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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Breast Cancer Nos Metastatic Recurrent Women Aged 18 years and over With an invasive breast cancer diagnosed by cytology or histology Tumors cT0 to cT3, CN0-3 No clinical evidence of metastasis at the time of Untreated including scored for breast cancer surgery in progress Patient receiving a social security system Patient mastering the French language Free and informed consent for additional biological samples, different questionnaires and collecting information on resource usage Metastatic breast cancer Local recurrence of breast cancer History of cancer within 5 years prior to entry into the trial other than basal cell skin or carcinoma in situ of the cervix Already received treatment for breast cancer ongoing Blood transfusion performed for less than six months Persons deprived of liberty or under supervision (including guardianship)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Thyroid Cancer Newly diagnosed with a first occurrence of thyroid cancer <2-4 weeks of diagnosis (i.e., histologically confirmed thyroid cancer (papillary, follicular, or medullary type; TNM classification system) Willing to participate in the EG meetings >18 years Alert and capable of giving free and informed consent Able to speak and read English or French Anaplastic thyroid cancer Karnofsky Performance Status (KPS) score <60 (rated by the Research Coordinator (RC) or referring physician) or expected survival <6 months according to clinical judgment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Chronic Pain Women Clinical diagnosis of chronic pelvic pain More than eighteen years Non-menstrual or noncyclic pelvic pain Duration of pain of at least 6 months Duration of pain less than 6 months Women who were pregnant in the last 12 months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Coronary Artery Stenosis Age ≥ 18 years Patient with an indication for PCI including angina (stable or unstable), silent ischemia (in absence of symptoms a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80 must be present), or recent STEMI. For STEMI the time of presentation to the first treating hospital, whether a transfer facility or the study hospital, must be >24 hours prior to randomization and enzyme levels (CK-MB or Troponin) demonstrating that either or both enzyme levels have peaked Non-target vessel PCI are allowed prior to randomization depending on the time interval and conditions as follows: a. During Baseline Procedure: i. PCI of non-target vessels performed during the baseline procedure itself immediately prior to randomization if successful and uncomplicated defined as: <50% visually estimated residual diameter stenosis, TIMI Grade 3 flow, no dissection ≥ NHLBI type C, no perforation, no persistent ST segment changes, no prolonged chest pain, no TIMI major or BARC type 3 bleeding. b. Less than 24 hours prior to Baseline Procedure: i. Not allowed (see #3). c. 24 hours-30 days prior to Baseline Procedure: i. PCI of non-target vessels 24 hours to 30 days prior to randomization if successful and uncomplicated as defined above. ii. In addition, in cases where non-target lesion PCI has occurred 24-72 hours prior to the baseline procedure, at least 2 sets of cardiac biomarkers must be drawn at least 6 and 12 hours after the non-target vessel PCI. If cardiac biomarkers are initially elevated above the local laboratory upper limit of normal, serial measurements must demonstrate that the biomarkers are falling. d. Over 30 days prior to Baseline Procedure: iii. PCI of non-target vessels performed greater than 30 days prior to procedure whether or not successful and uncomplicated Patient or legal guardian is willing and able to provide informed written consent and comply with follow-up visits and testing schedule. Angiographic (visual estimate) Treatment of up to three de novo target lesions, maximum of one de novo target lesion per vessel Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥2.5 mm to ≤4.25 mm and diameter stenosis ≥50% to <100% Lesion must be ≤28 mm long and can be covered by a single study stent with maximum length of 33 mm (note: multiple focal stenoses may be considered as a single lesion and be enrolled if they can be completely covered with one stent) TIMI flow 2 or 3 If more than one target lesion will be treated, the RVD and lesion length of each must meet the above criteria Planned procedures after the baseline procedure in either the target or non-target vessels STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital or in whom enzyme levels (either CK-MB or Troponin)have not peaked PCI within the 24 hours preceding the baseline procedure and randomization Non-target lesion PCI in the target vessel within 12 months of the baseline procedure History of stent thrombosis Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP Known LVEF <30% Subject is intubated Relative or absolute contraindication to DAPT for 12 months (including planned surgeries that cannot be delayed, or subject is indicated for chronic oral anticoagulant treatment) Hemoglobin <10 g/dL

