cofibrant operad as domain defines a cofibration of @xmath112-objects , but the converse implication does not hold . therefore we say that an operad @xmath78 is @xmath112-cofibrant when its unit morphism @xmath154 defines a cofibration in the category of @xmath112-objects . the category of algebras over a @xmath112-cofibrant operad @xmath78 inherits a semi - model structure in the sense that the axioms of model categories are satisfied for @xmath78-algebras only when we restrict the applications of the right lifting property of ( acyclic ) cofibations and of the factorization axiom to morphisms with a cofibrant domain . this is enough for the usual constructions of homotopical algebra . naturally the weak - equivalences ( respectively , fibrations ) of @xmath78-algebras are the morphisms of @xmath78-algebras @xmath155 which define a weak - equivalence ( respectively , a fibration ) in the category of dg - modules . in certain constructions , a homomorphism @xmath156 of degree @xmath157 is added to the internal differential of a dg - module @xmath81 to produce a new dg - module , with the same underlying graded @xmath20-module as @xmath81 , but the map @xmath158 as differential . since we have @xmath159 , the relation of differential @xmath160 amounts to the equation @xmath161 in @xmath162 . in this situation , we say that @xmath34 is a twisting homomorphism and we just use the pair @xmath163 to refer the new dg - module defined by the addition of @xmath34 to the internal differential of @xmath81 . when we apply this construction to an algebra @xmath33 over an operad @xmath78 , we assume that the twisting homomorphism satisfies the derivation relation @xmath164 to ensure that the twisted dg - module @xmath165 inherits a @xmath78-algebra structure from @xmath33 . we then say that @xmath166 is a twisting derivation . we call quasi - free @xmath78-algebra the twisted @xmath78-algebras @xmath165 associated to a free @xmath78-algebra @xmath167 . we have a one - one correspondence between derivations on free @xmath78-algebras @xmath168 and homomorphisms @xmath169 . we use the notation @xmath170 for the derivation associated to @xmath171 . in one direction , we have @xmath172 . in the other direction , the derivation @xmath173 is determined from @xmath169 by the derivation formula @xmath174 , for all @xmath175 . for a free @xmath78-algebra @xmath137 , a derivation @xmath173 satisfies the equation of twisting homomorphisms if and only if the associated homomorphism @xmath169 satisfies the equation @xmath176 in @xmath177 . we also apply the definition of twisted dg - modules to coalgebras over cooperads . we have a notion of quasi - cofree @xmath107-coalgebra , dual to the notion of quasi - free algebra over an operad , consisting of a twisted dg - module @xmath178 such that @xmath179 is a cofree @xmath107-coalgebra and @xmath180 is a @xmath107-coalgebra coderivation uniquely determined by a homomorphism @xmath181 such that @xmath182 in @xmath183 . in the context of coalgebras , we determine the twisting coderivation @xmath184 associated to a homomorphism @xmath185 by a graphical expression of the form : @xmath186\ar@{.}[r ] & \cdots\ar@{.}[r]\ar@{}[d]|{\displaystyle{\cdots } } & x_r\ar[dl ] \\ \ar@{.}[r ] & * + < 8pt>[f]{c}\ar[d]\ar@{.}[r ] & \\ \ar@{.}[r ] & 0\ar@{.}[r ] & } } \right\ } = \sum_{i } \pm\left\{\vcenter{\xymatrix@h=6pt@w=3pt@m=2pt@!r=1pt@!c=1pt { x_1\ar[drr]\ar@{.}[r ] & \cdots\ar@{.}[r ] & \alpha(x_i)\ar[d]\ar@{.}[r ] & \cdots\ar@{.}[r ] & x_r\ar[dll ] \\ \ar@{.}[rr ] & & * + < 8pt>[f]{c}\ar@{.}[rr]\ar[d ] & & \\ \ar@{.}[rr ] & & 0\ar@{.}[rr ] & & } } \right\ } \\ + \sum_{\substack{\tau\in\theta_2(r)\\ \rho_{\tau}(c ) } } \pm\left\{\vcenter{\xymatrix@h=6pt@w=4pt@m=2pt@r=8pt@c=4pt { & & \save [ ] .[rrd]!c * + < 4pt>[f-,]\frm{}*+<6pt>\frm{\{}*+<0pt>\frm{\ } } \restore\ar@{}[]!l-<8pt,0pt>;[d]!l-<8pt,0pt>_{\displaystyle\alpha } x_*\ar@{.}[r]\ar[dr ] & \cdots\ar@{.}[r ] & x_*\ar[dl ] & & \\ x_*\ar@{.}[r]\ar@/_6pt/[drrr ] & \cdots & & * + < 6pt>[f]{c_*}\ar@{.}[r]\ar@{.}[l]\ar[d ] & & \cdots\ar@{.}[r ] & x_*\ar@/^6pt/[dlll ] \\ \ar@{.}[rrr ] & & & * + < 6pt>[f]{c_*}\ar[d]\ar@{.}[rrr ] & & & \\ \ar@{.}[rrr ] & & & 0\ar@{.}[rrr ] & & & } } \right\}.\end{gathered}\ ] ] the notation @xmath187 refers to a cooperadic coproduct along a tree @xmath188 of an element @xmath189 and the expressions @xmath190 inside the sum refer to the factors of this cooperadic coproduct ( see ( * ? ? ? * proposition 4.1.3 ) for details ) . the notation @xmath191 refers to the category of trees with two vertices . the second sum ranges over all trees @xmath192 and , for each @xmath192 , over all terms of the expansion of @xmath187 . in the first sum , we just consider the restriction of @xmath185 to the summand @xmath193 and we sum up over all inputs of @xmath189 . the purpose of this section is to review applications of operadic bar duality to the definition of homology theories for algebras over an operad . the first reference addressing applications of homotopical algebra to algebras over operads in the setting of unbounded dg - modules over a ring is the article @xcite . the definition of a homology theory with trivial coefficients , in terms of quillen s homotopical algebra , was given earlier in @xcite in the context of @xmath194-graded dg - modules over a field of characteristic @xmath23 . the application of operadic bar duality to homotopical algebra of algebras over operads is explained in that reference in the same characteristic @xmath23 setting . briefly , the authors of @xcite prove that the existence of a cofibrant model given by an operadic cobar construction @xmath195 for an operad @xmath78 gives rise to an explicit cofibrant replacement functor on the category of @xmath78-algebras which can be used for homology computations . in @xcite we explain how to extend the applications of operadic bar duality to the context of unbounded dg - modules over a ring . more specifically , we prove that the functorial cofibrant replacement of algebras over an operad , defined @xcite , works in that framework provided that we restrict ourself to @xmath112-cofibrant operads and to algebras which are cofibrant as dg - modules . we review the definition of these cofibrant replacement functors very briefly before explaining the applications to the homology of algebras over operads in our setting . we explain at each step how the constructions apply to @xmath2-operads . in this section ( and in the next one ) , we assume that @xmath27 is the particular @xmath2-operad , arising from a filtration of the barratt - eccles operad @xcite , used in the proof of the koszul duality result of @xcite . this operad has , among others , the advantage of being free of finite rank over @xmath20 in each arity . thus we can dualize the dg - modules @xmath196 without special care . besides , the operad @xmath27 is connected so that the collection of dual dg - modules @xmath197 inherits a well - defined cooperad structure . to begin with , we say a few words about the operadic cobar construction @xmath195 . the operadic cobar construction is a functor which associates a connected operad @xmath195 to any cooperad @xmath107 . we do not really need the explicit definition of @xmath195 . just recall that @xmath195 is a cofibrant as an operad whenever the cooperad @xmath107 is @xmath112-cofibrant and that any morphism @xmath198 towards an operad @xmath78 is fully determined by a homogeneous morphism @xmath199 , of degree @xmath157 , vanishing on @xmath200 , and satisfying the equation : @xmath201 & \cdots & i_r\ar[dl ] \\ & * + < 6pt>[f]{c}\ar[d ] & \\ & 0 & } } \right\ } = \sum_{\substack{\tau\in\theta_2(i)\\ \rho_{\tau}(\gamma ) } } \pm\lambda_*\left\{\vcenter{\xymatrix@h=6pt@w=4pt@m=2pt@r=8pt@c=4pt { & i_*\ar[dr ] & \cdots & i_*\ar[dl ] & \\ i_*\ar[drr ] & \cdots & * + < 6pt>[f]{\theta(c_*)}\ar[d ] & \cdots & i_*\ar[dll ] \\ & & * + < 6pt>[f]{\theta(c_*)}\ar[d ] & & \\ & & 0 & & } } \right\},\ ] ] for any @xmath189 , where @xmath202 refers to the composition operation of the operad @xmath78 and we adopt conventions similar to [ background : twistedobjects ] to represent the expansion of the coproduct of a cooperad element @xmath189 . we refer to @xcite for details on this matter . we adopt the notation @xmath203 for the morphism associated to @xmath199 and we refer to @xmath204 as the twisting cochain associated to @xmath205 . for our @xmath2-operad , we have : [ koszuldualityreview : koszuldualitystatement ] the operad @xmath27 has a cofibrant model of the form @xmath206 , where @xmath29 is the @xmath0-fold operadic desuspension of the dual cooperad of @xmath27 in dg - modules . the proof of this assertion in @xcite is divided in several steps . the first step involves the definition of a morphism @xmath207 towards the operad of commutative algebras @xmath14 . the weak - equivalence @xmath208 is defined in a second step by a lifting process from the morphism @xmath209 . suppose now we have a @xmath112-cofibrant connected operad @xmath78 together with a cofibrant model of the form @xmath210 , where @xmath107 is a @xmath112-cofibrant operad . let @xmath211 be the augmentation of this cofibrant model . to any @xmath78-algebra @xmath33 , we associate a ( connected ) quasi - cofree @xmath107-coalgebra @xmath212 and a quasi - free @xmath78-algebra of the form @xmath213 . the homomorphism @xmath185 which determines the twisting coderivation of @xmath214 maps an element @xmath215 to the evaluation of the operation @xmath216 on @xmath217 . the homomorphism @xmath171 which determines the twisting derivation of @xmath218 is given by the composite @xmath219 where @xmath220 is yielded by the universal @xmath107-coalgebra structure of the quasi - cofree @xmath107-coalgebra @xmath214 . then : [ koszuldualityreview : cofibrantreplacements ] we have a weak - equivalence @xmath221 induced on generators @xmath222 by the augmentation of the cofree @xmath107-coalgebra @xmath223 and @xmath218 defines a cofibrant replacement of @xmath33 in @xmath78-algebras provided that @xmath33 is cofibrant as a dg - module . we refer to @xcite for the version of this statement in the context of @xmath194-graded dg - modules over a field characteristic @xmath23 and to @xcite for the proof in our setting . in @xcite , we check that the cooperad @xmath29 associated to our @xmath2-operad @xmath27 is @xmath112-cofibrant ( like the operad @xmath27 itself ) . hence the result of proposition [ koszuldualityreview : cofibrantreplacements ] holds for algebras over our @xmath2-operad . recall that the action of an operad @xmath78 on an algebra @xmath33 is determined by an operad morphism @xmath224 , where @xmath225 , the endomorphism operad of @xmath33 , is the operad such that @xmath226 . the evaluation of an operation @xmath141 on a tensor @xmath217 is defined by the evaluation of the map @xmath227 on @xmath228 . observe that the homomorphism @xmath229 in the definition of @xmath214 is , by adjunction , equivalent to the homomorphism @xmath230 such that @xmath231 is the composite @xmath232 giving the action of @xmath195 on @xmath33 through @xmath205 . hence the twisting derivation of @xmath214 is fully determined by the restriction of the @xmath78-algebra structure of @xmath33 to @xmath195 , and not by the @xmath78-algebra structure itself . in [ spherekoszulduality ] , we apply this observation to the operad @xmath27 because , in the case @xmath36 , we have a good characterization of the morphism @xmath233 . let @xmath78 be an augmented operad . the indecomposable quotient of @xmath78-algebra @xmath33 is defined as the quotient dg - module of @xmath33 under the image of operations @xmath234 , where @xmath76 ranges over the augmentation ideal of @xmath78 . thus : @xmath235 for a @xmath112-cofibrant augmented operad @xmath78 , we have a homology theory @xmath236 defined by the formula @xmath237 for any @xmath78-algebra @xmath33 , where @xmath218 is a cofibrant replacement of @xmath33 . in the case of a quasi - free @xmath78-algebra , we have an identity @xmath238 . thus , when we apply the definition of the homology @xmath77 to the functorial cofibrant replacement @xmath239 , we obtain the well - known assertion : [ koszuldualityreview : koszulhomology ] provided that the @xmath78-algebra @xmath33 is cofibrant as a dg - module , we have the relation @xmath240 . in the special case @xmath241 , this relation gives the identity : @xmath242 before applying this construction to the cochain algebra of a sphere , we go back to the general study of coalgebras @xmath80 . throughout the paper , we adopt the notation @xmath127 $ ] for a dg - module of rank one concentrated in ( lower ) degree @xmath128 . the reduced normalized cochain complex of a sphere @xmath243 is an instance of dg - module of this form . since upper gradings are changed to opposite lower gradings , we obtain precisely @xmath244 $ ] . the purpose of this section is to study coderivations of cofree coalgebras @xmath80 over a dg - module @xmath245 $ ] with the aim to determine , in the next section , the complex @xmath246 associated to @xmath36 . to make our description more conceptual , the idea , explained in the introduction , is to define the complex in a dual setting of generalized power series algebras rather than in a coalgebra setting . therefore we study the duality process first . from now on , we assume , if not explicitly recalled , that @xmath52 is a variable of degree @xmath53 . in our presentation , we consider the free @xmath78-algebra @xmath247 on a variable @xmath52 , which can be defined as the free @xmath78-algebra @xmath248 on the free dg - module of rank one spanned by @xmath52 . by definition , we have an identity @xmath249 . to define the free complete @xmath78-algebra @xmath250 , we just replace the sum in the expansion of the free @xmath78-algebra by a product ( formed within the category of dg - modules ) : @xmath251 . the free complete @xmath78-algebra is equipped with the topology defined by the nested sequence of dg - submodules @xmath252 . by * proposition 1.2.18 ) , the dual in dg - modules of a connected cooperad @xmath107 always forms a connected operad . now , if @xmath107 is equipped with a free @xmath112-structure , then the dual of the connected cofree coalgebra @xmath80 on @xmath245 $ ] can be identified with a complete free algebra @xmath250 over the operad @xmath253 , where @xmath52 is a variable of degree @xmath53 , because we have in this case @xmath254^{\otimes r})_{\sigma_r})^{\vee } \simeq(\operatorname{\mathsf{d}}(r)^{\vee}\otimes\operatorname{\bbbk}[-m]^{\otimes r})^{\sigma_r } \simeq(\operatorname{\mathsf{d}}(r)^{\vee}\otimes\operatorname{\bbbk}[-m]^{\otimes r})_{\sigma_r}$ ] and the duality transforms the sum into a product . in the sequel , we are rather interested in a converse duality operation , from free complete algebras over operads to coalgebras over cooperads . the dual of a connected operad @xmath255 does not inherit a cooperad structure in general , because we need a map @xmath256 to separate the factors of the coproduct of @xmath255 , but this condition is fulfilled when each dg - module @xmath139 is free locally of finite rank over @xmath20 and @xmath257 does form a cooperad in that situation . in the sequel , we apply the duality of dg - modules to the free complete @xmath78-algebra @xmath250 . in this case , the continuous dual with respect to the topology of @xmath250 is more natural to consider and the notation @xmath258 is used to refer to it . thus , we have by definition @xmath259 . besides , we will always assume that @xmath78 is equipped with a free @xmath112-structure when we apply the duality to @xmath250 . in that setting , we obtain : [ freecompletealgebras : dualityisomorphism ] assume again that @xmath52 is a homogeneous variable of degree @xmath53 . if the operad @xmath78 is equipped with a free @xmath112-structure and is locally a free module of finite rank over @xmath20 , then we have an isomorphism @xmath260)$ ] , where @xmath257 is the dual cooperad of @xmath78 . let @xmath261 denote the continuous homomorphism associated to an element @xmath262)$ ] , @xmath189 , where we use the notation @xmath263 for the canonical generator of the @xmath20-module @xmath264 $ ] . this homomorphism can be defined termwise by the relation @xmath265 , for @xmath266 , @xmath267 , and the duality formula @xmath268 for @xmath141 . the relation @xmath260)$ ] is just converse to the relation @xmath269)^{\vee}\simeq\widehat{\operatorname{\mathsf{p}}}(x)$ ] of [ freecompletealgebras : duality ] for @xmath257 . by suspension , we deduce from these duality relations an isomorphism between the suspended dg - module @xmath270 and the dg - module of homomorphisms @xmath271)\rightarrow\operatorname{\bbbk}[m]$ ] . recall that we also have a degree - preserving bijection between homomorphisms @xmath271)\rightarrow\operatorname{\bbbk}[m]$ ] and coderivations @xmath272)\rightarrow\operatorname{\mathsf{d}}(\operatorname{\bbbk}[m])$ ] . in fact this bijection defines an isomorphism of dg - modules when we equip the collection of coderivations @xmath272)\rightarrow\operatorname{\mathsf{d}}(\operatorname{\bbbk}[m])$ ] with the natural dg - module structure coming from dg - module homomorphisms . now , on the side of the free complete @xmath78-algebra @xmath250 , we obtain : [ freecompletealgebras : continuousderivations ] for any free complete @xmath78-algebra @xmath250 on one variable @xmath52 of degree @xmath273 , we have degree - preserving bijections between : 1 . the elements @xmath274 , 2 . the derivations of @xmath78-algebras @xmath275 which are continuous with respect to the topology of @xmath250 . this bijection defines an isomorphism of dg - modules too when we equip the collection of continuous derivations with the natural dg - module structure coming from dg - module homomorphisms . in the sequel , we adopt the notation @xmath276 for the continuous derivation associated to an element @xmath274 . to check the proposition , we essentially observe that @xmath277 is defined termwise by the formal identity @xmath278 extending the formula of [ background : twistedobjects ] . the sum runs over all inputs of the operation @xmath141 . then we use the continuity of the derivation to identify @xmath277 on the whole dg - module @xmath250 . in the converse direction , we simply retrieve the element @xmath279 associated to a derivation @xmath277 by the identity @xmath280 . from the explicit construction of the derivation @xmath276 , we obtain : [ freecompletealgebras : derivationadjunction ] let @xmath274 . let @xmath281)\rightarrow\operatorname{\bbbk}[m]$ ] be the homomorphism associated to @xmath279 by the duality isomorphism @xmath282)^{\vee}$ ] of [ freecompletealgebras : duality ] . the adjoint homomorphism of the derivation @xmath276 corresponds under the duality isomorphism @xmath260)$ ] to the coderivation @xmath283)\rightarrow\operatorname{\mathsf{d}}(\operatorname{\bbbk}[m])$ ] associated to @xmath284 . formal from the expression of the derivation @xmath277 in the proof of proposition [ freecompletealgebras : continuousderivations ] of the coderivation @xmath285 in [ background : twistedobjects ] , and from the expression of the duality isomorphisms . the construction of quasi - free algebras over an operad can be adapted to free complete algebras . in that situation , we consider twisted dg - modules of the form @xmath286 where the twisting morphism @xmath287 is a continuous derivation of @xmath250 associated to some element @xmath274 . as in the context of quasi - free algebras , the derivation relation implies that the equation of twisting homorphisms @xmath288 is fulfilled for @xmath287 if and only if it holds on the generating element @xmath52 of @xmath250 . because of the relation @xmath280 , this equation amounts to the identity @xmath289 in @xmath250 . the purpose of the next paragraphs is to explain that the composition structure considered in the introduction of this article models expressions of the form @xmath290 , where @xmath291 , and can be used to characterize twisting derivations on @xmath250 ( as well as twisting coderivations on the cofree coalgebra @xmath269)$ ] by the duality statement of proposition [ freecompletealgebras : derivationadjunction ] ) . to begin with , we review the definition of the composition structure considered in the introduction for a free complete algebra @xmath250 over any operad @xmath78 . this definition is borrowed to @xcite ( we also refer to @xcite for a variant of this composition structure ) . one first defines the composite of elements of homogeneous order @xmath292 by a sum of operadic substitution operations @xmath293 running over all entries of @xmath294 . this termwise composition operation is continuous , and hence , extends to the completion @xmath295 . for our purpose , we just consider the restriction of the obtained composition operation to the dg - module @xmath296 , in order to obtain the operation : @xmath297 note that this composition operation decreases degrees by @xmath273 , and becomes degree preserving only when we form @xmath273-desuspensions of the dg - module @xmath250 . this composition operation @xmath298 is , after desuspension , an instance of a pre - lie structure in the sense of @xcite , a product satisfying the identity @xmath299 the next lemma gives our motivation to introduce the pre - lie composition operation : [ freecompletealgebras : compositederivations ] for any pair @xmath291 , we have the identity @xmath300 in @xmath250 . this lemma is obvious from the explicit expression of the derivation @xmath277 associated to any @xmath274 in the proof of proposition [ freecompletealgebras : continuousderivations ] . this lemma implies : [ freecompletealgebras : twistingderivations ] the derivation @xmath276 associated to any @xmath274 defines a twisting derivation on @xmath250 if and only if we have the identity @xmath301 in @xmath250 . in the next sections , we use the identity of lemma [ freecompletealgebras : compositederivations ] to express the derivation @xmath277 associated by proposition [ freecompletealgebras : continuousderivations ] to any element @xmath274 . before proceedings to the study of the chain complex @xmath49 , we record some applications of the pre - lie composition structure to the definition of morphisms on the operad of @xmath3-algebras . first of all , recall that this operad is defined by the cobar construction @xmath302 , where @xmath303 is the dual cooperad of the operad of commutative algebras . the operad @xmath304 comes equipped with a weak - equivalence @xmath305 , where @xmath306 is the operad of lie algebras . hence , we have an identity @xmath307 and the homology @xmath308 is generated as an operad by an operation @xmath309 satisfying the identities of a lie bracket . this observation is used in [ homotopyinvariance ] . for the moment , we just want to record the following general proposition : [ freecompletealgebras : linfinitymorphisms ] if the operad @xmath78 is equipped with a free @xmath112-structure , then we have a bijection between : 1 . the operad morphisms @xmath310 ; 2 . and the elements @xmath274 , of degree @xmath64 , and such that the relation @xmath301 holds in @xmath250 , where we still assume that @xmath52 is a variable of degree @xmath53 . the cobar construction commutes with operadic suspensions . therefore we have an identity @xmath311 . since @xmath312 for all @xmath313 , the homomorphism @xmath314 associated to @xmath203 is equivalent to a collection of invariant elements in @xmath315 . we use the assumption about the @xmath112-structure of @xmath78 and the existence of an isomorphism @xmath316 to identify this collection with an element of the form @xmath274 . we easily check that the equation of [ koszuldualityreview : cobarconstruction ] for the twisting cochain @xmath204 amounts to the equation @xmath301 for the element @xmath279 and the proposition follows . the aim of this section is to make explicit the complex @xmath317 computing @xmath318 for the cochain algebra of a sphere @xmath36 . we still consider the particular @xmath2-operads @xmath27 arising from a filtration @xmath319 of the chain barratt - eccles operad @xmath320 . we do not need to review the definition of these operads @xmath27 and of the barratt - eccles operad @xmath320 . we are simply going to explain a representation of the @xmath2-algebra structure of @xmath38 in terms of realizations , for these operads @xmath27 , of intrinsic homotopical structures of @xmath2-operads . this representation will give the form of the complex @xmath317 associated to @xmath36 . we review the definition of the @xmath321-algebra structure of @xmath38 first , before explaining applications of the koszul duality result of @xcite to the cochain algebra @xmath38 . recall that the ( reduced normalized ) cochain complex of a @xmath128-sphere @xmath322 is identified with the free @xmath20-module of rank @xmath90 concentrated in ( lower ) degree @xmath323 : @xmath324.\ ] ] the associated endomorphism operad @xmath325 is identified with the @xmath128-fold operadic desuspension of the commutative operad @xmath14 because we have identities : @xmath326^{\otimes r},\operatorname{\bbbk}[-d ] ) = \operatorname{\bbbk}[rd - d ] = \lambda^{-d}\operatorname{\mathsf{c}}(r).\ ] ] hence , the @xmath17-structure of @xmath243 is determined by an operad morphism @xmath327 . the work @xcite gives an explicit representation of this morphism for the chain barratt - eccles operad . for our purpose , we use that @xmath328 is identified with a composite @xmath329 where @xmath330 denotes the augmentation of the barratt - eccles operad ( to which we apply the operadic suspension functor ) while @xmath331 denotes a new operad morphism @xmath332 ( to which we also apply the operadic suspension ) discovered in @xcite and defined by an explicit formula . in ( * ? * observation 0.1.10 ) , we observe that @xmath332 has restrictions giving operad morphisms @xmath333 , for each @xmath334 , and we prove : [ spherekoszulduality : suspensionkoszuldual ] the weak - equivalences @xmath208 , already considered in theorem [ koszuldualityreview : koszuldualitystatement ] , fit a commutative diagram @xmath335^{\sigma^*}\ar@{.>}[d]_{\psi_{n-1}}^{\sim } & b^c(\operatorname{\mathsf{d}}_n)\ar@{.>}[d]_{\psi_n}^{\sim } \\ \operatorname{\mathsf{e}}_{n-1}\ar[r]_{\iota } & \operatorname{\mathsf{e}}_n } } , \ ] ] where @xmath336 is the embedding morphism and @xmath337 is the morphism associated to @xmath333 by functoriality of the construction @xmath338 . we recall , just after theorem [ koszuldualityreview : koszuldualitystatement ] , that the weak - equivalence @xmath339 arises as a lifting @xmath340!r+<4pt,0pt>;[r ] & \operatorname{\mathsf{e}}\ar[d]^{\epsilon } \\ b^c(\operatorname{\mathsf{d}}_m)\ar@{.>}[ur]^{\psi_m}\ar[rr]_{\phi_m } & & \operatorname{\mathsf{c}}}\ ] ] of a certain morphism @xmath341 . the notation @xmath330 refers again to the augmentation of the barratt - eccles operad . by cobar duality , we have an equivalence @xmath342 , where : @xmath343^{\iota^*}\ar@{.>}[d]_{\psi_n^{\sharp}}^{\sim } & b^c(\operatorname{\mathsf{e}}_{n-1}^{\vee})\ar@{.>}[d]_{\psi_{n-1}^{\sharp}}^{\sim } \\ \lambda^n\operatorname{\mathsf{e}}_n\ar[r]_{\sigma } & \lambda^{n-1}\operatorname{\mathsf{e}}_{n-1 } } } .\ ] ] the notation @xmath344 now refers to the morphism associated to the embedding @xmath336 by functoriality of the construction @xmath345 . from this result , we deduce : [ spherekoszulduality : spherealgebramodel ] for every @xmath346 , we have a commutative diagram @xmath347_{\iota^*}\ar[rr]^{\sim } & & \operatorname{\mathsf{e}}_n\ar[d]^{\sigma}\ar@{^{(}->}[]!r+<4pt,0pt>;[r ] & \operatorname{\mathsf{e}}\ar[d]^{\sigma } \\ \vdots\ar[d]_{\iota^ * } & & \vdots\ar[d]^{\sigma } & \vdots\ar[d]^{\sigma } \\ b^c(\lambda^{-n}\operatorname{\mathsf{e}}_{m}^{\vee})\ar[r]_(0.43){\simeq } & \lambda^{m - n}b^c(\lambda^{-m}\operatorname{\mathsf{e}}_{m}^{\vee})\ar[r]_(0.6){\sim}\ar@/_1em/[drr]_{\lambda^{m - n}\phi'_{m } } & \lambda^{m - n}\operatorname{\mathsf{e}}_{m}\ar@{^{(}->}[]!r+<4pt,0pt>;[r ] & \lambda^{m - n}\operatorname{\mathsf{e}}\ar[d]^{\sim } \\ & & & \lambda^{m - n}\operatorname{\mathsf{c}}= \operatorname{\mathit{end}}_{\bar{n}^*(s^{n - m } ) } } \ ] ] giving the action of the @xmath2-operad @xmath348 on @xmath38 , where @xmath349 is a morphism homotopic to @xmath341 in the model category of operads . note : one can easily observe that the cobar construction commutes with operadic suspensions . to determine the form of the complex @xmath350 , we essentially use the observation of [ koszuldualityreview : endomorphismoperads ] and the representation of the morphism @xmath351 supplied by this theorem . by ( * theorem 5.2.2 ) or ( * ? ? ? * theorem c ) , any @xmath352-algebras @xmath353 and @xmath354 having the same underlying dg - module @xmath33 but a different @xmath352-structure determined by morphisms @xmath355 are connected by a chain of weak - equivalences of @xmath352-algebras when the morphisms @xmath356 are homotopic in the category of operads . hence , in our study of the cochain algebra @xmath38 , any choice of morphism @xmath351 in the homotopy class of the composite @xmath357 will give the right result . for that reason , we can replace the morphism @xmath349 in theorem [ spherekoszulduality : spherealgebramodel ] by @xmath341 , or any homotopy equivalent morphism @xmath358 . besides , the construction of @xcite gives a morphism @xmath341 well - characterized up to homotopy only . let us review the definition of these morphisms @xmath359 before going further in our study . the morphisms @xmath43 are , according to the recollections of [ koszuldualityreview : cobarconstruction ] , determined by homomorphisms of @xmath112-modules @xmath360 satisfying a certain equation . in @xcite , we observe that the definition of @xmath361 amounts to the definition of a collection of elements @xmath362 of degree @xmath363 , or equivalently to an element @xmath67 of degree @xmath64 in the completed @xmath58-algebra @xmath364 , where @xmath52 is again a variable of degree @xmath53 . the element @xmath365 simply represents the term of order @xmath57 of @xmath63 . recall that @xmath366 for all @xmath313 . the equivalence between @xmath365 and @xmath361 is given by the adjunction relation @xmath367 , for any @xmath368 , where @xmath369 is any representative of @xmath365 in @xmath370 . in the relation , we use the isomorphism @xmath371 defined by the norm of the @xmath115-action ( recall that @xmath115 acts freely on @xmath372 ) . by inspection of ( * lemma 1.1.2 ) , we immediately see that the equation of the homomorphism @xmath361 amounts to the equation @xmath373 in term of the element @xmath63 , where @xmath374 refers to the composition operation of [ freecompletealgebras : compositionstructure ] . hence , we have by proposition [ freecompletealgebras : twistingderivations ] : [ spherekoszulduality : twistingderivation ] the element @xmath63 associated to the homomorphism @xmath361 defining @xmath341 determines , for each @xmath50 , a twisting derivation @xmath375 such that @xmath69 , for any @xmath376 . then we observe : [ spherekoszulduality : derivationadjunctionrelation ] the adjoint homomorphism of the derivation @xmath375 corresponds , under the isomorphisms @xmath377)\simeq\lambda^{-n}\operatorname{\mathsf{e}}_n^{\vee}(\operatorname{\bbbk}[m - n ] ) = \operatorname{\mathsf{d}}_n(n^*(s^{n - m}))\ ] ] to the twisting coderivation @xmath378 of the complex @xmath379 computing @xmath380 . in [ koszuldualityreview : endomorphismoperads ] , we observe that the homomorphism @xmath381)\rightarrow\operatorname{\bbbk}[m - n]$ ] defining the coderivation of @xmath382 . corresponds , by adjunction , to the twisting cochain @xmath383 } = \operatorname{\mathit{end}}_{n^*(s^{n - m})}$ ] determining the action of the operad @xmath28 on @xmath384 . by theorem [ spherekoszulduality : spherealgebramodel ] , this twisting cochain is given by a composite : @xmath385},\ ] ] where @xmath344 is , up to operadic suspension , the dual of the embedding morphism @xmath42 . if we apply the formula of @xmath361 in terms of the element @xmath63 , then we obtain the identity @xmath386 for any @xmath387 , where we go back to the notation used around proposition [ freecompletealgebras : dualityisomorphism ] for the elements of @xmath388)$ ] . thus we immediately see that @xmath185 agrees with the homomorphism associated to @xmath83 in [ freecompletealgebras : dualityisomorphism]-[freecompletealgebras : continuousderivations ] , and the adjunction relation between the coderivation @xmath389 and the derivation @xmath69 associated to @xmath67 follows from the assertion of proposition [ freecompletealgebras : derivationadjunction ] . from this statement , we conclude : [ spherekoszulduality : homologycomplex ] we have an identity @xmath390 , where we consider the twisting derivation @xmath69 of lemma [ freecompletealgebras : continuousderivations ] and the continuous dual of the twisted complete @xmath58-algebra @xmath68 . the theorem of the introduction follows from this result and : [ spherekoszulduality : topologicalinterpretation ] take @xmath391 as ground ring . for any space @xmath7 whose homology @xmath392 is a degreewise finitely generated @xmath70-module , we have an identity @xmath393 where @xmath394 refers to the profinite completion of the @xmath0-fold loop space @xmath4 ( of which we take the continuous cohomology ) . we have explained around theorem [ spherekoszulduality : spherealgebramodel ] that the result of theorem [ spherekoszulduality : homologycomplex ] does not depend on the choice of the morphism @xmath341 in a certain homotopy class because any such choice gives rise to weakly - equivalent models of the @xmath2-algebra underlying @xmath384 . we prove in the next section that a wider homotopy invariance property holds for theorem [ spherekoszulduality : homologycomplex ] . we have a result similar to lemma [ spherekoszulduality : derivationadjunctionrelation ] for the complex @xmath395 computing the natural cohomology theory @xmath396 associated to @xmath2-operads . as a byproduct , we also have a cohomological analogue of the result of theorem [ spherekoszulduality : homologycomplex ] . at the complex level , we obtain an identity of the form @xmath397 where we equip the dg - module @xmath54 with the twisting cochain such that @xmath398 . in the previous section , we have used a filtration layer of the barratt - eccles operad as a preferred @xmath2-operad , but we mention in the introduction of this article that the result of our theorems holds for any choice of @xmath46-operad @xmath58 and for any choice of morphism @xmath43 . the goal of this section is precisely to prove this wide homotopy invariance property . recall that @xmath399 is identified with the operad of associative algebras @xmath16 for @xmath400 , with the @xmath273-gerstenhaber operad @xmath401 for @xmath402 . the associative operad is generated as an operad by an associative product operation @xmath403 , of degree @xmath23 . the @xmath273-gerstenhaber operad is generated by an associative and commutative product operation @xmath404 of degree @xmath23 and by a lie operation @xmath405 of degree @xmath406 satisfying a graded version of the poisson distribution relation . for the moment , we still consider the @xmath46-operad @xmath58 of @xcite , arising from the filtration of the barratt - eccles operad . in this context , the morphisms @xmath43 are characterized by the relation @xmath407 and @xmath408 in homology where we use the isomorphism @xmath409 ( established in @xcite ) , because we have : note that the relation @xmath408 is obvious for @xmath402 since @xmath14 is concentrated in degree @xmath23 . for the element @xmath63 associated to @xmath341 , the relation @xmath407 amounts to the identity @xmath414 = \mu$ ] in @xmath415 , where @xmath416 refers to the component of @xmath67 of order @xmath417 . recall that @xmath418 and the relation @xmath419 implies at order @xmath417 that @xmath416 defines a cycle in @xmath420 ( see ( * ? ? ? * lemma 1.1.2 ) ) . now we plan to extend the result of theorem [ spherekoszulduality : homologycomplex ] to @xmath2-operads @xmath421 which are @xmath112-cofibrant but not necessarily finitely generated in all degree and for each arity . in that context , we consider the operad @xmath304 , associated to the usual category of @xmath422-algebras , defined by the cobar construction @xmath302 , where @xmath303 is the dual cooperad of the operad of commutative algebras . recall that @xmath308 is isomorphic to the operad of lie algebras @xmath306 which is generated , as an operad , by an operation @xmath309 satisfying the identities of a lie bracket ( see [ freecompletealgebras : linfinityoperad ] ) . in the next statement , we use the operadic suspension of this operad @xmath423 for which the homology is generated , as an operad , by a lie bracket operation @xmath309 of degree @xmath417 . since we can not form the dual of @xmath424 when @xmath424 is not free of finite rank in all degree and for each arity , we can not use the relationship between twisting elements @xmath425 and morphisms @xmath426 , but we still have : [ homotopyinvariance : morphismrepresentation ] the definition of a morphism @xmath427 , amounts to the definition of an element @xmath428 , of degree @xmath64 , vanishing at order @xmath90 , and satisfying @xmath429 in @xmath430 . moreover , we have the identity @xmath431 in homology if and only if @xmath432 = \mu$ ] in @xmath433 , where @xmath434 represents the term of order @xmath417 of @xmath435 . the first part of the proposition is established in proposition [ freecompletealgebras : linfinitymorphisms ] . the second assertion of the proposition is an obvious consequence of the relation , established in the proof of proposition [ freecompletealgebras : linfinitymorphisms ] , between the homomorphism @xmath436 which determines @xmath48 and the element @xmath435 . suppose now we have an @xmath46-operad @xmath424 together with a morphism of the form of proposition [ homotopyinvariance : morphismrepresentation ] and let @xmath435 be the associated element in the free complete @xmath424-algebra @xmath430 . we aim at comparing the pair @xmath437 to a pair @xmath438 formed from the barratt - eccles operad . we already know that the operads @xmath58 and @xmath58 are connected by a chain of weak - equivalences : @xmath439{\phi}\pi_m\xrightarrow[\sim]{\psi}\xi_m.\ ] ] we can moreover assume that the morphism @xmath440 and @xmath441 are fibrations . we have then : [ homotopyinvariance : morphismcorrespondence ] we have elements @xmath442 and @xmath63 such that @xmath443 and @xmath444 and satisfying the identity @xmath445 = [ \omega_m(2 ) ] = \mu$ ] in homology , where as usual @xmath446 ( respectively , @xmath416 ) denotes the term of order @xmath417 of @xmath447 ( respectively , @xmath67 ) . the idea is to define the components @xmath448 of the element @xmath442 by induction on @xmath57 . for this , we use that the equation @xmath449 amounts at order @xmath57 to an equation of the form : @xmath450 where we use the standard partial composite notation of the operadic substitution operation occurring in the definition of the composition product @xmath451 . thus , whenever appropriate elements @xmath452 such that @xmath453 are defined for @xmath454 , the existence of @xmath448 amounts to the vanishing of an obstruction in @xmath455 . now this obstruction does vanish just because @xmath441 induces an isomorphism in homology , preserves operadic structures , and carries ( [ obstructionequation ] ) to the same equation for @xmath435 . hence we are done with the definition of @xmath447 . [ homotopyinvariance : complexequivalences ] we have a chain of weak - equivalences @xmath457{\phi}(\widehat{\pi}_m(x),\partial_m)^{\vee } \xrightarrow[\sim]{\psi}(\widehat{\xi}_m(x),\partial_m)^{\vee}\ ] ] between the continuous duals of the chain complexes formed from the elements of lemma [ homotopyinvariance : morphismcorrespondence ] . the commutation of @xmath440 and @xmath441 with operad structures readily implies that @xmath440 and @xmath441 induce dg - module morphisms between the twisted complexes . by the standard spectral sequence argument , we obtain that these dg - module morphisms are weak - equivalences since @xmath440 and @xmath441 induce weak - equivalences at the level of cofree coalgebras . [ homotopyinvariance : statement ] let @xmath458 be any nested collection of @xmath112-cofibrant operads equivalent to the nested sequence of the chain operads of little cubes . suppose we have an operad morphism @xmath459 satisfying @xmath431 in homology and consider the equivalent element @xmath428 such that @xmath429 . in this theorem , we do not have to assume that the operad @xmath424 are finitely generated . in particular , we can apply the theorem to the @xmath2-operads considered in @xcite formed by the semi - algebraic chain complex of the fulton - macpherson operad . b. fresse , _ koszul duality of operads and homology of partition posets _ , _ in _ `` homotopy theory : relations with algebraic geometry , group cohomology , and algebraic @xmath462-theory '' , contemp . math . * 346 * , amer . ( 2004 ) , 115215 . , _ operadic cobar constructions , cylinder objects and homotopy morphisms of algebras over operads _ , _ in _ `` alpine perspectives on algebraic topology ( arolla , 2008 ) '' , contemp . math . * 504 * , amer . math ( 2009 ) , pp . 125189 . v. hinich , v. schechtman , _ on homotopy limit of homotopy algebras _ , _ in _ `` @xmath462-theory , arithmetic and geometry ( moscow , 19841986 ) '' , lecture notes in mathematics * 1289 * , springer - verlag ( 1987 ) , pp .

the goal of this article is to make explicit a structured complex computing the cohomology of a profinite completion of the @xmath0-fold loop space of a sphere of dimension @xmath1 . our construction involves : the free complete algebra in one variable associated to any fixed @xmath2-operad ; an element in this free complete algebra determined by a morphism from the operad of @xmath3-algebras to an operadic suspension of our @xmath2-operad . as such , our complex is defined purely algebraically in terms of characteristic structures of @xmath2-operads . we deduce our main theorem from several results obtained in a previous series of articles namely : a connection between the cohomology of iterated loop spaces and the cohomology of algebras over @xmath2-operads , and a koszul duality result for @xmath2-operads . we use notably that the koszul duality of @xmath2-operads makes appear structure maps of the cochain algebra of spheres .

the collective rise of grains in one branch of a vertically vibrated u - tube and some related instabilities like heaping and granular transport in vibrated granular deep beds in partitioned containers has been the subject of research for decades @xcite . in this work we concentrate in the experimental characterization of the rate of growth of the rising column of grains in a partially filled u - tube for different frequencies . the mechanism responsible for this interesting behavior is still an open issue . in a previous work @xcite the behavior of a vertically vibrated granular system in a partially filled u - tube at low frequency was studied . a collective granular transport upward through one of the branches of the tube was observed for small grains . the experimental results were compared with a model based on the idea of cyclic fluidization @xcite . in that model it was assumed that for low frequencies and sufficiently high amplitudes of oscillations the granular bed fluidizes cyclically in such a way that an effective upward acceleration acts on the grains while these are in a fluidized state . consequently , an instability appears and the free surface of the bed on either branch of the u - tube rises while the other goes down . therefore , one of the branches of the tube is rapidly filled and simultaneously the other empties . that model captures some relevant aspects of the observed behavior for low frequencies , as for example the exponential growth of the granular column and the monotonic increase of the growth rate with the dimensionless acceleration of the vibration ; however , we have found some important quantitative discrepancies . the above model for the measured growth rate @xmath0 versus the maximum dimensionless acceleration @xmath1 of the container provides only a crude approximation for low frequencies . as the frequency is increased above @xmath2 , it becomes clear that the model is insufficient to describe this phenomenon . in this paper we extend the work in reference @xcite by exploring the growth rate of the height difference between the two free surfaces , for a wider range of frequencies . we obtain a differential equation for the change of the measured growth rates with the dimensionless acceleration of the vibrations . for the vibrational system we used a function generator ( gw instek sfg-2110 ) linked to an audio amplifier ( crown xls 202 ) feeding two coupled 1000 watts loudspeakers . for the granular material we used glass spheres with diameter between @xmath3 and @xmath4 and bulk static density @xmath5 . the top of the container was made permeable to air but not to grains ( using a @xmath6 nylon mesh ) . the container is a u - shaped tube @xmath7 tall , with square internal cross section of @xmath8 . the total mass of grains used was @xmath9 , chosen to completely fill one of the u - tube branches . and @xmath10 . the increase of the growth velocity with time can be readily appreciated . ] images of the experiments were recorded using a digital camera ( pixelink pl - b741f ) . filming against a back light ( see fig . [ fig1 ] ) , allowed us to analyze the images using a commercial software to obtain the difference in height @xmath11 between the two free surfaces as a function of time . , between the free surfaces at the two branches of the tube . this plot is for @xmath12 and @xmath13 . ] the excitation signal used was a sine wave . the maximum amplitude of oscillation that could be reached was @xmath14 . the excitation was controlled considering the maximum dimensionless acceleration defined as @xmath15 , where @xmath16 denotes the acceleration of gravity , @xmath17 the amplitude of the oscillations and @xmath18 the frequency of the oscillations . the value of @xmath1 was varied from @xmath19 to @xmath20 . lower values did not generate any instability and higher values of this quantity were not possible to achieve due to the limitations of the equipment . the height difference @xmath11 between the granular level in both branches of the u - tube grows exponentially with time ( see fig . [ fig2 ] ) . the growth rate @xmath0 is determined from the fit of the exponential @xmath21 , where @xmath22 is the initial height difference and @xmath23 is the time . the graph of the growth rate @xmath0 versus dimensionless @xmath1 is shown in fig.[fig3 ] . the horizontal axis begins at @xmath24 , because for @xmath25 , @xmath26 . for each curve the oscillation frequency is fixed and the amplitude is varied . for all frequencies investigated there was a seemingly continuous transition from zero growth at the lowest amplitudes to a finite @xmath0 at higher amplitudes . it is apparent that for the larger frequencies ( @xmath27 and @xmath28 ) the growth rate reaches a saturation value , for sufficiently large amplitudes . for three of the intermediate frequencies ( @xmath2 , @xmath29 and @xmath27 ) we see that @xmath0 reaches a point where it changes abruptly to zero at a threshold of @xmath1 ( see arrows in fig . [ fig3 ] ) this suggests the occurrence of a first order phase transition , but more work needs to be done to characterize this observed abrupt transition . for the lowest frequency measured ( @xmath30 ) we could not determine whether there is a saturation region or a transition from high nonzero growth rate to zero growth at high amplitudes because of the limitations of our equipment . our experimental data is well described by a boltzmann sigmoidal curve for @xmath0 versus @xmath1 . this fitting relation is given by eq . ( [ eq1 ] ) , and it has four fitting parameters : ( a ) the higher asymptote @xmath31 ( characteristic value for the higher growth rates ) ( b ) the size of the interval @xmath32 ( gives the range of growth rate from the lower asymptote to upper asymptote ) ; ( c ) the inflection point @xmath33 ; and ( d ) the width @xmath34 of the transition region . @xmath35.\ ] ] a plot of @xmath31 as a function of the frequency is shown in fig . this parameter is the saturation growth rate and gives an upper limit for the speed of the upward granular transport through the tube . we observe that the ability of the granular material to flow upwards is reduced as the frequency increases . for higher frequencies we can expect that the granular system approaches a liquid like behavior , and consequently , as the frequency rises it becomes more difficult for the granular bed to climb up . as a function of frequency . it is clear that higher frequencies reduce the ability of the granular material to flow upwards . ] for each frequency we can separate the observed behavior in fig . [ fig3 ] in three regions . one for which @xmath36 at low @xmath1 , the second one for which @xmath37 , for intermediate values of @xmath1 ; and a third region for which @xmath26 and @xmath1 is high . we can speculate that , for a given frequency , at low @xmath1 ; the granular bed behaves like a solid ; at intermediate values of @xmath1 ; a mixed state occurs were the solid like state and the fluid state combine in a complex way to produce the collective upward motion of the grains in one of the branches of the container ; and for sufficiently high @xmath1 the liquid like state dominates and the grains are unable to climb up on one of the branches of the tube . we will now focus below on two types of transitions that were observed . one of them was a ( seemingly continuous ) transition from zero growth at the lowest amplitudes to a finite @xmath0 at higher amplitudes . the other was a `` jump '' in the value of @xmath0 ( resembling a first order phase transition ) , which marked a transition from finite growth rate to no growth , when @xmath1 was sufficiently large . a detailed study of each transition requires further investigations . for the case of the abrupt transition , a different experimental setup capable of reaching larger amplitudes is necessary . nevertheless , our data could give us an insight on the nature of the transition at low @xmath1 . to probe the nature of the transition at low @xmath1 , we plot in fig . [ fig5 ] , @xmath38 versus @xmath39 . the parameter @xmath40 can be thought as a characteristic relaxation time for the evolution from a symmetric to an asymmetric configuration . the critical value @xmath41 of the adimensional acceleration was taken as the mean between the highest @xmath1 before @xmath0 becomes non zero , and the lowest value of @xmath1 for which @xmath0 is different from zero . at the lower amplitudes it was observed that the critical value @xmath41 for the transition from zero growth to nonzero @xmath0 , shifted to higher values of @xmath1 as the frequency increased . we can see how @xmath40 diverges as @xmath1 approaches the critical value @xmath41 . more experiments have to be done before we can determine the nature of this transition . diverges as @xmath1 approaches a critical value @xmath42 . the data shown correspond to all the non zero @xmath0 measured . ] finally , we want to concentrate on the region of nonzero growth , for each curve we fixed the frequency and changed the amplitude @xmath17 of vibration , assuming that @xmath43 , we can rewrite equation ( [ eq1 ] ) in the following form : @xmath44 where @xmath45 . this expression gives the value of the normalized growth rate as a function of @xmath1 . for each frequency equation ( [ eq2 ] ) is a solution of the following differential equation : @xmath46\gamma_n.\ ] ] this equation is analogous to the well know logistic equation so we can picture @xmath47 as a stable fixed point for @xmath48 . therefore as @xmath1 increases the growth rate approaches its maximum value ( which correspond to the stable fixed point ) . the smaller @xmath49 , the more energy needs to be supplied through vibration to reach the plateau of the curve @xmath50 . in fig . [ fig6 ] we plotted the width @xmath34 of the region where @xmath0 grows . we observe that @xmath34 rises with the frequency up to @xmath51 and then drops almost an order of magnitude . this behavior signals a qualitative change around @xmath51 . for this frequency @xmath49 is much smaller than for the other ones we measured , therefore around this particular frequency we need to supply more energy to the granular bed to make it go from zero growth rate to the fastest growth . versus the frequency of vibration . the parameter @xmath34 is a measure of the increase in energy supplied to the granular bed through vibrations , to go from zero growth to the plateau of the curve @xmath52 ( see fits in fig . [ fig3 ] ) for a given frequency . a sharp increase occurs around @xmath53 a physical model that would explain our data and the above relationship for the growth rate and the adimensional acceleration for a given frequency is beyond the scope of this paper , but we consider that the simplicity of the results should help to suggest the relevant conditions that need to be satisfied by a reasonable model for the behavior of a vertically shaken granular bed in a partially filled u - tube . we have made an experimental characterization of the rate of growth for the height difference @xmath11 between the free levels of the granular columns in a partially filled u - tube subject to vertical vibrations . we have observed a continuous transition from zero growth to non zero growth rate @xmath0 . the region of finite growth was well described by a differential equation analogous to the logistic equation . we also observed an abrupt transition from high values of @xmath0 to zero growth similar to a first order phase transition . this work has been done under the locti project : `` la acstica como punta de prueba de los medios porosos y sistemas granulares '' and ivic project 857 . it was also supported in part by fonacit under grant s1 - 2000000624 , and by did of the universidad simn bolvar . gutman , trans . 54 , 174 - 183 ( 1976 ) . p. evesque and j. rajchenbach , phys . 62 , 44 - 46 ( 1989 ) j. rajchenbach , eur . 16 , 149 - 152 ( 1991 ) . p. j. king , p. lopez - alcaraz , h. a. pacheco - martinez , c. p. clement , a. j. smith , m. r. swift , eur . j. e 22 , 219 - 226 ( 2007 ) . sanchez i. , darias r. , paredes r. , lobb c. , gutirrez g. , traffic and granular flow 07 , appert - rolland , c. ; chevoir , f. ; gondret , p. ; lassarre , s. ; lebacque , j .- p . ; schreckenberg , m. ( eds . ) ( 2009 ) . g. gutirrez , o. pozo , l.i . reyes , r. paredes , j.f . drake , e. ott , europhys . 67 , 369 ( 2004 ) . t. akiyama , k. s. shinmura , s. murakawa , k. m. aoki , granular matter 3 , 177 ( 2001 ) . w. chen , r. wei , physics letters a 244 , 389 - 393 ( 1998 ) . y. maeno , physica a 232 , 27 ( 1996 ) .

we investigate experimentally the behavior of the rate of growth of a column of grains , in a partially filled vertically shaken u - tube . for the set of frequencies used we identify three qualitatively different behaviors for the growth rate @xmath0 as a function of the dimensionless acceleration @xmath1 : 1 ) an interval of zero growth for low @xmath1 with a smooth change to nonzero growth , analogous to a continuous phase transition ; 2 ) a sigmoidal region for @xmath0 at intermediate values of the dimensionless acceleration @xmath1 ; and 3 ) an abrupt change from high values of @xmath0 to zero growth at high values of @xmath1 , similar to a first order phase transition . we obtain that our data is well described by a simple differential equation for the change of the growth rate with the dimensionless acceleration of the vertical vibrations .

cardiac stress testing is the basic screening tool for ischemic coronary artery disease ( cad ) . in the event of abnormal distribution of myocardial blood flow ( or positive result indicative of functionally significant ischemia ) , coronary angiography is performed as the current gold standard in the diagnosis of ischemic cad . this is particularly the case for patients presenting with suggestive chest pain and intermediate pre - test probability of significant cad . coronary angiography generally allows the clinician to draw definitive conclusions and guide management of ischemic coronary syndromes . nevertheless , there are a significant number of patients who , despite suggestive clinical symptoms and myocardial perfusion imaging ( mpi ) evidence of ischemia , have angiographically normal coronary arteries . data from the women 's ischemic syndrome evaluation study indicate that , of the over 500,000 people who undergo left heart catheterization every year , approximately 48% of women and 17% of men have no intraluminal lesions or < 50% narrowing of one or more coronary arteries.12 a significant number of these individuals continue to present for evaluation of anginal - like chest pain . also , there are significant subsets of these patients who present with recurrent classical angina and subsequently display mpi consistent with ischemia ; however , they do not develop any significant angiographic diseases . these patients have traditionally been stratified to an ambiguous area of the coronary disease spectrum , known as cardiac syndrome x ( csx ) . classified as having csx ( the current general consensus is that csx patients have abnormal treadmill and/or abnormal mpi ) , these patients are left with little definitive long - term prognostic information.3 they often continue to have classical anginal chest pain , without plausible ( cardiac and noncardiac ) causes to account for it following extensive workup . initial studies suggested that csx conferred no significant increase in the risk of adverse cardiac events as compared to their counterparts with normal mpi.456789101112 however , recent data have shown that patients with csx with endothelial dysfunction appear to have an increased risk for future adverse cardiac events.13141516 furthermore , much of the literature suggesting the syndrome as a benign condition rest largely on data from both observational and retrospective studies that have been underpowered to definitively reach this conclusion . most of these investigations were performed prior to the era of advanced cardiac imaging modalities , including magnetic resonance imaging ( mri ) and nuclear magnetic resonance ( nmr ) capable of assessing both endocardial and epicardial disease.1718 also , little is known of the overall risk of adverse events when adjustments for age , sex and demographics are made . despite a number of unresolved questions , the available data suggest an overall increased prevalence of csx in middle - aged caucasian females as compared to all other populations . this , coupled with an increased association with features of the metabolic syndrome and migraine headache disease has led many to postulate the syndrome to be one of microvascular origin.19 these patients tend to have other apparent associations including strong family history of cad and prothrombotic states.20 however , the long - term risk of adverse cardiac events in this population remains ill - defined at best and thus perpetuates the therapeutic dilemma for clinicians . finally , because a majority of csx data comes from homogenous samples , it is difficult to definitively extrapolate all results to a diverse population . the purpose of this study was to assess long - term clinical outcomes of patients who presented to the nashville metropolitan general hospital with the features of csx . further , employing the diverse patient population of our hospital , we sought to compare the outcomes seen in our institution to those from prior less diverse populations to compare clinical outcomes . the primary hypothesis was that patients with cardiac syndrome - x would have no significant differences in both the primary and secondary clinical endpoints as compared to individuals with negative nuclear stress tests and no subsequent angiography . following institute 's research board ( irb ) approval , we identified 49 patients with typical chest pain and normal or near - normal coronary angiograms : 28 men and 21 women , who presented to the nashville metro general hospital from 2002 to 2005 . inclusion criteria included established exertional angina , an abnormal nuclear stress test , suggesting ischemia ( reversible perfusion defect on mpi ) and normal or near - normal ( less than 40% luminal narrowing ) results on coronary angiography . similar data were collected for 37 randomly selected patients ( controls ) who had chest pain and negative ( normal ) nuclear perfusion stress tests in the same time period ; 22 of these were men and 15 were women . the time for follow - up of clinical outcomes was an average of 24 months with a range of 15 - 36 months . the exclusion criteria included a percutaneous transluminal coronary angioplasty ( ptca ) ; coronary artery bypass grafting ( cabg ) or prior myocardial infarction ; coronary spasm during the coronary angiography ; severely uncontrolled hypertension ( defined as blood pressure > 200/110 mmhg ) ; arrhythmias such as paroxysmal atrial fibrillation ( paf ) ; and left bundle branch block ( lbbb ) . our primary outcome was the combined endpoint of definite or suspected death from heart disease ( including sudden cardiac death ) , non - fatal myocardial infarction and fatal or non - fatal stroke , assessed in the entire cohort ( major adverse cardiovascular endpoints ) . secondary outcomes included examination of the number of subsequent hospitalizations for chest pain , number of emergency room visits for chest pain , development of clinical heart failure and the number of individuals requiring repeat cardiac catheterization . in addition , we assessed both the primary and secondary outcomes separately for men and women as well as for individual ethnic groups [ table 1 ] . also , the outcomes were correlated with known cardiovascular disease risk factors . we also examined the magnitude of the relationship of clinical endpoints to the frequency of individual baseline risk factors ( including smoking status , history of hypertension , diabetes , sex , cardiovascular medications , hdl and ldl cholesterol concentrations ) . the controls were screened randomly from a list of all patients undergoing nuclear stressing over the same 4-year period . specifically , every 7 patient - chart was selected ( contingent that they met none of the exclusion criteria ) for the control group until a number needed for statistical power was reached . this approach allowed us to determine the outcome differences of those stratified to the syndrome - x population , while still preserving the randomized allocation . all data are expressed as mean standard deviation ( sd ) . a p - value < 0.05 was considered statistically significant . statistical analysis involved the comparison of primary and secondary outcomes between the abnormal stress test cohort and the control cohort , respectively , by use of the z - test of proportions test . statistical analysis involved the comparison of primary and secondary outcomes between the abnormal stress test cohort and the control cohort , respectively , by use of the z - test of proportions test . a total of 53 patients were found to have positive nuclear stress testing and negative coronary angiography . however , only 47 individuals were eligible for the study , and the mean duration of follow - up was 19.1 8.4 months ( range 9 - 47 months ) , which yielded a total of 898 patient - months of follow - up . the mean age of the study population was 51.0 3.4 years ( range 30 - 74 years ) and the mean bmi was 33.0 1.4 kg / m . in this cohort , 42 ( 85.7% ) had hypertension , 28 ( 57.1% ) were smokers and 18 ( 38.2% ) had diabetes diagnosed prior to the index angiogram . the ethnicity of the study population is delineated in [ table 1 ] along with various other baseline characteristics . a total of 37 patients with negative nuclear stress testing and , thus , no subsequent coronary angiography were identified via the screening method described above . from the 37 individuals selected , the mean duration of follow - up was 29.3 6.8 months ( range 1 - 47 months ) , yielding 1,084 patient - months . the mean age of the study population was 51.7 2.9 years ( range 30 - 74 years ) and the mean bmi was 28.7 1.3 kg / m . in this cohort , 17 ( 47.2% ) had hypertension , 15 ( 40.5% ) were smokers and 6 ( 16.7% ) had diabetes diagnosed prior to the index angiogram [ table 1 ] . baseline demographics of the cases and controls the number of patients with adverse outcomes in the control group was 8 ( 21.6% ) . however , in the case group , the patients with adverse outcomes numbered 26 ( 53% ) . the difference between the two groups is statistically significant with a p - value of 0.0063 . the number of males with adverse outcomes was 13 ( 27.7% ) and 3 ( 8.1% ) in the case and control groups , respectively . the overall number of adverse outcomes in the control and case cohorts was 11 and 45 , respectively . furthermore , the number of cardiac - related hospitalizations was 4 and 35 in the control and case groups , respectively [ figure 1 ] . clinical cardiovascular outcomes of both cohorts within the positive - nuclear stress ( case ) group , 22 ( 46.8% ) patients had recurrent chest pain necessitating emergency room visitation as compared to only 9 ( 24.3% ) patients from the normal nuclear stress group during the same follow - up period . however , only individuals ( 2 or 4.3% ) from the positive stress cohort went on to undergo repeat cardiac catheterization for recurrent chest pain . incident chf was seen in 9 ( 19.1% ) patients of the case cohort and 2 ( 5.4% ) of the control group ( different patients from those with repeat catheterization ) in the period of follow - up . when the study population is reviewed for the development of acute coronary syndrome(s ) ( acs ) , only 2 ( 4.3% ) patients required hospitalization for a documented acs event . no patients from the control population went on to develop a documented ischemic event . in the case population , 1 patient suffered from a cerebrovascular event and 3 individuals developed a cardiac arrhythmia , respectively . our results show that , in a male - predominant cohort of chest pain patients , ischemia on mpi despite subsequent negative coronary angiography is associated with a long - term higher risk of adverse cardiovascular events as compared with chest pain patients without ischemia on mpi . these results consistently hold true across all pre - defined markers of cardiovascular outcomes , except when sudden cardiac death is considered ( no deaths ) . there is no significant deviation in this trend accounting for gender , race and ethnicity . however , it must be stated that this trend reaches statistical significance only when either the combined primary and secondary endpoints ( p = 0.005 ) or the secondary endpoint alone are evaluated . a level of statistical significance is not reached when the major adverse cardiovascular outcomes ( mace ) alone are examined . nevertheless , the case cohort does continue to demonstrate the same trend of increased incidence when mace alone is assessed ( despite not reaching statistical significance ) . the significant increase in cardiovascular morbidity demonstrated by the investigators appears to contradict a significant body of literature , indicating that the syndrome confers no additional additive risk of adverse cardiac events . but , as previously stated , the parameters considered in our population differs from the majority of previous populations studied . this includes the fact that a majority of prior studies have focused on outcome data in middle - aged caucasian women.21 we acknowledge that some of the additional risk seen in this population may be attributed to baseline cardiovascular risk factors , including the cad equivalent diabetes , which may account for some of the differences shown . however , despite the increased prevalence of diabetes and hypertension in our patients with adverse outcomes , the number did not reach statistical significance . in fact , only tobacco was found to confer a statistically significant association with long - term outcomes on matching the cohorts . , found that , in a retrospective analysis of 48 older male veterans undergoing coronary angiography , following abnormal stress testing , a statistically significant number of patients studied were at some level of increased risk for adverse cardiac outcomes.23 when estimating the ramifications of these findings , it is important to note that , individuals with chest pain and normal coronary arteriogram have been observed to represent 10 - 27% of those undergoing coronary arteriography after clinical suspicion of angina.2425 these figures represent a large number of individuals from the population in light of the prevalence of ischemic disease . in our institution , just over 8% were found to meet the inclusion described above ( as well as meet no exclusion criteria ) , which was not without precedence , as other investigators have found population incidences as low as 3% ( most studies employed a combination of at least three inclusion criteria , namely ( effort induced ) angina pectoris , positive exercise test result and a normal coronary angiogram).3 once individual cv outcomes are sub - analyzed , not surprisingly , a significant increase in the incidence of recurrent chest pain admissions is demonstrated . it is reasonable to argue that the higher volume of chest pain visits may be explained by the clinical history employed for qualification in this study in addition to the psychological impact of having a positive stress test . but , the increase in adverse outcomes post - index catheterization suggests that reasonable consideration should be given to future complaints of chest pain in this population . as stated above , when matched for clinical outcomes , patients with baseline hypertension and diabetes mellitus appeared to be at higher risk for future adverse events as compared to those free of these co - morbidities . furthermore , because diabetics are in constant state of increased systemic inflammation along with increased vascular endothelial dysfunction and diffuse small vessel disease , we argue that diabetics are predisposed to angiographically silent microvascular ischemia.2627 this postulation has been suggested by other investigators as well and our data also supports this . it is also important to note that the prevalence of tobacco ( an agent known to increase both inflammation and endothelial dysfunction leading to a pro - atherogenic state ) use was significantly higher in the study group . these findings led us to argue that the underlying pathogenesis of this syndrome involves subendocardial ischemia . it is because of this subendocardial ischemia that we suggest the use of calcium channel - blockers coupled with the judicious use of anti - platelet therapy.2728 treatments that improve endothelial function , such as angiotensin - converting enzyme inhibitors , estrogen , statins and lifestyle modifications , may be promising additions to treatment regimens for csx . however , due to the largely unknown pathogenesis of this syndrome and the lack of quality outcome data , we suggest large , randomized prospective trials aimed at answering these therapeutic questions ( with the additional use of mri and nmr to help define the microvasculature circulation ) . although a number of investigators have argued that csx is a disease limited almost exclusively to women , our findings imply otherwise . in fact , recent reviews suggest that over 43% of individuals proposed to meet criteria for syndrome x are male sex.3 the veterans association ( va ) study demonstrated an increase in adverse events among their all - male , predominantly , white cohort.23 in our selection of patients , we found that over 50% of individuals meeting criteria for syndrome however , potentially more interesting is that the population studied was significantly more ethnically diverse and may better represent entire csx cohort as a whole , an analysis called for by the va investigators . nevertheless , given the diverse nature of the patient population studied , it is reasonable to , at minimum , reject the hypothesis that male sex confers near immunity to the disease . aspirin is a standard therapy in patients considered to have underlying ischemia without significant contraindication ( data currently suggests contraindication to its use in patients who are believed to have been ruled - out for ischemic disease over concern for its non - steroidal anti - inflammatory properties ) . however , even after anti - platelet use is considered , there is no significant correlation with outcomes . in fact , all anti - platelet , vasodilator , calcium - channel and neurohormonal - modulating agents were used equally or significantly more frequently in the case cohort , suggesting that the observed outcomes were not due to non - treatment with these medications . we could not routinely screen for medication compliance given the retrospective nature of this study . however , since the study cohorts were both gender- and age - matched ( on review , there was a predominance of males who underwent stress testing at many institutions ) after meeting inclusion criteria , this approach should still lead to an unbiased estimate of the effects of a clinical presentation consistent with csx - like disease . first , the inherent limitations of a retrospective study must be acknowledged , including missing data and the inability to control for all confounders . second , because of the limited size of the study population , statistical power could not be reached when evaluating several of the secondary endpoints , including arrhythmia and chf admissions . however , as described above , the study did reach statistical power to sufficiently evaluate its primary endpoint . finally , limitations in data collection hindered determination of the effect of medications such as calcium - channel blockers on disease outcome . in summary , our study demonstrated that chest pain patients with a positive stress test and negative coronary angiograms are still at a higher risk of subsequent adverse cardiovascular events when compared to those with a negative stress test . these may be more appropriately labelled as false - negative coronary angiograms rather than this appears to be gender - neutral and more likely to be seen in those patients with multiple cardiovascular disease risk factors , including tobacco use , hypertension and diabetes . rather than dismissing these patients as having non - cardiac chest pain , aggressive preventive strategies might be useful in attenuating the morbidity and costs associated with this condition .

background : patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging ( mpi ) , but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma . they are often dismissed as having false - positive mpi. moreover , a majority of the available long - term outcome data for it has been derived from homogenous female populations . in this study , we sought to evaluate the long - term outcomes of this presentation in a multiethnic male - predominant cohort.materials and methods : we retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on mpi , but with no significant angiographic disease on subsequent cardiac catheterization ( cases ) . the occurrence of adverse cardiovascular outcomes ( chest pain , congestive heart failure , acute myocardial infarction and stroke ) post - index coronary angiogram was tracked . similar data was collected for 37 patients who also presented with chest pain , but normal mpi over the same period ( controls ) . overall average follow - up was over 22 months.results:fifty-three percent ( 26/47 ) of the cases had one or more of the adverse outcomes as compared with 22% ( 8/37 ) of controls ( p < 0.01 ) . of these , 13 ( 50.0% ) and 3 ( 37.5% ) were males , respectively.conclusions:ischemia on mpi is predictive of long - term adverse cardiovascular outcomes despite normal ( false - negative ) coronary angiography . this appears to be gender - neutral .

small cell lung cancer ( sclc ) represents 1320% of all new lung cancer diagnoses . it is the most aggressive histological subtype of lung cancer , with a strong predilection for early metastases . the brain is a common site of metastasis in sclc . at the initial diagnosis , at least 10% of the patients with sclc already have brain metastases , brain metastases signal stage iv disease and generally herald an ominous prognosis , but neuro- and radiosurgical therapeutic evolution has resulted in effective therapeutic approaches , leading to improvements in neurological status and survival [ 2 , 3 ] . a 69-year - old caucasian man was admitted to the emergency unit , complaining of progressive exophthalmos over the past 15 days ( fig . his medical history included heavy smoking ( 108 pack - years , until the day of admission ) . the patient reported fatigue without loss of weight for the last 6 months . on physical examination , auscultation of the lungs revealed diminished breath sounds and dullness to percussion in the upper left lung field . blood tests disclosed anemia , hematocrit 33.1% and hemoglobin 10.4 g / dl , with a pattern of chronic diseases . the serum chemistry findings were normal . 2a ) showed a sizable mass in the left upper lobe of the lung in contact with the pleura . chest computed tomography ( ct ) revealed a large round solid tumor with hilar and pre - vascular lymph node enlargement . the patient underwent magnetic resonance imaging ( mri ) of the brain and orbits to enable further evaluation . the mri revealed a soft - tissue mass in the outer posterolateral wall of the right orbital cavity with infiltration of the subcutaneous fat , muscles and skin ( fig . a ct of the upper and lower abdomen also showed no metastatic lesions . in an attempt to determine the exact histopathological nature of the lesion the findings included a bleeding multilobar mass infiltrating the main carina and projection of the adjacent bronchial mucosa due to external pressure at the rising of the right main bronchus . the patient additionally underwent an orbital biopsy ( ct - guided fine needle aspiration biopsy ) [ 4 , 5 ] . the patient was referred to the pulmonary department ( oncology unit ) for first - line chemotherapy with six regimens of cisplatin and etoposide , showing an initial complete response both at the primary site and the orbital metastasis ( fig . due to subsequent relapse to the lung , after the 4th cycle the patient underwent second - line chemotherapy with topotecan and carboplatine . at his last follow - up , a complete resolution of the exophthalmos he concluded six cycles with an initial partial response , but died 2 months after the last session . written informed consent was obtained from the patient upon discharge for publication of this case report and all accompanying images . sclc represents 1320% of all new lung cancer diagnoses . it is the most aggressive histological subtype of lung cancer , with a strong predilection for early metastases . the brain is a common site of metastasis in sclc , accounting for approximately 70% of cases [ 2 , 3 ] . at diagnosis , at least 10% of the patients already have brain metastases , and the majority of these will be symptomatic . central nervous system metastases signal stage iv disease and generally herald an ominous prognosis , but neuro- and radiosurgical advances have resulted in effective treatments of brain metastases , leading to improvement in neurological status and survival [ 6 , 7 , 8 ] . orbital metastases are a rare manifestation of systemic malignancies and account for only 113% of all orbital tumors [ 9 , 10 , 11 ] . however , the precise incidence of these lesions is difficult to estimate . it has increased in recent years because improvements in treatment modalities have resulted in improved survival in cancer patients . published reports indicate breast and lung tumors to be the most common primary neoplasms leading to eye metastasis , and metastases to the eye or orbit develop in approximately 0.712% of patients with lung cancer [ 9 , 10 , 11 ] . ophthalmologic symptoms may be preceded by systemic symptoms , especially if the primary site is the lung , gastrointestinal tract , thyroid or kidney . the most common manifestations of orbital metastases are diplopia , exophthalmos , inflammation , decreased visual acuity , pain , chemosis and eyelid swelling , depending on the site affected . symptoms usually occur acutely and progress rapidly , over the course of weeks to months [ 9 , 10 , 11 ] . regardless of the primary tumor type , prognosis is poor because patients with orbital metastases are usually at an advanced stage of the disease . in one report , the median survival time was 1.3 years , and the two - year survival rate was 27% [ 4 , 5 ] . the survival duration was not significantly different among patients with different types of primary neoplasms . available treatment options of orbital metastasis are external beam radiotherapy , plaque radiotherapy and newer methods like surgical resection , transpupillary thermotherapy and intravitreal chemotherapy . additionally , anti - vascular endothelial growth factor therapy can be used to slow the progress of maculopathy and neuropathy as well as spare vision after local radiotherapy [ 12 , 13 , 14 ] . systemic chemotherapy alone can also be used to treat metastatic tumors to the eye and orbit . however , chemotherapy of the primary cancer alone is not recommended in patients in whom the orbital lesion does not resolve with chemotherapy alone . in this case report , a thorough follow - up of the orbital lesion is presented radiographically , in combination with chemotherapy administration . even thought reduction in visual acuity due to orbital metastasis is rarely the first sign of lung cancer , the clinician should be alert . routine annual or biannual ophthalmic examination is recommended for patients with underlying primary cancers to allow early detection of metastasis and early intervention to protect vision and maintain quality of life .

small cell lung cancer is characterized by rapid growth and early metastasis . despite its sensitivity to cytotoxic therapy , until now treatments have failed to control or cure this disease in most patients . orbital metastases are a rare manifestation of systemic malignancies . breast and lung cancers represent more than two thirds of the primary cancer sites . metastases to the eye and orbit develop in approximately 0.712% of patients with lung cancer . here , we report a rare case of exophthalmos as the first manifestation of a metastatic carcinoma due to small cell lung cancer , and a 6-months follow - up with complete exophthalmic response to chemotherapy .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Domestic Violence Records Reporting Improvement Act of 2017''. SEC. 2. RESTRICTION ON NCHIP GRANTS. Section 102 of the Crime Identification Technology Act of 1998 (34 U.S.C. 40301) is amended by adding at the end the following: ``(g)(1) National Instant Criminal Background Check System.--For purposes of this subsection, the term `National Instant Criminal Background Check System' means the National Instant Criminal Background Check System established under section 103(b) of the Brady Handgun Violence Prevention Act (18 U.S.C. 922 note) for firearms eligibility determinations. ``(2) Domestic Violence Record Defined.--For purposes of paragraph (3), a domestic violence record is the following: ``(A) A record that identifies a person who is subject to a court order described in section 922(g)(8) of title 18, United States Code. ``(B) A record that identifies a person who was convicted in any court of a misdemeanor crime of domestic violence, as defined in section 921(a)(33) of title 18, United States Code, during the 5 years preceding the date of enactment of this subsection. ``(3) Report to Congress.--Not later than January 31 of each year, the Attorney General shall submit to the Committee on the Judiciary of the House of Representatives and the Committee on the Judiciary of the Senate a report identifying the percentage of records described in paragraph (2) from each State that are accessible through the National Instant Criminal Background Check System. ``(4) Methodology.--The method established to calculate the number of records identified in paragraph (2) accessible through the National Instant Criminal Background Check System, as set forth in paragraph (2) and State compliance with the required level of reporting under paragraph (6), shall be determined by the Attorney General, after consultation with the States, in accordance with the following: ``(A) A record of an individual convicted of a misdemeanor crime of domestic violence shall be counted as accessible through the National Instant Criminal Background Check System if a record identifying the individual has been submitted to the NICS Index or a record identifies the individual in the Interstate Identification Index and the record in the Interstate Identification Index either complies with paragraph (c)(2) of section 102 of the NICS Amendment Improvements Act of 2007 (34 U.S.C. 40912), or otherwise clearly indicates that the person is ineligible to purchase or possess firearms as a result of the conviction. ``(B) A record of an individual subject to a court order described in section 922(g)(8) of title 18, United States Code shall be counted as accessible through the National Instant Criminal Background Check System if either a record identifying the individual has been submitted to the NICS Index, or the individual is identified in the Protection Order File of the National Crime Information Center and the record in the Protection Order File of the National Crime Information Center clearly indicates that the person is ineligible to purchase or possess firearms as a result of the court order. ``(5) Grant Eligibility.--Starting in each year as stated below, a State shall not be eligible for a grant under this section for purposes that do not contribute to the accessibility of the records described in paragraph (2) through the National Instant Criminal Background Check System, unless at least the following percentage of such records from that State are accessible through the National Instant Criminal Background Check System, as determined by the Attorney General in accordance with paragraph (4): ``(A) 30 percent of such records, starting 2021; ``(B) 50 percent of such records, starting 2023; and ``(C) 70 percent of such records, starting 2025. ``(6) Reallocation.--Any funds that are not allocated to a State because of the failure of the State to comply with the requirements of this subsection shall be reallocated to States that meet such requirements.''. SEC. 3. NARIP FUNDING FOR DOMESTIC VIOLENCE REPORTING. (a) Implementation Assistance to States.--Section 103(c) of the NICS Improvement Amendments Act of 2007 (34 U.S.C. 40913) is amended-- (1) by inserting ``(1)'' after ``(c)''; and (2) by adding at the end, the following: ``(2) The Attorney General shall waive the requirement of a relief from disabilities program for any State to receive a grant under this section if the primary purpose of the grant is to improve the accessibility through the National Instant Criminal Background Check System of the records identified in subsection (g)(3) of section 102 of the Crime Identification Technology Act of 1998 (34 U.S.C. 40301).''. (b) Disposition Records Automation and Transmittal Improvement Grants.--Section 301(d) of the NICS Improvement Amendments Act of 2007 (34 U.S.C. 40941) is amended-- (1) by inserting ``(1)'' after ``(d)''; and (2) by adding at the end, the following: ``(2) The Attorney General shall waive the requirement of a relief from disabilities program for any State to receive a grant under this section if the primary purpose of the grant is to improve the accessibility through the National Instant Criminal Background Check System of the records identified in subsection (g)(3) of section 102 of the Crime Identification Technology Act of 1998 (34 U.S.C. 40301).''.

Domestic Violence Records Reporting Improvement Act of 2017 This bill amends the Crime Identification Technology Act of 1998 to require a state, as an eligibility condition to receive a grant under the National Criminal History Improvement Program, to provide to the National Instant Criminal Background Check System (NICS) a certain percentage&nbsp;of records related to domestic violence convictions and protection orders. Additionally, the bill amends the NICS Improvement Amendments Act of 2007 to waive the requirement for a state to certify, as an eligibility condition to receive a grant under the NICS Act Record Improvement Program (NARIP), that it has a relief from disabilities program, if the state's primary purpose for the NARIP grant is to improve access to domestic violence records in the NICS.

this work was supported by doe grant no.de-fg02-97er41048 .

using vector meson dominance ( vmd ) , tensor glueball photoproduction cross sections , asymmetries and widths are calculated . the predicted hadronic @xmath0 decays are comparable for different vector meson ( @xmath1 and @xmath2 ) channels with the @xmath3 width the largest but the radiative @xmath4 and @xmath5 decays are suppressed relative to @xmath6 by over a factor of 2 . this decay profile is distinct from typical meson branching rates and may be a useful glueball detection signature . results are compared to a previous vmd scalar glueball study . = 10000 = 12pt = 9.25 in = -.25 in = .3 in documenting hadron states with predominantly gluonic degrees of freedom , i.e. glueballs , has been a challenging and somewhat elusive pursuit . even though such states are consistent with quantum chromodynamics ( qcd ) and predicted by both lattice simulations @xcite and gluonic models @xcite , clear experimental evidence is lacking . the purpose of this letter is to motivate additional experimental investigations by providing estimates , based upon vmd , of tensor glueball photoproduction observables and also to detail a possible decay signature for hadronic states with a significant gluonic component . the latter entails comparable @xmath7 hadronic widths , with the largest branch to @xmath8 that promptly goes to @xmath9 , and somewhat suppressed @xmath4 and @xmath5 radiative decays relative to @xmath10 . as discussed below , this decay signature is not expected for hadrons with a predominantly quark structure . these results are essentially model - independent since they follow directly from the general principles of vmd , which has been found to agree with more fundamental qcd based meson radiative calculations @xcite , and the flavor independence of quark - gluonic couplings . consider the radiative decay @xmath11 of a neutral tensor hadron with arbitrary quark , gluon structure and mass @xmath12 . here @xmath13 , @xmath14 are the momenta of the photon and vector meson with mass @xmath15 ( @xmath16 ) . the most general , gauge invariant @xmath17 vertex is @xcite @xmath18 where @xmath19 , @xmath20 and @xmath21 are the photon , vector meson and @xmath22 polarization vectors and tensor , respectively . note that there are two possible coupling constants , @xmath23 and @xmath24 , which in vmd ( also tensor meson dominance ) are given by @xcite @xmath25 with @xmath26 the @xmath27 hadronic coupling constant , @xmath28 the @xmath29 leptonic decay constant and the sum is over all vector meson contributions consistent with isospin conservation for the @xmath27 vertex . the radiative decay widths are @xmath30 \ , \label{vgwidth}\ ] ] and @xmath31 , @xmath32 . focusing upon isoscalar tensor hadrons ( @xmath33 yields the radiative couplings @xmath34 since the @xmath35 and @xmath36 masses are almost equal ( @xmath37 775.8 mev , @xmath38 782.59 mev ) , the ratio of the @xmath36 to @xmath35 channel decays is simply @xmath39 application to tensor glueballs , i.e. @xmath40 , and assuming flavor independence for the glueball - vector meson couplings , @xmath41 , yields @xmath42 hence the ratio of decay widths is entirely governed by the leptonic decay constants whose magnitudes can be extracted from @xmath43 using @xmath44 the most recent measurements @xcite yield @xmath45 = 4.965 , @xmath46 = 17.06 and @xmath47 = 13.38 for a relative reduction @xmath48 . the @xmath49 channel , which is also reduced by this factor , is further suppressed kinematically . as discussed below , suppression of radiative decays to isoscalar vector meson channels is not generally expected for tensor mesons since they will have different @xmath50 couplings reflecting their various flavor contents . note also that the relative phase between the @xmath36 and @xmath2 couplings has been assumed to be the same as between their respective decay constants . depending upon phase convention ( i. e. @xmath51 ) the decay constants are often cited with opposite phases in the literature ( e.g. the @xmath52 relation @xmath53 @xcite where @xmath54 is the @xmath8 mixing angle ) . consistency requires the same relative sign between the couplings @xmath55 and @xmath56 since the latter , like the @xmath2 decay constant , is linear in the @xmath2 phase . because @xmath57 and @xmath58 are comparable in magnitude , @xmath59 is very sensitive to this relative phase and would be dramatically lower , .0064 , if indeed the net phase was negative . it is therefore important to more rigorously determine the relative phase of the vector meson coupling and decay constants and further study is recommended . similarly , the scalar glueball radiative decay widths are @xcite @xmath60 where @xmath61 is also given in vmd by eqs . ( [ gvmdr ] , [ gvmdo ] , [ gvmdp ] ) with @xmath22 replaced by @xmath62 , @xmath63 is the scalar glueball mass , @xmath64 is a reference mass fixed at 1 gev and @xmath65 . again vmd predicts the same suppression factor for radiative decays to isoscalar vector meson channels . the @xmath66 decays for @xmath62 and @xmath67 can also be obtained from vmd @xmath68 ^ 2 \frac{m_{g_0}^3}{m_0 ^ 2 } \label{g2gamma } \ , \ ] ] @xmath69 ^ 2m_{g_2 } \ .\ ] ] to compute the radiative widths the hadronic couplings @xmath70 must be specified . for the scalar glueball , ref . @xcite uses the value @xmath71 , but there is an error in eq.(37 ) of that paper which should instead read , @xmath72 = .62 $ ] , yielding the slightly larger value @xmath73 . the corrected coupling is now closer to 4.23 which was obtained by an independent scalar glueball mixing analysis @xcite . the tensor glueball coupling can be estimated by assuming the hadronic decays @xmath74 for @xmath75 , @xmath36 and @xmath2 dominate and saturate the entire tensor glueball width , i. e. @xmath76 this of course represents more of an upper bound for the coupling but for experimental planning it should provide sufficient photoproduction cross section estimates . using eq . ( 1 ) with the photon replaced by a second vector meson , @xmath77 , the tensor glueball hadronic widths are @xmath78 \ , \label{vv'width}\end{aligned}\ ] ] where @xmath79 if @xmath80 and 1 otherwise , @xmath81 , @xmath82 and @xmath83 . for identical mesons , @xmath80 @xmath84 \ . \label{vvwidth}\ ] ] taking @xmath85 ( mass 2011 mev , total width 202 mev ) and @xmath86 ( mass 2297 mev , total width 149 mev ) as tensor glueball candidates , eqs . ( [ fullwidth ] , [ vvwidth ] , [ vvwidth ] ) yield , @xmath87 , for @xmath85 and a similar value , @xmath88 , for @xmath86 . adopting the average , 1.37 , for the tensor coupling , the estimated glueball hadronic and radiative decays are summarized in tables 1 and 2 , respectively . .tensor glueball hadronic decays in mev [ cols="^,^,^,^,^",options="header " , ] from the tables it is clear that vmd and flavor independence predict roughly comparable hadronic @xmath7 widths . it is interesting that the largest branch is to the @xmath3 channel which has a clear , novel @xmath9 prompt decay . also noteworthy are the suppressed @xmath4 and @xmath89 decays relative to @xmath10 . hence even though the gluonic coupling has been assumed flavor blind , consistent with qcd , the glueball widths are not . as mentioned above this decay signature is not expected for mesons and several published studies find no @xmath36/@xmath35 suppression in meson radiative decays . indeed ref . @xcite , which also uses vmd for scalar meson radiative decays , actually predicts an enhancement for @xmath59 by an order of magnitude . related , tensor meson decay calculations @xcite to vector and pseudoscalar meson channels reveal branching ratios that are very sensitive to flavor , varying by over an order of magnitude . further , a recent meson decay model study @xcite , which compliments this work by advocating radiative decays as a flavor filter to clarify glueball mixing , predicts extremely flavor dependent radiative decays of scalar mesons . that investigation incorporates decay width renormalizations from mixing ( see below ) with a glueball component @xcite but does not include contributions from glueball decays . similarly , ref . @xcite repeats that analysis , again not including direct glueball decays , with relativistic quark model corrections and finds the same decay pattern but all widths are reduced by 50 to 70% . both studies detailed marked sensitivity of @xmath90 and @xmath5 decay widths to mixing and quark flavor . concerning experimental evidence for @xmath91 isoscalar hadrons with mass near 2 gev , the most recent pdg report @xcite list six states : @xmath92 , @xmath93 , @xmath85 , @xmath94 , @xmath86 and @xmath95 . also there is the @xmath96 which is a tensor candidate but it , along with the @xmath92 and @xmath94 , is omitted from the more important pdg summary table . for the four firm tensor states there is limited decay data and no quantitative branching ratios . the specific observed decays are : @xmath97 for @xmath85 and @xmath95 ; @xmath97 , @xmath98 and @xmath99 for @xmath86 ; @xmath100 , @xmath101 , @xmath102 , @xmath103 , @xmath98 and @xmath99 for @xmath93 . there is a clear need for additional , more detailed measurements . a final comment about glueball decays is in order regarding quarkonia - glueball mixing . in addition to the investigations discussed above , there have been several other mixing studies involving scalar hadrons @xcite but no published worked treating tensor states in the 2 gev region which is the focus here . for all theoretical models , the isoscalar @xmath91 @xmath104 states calculated in this mass region will mix with predicted nearby tensor glueballs and this will alter the unmixed decay scheme . if the mixing is weak the predicted vmd decay profile will not be appreciably modified and may be effective in identifying the existence of glueball dominated states . for strong or maximal mixing , the branching ratios will depend upon model details and the vmd predictions will be affected by hadronic couplings in the quark sector , especially their flavor dependence . in general significant mixing will distort the simple vmd glueball decay signature of suppressed @xmath4 and @xmath5 but comparable @xmath0 decay rates . an improved mixing analysis , including decay contributions from both the quark @xcite and glue sectors , is in progress and will be reported in a future communication . the glueball couplings can also be used to describe the photoproduction process , @xmath105 , where the energy - momentum 4-vectors ( helicities ) for the photon , proton , glueball and recoil proton are @xmath106 ) , @xmath107 ( @xmath108 ) , @xmath109 and @xmath110 ( @xmath111 ) , respectively . in the helicity representation the scalar glueball photoproduction amplitude , @xmath112 , is @xmath113 with @xmath114 the photon polarization 4-vector and @xmath115 the hadronic current obtained by application of feynman rules to the tree level @xmath116 , @xmath117 and @xmath118 channel qhd diagrams . the spin - averaged scalar glueball photoproduction cross section is @xmath119 \ , \nonumber\end{aligned}\ ] ] where @xmath120 is the photon @xmath121 energy . as detailed in ref . @xcite , the glueball cross section is dominated by @xmath122 channel exchanges for @xmath123 . accordingly only the @xmath122 channel amplitude is calculated and from ref . @xcite this is @xmath124 u(p,\sigma ) \ , \nonumber \label{eqt}\end{aligned}\ ] ] with @xmath125 , @xmath126 . the hadronic form factor , @xmath127 , vector meson propagator , @xmath128 , and remaining vector - nucleon couplings and transition moments are specified in ref . @xcite . because of higher spin , the tensor glueball production amplitude is more complicated . invoking vector and tensor dominance and eq . ( 1 ) , the photoproduction amplitude is @xmath129 \ .\end{aligned}\ ] ] the hadronic current @xmath130 has the same form as the scalar glueball result , @xmath131 , except that the ratio @xmath132 is replaced by @xmath133 . again focusing on forward angles , only @xmath122 channel diagrams are evaluated and since the formulation is covariant , the gottfried - jackson or glueball rest frame is used for mathematical convenience . the spin - averaged tensor glueball production cross section is @xmath134 \ , \nonumber\end{aligned}\ ] ] where @xmath135 , @xmath136 , @xmath137 and @xmath138 2.011 gev is the mass used in the cross section predictions presented here . for the above specified glueball couplings , the tensor and scalar photoproduction cross sections are displayed in figs . 1 , 2 and 3 . figures 1 and 2 depict the lab energy dependence for the forward @xmath121 angles @xmath139 and @xmath140 , respectively , while fig . 3 shows the angular distribution for 6 gev photon lab energy . again , since only @xmath122 channel amplitudes are included , results for angles greater than @xmath141 should be ignored . in contrast to the radiative widths , the cross sections are insensitive to the relative phase between the @xmath36 and @xmath2 couplings since @xmath35 exchange dominates ( see eq.(7 ) ) . while the scalar glueball cross section is somewhat larger , it is noteworthy that the magnitude of both cross sections is sufficient to expect reasonable count rates . indeed , measurements of this process , including vector meson decays , would appear feasible for the evisioned hall d project at jefferson lab . finally , photon transverse asymmetry observables , @xmath142 , are also predicted and are displayed in figs . 4 and 5 for the respective @xmath121 angles @xmath143 and @xmath140 . the scalar glueball asymmetry is greater than the tensor and both are large and increase with energy . in summary , both tensor and scalar glueball cross sections , asymmetries and decay observables have been predicted using vmd and flavor independence . the results indicate that photoproduction cross sections are measurable and that by detecting comparable hadronic @xmath7 decays , especially the novel @xmath144 branch , in conjunction with suppressed @xmath4 , @xmath5 transitions relative to @xmath10 , it may be possible to identify states having a significant gluonic component .

NEW YORK (AP) — A lawyer whose rant against Spanish speakers in a New York City eatery went viral posted an apology online on Tuesday, saying that how he expressed himself was "unacceptable." "To the people I insulted, I apologize," Aaron Schlossberg said in a post to his Twitter and LinkedIn accounts. "Seeing myself online opened my eyes — the manner in which I expressed myself is unacceptable and is not the person I am. I see my words and actions hurt people, and for that I am deeply sorry." Last week, Schlossberg was in a Manhattan restaurant and became incensed at hearing workers speak Spanish. In the rant caught on video, he threatened to call Immigration and Customs Enforcement to have the workers "kicked out of my country." In the uproar that followed, additional clips surfaced of Schlossberg engaged in other public rants and a complaint was filed with a lawyers' disciplinary committee. The building he was using as a business address terminated its agreement with him. Critics hired a mariachi band to play outside his apartment and former office space and they demanded his disbarment. "While people should be able to express themselves freely, they should do so calmly and respectfully," Schlossberg wrote in his apology. "What the video did not convey is the real me. I am not racist." He said he loved New York City in part because of its diversity. Schlossberg's office phone number was repeatedly busy.

– A lawyer whose rant against Spanish speakers in a New York City eatery went viral posted an apology online on Tuesday, saying that how he expressed himself was "unacceptable." "To the people I insulted, I apologize," Aaron Schlossberg said in a post to his Twitter and LinkedIn accounts. "Seeing myself online opened my eyes—the manner in which I expressed myself is unacceptable and is not the person I am. I see my words and actions hurt people, and for that I am deeply sorry." Last week, Schlossberg was in a Manhattan restaurant and became incensed at hearing workers speak Spanish. In the rant caught on video, he threatened to call ICE to have the workers "kicked out of my country." In the uproar that followed, additional clips surfaced of Schlossberg engaged in other public rants and a complaint was filed with a lawyers' disciplinary committee, the AP reports. The building he was using as a business address terminated its agreement with him. Critics hired a mariachi band to play outside his apartment and former office space and demanded his disbarment. "While people should be able to express themselves freely, they should do so calmly and respectfully," Schlossberg wrote in his apology. "What the video did not convey is the real me. I am not racist." He said he loved New York City in part because of its diversity.