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor Patients must sign an institutional review board (IRB)-approved informed consent document Patients must have been diagnosed with high-grade glioma World Health Organization (WHO) grade III: anaplastic astrocytoma, oligodendroglioma, ependymoma, or oligoastrocytoma; OR WHO grade IV: glioblastoma multiforme; or neuroepithelial tumors of uncertain origin (polar spongioblastoma, astroblastoma, or gliomatosis cerebri) As measured by conventional high spatial resolution MRI, the minimum diameter of the primary lesion (short axis) should be at least 5 mm Patients must be scheduled to receive: 1) standard chemotherapy with/without radiation therapy; OR 2) single-agent bevacizumab (Avastin) Patients with low-grade (WHO grade I or II) glioma Patients with metastatic disease Patients who have any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc), because such devices may be displaced or malfunction Patients who have any type of ferromagnetic bioimplant that could potentially be displaced Patients who have cerebral aneurysm clips Patients who may have shrapnel imbedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes) Patients with inadequate renal function (creatinine >= 1.5 times upper limit of normal) or acute or chronic renal insufficiency (glomerular filtration rate < 20 ml/min) Patients who are pregnant or breast feeding; urine pregnancy test will be performed on women of child bearing potential Patients who exhibit noticeable anxiety and/or claustrophobia or who exhibit severe vertigo when they are moved into the magnet bore Patients incapable of giving informed written consent, for the following reasons

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-21.0, Astrocytoma, Oligoastrocytoma, Mixed Ganglioneuroma Glioma Ganglioglioma Glioblastoma Multiforme Glioma Patient must have histological verification of one of the eligible diagnosis listed below. Biopsy is required at time of diagnosis, with the exception of optic pathway tumors. Patients with spinal cord disease are eligible if they have a lesion >1 cm in 2 dimensions. The following histologies are eligible Astrocytoma variants: fibrillary, protoplasmic, mixed Pilocytic astrocytoma, including pilomyxoid variants Pleomorphic xanthoastrocytoma Infantile desmoplastic astrocytoma Ganglioneuroma Oligodendroglial tumor Mixed glioma (including oligoastrocytoma) Anaplastic astrocytoma Anaplastic oligoastrocytoma Patient must not have had myelosuppressive chemotherapy ≤ 3 weeks prior to entry onto this study (or 6 weeks if prior nitrosourea) Patient must not have had any anti-neoplastic biologic agent ≤7 days prior to entry onto this study (or at least 3 half-lives for biologic agents with a long half-life) Patient must not have received craniospinal radiotherapy or involved field radiotherapy to the local tumor (and/or tumor designated as "measurable" for protocol purposes) ≤ 24 weeks prior to study entry; focal radiation to areas of symptomatic metastatic disease must not be given within 14 days of study entry Patient must not have received bevacizumab, or other anti-VEGF inhibitor in the last 3 months Patient must not require a major surgical procedure ≤ 21 days prior to beginning therapy Patient must not require an intermediate surgical procedure ≤14 days prior to beginning therapy Patient must not require a minor surgical procedure (i.e., Broviac line or infusaport placement) ≤ 7 days prior to beginning therapy, and the wound must be healed prior to initiation of therapy There should be no anticipation of need for major surgical procedures during the course of the study Patient must not have received any growth factors ≤7 days of entry onto this study Patient must not be taking clopidogrel, dipyridamole, or aspirin therapy >81 mg/day

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Glioblastoma Multiforme patients with glioblastoma or anaplastic astrocytoma legal age planned chemoradiation and adjuvant chemotherapy (according to Stupp et. al.) Fertile patients who refuse effective contraception during study treatment persistent drug and/or alcohol abuse patients not able or willing to behave according to study protocol patients in care patients that are not able to speak German

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, High Grade Glioma Patients with radiographically proven recurrent, intracranial high grade glioma will be eligible for this protocol. Patients must have evidence of tumor progression as determined by the Revised Assessment in Neuro-Oncology RANO following standard therapy High grade glioma includes glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified. (NOS) Magnetic resonance imaging (MRI) must be performed within 21 days prior to enrollment, and patients who are receiving steroids must be stable or decreasing for at least 5 days prior to imaging. If the steroid dose is increased between the date of imaging and enrollment, a new baseline MRI is required Patients must have completed only 1 prior course of radiation therapy and must have experienced an interval of greater than 12 weeks from the completion of radiation therapy to study entry Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade glioma is made There is no limit as to the number of prior treatments but patients must have radiographic evidence of progressive disease Recurrent tumor must be a solid, single, supratentorial, contrast-enhancing HGG which have a tumor diameter no larger than 4cm or volume of 34cm3 All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must be registered prior to treatment with study drug Patients must be> 18 years old, and with a life expectancy > 8 weeks Patients with Karnofsky performance status of > 70