SECTION 1. CONVEYANCE OF MUKILTEO LIGHT STATION, WASHINGTON. (a) Authority To Convey.-- (1) In general.--The Secretary of Transportation shall convey to the City of Mukilteo, Washington, by an appropriate means of conveyance, all right, title, and interest of the United States in and to the Mukilteo Light Station, consisting of approximately 1.46 acres of land, the lighthouse structure, a garage, 2 dwellings, and an office building. (2) Identification of property.--The Secretary may identify, describe, and determine the property to be conveyed under this subsection. (3) Exception.--The Secretary may not convey any historical artifact, including any lens or lantern, located on the property at or before the time of the conveyance. (b) Terms of Conveyance.-- (1) In general.--The conveyance of property under this section shall be made-- (A) without payment of consideration; and (B) subject to the conditions required by this section and other terms and conditions the Secretary may consider appropriate. (2) Reversionary interest.--In addition to any term or condition established under this section, the conveyance of property under this subsection shall be subject to the condition that all right, title, and interest in the property shall immediately revert to the United States if-- (A) the property, or any part of the property-- (i) ceases to be used as a nonprofit center for the interpretation and preservation of maritime history; (ii) ceases to be maintained in a manner that ensures its present or future use as a Coast Guard aid to navigation; or (iii) ceases to be maintained in a manner consistent with the provisions of the National Historic Preservation Act of 1966 (16 U.S.C. 470 et seq.); or (B) at least 30 days before that reversion, the Secretary of Transportation provides written notice to the owner that the property is needed for national security purposes. (3) Maintenance of navigation functions.--A conveyance of property under this section shall be made subject to the conditions that the Secretary of Transportation considers to be necessary to assure that-- (A) the lights, antennas, sound signal, electronic navigation equipment, and associated lighthouse equipment located on the property conveyed, which are active aids to navigation, shall continue to be operated and maintained by the United States for as long as they are needed for this purpose; (B) the owner of the property may not interfere or allow interference in any manner with aids to navigation without express written permission from the Secretary of Transportation; (C) there is reserved to the United States the right to relocate, replace, or add any aid to navigation or make any changes to the property as may be necessary for navigational purposes; (D) the United States shall have the right, at any time, to enter the property without notice for the purpose of maintaining aids to navigation; and (E) the United States shall have an easement of access to and across the property for the purpose of maintaining the aids to navigation in use on the property. (4) Obligation limitation.--The owner of property conveyed under this section is not required to maintain any active aid to navigation equipment on the property. (5) Property to be maintained in accordance with certain laws.--The owner of property conveyed under this section shall maintain the property in accordance with the National Historic Preservation Act of 1966 (16 U.S.C. 470 et seq.) and other applicable laws. (c) Maintenance Standard.--The owner of any property conveyed under this section, at its own cost and expense, shall maintain the property in a proper, substantial, and workmanlike manner. (d) Owner Defined.--For purposes of this section, the term ``owner'' means the City of Mukilteo, Washington, and any successor or assign of the City with respect to property conveyed to the City under this section.

Directs the Secretary of Transportation to convey all right, title, and interest of the United States in and to the Mukilteo Light Station (including land, the lighthouse structure, a garage, two dwellings, and an office building) to the City of Mukilteo, Washington. Subjects such conveyance to the condition that the lighthouse maintain its navigational functions.

the measurement of bottom ( @xmath1 ) mesons in @xmath3+@xmath3 and @xmath3+@xmath14 collisions is of interest to constrain the total bottom cross section as well as test our understanding of bottom quark production mechanisms and hadronization . there are extensive direct measurements of various @xmath1 mesons , as well as measurements of @xmath15 contributions over a broad range in transverse momentum and rapidity from the tevatron in @xmath3+@xmath14 at @xmath16 = 1.96 tev @xcite and the lhc in @xmath3+@xmath3 at @xmath1713 tev @xcite . in contrast , measurements from ua1 in @xmath3@xmath12@xmath14 at @xmath18 gev @xcite are statistically limited and only for @xmath19 5 gev@xmath20 . adding new measurements at lower energies and covering different kinematic regions is valuable for testing perturbative quantum chromodynamics ( pqcd ) calculations and constraining production mechanisms . the relativistic heavy ion collider ( rhic ) provides @xmath3@xmath12@xmath3 collisions at @xmath16 = 200 , 500 and 510 gev , which extends the kinematic reach for bottom measurements . at these smaller energies , bottom production is dominated by gluon - gluon fusion , while higher energy bottom production contains a larger fraction of flavor excitation and gluon splitting processes @xcite . the star experiment measured @xmath21 at midrapidity for @xmath22 5 gev/@xmath7 in @xmath3+@xmath3 at @xmath16 = 200 gev @xcite . our measurement at forward rapidity and @xmath23 within 05 gev@xmath20 in @xmath24 gev @xmath3+@xmath3 collisions at phenix can provide the validation of parton distribution functions ( pdf ) in a different gluon fractional momentum range @xmath25 . as the highest center of mass energy accessed by rhic collisions , bottom measurements at @xmath24 gev will also help us understand the energy dependence from rhic to lhc energies . inclusive production has a component referred to as `` prompt '' , that includes direct production , as well as decays from @xmath26 and @xmath27 . the term `` prompt '' is in contrast to `` nonprompt '' , which specifically refers to production through more long - lived decay parent hadrons ( i.e. @xmath1 mesons ) . the nonprompt component that comes from the decay of @xmath1 mesons , provides a clean channel to measure @xmath1-meson yields . at forward rapidities , the time dilation of the @xmath1 lifetime leads to a larger displacement from the event vertex before decaying to . we use this displacement to separate originating from @xmath1-meson decay from prompt through measurement of the decay particle s distance of closest approach ( dca ) to the primary event vertex . in this paper , the ratio of from @xmath1-meson decays to inclusive ( ) is determined for kinematics in the range of @xmath28 and rapidity @xmath8 through dca distributions in @xmath3+@xmath3 collisions at , using the phenix muon arms plus the forward and central silicon vertex tracker detectors . the @xmath9 cross section per unit rapidity at the mean @xmath1 hadron rapidity @xmath29 in 510 gev @xmath3+@xmath3 collisions is extracted from the obtained and the phenix inclusive cross section measured at 200 gev , scaled with color - evaporation - model ( cem ) calculations @xcite . the paper is organized as follows . section [ sec : experiment setup ] discusses the phenix detector setup for this analysis , in particular the fvtx and vtx detectors which are used for the primary vertex and the dca determination . section [ sec : analysis procedure ] describes the data reconstruction and simulation setup , signal and background determination , and fitting procedure . the acceptance@xmath30efficiency correction factor to achieve final results and the systematic uncertainty evaluation are discussed in section [ sec : analysis procedure ] as well . the results and interpretation are discussed in section [ sec : results_and_discussions ] and the conclusions are summarized in section [ sec : summary ] . the phenix detector setup for the 510 gev @xmath3+@xmath3 data taking in 2012 . ] the data set used in this analysis is from the 2012 run of @xmath3+@xmath3 at @xmath16 = 510 gev and the detector configuration of phenix for that running period is shown in fig . [ fig : phenix_2012 ] . for this measurement , the beam - beam counters ( bbc ) @xcite , the muon arm spectrometers @xcite , the central silicon vertex detector ( vtx ) @xcite and the forward silicon vertex detector ( fvtx ) @xcite are used . the bbc detector , which comprises 128 quartz erenkov counters with a pseudorapidity coverage of @xmath31 , determines when a collision event has taken place . the bbc provides the minimum - bias trigger , by requiring a coincidence between at least one hit in both the positive and negative acceptance of the bbc . the phenix muon detectors are divided into the north ( @xmath32 ) and the south ( @xmath33 ) arms . each muon arm spectrometer has full azimuthal coverage and is composed of hadron absorbers , a muon tracker ( mutr ) which resides in a radial field magnet , and a muon identifier ( muid ) . the mutr comprises three cathode strip wire chamber stations inside a magnet which provides a radial magnetic field with an integrated bending power of around 0.8 t@xmath34 m . the mutr measures track momentum @xmath3 with a resolution of @xmath35 0.05 at @xmath36 gev@xmath20 . the hadron absorber comprises 19 cm of copper , 60 cm of iron and 36.2 cm of stainless steel along the beam axis . the absorbers are situated in front of the mutr to provide hadron ( mostly pion and kaon ) rejection . the mutr has a position resolution at each station of around 100 @xmath37 m , which , together with a precisely determined vertex , results in a mass resolution of around 95 mev for dimuon pairs within the mass region . the downstream muid comprises 5 sandwiched planes of iarocci proportional tubes and steel . the mutr+muid system together with the steel absorbers have approximately 10 interaction lengths of material . in this analysis , the dimuon trigger is used which requires two roads " found in the muid tubes with at least one road " reaching the last plane of the muid . the vtx ( installed in 2011 ) comprises two inner pixel layers and two outer strip layers distributed from 2.5 cm to 14.0 cm along the radial direction , covering @xmath38 radians in azimuth and @xmath39 cm along the @xmath40 axis ( beam direction ) . the radii of the inner silicon pixel detectors are 2.5 and 5.0 cm , and the radii of the outer silicon strip detectors are on average 10.0 and 14.0 cm . each pixel of the inner vtx layers covers a 50 @xmath37 m @xmath30 450 @xmath37 m active area @xcite . the fvtx , installed in front of the hadron absorbers in 2012 , comprises 4 silicon disks perpendicular to the beam axis and placed at approximately @xmath40 = @xmath41 cm , @xmath42 cm , @xmath43 cm and @xmath44 cm . the rapidity coverage of the fvtx overlaps the muon arm coverage . each fvtx disk comprises 48 individual silicon sensors ( wedges ) and each wedge contains two columns of strips that each span an azimuthal segmentation of @xmath45 . the column comprises mini - strips with 75 @xmath37 m width in the radial direction . the strip length in the azimuthal ( @xmath46 ) direction varies from 3.4 mm at the inner radius to 11.5 mm at the outer radius for the largest stations @xcite . for track reconstruction with the combined fvtx+vtx detectors , only the two inner pixel layers in the vtx are used . the fvtx enhances the existing muon arm tracking performance in several ways . the fvtx helps reject hadrons that undergo multiple scattering or decay inside the hadron absorber by requiring a good joint fit of fvtx and mutr tracks . it also provides a better opening angle determination than the mutr alone can provide , which results in an improved mass resolution for dimuon pairs . finally , the additional precision tracking added in front of the hadron absorber by the fvtx makes the measurement of displaced tracks possible when combined with a determination of the primary vertex position . due to limited resolutions in the @xmath40 and azimuthal @xmath46 components of the fvtx detector , the separation of prompt and decay muons is realized with the fvtx using the dca measurement instead of measuring the displaced vertex of decayed muons . because the fvtx has better resolution in the radial direction than in the azimuthal direction , the radial dca ( dca@xmath47 ) is the primary variable used in this analysis . the primary vertex is reconstructed using all fvtx and vtx tracks which pass the track quality cut @xmath48 , where ndf is the number of degrees of freedom . figure [ fig : define_dca ] illustrates the projection of a muon from a @xmath1 meson to decay in the transverse vertex plan and how to calculate the @xmath49 . a track reconstructed in the fvtx is extrapolated to the transverse plane ( @xmath50-@xmath51 ) at the @xmath40 location of the primary collision vertex . dca is defined as the vector @xmath52 formed between this intersection point and the @xmath50-@xmath51 collision vertex point in the same transverse plane of the collision vertex . the is the component of the dca which is measured in the same radial direction as the fvtx strips , @xmath53 prompt particles from the primary collision vertex have a symmetric distribution centered at zero , with the width determined by the intrinsic detector and vertex resolutions , while the shape is asymmetric for decay particles from a displaced decay vertex . as illustrated in the fig . [ fig : define_dca](b ) , the definition of results in an asymmetric distribution for muons from @xmath54 decay due to the projection onto the transverse @xmath50-@xmath51 plane of the primary vertex . this is confirmed by the full simulation shown in section [ sec : simulation setup ] . this analysis starts with the identification of good candidates by selecting dimuon pairs found by the mutr that are matched to muid tracks . separately , track finding is performed in the fvtx / vtx system where reconstructed tracks are required to contain at least one fvtx hit and a total of at least three fvtx+vtx hits . then , for each reconstructed mutr track , the fvtx / vtx tracks are searched for potential matches . the collision point is determined from vtx and fvtx tracks . first , regions where there is a concentration of track crossings are determined . the center of gravity of each of these regions defines a collision point . for each region , the center of gravity is used to initiate a minimization of the summed dca of the tracks . during the minimization , tracks with large displacements are removed to improve the fidelity of the final vertex reconstruction . the vertex determination in each event is strongly affected by the small vtx and fvtx track multiplicities in @xmath3+@xmath3 collisions . events containing decay products can also skew the vertex determination . therefore , in this analysis we take advantage of the beam stability in @xmath50 and @xmath51 during the fill ( 5 - 12 hours ) and use the measured average @xmath50 and @xmath51 position of all events in the fill to determine our primary @xmath50 and @xmath51 vertex . the spread of the primary @xmath50 and @xmath51 vertex position based on the beam spot size is around 80 @xmath37 m in rms . the @xmath40 position is still determined on an event - by - event basis for events that have a vtx+fvtx track multiplicity @xmath552 . events with smaller multiplicity are thrown out . for events with more than one reconstructed vertex , the vertex with the best reconstruction quality is selected as the primary vertex . for the reconstructed events , we obtain an average @xmath40 resolution of approximately 180 @xmath37 m in 510 gev @xmath3+@xmath3 collisions . after matching to the fvtx tracks , the is determined using the mutr+muid+fvtx combined track fit and the primary vertex location . the next step in the analysis is to characterize the of muons from prompt decay and from @xmath1-meson decay through simulation . the final analysis step uses a fit function for the muon spectra that includes the prompt @xmath0 , from @xmath1-meson decay , and background components to extract the fraction of from @xmath1-meson decay in the data , using a log - likelihood fit . details of the analysis procedure are explained step by step in the following sections . the precise primary @xmath40 vertex reconstruction is limited by the vtx acceptance and therefore only events within a @xmath40 vertex ( @xmath56 ) window of ( -10 , 10 ) cm are selected for this analysis . events with poorly determined primary @xmath40 vertices are removed by requiring less than 400 @xmath37 m calculated uncertainty on the @xmath40-vertex . runs without an accurately determined average @xmath50 , @xmath51 position of the beam center are rejected . the number of events with mb and dimuon triggers surviving after these vertex selections is 3.5 @xmath30 10@xmath57 , which is equivalent to a total integrated luminosity of 0.47 @xmath58 . the event rejection fraction is around 67% . during the 2012 @xmath3+@xmath3 run , there were some areas of the fvtx detector which were not yet operational due to various electronics issues . when the fvtx - mutr matching algorithm tries to find an fvtx track in a dead area , there is a tendency for it to match to a track in a live region neighboring the dead one instead , pulling the matching distributions away from the central value of 0 . because of this tendency to pull tracks away from a symmetric distribution , fiducial cuts are applied to remove tracks that point to the vicinity of a dead region in the fvtx detector . detector misalignments can shift the projected track position in the vertex plane and thus distort the distributions . before proceeding with the data analysis , alignment corrections are applied to the data in two stages , before and after the track reconstruction . the pre - production alignment left residual @xmath46-dependent misalignments , which were up to 100 @xmath37 m in certain detector regions . tilts which shift the fvtx silicon sensors out of the normal @xmath50-@xmath51 plane were corrected in a post - production alignment procedure , reducing the final misalignment values to less than 30 @xmath37 m . a final verification of the fvtx alignment to the vtx , which is the most critical alignment for dca analyses , is performed using real data . tracks which show muid activity in the fourth gap , but not in the last gap are first selected . the majority of these tracks are from stopped hadrons , which are predominantly prompt particles , and provide a high statistics sample for studying alignment . events with a large vertex uncertainty , tracks next to dead areas , and bad quality fvtx tracks are removed from this sample . to remove the hadron decay component , a minimum longitudinal momentum cut of ( @xmath59 gev/@xmath7 ) is required . after the misalignment corrections described above are applied , the is then extracted for these tracks and checked for any indications of residual misalignments . the mean of these distributions is found to be flat along the @xmath46 direction ( within the measurement precision ) and the overall offsets of the distributions are within 30 @xmath37 m in both arms . these offset values are much smaller than the detector position resolution . variations of the mean and spread which could occur if there were beam instability , detector , trigger or acceptance@xmath30efficiency changes , are checked by examining the distributions as a function of run and bbc instantaneous rate . the mean values of the distributions across all runs are found to be within one standard deviation ( of the intrinsic distribution width ) after quality assurance checks . [ cols="^,^,<",options="header " , ] lccc & + -2.2 @xmath60 -1.2 & 8.3% @xmath5 2.9%(stat ) @xmath5 1.9%(syst ) + 1.2 @xmath60 2.2 & 7.8% @xmath5 3.9%(stat ) @xmath5 1.9%(syst ) + + 1.2 @xmath61 2.2 & 8.1% @xmath5 2.3%(stat ) @xmath5 1.9%(syst ) + the final results are summarized in table [ tab : final_results ] . because the collision is a symmetric system , the results from the two arms are combined into a statistical average , giving a fraction of from @xmath1-meson decays in the 1.2 @xmath61 2.2 region of @xmath62 . this result is integrated in the @xmath635 gev/@xmath7 interval . in @xmath3+@xmath3 collisions at @xmath16 = 510 gev and @xmath8 rapidity region , comparison of phenix @xmath1 @xmath64 @xmath0 fraction ( ) measured in integrated @xmath23 range of @xmath28 with @xmath23 dependent ( shown in solid red ) and @xmath23 integrated within 05 gev@xmath20 region ( shown in dashed blue ) @xmath1 @xmath64 @xmath0 fraction predicted by the fonll+cem @xcite model in 500 gev @xmath3+@xmath3 collisions . the uncertainty of the phenix measurement is statistical and systematic combined . ] the average @xmath9 cross section per unit rapidity ( @xmath65 ) is determined by the @xmath66 @xmath0 fraction ( ) discussed in the paper and the extracted inclusive cross section in 510 gev @xmath3+@xmath3 collisions from phenix 200 gev @xmath3+@xmath3 measurements and the energy scaling factor provided by the cem model@xcite . extrapolated @xmath10 ( shown as open red circles ) at @xmath1 hadron mean rapidity @xmath67 in 510 gev @xmath3+@xmath3 collisions compare with the fonll - calculated @xmath1 hadron rapidity dependent @xmath1 cross section ( shown as blue solid line ) . the phenix result is also comparable with the ua1 630 gev @xmath3+@xmath14 extrapolated @xmath68 @xcite . the uncertainty of the extrapolated value at phenix and ua1 combines the statistical and systematic uncertainty from experiment with the cem model uncertainty . the uncertainty of fonll calculations contains both scaling uncertainty and @xmath69 quark mass variations . ] comparisons to global measurements within the same inclusive @xmath23 region from cdf @xcite , alice @xcite , cms @xcite and lhcb @xcite experiments are shown in fig . [ fig : global_data]-a . the result from phenix is also compared with the @xmath70-dependent fraction from other experiments using the average @xmath71 2.2 of our inclusive sample as shown in fig . [ fig : global_data]-b . the lhcb experiment has measurements over a wide rapidity , @xmath72 ; only results from @xmath73 and @xmath74 are shown in fig . [ fig : global_data ] . the @xmath73 rapidity range is close to the kinematic range accessed by other measurements . the result from this measurement is consistent with those from the higher energy collisions within uncertainties , although it does not exclude the possibility of a decrease of the toward lower collision energy . figure [ fig : fonll_cem ] presents the comparison between the 510 gev @xmath3+@xmath3 phenix result and the fixed - order next - to - leading - log ( fonll)+cem ( fonll+cem ) @xcite model prediction for the @xmath15 fraction ( @xmath75 ) in 500 gev @xmath3+@xmath3 collisions . the energy dependence between 500 gev and 510 gev is small , and corresponding results expected to be quite indistinguishable . the measured fraction at phenix is consistent with the fonll+cem model prediction within uncertainties . the cms nonprompt and prompt cross section measurements at 7 tev @xmath3+@xmath3 collisions @xcite have been compared to the fonll+cem model as well . the cem model underestimated the prompt cross section within @xmath76 and @xmath77 gev@xmath20 region measured by the cms experiment in 7 tev @xmath3+@xmath3 collisions , while the nonprompt cross section measured in the same kinematic region and experiment is consistent with the fonll calculations . then the fonll+cem model over - predicts the 7 tev @xmath21 fraction . the fonll calculations can reasonably describe the nonprompt cross section results at lhcb @xcite , but the theory predictions for prompt cross section in @xmath78 gev@xmath20 region currently is missing . the @xmath15 fraction is also related to the inclusive cross section per unit rapidity @xmath79 and the @xmath9 cross section per unit rapidity @xmath10 as shown in eq.([eq : b_xsec ] ) . @xmath80 where @xmath81 is the branching ratio of @xmath1 hadron decays to @xmath0 and we assume the @xmath69 ( @xmath82 ) quark to @xmath1-hadron fragmentation is 1 . the factor of two in eq.([eq : b_xsec ] ) accounts for the fact that both @xmath83 and @xmath84 contribute to the @xmath83 fraction . eq.([eq : b_xsec ] ) can be rewritten as : @xmath85 therefore , @xmath10 can be derived from eq.([eq : b_xsec2 ] ) . to do this , we use @xmath86 @xmath37b ( @xmath87 @xmath37b ) at mean rapidity @xmath88 ( @xmath89 ) in 510 gev @xmath3+@xmath3 collisions , and @xmath90 @xcite . here , @xmath91 gev@xmath92 is extrapolated as @xmath93 gev@xmath94 , where the scaling factor @xmath95 is @xmath96 according to the cem model@xcite , and @xmath93 gev)@xmath97 ( @xmath98 ) at mean rapidity @xmath99 @xcite . the extracted @xmath10 is @xmath100 ( @xmath101 ) @xmath37b at @xmath1 hadron mean rapidity = 1.7 ( -1.7 ) in 510 gev @xmath3+@xmath3 collisions . the weighted average of the two measurements is @xmath102 at @xmath1-hadron rapidity@xmath103 . as shown in fig . [ fig : fonll_xsec ] , these values are comparable with the fonll - calculated @xmath1-hadron rapidity - dependent @xmath1 cross section within large uncertainties @xcite . the fonll calculation uses the @xmath69 quark mass @xmath104 gev@xmath105 to calculate the central value . the uncertainty of fonll is determined by varying the @xmath69 quark mass between 4.5 to 5.0 gev@xmath105 and keeping the renormalization and factorization scales equal to the transverse mass , @xmath106 @xcite . these values are also comparable to the ua1 @xmath18 gev @xmath3+@xmath14 average @xmath9 cross section per unit rapidity ( @xmath107 gev@xmath108 @xmath37b ) within @xmath109 rapidity range @xcite . we have presented a new measurement of the nonprompt over inclusive production ratio in collisions at @xmath16 = 510 gev , integrated over the kinematical domain , @xmath28 gev/@xmath7 and rapidity @xmath8 and the result is @xmath110 . this measurement extends the previously measured values at cdf and lhc to lower energy , and is found comparable to these values measured at higher energies ; it is also within 1.0 standard deviation of the fonll+cem expectation that has a significant energy and rapidity dependence . the extrapolated @xmath10 is @xmath111 at @xmath1 hadron mean rapidity @xmath103 in 510 gev @xmath3+@xmath3 collisions , which is comparable with both the fonll calculations in 500 gev @xmath3@xmath12@xmath3 collisions and the ua1 extracted result in 630 gev @xmath3+@xmath14 collisions . the weak dependence on the center of mass energy in fig . [ fig : global_data]-a for the could indicate that the variation of the bottom yield versus energy is compensated by a similar variation of the prompt yield . it is also noteworthy that only a factor of two decrease of the over the yield is expected going from lhc energies to @xmath16 = 510 gev according to fonll estimations @xcite . however , modeling of the hadronization of the bound at low @xmath70 is still a challenge to qcd calculations . the present results provide complementary information to the surprisingly weak evolution of in the @xmath16 = 0.5113 tev domain , for central or near central rapidity and low @xmath23 production . the analysis procedure developed in this study will be applied to other data sets at different center of mass energies taken by phenix . a similar method can also be applied to the study of @xmath1- and @xmath112-meson semileptonic decays to muons , which will help to understand the production mechanism of charm and bottom , and provide a complementary measurement to the one presented in this paper . we thank the staff of the collider - accelerator and physics departments at brookhaven national laboratory and the staff of the other phenix participating institutions for their vital contributions . we acknowledge support from the office of nuclear physics in the office of science of the department of energy , the national science foundation , abilene christian university research council , research foundation of suny , and dean of the college of arts and sciences , vanderbilt university ( u.s.a ) , ministry of education , culture , sports , science , and technology and the japan society for the promotion of science ( japan ) , conselho nacional de desenvolvimento cientfico e tecnolgico and fundao de amparo pesquisa do estado de so paulo ( brazil ) , natural science foundation of china ( people s republic of china ) , croatian science foundation and ministry of science , education , and sports ( croatia ) , ministry of education , youth and sports ( czech republic ) , centre national de la recherche scientifique , commissariat lnergie atomique , and institut national de physique nuclaire et de physique des particules ( france ) , bundesministerium fr bildung und forschung , deutscher akademischer austausch dienst , and alexander von humboldt stiftung ( germany ) , national science fund , otka , kroly rbert university college , and the ch . simonyi fund ( hungary ) , department of atomic energy and department of science and technology ( india ) , israel science foundation ( israel ) , basic science research program through nrf of the ministry of education ( korea ) , physics department , lahore university of management sciences ( pakistan ) , ministry of education and science , russian academy of sciences , federal agency of atomic energy ( russia ) , vr and wallenberg foundation ( sweden ) , the u.s . civilian research and development foundation for the independent states of the former soviet union , the hungarian american enterprise scholarship fund , and the us - israel binational science foundation . 27ifxundefined [ 1 ] ifx#1 ifnum [ 1 ] # 1firstoftwo secondoftwo ifx [ 1 ] # 1firstoftwo secondoftwo `` `` # 1''''@noop [ 0]secondoftwosanitize@url [ 0 ] + 12$12 & 12#1212_12%12@startlink[1]@endlink[0]@bib@innerbibempty link:\doibase 10.1016/0370 - 2693(96)00067 - 6 [ * * , ( ) ] link:\doibase 10.1103/physrevd.71.032001 [ * * , ( ) ] @noop `` , '' link:\doibase 10.1140/epjc / s10052 - 011 - 1575 - 8 [ * * , ( ) ] @noop `` , '' ( ) , @noop `` , '' ( ) , link:\doibase 10.1140/epjc / s10052 - 016 - 4050 - 8 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/0370-2693(91)90227-h [ * * , ( ) ] link:\doibase 10.1007/s100520000460 [ * * , ( ) ] , link:\doibase 10.1016/j.physletb.2013.04.010 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.95.122001 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/s0168-9002(02)01956-3 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/s0168-9002(02)01955-1 [ * * , ( ) ] @noop `` , '' link:\doibase 10.1103/physrevc.93.034904 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/j.nima.2014.04.017 [ * * , ( ) ] link:\doibase 10.1016/j.cpc.2008.01.036 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/s0168-9002(03)01368-8 [ * * , ( ) ] ( ) @noop \doibase http://dx.doi.org/10.1016/0370-2693(91)90228-i [ * * , ( ) ] link:\doibase 10.1007/bf01641885 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevd.85.092004 [ * * , ( ) ] @noop `` , '' @noop `` , '' ( ) , @noop `` , '' ( ) ,

we report the first measurement of the fraction of @xmath0 mesons coming from @xmath1-meson decay ( @xmath2 ) in @xmath3+@xmath3 collisions at @xmath4 510 gev . the measurement is performed using the forward silicon vertex detector and central vertex detector at phenix , which provide precise tracking and distance - of - closest - approach determinations , enabling the statistical separation of @xmath0 due to @xmath1-meson decays from prompt @xmath0 . the measured value of @xmath2 is 8.1%@xmath52.3% ( stat)@xmath51.9% ( syst ) for @xmath0 with transverse momenta @xmath6 gev/@xmath7 and rapidity @xmath8 . the measured fraction @xmath2 at phenix is compared to values measured by other experiments at higher center of mass energies and to fixed - order - next - to - leading - logarithm and color - evaporation - model predictions . the @xmath9 cross section per unit rapidity ( @xmath10 ) extracted from the obtained @xmath2 and the phenix inclusive @xmath0 cross section measured at 200 gev scaled with color - evaporation - model calculations , at the mean @xmath1 hadron rapidity @xmath11 in 510 gev @xmath3@xmath12@xmath3 collisions , is @xmath13b , and it is consistent with the fixed - order - next - to - leading - logarithm calculations .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Triad Program Act''. SEC. 2. FINDINGS. The Congress finds that-- (1) older Americans are among the most rapidly growing segments of our society; (2) currently, the elderly comprise 15 percent of our society, and predictions are that by the turn of the century they will constitute 18 percent of our Nation's population; (3) older Americans find themselves uniquely situated in our society, environmentally and physically; (4) many elderly Americans are experiencing increased social isolation due to fragmented and distant familial relations, scattered associations, limited access to transportation, and other insulating factors; (5) physical conditions such as hearing loss, poor eyesight, lessened agility, and chronic and debilitating illnesses often contribute to an older person's susceptibility to criminal victimization; (6) our elders are too frequently the victims of abuse and neglect, violent crime, property crime, consumer fraud, medical quackery, and confidence games; (7) studies have found that elderly victims of violent crime are more likely to be injured and require medical attention than are younger victims; (8) victimization data on crimes against the elderly are incomplete and out of date, and data sources are partial, scattered, and not easily obtained; (9) although a few studies have attempted to define and estimate the extent of elder abuse and neglect, both in their homes and in institutional settings, many experts believe that this crime is substantially underreported and undetected; (10) similarly, while some evidence suggests that the elderly may be targeted in a range of fraudulent schemes, neither the Uniform Crime Report nor the National Crime Survey collects data on individual- or household-level fraud; (11) law enforcement officers and social service providers come from different disciplines and frequently bring different perspectives to the problem of crimes against the elderly; (12) these differences, in turn, can contribute to inconsistent approaches to the problem and inhibit a genuinely effective response; (13) there are, however, a few efforts currently under way that seek to forge partnerships to coordinate criminal justice and social service approaches to victimization of the elderly; (14) the Triad program, sponsored by the National Sheriffs' Association (NSA), the International Association of Chiefs of Police (IACP), and the American Association of Retired Persons (AARP), is one such effort; (15) recognizing that older Americans have the same fundamental desire as other members of our society to live freely, without fear or restriction due to the criminal element, the Federal Government seeks to expand efforts to reduce crime against this growing and uniquely vulnerable segment of our population; and (16) our goal is to support a coordinated effort among law enforcement and social service agencies to stem the tide of transgenerational violence against the elderly and to support media and nonmedia strategies aimed at increasing both public understanding of the problem and the elderly person's skills in preventing crime against themselves and their property. SEC. 3. PURPOSE. The purpose of this Act is to address the problem of crime against the elderly in a systematic and effective manner with a program of practical and focused research, development, and dissemination designed to assist States and units of local government in implementing specific programs of crime prevention, victim assistance, citizen involvement, and public education that offer a high probability of improving the coordinated effectiveness of law enforcement and social service efforts. The efforts of local coalitions, such as the Triad model being piloted in a number of areas by National Sheriffs' Association, International Association of the Chiefs of Police, and American Association of Retired Persons, are of particular interest. SEC. 4. NATIONAL ASSESSMENT AND DISSEMINATION. (a) In General.--The Director of the National Institute of Justice (referred to as the ``Director'') shall conduct a national assessment of-- (1) the nature and extent of crimes against the elderly; (2) the needs of law enforcement, health, and social service organizations in working to prevent, identify, investigate, and provide assistance to victims of those crimes; and (3) promising strategies to respond effectively to those challenges. (b) Matters to be Addressed.--The national assessment made pursuant to subsection (a) shall address-- (1) the analysis and synthesis of data from a range of sources in order to develop accurate information on the nature and extent of crimes against the elderly, including identifying and conducting such surveys and other data collection efforts as are needed and designing a strategy to keep such information current over time; (2) the problem of the most vulnerable and hard-to-reach elderly who are in poor health, are living alone or without family nearby, or are living in high crime areas; (3) the problem of elderly who are abused and neglected, sometimes in the home and sometimes in health care facilities, sometimes subjected to physical abuse and at other times to verbal aggression and neglect; (4) the problem of fear of victimization, which inhibits the freedom of the elderly and can make them prisoners in their homes; (5) the identification of strategies and techniques that have been shown to be effective, or appear to hold promise of being effective, in responding to the problems described in this subsection and in preventing, reducing, and ameliorating the impact of crime against the elderly; (6) the analysis of the factors that enhance or inhibit development of a coordinated response by law enforcement, health care, and social service providers to crimes against the elderly and the treatment of elderly victims; and (7) the research agenda needed to develop a comprehensive understanding of the problems of crimes against the elderly, including the changes anticipated in the crimes themselves and appropriate responses as our society increasingly ages, and the identification and evaluation of effective and fiscally feasible approaches to prevent and reduce victimization of our Nation's elderly citizens. (c) Dissemination.--Based on the results of the national assessment and analysis of successful or promising strategies in dealing with the problems described in subsection (b) and other problems, including coalition efforts such as the Triad programs referred to in sections 2 and 3, the Director shall disseminate the results through reports, publications, clearinghouse services, public service announcements, and programs of evaluation, demonstration, training, and technical assistance. SEC. 5. PILOT PROGRAMS. (a) Awards.--The Director may make awards to coalitions of local law enforcement agencies, victim service providers, and organizations representing the elderly for pilot programs and field tests of particularly promising strategies and models for forging partnerships for crime prevention and service provision based on the concepts of the Triad model, which can then be evaluated and serve as the basis for further demonstration and education programs. (b) Eligibility.--Pilot programs funded under this section may include existing general service coalitions of law enforcement, victim service, and elder advocate organizations that wish to use additional funds to work at a particular problem in their community, such as fraud, burglary, or abuse and neglect, or to target a particular geographic area in need of intensive services. SEC. 6. EVALUATION AND DISSEMINATION AWARDS. In conjunction with the national assessment under section 4 and the pilot programs under section 5, the Director may make awards to-- (1) coalitions of national law enforcement, victim service, and elder advocate organizations, for the purposes of providing training and technical assistance in implementing pilot programs, including programs based on the concepts of the Triad; (2) research organizations, for the purposes of-- (A) investigating the types of elder victimization shown by the national assessment to present particularly critical problems or to be emerging crimes about which little is known; (B) evaluating the effectiveness of selected pilot programs; and (C) conducting the research and development identified through the national assessment as being critical; and (3) public service advertising coalitions, for the purposes of mounting a program of public service advertisements to increase public awareness and understanding of the issues surrounding crimes against the elderly and promoting ideas or programs to prevent them. SEC. 7. AUTHORIZATION OF APPROPRIATIONS. Of amounts authorized to be appropriated to the National Institute of Justice under section 1001(a)(2) of the Omnibus Crime Control and Safe Streets Act of 1968 (42 U.S.C. 3793(a)(2)), $5,000,000 shall be available to carry out this Act, of which-- (1) up to $2,000,000 may be used to fund up to 20 pilot programs; (2) up to $1,000,000 may be used to fund a national training and technical assistance effort; (3) up to $1,000,000 may be used to develop public service announcements; and (4) up to $1,000,000 may be used for the national assessment, the evaluation of pilot programs, and the carrying out of the research agenda.

National Triad Program Act - Requires the Director of the National Institute of Justice to conduct a national assessment of: (1) crimes against the elderly; (2) the needs of law enforcement, health, and social service organizations in working to assist victims; and (3) promising strategies to respond effectively. Specifies that such assessment shall address the problems of elderly who are living alone or in high crime areas and who are abused and neglected and the fear of victimization. Authorizes the Director to make awards to: (1) coalitions of local law enforcement agencies, victim service providers, and organizations representing the elderly for pilot programs and field tests of promising strategies and models for forging partnerships for crime prevention and service provision. Specifies that pilot programs may include existing general service coalitions of law enforcement, victim service, and elder advocate organizations that wish to use additional funds to work at a particular problem in their community or to target a particular geographic area; (2) research organizations to investigate the types of elder victimization that present particularly critical problems or emerging crimes about which little is known, to evaluate the effectiveness of selected pilot programs, and to conduct critical research and development; and (3) public service advertising coalitions to increase public awareness of, and promote ideas or programs to prevent, crimes against the elderly. Authorizes appropriations.

the magnetic fields that are observed in galaxies and galaxy clusters are believed to result from the dynamo amplification of weak magnetic field seeds , whose origin remains a mystery . intergalactic magnetic fields ( igmfs ) , deep in the voids between galaxies , provide the most accurate image of the weak primordial seed fields and could be linked to the early stages in the evolution of the universe ( see e.g. @xcite for a recent review ) . among the several methods used to study cosmological magnetic fields ( see e.g.@xcite for a recent review ) , the observation ( or nondetection ) of cascade emission from blazars can potentially measure very weak igmfs . a number of blazars have been observed to emit both very - high - energy ( vhe , @xmath5 gev ) @xmath0-rays with ground - based @xmath0-ray instruments and high - energy ( he , mev / gev ) @xmath0-rays with the fermi gamma - ray space telescope @xcite . most of the detected tev @xmath0-rays are from the nearest sources since such high energy @xmath0-rays can not propagate over long distances in intergalactic space due to interactions with the extragalactic background light ( ebl ) . of course , some higher - redshift sources still have detectable tev emission ( e.g. blazar pks1424 + 240 , which has redshift lower limit of @xmath6 @xcite ) , but with highly absorbed spectra consistent with theoretical calculations of the attenuation by the ebl . these interactions of tev @xmath0-rays with the ebl produce electron - positron pairs that subsequently are cooled by inverse compton ( ic ) interactions with the cosmic microwave background ( cmb ) , ultimately leading to gev @xmath0-ray emission from these pair cascades . since magnetic fields deflect the electron - positron pairs changing the angular distribution of cascade emission , searches for extended gev emission around blazars can provide an avenue for constraining the igmf . due to the low gev @xmath0-ray flux from extragalactic sources , it is difficult to examine the angular extent of the photon events from a single blazar or even to assess the joint likelihood for detailed fits to a set of individual sources where individual source parameters are taken to be completely independent . to overcome this limitation , stacking sources has been used to make such statistical analysis feasible . despite early hints at a signal in the stacking analysis of 170 brightest active galactic nuclei ( agns ) using 11-month fermi observations @xcite , by comparing with the gev emission from the crab nebula [ which is essentially a point source for the fermi large area telescope ( fermi - lat ) ] , a. neronov et al . @xcite found no significant evidence of extended emission and argued that the apparent excess could be attributed to an underestimation of the real psf @xcite . a subsequent analysis by ackermann et al . @xcite comparing an updated psf to one hundred stacked bl lac agns did not find any statistically significant halo - emission either . the cascade emission from individual blazars has also been studied by modeling the intrinsic tev spectra and adopting ebl and cosmological microwave background ( cmb ) models ( e.g. @xcite ) . delays in arrival time of the cascade emission were used to explain the non - dectection of several tev sources in fermi energy , and to derive a lower bound of the igmf strength ( e.g. @xmath7 in @xcite ) . the angular extent of the cascade signals caused by igmfs above @xmath8 also provided an explanation for the non - detection of tev sources 1es 0229 + 200 and 1es0347 - 121 by fermi @xcite . w. essey et al . reported a possible _ measurement _ of igmfs in the range @xmath9@xcite based on the tev - gev spectra . very recently , a study of 1es0347 - 121 spectral energy distribution ( sed ) provided an igmf estimation of @xmath10 @xcite . fitting to tev data from , e.g. , veritas and hess , such studies yielded detailed predictions of the cascade emission , but invariably made assumptions about the sources , e.g. the relationship of the long - term tev emission to measurement of a few flares . the upper bound of the igmf strength with correlation length above @xmath11 mpc is below @xmath12 constrained by the non - detection of the large scale cmb anisotropies , and is given to be @xmath13 by the galaxy cluster simulation , as summarized in @xcite . the likely range of the igmf strength from previous studies is given from @xmath14 to @xmath13 . as the energies of the primary @xmath0-rays increase , the pair production occurs closer to the source , reducing the angular size of the cascade . depending on the strength of the igmf and the redshift of the source , the highest energy emission might not be resolved by the fermi psf . while at lower energies ( especially for the nearest sources ) , the emission may be too diffuse to be readily detected . it follows that only a few blazars would have cascade emission that can be statistically detected through their angular profiles . in our study , we combine data from 24 isolated high - synchrotron - peaked ( hsp ) bl lacs which are _ a - priori _ selected to provide the best prospects for detection and adequate photon counting statistics . both frequentist likelihood ratio test ( lrt ) statistics and bayes factors are evaluated for estimating the pair halo parameters ( the angular size and halo fraction ) , which consequently provide the possible range of igmf strength . we use the fermi - lat pass 7 reprocessed data through february 2014 : source class front - converted photon events are binned into four logarithmically spaced energy ranges to roughly equalize counts ( see table [ tab:1 ] ) . the source candidates are selected from the agn associated sources in the fermi - lat high - energy catalog ( 1fhl @xcite ) . the regions of the galactic disk and fermi bubbles are excluded to avoid anisotropic background emission @xcite . data is also divided into angular bins to provide adequate statistics . source bins of equal solid angle are set around the direction of the source , surrounded by a larger background bin with an outer boundary of @xmath15 . to reduce systematic errors from nearby sources , we require that no nearby sources ( those bright enough to appear in the 2fgl catalog ) are within @xmath16 of the stacked sources and correct for the impact of any remaining nearby sources by defining an exclusion region of radius @xmath17 ( @xmath18 ) about these sources ; we account for these exclusion regions by assuming that the signal and background effective area is reduced in proportion to the excluded solid angle . the size of the source bins @xmath19 , is a function of energy chosen to be greater than the 95% containment angle of the psf in the corresponding energy range @xcite ( see table [ tab:1 ] ) . .energy bins and values of @xmath19 [ cols="^,^,^,^,^ " , ] [ tab : s2 ] following the discussion in a. neronov and d. v. semikoz @xcite ( see also @xcite ) , we derive the typical angular size of a pair halo as a function of the observed energy of cascade photons @xmath20 , the typical redshift of the source @xmath21 , and the igmf strength @xmath22 at the present epoch , given by @xmath23^{-2}\left(\frac{e_\gamma}{100\mathrm{gev}}\right)^{-1}\left(\frac{b_0}{10^{-16}\mathrm{g}}\right)\left[\frac{d_\gamma(e_\gamma , z_s)}{d_s(z_s)}\right ] , \label{eq : s1}\ ] ] the basic geometry of propagation of the direct and cascade @xmath0-rays from the source to the observer ( see fig . 3 in @xcite ) gives the typical opening angle of the cascade emission , with the small angle approximation , as @xmath24 where @xmath25 and @xmath26 are the commoving mean free path for pair production and the commoving distance to the source , respectively , and @xmath27 is the deflection angle of electron - positron pairs by the igmf . assuming that the correlation length of the igmf @xmath28 is much greater than the mean free path for ic scattering @xmath29 , @xmath27 can be estimated as the ratio of @xmath29 and the larmor radius of electron @xmath30 in the magnetic field , which are given by @xmath31 @xmath32 where we assumed that the pair produced electron / positron has half the energy of the initial photon , @xmath33 . we related the magnetic field at the time of the pair production and ic scattering , @xmath34 , to the magnetic field today , @xmath22 , assuming that it is only affected by the @xmath35 redshift dilution . for @xmath36 tev , @xmath37 , where @xmath38 is the typical energy of a cmb photon hence , we can use the thomson approximation where the energy of cascade @xmath0-rays produced by ic scattering , as observed on earth , is given by @xmath39 inserting the typical energy of a cmb photon at redshift @xmath40 , when the ic occurs , @xmath41 , we obtain @xmath42 hence , the deflection angle is given by @xmath43 eq . [ eq : s1 ] can be obtained by substituting eq . [ eq : s7 ] into eq . [ eq : s2 ] . assuming a spatially flat friedmann - lematre - robertson - walker ( flrw ) universe , if a tev photon is emitted at time @xmath44 from the agn and pair produces on an ebl photon at time @xmath45 , the commoving distances @xmath25 and @xmath26 are given by @xmath46 @xmath47 where @xmath48 is the scale factor at time @xmath49 . using the change of variables @xmath50 and @xmath51 , we can express the comoving distance ( eq . [ eq : s8 ] , [ eq : s9 ] ) in terms of the redshift of emission and pair production , @xmath21 and @xmath40 . @xmath52 @xmath53 for the redshifts of interest , we can take the universe as made of matter and cosmological constant only , and the hubble parameter is given by @xmath54 for a flat matter-@xmath55 flrw universe . note that @xmath40 in eq . [ eq : s1 ] and eq . [ eq : s11 ] can not be measured directly . taking the expression of the mean free path ( which assumes a redshift dependence of the ebl number density @xmath56 ) from @xcite : @xmath57 where @xmath58 accounts for the ebl model uncertainties , and eq . [ eq : s6 ] is used to express the mean free path @xmath59 in terms of @xmath20 . the optical depth of the @xmath0-ray propagating from the source grows as @xmath60 the time of pair production corresponds to when @xmath61 reaches 1 , and can be found implicitly from @xmath62 eq . [ eq : s15 ] allows us to solve for @xmath63 implicitly in terms of @xmath20 and @xmath21 . we can then obtain @xmath64 and @xmath65 from eq . [ eq : s11 ] and eq . [ eq : s12 ] , and find the angular size of pair halos @xmath66 as a function of @xmath20 , @xmath21 , and @xmath22 from eq . [ eq : s1 ] . for large @xmath21 and @xmath20 , one can assume that @xmath67 @xcite , leading to @xmath68 however , this assumption is not true in general . in particular , it overestimates the angular extent of the pair halos around low redshift sources . hence , we do not make this assumption when using eq . [ eq : s1 ] to estimate @xmath22 from the most likely values of @xmath66 . from eq . [ eq : s1 ] , it is obvious that @xmath69 . the @xmath21 and @xmath20 dependence of @xmath66 , however , is not explicit . figure [ fig : s3 ] shows the sensitivity of @xmath66 to various model parameters assuming an igmf of @xmath70 and using eq . [ eq : s1 ] : the @xmath21 dependence of @xmath66 for @xmath71 is shown in figure [ fig : s3](a ) , and the @xmath20 dependence of @xmath66 for @xmath72 is shown in figure [ fig : s3](b ) . from figure [ fig : s3](a ) , we find it is quite unlikely to detect the extended emission from high - redshift sources , supporting our selection criteria for stacking sources based on redshift . we can also find , from figure [ fig : s3](b ) , that lower energy electrons are deflected by larger angles , consistent with the results we have obtained in this study ( as discussed in the main text ) . , given by eq . [ eq : s1 ] . ( a ) the @xmath21 dependence of the typical angular size @xmath66 of pair halos at @xmath71 . ( b ) the @xmath20 dependence of the typical angular size @xmath66 of pair halos from agns with redshift @xmath72.,width=491 ] we identify 24 hsp bl lacs with redshift @xmath2 that satisfy our selection criteria and we stack their photon events , as shown in fig . [ fig:1s](a ) ( @xmath0-ray counts map in 1 gev-1.58 gev ) . as a control population , 26 fsrqs ( with any redshift ) are also selected by the same criteria . [ fig:1s](b ) shows the difference of the @xmath0-ray counts in 1 gev-1.58 gev between the two source populations . the background counts of these two stacked sources calculated by averaging the counts in the background bin are then subtracted from their total counts . to make the two populations comparable , the background - subtracted counts of the stacked fsrqs are normalized to the same level as that of the stacked bl lacs at the center . we smooth the counts maps by using a gaussian kernel with full width at half maximum of @xmath73 , and subtract the normalized fsrqs counts from the bl lacs. in fig . [ fig:1s](b ) , the difference map shows an excess of the @xmath0-ray emission around the stacked bl lacs over the stacked fsrqs . @xmath0-ray counts maps of the stacked sources in the 1gev-1.58gev energy bin . the large circles show the outer edge of the detection region . ( a ) counts map of the stacked bl lacs . ( b ) smoothed counts difference between the stacked bl lacs and the center - normalized stacked fsrqs . positive values indicate the bl lacs counts are greater than the normalized counts of the fsrqs in that angular region , width=529 ] . we choose the crab and geminga pulsars as our calibration sources since they are effective point sources for fermi - lat @xcite . figure [ fig : s4 ] shows the angular distribution of photon events around the stacked pulsars and the angular distribution of the effective psfs calculated for the same observation times and the observed spectrum . we use the fermi science tools to calculate the psf for the same observational parameters as our different data sets . we also plot these calculated psf profiles for the 24 stacked bl lacs and the 26 stacked fsrqs in the same figure . there is only a very slight difference among their psfs , hence the normalized stacked profiles of the three set of sources are roughly comparable . the good consistency in the angular distributions determined with both the pulsar and psf data sets leave the appearance of extended emission about the bl lac data set ( as shown in fig . [ fig:1s ] ) the notable exception . we calculate the normalized angular profiles for the stacked pulsars , the 24 bl lacs , and the 26 fsrqs , as shown in fig . [ fig : s4l ] ( the same profiles as shown in fig . 1 in the main text , including the other two higher energy bins ) . again , in the lower energy bins , the normalized angular profiles of stacked bl lacs have lower scaled counts per unit solid angle at small @xmath74 , providing evidence for extended emission since the additional counts in the extended halo reduce the scaled counts at small angles after normalization . in our study , we evaluate the likelihood in the two - dimensional space of @xmath75 and @xmath66 . as described in the main text , the model hypothesis @xmath76 is defined on a multidimensional space of model parameters @xmath77 , where @xmath78 and @xmath79 are a set of background values ( in counts per unit solid angle ) and a set of normalization factors , respectively , for a group of stacked sources . we define @xmath80 as a subset of @xmath76 for a given pair of @xmath75 and @xmath66 . @xmath81 corresponds to the null hypothesis with @xmath82 constrained by @xmath83 or @xmath84 . the values of the likelihood ratio @xmath85 are evaluated and displayed in two - dimensional ( @xmath86)-space , where @xmath87 denotes the set of observations @xmath88 ( see main text ) , and @xmath89 is the supremum function . as discussed in the main text , since @xmath90 is a very small number , a direct frequentist approach where one calculates the joint likelihood @xmath91 would lead to a non - converging test statistic ( ts ) distribution and potentially result in a type ii error @xcite . to overcome the problem of small sample size , we repartition the data into two sets : the stacked angular distribution @xmath92 obtained by summing over sources @xmath93 , and the stacked source distribution @xmath94 obtained by summing over angular bins @xmath95 , where @xmath96 and @xmath97 are the total number of angular bins and stacked sources , respectively . given @xmath98 number of samples , the probability of partitioning the samples into @xmath99 parts with @xmath100 samples in each part follows a multinomial distribution @xmath101 where @xmath102 are the probabilities giving @xmath103 in each part , respectively . hence , the likelihood of obtaining @xmath104 and @xmath105 , @xmath106 , is the probability of having a @xmath107 total counts with the two independent ways of repartitioning the data given by @xmath104 and @xmath105 , respectively . thus we have @xmath108 for a given set of model parameters @xmath109 , the estimators @xmath110 , @xmath111 and @xmath112 can be calculated using eq . 3 in the main text . note that we can always rewrite a joint poisson distribution ( e.g. eq . [ eq : s16 - 0 ] ) as the product of a poisson distribution and a multinomial distribution @xmath113 where @xmath114 , @xmath115 , and @xmath116 . this likelihood @xmath117 is combined with the likelihood of getting a set of @xmath118 counts detected in each background bin around each source @xmath119 : @xmath120 we subsequently evaluate the joint likelihood @xmath121 where @xmath122 , @xmath123 , and @xmath124 are all relatively large numbers of counts , as discussed in the main text . the supremum likelihood value for a given @xmath75 and @xmath66 is found in the @xmath125-dimensional space of model parameters @xmath78 and @xmath79 ( where @xmath126 for the stacked pulsars , @xmath127 for the bl lacs , and @xmath128 for the fsrqs ) using powell s method @xcite . the resulting likelihood ratio maps ( fig . [ fig : s5 ] ) show peaks at non - zero @xmath75 and @xmath66 in the first energy bins , while the likelihood maps for the higher energy bins peak close to the axes , consistent with the null hypothesis . this matches our expectation based on the decreasing angular scale of the halo for increasing energy as seen in eq . [ eq : s1 ] . so we do not include an additional trials factor for looking in these different energy bins . furthermore , we calculate the likelihood maps for the simulated point source ( labelled psf ) with a total number of events in each energy bin set to that of the stacked bl lacs in the first energy bin . whenever calculating the simulated point - source maps we use the instrument response parameters for the corresponding observing time and source position obtained by using the fermi science tools . the likelihood maps for the stacked fsrqs , pulsars , together with their corresponding maps for simulated point sources with the same number of counts , as shown in figure [ fig : s6 ] . from the distributions of the maximum likelihood and the values of the likelihood ratio , we can find significant difference between the observed bl lacs and the simulated point source , while the fsrqs and pulsars are shown to appear as point sources for fermi - lat . a classical likelihood ratio test ( lrt ) applied to this problem is potentially inaccurate since the probability distribution of the test statistic ( ts ) is non - trivial . wilks theorem gives a useful approximation : the distribution of a @xmath129 ( the likelihood ratio @xmath55 as defined in the main text ) for nested hypotheses will be asymptotically @xmath130-distributed as the sample size goes to infinity . however , the theorem is only valid under certain conditions including restrictions on the sample population and the formulation of the hypotheses to be tested @xcite . in this study , the set of the model parameters @xmath131 is not open and the null hypothesis is defined on the boundaries of the domain . in such a case , we can not directly apply wilks theorem to determine the distribution of the ts @xcite . in the study of @xcite , a monte carlo ( mc ) method is used to check the distribution of ts , and a multiplicative factor of @xmath132 is found in the resulting @xmath130-distribution because the null hypothesis stands on the symmetric boundaries of the parameter space , which indicates that half of the mc samples give positive ts values following a @xmath130-distribution , while the rest of the mc samples maximize the likelihood under the null hypothesis , giving @xmath133 . we also apply the mc method to determine the distribution of the ts . we find that the probability distribution of the non - zero ts values lays between the distributions of @xmath134 and @xmath135 , and the ratio of non - zero ts values to the total mc samples @xmath136 given by the mc simulation , as shown in figure [ fig : s7 ] . in our study , the maximum likelihood ratio gives a ts of @xmath137 ( as shown in fig . 2 in the main text ) , corresponding to a p - value of @xmath138 , as shown in fig . [ fig : s7 ] . this p - value indicates a significance which is equivalent to the probability of getting a normal - distributed sample @xmath139 for @xmath140 with @xmath141 ( i.e. @xmath142 significance ) . we emphasize that this method , based on repartitioned data , uses only measured ( not weighted ) counts for which the probability distribution function is known exactly . while this method gives good convergence ( in finding the maximum likelihood value ) , it does so with the loss of some information . the following bayesian analysis keeps all information and results in the conclusion that the data reveal somewhat stronger evidence in support of the pair - halo hypothesis . in the above frequentist analysis , we can not provide an analytical function for the distribution of the ts values . and we have to combine the counts into different sets to overcome the problem of small sample size . alternatively , as suggested by @xcite , we can test the statistical significance of the extended emission by evaluating the bayes factors @xcite , which can well handle the small sample size problem , but needs much more computational time @xcite . we introduce a hypothesis of extended emission for a given @xmath143 and @xmath144 , @xmath145 , which is defined as a subset of @xmath76 ( see the main text ) for @xmath146 and @xmath147 . the bayes factors of @xmath148 against the null hypothesis @xmath81 are given by : @xmath149 where @xmath150 is the bayesian likelihood function . applying bayes theorem , the likelihood function is given by the bayesian probability , which is obtained by integrating ( not maximizing ) over the parameter space @xcite . hence , for a hypothesis @xmath151 , @xmath152 where @xmath153 is the set of observed counts @xmath88 in the angular bins , @xmath131 is the set of model parameters , and @xmath154 is the set of poisson estimators @xmath155 given by the halo model . for a bayesian method , the problem of limited statistics in the ( @xmath93 , @xmath95 ) bins is eliminated @xcite , the posterior density in eq . [ eq : s18 ] can be straightly given by eq . [ eq : s16 - 0 ] . the prior density @xmath156 is the probability density for getting a set of model parameters @xmath157 with a hypothesis @xmath158 . it can be assigned by using the probability of getting the total number of counts in all the source bins ( @xmath159 ) and in the background bin ( @xmath160 ) around each source @xmath93 . these measurements can help us to evaluate @xmath156 if we assume that they are prior measurements which can provide us the knowledge of how the data from the stacked sources are combined , revealing the prior information of the model parameters @xmath78 and @xmath79 . the measurements of @xmath161 and @xmath162 can also be treated as poisson experiments . hence , @xmath163\times\delta(f_{\mathrm{halo}}-f^*_{\mathrm{halo}})\delta(\theta-\theta^ * ) , \label{eq : s19}\ ] ] from eq . [ eq : s16 - 0 ] , [ eq : s18 ] , and [ eq : s19 ] , the bayesian likelihood ( eq . [ eq : s18 ] ) can be rewritten as @xmath164\\ \times \prod_{i=1}^n\left[\mathcal{p}\left(n_{\mathrm{on},i}\bigg|\sum_{j=1}^{m-1}\lambda_{i , j}\right)\mathcal{p}(n_{\mathrm{off},i}|\lambda_{i , m})\right]\times\delta(f_{\mathrm{halo}}-f^*_{\mathrm{halo}})\delta(\theta-\theta^ * ) . \end{aligned } \label{eq : s20}\ ] ] @xmath165 is then just a special case of eq . [ eq : s20 ] when @xmath166 or @xmath167 . the bayes factors can be consequently obtained via evaluating this multi - dimensional integral . in the 1 gev-1.58 gev energy bin , there are a number of hypotheses @xmath145 that show evidence against the null hypothesis @xmath81 . recalling the interpretation of @xmath168 in half - units on the @xmath169 scale , the @xmath170 , @xmath171 , and @xmath3 provide substantial , strong , or decisive evidence against the null hypothesis , respectively @xcite . we plot the contours of such levels of @xmath172 in the @xmath143-@xmath144 coordinates [ as shown in fig . 3(a ) in the main text ] . we can see decisive evidence for non - zero @xmath173 and @xmath144 . for the higher energy bins , there is no hypothesis @xmath145 giving substantial evidence against @xmath81 ( @xmath174 ) , agreeing with the results shown in the frequentist analysis . the information about the igmf is contained in the extended emission . here we focus on the model factor @xmath66 , and seek to get the quantitative significant range of its values for the stacked bl lacs . we introduce a hypothesis @xmath175 for a given @xmath144 with all possible values of @xmath75 . although the prior distribution of @xmath75 is very hard to determine , one can assume that the marginal density ( the whole bayesian integrand ) is dominated by the posterior density ( this will usually be the case for large samples @xcite ) , so that we do not pre - assume any knowledge of @xmath75 before doing the experiment . in that case , the bayes factors of @xmath175 can be evaluated by integrating the bayesian likelihood @xmath150 over all possible values of @xmath75 . thus , the resulting bayes factors @xmath176 of @xmath175 against @xmath81 are given as a function of @xmath144 [ as shown in fig . 3(b ) in the main text ] . summarizing , there is decisive evidence in the 1 gev-1.58 gev energy bin in favor of the pair halos with angular extent @xmath177 . m. ackermann _ et al . _ , 209 , 34 ( 2013 ) . p. l. nolan _ et al . _ , astrophys . j. suppl . 199 , 31 ( 2012 ) . r. e. kass , a. e. raftery , j. am . 90(430 ) , 773 - 795 ( 1995 ) . h. jeffreys , theory of prabability ( 3rd ed . ) , oxford , u.k . : oxford university press ( 1961 ) . a. neronov , d. v. semikoz , phys . d 80 , 123012 ( 2009 ) . h. tashiro , t. vachaspati , phys . d 87 , 123527 ( 2013 ) . a. neronov , d. v. semikoz , p. g. tinyakov , i. i. tkachev , astron . 526 , a90 ( 2011 ) . m. ackermann _ et al . _ , astrophys . j. 765 , 54 ( 2013 ) . s. s. wilks , the annals of mathematical statistics 9 , 6062 ( 1938 ) . s. a. baldwin , g. w. fellingham , psychological methods 18(2 ) , 151 - 164 ( 2013 ) . m. j. d. powell , computer journal 7(2 ) , 155162 ( 1964 ) . r. protassov , d. a. van dyk , a. connors , v. l. kashyap , a. siemiginowska , astrophys . j. 571 , 545 ( 2002 ) . j. r. mattox _ et al . _ , astrophys . j. 461 , 396 ( 1996 ) .

we report on the results of a search for @xmath0-ray pair halos with a stacking analysis of low - redshift blazars using data from the fermi large area telescope . for this analysis we used a number of _ a - priori _ selection criteria , including the spatial and spectral properties of the fermi sources . the angular distribution of @xmath1 1gev photons around 24 stacked isolated high - synchrotron - peaked bl lacs with redshift @xmath2 shows an excess over that of point - like sources . a statistical analysis yields a bayes factor of @xmath3 , providing evidence in favor of extended emission against the point - source hypothesis , consistent with expectations for pair halos produced in the igmf with strength @xmath4 .

in 1974 , a little more than a decade after his first thoughts about working on a model organism , brenner published four manuscripts , including one entitled the genetics of caenorhabditis elegans(brenner 1974 ) and a new field began . in this influential paper ( brenner 1974 ) , brenner outlined methodology for isolation , complementation , and mapping of worm mutants . importantly , the publication also included the successful isolation of several hundred mutants affecting behavior and morphology , a discussion of the number of defined genes , and an estimation of mutation frequency . since that time , many discoveries including dissection of programmed cell death ( coulson et al . 1986 ; ellis et al . 1991 ) , the systematic cloning of the genome ( coulson et al . 1986 ; crawford 2001 ) , the deciphering of the entire dna sequence ( consortium 1998 ) , micrornas ( lee et al . 1993 ; reinhart et al . 2000 ) , rna interference ( fire et al . 1998 ) , and the use of gfp ( chalfie et al . 1994 ) have been done in c. elegans which has led to an expansion in the number of researchers working with c. elegans . for research on aging , early studies in c. elegans focused on the feasibility of measuring lifespan and the use of 5-fluoro-2-deoxyuridine ( fudr ) to maintain synchronous cultures of aged animals ( hosono 1978a , 1978b ) . in 1977 , klass ( 1977 ) published that c. elegans was a good system for aging studies as he established a method to consistently measure lifespan , and he concluded that this could lead to future detailed analysis combining genetics and biochemistry . in these early studies , klass found that altering either temperature or the amount of food resulted in a change in lifespan . in addition , only small effects on lifespan were observed based on parental age or parental lifespan . klass performed a clonal genetic screen for mutants with altered lifespan and identified five mutants ( klass 1983 ) . interestingly , later genetic work on these mutants in the laboratory of tom johnson , mapped all of them to a single genetic locus , named age-1 ( friedman & johnson 1988 ) . this was the first breakthrough in aging research for studies based on c. elegans as this study revealed that it was possible to identify mutants that altered lifespan and more importantly , individual genes could modulate lifespan . from the initial characterization of mutants that altered lifespan , however , lifespan is a single measureable parameter that defines the amount of time an organism is alive but does not give any indication for how an animal is actually aging . for this reason , healthspan , defined as the time that an individual is active , productive and free from age - associated disease , is starting to become the focus of aging research ( reviewed in ( tissenbaum 2012 ) ) . equally important for aging research a regulated process should indicate that this is a trait that would be selected for over time . however , fitness competitions between wild type and daf-2 mutants , show that after four generations , none of the daf-2 mutants remained primarily because of the early fertility defects in the daf-2 mutants ( jenkins et al . 2004 ) . therefore , similar to other studies with long - lived mutants and consistent with the antagonistic pleiotropy theory of aging ( lakowski & hekimi 1996 ; gems et al . 1998 ; chen , pan et al . 2007 ; chen , senturk et al . 2007 ; curran & ruvkun 2007 ; anderson et al . 2011 ) , daf-2 mutants exhibit a heavy fitness cost with lifespan extension ( jenkins et al , lifespan and aging should not be used interchangeably and the use of the word regulation should be monitored ( reviewed in ( lithgow 2006 ; tissenbaum 2012 ) ) . several years after the age-1 gene was identified , another gene was shown to modulate lifespan . similar to mutation in age-1 , daf-2 mutants showed adult lifespan extension ( kenyon et al . interestingly , previously , both daf-2 and age-1 had showed similarity based on a different phenotype . under favorable growth conditions , c. elegans develop from an egg through four larval stages ( l1-l4 ) each separated by a molt , and then a final molt into a reproductive self - fertilizing adult hermaphrodite . in response to unfavorable growth conditions , in particular , high levels of a secreted pheromone ( i.e. crowding , low food ) , worms can enter an alternative developmental mode ( at the l3 stage ) forming dauer larvae ( riddle & albert 1997 ) . dauer ( german for enduring ) larvae ( alternate l3 ) maximize survival until conditions become more favorable , whereupon they will molt and form a reproductive adult . both daf-2 and age-1 were initially isolated in this type of screen because both daf-2 and age-1 ( originally identified as daf-23 ) mutants show a dauer constitutive ( daf - c ) phenotype such that even under good growth conditions , mutants will enter the dauer stage ( albert et al . . genetic epistasis analysis placed these two genes in a similar genetic epistasis pathway for dauer formation that was distinct from the other daf - c mutants ( vowels & thomas 1992 ) . these studies also revealed that both daf-2 and age-1 mutants could be suppressed by a mutation in the daf-16 gene ( albert et al . 1981 ; riddle 1988 ; vowels & thomas 1992 ; riddle & albert 1997 ) . daf-16 ( also known as daf-17 ) was also isolated in these early dauer formation genetic screens because daf-16 mutants show a dauer defective ( daf - d ) phenotype such that even under poor growth conditions , mutants will not enter the dauer stage ( albert et al . 1981 ; riddle 1988 ; vowels & thomas 1992 ; riddle & albert 1997 ) . subsequent molecular cloning beginning in 1996 , explained why these genes were separate and distinct from other pathways . the genes encoded for members of an insulin / igf-1 signaling ( iis ) pathway where daf-2 encoded for an iis receptor , age-1 encoded for the catalytic subunit of the pi 3-kinase , and daf-16 encoded for a forkhead box o ( foxo ) transcription factor downstream of the pi 3-kinase signaling cascade . since then , studies have shown that the iis pathway is evolutionarily conserved such that mutations in this pathway in flies and mice are also linked to lifespan extension ( barbieri et al . 2003 ; yen et al . 2011 ) . molecular and genetic studies in drosophila and c. elegans have identified foxo as a central regulator of lifespan ( lin et al . modulation of drosophila foxo ( dfoxo ) and c. elegans foxo ( daf-16 ) dosage can either decrease or increase the lifespan of the organism ( lin et al . importantly , advances in genomic research have led to new findings in the area of genome - wide association studies in humans . multiple human population studies have found an association between single nucleotide polymorphisms ( snps ) in human foxo3 and human lifespan extension ( lunetta et al . 2007 ; willcox et al . 2008 ; anselmi et al . 2009 ; flachsbart et al . 2009 ; li et al . 2009 ; soerensen et al . 2010 ; zeng et al . 2011 ) , and the strength of the association appears to increase with age ( flachsbart et al . therefore , foxo3 has emerged as a candidate longevity gene in humans . taken together , just over a decade from the molecular identification of daf-16 in c. elegans , multiple studies have linked snps associated with human daf-16/foxo3 and human lifespan extension . early studies on dauer larvae showed that dauers were ageless ; namely once a dauer recovers and develops into a reproductive hermaphrodite , the subsequent adult lifespan ( post - dauer ) is independent from the time spent as a dauer ( klass & hirsh 1976 ) . therefore , it was thought that daf-2 and age-1 were long lived merely due to activation of part of the dauer program manifested in the adult . however , ( kenyon et al . 1993 ) addressed these concerns by performing lifespan analyses on several other daf - c mutants ( later shown to be part of a tgf- signaling cascade ) and found that these mutants did not affect lifespan and the issue seemed resolved . however , approaches including genome- wide microarrays and unbiased lc / ms proteomics have shown that the profiles of adult long - lived daf-2 mutants are most similar to wild - type dauer larvae ( mcelwee et al . 2004 ; mcelwee et al . moreover , recent studies ( shaw et al . 2007 ) re - examined the tgf- daf - c mutants and found in contrast to earlier studies , these mutants showed lifespan extension . similarly , recent genetic data revealed that the connections between the iis pathway and the tgf- signaling pathway are intertwined to modulate both lifespan and dauer formation ( narasimhan et al . , multiple studies suggest that the longevity of daf-2 mutants is due to activation of the dauer program in the adult . despite the fact that a dauer program , an alternative hibernation state to delay reproduction until growth conditions are favorable , seems worm specific , the signaling pathways that were identified to regulate dauer formation modulate longevity from worms to mice , and why has c. elegans been used so successfully for aging research ? what would make an organism suitable for aging research ? as suggested by sydney brenner in 1963 , the ability to easily and cheaply grow large quantities of worms in the lab is very helpful for aging research , especially when identifying long - lived mutants . c. elegans also have a relatively short lifespan ( average approximately 17 days at 20 c ) , and the lifespan is largely invariant . the latter allows for identification of mutants that shorten or lengthen average lifespan by a little as 1015% and still be of statistical significance . additional benefits of using c. elegans include that the entire genome is sequenced and annotated , the availability of an rnai library comprising approx . 80% of the genes in the genome , the ease of generating transgenic strains and the recent development of gene - targeting approaches . this has allowed for extensive forward and reverse genetic screens for genes that modulate lifespan . the rnai library allows rnai to be done by feeding worms bacteria that produce the desired dsrna and then either the worm or their progeny are scored for a longevity phenotype ( ahringer 2006 ) . using genome - wide rnai feeding libraries , the importance of the mitochondria , signal transduction , the response to stress , protein translation , gene expression , and metabolism were found to modulate lifespan ( dillin et al . , 2002 ; lee et al . , 2003 ; 2005 ; hansen , hsu et al . 2005 ; hansen , taubert et al . , 2007 ) . another advantage working with c. elegans for studying the aging process is that the lifespan assay is straightforward , which allows for large numbers of worms to be assayed in a single experiment . therefore , statistical significance can be tested in addition to the analysis of mortality rates . together , these techniques allow one to comprehensively survey the worm genome for genes that modulate lifespan . this has led to the identification of more than 200 genes and regimens that modulate lifespan in c. elegans and revealed evolutionarily conserved pathways that modulate lifespan . therefore , the combination of the short , invariant lifespan , ease of assays , ample genetic , molecular and genomic tools , and evolutionary conservation has allowed c. elegans to develop into a premiere model system for aging research . despite all the excellent advantages of working with c. elegans for aging research , there are also several disadvantages for c. elegans as a model for human aging . first , c. elegans have a simple body plan , and lack many defined organs / tissues including a brain , blood , a defined fat cell , internal organs , and is evolutionarily distant from humans . second , c. elegans are also only 1 mm in length which makes biochemistry more difficult . typically , all biochemistry , microarray , immunoprecipitation , and chromatin immunoprecipitation is performed on whole worm extracts of either mixed - stage animals or animals at a similar growth stage . this may lead to limited understanding of any tissue - specific signaling such as whether a gene is expressed in the hypodermis or the intestine . finally , c. elegans cell culture is limited with no system equivalent to drosophila s2 cells . c. elegans has proved to be an invaluable animal for aging research . thus far , research has focused on the use of lifespan as a measurement of the aging process . these studies have led to the identification of hundreds of genes and regimens that modulate lifespan . although the initial studies identified genes that altered lifespan and affected dauer diapause , these signaling pathways have nonetheless identified longevity - associated pathways across phylogeny . however , to truly use c. elegans for aging research , future studies should focus on understanding the connection between longevity and how an animal ages , with a focus on health . aging involves the coordination of multiple systems in an organism and how they change as a function of time . we should strive to use model systems to reveal this systemic coordination on a molecular and genetic level , and how this leads to healthy aging rather than simply lifespan extension .

over a century ago , the zoologist emile maupas first identified the nematode , rhabditis elegans , in the soil in algiers . subsequent work and phylogenic studies renamed the species caenorhabditis elegans or more commonly referred to as c. elegans ; ( caeno meaning recent ; rhabditis meaning rod ; elegans meaning nice ) . however , it was not until 1963 , when sydney brenner , already successful from his work on dna , rna , and the genetic code , suggested the future of biological research lay in model organisms . brenner believed that biological research required a model system that could grow in vast quantities in the lab , were cheap to maintain and had a simple body plan , and he chose the nematode c. elegans to fulfill such a role . since that time , c. elegans has emerged as one of the premiere model systems for aging research . this paper reviews some initial identification of mutants with altered lifespan with a focus on genetics and then discusses advantages and disadvantages for using c. elegans as a model system to understand human aging . this review focuses on molecular genetics aspects of this model organism .

nutritional problems are often present in children with cerebral palsy ( cp ) , especially in those with severe motor impairment ( 1 ) . reasons for nutritional disorders in these patients are multifactorial , so malnutrition can be caused by motor impairment , digestive problems , medications which patient uses , endocrine disorders and social environment . calorie intake in children with cp is lower compared to the control group of children of the same age . the analysis of the three - day menu demonstrated significantly lower energy intake in children with moderate and severe developmental disorders , that suggests there is a feeding problem as a cause of malnutrition of these children ( 2 ) . the reason for that may be modified food texture , as well as food inappropriate for patient s age . some patients are dependent on the parents / careers feeding due to inability to express hunger and thirst and the inadequate hand - mouth coordination ( 3 ) . energy needs of children with cp are different compared to healthy children , as well as depending on the type of cp . children who are physically active , those involved in an intensive rehabilitation , children with seizures or frequent infections have increased energy needs ( 4 ) . oromotor dysfunction ( omd ) affects up to 90% of patients with cp and is major determinant of malnutrition in children with a neurodevelopmental disorder ( 5 , 6 ) . inadequate sucking , dysfunctional swallowing , increased pharyngeal reflex , sialorrhea due to inadequate mouth closure and decreased ability to chew make oral feeding difficult . for example , patients with unilateral spastic cp whose body height and triceps skinfold thickness is within the normal range , have significantly lower limb length and circumference of the affected side compared to unaffected side ( 7 ) . another study also found that the affected limb had delayed skeletal maturation and reduced bone density compared to the unaffected side ( 8) . it looks like that muscle atrophy in the affected side interferes with the growth , independent of poor nutritional intake . the aim of this study was to assess nutritional status of children with cp , treated at the pediatric clinic , clinical centre of sarajevo university and to evaluate causes of malnutrition in these patients . patients were divided into two groups according to motor disorder severity , the gross motor function classification system ( gmfcs ) among which testing was performed . the group of patients with minor motor impairment ( mmi ) consisted of patients with gmfcs i - iii , and the group of patients with severe motor impairment ( smi ) consisted of patients with gmfcs iv - v . exclusion criteria were : patients with progressive neurodegenerative and central nervous system lesions , other neurological disorders which are not cp , cp patients with associated chronic diseases that may affect nutritional status . detailed anthropometry was performed and included measurement of body weight ( bw ) , body height ( bh ) , body mass index ( bmi = bw / bh ) , head circumference ( hc ) , subscapular skinfold thickness ( sst ) , triceps skinfold thickness ( tst ) , mid upper arm muscle circumference ( muamc ) . mid upper arm muscle circumference was determined according to the formula : muamc = uac( x tst / 10 ) where uac is upper arm circumference . standardized methods of measuring were used for all the measurements , and thereafter z scores were calculated to enable more accurate comparisons regardless of patient age and sex . for comparison we used following growth charts : body weight , body height , body mass index the cdc ( centers for disease control and prevention ) growth curves , 2000 ( 9 ) ; head circumference a reference growth curve for children birth-18 years ; roche af ( 10 ) ; subscapular skinfold thickness and triceps skinfold thickness a reference curve for triceps and subscapular skinfold thickness in us children and adolescents ; addo and himes , ( 11 ) ; mid upper arm muscle circumference a reference curve for muscle mass and body fat of the upper extremities ; frisancho ( 12 ) . those who met one or more of the following criteria were indicated as malnourished subjects : bw < -2 z scores , bh < -2 z scores , tst < -2 z scores , sst < -2 z scores . those who met one or more of the following criteria were indicated as obese respondents : bw > 2 z score , bmi > 2 z score , tst > 2 z score , sst > 2 z score . we used a form that was made for the purpose of the study , modified according to forms used in similar published studies of relevant centers ( 13 , 14 , 15 ) . the form includes information related to eating habits and problems during feeding , which may affect nutritional status . omd has been confirmed in our study based on the presence of one or more of the following features : dysarthria , sialorrhea , asymmetry of oral tissues when resting or during speech or feeding as well as presence of eating and swallowing difficulties . the level of omd was estimated according to eating and swallowing problems : no eating problems , eats normal food;mild problems , eats chopped or mashed food;moderate problems , requires very mushy , chopped or liquid food;severe problems , requires a dense liquid , puree or needs feeding through a tube . no eating problems , eats normal food ; mild problems , eats chopped or mashed food ; moderate problems , requires very mushy , chopped or liquid food ; severe problems , requires a dense liquid , puree or needs feeding through a tube . the patients were divided according to the independence in feeding ( fully independent , partially independent , totally dependent on the parent / career ) , according to the meal length ( < 15 min , 15 - 30 min , > 30 min ) and according to the length of daily feeding time ( 3h , > 3h ) . statistical methods used in data processing included percentages and rates , median , minimum , maximum , test , mann - whitney u test . they were classified according to the severity of neurologic dysfunction into two groups between which the analysis was done . mmi group consisted of 34 ( 42.5% ) and smi group of 46 ( 57.5% ) patients . there were 18 ( 52.9% ) boys and 16 ( 47.1% ) girls in the group of mmi , while there were 29 ( 63.0% ) boys and 17 ( 37.0% ) girls in the group of smi . table 1 . shows the median , minimum and maximum of monitored anthropometric parameters in all patients , in the group of patients with minor and group with severe motor impairment and the median of same parameters in boys and girls . we noted discrepancies in all anthropometric parameters of patients with cp compared to healthy children . these deviations were noted in both groups , but are much more pronounced in patients with smi . the median z scores of bw , bh , hc , sst and tst were significantly lower in the smi group compared to the mmi group . girls had significantly higher median values of bh than boys , and the difference between the median values of muamc in groups of boys and girls is on the borderlines of statistical significance . legend : mmi minor motor impairment , smi severe motor impairment , bw body weight , bh body height , subscapular skinfold thickness , tst triceps skinfold thickness , muamc mid upper arm muscle circumference . classifying subjects in three groups of malnourished , normal weight and obese we obtained the following results ( graph 1 . ) . 38 ( 47.5% ) of respondents were underweight in the total group , out of which 9 ( 26.5% ) in the mmi group , while there were 29 ( 63.0% ) in the smi group , thus significantly higher ( = 11:55 ; df = 2 , p < 0.01 ) . in our study , there were 9 ( 11.3% ) obese patients in the total group with no statistically significant difference in the incidence of obesity ( = 01.07 , df = 2 > 0.05 ) between the two groups , there were 4 ( 11.8% ) in the mmi group and 5 ( 10.9% ) obese patients in the smi group . the frequency of patients with different degrees of nutritional status in the group with mild or severe motor impairment . table 2 . shows the frequency of omd , independence in feeding , length of meals and daily feeding time in patients . the frequency of omd is significantly higher in the smi group ( p < 0.01 ) , where 41 ( 89.1% ) patient had omd , while 21 patients ( 61.8% ) had omd in the mmi group . there are also significant differences in the severity of omd between these two groups ( p < 0.01 ) , 13 ( 31.7% ) patients had the third degree of omd in the smi group and the same number of them had the fourth degree of omd and not a single patient had the third and fourth degree of omd in the mmi group , respectively , all the patients had the first and second degree of omd . by monitoring the impact of the presence of omd on malnutrition we showed that patients who had omd were more often malnourished ( p < 0.05 ) . evaluation of the impact of degree of omd on the occurrence of malnutrition was done by comparing the degree of omd and tst and we received the result which was on the borderline of statistical significance ( p = 0.0286 ) . oromotor dysfunction , independence in feeding , length of meals and length of daily feeding in patients with varying degrees of motor impairment . legend : mmi minor motor impairment , smi severe motor impairment , omd oromotor dysfunction , complete dependence on the parents / careers feeding was significantly more frequent in the group of patients with smi compared to the group with mmi ( p < 0.01 ) . the probability of occurrence of malnutrition significantly increases with decreasing independence in feeding ( p < 0.01 ) . there were found no statistically significant differences among the groups of subjects with smi or mmi in the frequency of meals of varying duration of meal ( up to 15 minutes , 15 - 30 minutes , over 30 minutes ) ( p > 0.05 ) , nor the duration of the daily feeding ( under or up to 3 hours or over 3 hours ) ( p > 0.05 ) . the probability of occurrence of malnutrition significantly increases with increasing length of meal ( p < 0.05 ) and length of daily feeding ( p < 0.05 ) . our study , like many other studies before , indicates that children with cp significantly differ from the general population in their growth ( 16 , 17 ) . however , it is still unclear to what extent deviant growth represents standard growth for this population or whether it is the result of suboptimal nutrition , resulting in stunting . normal growth in children is generally accepted as a marker of health , while abnormal growth may be considered as a sign of disruption in child s nutrition , environment or health . growth that would be considered normal for children with cp has not been established , so it is often difficult to distinguish between children with cp , who are healthy from those who are sick . abnormalities in growth and body build in children with cerebral palsy are the result of various causes , some of which may be affected to enhance growth . there are evidences of a significant deviation of all seven anthropometric parameters in relation to the reference values of healthy children in our research . bw , bh , hc , sst and tst were markedly lower in patients with smi , indicating a small amount of fat tissue in these patients , and a reduced growth in height and growth of bone structures . bmi was not significantly different among the groups , because reduced bw follows reduced bh . muamc is lower in patients with smi , but does not significantly differ from that of patients with mmi . it was observed , in the total group , in 47.5% of subjects , in the mmi group in 26,5% , and in the smi group in 63.0% . malnutrition is slightly lower in other countries : 2016 karagiozoglou lt recorded a 38.1% undernourished patients ( 18 ) in greece in the total group of respondents , 2006 bertoli s found 41.2% ( 19 ) in italy , and 2001troughton ker 2001 41.2% patients ( 20 ) in ireland . in 2012 , dahlseng mo published a study conducted in norway where 20% of patients with smi were malnourished , which is significantly lower than in our patients ( 21 ) . these differences can be explained by possible late involvement of patients in treatment , as well as by parents / careers refusal of adequate treatment , because they minimize this problem in regard to other difficulties these patients have . during the research period , there is also increased frequency of obesity among patients with cp , besides very frequent malnutrition . obesity in patients with cp , which may have a negative impact on overall health and increased incidence of cardiovascular diseases in adulthood , negatively affects the mobility and functionality of children with cp and has a negative effect on the implementation of the rehabilitation of these patients after orthopedic surgery . ( 22 ) showed that obesity among ambulatory children with cp had increased over the last years , and the same trend may be present among more severely impaired children . compared to other studies done in recent years , the incidence of obesity in our patients is much lower . in a study published in 2010 . in norway , the prevalence of obesity in children with cp , aged 6 - 11 years , was 17% ( 23 ) . another study in the united states announced that the prevalence of obesity among children with mild cp increased from 7.7% to 16.5% ( 22 ) over the last decade . the differences in the values obtained in our study are possible primarily due to lower use of gastrostomy . malnutrition of children with cp is often caused by omd , which prevents the child to safely consume calories and nutrients needed for growth ( 6 ) . by using different diagnostic methods , such as assessments of a history provided by parents , the presence of characteristic signs with clinical examination various studies obtained data on the presence of omd in 58 - 90% of children with cp ( 5 , 6 , 15 ) . we have proved the existence of omd in 62 ( 77.5% ) patients in the total group , and in 21 ( 61.8% ) patients with the mmi , and in 41 ( 89.1% ) patients with smi . omd is significantly more common among patients with smi , and also higher degrees of omd are more common in patients with smi . omd significantly affects the onset of malnutrition . by monitoring malnutrition in relation to the omd we noted that in mmi group there are more underweight patients among those who have omd ( 38.1% ) compared to those who do not have omd 1 ( 7.7% ) . in the group of patients with smi this indicates that the existence of omd in patients with mmi has a significant effect on the occurrence of malnutrition . on the other side , the occurrence of malnutrition in patients with smi , besides omd , is influenced by other factors such as neurological damage , and numerous other factors such as frequent morbidity , various infections , epilepsy , hormonal problems . according to some authors , the measuring of tst is the best and the simplest way of assessing the nutritional status of children with cp ( 24 ) . we compared the degree of omd and tst and received the result which is on the borderline of statistical significance ( spearman s rho = -0.245 , p = 0.0286 ) which indicates the possible impact of the degree of omd on nutritional status . patients with cp are often partially or totally dependent on the career s feeding . the cause for this may , besides omd , which is very common , also be immobility , inadequate function of the upper extremities , impaired hearing , vision , inability to communicate , poor cognitive abilities . the number of patients dependent on the parent / career s feeding , in our group of patients , is significant , where 31 ( 67.4% ) of them in the smi group is totally dependent . parents try to compensate problems with feeding of these patients with cp in various ways , among others by prolonging the duration of the meal , which prolongs the total time of daily feeding . pb sullivan believes that the length of daily feeding can be a reliable measure of the severity of feeding impairment and if the parent / career spends 3 or more hours per day feeding his child with cp , then serious thought should be given to the introduction of tube feeding ( 14 ) . our patients with cerebral palsy , namely those with severe motor impairment , are significantly underweight compared to healthy peers . one of the causes is oromotor dysfunction , which has a negative impact on the nutritional status not only in children with more severe motor impairment , but also in those with minor motor impairment . dependence on the parent / career during feeding and length of mealtime are also important . regular monitoring of the nutritional status of these children is necessary , as well as adequate and timely treatment to improve their health status , thus the quality of life for them and their families .

introduction : patients with cerebral palsy ( cp ) , besides the basic neurological damage , are also often undernourished . adequate nutrition for children is very important during the period of intensive growth and development , which is of particular importance in patients with cp.goal:to evaluate the nutritional status of patients with cp who are treated at the pediatric clinic , clinical centre of sarajevo university and causes of malnutrition in these patients.materials and methods : eighty patients with cp underwent anthropometric assessment ( body weight , body height , body mass index , head circumference , subscapular skinfold thickness , triceps skinfold thickness and mid upper arm muscle circumference ) . severity of cp was classified based on the gross motor function classification system ( gmfcs ) . we compared the anthropometric parameters of our patients with normal values of healthy children , as well as with degree of motor impairment , oromotor dysfunction , feeding assistance , length of meals and daily feeding time.results:there were significant differences in all monitored parameters in relation to normal values , with 38 ( 47.5% ) malnourished patients in the total group , out of which 29 ( 63.0% ) with severe motor impairment and with 9 ( 11.3% ) obese patients in the total group . the presence of oromotor dysfunction and other monitored parameters had a significant impact on the nutritional status of these patients.conclusion:in severely disabled patients with cp there is a risk of profound malnutrition . early identification and treatment of these patients is very important for their growth , development and health .

SECTION 1. SHORT TITLE; REFERENCES. (a) Short Title.--This Act may be cited as the ``Accuracy in Campus Crime Reporting Act of 1997''. (b) References.--Except as otherwise provided therein, whenever in this Act an amendment or repeal is expressed in terms of a section or other provision, such amendment or repeal shall be considered to be made to a section or other provision of the Higher Education Act of 1965 (20 U.S.C. 1001 et seq.). SEC. 2. DISCLOSURE OF CRIMES REPORTED AND DAILY CRIME LOG. (a) Annual Statistics.--Section 485(f)(1)(F) (20 U.S.C. 1092(f)(1)(F)) is amended-- (1) by striking ``campus security authorities or local police agencies'' and inserting ``campus security or law enforcement; other campus officials (including administrators, deans, disciplinary officers, athletic department officials, housing officials, and counselors) to whom crimes are reported; or local law enforcement''; (2) by striking clauses (i) through (vi) and inserting the following: ``(i) homicide, including-- ``(I) murder or nonnegligent manslaughter; or ``(II) negligent manslaughter; ``(ii) sex offenses, forcible or nonforcible; ``(iii) robbery; ``(iv) aggravated assault; ``(v) burglary; ``(vi) larceny; ``(vii) motor vehicle theft; ``(viii) arson; ``(ix) simple assault; and ``(x) vandalism.''. (b) Annual Statistics.--Section 485(f)(1)(H) (20 U.S.C. 1092(f)(1)(H)) is amended by striking ``arrests for'' and inserting ``incidents of''. (c) Annual Submission.--Paragraph (4) of section 485(f) (20 U.S.C. 1092(f)(4)) is amended to read as follows: ``(4)(A) Each institution participating in any program under this title shall annually submit to the Secretary a copy of the statistics required to be made available pursuant to paragraphs (1)(F) and (1)(H). ``(B) The Secretary shall collect such statistics and report each set in its entirety, with each institution and campus clearly identified, to the Committee on Education and the Workforce of the House of Representatives, the Committee on Labor and Human Resources of the Senate, each participating institution, and the public via printed and electronic means as the Secretary shall determine. This report shall be issued on or before February 1 of each year.''. (d) Compilation Method.--Paragraph (6) of section 485(f) (20 U.S.C. 1092(f)(6)) is amended to read as follows: ``(6)(A) The statistics described in paragraphs (1)(F) and (1)(H) shall be compiled in accordance with the standards and definitions used in the uniform crime reporting system of the Department of Justice, Federal Bureau of Investigation, and the modifications in such standards and definitions as implemented pursuant to the Hate Crime Statistics Act (28 U.S.C. 534, note). ``(B) The accuracy of the statistics described in paragraphs (1)(F) and (1)(H) shall be certified by each official charged with compiling statistics for inclusion.''. (e) Crime Logs.--Section 485(f) is further amended-- (1) by redesignating paragraphs (4) through (7) as paragraphs (5) through (8), respectively; and (2) by inserting after paragraph (3) the following new paragraph: ``(4)(A) Each institution participating in any program under this title which maintains either a police or security department of any kind shall make, keep, and maintain a daily log, written in a form that can be easily understood, recording in chronological order all crimes reported to such police or security department, including-- ``(i) the nature, date, time, and general location of each crime; ``(ii) the disposition of the complaint, if known; ``(iii) if citations have been issued or charges made, the names and addresses of all persons cited or charged, and the charges against them; and ``(iv) if an arrest has been made, the names and addresses of all persons arrested and the charges against such persons arrested. ``(B) Unless otherwise required by law, each institution may, but is not required to, identify in its log the alleged victim or victims, witnesses, or suspects who have not been arrested or cited, relating to any investigation of a crime. ``(C)(i) All entries which are required pursuant to this paragraph shall, except where disclosure of such information is prohibited by law, be open to public inspection within 24 hours of the initial report being made to the department, a campus security authority, or other campus official. ``(ii) Where there is clear and convincing evidence that the release of such information would jeopardize an ongoing criminal investigation or the safety of an individual, cause a suspect to flee or evade detection, or result in the destruction of evidence, such information may be withheld until that damage is no longer likely to occur from the release of such information. Under no circumstances, however, shall this exception permit the nonreporting of the nature, date, time, and general location of a reported crime. ``(iii) All exceptions to the reporting provisions of this paragraph are to be construed as narrowly as possible. Only that information which is protected from release by law shall remain confidential. All other information relating to each report shall be public. ``(D) Reports may be disseminated by electronic media, including computer networks, where it is reasonably assured the information will reach most of the campus population in a timely fashion.''. (f) Victims' Rights.--Paragraph (8) of section 485(f) (as redesignated by subsection (e) of this section) is amended by striking subparagraph (C). (g) Disciplinary Proceedings.--Section 485(f) is further amended by adding at the end the following new paragraph: ``(9)(A) Each institution of higher education participating in any program under this title shall develop and distribute as part of the report described in paragraph (1) a statement of policy regarding-- ``(i) such institution's on-campus disciplinary practices in cases of alleged infractions of the institution's code of conduct, or other policies, resulting from an act or series of acts that would constitute a crime or crimes within the meaning of local, State, or Federal law, whether or not those acts have actually resulted in criminal charges, prosecution, or conviction; and ``(ii) the procedures followed once a crime has occurred. ``(B) The policy described in subparagraph (A) shall include a clear statement that-- ``(i) all students reporting an offense shall be informed of their options to notify proper law enforcement, including on-campus and local police; ``(ii) the accuser and the accused are entitled to the same opportunities to have others present during a campus disciplinary proceeding; ``(iii) both the accuser and the accused shall be informed of the outcome of any campus disciplinary proceeding brought alleging criminal misconduct; ``(iv) any campus disciplinary proceeding brought alleging criminal misconduct shall be open; and ``(v) all records of any such campus disciplinary proceeding brought alleging criminal misconduct shall be open to public inspection during the regular business hours of the custodian of such records, except for previously created education records not related to criminal allegations which are used during the course of the proceeding.''. (h) Effective Date.--The amendments made by this section shall take effect on January 1, 1998. SEC. 3. EXEMPTION OF ALLEGATIONS OF CRIMINAL ACTIVITY FROM EDUCATION RECORDS DEFINITION. (a) Amendment.--Section 444(a)(4)(B) of the General Education Provisions Act (20 U.S.C. 1232g(a)(4)(B)) is amended-- (1) by redesignating clauses (iii) and (iv) as clauses (iv) and (v), respectively; and (2) by inserting after clause (ii) the following new clause: ``(iii) records which are made or maintained by any officer, office, department, or individual employee of an educational agency or institution about-- ``(I) individuals accused of committing or participating in any criminal activity as defined in local, State, or Federal law alleged to have occurred while the individual was a student in attendance, including audit or noncredit, at an educational agency or institution, whether or not those acts have actually resulted in criminal charges, prosecution, or conviction which are relative to the alleged misconduct; ``(II) the accused in subsequent internal disciplinary proceedings of any kind resulting from, or related to, the alleged activity, regardless of the terminology or nature of the institutional infraction or policy violation alleged; ``(III) the time, duration, attendance policy, and location or locations of any such disciplinary proceedings; ``(IV) the findings relative to the accused of any such disciplinary proceedings; ``(V) the current disposition or status of the case, the sanctions incurred (if any), and any subsequent findings or amendments to such sanctions; ``(VI) accusations of criminal misconduct and related sanctions from any previously attended educational agencies or institutions where such records were created on or after September 1, 1998, and which are maintained by the institution currently or most recently attended by the individual; and ``(VII) any criminal acts required to be reported under paragraph (1)(F), (1)(H), or (4) of section 485(f) of the Higher Education Act of 1965 (20 U.S.C. 1092(f)).''. (b) Effective Date.--The amendments made by this section shall take effect on September 1, 1998. SEC. 4. ENFORCEMENT. (a) Enforcement.--Section 485(f) (20 U.S.C. 1092(f)) (as amended by section 2) is further amended by adding at the end the following new paragraph: ``(10)(A) If any participating institution of higher education fails or refuses to comply with any provision of this subsection, the Secretary shall forthwith terminate all assistance to the institution under the applicable program affected, or issue such other orders as specified below as the Secretary may deem appropriate to achieve such compliance. ``(B) For each separate count of noncompliance found, the Secretary shall suspend not less than 1 percent of the financial assistance provided by the Department to such institution.''. (b) Retaliation.--Section 485(f) (as amended by subsection (a)) is further amended by adding at the end the following new paragraph: ``(11) No participating institution or other person shall intimidate, threaten, coerce, or otherwise discriminate against any individual for the purpose of interfering with the implementation of any provision of this subsection, or any rights or privileges accorded under this subsection, or because the individual has complained, testified, assisted, or otherwise participated in any aspect of an investigation, proceeding, or hearing.''. (c) Program Participation Agreement Requirements.--Section 487(a)(12) (20 U.S.C. 1094(a)(12)) is amended-- (1) by striking ``and'' at the end of subparagraph (A); (2) by striking the period at the end of subparagraph (B) and inserting ``; and''; and (3) by adding at the end the following new subparagraph: ``(C) the policies and crime statistics disclosed under section 485(f) are comprehensive and accurate.''. (d) Effective Date.--The amendments made by this section shall take effect on September 1, 1998.