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Bladder, Neurogenic Diagnosis of traumatic or nontraumatic suprasacral spinal cord injury (SCI) or multiple sclerosis (MS, based on a neurologist assessment and/or the McDonald criteria)(28) Age >18 years Stable method of bladder management for >3months (either spontaneous or provoked voiding, or intermittent catheterization) Bothersome urinary symptoms (urinary frequency, urgency, or urgency incontinence based on standard ICS definitions(29)) and completed 3 day voiding diary demonstrating at least 1 episode of non-stress based urinary incontinence over the 72hr period (this may be urgency based incontinence or unaware incontinence) Patient is able to read and speak English Based on Screening visit history Participation in another drug or device study in the 60 days prior to the screening visit Previous urologic surgery: Transurethral prostatectomy, bladder augmentation, sphincterotomy, bladder neck sling, artificial urinary sphincter, catheterizable channel, implantable electrostimulator/neuromodulator Current use of suprapubic catheter/foley catheter Unstable cardiac disease (uncontrolled hypertension, myocardial infarction, unstable angina, severe congestive heart failure (NYHA 3 or 4), ventricular arrhythmia (such as torsades de pointes), or stroke within the last 6 months) Clinically significant abnormal ECG The investigator believes the patient has an increased risk of QT prolongation (based on review of the screening ECG and patients concurrent medications) History of significant renal dysfunction within 1 year, or serum creatinine >150umol/L at screening visit (visit 1) History of significant liver disease within 1 year, or serum AST/ALT >2 times upper limit of normal, GGT >3 times upper limit of normal, total bilirubin >2 times upper limit of normal at screening visit (visit 1) History of pelvic radiation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 70.0-999.0, Glioma Patients aged ≥ 70 years Karnosky performance status (KPS) ≤60 Histologically confirmed HGG after tumor biopsy GBM Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Anaplastic Oligodendroglioma without IDH1 mutation and no codeletion 1p19q Estimated survival ≥ 3 months Normal liver, Kidney and bone marrow function Written informed consent Prior radiation therapy Other primary cancer

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Type 2 Diabetes Mellitus Informed consent obtained before trial-related activities (i.e., any activity that would not have been performed during routine patient management) Type 2 diabetes Adult patients over 18 years of age and less than or equal to 80 years of age HbA1c greater than or equal to 7.5% (NGSP standard=DCCT standard)=58 mmol/mol (IFCC standard) and less than or equal to 11.5%=102 mmol/mol Treated with MDI for at least the last 6 months Treated with/without metformin as only diabetes therapy apart from insulin Fasting C-peptide of 0.10 nmol/l or greater (ref. 0.25-1.0 nmol/l) BMI greater than 27,5 kg/m2 and less than 45 kg/m2 Type 1 diabetes Fasting glucose less than 6.0 mmol/l or greater than 15.0 mmol/l Unstable cardiovascular disease, NYHA Class II or greater heart failure , new symptoms of cardiovascular disease) Proliferative diabetic retinopathy or clinically significant macula oedema. Retinal photograph should not be older than 3 years Systemic glucocorticoid treatment during the last 3 months, however, patients using systemic corticoid treatment only for substitution of cortisol deficiency (physiologic doses) such as Addisons Disease, do not need to be excluded Acute coronary syndrome, stroke, coronary artery intervention or myocardial infarction during the previous 6 months Creatinine greater than 150 micromol/l Liver transaminases greater than double of the normal reference interval Treatment with other oral antidiabetic agents than metformin during the previous 3 months Treatment with GLP-1 receptor agonists within 90 days of screening