Accuracy in Campus Crime Reporting Act of 1997 - Amends the Higher Education Act of 1965 (HEA) to revise campus security policy reporting and crime statistics disclosure requirements. Includes other campus officials (as well as campus security or law enforcement, or local law enforcement) among those officials that must report, for statistical disclosure purposes, if specified types of criminal offenses are reported to them. Specifies additions to the list of such offenses. Makes annual submission of campus crime statistics mandatory for all institutions participating in any student aid program under HEA title IV (participating institutions). (Currently such submissions are only required upon the request of the Secretary of Education). Directs the Secretary to report each set of such statistics, clearly identifying each institution and campus, not only to specified congressional committees but also to each participating institution and to the public via printed and electronic means. Requires each official charged with compiling such statistics to certify their accuracy. Repeals a disclaimer that nothing in certain provisions relating to institutional policy on prevention of sexual assaults and procedures after such an assault may be construed to confer a private right of action upon any person to enforce such provisions. Requires any participating institution which maintains a police or security department to keep a daily log of specified crime information open to public inspection. Requires any participating institution to develop and distribute a statement of its disciplinary practices and procedures with respect to crimes, including specified information and policies. Amends the General Education Provisions Act to exclude allegations of criminal activities from the education records subject to family access. Sets forth methods of enforcement of HEA campus security provisions. Directs the Secretary to terminate all assistance to an institution under an applicable program, or issue other specified orders the Secretary deems appropriate to achieve compliance, if any participating institution fails or refuses to comply with requirements for disclosure of campus security policy and campus crime statistics. Prohibits institutional retaliation against individuals for exercising rights or participating in proceedings under such campus security provisions. Requires, under student aid program agreements, that the campus security policies and crime statistics disclosed be comprehensive and accurate.

p. aeruginosa is one of the causative agents of hospital - acquired infections , especially in burn patients , which is not only due to its high prevalence and severity but also because of its innate and acquired resistance to antibacterial drugs ( 1 ) . carbapenems ( imipenem , meropenem , doripenem and ertapenem ) are classified as -lactam antibiotics . this class of antibiotics has a broad spectrum of activity and is the drug of choice for treatment of serious infections caused by p. aeruginosa . these antibiotics are relatively stable to hydrolysis by most -lactamases ( 2 , 3 ) but metallo--lactamases ( mbl ) , which belong to class b of the structural classification of -lactamases , are able to efficiently hydrolyze all -lactams with the exception of monobactames ( 4 - 6 ) . these enzymes require divalent cations , usually zinc , as metal cofactors for enzyme activity and are inhibited by metal chelators such as ethylenediamine tetra acetic acid ( edta ) ( 7 ) . furthermore , mbls are encoded either by genes that are part of the bacterial chromosome in some bacteria or by heterologous genes acquired by transfer of mobile genetic elements . therefore , acquired mbl can be spread among various strains of bacteria such as p. aeruginosa . the most important types that contribute to epidemiological and clinical studies are the imp - type , vim - type , spm - type and ndm - type enzymes ( 8) . immediate detection of mbl - producing p. aeruginosa is important to prevent the spread of the organism within and between hospitals , and to accurately treatment infections caused by this bacterium . various methods have been suggested for the screening of mbl - producing p. aeruginosa including phenotypic and molecular techniques ( 9 ) . phenotypic methods are based on the ability of metal chelators such as edta to inhibit the enzyme activity . these tests include double disk synergy test ( ddst ) , combined disk ( cd ) assay , the hodge test and e test ( 10 , 11 ) . none of these methods alone can recognize all mbls ; this is probably due to the variability of these enzymes ( 12 ) . molecular techniques including pcr , dna probes , cloning and sequencing are more sensitive and specific for detection of mbls , but they are not routinely available in most clinical laboratories and are technically difficult ( 9 , 12 ) . due to the importance of rapid and precise detection of mbls , in this study we examined the molecular epidemiology of carbapenem - resistant p. aeruginosa isolates in the burn and non - burn patients by the pcr method and detected mbls by two phenotypic tests , including cd and e test and compared the phenotypic test results with that of the pcr method . this investigation was approved by the ethics committee of the ahvaz jundishapur university of medical sciences . during the period from june 2011 to isolates , were collected from teaching hospitals microbiology laboratories ( two general and one burn hospital ) in ahvaz , located in the south west of iran . identification of p. aeruginosa was done using previously described standard phenotypic tests ( 13 ) , and verified by pcr amplification with specific primers for p. aeruginosa gyrb gene ( primer sequence : gyrb - f : 5'- cctgaccatccgtcgccacaac-3 ' , gyrb - r : 5'-cgcagcaggatgccgacgcc-3 ' with product size 222bp ) ( 14 ) . antibiotic susceptibility testing for all the collected samples was done by the kirby - bauer method as recommended by the clinical and laboratory standards institute ( clsi ; 2011 ) ( 15 ) . the following antibiotics were tested : imipenem ( 10 g ) , meropenem ( 10 g ) , doripenem ( 10 g ) , ertapenem ( 10 g ) , ceftazidime ( 30 g ) , cefepime ( 30 g ) , piperacillin ( 100 g ) , piperacillin / tazobactam ( 100/10 g ) , gentamicin ( 10 g ) , amikacin ( 30 g ) , tobramycin ( 10 g ) , ciprofloxacin ( 5 g ) , aztreonam ( 30 g ) , polymyxin b ( 300 units ) , colistin ( 10g ) ( mast group ltd , uk ) . when the isolate was resistant to three or more classes of antipseudomonal agents ( i.e. penicillins / cephalosporins , carbapenems , aminoglycosides and fluoroquinolones ) , that isolate was considered as multidrug resistant ( mdr ) . if more than one agent within a class were used , the isolate was considered resistant to all of the agents ( 16 ) . the minimum inhibitory concentrations ( mics ) of carbapenems ( imipenem [ imi ] , meropenem [ mrp ] , doripenem [ dor ] , and ertapenem [ etp ] ) were obtained by the e - test ( liofilchem , italy ) as described by the manufacturer s instructions . susceptibility and mics breakpoints were defined according to clsi ( 15 ) except for doripenem and ertapenem which were referred to the criteria for imipenem and meropenem because they were not determined by the clsi . p. aeruginosa ptcc 1430 ( atcc 27853 ) and escherichia coli ptcc 1399 ( atcc 25922 ) were used as control strains in all susceptibility assays . for the cd assay , as previously described ( 11 , 17 ) , a bacterial suspension equivalent to 0.5 mcfarland was inoculated onto a muller - hinton s ( mh ) agar ( merck , germany ) plate . two 10 g disks of each carbapenem ( imi , mem , dor and etp ) were initially placed on the mh plates and 10 l of mbl inhibitor solution ( 0.5 m edta ) was added to one of them to obtain the 750 g concentration . after a 24 hour incubation period at 35c , inhibition zone diameter of each disk was measured and compared with each other . if the difference of inhibition zone between carbapenem disk and carbapenem - edta disk was 7 mm , the isolate was considered as a mbl - producer ( 17 ) . mbl e - test ( imipenem ( imi ) [ 4 - 256 g / ml ] and imipenem / edta ( imd ) [ 1 - 64 g / ml ] ) ( liofilchem , italy ) was performed according to the manufacturer s recommendations . briefly , the strips were placed onto mh plates that had been inoculated with a bacterial suspension equivalent to 0.5 mcfarland and incubated at 35c . the test was considered positive when the imi / imd ratio was 8 g / ml . polymerase chain reaction ( pcr ) analysis was performed for blaimp , blavim , blaspm and blandm genes . for blaspm and blandm genes , ( 18 ) ( spm - f : 5'-aaaatctgggtacgcaaacg-3 ' , spm - r : 5'- cattatccgctggaacagg-3 ' with product size of 271 bp and annealing temperature at 59 c ) ( ndm - f : 5'-ggtttggcgatctggttttc , ndm - r : cggaatggctcatcacgatc-3 ' with product size of 621 bp and annealing temperature at 52 c ) and newly primers designed were used for blaimp and blavim genes ( vim - f : 5'- ggtctcattgtccgtgatggtg-3 ' , vim - r : 5'-ggaatctcgctcccctctacct-3 ' with product size of 242 bp and annealing temperature at 60c ) ( imp - f : 5'-tccccacgtatgcatctgaattaac-3 ' , imp - r : 5'-cggactttggccaagcttctatatt-3 ' with product size of 258 bp and annealing temperature at 61c ) . briefly , frozen bacteria were sub cultured onto mueller hinton s agar ( merck , germany ) before dna extraction . one to five bacterial colonies were suspended in 500 l of 1x tris - edta buffer and heated at 95c for 10 minutes and placed at room temperature for 5 minutes . the suspension was then placed at -20c for 10 minutes and after centrifugation at 14,000 rpm for 10 minutes at 4c , 2 l of supernatant was used as the template for a 50 l pcr reaction . the master mixture for detection of all genes consisted of : 5 l of 10x reaction buffer , 2 l of 50 mm mgcl2 , 1 l of 2.5 mm dntps , 2 l of each 20 pmol/l primer , 0.4 l taq polymerase 5 u/l and 35.6 l distilled water . dna was amplified in a mastercycler eppendorf ( eppendorf , germany ) under the following conditions : initial denaturation for 3 minutes at 94c followed by 35 cycles at 94c for 45 seconds , at specific annealing temperature for 45 seconds , then at 72c for 45 seconds . a final extension was performed for 5 minutes at 72c and pcr products were kept at 4c . amplicons were electrophoresed on a 1.5 % agarose gel with 0.5 g / ml ethidium bromide in 1x tris borate edta buffer . gels were visualized and photographed under ultraviolet illumination ( primers were obtained from tag copenhagen a / s , denmark and all chemical materials from cinnagen , iran ) . p. aeruginosa ptcc 1430 ( atcc 27853 ) reference strain was used as the blambl gene s negative control strain . the results were analyzed using the epi info 7 ( cdc , usa ) software for windows . cross tabulation was done and sensitivity ( sn ) , specificity ( sp ) , and positive ( ppv ) and negative predictive values ( npv ) of phenotypic tests were calculated for carbapenem resistant isolates against blambl genes ; pcr was the gold standard . this investigation was approved by the ethics committee of the ahvaz jundishapur university of medical sciences . during the period from june 2011 to isolates , were collected from teaching hospitals microbiology laboratories ( two general and one burn hospital ) in ahvaz , located in the south west of iran . identification of p. aeruginosa was done using previously described standard phenotypic tests ( 13 ) , and verified by pcr amplification with specific primers for p. aeruginosa gyrb gene ( primer sequence : gyrb - f : 5'- cctgaccatccgtcgccacaac-3 ' , gyrb - r : 5'-cgcagcaggatgccgacgcc-3 ' with product size 222bp ) ( 14 ) . antibiotic susceptibility testing for all the collected samples was done by the kirby - bauer method as recommended by the clinical and laboratory standards institute ( clsi ; 2011 ) ( 15 ) . the following antibiotics were tested : imipenem ( 10 g ) , meropenem ( 10 g ) , doripenem ( 10 g ) , ertapenem ( 10 g ) , ceftazidime ( 30 g ) , cefepime ( 30 g ) , piperacillin ( 100 g ) , piperacillin / tazobactam ( 100/10 g ) , gentamicin ( 10 g ) , amikacin ( 30 g ) , tobramycin ( 10 g ) , ciprofloxacin ( 5 g ) , aztreonam ( 30 g ) , polymyxin b ( 300 units ) , colistin ( 10g ) ( mast group ltd , uk ) . when the isolate was resistant to three or more classes of antipseudomonal agents ( i.e. penicillins / cephalosporins , carbapenems , aminoglycosides and fluoroquinolones ) , that isolate was considered as multidrug resistant ( mdr ) . if more than one agent within a class were used , the isolate was considered resistant to all of the agents ( 16 ) . the minimum inhibitory concentrations ( mics ) of carbapenems ( imipenem [ imi ] , meropenem [ mrp ] , doripenem [ dor ] , and ertapenem [ etp ] ) were obtained by the e - test ( liofilchem , italy ) as described by the manufacturer s instructions . susceptibility and mics breakpoints were defined according to clsi ( 15 ) except for doripenem and ertapenem which were referred to the criteria for imipenem and meropenem because they were not determined by the clsi . p. aeruginosa ptcc 1430 ( atcc 27853 ) and escherichia coli ptcc 1399 ( atcc 25922 ) were used as control strains in all susceptibility assays . for the cd assay , as previously described ( 11 , 17 ) , a bacterial suspension equivalent to 0.5 mcfarland was inoculated onto a muller - hinton s ( mh ) agar ( merck , germany ) plate . two 10 g disks of each carbapenem ( imi , mem , dor and etp ) were initially placed on the mh plates and 10 l of mbl inhibitor solution ( 0.5 m edta ) was added to one of them to obtain the 750 g concentration . after a 24 hour incubation period at 35c , inhibition zone diameter of each disk was measured and compared with each other . if the difference of inhibition zone between carbapenem disk and carbapenem - edta disk was 7 mm , the isolate was considered as a mbl - producer ( 17 ) . mbl e - test ( imipenem ( imi ) [ 4 - 256 g / ml ] and imipenem / edta ( imd ) [ 1 - 64 g / ml ] ) ( liofilchem , italy ) was performed according to the manufacturer s recommendations . briefly , the strips were placed onto mh plates that had been inoculated with a bacterial suspension equivalent to 0.5 mcfarland and incubated at 35c . the test was considered positive when the imi / imd ratio was 8 g / ml . for the cd assay , as previously described ( 11 , 17 ) , a bacterial suspension equivalent to 0.5 mcfarland was inoculated onto a muller - hinton s ( mh ) agar ( merck , germany ) plate . two 10 g disks of each carbapenem ( imi , mem , dor and etp ) were initially placed on the mh plates and 10 l of mbl inhibitor solution ( 0.5 m edta ) was added to one of them to obtain the 750 g concentration . after a 24 hour incubation period at 35c , inhibition zone diameter of each disk was measured and compared with each other . if the difference of inhibition zone between carbapenem disk and carbapenem - edta disk was 7 mm , the isolate was considered as a mbl - producer ( 17 ) . mbl e - test ( imipenem ( imi ) [ 4 - 256 g / ml ] and imipenem / edta ( imd ) [ 1 - 64 g / ml ] ) ( liofilchem , italy ) was performed according to the manufacturer s recommendations . briefly , the strips were placed onto mh plates that had been inoculated with a bacterial suspension equivalent to 0.5 mcfarland and incubated at 35c . the test was considered positive when the imi / imd ratio was 8 g / ml . polymerase chain reaction ( pcr ) analysis was performed for blaimp , blavim , blaspm and blandm genes . for blaspm and blandm genes , ( 18 ) ( spm - f : 5'-aaaatctgggtacgcaaacg-3 ' , spm - r : 5'- cattatccgctggaacagg-3 ' with product size of 271 bp and annealing temperature at 59 c ) ( ndm - f : 5'-ggtttggcgatctggttttc , ndm - r : cggaatggctcatcacgatc-3 ' with product size of 621 bp and annealing temperature at 52 c ) and newly primers designed were used for blaimp and blavim genes ( vim - f : 5'- ggtctcattgtccgtgatggtg-3 ' , vim - r : 5'-ggaatctcgctcccctctacct-3 ' with product size of 242 bp and annealing temperature at 60c ) ( imp - f : 5'-tccccacgtatgcatctgaattaac-3 ' , imp - r : 5'-cggactttggccaagcttctatatt-3 ' with product size of 258 bp and annealing temperature at 61c ) . briefly , frozen bacteria were sub cultured onto mueller hinton s agar ( merck , germany ) before dna extraction . one to five bacterial colonies were suspended in 500 l of 1x tris - edta buffer and heated at 95c for 10 minutes and placed at room temperature for 5 minutes . the suspension was then placed at -20c for 10 minutes and after centrifugation at 14,000 rpm for 10 minutes at 4c , 2 l of supernatant was used as the template for a 50 l pcr reaction . the master mixture for detection of all genes consisted of : 5 l of 10x reaction buffer , 2 l of 50 mm mgcl2 , 1 l of 2.5 mm dntps , 2 l of each 20 pmol/l primer , 0.4 l taq polymerase 5 u/l and 35.6 l distilled water . dna was amplified in a mastercycler eppendorf ( eppendorf , germany ) under the following conditions : initial denaturation for 3 minutes at 94c followed by 35 cycles at 94c for 45 seconds , at specific annealing temperature for 45 seconds , then at 72c for 45 seconds . a final extension was performed for 5 minutes at 72c and pcr products were kept at 4c . amplicons were electrophoresed on a 1.5 % agarose gel with 0.5 g / ml ethidium bromide in 1x tris borate edta buffer . gels were visualized and photographed under ultraviolet illumination ( primers were obtained from tag copenhagen a / s , denmark and all chemical materials from cinnagen , iran ) . p. aeruginosa ptcc 1430 ( atcc 27853 ) reference strain was used as the blambl gene s negative control strain . the results were analyzed using the epi info 7 ( cdc , usa ) software for windows . cross tabulation was done and sensitivity ( sn ) , specificity ( sp ) , and positive ( ppv ) and negative predictive values ( npv ) of phenotypic tests were calculated for carbapenem resistant isolates against blambl genes ; pcr was the gold standard . from 226 pseudomonas spp isolates , 223 isolates of p. aeruginosa that had been verified using pcr of the gyrb gene were enrolled in the study . the sources of p. aeruginosa clinical isolates according to specimens and wards are shown in table 1 . among these isolates 131 ( 58.7% ) were resistant to imipenem , 71 ( 31.8% ) to meropenem , 30 ( 13.5% ) to doripenem and 166 ( 74.4% ) to ertapenem , according to the kirby - bauer method . the p. aeruginosa isolates , 99 ( 44.4% ) were mdr from of which 77 ( 34.5% ) and 22 ( 9.9% ) isolates were observed in burn patients and non - burn patients , respectively . overall , 30 ( 13.45% ) isolates were resistant to all of the carbapenems ( imp mic 258 and mrp , dor and etp mic 32 ) and 169 ( 75.8% ) isolates were resistant to carbapenems ( imipenem and/or meropenem and/or doripenem and/or ertapenem ) . the mics of carbapenems were determined by the e - test and the results are shown in table 3 . among the 169 carbapenem resistant isolates , we found that 102 ( 60.4% ) isolates exhibited 7 mm zone diameters by imi disk/750 g edta , 81 ( 47.9% ) isolates by mem disk/750 g edta , 78 ( 46.2% ) isolates by dor disk/750 g edta and 132 ( 78.1% ) isolates by ert disk/750 g edta . all of the imipenem - resistant isolates were mbl e - test positive , except one isolate that showed imi / imd ratio 8 g / ml ( 2.6 g / ml ) and five intermediate imipenem resistant isolates were mbl e - test positive . also , all the imipenem susceptible isolates were mbl e - test negative . amongst carbapenem resistant isolates , 134 ( 79.3% ) isolates were mbl e - test positive . the results of sn , sp , pvp and pvn of phenotypic methods of carbapenem resistant isolates are shown in table 4 . blaimp and blavim genes were detected in 26 ( 11.7% ) and 1 ( 0.4% ) of the isolates , respectively , all of which were carbapenem - resistant ( figure 1 and figure 2 ) . combined disk test and mbl e - test were positive for isolates that harbored blaimp and blavim genes and all of them were mdr . amplified products of blaimp and blavim genes underwent bidirectional sequencing using the abi 3730 xl dna analyzer ( applied biosystems , usa ) . sequences were compared to those of the blaimp and blavim genes by using the information of the blast program from the national center for biotechnology ( www.ncbi.nlm.nih.gov/blast/ ) . the sequencing of the pcr products confirmed the presence of a deference with other blaimp sequences registered in genebank , in one of the blaimp genes positive isolates ( pa111 ) ( accession no . in addition to its high level of resistance to carbapenems , this isolate showed resistance to other tested antibiotics tested ( except colistin and polymyxin b ) . s : sensitive , i : intermediate , r : resistant , n : number of isolates , % : percentage . abbrevitions : sn , sensitivity ; sp ; specificity , ppv ; positive predictive values ; npv ; negative predictive values . lane 4 : positive control ( clinical p. aeruginosa with sequenced blavim gene ) . antibiotic resistance among gram - negative pathogens such as p. aeruginosa is one of the major problems in treating hospitalized patients . in p. aeruginosa , imipenem and meropenem are used routinely for the treatment of nosocomial infections but increasing resistance to these antibiotics , has limited their effectiveness . in our country , doripenem and ertapenem are rarely used , but imipenem and meropenem are being commonly used . during the recent years , the rate of imipenem resistance has been reported to be between 11% to 61% in iran ( 3 , 19 - 23 ) and 12.9% to 38% ( 24 - 28 ) in other parts of the world . in the present study , imipenem resistance was 57.8% , which was within the range of iranian studies but more than other countries . as expected , high resistance to ertapenem was seen ( 74.4% ) ; however , 43 ( 19.3% ) isolates were ertapenem susceptible . even though doripenem is not used in our country , the rate of resistance to this antibiotic was relatively high ( 13.5% ) , but interestingly , doripenem resistant isolates were mostly mbl - producers ( 27/29 ) . doripenem activity correlates with that of meropenem , where both have higher affinity for penicillin binding protein ( pbp ) 2 , pbp3 and pbp4 compared to other pbps in p. aeruginosa . this affinity profile differs from that of imipenem ( 29 ) . in this study , after doripenem , colistin and polymyxin b , meropenem was the most effective antibiotic against p. aeruginosa and it can be said that the use of this antipseudomonal drug is more suitable for treatment of p. aeruginosa infections . multiple phenotypic tests are used for the detection of mbl - producing p. aeruginosa ; in this study we used two of these tests . the sensitivities obtained for the cd test with imi , mem and dor disk/750 g edta and mbl e - test were 100% , yet the result for the cd test with the ert disk/750g edta was less than other carbapenems . also , the specificity of the cd test with all of the carbapenems and the mbl e - test were low . qu et al . reported 100% sn , sp , pvp and pvn for cd assay with imi disk/750 g edta and 85.7% , 100% , 100% and 98.8% for the mbl e - test , respectively ( 11 ) . moreover , pitout et al . reported 96% and 100% sn and 91% and 97% sp for imi and mem disks with 930 g edta / disk , respectively and 96% and 91% for mbl e - test ( 10 ) . our results showed that the dor disk with 750 g edta had the highest specificity yet the other tests did not show a reasonable percentage for specificity . several factors contribute to these differences such as : the difference between various regions strains , the type of materials and antibiotics , the amount of edta/ disk and the errors made by the person performing the tests . however , we recommend using the cd test for detecting mbl - producing p. aeruginosa , since this test is simple to perform , can be easily introduced into the workflow of a clinical laboratory , and is less expensive than the mbl e - test . by pcr , we only detected one isolate harboring blavim and most of the positive isolates for mbl genes were blaimp positive . in a previous study by khosravi and mihani performed on burn patients in ahvaz , 8 ( 19.51% ) isolates were positive for blavim genes , whereas none of the isolates were positive for blaimp genes ( 3 ) . also , bahar et al . ( 19 ) detected 23 ( 12.3% ) blavim positive in burn patients , similar to the khosravi and mihani study ( 3 ) , they did not find any blaimp positive samples . the results of pcr revealed that 18 ( 17.31% ) and 6 ( 5.77% ) imipenem non - susceptible isolates of p. aeruginosa carried blavim and blaimp genes , respectively ( 23 ) . franco et al . reported mbl genes in 30% isolates , 81% of those were blaspm positive and 19% were blaimp positive ( 26 ) . in our study , we did not find any blaspm positive isolates . detected 44.8% ( 13/29 ) mbl producers among 29 isolates resistant to imipenem and/or cefazidime by phenotypic evaluation , amongst which 46.2% ( 6/13 ) were positive for the blaspm-1 gene ( 30 ) . also in the present study , we found an isolate that carried a blaimp gene with different sequence . this isolate must be further evaluated for integron / plasmide structure . in summary , understanding and continuously monitoring the prevalence and resistance mechanisms of carbapenem - resistant p. aeruginosa enables us to formulate appropriate treatment strategies to fight against nosocomial infections .

background : carbapenems are important drugs used for the treatment of pseudomonas aeruginosa infections , however metallo--lactamases ( mbl ) are able to efficiently hydrolyze these classes of drugs . immediate detection of the mbl - producing p. aeruginosa is necessary in order to accurately treat infections caused by this organism.objectives:to determine the prevalence of mbl producing p. aeruginosa in burn and non - burn patients by two phenotypic tests and polymerase chain reaction ( pcr ) and to compare phenotypic tests with pcr.materials and methods : a total of 223 non - duplicate strains of p. aeruginosa were collected from three teaching hospitals of ahvaz , iran . antimicrobial susceptibility and minimum inhibitory concentrations ( mics ) of carbapenems ( imipenem , meropenem , doripenem and ertapenem ) were determined by the kirby - bauer and e - test methods . combined disk ( cd ) test , mbl e - test and pcr were performed for carbapenem - resistant p. aeruginosa isolates.results:amongst all the p. aeruginosa isolates , 58.7% were resistant to imipenem while 31.8% , 13.5% and 74.4% were resistant to meropenem , doripenem and ertapenem , respectively . amongst all the p. aeruginosa isolates , 44.4% were multidrug resistant and 13.45% were resistant to all of the carbapenems . the cd test with doripenem disk / 750 g ethylene diamine tetra acetic acid ( edta ) had the highest efficiency compared to the other phenotypic tests . blaimp and blavim genes were detected in 11.7% and 0.4% of isolates , respectively . blaspm and blandm genes were not observed.conclusions:epidemiological and regional evaluation of mbl - producing p. aeruginosa through simple and inexpensive methods should be considered for effective treatment of carbapenem - resistant p. aeruginosa infections .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Targeted Tax Lien Act of 2010''. SEC. 2. MODIFICATIONS TO LIEN NOTICE FILING PROCEDURES. (a) In General.--Section 6323 of the Internal Revenue Code of 1986 (relating to validity and priority of tax liens against certain persons) is amended by adding at the end the following new subsection: ``(k) Required Procedures Before Filing Notice of Lien.-- ``(1) Secretarial determination.-- ``(A) In general.--The Secretary may not file a notice of lien with respect to any taxpayer unless-- ``(i) the lien attaches to distrainable property, and ``(ii) weighing all facts and circumstances pertaining to the collection of a taxpayer's delinquent tax assessment, the Secretary determines that-- ``(I) the benefit to the Federal Government of the filing outweighs the harm to the taxpayer, and ``(II) the filing will not jeopardize the taxpayer's prospective ability-- ``(aa) to comply with the internal revenue laws, and ``(bb) if the taxpayer is an otherwise viable business taxpayer, to continue to secure funding to maintain business operations. ``(B) Factors to consider.--In making the determination under subparagraph (A)(ii), the Secretary shall consider-- ``(i) the amount due, ``(ii) the lien filing fee, ``(iii) the value of the taxpayer's equity in the property or rights to property, ``(iv) the taxpayer's tax compliance history, ``(v) extenuating circumstances, if any, that explain the delinquency, and ``(vi) the effect of the filing on the taxpayer's ability to obtain financing, generate future income, and pay current and future tax liabilities. ``(2) Taxpayer appeal prior to filing.--The Secretary may not file a notice of lien with respect to any taxpayer unless-- ``(A) the Secretary notifies the taxpayer that the Secretary has determined to file such a notice with respect to the taxpayer, and ``(B) the taxpayer is afforded an opportunity to appeal such determination to the Internal Revenue Service Office of Appeals. The Secretary shall make reasonable efforts to provide the notice under subparagraph (A) by telephone or direct personal contact. ``(3) Supervisory approval required for liens in certain cases.-- ``(A) In general.--In any case to which this paragraph applies, a notice of lien may not be filed unless the immediate supervisor (or such higher level official as the Secretary may designate) of the individual making the initial determination under paragraph (1) has individually reviewed and approved such determination. ``(B) Cases to which paragraph applies.--This paragraph shall apply in any case in which-- ``(i) the collection of the liability would create an economic hardship within the meaning of section 6343(a)(1)(D), ``(ii) the taxpayer has no equity in assets, or ``(iii) there has been no personal contact with the taxpayer to discuss collection alternatives, including an offer in compromise and partial payment installment agreement.''. (b) Effective Date.--The amendment made by this section shall take effect on the date of the enactment of this Act. SEC. 3. MODIFICATION OF REQUIREMENTS RELATING TO TAX LIEN INFORMATION CONTAINED IN CONSUMER CREDIT REPORTS. (a) In General.--Paragraph (3) of section 605(a) of the Fair Credit Reporting Act (15 U.S.C. 1681c(a)(3)) (relating to information contained in consumer reports) is amended to read as follows: ``(3) Tax liens.--The following tax liens: ``(A) Any tax lien released pursuant to section 6325(a) of the Internal Revenue Code of 1986 not more than 2 years after the date that the notice of such lien was filed. ``(B) Any tax lien released pursuant to section 6325(a) of such Code-- ``(i) more than 2 years after the date that the notice of such lien was filed, and ``(ii) more than 2 years before the report. ``(C) Any tax lien if-- ``(i) the notice of such lien was not refiled during the required refiling period (as defined in section 6325(g)(3) of such Code), and ``(ii) such period ends more than 6 years before the report. ``(D) Any tax lien the notice of which is withdrawn pursuant to section 6323(j)(1) of such Code. ``(E) Any tax lien released pursuant to section 6326(b) of such Code if the notice of such lien was erroneously filed.''. (b) Effective Date.--The amendment made by this section shall take effect on the date of the enactment of this Act.

Targeted Tax Lien Act of 2010 - Amends the Internal Revenue Code to require the Secretary of the Treasury to determine, prior to filing a notice of tax lien for unpaid taxes, that: (1) the lien attaches to distrainable property; (2) the benefit to the government of filing such lien outweighs the harm to the taxpayer; and (3) the filing of such lien will not jeopardize the taxpayer's prospective ability to comply with tax laws or an otherwise viable business taxpayer's prospective ability to secure funding to maintain business operations. Amends the Fair Credit Reporting Act to limit the period in which certain released or erroneously filed federal tax liens may be reported on a consumer 's credit report.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Great Lakes Nutrient Removal Assistance Act''. SEC. 2. FINDINGS. Congress finds that-- (1) ineffective wastewater treatment is one of the most common sources of water pollution; (2) nutrient pollution, particularly phosphorus loading, continues to be one of the most significant water quality issues facing the Great Lakes System; (3) limiting phosphorus loads is key to controlling excessive algal growth, and a coordinated Great Lakes System- wide strategy to change how nutrients are discharged is urgent; and (4) nutrient removal technology is one of the most reliable, cost effective, and direct methods for reducing the flow of phosphorus and other harmful nutrients from point sources in the Great Lakes System. SEC. 3. NUTRIENT REMOVAL TECHNOLOGY GRANT PROGRAM. Section 118 of the Federal Water Pollution Control Act (33 U.S.C. 1268) is amended by adding at the end the following new subsection: ``(i) Nutrient Removal Technology Grant Program.-- ``(1) Grant program.-- ``(A) Establishment.--Not later than 1 year after the date of enactment of this subsection, the Administrator shall establish a program within the Environmental Protection Agency to make grants to Great Lakes States, and municipalities thereof, to install, at eligible facilities, nutrient removal technologies that are designed to reduce total nutrients in discharged wastewater. ``(B) Priority.--In making a grant under this subsection, the Administrator shall-- ``(i) consult with the Program Office; and ``(ii) give priority to eligible facilities at which the installation of nutrient removal technologies would-- ``(I) produce the greatest nutrient load reductions at points of discharge; ``(II) result in the greatest environmental benefits to the Great Lakes System; and ``(III) help meet the objectives related to nutrients outlined in Annex 4 of the Great Lakes Water Quality Protocol of 2012. ``(C) Application.--A Great Lakes State, or municipality thereof, may submit to the Administrator an application for a grant under this subsection in such form, and including such information, as the Administrator may prescribe. ``(D) Grant.--If the Administrator approves an application submitted under this subsection, the Administrator may make a grant to the applicant in an amount not to exceed 55 percent of the cost of installing the nutrient removal technologies at the eligible facility with respect to which the application was submitted. ``(2) Definitions.--In this subsection: ``(A) Great lakes water quality protocol of 2012.-- The term `Great Lakes Water Quality Protocol of 2012' means the Great Lakes Water Quality Protocol of 2012, signed at Washington on September 7, 2012 (further amending the Great Lakes Water Quality Agreement). ``(B) Eligible facility.--The term `eligible facility' means a municipal wastewater treatment facility that-- ``(i) as of the date of enactment of this subsection, has a permitted design capacity to treat an annual average of at least 500,000 gallons of wastewater per day; and ``(ii) is located within the Great Lakes System in any of the Great Lakes States. ``(3) Authorization of appropriations.-- ``(A) In general.--In addition to other amounts authorized under this section, there is authorized to be appropriated to carry out this subsection $100,000,000 for each of fiscal years 2016 through 2020. Such sums shall remain available until expended. ``(B) Administrative costs.--The Administrator may use not to exceed 4 percent of any amount made available under subparagraph (A) to pay administrative costs incurred in carrying out this subsection.''.

Great Lakes Nutrient Removal Assistance Act This bill amends the Federal Water Pollution Control Act (commonly known as the Clean Water Act) to require the Environmental Protection Agency (EPA) to establish a program to provide grants to states in the Great Lakes System (i.e., Illinois, Indiana, Michigan, Minnesota, New York, Ohio, Pennsylvania, and Wisconsin) and municipalities in those states to install nutrient removal technologies at a municipal wastewater treatment facility that has a permitted design capacity to treat an annual average of at least 500,000 gallons of wastewater per day. The EPA must give priority to facilities at which nutrient removal technology installations would: (1) produce the greatest nutrient load reductions at points of discharge, (2) result in the greatest environmental benefits to the Great Lakes System, and (3) help meet the objectives related to nutrients outlined in Annex 4 of the 2012 Great Lakes Water Quality Agreement.