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-85.0, Primary Knee Replacement Male or female 2. Needs a primary TKR on the left or right knee 3. Diagnose of non-inflammatory degenerative joint disease (e.g., osteoarthritis, post-traumatic arthritis, avascular necrosis, etc.) 4. Over 18 years old 5. BMI>=30 6. Able to Understand what participation in the study entails and give written informed consent, and Follow surgeon/staff instructions, and Return for all follow-up evaluations, and Able and willing to undergo a preoperative full-leg, standing radiographs (all cases) Willing to consent (patient or his/her legal guardian) to participate in the study by signing and dating an approved consent Meet an acceptable preoperative medical clearance and is free of or treated for cardiac, pulmonary, hematological or other conditions that would pose excessive operative risk. 7. Presence of varus or valgus deformity of 15 degrees or less Currently enrolled in an investigational new drug or device study 2. Active Infection (including septic knee, distant infection, or osteomyelitis) 3. Severe hip arthrosis 4. Neurological disorders (including, but not limited to Parkinson's disease) 5. Prior ipsilateral unicompartmental knee arthroplasty, TKA, knee fusion or patellectomy 6. Hip or knee ankylosis 7. Inflammatory joint disease. 8. Either rheumatoid or post-traumatic knee arthritis 9. Scheduled for simultaneous bilateral TKA 10. Indications of intra and/or extra-articular deformations that would eliminate or tend to eliminate adequate implant support or prevent the use of an appropriately sized implant, such as polio, history of tibial plateau fracture, etc. 11. Any metal within 150 mm of the joint line for the operative-side knee 12. Knee deformities greater than 15 degrees of fixed varus, valgus, or flexion contracture on initial physical examination 13. A female who is pregnant or lactating 14. Current involvement in any personal injury litigation, medical-legal or worker's compensation claims 15. Arterial disease or stents that would the use of a tourniquet 16. Insufficient quality or quantity of bone to support the implant due to prior knee surgery (or surgeries), cancer, metabolic bone disease, osteoporosis/osteopenia (diagnosed or treated with medication), active/old/remote infection, etc. 17. Mental condition that may interfere with his/her ability to give an informed consent or interfere with his/her ability or willingness to fulfill the requirements of the study. 18. Condition that would place excessive demands on the implant (e.g., Charcot's joints, muscle deficiencies, multiple joint disabilities, skeletal immaturity, etc.). 19. Collateral ligament insufficiency. 20. Immunosuppressive disorder (e.g., AIDS, etc.) that would require cytotoxic drugs, corticosteroids, large dose of irradiation, or antilymphocytic serum. 21. An existing condition that would, in the opinion of the investigator, compromise participation or follow-up in this study

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioma Presumed recurrent glioma Age > 18 years Normal bone marrow function (WBC > 3000, Platelets > 100,000) Pregnancy History of photosensitivity, porphyria, or exfoliative dermatitis Hepatic dysfunction in the last 12 months [defined by aspartate aminotransferase(AST), alanine aminotransferase (ALT) , alkaline phosphatase (ALP) , bilirubin > 2.5 x normal] Serum creatinine > 180 µmol/L Estimated Glomerular Filtration Rate (eGFR)< 60 ml/min/1.73m2 Inability to undergo MRI with contrast

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Carpal Tunnel Syndrome Compression Neuropathy Patients will be recruited from the University of Alberta Hospital referred for CTS. will adult patients (over age 18) with at least one of the following symptoms: 1. numbness and parenthesis in the median nerve distribution; 2. Precipitation of those symptoms by repetitive motions that are relieved by rubbing and or shaking the hands; 3. Nocturnal awakening by those sensory symptoms, or 4. Weakness of thumb abduction and thenar atrophy Motor unit loss in the median nerve less than 2 SD below the mean for the age as determined by nerve conduction studies. 2. The presence of other neurologic conditions 3. Previous carpal tunnel release surgery 4. Cognitive impairment that renders the patient unable to provide informed consent; 5. Pregnancy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 7.0-18.0, Cerebral Palsy Children with unilateral spastic CP (with perinatal acquired hypoxic ischemic incidents) aged 7 to 18 years MACS levels I-III mentally able to perform the measurements Healthy Controls children attending primary or secondary school agd 7 to 18 years Surgical intervention <6 months Botulinum Toxin A treatment in the upper extremity < 6 months contractures in the upper extremity that might interfere with task performance Healthy Controls muscle disease lesion, fracture or cast < 6 months

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Metastatic Malignant Neoplasm in the Brain Primary Brain Neoplasm Recurrent Brain Neoplasm Have a diagnosis or suspected diagnoses of brain tumor (primary, recurrent, or metastatic) by standard clinical diagnosis such as pathology or imaging Planned for treatment with radiation, chemotherapy and surgical resection or any of these treatment strategies combined Inability to provide informed consent Pregnancy Inability to lie still for the imaging study Weight over 350 lbs