the capability to grow nanoscale layers of atoms or molecules on a substrate forms an important part of modern nanotechnology . particles emitted from a source are deposited on the growing surface whose characteristics are determined by parameters such as growth temperature , surface diffusion , bulk relaxation , and particle attachment vs detachment rates . in addition to being clearly relevant for device applications , such surface growth problems also constitute an important class of generic nonequilibrium phenomena @xcite which can not be described in terms of standard equilibrium ensemble theory . a key goal of both theoretical and experimental investigations is the characterization and understanding of the resulting surface morphology , especially in terms of its statistical properties such as spatial and temporal height - height correlations . while local features may play an important role for device performance , large - scale , long - time characteristics offer better opportunities for theoretical understanding . they are often universal , i.e. , independent of microscopic details , depending only on global constraints such as symmetries and conservation laws . here , we will explore the consequences of a _ reduced _ symmetry , which results if the particles arrive under an oblique ( non - normal ) angle . let us briefly review different classes of models for surface growth . the first issue is whether surface overhangs and shadowing effects can be neglected . for models with near - grazing incidence , this is usually a poor approximation . focusing on vapor - deposited thin films , meakin and krug @xcite considered ballistic deposition under these conditions . they found that columnar patterns form which shield parts of the growing surface from incoming particles and characterized these structures in terms of anisotropic scaling exponents , differentiating parallel and transverse directions @xcite . in contrast , for normal or near - normal incidence , overhangs and shadowing can often be neglected , and a description in term of a stochastic equation of motion for a single - valued height variable becomes possible . a second important issue is whether particles , once attached to the surface , can desorb again . if desorption does occur , the surface relaxation is not conserved , and the _ leading _ nonlinearity in the langevin equation is of the kardar - parisi - zhang form @xcite . models of this type are most appropriate for chemical vapor deposition ( see , e.g. , @xcite ) and sputtering processes @xcite . anisotropies have also been included by different authors @xcite . in contrast , desorption can often be neglected in mbe - type processes which occur at low growth temperatures ( see , e.g. , @xcite ) . in this case , the surface relaxation terms in the langevin equation conserve the number of particles . for models of this type , the universal behavior depends on whether the incident beam is normal to the substrate or not . for normal incidence , the system remains isotropic on large scales while oblique incidence generates anisotropies which persist under coarse - graining . while the former case has been investigated extensively ( see , e.g. , @xcite ) , only partial results are available for the latter @xcite . noting that the reduced symmetry generates novel leading nonlinearities suggesting potentially distinct universal behavior , we consider surface growth under oblique incidence more systematically in the following . our analysis begins with a model first suggested by marsili _ _ @xcite to describe mbe - type or ballistic deposition processes with oblique particle incidence . based on a coarse - grained description in terms of a langevin equation , the model adopts an idealized perspective @xcite , neglecting particle desorption and bulk defect formation . as a result , the surface relaxation becomes mass - conserving and can be written as the gradient of a current , in an appropriate reference frame . in contrast , the noise term in the langevin equation is not mass - conserving , since it models the random arrivals of particles . anisotropies emerge naturally in the langevin equation , since the particle beam selects a preferred ( `` parallel '' ) direction in the substrate plane . extending the analysis of @xcite , we explore the consequences of an effective anisotropic surface tension . generated by the interplay of interatomic interactions and kinetic effects , such as schwoebel barriers , it plays a central role for the long - time , long - distance properties of the model . due to the anisotropy , it will generically take different values , denoted @xmath0 and @xmath1 , in the parallel and transverse directions . depending on which of these parameters vanishes first , ripple - like surface instabilities are expected , aligned transverse to the soft direction . this leads to four different regimes with potentially scale - invariant behaviors . we analyze these four regimes , identify the scale - invariant ones , and discuss the associated anisotropic roughness exponents , using techniques from renormalized field theory . the original theory of @xcite is recovered only if both couplings , @xmath0 _ and _ @xmath1 , vanish simultaneously . the paper is organized as follows . we first present the underlying langevin equation for a single - valued height field and briefly review the physical origin of its constituents . we also give a full discussion of its symmetries which are important for the subsequent analysis . we then turn to the renormalization group ( rg ) analysis . identifying a set of effective coupling constants , and exploiting a ward identity following from a ( continuous ) tilt invariance , we compute the naively divergent one - particle irreducible ( 1pi ) vertex functions to one - loop order near the upper critical dimension . we analyze the four different cases separately : ( o ) both @xmath0 and @xmath1 are positive ; ( i ) @xmath0 remains positive while @xmath1 vanishes ; ( ii ) @xmath0 vanishes while @xmath1 remains positive ; and finally , ( iii ) both @xmath0 and @xmath1 vanish simultaneously . a renormalization group equation allows us to derive the scaling properties of correlation and response functions for those cases which possess infrared ( ir ) stable fixed points . we identify a complete set of critical exponents , including _ four different _ roughness exponents for each case . two of these characterize real - space scans along and transverse to the beam direction , and the remaining two are needed to describe scattering ( i.e. momentum space ) data with parallel or transverse momentum transfer . if surface overhangs and shadowing effects are neglected , the surface can be described by a single - valued height field , @xmath2 . here , @xmath3 denotes a @xmath4-dimensional vector in a reference ( substrate ) plane , and @xmath5 denotes time . @xmath6 is measured along the @xmath7-axis which is normal to the substrate plane . the no - overhang assumption can be justified _ a posteriori _ provided the interface roughness exponents are less than unity @xcite . the time evolution of the interface is described by a langevin equation , combining deterministic terms , @xmath8 $ ] , and the effects of randomness , @xmath9 , in the form @xmath10+\eta\label{generic_langevin}%\ ] ] the conserved nature of the ( deterministic ) surface relaxation can be captured by writing @xmath8=\nabla\mathbf{\cdot f}[h]$ ] . several different terms , arising from surface diffusion and the incident flux , contribute to @xmath8 $ ] and are discussed in the following . the incident particle current has a normal component @xmath11 and a component parallel to the substrate plane , @xmath12 . for particles of finite size @xmath13 , the effective flux must be measured at a distance @xmath13 normal to the surface @xcite . since we focus on the long time , large distance characteristics of the growing surface , the corresponding contributions to @xmath8 $ ] can be written as a gradient expansion , neglecting higher order terms : @xmath14=-j_{z}+\mathbf{j}_{\parallel}\cdot\mathbf{\nabla}% h+r_{o}j_{z}\nabla^{2}h - r_{o}\mathbf{j}_{\parallel}\cdot\left ( \mathbf{\nabla } h\right ) \,\nabla^{2}h \label{music}%\ ] ] the first two terms of eq . ( [ music ] ) can be removed by transforming into an appropriate co - moving frame , via @xmath15 . next , we consider the effects of diffusion _ along _ the surface . this restriction generates a _ term , of the form @xcite @xmath16 several comments are in order . first , we note the presence of the term @xmath17 @xmath18 in eq . ( [ music ] ) . similar terms can arise from a step edge ( schwoebel ) barrier @xcite , coming with a negative sign , or a surface tension with a positive sign . this allows for the possibility that the net contribution @xmath18 might vanish , playing the role of a critical parameter . even if we follow @xcite and set it to zero in the bare theory , it is actually generated under rg transformations and therefore intrinsically present . second , the full rotational symmetry within the @xmath4-dimensional space of the substrate is broken by the nonlinear term in eq . ( [ music ] ) . as a consequence , any coarse - graining of the microscopic theory should give rise to different couplings in the parallel and transverse subspaces , and this is in fact borne out under the renormalization group . if the full anisotropy is incorporated into the theory , restricting rotational invariance to the @xmath19-dimensional _ transverse _ subspace , the langevin equation ( [ generic_langevin ] ) takes the form @xmath20 after some minor renamings . here , @xmath21 ( @xmath22 denotes derivatives ( gradients ) in the parallel ( transverse ) subspaces . it should be noted that the nonlinearity has also been split into two distinct terms , with couplings @xmath23 and @xmath24 . the langevin noise @xmath25 models the random particle aggregation at the surface , with zero average and second moment @xmath26 in principle , one could also incorporate a noise term of the form @xmath27 generated by ( conserved ) particle diffusion . in comparison to the aggregation noise , this contribution turns out to be irrelevant . however , one could imagine situations where diffusion is extremely fast , and aggregation occurs only very infrequently , so that eq . ( [ noise_correl ] ) should be replaced by its diffusive counterpart . this `` conserved '' ideal mbe @xcite is not considered here , and will be left for future study . ( [ full_problem ] ) can be written in terms of surface currents @xmath28 and @xmath29 , according to @xmath30 with @xmath31 eq . ( [ full_problem ] ) , or its equivalent form , eq . ( [ currents ] ) , is the starting point for the field - theoretic analysis . its behavior is determined by the leading terms in the gradient expansion . we can gain some qualitative insight by considering the linear terms first . to ensure stability of the homogeneous phase , the coupling constants @xmath32 and @xmath33 must be positive , and the cross - coupling @xmath34 may not exceed @xmath35 . the two couplings @xmath36 and @xmath37 play the role of critical parameters . if both are positive , the nonlinearities become irrelevant , and the problem reduces to the ( gaussian ) edwards - wilkinson equation @xcite . in contrast , if one or both of them vanish , the surface develops characteristic spatial structures . these take the form of ripples ( reminiscent of corrugated roofing ) , if only one of the two couplings goes through zero ; if both couplings become negative , the surface develops mounds or `` wedding cakes '' @xcite . focusing only on the onset of these instabilities , four different cases emerge which are discussed systematically in the following section : ( o ) the linear theory @xmath38 , @xmath39 ; ( i ) a line of continuous transitions @xmath38 , @xmath40 ; ( ii ) a line of _ possibly first _ order transitions @xmath41 , @xmath39 ; and ( iii ) the multicritical ( critical end- ) point @xmath41 , @xmath40 . the qualitative phase diagram is shown in fig . ( [ phdia ] ) . ew denotes the edwards wilkinson region . the line labelled @xmath42 marks a line of ( possibly ) discontinuous transitions , and line @xmath43 corresponds to continuous transitions , both to inhomogeneous structures . the dashed lines denote very qualitative transition linesn between different structures , and mcr labels the multicritical point . , width=283 ] to unify the discussion , we first recast the langevin equation ( [ currents ] ) as a dynamic field theory . in this formulation , all statistical averages are expressed as path integrals , with weight @xmath44 . in order to treat correlation and response functions in an analogous manner , it is convenient to introduce a response field @xmath45 , and formulate the dynamic response functional , following standard methods @xcite : @xmath46=\gamma\int d^{d}x \ , dt \big\ { \tilde{h}\big [ \gamma^{-1}\partial_{t}h+\partial_{\parallel}j_{\parallel}+\nabla_{\perp } \mathbf{j}_{\perp}\big ] -\tilde{h}^{2}\big\ } \ , . \label{def_j}%\ ] ] before we turn to any computational details , we argue that the model is renormalizable . in other words , in each loop order we need to add only those primitive counterterms which can be absorbed in a renormalization of the fields and the coupling constants . as a first step in this procedure , we consider the symmetries exhibited by ( [ def_j ] ) since they place constraints on possible counterterms . the invariance against a shift of coordinates in the @xmath7-direction leads to the symmetry @xmath47 . hence , the surface height @xmath6 arises in the functional only in form of derivatives . second , the functional is invariant under tilts of the surface by an infinitesimal `` angle '' @xmath48 , i.e. , @xmath49 provided the tilt is accompanied by an appropriate change of the parameters , namely , @xmath50 and @xmath51 . further , particle conservation on the surface lead to the invariance transformation @xmath52 , @xmath53 . therefore , we have a @xmath54-dimensional ( infinitesimal ) symmetry group @xmath55 which does not change the form of the dynamic functional or the functional integration measure , provided it is accompanied by an appropriate transformation of the parameters @xmath36 and @xmath37 . in addition , we have a discrete symmetry , namely , inversion invariance in the @xmath56 subspace:@xmath57 finally , of course , we have isotropy in the transverse subspace . these symmetries can be considered as the fundamental defining elements of ideal mbe processes . the renormalizability of our model can now be argued , following standard methods @xcite . in each loop order , the successive construction of the perturbation series produces only _ primitive _ ultraviolet ( uv ) divergences , provided that all counterterms constructed in lower orders are included to cancel _ non - primitive _ divergences which appear in subdiagrams . if the regularization procedure respects the symmetries of the model , then the remaining primitive divergences also preserve the symmetries . thus , these divergences have the same form as the relevant terms of the initial model and their counterterms can be absorbed in a renormalization of the initial parameters . this presumes , of course , that all relevant interaction terms ( i.e. , composite fields with coupling constants of positive naive dimension ) with the correct symmetries have been included in the initial dynamic functional , and all irrelevant couplings have been omitted . with regards to our model , a straightforward analysis of the relevant diagrams shows that we have indeed captured all relevant terms in the original langevin equation ( [ full_problem ] ) . hence , the model is renormalizable . in this section , we assemble the basic components of the perturbative analysis , leaving technical details to the appendix . we first write the dynamic functional , @xmath58 $ ] as the sum of two parts . $ ] contains the gaussian terms of the theory , @xmath60 & = & \gamma\int d^{d}x \ , dt \big\ { \tilde { h}\bigl ( \gamma^{-1}\partial_{t}+\mu_{\parallel}\partial_{\parallel}^{4}% + \mu_{\perp}(\nabla_{\perp}^{2})^{2 } \nonumber \\ & + & 2\mu_{\times}\partial_{\parallel}% ^{2}\nabla_{\bot}^{2}-\tau_{\parallel}\partial_{\parallel}^{2}-\tau_{\perp } \nabla_{\bot}^{2}\bigr ) h-\tilde{h}^{2}\big\ } \label{def_j_0}%\end{aligned}\ ] ] while @xmath61 $ ] takes the nonlinear interactions into account:@xmath62=-\gamma\int d^{d}x \ , dt\ \tilde{h}% \,(\partial_{\parallel}h)\,\bigl ( \lambda_{\parallel}\partial_{\parallel}% ^{2}h+\lambda_{\perp}\nabla_{\perp}^{2}h\bigr ) \label{def_j_int}%\ ] ] arbitrary correlation and response functions can now be computed as functional averages with statistical weight @xmath58 $ ] : @xmath63\mathcal{d}[\tilde{h}]\circ \mathrm{e}^{-\mathcal{j}[\tilde{h},h]}\ , . \nonumber\end{aligned}\ ] ] due to the anisotropy , it is possible to rescale parallel and transverse lengths independently . considering a simple rescaling of _ parallel _ lengths first , via @xmath64 , the functional remains invariant provided @xmath65 , @xmath66 and @xmath67 , @xmath68 , @xmath69 while @xmath70 and @xmath71 likewise , if only _ _ transverse__lengths are rescaled , via @xmath72 , the functional remains invariant provided @xmath73 , @xmath74 and @xmath75 , @xmath76 , @xmath77 while @xmath78 and @xmath79 . in addition , there is an overall length scale @xmath80 which accounts for the dimension of fields and coupling constants under the renormalization group . when we consider the three different cases below , these scale invariances will allow us to define appropriate effective expansion parameters , in order to eliminate redundant couplings @xcite . our goal is to compute the green functions @xmath81^{n}[\tilde{h}]^{\tilde{n}}\rangle^{\mathrm{cum}}$ ] , i.e. , the cumulant averages of all possible products of fields @xmath82 , @xmath83 , or equivalently , the associated one - particle irreducible ( 1pi ) vertex functions , @xmath84 , with @xmath85 ( @xmath86 ) @xmath6 ( @xmath87- ) amputated legs , order by order in a diagrammatic perturbation expansion . the notation @xmath88 is short - hand for the full space- and time - dependence of these functions . as a first step in this process , we collect the elements of perturbation theory and introduce their graphic representation . using @xmath89 to denote averages taken with the ( gaussian ) weight @xmath90 , we will need the bare propagator , @xmath91 as well as the bare correlator , @xmath92 both in spatial fourier space . in the following , we write @xmath93 as short - hand for @xmath94 . defining @xmath95 we find@xmath96 here the heaviside function @xmath97 is defined with @xmath98 . diagrammatically , these two functions are represented as lines : [ diagram_propagators]@xmath99 turning to the interaction terms , it is convenient to rewrite them in a symmetrized form . in fourier space , the expression for the three - point vertex reads @xmath100 \big\ } \,\label{full_vertices}%\end{aligned}\ ] ] with @xmath101 . our sign convention is such that all momenta attached to a vertex are incoming . diagrammatically , the whole vertex is represented as @xmath102 returning to eqs . ( [ def_j_0 ] ) and ( [ def_j_int ] ) , we now perform dimensional analysis . in the ( infrared ) limit of small momenta and frequencies , the gaussian part of the dynamic functional is dominated by different terms , depending on the behavior of the control parameters @xmath36 and @xmath37 . _ case _ ( o ) . if both @xmath36 and @xmath37 are finite and positive , the theory turns out to be purely gaussian . quartic derivatives can be neglected in the infrared limit ; as a result , @xmath103 simplifies to @xmath104 . since both parallel and transverse momenta appear only quadratically here , it is natural to choose a momentum scale @xmath105 such that @xmath106 , and @xmath107 . time @xmath108 scales as @xmath109 , and the fields have dimensions @xmath110 and @xmath111 . the nonlinear couplings scale as @xmath112 and are therefore irrelevant in any dimension @xmath113 . the resulting theory is a simple anisotropic generalization of the edwards - wilkinson equation @xcite , @xmath114 the anisotropies in the quadratic terms affect only nonuniversal amplitudes and can be removed by a simple rescaling , without losing any information of interest . as is well known , the two - point correlation function scales as @xmath115 from which one immediately reads off the ( isotropic ) roughness exponent @xmath116 and the dynamic exponent @xmath117 . for a detailed discussion see @xcite . since this case is so familiar , we will not consider it any further . ( i ) . if @xmath36 remains finite and positive but @xmath37 is infinitesimal , the two leading terms in the dynamic functional are @xmath118 and @xmath119 . hence , even in the gaussian theory , parallel and transverse momenta already scale differently , reflected in the choice @xmath120 and @xmath121 . if we introduce an anisotropic scaling exponent @xmath122 via @xmath123 , we recognize that @xmath124 at the tree level . continuing with the two leading terms , we note @xmath125 , and set @xmath126 via a transverse rescaling with an appropriate @xmath127 . time scales as @xmath128 , and @xmath32 @xmath129 are both irrelevant . the only strongly relevant parameter of the theory is @xmath130 . introducing the effective dimension @xmath131 , one finds @xmath132 and @xmath133 . for the nonlinear couplings , we obtain @xmath134 and @xmath135 . since @xmath136 is clearly positive , the coupling @xmath23 becomes irrelevant . the upper critical dimension @xmath137 for the theory is determined by @xmath24 , via @xmath138 which leads to @xmath139 . the invariant dimensionless effective expansion parameter is @xmath140 as shown by the rescaling @xmath141 , @xmath142 . the resulting propagators are controlled by @xmath143 where the @xmath144-term determines the uv behavior and @xmath1 plays the role of the ir cutoff . at the tree level , this case corresponds to a critical line parameterized by @xmath36 . _ case _ ( ii ) . here , @xmath37 remains finite while @xmath36 vanishes . the gaussian part of the functional is dominated by @xmath145 and @xmath146 . again , parallel and transverse momenta scale differently , but their roles are now reversed : @xmath147 and @xmath148 , with @xmath124 at the tree level . both @xmath149and @xmath37 scale as @xmath150 , while @xmath151 and @xmath34 are irrelevant . defining the effective dimension as @xmath152 , one still has @xmath153 and @xmath154 ; we also recover @xmath155 . now , however , the strongly relevant perturbation is @xmath156 . the two nonlinearities switch roles so that @xmath157 and @xmath158 . clearly , @xmath24 is irrelevant in all dimensions while @xmath23 becomes marginal at the upper critical dimension @xmath159 . the invariant dimensionless effective expansion parameter follows from the rescalings as @xmath160 . the momentum dependence of the propagators simplifies to @xmath161 . as in the previous case , at the tree level this situation corresponds to a critical line parametrized by @xmath37 . however , we will see below that the order of the transition may well become first order once fluctuations are included . _ case _ ( iii ) . finally , we consider the multicritical point where both @xmath37 and @xmath36 vanish . both momenta scale identically , as @xmath162 , so that @xmath163 at the tree level again , we may set @xmath126 . one obtains @xmath164 @xmath128 , @xmath165 , and @xmath153 , @xmath166 , with @xmath167 . the full propagators come into play . both nonlinear couplings , @xmath23 and @xmath24 , have the same upper critical dimension @xmath168 . the effective expansion parameters are @xmath169 , @xmath170 , and @xmath171 . in this case , the anisotropy exponent @xmath122 vanishes at the tree level . in the following , we analyze the three nontrivial cases in a one - loop approximation , using dimensional regularization combined with minimal subtraction @xcite . the essential components are the 1pi vertex functions @xmath172 . focusing on the ultraviolet singularities , only those @xmath173 with positive engineering dimension are to be considered . taking into account the symmetries and the momentum - dependence carried by the derivatives on the external legs , the set of naively divergent vertex functions is reduced to @xmath174 and @xmath175 . specifically , at the upper critical dimension of cases ( ii ) and ( iii ) , @xmath174 is quadratically divergent and @xmath175 is marginal . in case ( i ) , @xmath174 is already marginal after accounting for the external momenta . in this section , we summarize the calculation of @xmath174 and @xmath175 , to one loop order . details are relegated to the appendix . the main features which recur in all three cases are the following . if @xmath174 is quadratically divergent , this divergence is first removed by an additive renormalization , i.e. , a shift of the critical parameter(s ) . specifically , the true critical point is located through the singularity of the parallel and/or transverse static susceptibilities , @xmath176 and @xmath177 , defined by @xmath178 we find that nontrivial shifts are only required for cases ( ii ) and ( iii ) , and only for @xmath36 . the remaining logarithmic divergences are then computed using dimensional regularization , so that ultraviolet divergences appear as simple poles in @xmath179 . in a minimal subtraction scheme , we focus exclusively on these poles and their amplitudes . since the nonlinearities are cubic in the field , the expansion is organized in powers of @xmath180 , @xmath181 , and @xmath182 ; i.e. , the first correction to the tree level is always _ quadratic _ for @xmath174 and _ cubic _ for @xmath175 . the tilt invariance leads to a ward identity connecting @xmath174 and @xmath175 , namely , [ ward_identity]@xmath183 here , @xmath184 and @xmath185 denote the momenta and frequencies labelled with subscripts @xmath43 and @xmath186 in eq . ( [ full_vertices ] ) . by virtue of this symmetry , it will be sufficient to compute @xmath174 in order to extract the renormalization of _ all parameters _ , including those of the coupling constants @xmath187 and @xmath24 . more specifically , the tilt transformation @xmath188 , @xmath189 , @xmath190 shows that the parameter @xmath48 renormalizes as the field @xmath6 itself . hence , the term @xmath191 renormalizes exactly like @xmath36 , and @xmath192 like @xmath37 . next , we collect a few general properties of the diagrams contributing to @xmath193 which follow from the special form of the interactions , eq . ( [ def_j_int ] ) . we first consider diagrams where the external @xmath6-leg carries two transverse derivatives . such diagrams can arise only from the interaction @xmath194 . thanks to particle conservation , all these graphs sum in such a way as to generate at least one spatial derivative on the external @xmath87-leg . moreover , either parallel inversion or transverse rotation symmetry guarantees that , in fact , there are at least two such derivatives . thus , there are no corrections to the term @xmath195 in @xmath90 , eq . ( [ def_j_0 ] ) . similarly , since external @xmath87- and @xmath6-legs always come with at least one spatial derivative , there are no perturbative contributions to the terms @xmath196 and @xmath197 . hence , these three terms are not renormalized . further , if the coupling constant @xmath24 is zero , as in case ( ii ) , only diagrams with parallel derivatives on all legs are generated , and so operators carrying no parallel , or mixed parallel and transverse , derivatives suffer no renormalization . in contrast , when @xmath198 , there is no such simplification since this vertex can contribute to purely `` parallel '' terms . if both coupling constants @xmath187 and @xmath24 are nonzero , they mix under the rg , and we have to renormalize the couplings by matrices , rather than simple multiplicative factors . with these considerations in mind , we propose the following renormalization scheme : @xmath199 @xmath200 accounts for the shift of the critical point in cases ( ii ) and ( iii ) . the ward identities then lead to the renormalizations @xmath201 the five renormalization factors @xmath202 , @xmath203 , @xmath204 , @xmath205 , and @xmath206 must be calculated from the @xmath207-poles of the dimensionally regularized perturbation series of @xmath208 in minimal subtraction , they are of the form @xmath209 , @xmath210 , where the @xmath211 and @xmath212 are expansions in the renormalized effective coupling constants . here , the subscript @xmath213 stands as a placeholder for any member of the set of indices . the individual characteristics of the three cases of interest are now treated sequentially . ( i ) : @xmath40 and @xmath214 . this is the simplest non - trivial case . only one parameter , @xmath37 , needs to be tuned to access criticality . since @xmath187 is irrelevant , it may be set to zero . neglecting all other irrelevant terms as well , the functional simplifies to @xmath215 h-\tilde{h}% ^{2}-\lambda_{\perp}\tilde{h}(\partial_{\parallel}h)\nabla_{\perp}^{2}h\big\}\ ] ] in this case @xmath216 . all divergences are parameterized by @xmath179 where @xmath139 . following standard methods ( for details see [ parfiniteperpvanish ] ) , we obtain the following expression for the singular part of the two - point vertex function , @xmath217 + \gamma\frac{u^{2}}{8\varepsilon}\big [ 2\tau_{\parallel}q_{\parallel}^{2}-(\mathbf{q}_{\bot}^{2})^{2}\big ] + o(u^{4 } ) \label{gamma11_i}%\ ] ] where @xmath218 is the effective expansion parameter . @xmath219 is a geometric factor which appears in all integrals : @xmath220 and @xmath221 is the surface area of the @xmath4-dimensional unit sphere . the renormalized vertex function @xmath174 is defined by demanding that @xmath222 be pole - free . one finds @xmath223 the corresponding wilson functions are defined as the logarithmic derivatives of the associated @xmath202-factors , at constant bare quantities , i.e. , @xmath224 . the logarithmic derivatives of the control parameters and of the relaxation coefficient are then given by [ def_zetas]@xmath225 the flow of the dimensionless effective coupling constant @xmath226 under renormalization is controlled by the gell - mann low function , @xmath227 \ , . \label{beta_u_i}%\ ] ] the renormalizability of the theory demands that all the wilson functions be free of @xmath207-poles ; moreover , in minimal subtraction it can be shown @xcite that the perturbative corrections do not contain @xmath207 any more . it is easy to demonstrate that all wilson functions are determined by the first term , @xmath228 , in the laurent expansion of the @xmath202-factors . so , we obtain @xmath229 \ , . \label{beta_i}%\end{aligned}\ ] ] the renormalization group equation ( rge ) for the green functions simply states that the bare theory is independent of the external momentum scale @xmath105 : @xmath230 explicitly , this partial differential equation becomes @xmath231 g_{n,\tilde{n}}% = 0\ , . \label{rge_i}%\ ] ] it will lead to asymptotic scaling , provided @xmath232 possesses an infrared stable fixed point @xmath233 , i.e. , a solution of @xmath234 with @xmath235 . to one loop order , eq . ( [ beta_i ] ) allows for a single fixed point with the desired properties , namely , @xmath236 where the sign is determined by the sign of the initial coupling constant @xmath24 . clearly , this @xmath233 is non - zero in the @xmath237-expansion . under the ( reasonable ) assumption that the full ( resummed ) series for @xmath238 is non - zero at the integer values of @xmath207 corresponding to physical dimensions , eq . ( [ beta_u_i ] ) gives us the exact relation @xmath239 in the following , wilson @xmath240-functions , evaluated at the fixed point , will simply be denoted by a superscript @xmath241 . the solution of the rge ( [ rge_i ] ) is easily found by applying the method of characteristics . at the stable fixed point @xmath233 we obtain the scaling solution @xmath242 where @xmath243 is an arbitrary flow parameter . the parallel and transverse scale invariances , together with dimensional analysis , give us an additional scaling relation for the green functions , namely @xmath244 combining these two relations , choosing @xmath245 and recalling @xmath246 , we arrive at the final scaling form for the green functions . suppressing unneeded arguments , we can choose to write them in the form @xmath247 where the scaling exponents @xmath122 and @xmath9 can be expressed in terms of wilson functions , evaluated at the fixed point : @xmath248 since we have only two independent renormalizations , the remaining exponents follow from scaling laws , namely , @xmath249 and @xmath250 eq . ( [ exact_i ] ) , provided it holds , can be exploited to give another exponent identity : @xmath251 to conclude , only a _ exponent , e.g. , @xmath9 has to be computed order by order in perturbation theory . then , all others follow from exponent identities which are exact , at least within perturbation theory . our one - loop calculation results in @xmath252 _ case _ ( ii ) : @xmath41 and @xmath253 . this is the second non - trivial case . neglecting irrelevant terms , the dynamic response functional simplifies to @xmath46=\gamma\int d^{d}x\ , dt\ \big\ { \tilde{h}\big [ \gamma^{-1}\partial_{t}+\mu_{\parallel}\partial_{\parallel}^{4}-\tau _ { \parallel}\partial_{\parallel}^{2}-\tau_{\perp}\nabla_{\perp}^{2}\big ] h-\tilde{h}^{2}-\lambda_{\parallel}\tilde{h}(\partial_{\parallel}% h)\partial_{\parallel}^{2}h\big\}\ ] ] in this case , we define @xmath179 with @xmath159 . since @xmath193 is quadratically divergent in this case , an additive renormalization of the critical parameter , @xmath254 , is required ( see [ parvanishperpfinite ] ) . once this is accounted for , we obtain the following one - loop expression for the singular part of @xmath174 : @xmath255 where @xmath226 is the effective expansion parameter now defined as @xmath256 with a geometric factor @xmath257 eq . ( [ eq : gamma11_ii ] ) gives rise to renormalizations of @xmath32 and @xmath36 . since the vertex @xmath258 carries only parallel momenta in this case , there are no contributions of order @xmath259 at any order , implying the absence of field renormalizations . hence , @xmath260 . the remaining poles are absorbed into the renormalization factors @xmath261 defining the gell - mann low function of @xmath226 , as well as the wilson functions , in analogy to the previous case , we obtain @xmath262 \,=u\big [ -\varepsilon-\frac{1}{8}u^{2}+o(u^{4})\big ] \nonumber\end{aligned}\ ] ] the fixed point equation @xmath234 does not yield a stable real fixed point , at least to this order in perturbation theory . it remains an open question whether such a fixed point , and the associated scaling properties , might emerge at higher orders . restricting ourselves to our current results , the absence of an infrared stable fixed point might suggest a first order transition . a more detailed analysis of the underlying mean - field theory or a careful computational study would be required to shed more light on this issue . both are beyond the scope of this article . _ case _ ( iii ) : @xmath41 and @xmath263 . finally , we turn to the analysis of the multicritical point . this situation was previously considered in @xcite , using a momentum shell decimation scheme . this procedure requires considerable care for field theories with strong anisotropy and nonlinearities carrying multiple derivatives , since the corrections depend on the way in which the hard momentum cutoff is implemented . moreover , the hard momentum shell cutoff introduces long - ranged correlations on the scale of the cutoff momentum which must be handled very carefully . whatever the source of the discrepancies , even after meticulous checks we were unable to reproduce the earlier results . the full functional , eqs . ( [ def_j_0 ] ) and ( [ def_j_int ] ) , as well as the full ( bare ) propagators and correlators , eq . ( [ def_bare_props ] ) , now come into play . to ensure the stability of the critical theory at the tree level , we demand @xmath264 . this limits the physical range of @xmath32 and @xmath34 to @xmath265 and @xmath266 . to complicate matters further , both nonlinear couplings , @xmath23 and @xmath24 , are marginal at the upper critical dimension @xmath168 . however we know that , thanks to the ward identity , all renormalizations can still be obtained from the two - point function , @xmath174 . a first analysis of diagrams contributing to @xmath193 shows that two of them are quadratically divergent . since both of them carry a momentum prefactor of @xmath267 , they can be absorbed in an additive renormalization , i.e .. , a shift of the bare control parameter @xmath268 , as remarked before . no shift of the bare @xmath269 is needed . leaving details to [ parvanishperpvanish ] , our one - loop result for @xmath174 is now considerably more complex , thanks to the presence of both vertices . in order to eliminate redundant parameters , it is again convenient to define invariant dimensionless coupling constants , guided by the parallel and transverse rescalings : [ effective_couplings_caseiii]@xmath270 where the constant @xmath271 is defined by @xmath272 the definition of the effective coupling constants contains a suitable @xmath273-dependent denominator , which is common to all integrals . collecting the results from [ parvanishperpvanish ] , we find the singular parts @xmath274 \nonumber\\ & -&\gamma\mu_{\parallel}^{1/2}q_{\parallel}^{2}\biggl [ u_{\vert}^{2}\big ( \frac{b_{1}}{\varepsilon}\mu_{\parallel}^{-1/2}\tau_{\parallel}+\frac{b_{1}% } { \varepsilon}\tau_{\perp}\big ) + u_{\bot}^{2}\big ( \frac{b_{2}}{\varepsilon } \mu_{\parallel}^{-1/2}\tau_{\parallel}+\frac{b_{3}}{\varepsilon}\tau_{\perp } \big ) \biggr ] \nonumber\\ & - & \gamma\mu_{\parallel}q_{\parallel}^{4}\big [ u_{\vert}^{2}\frac{c_{1}% } { \varepsilon}+u_{\bot}^{2}\frac{c_{2}}{\varepsilon}\big ] -\gamma ( \mathbf{q}_{\bot}^{2})^{2}u_{\bot}^{2}\frac{a_{1}}{\varepsilon}% \label{gamma11_iii}\\ & - & \gamma\mu_{\parallel}^{1/2}q_{\parallel}^{2}\mathbf{q}_{\bot}^{2}\big [ u_{\vert}^{2}\frac{d_{1}}{\varepsilon}+u_{\bot}^{2}\frac{d_{2}}{\varepsilon } + u_{\vert}u_{\bot}\frac{d_{3}}{\varepsilon}\big ] \,.\nonumber\end{aligned}\ ] ] here , @xmath275 , @xmath276 , ... , @xmath277 are @xmath273-dependent functions whose explicit forms are listed in [ parvanishperpvanish ] . according to the general renormalization scheme , eq . ( [ gen_ren_scheme ] ) , the full set of five renormalization factors now comes into play . at one loop order , we read off [ zfactors_caseiii_a]@xmath278 here , @xmath279 is short - hand for the two - loop corrections which are of fourth order in the couplings @xmath280 and @xmath281 . defining @xmath282 , @xmath283 as before , one obtains to one loop order @xmath284 we now consider the gell - mann low functions for the three dimensionless effective couplings @xmath280 , @xmath281 , and @xmath273 : [ beta_iiia ] @xmath285 we seek a set of fixed points @xmath286 such that all three @xmath127-functions vanish simultaneously . the eigenvalues of the linearized system , evaluated in the vicinity of each fixed point , provide information about its stability . if all of them are positive , the fixed point is infrared stable ; otherwise , it is unstable in one or more directions . there is only one nontrivial , physical ( i.e. , real ) infrared stable fixed point given by @xmath287 for @xmath288 , we find another root @xmath289 , but this solution must be excluded since it leads to a linearly unstable theory ( see the discussion after eq . ( [ currents ] ) ) . there are numerous fixed points with @xmath290 and @xmath291 , but these are all infrared unstable or nonphysical , in the sense that either @xmath292 or @xmath293 are imaginary or @xmath294 . in contrast to earlier results by @xcite , we do not find a physically viable fixed point with @xmath290 . we have also carefully considered the possibility of `` degenerate fixed points '' with @xmath295 or @xmath296 ; none of these are stable . returning briefly to eq . ( [ gamma11_iii ] ) , we note that the critical parameter @xmath36 appears only in the combination @xmath297 , which is actually the appropriate scale - invariant form . this suggests a slight modification of the general renormalization scheme , eq . ( [ gen_ren_scheme ] ) , so that the renormalizations of the critical control parameters are now written as @xmath298 their derivatives can be expressed in terms of the @xmath240-functions of eq . ( [ zeta_iii]):@xmath299 one can see quite easily that @xmath288 is an invariant subspace of the rg , since the coupling @xmath280 alone can not generate any corrections to @xmath293 . assuming that the stable fixed point , at higher orders of perturbation theory , remains characterized by @xmath300 , @xmath301 , while @xmath288 , we can establish the ( exact ) relations @xmath302 which will lead to exponent identities , as we shall presently see . at the fixed point , the rge takes the simplified form @xmath303 g_{n,\tilde{n}}=0\ , . \label{rge_iii}%\ ] ] the two critical control parameters @xmath304 are diagonalized by introducing the new independent variables @xmath305 , defined by @xmath306 this new critical control parameter @xmath307 takes over the role of @xmath36 in the mean - field approximation . the solution of the rge ( [ rge_iii ] ) is given by @xmath308 where @xmath243 is an arbitrary scale , and @xmath309 results from @xmath310 after the variable transformation to @xmath311 . combining this equation with the simple parallel and transverse scale invariances , we arrive at the scaling form [ g - scal_iii]@xmath312 where @xmath313 is again given by eq . ( [ deltann ] ) while the other exponents take the values @xmath314 the result to all orders , eq . ( [ exakt_iii ] ) , leads to an exact relation between @xmath122 and @xmath315 : @xmath316 once again , only a single exponent must be computed _ explicitly _ within the @xmath207-expansion , e.g. , @xmath122 . our one - loop calculation yields @xmath317 and for the mixing of the critical control parameters @xmath318 let us briefly return to the assumption that the stable fixed point is characterized by @xmath319 . thanks to eq . ( [ beta_iii ] ) and the associated linear stability matrix , we can determine the stability criterion , i.e. , the correction - to - scaling exponent of @xmath320 , to all orders in perturbation theory . the condition for @xmath319 to be stable is @xmath321 which generates bounds for the critical exponents @xmath122 and @xmath315 , namely,@xmath322 if the stability condition @xmath321 or equivalently , the second bound of eq . ( [ bdg-1 ] ) , is violated at some dimension @xmath4 , the fixed point structure of the theory changes fundamentally . now @xmath323 is stable , and eq . ( [ beta_iii ] ) gives us the ( exact ) relations @xmath324 instead of eqs . ( [ exakt_iii ] ) . we lose one condition , and this leads to two independent critical exponents , as opposed to a single one . following the same analysis as before , we arrive at the relations [ exp_iii - unst]@xmath325 the scaling behavior of the green functions still follows eq . ( [ g_iii ] ) , but @xmath326 can no longer be related to @xmath122 . the roughness exponents of the surface are easily identified , once the scaling properties of the underlying field theory are known . for isotropic theories , they can be read off directly from the height - height correlation function , @xmath327 if its asymptotic scaling behavior of can be written in the form @xmath328 here , @xmath329 denotes the roughness exponent and @xmath7 the dynamic exponent of the surface while @xmath330 is a universal scaling function . similarly , in fourier space , the behavior of @xmath331 translates into @xmath332 with the same roughness exponent @xmath329 . in our case , the situation is slightly more subtle @xcite , due to the presence of strong anisotropy @xcite . first of all , surface fluctuations along the parallel and the transverse directions in real space need not be controlled by the same indices , leading us to define two exponents , @xmath177 and @xmath176 , via @xmath333 a similar situation should be expected in fourier space , prompting us to define two additional exponents , @xmath334 and @xmath335 , via [ aniso_ms_scaling]@xmath336 of course , all of these expressions are only meaningful if the four scaling functions @xmath337 , @xmath338 , @xmath339 and @xmath340 approach finite and non - zero constants when their arguments vanish . generically , the four roughness exponents take different numerical values ; however , they can all be expressed in terms of the exponents @xmath122 and @xmath9 , according to the identities @xmath341 \quad \quad \chi_{\vert}=\frac{1}{2}\bigl [ 4-\left ( d+\delta\right ) -\eta\bigr]/ ( 1+\delta ) \label{chi_rs } \nonumber \\ \tilde{\chi}_{\bot}=\frac{1}{2}\bigl [ 4-d-\eta\bigr ] \qquad \qquad \,\,\ , \tilde { \chi}_{\vert}=\frac{1}{2}\bigl [ 4-\eta\bigr]/ ( 1+\delta ) - \frac{d}{2 } \label{chi_ms}%\end{aligned}\ ] ] the key observation is that @xmath342 only if the anisotropy exponent @xmath122 vanishes . in the following , we explicitly compute the roughness exponents for the two cases ( i ) and ( iii ) . for case ( ii ) , the renormalization group gives us no such information , since that would require the existence of an infrared stable fixed point . if , in fact , the presence of a first order transition line were to be confirmed eventually , the whole concept of scaling exponents would be inapplicable here . ( i ) for this theory , characterized by positive @xmath36 while @xmath37 vanishes , we found that all exponents could be expressed in terms of @xmath343 . writing all four roughness exponents in terms of this single index , we arrive at expressions which are exact to all orders in @xmath344 : @xmath345 the mean - field values are easily recovered by setting @xmath346 . the physically most interesting case corresponds to a surface grown on a two - dimensional substrate , i.e. , @xmath347 and @xmath348 . for this situation , one obtains @xmath349 and @xmath350 while @xmath351 and @xmath352 . remarkably , the exponent @xmath349 is actually _ exact _ , at least to all orders in perturbation theory . _ case _ ( iii ) : at the multicritical point one has @xmath353 , @xmath354 , and a nontrivial @xmath122 . hence , one obtains @xmath355/2 \quad \quad \chi_{\vert}=\frac{4-\left ( d+\delta\right)}{2(1+\delta ) } \label{chi_rs3 } \nonumber \\ \tilde{\chi}_{\bot}=\bigl [ 4-d\bigr]/2 \qquad \qquad \,\,\ , \tilde { \chi}_{\vert}= \frac{2}{(1+\delta ) } - \frac{d}{2 } \label{chi_ms3}%\end{aligned}\ ] ] all of them are negative near the upper critical dimension @xmath168 . in order to access the physical ( @xmath347 ) situation , one has to set @xmath356 here which gives a huge anisotropy exponent , @xmath357 , if one naively uses the one - loop results . while roughness exponents can in principle be calculated , it does not appear meaningful to compare them to experimental data . yet , we emphasize again that the exponents calculated here do not agree with @xcite . to summarize , we have analyzed the effect of strong anisotropies on the universal behavior of a surface grown under ideal mbe - type conditions . the anisotropy is generated by an incident particle beam which is tilted away from the normal . this arrangement manifestly breaks rotational invariance in the substrate plane . as a consequence , the effective surface tension becomes anisotropic , being characterized by two parameters , @xmath36 and @xmath37 , as opposed to a single one in the isotropic case . if both are positive , the surface is described by the edwards - wilkinson model . however , as temperature or other growth parameters are varied , the two control parameters need not vanish simultaneously , leading to different dynamic and spatial instabilities and ordered structures . clearly , there are three distinct scenarios : ( i ) @xmath38 while @xmath37 goes to zero , ( ii)@xmath358 while @xmath37 remains positive , and ( iii ) both parameters vanish . each of these three cases is described by its own characteristic field theory with distinct upper critical dimensions : @xmath359 , @xmath360 , and @xmath361 for cases ( i ) , ( ii ) , and ( iii ) , respectively . to display scale - invariant behavior in the long - time , large - distance limit , a field theory must possess one , or more , infrared stable fixed points . our one - loop analysis reveals that only cases ( i ) and ( iii ) have this property . in contrast , case ( ii ) may correspond to a line of first - order phase transition whose characteristics lie outside the scope of our rg techniques . for the two scale - invariant theories , we find two distinct , novel surface universality classes , and derive the associated scaling behavior of the height - height correlation function . an intriguing feature of both universality classes is the emergence of a strong anisotropy exponent , which reflects different scaling behavior in the parallel and transverse directions . as an immediate consequence , we need to introduce four different roughness exponents , to characterize surface fluctuations in real and momentum space , observed along the parallel vs the transverse directions . while all four are related by exponent identities , care must nevertheless be exercised when analyzing experimental data . we conclude with a few comments on the phase diagram . the first case clearly corresponds to a second order line , parameterized by @xmath36 . assuming that the first order nature of the second case , parameterized by @xmath37 , can be confirmed , the third case @xmath362 would turn out to be a critical endpoint . since it requires the tuning of two parameters , it may be quite difficult to access in a typical experiment . in contrast , either the second or the first order lines should be more easily observable . from an rg perspective , even if the @xmath363 term is absent initially , it is immediately generated under rg transformations , leading to a non - zero critical value of @xmath36 ; this is not the case for the @xmath364 contribution . for this reason , we believe that the most physically relevant theory ( beyond edwards - wilkinson behavior ) is the one with @xmath38 and @xmath365 . our key results for this model are the roughness exponents for real - space surface scans . for a two - dimensional surface embedded in a three - dimensional space , we find @xmath349 for scans along the transverse direction , and @xmath350 for parallel scans . there appears to be some experimental evidence for these exponents @xcite but more data are needed before this issue can be settled . we thank u.c . tuber , r.k.p . zia , j. krug , a. hartmann , and e. yewande for helpful discussions . this work is partially supported by the nsf through dmr-0308548 and dmr-0414122 . gp acknowledges the alexander von humboldt foundation for their support . in the following , some technical details of the above calculations are presented . we prefer the time - momentum representation of the propagators and correlators , since it displays the causal structure of the feynman diagrams most directly . in this representation , each @xmath174- ( or self energy ) diagram has a single @xmath87-leg at the outgoing vertex with the largest time argument , and a single @xmath6-leg at the incoming vertex with the smallest time argument . to find the uv divergent @xmath366 contribution , we just integrate over the time difference of these two vertices to characterize the theory fully , it suffices to calculate the vertex function @xmath174 . the only one loop diagram which must be evaluated is @xmath369[1cm]{1.6cm}{\psarc ( 0.8,0){0.55}{0}{360}% \psarc{<-}(0.8,0){0.55}{270}{0}% \psline{<-}(0,0)(0.25,0 ) \psline ( 1.35,0)(1.6,0 ) } + \dots \label{one_loop_gamma11_tauperp0}%\ ] ] using the diagrammatic building blocks associated with eqs . ( [ def_bare_props ] ) and ( [ full_vertices ] ) . this graph represents the one loop contribution to the self - energy . after integrating over the time difference of the two vertices , it takes the form @xmath370[1 cm]{2cm}{\psarc ( 0.8,0){0.55}{0}{360}\psarc{<- } ( 0.8,0){0.55}% { 270}{0}\psline{<-}(0,0)(0.25,0)\psline ( 1.35,0)(1.6,0)}=-\gamma\lambda _ { \bot}^{2}\int\frac{d^{d}p}{(2\pi)^{d}}\frac{\bigl [ -(\mathbf{q}_{\bot}% ^{2})^{2}p_{\vert}^{2}+2\mathbf{q}_{\bot}^{2}(\mathbf{q}_{\bot}\cdot \mathbf{p}_{\bot})p_{\vert}^{2}+q_{\vert}^{2}(\mathbf{p}_{\bot}^{2})^{2}% \bigr ] } { \gamma(\mathbf{p})\left [ \gamma(\mathbf{p})+\gamma ( \mathbf{q}-\mathbf{p})\right ] \,.}\label{integral1_case_tperp0}%\ ] ] several finite terms have been dropped , following a dimensional regularization and minimal subtraction scheme . the function @xmath371 contains , up to a factor @xmath372 , the full momentum dependence of the inverse propagator @xmath373 dimensional analysis immediately suggests that the terms in the bracket of eq . ( [ integral1_case_tperp0 ] ) diverge logarithmically , except possibly the term @xmath374 , which is , at least naively , linearly divergent . the denominator in eq . ( [ integral1_case_tperp0 ] ) is now expanded in small external momenta , and multiplied with the numerator , keeping only divergent contributions . after some straightforward algebra , we arrive at @xmath375 \label{int}\ ] ] the integrals @xmath376 are defined as @xmath377 with the proportionality indicating the degree of divergence based on simple power counting in @xmath378 . clearly , all integrals appearing in eq . ( [ int ] ) are only logarithmically divergent ; the ( naive ) linear divergence vanishes by symmetry . using the effective coupling @xmath226 introduced in eq . ( [ def_u_i ] ) , the integrals are @xmath379 and one finally arrives at eq . ( [ gamma11_i ] ) . the diagrammatic representation of @xmath174 , to one loop , is again given by eq . ( [ one_loop_gamma11_tauperp0 ] ) . however , the relevant interaction vertex here is @xmath23 , so that the one loop integral reads @xmath382 } \label{gamma11_integral1_case_tpar0}%\ ] ] and the momentum dependence of the inverse bare propagator is controlled by @xmath383 as in the previous section , the integral ( [ gamma11_integral1_case_tpar0 ] ) can not be performed in closed form . again , we expand the denominator of eq . ( [ gamma11_integral1_case_tpar0 ] ) in powers of @xmath384 and @xmath385 , noting that higher orders become more and more convergent . keeping only divergent terms , the singular part of @xmath174 takes the form @xmath386 -\gamma \lambda_{\vert}^{2}q_{\vert}^{2}\int\frac{d^{d}p}{(2\pi)^{d}}\frac{p_{\vert } ^{4}}{2\gamma(\mathbf{p})^{2}}\\ & -\gamma\lambda_{\parallel}^{2}q_{\parallel}^{4}\int\frac{d^{d}p}{(2\pi ) ^{d}}\left\ { \frac{p_{\vert}^{2}}{2\gamma(\mathbf{p})^{2}}-\frac{7\mu _ { \parallel}p_{\vert}^{6}}{2\gamma(\mathbf{p})^{3}}+\frac{4\mu_{\parallel}% ^{2}p_{\vert}^{10}}{2\gamma(\mathbf{p})^{4}}+\dots\right\ } + o(\lambda _ { \parallel}^{4})\ .\nonumber\end{aligned}\ ] ] the leading singularity , i.e. , the first integral above , is found to be quadratically divergent . it contributes to the renormalization of @xmath36 and can therefore be controlled by an _ additive _ renormalization . we shift the critical parameter by an amount @xmath387 , defined through the vanishing of the parallel susceptibility , eq . ( [ susc ] ) . evaluating @xmath176 to first order yields @xmath388 the general renormalization scheme , eq . ( [ gen_ren_scheme ] ) , then allows us to determine @xmath389 in one loop . reparameterizing @xmath174 in terms of the shifted @xmath0 subsequently removes the quadratic divergence and leaves us with logarithmic divergences only . hence , the vertex function reads , to first order , @xmath390\end{aligned}\ ] ] with the integrals @xmath391 defined by @xmath392 again , the proportionality indicates the degree of divergence based on @xmath393 . using the effective coupling @xmath226 introduced in eq . ( [ effective_coupl_case_tpar0 ] ) , the integrals can be evaluated : @xmath394 which finally results in eq . ( [ eq : gamma11_ii ] ) . the calculation of the self energy follows the same standard methods as above . however , the technical details become more involved , for two reasons . first , the full momentum dependence of the inverse propagator , @xmath395 comes into play , with the two critical parameters , @xmath37 and @xmath36 , serving as infrared cutoffs . second , both nonlinearities , parametrized by @xmath23 and @xmath24 , are now marginal at the upper critical dimension @xmath168 . as before , we start with the diagrammatic representation , eq . ( [ one_loop_gamma11_tauperp0 ] ) . due to the presence of the full vertex , eq . ( [ full_vertices ] ) , the one - loop integral is given by @xmath396 } % \ ] ] where @xmath397 summarizes the momenta contributed by the vertices:@xmath398 \left [ \mathbf{q}_{\bot}^{2}p_{\vert}-q_{\vert}\mathbf{p}% _ { \bot}^{2}\right ] \right\ } \\ & + & \lambda_{\vert}\lambda_{\bot}q_{\vert}\left ( q_{\vert}-p_{\vert}\right ) p_{\vert}\left [ 2(\mathbf{q}_{\bot}\cdot\mathbf{p}_{\bot})p_{\vert } -2\mathbf{q}_{\bot}^{2}p_{\vert}\right]\end{aligned}\ ] ] as for case ( ii ) , a shift of the critical parameter @xmath36 absorbs a quadratic divergence in @xmath174 . demanding that the inverse ( parallel ) susceptibility , eq . ( [ susc ] ) vanishes at the true critical point , one finds in one loop order @xmath399 again , we retain only logarithmic divergences in @xmath174 if we reparameterize it in terms of a shifted @xmath400 . expanding the denominator to @xmath401 results in a sum of integrals of the form @xmath402 formally , these look like eq . ( [ integral_iii ] ) , but it is essential to realize that @xmath371 takes the more complicated form ( [ prop_iii ] ) . to evaluate the @xmath376 , it is convenient to introduce a new integration variable , @xmath403 , to replace @xmath384 . this has the significant advantage that all @xmath207-poles are already explicitly displayed , once the @xmath385-integration has been performed . the remaining integrals over @xmath404 can be evaluated at @xmath346 and are perfectly straightforward . they take the form @xmath405 with @xmath406 . clearly , these @xmath407 s lead to @xmath273-dependent coefficients for the different contributions to @xmath174 . the result is summarized in eq . ( [ gamma11_iii ] ) with the @xmath273-dependent functions [ parameter_integrals_caseiii]@xmath408 tallying up all the contributions to @xmath174 , and removing the divergences by renormalization , one arrives at the @xmath202-factors listed in eq . ( [ z_iii ] ) . leamy , g.h . gilmer , and a.g . dirks , in _ current topics in materials science _ , vol . 6 , edited by e. kaldis ( north - holland , amsterdam,1980 ) mazor , j. srolovitz , p.s . hagan , and b.g . bukiet , phys . lett . * 60 * , 424 ( 1988 ) ; m. marsili , a. maritan , f. toigo , and j.r . banavar , rev . phys . * 68 * , 963 ( 1996 ) w.w . mullins , solid surface morphologies governed by capillarity . in : _ metal surfaces : structure , energetics and kinetics _ , edited by n.a . gjostein and w.d . robertson ( metals park , ohio : american society of metals 1963 ) h.k . janssen , z. phys . b * 23 * , 377 ( 1976 ) ; r. bausch , h.k . janssen , and h. wagner , z. phys . b * 24 * , 113 ( 1976 ) ; h.k . janssen , in _ dynamical critical phenomena and related topics _ ( _ lecture notes in physics _ , vol . 104 ) , edited by c.p . enz , ( springer , heidelberg , 1979 ) f.j . wegner , in _ phase transitions and critical phenomena _ , vol . 6 , eds . c. domb and m.s . green ( academic press , new york , 1976 ) b. schmittmann , gunnar pruessner , and h.k . janssen , to be submitted to physical review b ( 2006 ) . this is analogous to the scaling of driven diffusive systems and lifshitz points . see , e.g. , b. schmittmann and r.k.p . zia , in _ phase transitions and critical phenomena _ , vol . 17 , eds . c. domb and j.l . lebowitz ( academic press , new york 1995 ) .

using renormalized field theory , we examine the dynamics of a growing surface , driven by an obliquely incident particle beam . its projection on the reference ( substrate ) plane selects a `` parallel '' direction , so that the evolution equation for the surface height becomes anisotropic . the phase diagram of the model is controlled by the properties of an effective anisotropic surface tension . our renormalization group analysis suggests the existence of a line of continuous transitions and a line of ( potentially ) first - order transitions , which meet at a multicritical point . the full scaling behavior for the continuous line and the multicritical point is discussed in detail . two novel universality classes for scale - invariant surface fluctuations are found .