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-65.0, Anterior Cruciate Ligament Reconstruction Volumetric Muscle Loss Chronic Thigh Muscle Weakness Knee Arthroscopy One of the following: (1) s/p ACL reconstruction within the last three months prior to initiation of study training, (2) s/p knee arthroscopy within the last 2 weeks prior to initiation of study training, (3) S/p lower extremity trauma, unilateral with thigh weakness of at lest a 20% deficit compared to contralateral side and at least 6 months out from most recent trauma or surgery Fluent in English and able to consent Contralateral lower extremity involvement resulting in less than normal range of motion, muscle strength, or daily pain greater than 5/10 Pregnancy, verbal reporting Recent history of deep vein thrombosis, within the 12 months or on active treatment History of endothelial dysfunction, peripheral vascular disease, hypertension, diabetes, or people prone to capillary ruptures (bruising) (determined by verbal reporting by the patient) Active Infection Cancer (current diagnosis)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-40.0, Diagnostic and Monitoring Anesthesiology Devices Associated With Adverse Incidents Parturients elective cesarean section ASA class I or class II Emergent cesarean section Skin lesions over the site of local anesthetic injection Skin lesions over the sites where NIRS patches are about to be attached Patients with history of being allergic to NIRS patches Patients with coagulopathy or other contraindications for spinal anesthesia

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-90.0, Lumbar Spinal Stenosis Younger than 90 years old no communication barriers (e.g., English speaking, household telephone) Affirmative response to each of the three following questions a) Do patients have pain, weakness, numbness, or tingling in their legs when walking standing? b) Does this pain, weakness, numbness or tingling in their legs interfere with their daily activities? c) Have patients tried at least one non-surgical treatment for their leg symptoms (e.g., physical therapy, pain medications, spinal injection)? Have been scheduled for surgery on lower back for a condition called lumbar spinal stenosis non degenerative causes of LSS such as tumor infection trauma hemorrhage or epidural lipomatosis Prior lumbar spinal surgery spondylolisthesis with spinal instability significant cognitive impairment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Chronic Low Back Pain Mechanical Low Back Pain adults between 18 and 60 years old nonspecific low back pain : pain located between the twelfth rib and the inferior gluteal fold for which no specific source of pain could be identified chronic low back pain : pain present for 12 weeks or more, and included both constant and recurrent patterns of pain able to read and understand French History of surgery or major trauma to the spine Current use of medication known to impair physical effort and pain perception Lumbar scoliosis of more than 20° Collagenosis, severe osteoporosis Neuromuscular disease Malignant tumor Non-controlled hypertension Infection Radiculopathy Progressive neurologic defect

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Acute Oral Mucositis Pain Documentation of Disease: Histologic documentation of malignancy currently undergoing a course of RT (with or without chemotherapy) including the oral cavity and/or oropharyngeal area to a dose of at least 4500 cGy using more than 5 fractions (i.e., stereotactic body radiation therapy [SBRT] is not allowed). 2. Physical exam demonstrating evidence of radiotherapy-related mucositis in the visible oral cavity and/or oropharynx consistent with mucous membrane toxicity greater than 0 using the Acute Radiation Morbidity Scoring Criteria. 3. At least 4 (out of 10) patient-reported oral pain related to oral mucositis secondary to RT for which the patient seeks relief, as measured on the Oral Pain Assessment. Note: The pain score must be at least 4 at the time that the patient starts the first dose of study medication. The patient may be enrolled to the study if s/he, at times, has a pain score of at least 4, so long as initiation of study treatment begins when the pain score is at least 4. 4. Ability to complete questionnaire(s) by themselves or with assistance. 5. No known allergy to diphenhydramine, lidocaine, antacid (aluminum hydroxide, magnesium hydroxide, and simethicone), doxepin, tricyclic antidepressants, or any known component of the drug formulation in the testing arms. 6. No use of any anti-arrhythmic medication (except for beta-blockers) including lidocaine, linezolid, ipratropium, or medications with high anti-cholinergic potency (including neostigmine, a tricyclic antidepressant or a monoamine oxidase inhibitor) within 2 weeks prior to registration. 7. No current diagnosed untreated or unresolved oral candidiasis or oral HSV infection. 8. No history of untreated narrow angle glaucoma within 6 weeks prior to registration. 9. No untreated urinary retention within 6 weeks prior to registration. 10. No current use of glutamine or sucralfate powders at the time of registration (no washout required). 11. No cryotherapy for prophylactic mucosal protection within 6 weeks prior to registration. 12. Not pregnant, because patients eligible for this study will be receiving radiotherapy, which has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 28 days prior to registration is required. 13. Age ≥ 18 years 14. ECOG Performance Status 0, 1, or 2