the high energy frontier will soon be explored by four detector experiments recording the results of collisions of the large hadron collider ( lhc)located at the european center for nuclear research ( cern ) in geneva , switzerland . designed to record , identify , and study the higgs boson and a wide array of potential new physics signatures as well as @xmath0 mesons and quark - gluon plasma , these experiments ultimately hope to observe an inconsistency between nature and the standard model ( sm ) of high energy physics . however , since the typical production and detection probabilities for interesting processes are eleven orders of magnitude smaller than that of uninteresting sm backgrounds , these experiments must sift through forty million events per second while the lhc is colliding beams , recording roughly one in two hundred thousand events in order to accommodate bandwidth constraints . the resultant 1 to 2 petabytes ( pb ) of monthly data must then be processed and analyzed offline into a form which is suitable for extraction of measurements . the unprecedented scale of the required computing resources and the complexity of the computing challenges have made computing an important element of hep . each lhc experiment has deployed its own `` computing model '' ( cm ) , which consists of several classes ( `` tiers '' ) of facilities which together comprise a grid of resources held bound by fast links and special middleware . in atlas experiment , the tier-0 facility at cern will perform the first - pass processing of the data . the ten national tier-1 facilities will reprocess these data with better calibrations within two months after data collection . meanwhile , the roughly thirty tier-2 facilities placed at specific universities and labs will focus on simulations and data analysis . in addition , considerable effort is directed towards development of : * monte carlo tools ( which link theory and experiment ) , * detector simulation frameworks , * algorithmic and statistical analysis tools , * data processing frameworks and algorithms , * grid middleware , * data production and management systems , and * underlying data persistency and database infrastructure . ultimately the performance of these software components , many of which are used by multiple experiments , determines the scale of computing resources required by hep experiments . despite the impressive scale of the lhc computing grid and the sophistication of underlying software technologies , a dearth of computing resources will be one of the primary bottlenecks in extracting measurements from lhc data . for example , figure [ fig : cm ] shows the percentage of atlas tier 2 resources required in 2010 for fast and full simulation production as function of the fraction of recorded data . the atlas cm model expects that physics analysis activity will require roughly half of the resources at atlas tier 2s , leaving the other half for simulation . but we see that the allocating the nominal 50% of tier 2 resources to simulation limits the volume of fully simulated data to roughly 20% of the data the atlas detector will collect . this deficiency will fundamentally limit the significance of the comparisons between recorded data and theoretical predictions ( via detailed detector modeling ) which are necessary to make any statements about nature . therefore atlas must rely on less accurate fast simulations to produce monte carlo statistics comparable to the recorded data . and if data needs to be resimulated , as is often the case in the first years of an experiment , cpu resources must be borrowed from analysis activity , thereby stalling extraction of measurements . in addition , the experiment cms do not typically provide physicists the necessary resources for the cpu - intensive activities which in the past decade have come to characterize analyses of hep data at the tevatron and the @xmath0 factories . these activities include sophisticated fits , statistical analysis of large `` toy '' monte carlo models , matrix element calculations , and use of the latest discriminant techniques , such as boosted decision trees . physicists must therefore rely on leveraged resources and emerging technologies to accomplish such tasks . in tandem with these developing needs in high - energy physics , the role of computing in both business and everyday life has evolved significantly . in the early 1990s , the html protocol was developed in the context allowing the hundreds of collaborating physicists in hep experiments at cern to communicate with their global group of colleagues . this development was crucial to the later transformation of the internet from an academic tool to a global medium . today , computing is seen as a commodity , and a critical component of the world economy . major companies like google and amazon manage huge data centers and sell cpu cycles , disk , and bandwidth by the minute and megabyte . regular innovations in data processing , delivery , organization , and communication continuously drive significant business and social progress . figure [ fig : googletrends ] compares the google search volume for `` grid computing '' with technologies such as solid - state drives ( ssds ) , general purpose graphics processing units ( gpgpu ) , virtualization , and cloud computing . we see that while hep has been building large and expensive grid sites along with the necessary grid software , virtualization and cloud computing have developed a wider appeal . fortunately , efforts to take advantage of these technologies have recently begun in hep . virtualization is likely to help address problems in hep computing that can be traced back to the fact that hep experiment software generally require specific operating systems ( os ) and are typically difficult to install . virtualization provides a means of providing single file ( ie a virtual hard drive image ) which can be pre - packaged with all necessary software , including the os , and can run on any modern `` host '' machine regardless of the host hardware and os . the first benefit of virtualization is that average physicists can simply download such an file and then instantly be able to use their experiment s software on their personal computer without a great deal of expertise . the cernvm @xcite effort have been particularily successful in this area . similarly system administrators can use virtualization to simplify deployment of the complicated set of software packages required by grid sites . this route is particularly attractive for tier 3 sites that do not necessary have a full - time system administrator . but perhaps the most promissing application of virtualization is in the area of oppertunistic computing where idle desktop computers ( for example , in university offices , class - rooms , and labs ) , can be used to assist data simluation . the appeal of cloud computing is the promise of on - demand access to vast computing resources hosted by companies that can provide attractive pricing due to the economy of scale . so , for example , a hep experiment can short - term lease huge cpu resources for data simulation . it is noteworthy that cloud computing has an implicit reliance on virtualization for delivering the appropriate software environment to the cloud resource . at this point , it is not clear that such cloud computing is appropriate for hep . current cloud computing offerings such as amazon s ec2 are targeted for web - hosting rather than large data processing tasks and therefore offer prohibitive pricing and performance for hep applications . what s more , the large cloud computing providers such as amazon and microsoft favor their own proprietry software solutions that lock their clients to their cloud and have avoided open efforts such the `` open cloud manifesto '' by ibm . in addition some in the industry view the clound computing vision as an unrealistic `` myth '' . nonetheless , many within the hep community are exploring the potential of hep computing . for example nimbus now provides a means of turning amazon ec2 resources into a self - configuring cluster for hep computing . a very promising technology , that is now becoming cost - effective , is ssd . because these storage devices have no mechanical or moving parts , they provide impressive input / output ( i / o ) rates , in particular huge gains in random read access in comparison to traditional hard drives ( hd ) . two high i / o hep applications that can benefit from ssds immediately come to mind . first is ntuple data analysis , a task that is typically characterized by rapid iterations over upto terabytes of data . the second is in computing sites where hundreds of processes running on multiple cores access data stored on a single storage device . since ssds present the same interface as hds , their deployment in hep environments is rather easy . the primarly limitation is then the additional cost of the ssds , which we may expect to lead to ssd / hd hybrid solutions where hds are used for long - term storage and data is prestaged to ssds for faster access . we may also note that while hep has traditionally interpreted moore s law as predicting faster processors , the industry has shifted to more cores per processor . thus we find that though many hep applications in principle lend themselves to parallelization , very few existing hep software were fundamentally designed with parallel processing on multiple cores in mind . recently , the omnipresence of dual and quad - core processors has prompted some parallelization efforts within the hep community . these efforts take advantage of the embarrassingly parallel nature of hep computations by simply running multiple instances ( or threads ) of the software . the only challenge then is sharing memory across these parallel threads in applications that have a large memory footprint such as simulation and reconstruction . assuming that memory cost is nt a factor , the problem then becomes the processor to memory bandwidth which can be saturated when a large number of cores access large amount of memory . this bandwidth limitation constrains performance gain when scaling to large number of cores per processor . as a result , most hep multi - core optimization efforts are concentrated on processing forking and thread safety . while central processing units ( cpus ) have been evolving towards more cores , graphics processing units ( gpus ) that were originally targeted to the personal computer gaming enthusiasts have evolved to be capable of computing traditionally performed on the cpu . these modern processors that are also now present in many desktops and computers are known as the general purpose graphical processor units ( gpgpus ) . despite that fact that for specific computing tasks , these gpgpus can marshall thousands of simplified processing units in parallel in order to reduce computing times by orders of magnitude , they have yet to capture the attention of hep as a whole . a very simple study of read / write rates of root @xcite analyses illustrates the potential of ssds and gpgpus on the data analysis iteration rate . for this study , we consider two simple root applications , one which creates an ntuple ( ttree ) with random data ( simple types such as bools , ints , floats , and vectors of simple types ) , and another that reads histograms all quantities in these ntuples . we find that simple read / write rates stablilize with about 20 variables of each type per event ( 3 kb / event ) and 600 events . table [ fig : ssdhd ] summarizes the results of the study . with root s data compression turned off , a single instance of each application achieve approximately 25 mb / s read or write rate on a hard drive which provide 70 mb / sec sequential read . with compression turned on ( providing 30% file size reduction ) , this figure falls to 4 and 16 mb / s read and write , respectively , illustrating that ( de)compression is the main bottleneck in input / output bound root analyses . ideally , the gpu can be used to eliminate this bottleneck . in order to observe the benefits of the fast random access of ssds , we ran eight instances of these applications with the data stored on a single hd or ssd . we also observe that only uncompressed data writing appears to be limited by disk access . and though ssds generally provide faster rates , the improvement is significantly less where the i / o is limited by ( de)compression . [ cols="<,^,^,^,^ " , ] [ fig : ssdhd ] from the cell processor in the playstation 3 ( ps3 ) to in newer - generation graphic processing units ( gpus ) used in desktop and laptop computers , we find the building blocks for high - performance computing ( hpc ) systems already present in devices we daily use . originally driven by the gaming industry , gpu architectures have recently been developed to also support general - purpose computing . these gpus offer impressive power consumption / performance and price / performance ratios . the omnipresence of these general purpose gpus have pushed industry leaders such as microsoft and apple into a race to develop strategies that take advantage their capabilities . the raw computational horsepower of gpus is staggering . a single modern gpus provides nearly one tflops ( @xmath1 floating - point operations per second ) @xcite , roughly 20 times more than a typical multi - core cpu . what s more , the trend over the past decade exhibits an exponential growth in the ratio of the computational power of gpu to cpu . while use of computer graphics hardware for general - purpose computation has been an area of active research for many years ( eg @xcite , @xcite @xcite ) , the wide deployment of gpus in the last several years has resulted in an increase in experimental research with graphics hardware . some notable work include password cracking @xcite , artificial neural networks @xcite , solving partial differential equations ( pdes ) @xcite , line integral convolution and lagrangian - eulerian advection @xcite , and protein folding ( folding@home ) @xcite . in hep , the developers of the fairroot demonstrated a two orders of magnitude acceleration of track fitting in high multiplicity environments using gpus @xcite . currently , the primary players in the gpu arena are nvidia and amd ( through the purchase of ati ) . nearly all of nvidia s gpus , from the low - end laptop gpu to the professional tesla line , can be programmed using their compute unified device architecture ( cuda ) , a parallel programming compiler and software environment designed for issuing and managing general purpose computations on the gpu through extensions to the standard c language . there are also standard numerical libraries for fft ( fast fourier transform ) and blas ( basic linear algebra subroutines ) . ati / amd has also developed a proprietary gpgpu hardware and software known as data parallel virtual machine ( dpvm ) . however , their focus seems to now shifted to open computing language ( opencl ) , a gpu software standard originally developed by apple and then released to an open consortium which includes all the relevant companies as signatories @xcite . the primary appeal of opencl is it s architecture independence which is achieved through run - time compilation of computing software kernels . the first publicly available implementation of opencl was recently released last week as part of apple s snow leopard operating system . other , less popular , gpu architectures and software include clearspeed @xcite , brookgpu @xcite , amd stream computing , and sh @xcite . finally , a very promising upcoming product is intel s larabee , a x86-based many - core gpu which is rumored to be release later this year . the processing model for gpu is very different than cpu . whereas cpus are optimized for low latency , gpus are optimized for high throughput . gpus are essentially stream processors , hardware that operates in parallel by running a single computation on many records in a stream at once . the limitation is that each parallel computation may only process independent memory elements that can not share memory with others . the result is that gpus are generally suitable for computations that exhibit specific characteristics . they must be compute intensive with large number of arithmetic operations per i / o or global memory reference . they must be amiable to data parallelism , where the same function is applied to all records of an input stream and a number of records can be processed simultaneously without waiting for results from previous records . and they must exhibit data locality , a specific type of temporal locality common in signal and media processing applications , where data is produced once , read once or twice later in the application , and never read again . hep applications that are good candidates for gpgpu acceleration include monte carlo integration for matrix element methods , discriminant training or calculation in multivariate analysis , maximum - likelihood fitting , compression / decompression during data input / output , event generation , full or fast detector simulation , event reconstruction ( in particular for the high level trigger ) , and detector alignment . the difficulty with employing gpgpus is that existing applications can not be simply rebuilt to run on gpgpus , but must rather treat the gpu as a co - processor . the software must explicitly adopt a data - parallel processing model where the data is broken into chunks and independently processed by algorithms which are highly constrained in both their memory access and complexity . a practical approach of gpgpu accelerating existing applications is to rewrite computational bottlenecks to prepare the data on the cpu , transfer it to the gpu memory , execute the computation on the gpu , and then transfer the results back . even modest acceleration of detector simulation and reconstruction using gpgpu will have a significant impact on hep computing . for reconstruction , where thousands of tracks and hundreds of thousands calorimeter cells must be processed , any gain directly translates to higher trigger output . for simulation , where thousands of particles must be propagated through detector and magnetic fields , gains translate into fewer computing resource requirements . the practical time - scale for deployment of such gpgpu accelerated strategies is for lhc upgrade . while strategies for gpgpu acceleration of tracking and calorimetry are rather straight - forward , the complexity of geant4 @xcite and the fact that it was nt written with parallelization in mind , make simulation a much more difficult problem . taking full advantage of gpgpus in simulation will likely only be possible in the next generation software ( perhaps geant5 ) one promising interim strategy is to employ multiple parallel geant4 threads running on the cpu ( see geant4 parallelization efforts of @xcite ) that offload specific calculations ( eg magnetic field extrapolation ) to a service that can batch perform the calculation using the gpu .

while in the early 90s high energy physics ( hep ) lead the computing industry by establishing the http protocol and the first web - servers , the long time - scale for planning and building modern hep experiments has resulted in a generally slow adoption of emerging computing technologies which rapidly become commonplace in business and other scientific fields . i will overview some of the fundamental computing problems in hep computing and then present the current state and future potential of employing new computing technologies in addressing these problems .

Both men get tagged “moderate,” but for different reasons. Mr. Romney is a technocrat, a business leader who focuses on getting the job done. As governor, that meant governing in a way that suited Massachusetts. Today the job is winning the presidency, and if that means “evolving” in his views as the primary electorate swings further right, and running away from his signature accomplishment as governor, so be it. You’d think that even if they don’t like it, those on the extremes would respect the fact that those of us in the sensible center decide general elections — and seek out a candidate who appeals to us. But the unhealthy demand for ideological purity obscures a hopeful fact about the GOP presidential field: There are actually two sensible, experienced grownups. And while Mr. Romney is far more appealing than any of the other choices, former Utah Gov. Jon Huntsman is more principled, has a far more impressive resume and offers a significantly more important message. AFTER MONTHS of flirting with candidates who considered inexperience an asset, obstinance and vitriol a virtue and extremism — even flakiness — a job requirement, Republican voters seem to be settling down. Increasingly, they are rallying around a grownup who has impressive experience as a chief executive, in and out of government, and a history of making things work rather than pursuing ideological fetishes. Yet nearly two-thirds of Republican primary voters still reject Mitt Romney, and his opponents are convinced they can raise that number by screaming: “Moderate! Moderate! Moderate!” Mr. Huntsman is a true conservative, with a record and platform of bold economic reform straight out of the free-market bible, but he’s a realist, whose goal is likewise to get things done. Under his leadership, Utah led the nation in job creation, and the Pew Center on the States ranked it the best-managed state in the nation. He also is head and shoulders above the field on foreign policy. He served as President George H.W. Bush’s U.S. ambassador to Singapore and President George W. Bush’s deputy U.S. trade representative and U.S. trade ambassador, and the next entry on that resume is even more impressive: He was a popular and successful governor in an extremely conservative state, well positioned to become a leading 2012 presidential contender, when Mr. Obama asked him to serve in arguably our nation’s most important diplomatic post, U.S. ambassador to China. It could be political suicide, but he didn’t hesitate. As he told our editorial board: “When the president asks you to serve, you serve.” We don’t agree with all of Mr. Huntsman’s positions; for but one example, he championed one of the nation’s biggest private-school voucher programs. And with George Will calling him the most conservative candidate and The Wall Street Journal editorial page endorsing his tax plan, independent voters might find less to like about his positions than, say, Mr. Romney’s or Newt Gingrich’s. What makes him attractive are the essential values that drive his candidacy: honor and old-fashioned decency and pragmatism. As he made clear Wednesday to a room packed full of USC students on the first stop of his “Country First” tour, his goal is to rebuild trust in government, and that means abandoning the invective and reestablishing the political center. Don’t expect him to engage in meaningless hyperbole or apologize for his occasional moderate positions. As he explained recently: “We have to draw from ideas that are doable and not so outlandishly stupid that they create a lot of political infighting and finger-pointing and never, ever in a thousand years are going to get done.” And don’t expect him to spout ridiculous superlatives about the existential threat the incumbent poses to our nation; President Obama simply has failed to lead or has led in the wrong direction, he argues. Why on earth would we want a candidate to say anything worse about his opponent? Explain why he’s wrong, and why you’re right, and let the voters choose. We need a president who can work within our poisonous political environment to solve our nation’s problems, not simply score partisan points. Someone who understands that negotiation is essential in a representative democracy, and that there are good ideas across the political spectrum. Someone who has a well-defined set of core values but is not so rigid that he ignores new information and new conditions. Someone who has shown himself to be honest and trustworthy. And competent. Someone whose positions are well-reasoned and based on the world as it is rather than as he pretends it to be. Someone with the temperament and judgment and experience to be taken seriously as the commander in chief and leader of the free world. We think Mr. Romney could demonstrate those characteristics. Mr. Huntsman already does. And we are proud to endorse him for the Republican nomination for president of the United States. ||||| MYRTLE BEACH, S.C. - Jon Huntsman will aim to give Mitt Romney a boost going into the final week before the South Carolina primary, endorsing his one-time rival in the hopes of helping him clinch the nomination. The former Utah governor's announcement - set for 11 a.m. Monday in a speech at the Convention Center here - comes after several days of discussion within the campaign about the consequences of splitting moderate voters with Romney in Saturday's vote. Resigned to the fact that Huntsman wouldn't win, they believed that their votes would be better used helping Romney hold off his conservative challengers and wrap up the primary race early. Text Size - + reset But those conservative challengers greeted the Huntsman news with a shrug. "Moderates are backing moderates," Rick Santorum said at a diner in Columbia Monday. "That's sort of the bottom line. No surprise there. Gov. Huntsman ran as a moderate, trying to compete for Gov. Romney for the establishment moderate vote. And Gov. Romney had a leg up on him being a solid moderate that the establishment could get behind. Gov. Huntsman wasn't able to crack through that. So I'm not surprised by that all, and I anticipated that actually sooner than today." Newt Gingrich said he believed Huntsman’s exit helps him. “It narrows down the field and I think the next five or six days are going to tell the tale,” Gingrich told POLITICO Monday morning. “If the conservatives consolidate, it’s clear that I’ll beat Romney.” Gingrich warned against conservatives splitting the vote. “The next five days are going to be wild. Really, the test here is really simple: if the conservatives consolidate, Romney loses decisively. If they don’t consolidate, it’s going to be very close,” Gingrich said. Huntsman's decision to drop out comes less than a week after he claimed victory from his third-place finish in the New Hampshire primary, the contest he'd staked his candidacy on ever since entering the race last summer. Huntsman experienced a surge of support in the closing days before that vote, but he still fell well short of Ron Paul - and even further behind Romney, whom he'd sniped at in the closing days. A source said that Huntsman's rationale for now backing Romney, who he has criticized for weeks on the campaign trail as lacking a "core," is that he didn't want to block the person best prepared in the field to beat Obama, and then to lead the country and grapple with the economy. "Jon Huntsman is proud of the campaign he ran and the message of restoring trust in Washington," said a campaign official familiar with his thinking. "He didn't want to stand in the way of the candidate most likely to beat Barack Obama and turn the economy around. That's Mitt Romney." Although Huntsman was only polling at about 5 percent in South Carolina, his voters are most likely to wind up with Romney. If either Newt Gingrich or Rick Santorum makes a run at the frontrunner in the final week, those handful of votes that otherwise would've gone to Huntsman could prove pivotal.

– Jon Huntsman will officially drop out of the presidential race and endorse Mitt Romney at 11am today in South Carolina—but why? Just last Tuesday, Huntsman was suggesting that Romney was "pretty much unelectable" after his statement about liking to fire people. Politico explains: Huntsman "didn’t want to stand in the way of the candidate most likely to beat Barack Obama and turn the economy around," says one campaign official. "That’s Mitt Romney." And Huntsman's handful of South Carolina voters will likely switch to Romney—even a small number of extra votes could help Romney clinch the win—which is why Huntsman, who wants to be seen as a team player since Romney will likely be the nominee, will exit now rather than after the South Carolina primary. Huntsman also saw a better chance to control the coverage of his exit by getting out now. If he waited until after the primary, his withdrawal could be overshadowed by Rick Perry's anticipated departure. By leaving now, Huntsman departs on the high note of his New Hampshire third-place finish, which came after a surge in the polls. Even so, that finish was "too little too late," says one official, and the campaign didn't have any money for TV, radio, or direct-mail ads this coming week. There was no fundraising bump after the New Hampshire primary, Huntsman himself was reluctant to loan the campaign more money, and even his father was wary of providing any additional funding to a pro-Huntsman super PAC. Nate Silver concurs with Politico's assessment that Huntsman's exit will help Romney. In the New York Times, he compiles the results of seven recent Public Policy Polling surveys and finds that 32% of Huntsman supporters named Romney as their second choice. Next up was Ron Paul, whom 15% picked as a second choice. (But 24% of Huntsman backers were undecided.) In a bit of irony, Huntsman's exit came on the very day South Carolina's biggest newspaper, The State, endorsed him.

German police announced Monday that they are on the lookout for thieves who stole an entire vineyard of grapes last week. According to the police report, “The unknown offenders … used a professional harvesting machine over the entire surface” to collect the grapes on Wednesday afternoon. They had taken 3,527 pounds used to make Riesling wine valued at around $9,200, German broadcaster Deutsche Welle reported. Thomas Lohnes/Getty Authorities in the vineyard-rich Rhineland-Palatinate region in western Germany are asking the public for help in catching those responsible for the crime, which reportedly took place right next to the parking lot of a major supermarket. Grape theft has occurred in Germany before, and cases are almost never solved. Following the theft of 350 kilograms of grapes, enough to make 350 bottles of wine in 2016, police told Die Welt that “no one is surprised when a harvester drives through the vineyards in the fall.” People are usually unaware that a crime is being committed and vineyard owners don’t check on the fruit daily, meaning that police cannot always determine when the theft occurred. Authorities in another European country, however, have found a way to catch those responsible for stealing grapes. “Horses are the best way of getting around places where you can’t go by car,” Nicolas Krust, a member of the “green brigade” in the Haut-Rhin region of eastern France said, according to Agence France-Presse. Krust is one of 16 officers on horseback that patrol the region, looking for people who litter, ticket illegally parked cars and watch for potential grape thieves. Locals believe that crime has fallen because of the unit. “For several years we haven’t had many problems with theft which is linked to the presence of the green brigade,” Roland Martin, the mayor of Wuenheim, said In the United States, two-and-a-half tons of grapes were reportedly stolen overnight in a Virginia vineyard last month, leaving the owner of Firefly Hill Vineyards with a loss of $50,000. “I can handle losing a crop to Mother Nature, but to come in and take my crop in the middle of the night and steal what we’ve worked for eight months, that’s disheartening,” David Dunkenberger said, according to The Washington Post. “You work your whole year for the harvest day and we were about to have that. We were almost there, and somebody stole it,” he said, mentioning that he has no idea who could have committed the crime or what they were planning to use the grapes for. ||||| These crawls are part of an effort to archive pages as they are created and archive the pages that they refer to. That way, as the pages that are referenced are changed or taken from the web, a link to the version that was live when the page was written will be preserved.Then the Internet Archive hopes that references to these archived pages will be put in place of a link that would be otherwise be broken, or a companion link to allow people to see what was originally intended by a page's authors.The goal is to fix all broken links on the web . Crawls of supported "No More 404" sites. ||||| Image copyright Renate007/Wikimedia Commons Image caption Deidesheim lies at the heart of Riesling country Police in southern Germany are looking for thieves who stole an entire vineyard of grapes from under their noses. The criminals made off with the field full of grapes by "running a professional harvesting machine over the entire vineyard", the police said, according to the local Rheinpfalz newspaper. Most galling of all for the police is the fact that the vineyard does not lie on some remote hillside, but is to be found right next to the car park of a major supermarket on the outskirts of the village of Deidesheim. The resourceful thieves struck at some point between teatime last Wednesday and sunset the following day, netting 1,600 kg (3,527 lb) of the white grapes used to make Riesling wine. The haul is estimated to be worth 8,000 euros (£7,110; $9,272). Image copyright Kallistratos/Wikimedia Commons Image caption The local Goat Auction is the occasion for a wine festival The police are keen for any information on the theft, as it is not the first in their part of Rhineland-Palatinate Region. Last year alone 600-800 kg of grapes were stolen in the surrounding Bad Duerkheim district. Rhineland-Palatinate is home to six of Germany's 13 wine-producing regions, and is famous for Riesling and sparkling wine. Its 13,000 vineyards account for 90% of Germany's wine exports. You might also be interested in: Runners tackle Moldova wine cellar 10k race Bolney vineyard raiders steal 5,000 bottles of wine French thieves nab grape harvest Local vintners have long suspected that rival wine-growers may be responsible. They note how the thieves unerringly select the choicest grapes, steal them just as they ripen, and have access to specialised harvesting equipment. "The motive is jealousy," Stephan Altmann told Die Welt newspaper when his Winning Vineyard was plundered two years ago. A local policeman added that harvesting machines heading into fields at dusk are a common sight in the area, and so not necessarily bound to arouse suspicion. The Deisdesheim winemakers could take the advice of their neighbours in France's Soultz-Haut-Rhin district, where local farmers swear that grape theft has been cut drastically by environmental officers on horseback patrol, France 3 TV reports. Image copyright France 3 TV Image caption France says horse patrols deter grape thieves Reporting by Martin Morgan Next story: Mistaken identity as Pakistan embarrassed by wallet theft Use #NewsfromElsewhere to stay up-to-date with our reports via Twitter.

– Brazen thieves have swept into southern Germany and stolen 3,527 pounds of grapes—leaving an entire vineyard stripped bare, Newsweek reports. A police report issued Monday says the perpetrators used a professional harvesting machine to gather up $9,200 of grapes used to make Riesling wine. Amazingly, the vineyard in Rhineland-Palatinate sits beside a supermarket parking lot, but authorities say no one raised an eyebrow. "No one is surprised when a harvester drives through the vineyards in the fall," says a police source. It's nothing new, either: Between 1,300 and 1,700 pounds of grapes were stolen in the surrounding Bad Duerkheim district last year, per the BBC, and a Virginia vineyard allegedly had two and a half tons of grapes worth $50,000 stolen last fall. "I can handle losing a crop to Mother Nature, but to come in and take my crop in the middle of the night and steal what we’ve worked for eight months, that's disheartening," the vineyard owner tells the Washington Post. In Germany, vintners have blamed vineyard thefts on rivals: "The motive is jealousy," vineyard owner Stephan Altmann told Die Welt two years ago.

a replication - deficient recombinant adenovirus expressing human hsp72 was constructed using the adeasy system ( qbiogene , carlsbad , ca , usa ) . the cdna for hsp72 ( approved gene symbol hspa1a ) was amplified by reverse transcription - polymerase chain reaction ( pcr ) using total rna extracted from hela cells that were previously heat shocked at 42 for 30 minutes . the amplified product was cloned into the pshuttle - cmv vector and verified by sequencing . the vector was then transfomed into escherichia coli strain bj5183 together with the padeasy-1 vector that contains the entire adenovirus serotype 5 genome except the e1 and e3 regions . the recombinant adenoviral constructs were selected and transfected into the hek-293 packaging cell line to produce viral particles . viral titers were determined by limiting dilution on 293 cells and the absence of the e1a gene in the viral constructs was confirmed by pcr . the rat retinal ganglion cell line , rgc-5 , neeraj agarwal ( university of north texas health science center , fort worth , tx , usa ) . rgc-5 cells were maintained in medium containing dulbecco 's modified eagle 's medium ( life technologies , rockville , md , usa ) , 10% fetal bovine serum , and antibiotics at 37 in a humidified 5% co2 - 95% air atmosphere . rgc-5 cells grown to 70% confluence in a 24-well plate were transduced with a recombinant adenovirus expressing hsp72 for 2 hours at a multiplicity of infection ( moi ) of 5 to 50 plaque forming units ( pfu ) per cell . forty - eight hours after transduction , adherent cells were lysed with 0.4 ml of 1 laemmli sample buffer and boiled for 5 minutes . the protein samples were resolved by sodium dodesyl sulfate polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane . the membrane was blocked with 5% skim milk overnight , incubated for 2 hours with anti - hsp72 antibody ( stressgen , victoria , canada ) , and reacted for 2 hours with peroxidase - conjugated anti - mouse antibody ( amersham , buckinghamshire , uk ) , followed by being probed with a chemiluminescence kit ( amersham ) . rgc-5 cells grown in a chamber slide were transduced for 2 hours at an moi of 20 pfu per cell . forty - eight hours post - transduction , the cells were fixed with 4% paraformaldehyde , permeabilized with 0.5% triton x-100 , and blocked with 2% bovine serum albumin . the cells were then incubated for 2 hours with anti - hsp72 antibody , reacted for 2 hours with alexa fluor 568-conjugated goat anti - mouse igg ( molecular probes , eugene , or , usa ) , and counterstained with 4',6-diamidino-2-phenylindole . rgc-5 cells were dispensed in a 96 well plate at a concentration of 1 10 cells per well and transduced for 2 hours at an moi of 5 and 20 pfu . the cells were washed , replenished with 100 l of media containing 5 to 20 m etoposide and cultured further . after 48 hours , 10 ul of reagent for used in the cytotoxicity assay ( wst-8 ; dojindo , rockville , md , usa ) per well was added , and the absorbance at 450 nm was read by an automatic microplate reader after 1 hour of incubation . a replication - deficient recombinant adenovirus expressing human hsp72 was constructed using the adeasy system ( qbiogene , carlsbad , ca , usa ) . the cdna for hsp72 ( approved gene symbol hspa1a ) was amplified by reverse transcription - polymerase chain reaction ( pcr ) using total rna extracted from hela cells that were previously heat shocked at 42 for 30 minutes . the amplified product was cloned into the pshuttle - cmv vector and verified by sequencing . the vector was then transfomed into escherichia coli strain bj5183 together with the padeasy-1 vector that contains the entire adenovirus serotype 5 genome except the e1 and e3 regions . the recombinant adenoviral constructs were selected and transfected into the hek-293 packaging cell line to produce viral particles . viral titers were determined by limiting dilution on 293 cells and the absence of the e1a gene in the viral constructs was confirmed by pcr . the rat retinal ganglion cell line , rgc-5 , was originally provided as a gift from dr . neeraj agarwal ( university of north texas health science center , fort worth , tx , usa ) . rgc-5 cells were maintained in medium containing dulbecco 's modified eagle 's medium ( life technologies , rockville , md , usa ) , 10% fetal bovine serum , and antibiotics at 37 in a humidified 5% co2 - 95% air atmosphere . rgc-5 cells grown to 70% confluence in a 24-well plate were transduced with a recombinant adenovirus expressing hsp72 for 2 hours at a multiplicity of infection ( moi ) of 5 to 50 plaque forming units ( pfu ) per cell . forty - eight hours after transduction , adherent cells were lysed with 0.4 ml of 1 laemmli sample buffer and boiled for 5 minutes . the protein samples were resolved by sodium dodesyl sulfate polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane . the membrane was blocked with 5% skim milk overnight , incubated for 2 hours with anti - hsp72 antibody ( stressgen , victoria , canada ) , and reacted for 2 hours with peroxidase - conjugated anti - mouse antibody ( amersham , buckinghamshire , uk ) , followed by being probed with a chemiluminescence kit ( amersham ) . rgc-5 cells grown in a chamber slide were transduced for 2 hours at an moi of 20 pfu per cell . forty - eight hours post - transduction , the cells were fixed with 4% paraformaldehyde , permeabilized with 0.5% triton x-100 , and blocked with 2% bovine serum albumin . the cells were then incubated for 2 hours with anti - hsp72 antibody , reacted for 2 hours with alexa fluor 568-conjugated goat anti - mouse igg ( molecular probes , eugene , or , usa ) , and counterstained with 4',6-diamidino-2-phenylindole . rgc-5 cells were dispensed in a 96 well plate at a concentration of 1 10 cells per well and transduced for 2 hours at an moi of 5 and 20 pfu . the cells were washed , replenished with 100 l of media containing 5 to 20 m etoposide and cultured further . after 48 hours , 10 ul of reagent for used in the cytotoxicity assay ( wst-8 ; dojindo , rockville , md , usa ) per well was added , and the absorbance at 450 nm was read by an automatic microplate reader after 1 hour of incubation . to express hsp72 exogenously in rgc-5 cells that are not easily transfected by conventional methods , the cells were transduced with a recombinant adenovirus expressing human hsp72 . western blot analysis showed that protein bands of 72 kda corresponding to hsp72 were clearly detected in lysates of cells transduced with a recombinant adenovirus expressing human hsp72 . the intensities of the bands were found to be in proportion to the degree of viral transduction . in untransduced control cells , immunocytochemistry yielded consistent results showing that cytoplasmic staining for characteristic hsp72 expression could be detected exclusively in transduced cells but not in untransduced cells , confirming the adenovirus - mediated hsp72 gene expression ( fig . 1b ) . to examine the effect of hsp72 on the death of rgc-5 cells caused by apoptosis , the cells were treated with etoposide immediately after viral transduction . compared with control cells ( fig . 2a ) , early cell death was seen in a small proportion of cells in the culture without serum ( fig . 2b ) , and the degree of cell death was accelerated by the treatment of etoposide ( fig . . however , the etoposide - induced cell death appeared to be blocked by hsp72 expression , as observed by the enhanced viability of cells that were transduced immediately before etoposide treatment ( fig . to confirm the effect of hsp72 on the survival of rgc-5 cells , a cell proliferation assay was performed on cells treated with etoposide following viral transduction ( fig . the rate of viable cells was reduced by 44.8 6.7% and 80.8 9.2% relative to control cells at 5 and 20 m etoposide , respectively . viral transduction itself might be toxic to cells because cell viability was slightly decreased when hsp72 was expressed in control cells . the hsp72 expression , however , seemed to be protective to cells undergoing apoptosis in that the rate of cell death in the cultures exposed to etoposide was progressively reduced as the degree of viral transduction increased . at the highest level of hsp72 expression , the number of viable cells recovered was increased by 24.0 3.1% and 94.1 10.3% over that in the control cultures at 5 and 20 m etoposide , respectively . in this study , we addressed whether hsp72 can protect rgc-5 cells from apoptotic cell death . rgc-5 cells are the only immortalized rgc cell line established to date and are used widely in glaucoma research , although it is uncertain whether the cell line is of mouse or rat origin . to investigate directly the effect of hsp72 on the death of rgc-5 cells , it is necessary to express the protein exogenously in the cells . to overcome this obstacle , we constructed a recombinant adenovirus in which a human hsp72 cdna is under the control of the human cytomegalovirus promoter for its constitutive expression and demonstrated that the viral vector was successful in both transducing rgc-5 cells and expressing its transgene inside the cells . we showed that the degree of cell death by etoposide was inversely proportional to the degree of viral transduction in the cells . etoposide , an inhibitor of topoisomerase ii , is a well - known apoptosis - inducing reagent . therefore , our results present direct evidence for the cytoprotective ability of hsp72 against apoptotic cell death . the protective role of heat shock was first described in light - damaged rat retina and hsp72 protein was identified as the entity primarily responsible for the response . a growing body of evidence has accumulated that induction of hsp72 is essential for neuronal tolerance to a wide variety of stressful conditions including ischemic or excitotoxic insults , seizure , oxidative stress , and apoptotic stimuli . the present study demonstrates that hsp72 expression itself is sufficient to protect rgc-5 cells from apoptotic cell death . apoptosis , or programmed cell death , of rgcs is one of the earlier signs of the pathogenesis of glaucoma . because inhibition of rgc death or a halt of its progression is the key to glaucoma treatments , the ability of hsp72 to intervene in the process of apoptosis is attractive as a novel therapeutic intervention in glaucoma . gene therapy , which is a practical alternative to current therapies that are limited to reduction of elevated intraocular pressure , is an approach by which hsp72 could be useful in a clinical context . recent studies reported that hsp72 induction by zinc or geranylgeranylacetone administration increased rgc survival in a rat glaucoma model , suggesting that hsp72 could be therapeutic for glaucoma . the eye may perhaps be the first organ for which gene therapy is used routinely in a clinical setting because it has advantages such as well - defined anatomy with small size , translucent media allowing excellent visual localization , and easy accessibility by which therapeutic agents can be delivered to the vicinity of cells with a particular defect . the replication - deficient adenovirus generated in this study is a sophisticated gene delivery tool and such viral - based vectors are expected to have enormous potential as a mammalian expression system for gene therapy . recently , it has been reported that hsp72 can be identified in the extracellular compartments and the extracellular hsp72 acts as a cytokine that induces inflammation and modulates the innate immune response [ 17 - 20 ] . the dual role of hsp72 as a molecular chaperone and cytokine suggests that fine tuning its expression may be a potential route for a novel therapeutic approach to glaucoma and other neurodegenerative diseases .

purposeto assess whether the expression of heat shock protein 72 ( hsp72 ) protects rat retinal ganglion cells ( rgc-5 ) from apoptotic cell death.methodshsp72 expression in rgc-5 cells transduced with replication - deficient recombinant adenovirus was analyzed by western blot analysis and immunofluorescence . the effect of hsp72 expression on etoposide - induced apoptotic cell death was examined by microscopic analysis and confirmed by cell proliferation assay.resultswestern blot analysis and immunofluorescence clearly showed adenovirus - mediated hsp72 expression in rgc-5 cells . treatment with etoposide resulted in the death of a proportion of the cells by apoptosis . however , this apoptotic cell death was significantly reduced in cells expressing hsp72 , with the reduction in cell death correlating to the level of hsp72 expression.conclusionsover-expression of hsp72 alone is sufficient to rescue neuronal cells from apoptotic cell death , suggesting that fine - tuning its expression may be an effective neuroprotective approach in retinal degenerative disease .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Montgomery GI Bill Educational Assistance Transferability Act of 2008''. SEC. 2. REMOVAL OF CERTAIN LIMITATIONS ON TRANSFER OF ENTITLEMENT TO BASIC EDUCATIONAL ASSISTANCE. (a) In General.--Section 3020 of title 38, United States Code, is amended-- (1) in the heading, by striking ``: members of the Armed Forces with critical military skills''; (2) in subsection (a)-- (A) by striking ``with critical military skills and at such Secretary's sole discretion''; and (B) by striking ``, subject to the limitation under subsection (d)''; (3) in subsection (b)-- (A) in paragraph (1), by striking the semicolon at the end and inserting ``; and''; (B) by striking paragraph (2); and (C) by redesignating paragraph (3) as paragraph (2); (4) by striking subsection (d); and (5) by redesignating subsections (e) through (m) as subsections (d) through (l), respectively. (b) Conforming Amendments.--Such section is further amended-- (1) in subsection (g)(2), as redesignated by subsection (a)(5) of this section, by striking ``under subsection (e)(2)'' and inserting ``under subsection (d)(2)''; (2) in subsection (h)(2), as redesignated by subsection (a)(5) of this section, by striking ``under subsection (b)(3)'' and inserting ``under subsection (b)(2)''; and (3) in subsection (j), as redesignated by subsection (a)(5) of this section-- (A) by striking ``under subsection (f)(2)'' and inserting ``under subsection (e)(2)''; and (B) by striking ``in subsection (h)(5)'' and inserting ``in subsection (g)(5)''. (c) Clerical Amendment.--The table of sections at the beginning of chapter 30 of such title is amended by amending the item relating to section 3020 to read as follows: ``3020. Transfer of entitlement to basic educational assistance.''. SEC. 3. TRANSFER OF ENTITLEMENT TO EDUCATIONAL ASSISTANCE UNDER THE RESERVE MONTGOMERY GI BILL. (a) Selected Reserve.-- (1) In general.--Chapter 1606 of title 10, United States Code, is amended by adding at the end the following new section: ``Sec. 16138. Transfer of entitlement to educational assistance ``(a) In General.--An individual described in subsection (b) who is entitled to educational assistance under this chapter may elect to transfer to one or more of the dependents specified in subsection (c) a portion of such individual's entitlement to such assistance. An individual transferring entitlement under this section shall submit written notice to the Secretary concerned not later than the expiration date of the period described in section 16133 of this title that is applicable to such individual. ``(b) Eligible Individuals.--An individual referred to in subsection (a) is any member of the armed forces who, at the time of the approval by the Secretary concerned of the member's request to transfer entitlement to basic educational assistance under this section-- ``(1) has completed six years of service in the Selected Reserve; and ``(2) enters into an agreement to remain a member of the Selected Reserve for a period of not less than four years. ``(c) Eligible Dependents.--An individual may transfer entitlement under this section as follows: ``(1) To the individual's spouse. ``(2) To one or more of the individual's children. ``(3) To a combination of the individuals referred to in paragraphs (1) and (2). ``(d) Designation of Transferee.--An individual transferring entitlement under this section shall-- ``(1) designate the dependent or dependents to whom such entitlement is being transferred; ``(2) designate the number of months of such entitlement to be transferred to each such dependent; and ``(3) specify the period for which the transfer shall be effective for each such dependent. ``(e) Revocation and Modification.--An individual transferring entitlement under this section may modify or revoke at any time the transfer of any unused portion of the entitlement so transferred. The modification or revocation of the transfer of entitlement under this subsection shall be made by the submittal of written notice of the action to both the Secretary concerned and the Secretary of Veterans Affairs. ``(f) Commencement of Use.--If the dependent to whom entitlement is transferred under this section is a child, the use of the transferred entitlement may not commence until the child-- ``(1) completes the requirements of a secondary school diploma (or equivalency certificate); or ``(2) attains 18 years of age. ``(g) Time Limitation for Use of Eligibility and Entitlement.-- Notwithstanding section 16133 of this title, and subject to subsection (d)(3), a dependent to whom entitlement is transferred under this section may use such entitlement until the later of-- ``(1) the expiration date of a 15-year period beginning on the date on which the individual who transferred such entitlement to the dependent becomes entitled to such assistance; and ``(2) the date that is 10 years after the date the individual who transferred such entitlement to the dependent is separated from the Selected Reserve. ``(h) Additional Administrative Matters.-- ``(1) Use of entitlement charged to transferring individual.--The use of any entitlement transferred under this section shall be charged against the entitlement of the individual making the transfer at the rate of one month for each month of transferred entitlement that is used. ``(2) Entitlement to assistance.--Except as provided under paragraphs (2) and (3) of subsection (d) and subsection (g), and subject to paragraph (5), a dependent to whom entitlement is transferred under this section is entitled to educational assistance under this chapter in the same manner as the individual from whom entitlement was transferred. ``(3) Monthly rate of education assistance payable.--The monthly rate of educational assistance payable to a dependent to whom entitlement is transferred under this section shall be the monthly amount payable under section 16131 of this title to the individual making the transfer. ``(4) Use of transferred entitlement not affected by death of transferor.--The death of an individual transferring entitlement under this section shall not affect the use of the transferred entitlement by the dependent to whom entitlement is transferred. ``(5) Age limitation.--Notwithstanding subsection (g) and section 16133 of this title, a child to whom entitlement is transferred under this section may not use any entitlement so transferred after attaining the age of 26 years. ``(6) Transferability to non-child of entitlement for purpose of secondary school diploma.--Except as provided in subsection (f), the purposes for which a dependent to whom entitlement is transferred under this section may use such entitlement shall include the pursuit and completion of the requirements of a secondary school diploma (or equivalency certificate). ``(i) Overpayment.--In the event of an overpayment of basic educational assistance with respect to a dependent to whom entitlement is transferred under this section, the dependent and the individual making the transfer shall be jointly and severally liable to the United States for the amount of the overpayment for purposes of section 3685 of title 38. ``(j) Regulations.--The Secretaries concerned shall prescribe regulations for purposes of this section. ``(k) Secretary Concerned Defined.--Notwithstanding section 101(a)(9) of this title, in this section the term `Secretary concerned' means-- ``(1) the Secretary of the Army with respect to matters concerning the Army; ``(2) the Secretary of the Navy with respect to matters concerning the Navy or the Marine Corps; ``(3) the Secretary of the Air Force with respect to matters concerning the Air Force; and ``(4) the Secretary of Defense with respect to matters concerning the Coast Guard, or the Secretary of Homeland Security when it is not operating as a service in the Navy.''. (2) Clerical amendment.--The table of sections at the beginning of such chapter is amended by adding at the end the following new item: ``16138. Transfer of entitlement to educational assistance.''. (b) Conforming Amendments.-- (1) Time limitation.--Section 16133(a) of such title is amended by inserting ``and section 16138 of this title'' after ``subsection (b)''. (2) Biennial report.--Section 16137 of such title is amended by inserting after the second sentence the following: ``Each such report shall also include the number of members of the Selected Reserve of the Ready Reserve of each armed force transferring entitlement to educational assistance under section 16138.''.

Montgomery GI Bill Educational Assistance Transferability Act of 2008 - Amends the Montgomery GI Bill educational assistance program to authorize the Secretary of the military department concerned to permit any member of the Armed Forces (currently, only members with critical military skills) entitled to basic educational assistance to elect to transfer a portion of such assistance to one or more dependents. Removes the 18-month limitation on the number of months of entitlement authorized to be transferred. Provides similar eligibility for the transfer of educational assistance for members of the Selected Reserve who have completed at least six years of service and enter into an agreement to remain a member of such Reserve for at least four more years.

the internet is a technology that facilitates accessing various kinds of information resources and information exchange easily via an inexpensive and safe way . although a standardized definition of internet addiction has not been uniformly agreed upon , some researchers define the internet addiction as having less ability to control enthusiasm for internet activities , losing the importance of the time without being connected to the internet , extreme nervousness and aggressive behaviour when deprived , and progressive deterioration in work , and social and family functionings [ 1 , 2 ] . researchers point that the internet addiction may be seen at every age in both sexes and begin at earlier ages than other addictions . prevalence statistics of internet addiction among adolescents vary widely from 2% to 20% across cultures and societies for this reason , the internet addiction may cause physical and social problems as well as psychological disturbances . a number of studies have underlined the unfavorable effects of internet addiction on physical and mental well - being and most of the adolescents with internet addiction were also reported to have another psychiatric disorder [ 7 , 8 ] . mood disorders , substance use disorders , attention - deficit hyperactivity disorder ( adhd ) , disruptive behaviour disorders , anxiety disorders , sleep disorders , eating disorders , and epileptic seizures are some proven internet addiction - related clinical situations . others have argued that the internet addiction is actually a behaviour pattern which plays role in some of the negative cognitions that compensate for failed areas of life just as seen in depression . in this context , excessive use of the internet can be seen as a rewarding behavior , and through learning mechanisms , it may be used as an insufficient strategy to cope with some negative feelings . temperament traits of novelty or sensation seeking are reported to be significantly higher in substance users than in nonusers . most authors agree that these traits increase the risk of drug addiction in general , presumably because of an increased tendency to experiment with drugs . in studies investigating the temperament features of adolescents with internet addiction , it was revealed that students with internet addiction were easily affected by feeling , emotionally less stable , imaginative , absorbed in thought , self - sufficient , experimenting , and preferred their own decisions . adolescents with internet addiction were also shown to have higher scores on neuroticism and psychoticism temperament categories than those of the control group . however , to our knowledge , there is not a study in the literature addressing the correlation between affective temperament profiles and the internet addiction . the first aim of this study was to investigate internet addiction and the relevance to the sociodemographic properties among a sample of turkish adolescent population . second , it was aimed to compare the affective temperament profiles and emotional and behavioural characteristics of adolescents with or without the internet addiction . the study population included high school students attending erzurum ataturk high school in turkey in the 2010 - 2011 academic year ( n = 325 ) . the study sample included 303 students who were present in classes on the day when data were collected , who agreed to participate in the study , and who filled in the questionnaires completely ( response rate = 93.2% ) . the ethical committee approval was obtained from the institute of health sciences of ataturk university . the students who were given information about the study and who accepted to participate in the study were included . also , approval was obtained from the directorate of school education , affiliating with the ministry of education . four instruments were used to collect data : a sociodemographic characteristics data form , internet addiction scale , the strengths and difficulties questionnaire , and the temperament evaluation of memphis , pisa , paris , and san diego autoquestionnaire . we developed a 12-item sociodemographic questionnaire with items pertaining to age , sex , grade , average monthly household income , extent and type of internet use ( e.g. , where do you use the internet ? ) , and presence of the computer in the home . the ias is a self - report instrument consisting of 31 items ( e.g. , i have attempted to spend less time on the internet but i have been unable to do so . ) based on the diagnostic and statistical manual of mental disorders , fourth edition , substance dependence criteria , and 2 additional criteria recommended by griffiths . the ias is a highly reliable and internally consistent measure ( cronbach = .95 ) . the scale was translated into turkish , and psychometric properties of the turkish version of the scale were evaluated among high school students revealing a highly significant test - retest reliability . an interitem reliability reduced the initial scale from 31 to 27 items ( with cronbach of .94 ) . scale items are rated on a 5-point likert scale ( 1 , never ; 2 , rarely ; 3 , sometimes ; 4 , frequently ; 5 , always ) , with higher scores representing greater internet addiction . a cutoff score of 81 ( 3 27 items ) was suggested as indicative of internet addiction . the sdq was developed to determine adolescents ' areas of strengths and problematic behaviours . the tool contains 25 questions which asks about behavioural characteristics , some of which are positive , and some of which are negative . these questions are listed under five subheadings : ( 1 ) conduct problems ; ( 2 ) hyperactivity - inattention ; ( 3 ) emotional symptoms ; ( 4 ) peer problems ; and ( 5 ) prosocial behaviour . the validity and reliability of the turkish version of sdq was performed by gvenir et al . with an acceptable internal consistency ( cronbach 's alpha = 0.73 ) . the autoquestionnaire version of the temperament evaluation of memphis , pisa , paris , and san diego ( temps - a ) is a self - report instrument developed by akiskal et al . . the complete questionnaire measures affective temperamental traits , present in the subject 's whole life , represented in five dimensional scales : depressive , cyclothymic , hyperthymic , irritable , and anxious . in this study , the turkish version was used . statistical package for social sciences software ( spss 15 , chicago , il , usa ) was used for the analysis . pearson 's chi - square test was used to analyze the differences in means and proportions between groups . spearman 's or pearson 's correlation tests were used to evaluate the association between the ias and the subscales of the sdq and the temps - a . a p value of < 0.05 was considered significant . a total of 210 boys ( 69.2% ) and 92 girls ( 30.8% ) completed the scale and questionnaires . of the sample , 20 ( 6.6% ) the proportion of boys who were classified as internet addicts was 6.2% . for girls , the corresponding proportion was 7.6% ; the difference was not statistically significant . having a computer in the home was found to be significantly related with internet addiction . table 1 lists the baseline subject characteristics by the presence or absence of internet addiction . the mean ias scores were significantly higher in adolescents who had a computer in home than those who had not ( p < 0.001 ) . additionally , students who had been using internet for more than two years were found to score higher on the ias than those who had been using internet for two years or less ( p < 0.001 ) . the ias scores were also significantly higher in adolescents who had been using the internet in home than in those who had been using the internet in other places ( p < 0.001 ) . the prevalence rate of anxious temperament for internet addicts was 15% , whereas that for nonaddicts , it was 2.8% ( p temperament subtypes and their distribution in terms of the internet addiction status are shown in table 2 . the mean ias scores were found to be higher in adolescents with anxious temperament ( 63.9 25.3 ) than those without anxious temperament ( 47.9 18.1 ) ( p < 0.05 ) . presence or absence of other temperament subtypes was not associated with significantly different scores on the ias . according to pearson 's correlation coefficient , significant correlations were detected between internet addiction and dysthymic ( r = 0.199 ; p < 0.01 ) , cyclothymic ( r = 0.249 ; p < 0.01 ) , hyperthymic ( r = 0.156 ; p < 0.01 ) , irritable ( r = 0.254 ; p < 0.01 ) , and anxious ( r = 0.205 ; p < 0.01 ) temperaments . adolescents with and without internet addiction were also compared according to their temps - a and sdq scores ( table 3 ) . although no difference was observed in temps - a scores , students with internet addiction scored higher on conduct problems ( p < 0.05 ) and total difficulties ( p < 0.05 ) subscales of sdq than students without internet addiction . moreover , there was a positive and statistically significant correlation between ias and conduct problems ( r = 0.146 ; p < 0.05 ) , hyperactivity - inattention ( r = 0.133 ; p < 0.05 ) , emotional symptoms ( r = 0.138 ; p < 0.05 ) , and total difficulties ( r = 0.160 ; p < 0.01 ) . in the present study , the prevalence of internet addiction was found to be 6.6% , which is similar with the rate found in other studies evaluating similarly aged students [ 22 , 23 ] . according to our findings , the risk of becoming an internet addict increases with the increase in the accesibility of internet . additionally , internet use with a duration of more than two years was also found to be related to increased internet addiction risk . in our study , presumably because of low participation rates in girls , there was no significant difference between boys and girls according to ias scores . contrary to our finding , turkey statistical institute has stated that computer and internet use was more prevalent among boys than in girls in 2010 data . other studies from turkey have also shown that boys were more prone to the effects of harmful internet use [ 17 , 25 ] . in a study which evaluated 535 primary school students using child behavior checklists , adhd scores have been found to be higher in adolescents with internet addiction than in those without . additionally , yen et al . , evaluating 2793 college students , revealed that there was a relationship between the internet addiction and attention deficit hyperactivity disorder ( adhd ) . they have also shown that the most prominent relation between the internet addiction was with attention deficit symptom cluster . similarly , in the present study , internet addiction scores were found to be positively related to attention deficit and hyperactivity scores . according to the rewarding withdrawal syndrome , because of the d2 receptor deficiency , children with adhd have marked tendency to predisposition for pathological gambling , substance and alcohol use , and impulsive and compulsive behaviours . the internet addiction , according to the reward deficiency hypothesis , may function as an unnatural reward and may accompany adhd symptoms by this way . dependent personality traits have been shown to be related with impulsivity , novelty seeking , psychoticism , and social relation problems in several studies [ 29 , 30 ] . landers and lounsbury evaluated 117 undergraduate students and found that the internet usage was negatively related to three of the big five traits , agreeableness , conscientiousness , and extraversion as well as two narrow traits ; optimism and work drive , and positively related to tough - mindedness . in a study conducted among college students in turkey , psychoticism was shown to be the only personality dimension related to establishing new relationships and having internet only friends . moreover , extroversion was the only personality dimension that is related to maintaining long - distance relationships and supporting daily face - to - face relationships . in our study , a positive and highly significant correlation was found between the internet addiction scores and depressive , cyclothymic , hyperthymic , irritable , and anxious temperament scores . furthermore , the frequency of anxious temperament was found to be significantly higher in students with internet addiction than those without . behavioural addictions demonstrate the core features of physical and psychological addictions such as mental rumination , mood variability , tolerance , withdrawal , interpersonal conflict , and relapse . according to the self - medication hypothesis , the patients usually use the substances to change their unwanted temperament status , to reduce their unbearable anxiety , and to cope with cognitive impairments . this can be seen in the internet addiction , which is also a behavioral addiction . namely , repeating efforts to get online may be a way of decreasing the severity of withdrawal symptoms such as anxiety . additionally , the explanation of increased internet addiction frequency in individuals with anxious temperament may be related to self - medication hypothesis . adolescents who are deprived of emotional and psychological support have been reported to be under increased risk for internet addiction . morahan - martin and schumacher revealed that 22.7% of the internet users had trouble with peer and family relations and had difficulty in work and school activities because of the internet usage . in our study sample , total strength scores and conduct problems scores of the sdq have been found to be significantly higher in the students with internet addiction . also , there was a positive correlation between the internet addiction scores and total difficulties , conduct problems , hyperactivity - inattention , and emotional symptoms scores . according to these findings first , since the sample of this study included students of a high school , the results of the study can not be generalized to the larger population in turkey . second , the sample size was modest to draw definite conclusions . also , high school education was not mandatory in turkey when this study was conducted . families in the east and southeast of turkey invest more in the education of their sons than their daughters . finally , the cross - sectional research design of the present study could not confirm causal relationships of temperament profiles and behavioural problems with internet addiction . according to the findings of the present study , internet addiction is a relatively common phenomena among the adolescents . there is a relation between the internet addiction and attention deficit and hyperactivity symptoms and also with anxious temperament . furthermore , behavioural problems are more frequent in adolescents who have problematic internet use . because of the cross - sectional nature of this study , it is not possible to define the direction of the causality of the results . there is a need for further prospective studies evaluating the temperament features of adolescents who are at risk for the internet addiction in larger study populations .

the purpose of this study was to investigate the association of affective temperament profiles and emotional and behavioural characteristics with internet addiction among high school students . the study sample included 303 high school students . a sociodemographic characteristics data form , internet addiction scale ( ias ) , the strengths and difficulties questionnaire , and the temperament evaluation of memphis , pisa , paris , and san diego autoquestionnaire were used to collect data . of the sample , 6.6% were found to be addicted to internet . having a computer in the home ( p < 0.001 ) and using the internet for more than two years ( p < 0.001 ) were found to be related to higher scores on the ias . the prevalence rate of anxious temperament for internet addicts was more than that for nonaddicts ( p < 0.001 ) . dysthymic ( r = 0.199 ; p < 0.01 ) , cyclothymic ( r = 0.249 ; p < 0.01 ) , hyperthymic ( r = 0.156 ; p < 0.01 ) , irritable ( r = 0.254 ; p < 0.01 ) , and anxious ( r = 0.205 ; p < 0.01 ) temperaments ; conduct problems ( r = 0.146 ; p < 0.05 ) , hyperactivity - inattention ( r = 0.133 ; p < 0.05 ) , emotional symptoms ( r = 0.138 ; p < 0.05 ) , and total difficulties ( r = 0.160 ; p < 0.01 ) were found to be correlated with ias scores . according to these findings , there is a relation between the internet addiction and affective temperament profiles , especially with anxious temperament . furthermore , emotional and behavioural problems are more frequent in adolescents who have problematic internet use .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Personal Information Privacy Act of 1997''. SEC. 2. CONFIDENTIAL TREATMENT OF CREDIT HEADER INFORMATION. Section 603(d) of the Fair Credit Reporting Act (15 U.S.C. 1681a(d)) is amended by inserting after the first sentence the following: ``The term also includes any other identifying information of the consumer, except the name, address, and telephone number of the consumer if listed in a residential telephone directory available in the locality of the consumer.''. SEC. 3. PROTECTING PRIVACY BY PROHIBITING USE OF THE SOCIAL SECURITY NUMBER FOR COMMERCIAL PURPOSES WITHOUT CONSENT. (a) In General.--Part A of title XI of the Social Security Act (42 U.S.C. 1301 et seq.) is amended by adding at the end the following: ``prohibition of certain misuses of the social security account number ``Sec. 1146. (a) Prohibition of Commercial Acquisition or Distribution.--No person may buy, sell, offer for sale, take or give in exchange, or pledge or give in pledge any information for the purpose, in whole or in part, of conveying by means of such information any individual's social security account number, or any derivative of such number, without the written consent of such individual. ``(b) Prohibition of Use as Personal Identification Number.--No person may utilize any individual's social security account number, or any derivative of such number, for purposes of identification of such individual without the written consent of such individual. ``(c) Prerequisites for Consent.--In order for consent to exist under subsection (a) or (b), the person engaged in, or seeking to engage in, an activity described in such subsection shall-- ``(1) inform the individual of all the purposes for which the number will be utilized and the persons to whom the number will be known; and ``(2) obtain affirmatively expressed consent in writing. ``(d) Exceptions.--Nothing in this section shall be construed to prohibit any use of social security account numbers permitted or required under section 205(c)(2) of this Act, section 7(a)(2) of the Privacy Act of 1974 (5 U.S.C. 552a note; 88 Stat. 1909), or section 6109(d) of the Internal Revenue Code of 1986. ``(e) Civil Action in United States District Court; Damages; Attorneys Fees and Costs; Nonexclusive Nature of Remedy.-- ``(1) In general.--Any individual aggrieved by any act of any person in violation of this section may bring a civil action in a United States district court to recover-- ``(A) such preliminary and equitable relief as the court determines to be appropriate; and ``(B) the greater of-- ``(i) actual damages; and ``(ii) liquidated damages of $25,000 or, in the case of a violation that was willful and resulted in profit or monetary gain, $50,000. ``(2) Attorney's fees and costs.--In the case of a civil action brought under paragraph (1) in which the aggrieved individual has substantially prevailed, the court may assess against the respondent a reasonable attorney's fee and other litigation costs and expenses (including expert fees) reasonably incurred. ``(3) Statute of limitations.--No action may be commenced under this subsection more than 3 years after the date on which the violation was or should reasonably have been discovered by the aggrieved individual. ``(4) Nonexclusive remedy.--The remedy provided under this subsection shall be in addition to any other lawful remedy available to the individual. ``(f) Civil Money Penalties.-- ``(1) In general.--Any person who the Commissioner of Social Security determines has violated this section shall be subject, in addition to any other penalties that may be prescribed by law, to-- ``(A) a civil money penalty of not more than $25,000 for each such violation, and ``(B) a civil money penalty of not more than $500,000, if violations have occurred with such frequency as to constitute a general business practice. ``(2) Determination of violations.-- Any violation committed contemporaneously with respect to the social security account numbers of 2 or more individuals by means of mail, telecommunication, or otherwise shall be treated as a separate violation with respect to each such individual. ``(3) Enforcement procedures.--The provisions of section 1128A (other than subsections (a), (b), (f), (h), (i), (j), and (m), and the first sentence of subsection (c)) and the provisions of subsections (d) and (e) of section 205 shall apply to civil money penalties under this subsection in the same manner as such provisions apply to a penalty or proceeding under section 1128A(a), except that, for purposes of this paragraph, any reference in section 1128A to the Secretary shall be deemed a reference to the Commissioner of Social Security. ``(g) Regulation by States.--Nothing in this section shall be construed to prohibit any State authority from enacting or enforcing laws consistent with this section for the protection of privacy.''. (b) Effective Date.--The amendment made by this section applies with respect to violations occurring on and after the date which is 2 years after the date of enactment of this Act. SEC. 4. RESTRICTION ON USE OF SOCIAL SECURITY NUMBERS BY STATE DEPARTMENTS OF MOTOR VEHICLES. (a) Restriction on Governmental Use.--Section 2721(b)(1) of title 18, United States Code, is amended by striking ``its functions.'' and inserting ``its functions, but in the case of social security numbers, only to the extent permitted or required under section 205(c)(2) of the Social Security Act (42 U.S.C. 405(c)(2)), section 7(a)(2) of the Privacy Act of 1974 (5 U.S.C. 552a note, 88 Stat. 1909), section 6109(d) of the Internal Revenue Code of 1986, or any other provision of law specifically identifying such use.''. (b) Prohibition of Use by Marketing Companies.--Section 2721(b)(12) of title 18, United States Code, is amended by striking ``For'' and inserting ``Except in the case of social security numbers, for''.

Personal Information Privacy Act of 1997 - Amends the Fair Credit Reporting Act to redefine the term "consumer report" to exclude identifying information listed in a local telephone directory (thereby ensuring that the personal identification information in the credit headers accompanying credit reports of unlisted individuals remains confidential). Amends part A (General Provisions) of title XI of the Social Security Act to prohibit the commercial acquisition or distribution of an individual's social security number (or any derivative of it) as well as its use as a personal identification number without the individual's written consent. Provides for a civil action in a U.S. District Court by any individual aggrieved by any violation of this prohibition. Provides for civil money penalties for violations as well. Amends the Federal criminal code to require the uses of social security numbers by State departments of motor vehicles to be consistent with the uses authorized by the Social Security Act, the Privacy Act, and by any other statutes explicitly authorizing their use. Prohibits the use of social security numbers by marketing companies.

type 1 diabetes is an autoimmune disease resulting from destruction of pancreatic - cells by infiltrating immune cells . the nod mouse is an important model of spontaneous autoimmune diabetes that has been used to understand type 1 diabetes pathogenesis and develop therapeutics to prevent - cell destruction . similar to humans who have genetic susceptibility to type 1 diabetes and islet autoimmunity , not all nod mice progress to overt diabetes , and progression to diabetes occurs at a variable time point after the start of autoimmunity [ 2 , 3 ] . nod mice have alterations in leukocyte populations as compared to other mouse strains [ 4 , 5 ] . it is therefore possible that the extent of change may associate with the likelihood and rate of diabetes development in individual mice and that this may reveal markers that may help stratify the rate of progression to diabetes in man . we , therefore , quantified leukocyte populations in peripheral blood from nod and nor mice in biweekly intervals from 4 weeks to 36 weeks of age or until diabetes onset . we compared trajectories of t cell and b cell subpopulations and of nk cells , granulocytes , and monocytes between nod and nor mice and within nod mice that progressed and did not progress to diabetes . nod ( n = 71 ) and nor ( n = 40 ) mice were longitudinally followed up ( suppl . figure a.1 in supplementary material available online at http://dx.doi.org/10.1155/2016/4208156 ) . in the experimental groups ( nod , n = 58 mice ; nor , n = 22 mice ) , follow - up included biweekly venous blood sampling ( heparin coated tubes ) for facs phenotyping , determination of insulin autoantibody ( iaa ) levels , and blood glucose concentration and for assessment of weight . in addition , a control group of 13 nod and 18 nor mice was naturally followed up for growth and diabetes development without blood sampling to assess whether frequent blood sampling would affect diabetes development . all mice were kept under the same specific pathogen - free ( spf ) conditions at the institute of diabetes research , helmholtz zentrum mnchen . diabetes development was monitored by weekly measurement of urine glucose ( diastix , bayer , leverkusen , germany ) and confirmed by a venous blood sugar level > 13.9 mouse breeding and experiments were carried out in accordance with german legal guidelines and were approved by the local animal welfare authority ( license number tva 70/07 ) . cells were resuspended and incubated with fc - blocking solution and subsequently with surface antibodies for 15 minutes on ice ( suppl . dead cells were excluded using propidium iodide - staining and leukocytes were gated via cd45 . data were acquired with an lsr ii - hts cytometer ( franklin lakes , nj , usa ) . the resulting data were analyzed with flowjo ( flowjo enterprise , oregon , usa ) using boolean gating ( suppl . kaplan - meier survival analyses and log - rank statistics were used to estimate diabetes progression in nod mice . longitudinal trajectories of iaa , t , b , and other cell subpopulations were modeled using first- , second- , and third - order polynomial growth models for each measure and model selection performed according to the akaike information criterion . trajectories were compared between ( a ) nod and nor mice , ( b ) nod mice that developed overt diabetes and nod mice that did not develop diabetes and between nod mice that progressed rapidly ( by age of 21 weeks which was the median age of diabetes development in nod mice that developed diabetes ) and nondiabetic nod mice . for comparisons , trajectories were analyzed until age of 30 weeks except for comparisons with the nod mice that developed diabetes rapidly , which were analyzed until age of 21 weeks . the overall level of significance was set to a two - tailed p value of 0.05 . for the group comparisons of the 14 cell subpopulations we accounted for multiple testing resulting in the bonferroni corrected significance level of 0.004 . longitudinal trajectories were visualized by time pointwise means and confidence intervals ( ci ) and smoothed locally via loess . in the experimental groups , 33 of the 58 female nod mice developed diabetes at a median age of 22 weeks ( iqr 18 to 27 weeks ) and a cumulative risk at age of 36 ( end of the study ) of 32% ( ci 21%49% ) . none of the 22 nor mice developed diabetes during follow - up . the incidence of diabetes in nod mice was stable from age of 16 weeks ( 9% per 2 follow - up weeks from age of 10 weeks to age of 30 weeks , figure 1(a ) ) . no difference in diabetes development was observed between the nod mice that were bled weekly as part of the study ( 57% by age of 36 weeks ) and nod mice that were not bled ( 62% , p = 0.89 ) , indicating that frequent blood sampling did not affect diabetes development ( figure 1(b ) ) . weights were comparable between the nor and nor mice and between the nod mice that developed diabetes and nod mice that remained diabetes - free ( suppl . trajectories of iaa were higher in nod mice than in nor mice ( figure 2(a ) , p = 0.001 ) and higher in nod mice that developed diabetes as compared to nod mice that did not develop diabetes ( figure 2(b ) , p = 0.002 ) . trajectories of total t cells ( cd3 ) , t helper cells ( cd4cd3 ) , and cytotoxic t cells ( cd8cd3 ) were higher in nod mice compared to nor mice ( p < 0.001 , figure 3(a ) ) . despite this , cd4cd25 regulatory t cells and the cd44 subpopulation of cd8 t cells were lower in nod mice compared to nor mice ( p < 0.001 , figure 3 ) . no differences were found for any of the t cell populations between nod mice progressing to diabetes and nod mice that remained diabetes - free ( figure 3(b ) ) , nor between the nod mice that developed diabetes early as compared to mice that remained diabetes - free ( suppl . trajectories of total b cell frequencies ( cd19 and cd19b220igd ) and b cell subpopulations were significantly different between nod and nor mice with nod mice presenting higher frequencies of later stage b cells ( p < 0.001 , figure 4 ) . within the b cell compartment , nor mice showed a higher percentage of nave ( igdigm ) and activated ( igdigm ) b cells , whilst nod mice had higher percentages of igd igm cells ( figure 4 ) . the trajectories of b cells and b cell subpopulations were similar between nod mice that progressed to diabetes and nod mice that remained diabetes - free ( figure 4 ) . the trajectories of granulocyte and monocyte frequencies were lower in nod mice compared to nor mice and the trajectory of nk cell frequencies was higher in the nod mice ( figure 5 ) . no differences were found within nod mice relative to diabetes progression ( figure 5 ) . here we used the nod mouse model to portray longitudinal alterations of multiple leukocyte populations from birth to age of 36 weeks with the intention to identify potential biomarkers that may associate with the likelihood and rate of autoimmune diabetes development . we found profound differences in the circulating b cell compartment of nod compared to nor and additionally significant but less pronounced differences in t cells , granulocytes , and monocytes . however , none of these differences were able to predict which nod mice would develop diabetes or when the mice would develop diabetes . the only assessed immune marker which distinguished progressor from nonprogressor nod mice was the autoantibody response to insulin as previously described . the study is unique because it included prospective frequent phenotyping and utilized advanced statistical modeling of longitudinal data for the analysis . limitations include the low blood volume that restricts how many cell populations were examined as well as the ability to precisely measure rare cell phenotypes . since we did not examine cells in lymphoid organs and in the pancreas , we do not know if any of the observed alterations are generalized to the immune and hematopoietic systems . some of the findings in the nod mice were similar to what is observed in man . the relationship between increased iaa and more diabetes development is reflected by the faster rate of progression in antibody children if they have an earlier seroconversion or have higher islet autoantibody titers [ 13 , 14 ] . similar to nod mice , although much less pronounced , girls with islet autoantibodies progress to diabetes faster than boys . finally , it appears that both nod mice and multiple islet autoantibody positive children progress to diabetes at a constant rate . in mice , this is from around 10 weeks of age in our colony , while in children it is from the time of seroconversion . such a constant rate raises the possibility that progression is stochastic rather than induced by single events . nod mice are reported to have alterations in immune cell numbers and function [ 16 , 17 ] . we confirm this and show that , as compared to genetically similar nor mice , they have more circulating cd4 and cd8 t cells but lower circulating cd4cd25 t cells . most striking were the novel differences observed in the b cell population with a more general evidence of b cell maturation from early age in the nod mice . fiorina and colleagues describe that depletion of mature ( cd22-positive ) b cells reverses autoimmune diabetes in nod mice , which argues for a role of b cells in diabetes development in nod mice . more subtle differences in circulating b cell subpopulations have also been observed in patients with type 1 diabetes . we confirmed that nor mice have insulin autoantibodies , but to a lower extent than nod mice as previously demonstrated . circulating monocyte and some of the observed differences in blood cell populations may provide susceptibility to developing autoimmunity . disappointingly , however , none of the differences were in any way related to whether the nod mice progressed to diabetes , suggesting that they neither contribute to progression nor reflect other changes that occur during progression . longitudinal trajectories of leukocyte subpopulations were not found to be valuable biomarkers to predict disease progression in nod mice .

immune phenotyping provides insight into disease pathogenesis and prognostic markers . trajectories from age of 4 to 36 weeks were modeled for insulin autoantibodies and for leukocyte subpopulations in peripheral blood from female nod ( n = 58 ) and nor ( n = 22 ) mice . nod mice had higher trajectories of insulin autoantibodies , cd4 + and cd8 + t lymphocytes , b lymphocytes , igd+igm b lymphocytes , and nk cells and lower trajectories of cd4+cd25 + t lymphocytes , igm+ b lymphocytes , granulocytes , and monocytes than nor mice ( all p < 0.001 ) . of these , only the increased iaa trajectory was observed in nod mice that developed diabetes as compared to nod mice that remained diabetes - free . therefore , the profound differences in peripheral blood leukocyte proportions observed between the diabetes - prone nod mice and the diabetes - resistant mice do not explain the variation in diabetes development within nod mice and do not provide markers for diabetes prediction in this model .

A firefighter walks past a home destroyed by the Carr Fire on Sunriver Lane in Redding, Calif., on Friday, July 27, 2018. A spokesman says the number of homes and structures threated by the Northern... (Associated Press) A firefighter walks past a home destroyed by the Carr Fire on Sunriver Lane in Redding, Calif., on Friday, July 27, 2018. A spokesman says the number of homes and structures threated by the Northern California wildfire has increased after the fire exploded overnight. (AP Photo/Noah Berger) (Associated Press) REDDING, Calif. (AP) — The Latest on California's devastating wildfires (all times local): 8:15 p.m. Firefighters say 500 structures have been destroyed in a raging Northern California wildfire and another 5,000 are threatened. Cal Fire released the updated figure Friday, though the number of homes burned in the so-called Carr Fire is expected to increase. Earlier Friday, fire officials said 65 structures had been destroyed by the fast-moving blaze in Shasta County. The blaze grew to 75 square miles (194 square kilometers) by Friday night. It began Monday with a mechanical failure of a vehicle. It grew completely out of control on Thursday, tearing through two small communities and reaching the city of Redding. Tens of thousands of people fled the city in fear of their lives from the blaze, which has killed two firefighters. ___ 7:20 p.m. Yosemite Valley won't be open to all visitors for another week because of a massive wildfire that has grown to nearly 72 square miles (186 square kilometers). Yosemite National Park officials said Friday that the park won't reopen to everyone until the afternoon of Aug. 3. They say "limited visitor services" will be available inside the valley until then. Yosemite Valley has been closed since July 25 because of smoke from a fire now 29 percent contained. The closure has been heartbreaking for travelers, many of whom had planned their trips months in advance to hike and climb amid the spectacular views in Yosemite. At least 1,000 campground and hotel bookings had been canceled through Thursday. ___ 5:45 p.m. The police chief of the Northern California city hit hard by a fast-moving wildfire is among those whose homes went up in flames. Redding Police Chief Roger Moore told the Los Angeles Times that he and two other police officers lost their homes in Shasta County's Carr Fire. Moore estimates at least 100 homes were destroyed overnight Thursday as the flames jumped the Sacramento River and raced into the outskirts of Redding. More than 37,000 residents have been evacuated. The city of 92,000 is about 100 miles (160 kilometers) south of the Oregon border. Moore said the family saved valuables such as photos and documents, but his wife and children are anxious and sad. ___ 3:30 p.m. An Associated Press reporter has counted at least 125 homes destroyed by a deadly blaze in Northern California. Earlier Friday, fire officials said 65 structures had been destroyed by the fast-moving blaze in Shasta County. The AP reporter on Friday afternoon counted 66 burned homes in the Lake Redding Estates neighborhood and another 60 in nearby Lake Keswick Estates. The explosive wildfire in Northern California has killed two firefighters and officials say thousands have abandoned their homes in and around Redding. Authorities are warning that the blaze will probably burn deeper into urban areas before there is any hope of containing it. ___ 3:15 p.m. A fire official says winds fanning a deadly blaze in Northern California were so strong that trees were ripped from the ground, flew in the air and landed across the street. California Department of Forestry and Fire Protection spokesman Chad Carroll said Friday many of those trees landed on homes. He says that winds were so extreme Thursday that embers traveled up to a mile ahead of the flames. Carroll says the wildfire that started Monday and has killed two firefighters is mainly burning near the city of Redding, which has about 90,000 residents. But he says extreme winds are expected again Friday afternoon and says people in the area should be ready to evacuate. Mandatory evacuations were extended overnight to include the city of Shasta Lake, which has about 10,000 residents. ___ 2:20 p.m. Residents of a Redding, California, neighborhood where several homes were destroyed say they had to scramble to escape the blaze. Jim Chapin says he got home at around 7:30 p.m. Thursday and police were there telling people to evacuate the Lake Redding Estates neighborhood. Chapin says his wife left, but he stayed behind to hose down the roof, gutters and fallen leaves. He says that shortly afterward, the fire was burning trees behind neighbors' homes and ferocious winds whipped up branches, burning leaves, garbage-can lids, wood and other debris. Chapin says the streets were so jammed with traffic that there was no way for firefighters to come in. The 79-year-old returned to the neighborhood Friday and cried when he found his home still standing. ___ 1:10 p.m. The Redding, California, firefighter killed by a massive blaze in Northern California has been identified as Jeremy Stoke. The Redding firefighters union says Stoke was a fire inspector but released no other information. He was the second victim of the blaze that started Monday in Shasta County. Crews on Thursday found the body of a bulldozer operator who was hired privately to clear vegetation in the blaze's path. Officials said the fire burned over the operator as he worked to try to contain the blaze. ___ 12:30 p.m. California Department of Forestry and Fire Protection spokesman Scott McLean says at least 37,000 people had to evacuate after a fatal blaze tore through Northern California communities. McLean says they are asking people to promptly heed evacuation orders. Fire officials say strong winds pushed the massive wildfire into the city of Redding on Thursday. Dennis Beck, chief of the Shasta Lake Fire Protection District, tells the Record Searchlight that firefighters are bracing for winds forecast for Friday afternoon that could blow the blaze into the city of Shasta Lake, north of Redding. Beck says the entire city remains under mandatory evacuation. He says easterly winds that could reach up to 8 miles per hour are expected by 4 p.m. Friday. ___ 12:15 p.m. Officials say the three firefighters injured while fighting a massive blaze burning in Northern California were treated for burns to their ears, face and hands. The Marin County Fire Department says its three firefighters were assigned to defend buildings when they were hit by a "sudden blast of heat." The department says all were treated at Mercy Medical Center in Redding, California, and released and that one of them will be evaluated at UC Davis Burn Center in Sacramento. One firefighter and a bulldozer operator have been killed by the fire. Hospital spokesman Mike Mangas says five civilians were also treated for fire-related injuries. He says their injuries are not serious. He says six babies in the hospital's neonatal intensive care unit where premature newborns receive care were evacuated to the UC Davis Children's Hospital out of precaution. ___ 12:00 p.m. Steve Hobson says he thought he'd stay behind to save his house as a Northern California wildfire raged but heat from the flames burned his skin and the smoke made it hard to breathe. The former urban and wildland firefighter from the city of Redding said Friday he felt the fire sucking the air from the around him, whipping up swirling embers in a "fire tornado." He says police pounded on doors telling everyone to leave and that he fled through walls of burning embers on both sides of the street. He returned to his home Friday morning and found the perimeter fence of his house burned along with a backyard shed. But he says his house made it through the night. ___ 11:38 a.m. A spokesman says the number of homes and structures threated by a Northern California wildfire has increased tenfold to 5,000 after the fire exploded overnight. CalFire spokesman Scott Kenney said Friday that the updated number reflects recent evacuations. Kenney says the fire is only 3 percent contained and could spread in any direction. Officials have put the destruction at 65 structures, though it is likely to jump much higher. Dozens of homes were destroyed in subdivisions along the Sacramento River. At least two dozen homes in Redding Lakes Estates were smoldering, though others escaped the flames unscathed. Aerial footage showed dozens of homes were also in ruins in Keswick Lake Estates to the north. ___ 11:17 a.m. A 32-year-old man has been charged with intentionally starting nine Southern California fires, including one that has chased thousands of residents of from mountain communities. The Riverside County District Attorney's Office says Brandon McGlover of Temecula will be arraigned Friday on 15 felony counts that carry a potential sentence of life in prison. All nine fires were set Wednesday in the Idyllwild, Anza and Sage areas about 100 miles east of Los Angeles. One became the Cranston Fire that has grown to 18 square miles (46 square kilometers) in the Idyllwild area of the San Jacinto Mountains. Five homes have been destroyed, more than 4,900 structures are threatened and an estimated 6,000 people have been evacuated. McGlover is being held in lieu of $1 million bail. He's scheduled to appear in court Friday afternoon at the Southwest Justice Center in Murrieta. ___ 11:00 a.m. An official says more than 5,000 people have been evacuated to shelters and that authorities expect a destructive blaze in Northern California to continue moving into urban areas. California Governor's Office of Emergency Services spokesman Kelly Huston says they are coordinating bringing in aircraft from the California National Guard to help fight the flames. Officials say the extremely erratic wildfire near the city of Redding is growing rapidly amid scorching temperatures, low humidity and windy conditions. Temperatures are forecast to reach 110 degrees (43 Celsius) on Friday. Huston says officials are moving emergency supplies including cots and food to four shelters set up in Shasta County. He says the shelters are preparing for what could be a "longer-term" event. ___ 10:20 a.m. A hospital official says eight people with fire-related injuries have been treated at the Mercy Medical Center in Redding, California. Hospital spokesman Mike Mangas says three of the injured are firefighters hurt in a fatal blaze burning in Shasta County. He says none of the injuries are serious. Mangas says people are arriving at the hospital with respiratory problems. Mangas says six babies in its neonatal intensive care unit, which cares for premature newborns, were evacuated out of precaution. He says the hospital was preparing high-risk patients to be evacuated, but the hospital remains open and fully functional. ___ 9:25 a.m. Residents of Northern California communities impacted by a massive wildfire say they had minutes to evacuate after officials knocked on their doors in the middle of the night as the fire expanded rapidly. Sharon Stapleton tells the Record Searchlight newspaper that she and her husband grabbed a pillow, some shirts and pants, medicine, important documents and their two dogs and left in their sport utility vehicle and their motor home. Stapleton says they left after a police officer knocked on their door Thursday, which was her 71st birthday. Stapleton says she celebrated while sitting on a folding chair on the grassy lawn outside a shopping center in Redding, California, making calls to find out if their rented home survived. She says some of her neighbors stayed put, hoping to ride out the firestorm. ___ 8:30 a.m. Fire officials say 65 structures have been destroyed by a fatal wildfire tearing through rural Northern California towns. That's up from a previous report of 15 destroyed. The California Department of Forestry and Fire Protection says 500 other buildings are threatened by the massive blaze that has killed two firefighters. Officials say the extremely erratic wildfire in and around the city of Redding is growing rapidly amid scorching temperatures, low humidity and windy conditions. The blaze that began Monday grew overnight Thursday to 70 square miles (180 square kilometers). ___ 8:05 a.m. Official say a firefighter has been killed by a massive Northern California wildfire, raising the death toll to 2. The California Department of Forestry and Fire Protection said Friday that a firefighter with the fire department in the city of Redding was killed fighting the blaze in Shasta County. The department says it is investigating the death. No other details were provided. The blaze on Thursday killed a bulldozer operator as he worked to try to contain the blaze. ___ 7:40 a.m. A wildfire in the San Jacinto Mountains of Southern California has grown to 18 square miles (46 square kilometers). Authorities say just 3 percent of the fire's perimeter is contained Friday morning. Conditions are calm but gusty winds are expected by afternoon. The fire allegedly was intentionally set Wednesday and quickly spread through timber and brush near the town of Idyllwild and other communities about 100 miles (160 kilometers) east of Los Angeles. More than 4,900 structures are threatened and an estimated 6,000 people have been evacuated. In the Sierra Nevada, the Ferguson Fire continues to grow just outside Yosemite National Park. Authorities say it is now nearly 72 square miles (186 square kilometers), but containment has increased to 29 percent. Yosemite Valley and the Wawona and Mariposa Grove areas of the national park remain closed. ___ 7:10 a.m. Hundreds of people who fled their homes because of a massive Northern California wildfire are crowding into shelters as the blaze brightens the sky with a red glow. Videos posted to social media show long lines of cars slowly moving on a highway near the city of Redding as the wildfire rages on the hills behind. Dozens of evacuees are going to Shasta College, where officials have set up a shelter. Another shelter has been set up at an elementary school. Mandatory evacuations were ordered overnight for the city of Shasta Lake, which has about 10,000 residents. People in the western part of Redding, which has about 92,000 residents, were also asked to evacuate. The blaze grew overnight to 70 square miles (180 square kilometers). ___ 6:40 a.m. More evacuations have been ordered as a devastating wildfire torches an area in and around the Northern California city of Redding. The blaze that broke out Monday exploded late Thursday and raced into small communities west of Redding before entering the city limits. Fire officials say dozens of homes have burned, though conditions make it impossible to determine an accurate count and the number could climb much higher. A bulldozer operator on the fire lines was killed and three firefighters suffered burns. Some civilians also have been injured. Mandatory evacuations were extended overnight to include the city of Shasta Lake, which has about 10,000 residents. Parts of Redding, which has about 92,000 residents and is the largest city in the region, also have been evacuated. ___ 2 a.m. An explosive wildfire tore through two small Northern California communities, killing a bulldozer operator on the fire lines, burning three firefighters, destroying dozens of homes and forcing thousands of terrified residents to flee. Flames swept through the communities of Shasta and Keswick before jumping the Sacramento River on Thursday and reaching Redding It's a city of about 92,000 people and the largest in the region. Residents in the western part of Redding who hadn't been under evacuation orders were caught off guard and had to flee with little notice, causing miles-long traffic jams as flames turned the skies orange. Many firefighters turned their focus from the flames to getting people out alive. ||||| A raging wildfire in Northern California that swelled in size Friday has killed two people and injured at least three firefighters, officials said. Interested in ? Add as an interest to stay up to date on the latest news, video, and analysis from ABC News. Add Interest The Carr Fire in Shasta County has claimed the lives of a bulldozer operator and a city of Redding firefighter, according to officials from the California Department of Forestry and Fire Protection, the U.S. National Park Service and the Shasta County Sheriff's Office. The "mechanical failure of a vehicle" ignited the blaze in Whiskeytown on Monday, officials said. The fire had burned an area of more than 48,000 acres by Friday night, with a containment of just 5 percent. Josh Edelson/AFP/Getty Images Justin Sullivan/Getty Images Mark McKenna via ZUMA The flames ripped through northwest Shasta County then spread southeast, sweeping across the Sacramento River late Thursday and roaring toward the city limits of Redding, which is home to 92,000. At least 500 homes, businesses and other structures have been destroyed by the fast-moving fire, while 75 others have been damaged. Another nearly 5,000 structures remain threatened, officials said. "A lot of our challenges right now with this fire is the weather. Our humidity is really low," Eric Colter, with the Redding Bureau of Land Management, told ABC station KGO in San Francisco. "High temperatures and we're getting a lot of evening and late afternoon winds." Noah Berger/AP Justin Sullivan/Getty Images The blaze is "taking everything down in its path," and the situation on the scene is "very dynamic" and "a heck of a fight,” Scott McLean, a spokesman for the crews battling the Carr Fire, told The Associated Press. A total of 3,410 people are working to contain the fire, along with 328 engines, 17 helicopters and 62 bulldozers. Gusty winds reaching 60 mph are fanning the flames and creating fire tornadoes, or "firenadoes," that move erratically and are strong enough to overturn vehicles "like toys," McLean told reporters at a news conference late Thursday. Fred Greaves/Reuters NASA via AP Officials have ordered road closures and the evacuation of thousands of homes threatened by the Carr Fire. The California Highway Patrol is going door to door to assist, Sgt. Tim Hinkson told reporters. ABC News' Max Beller, Frank Elaridi, Courtney Han, Will Gretsky and Rex Sakamoto contributed to this report. ||||| The wildfires tearing through northern California have grown in size overnight, and hundreds of homes and businesses have been lost to the flames. Two people have been killed so far by the Carr Fire, and another three firefighters have been injured, CNN reported. By Friday night, the blaze had destroyed an area of more than 48,000 acres. The fire raging in Shasta County has killed a bulldozer operator and a firefighter, according to the California Department of Forestry and Fire Protection, the U.S. National Park Service and the Shasta County Sheriff's Office. REUTERS/Fred Greaves The town of Redding and its 92,000 people are in the path of the fire, which spread across the Sacramento River overnight. Emergency services have only managed a five percent containment thus far. At least 500 homes, business and other structures have been consumed by the fire, with another 75 damaged. As many as 5,000 buildings are still threatened by the inferno, which has doubled in size in just 12 hours. Around 38,000 people have been evacuated from the burn area, and 800 troops from the state national guard deployed to assist firefighting efforts. The “mechanical failure of a vehicle” started the fire in Whiskeytown on Monday, officials said. Low humidity and high winds are exacerbating the blaze. The winds are causing the formation of fire tornados, or “firenadoes,” which are strong enough to overturn vehicles according to Scott McLean, a spokesman for the crews battling the Carr Fire. He told the Associated Press that the fire is “taking everything down in its path,” and that the situation is “very dynamic” and “a heck of a fight.” More than 3,400 people are fighting the spreading flames, using 328 engines, 17 helicopters and 62 bulldozers. Evacuation orders have been causing heavy traffic as residents flee. The fire’s rapid spread caught many residents off guard. Even local television channel KRCR had to halt its broadcast and leave the news station. During a live show, anchor Allison Woods told viewers, “Right now we are being evacuated—that's why we are kind of closing out right now. We are going to leave the station because [it] is now unsafe to be here.” REUTERS/Fred Greaves California Governor Jerry Brown has declared a state of emergency for the Riverside and Shasta counties in response to fires. He wrote to President Donald Trump and the Federal Emergency Management Agency (FEMA) requesting assistance for the communities affected by the blaze. “Supplemental federal assistance is necessary to save lives and to protect property, public health and safety, and to lessen the effects of this imminent catastrophe,” the governor wrote. Brown asked for “shelter supplies and water for 30,000 evacuated residents in Shasta County; U.S. Department of Agriculture's assistance in evacuating large animals; mass care; evacuation assistance for individuals with access and functional needs; and ambulatory transport.” The Carr inferno is one of 89 active large fires burning in 14 U.S. states, six of which are in California. Another, the Ferguson Fire, has forced Yosemite National Park to close after one person was killed and several more injured. So far, 46,675 acres have been destroyed. Around 3,800 firefighters are responding, and have achieved 29 percent containment. ||||| The latest on the Carr Fire burning in Redding: Premium content for only $0.99 For the most comprehensive local coverage, subscribe today. SUBSCRIBE NOW Fatalities: Two confirmed, Don Ray Smith, 81, of Pollock Pines, a private bulldozer operator killed Thursday while trying to contain the flames; fire inspector Jeremy Stoke, a Redding firefighter since 2004 who was killed battling the fire Thursday night. Family members said Saturday three others – a 70-year-old grandmother and children, ages 4 and 5, were killed. Shasta County Sheriff’s Office has not confirmed that, but says 14 people are missing. This is a breaking story, we’re reporting live updates here. Injuries: Three Marin County firefighters suffered burns and were treated. Mercy Medical Center in Redding reported treating eight people for burn-related injuries, none serious. Missing: At least 11 other people are missing Size: 85,000 acres, or about 132 square miles. The fire is larger than the 61-square-mile size of Redding, which has a population of about 92,000. Containment: 5 percent. No estimate of when Cal Fire will reach full containment. Carr Fire Red circles on this live-updating map are actively burning areas, as detected by satellite. Orange circles have burned in the past 12 to 24 hours, and yellow circles have burned within the past 48 hours. Yellow areas represent the fire perimeter. Source: National Interagency Fire Center Cause: Vehicle malfunction on Monday afternoon at Highway 299 and Carr Powerhouse Road in Whiskeytown. Evacuations: More than 38,000 have been ordered to evacuate from communities on both sides of the Sacramento River. See the complete list of evacuations here. Damages: 500 homes destroyed, 75 damaged, 4,978 threatened. Weather outlook: High temperatures of up to 110 degrees are expected Saturday afternoon. At noon, the temperature was recorded as 88 degrees. A red flag warning is effect through Monday morning for the region. Firefighting resources: 3,410 firefighting personnel, 328 engines, 17 helicopters, 62 bulldozers. Updates: This is a breaking story, we’re reporting live updates here. Video updates: See the latest videos on our video page including a 360-degree view of the fire approaching Igo and a view of what its like to drive through Keswick after the flames. On our Facebook page: Like us to get the latest updates and see live video as it happens.

– California's latest wildfire is only getting worse, and "firenadoes" aren't helping. That's the term used by a spokesman for the crews battling what is known as the Carr Fire in Shasta County, reports ABC News. Think winds of about 60mph fanning flames into a "fire tornadoes" that can overturn vehicles "like toys," explains Scott McLean. And this all started in a mundane way: Authorities say a vehicle broke down Monday afternoon by Highway 299 in Whiskeytown, reports the Sacramento Bee, triggering a brush fire that soon spun out of control. The blaze worsened overnight, expanding to 75 square miles, or about 48,000 acres, reports the AP. Authorities say 500 structures have been destroyed and another 50,000 are in danger. Two people fighting the wildfire have been killed and three others injured, reports CNN. One of those killed was a firefighter from Redding, Jeremy Stoke, and the other was a private bulldozer operator, unidentified. The fire has forced the evacuation of nearly 40,000 people so far. (An arsonist is blamed for a different wildfire.)