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-85.0, Motor Weakness in Two or Four Limbs Damage in the Anterior Spinal Artery (ASA) Temperature and Superficial Sensation Urinary Retention or Bowel Disorder Patients with vascular risk factors 2. Patients with sudden weakness of the lower or upper limbs together with bowel disorder. 3. Window treatment not over 6 hours since the start of the event till the start of the treatment. 4. Patient without dissection of the aorta in the abdomen. 5. Patient without contraindication to IVtPA. 6. Patient with no etiology found after clarification Refusal to sign an ICF. 2. Reason for weakness is known. 3. Patient with contraindication IVtPA. -

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 14.0-50.0, Severe Aplastic Anemia In line with the 2009 Edition (United Kingdom) aplastic anemia diagnostic for SAA or VSAA; 2. Age less than 50 years old,willing to transplant； 3. No HLA-identical sibling donor； 4. Have HLA-mismatched related donors or unrelated donors ( ≥5/10 HLA matched loci in related donors; ≥8/10 HLA matched loci in unrelated donors ) 5. No serious infection or acute hemorrhage; 6. Cardiac ultrasound examination showed left ventricular ejection fraction is greater than 50%; 7. Both transaminase and serum creatinine level are no more than twice times the upper limit of normal value (ULN); 8. No acute infectious disease; 9. Ability to understand and the willingness to sign a written informed consent document. 10. ECOG score of 0-2 points Patients with severe infection or active bleeding; 2. With severe cardiac insufficiency, left ventricular ejection fraction <50%; 3. With severe liver dysfunction, liver function (ALT and the TBIL) is higher than the ULN 3 times; 4. With severe renal insufficiency, renal function (Cr) is twice higher than the ULN; or 24-hour urine creatinine clearance rate (Ccr) lower than 50ml/min; 5. Active tuberculosis, severe acute hepatitis and other infectious diseases in active period; 6. ECOG score more than 3 points; 7. Accompanied by malignant tumors and other clonal disease; 8. Poor compliance and the researchers considered unsuitable for MSC infusion

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Malignant Glioma Malignant Glioma, patients enrolled in study GLI01S Corresponding to contraindication of Gliadel Not applicable to indications of Gliadel

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Scarring Spinal Stenosis Herniated Disc Are 18 (eighteen) years of age or older at the time of surgery. 2. Patients with single or multi-level spinal stenosis undergoing open lumbar laminectomy, or patients with single-level herniated nucleus pulposus undergoing single-level lumbar microdiscectomy 3. Are willing and able to return for the scheduled follow-up visits, follow post operative instructions and undergo the required radiographic exams for up to 5 time points between 4 weeks and 24 months post-surgery (6 weeks ± 2 weeks, 12 weeks ± 2 weeks, 6 months ±1 month, 1 year±2 months, and 2 years ±2 months post-surgery), including one study MRI-scan at 12 weeks ±2 weeks for the first 20 patients enrolled. 4. Are willing and able to sign study specific informed consent Non-English speaking patients 2. Non-surgical candidate defined as any patient deemed by the surgeon not to be a surgical candidate cannot participate for the following reasons: that patient does not meet indications for lumbar laminectomy or microdiscectomy surgery, patient has a contraindication to surgery such as medical comorbidities, pregnancy, etc. 3. Allergic to aminoglycoside antibiotics 4. Is a prisoner 5. Is involved in worker's compensation or other litigation relative to the spine injury 6. Has a history of drug or alcohol abuse within the last 12 months 7. Is currently participating in another drug or device clinical trial 8. Previous spinal surgery 9. History of deformity, mechanical instability, or spinal fusion requirement 10. History of hard or soft-tissue spinal infection 11. Has signs or symptoms of any disease, such as autoimmune disease, which could result in allograft failure, or has experienced allograft failure in the past 12. Patients unable to undergo a MRI

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-69.0, Breast Cancer for breast cancer survivor group Female Between the age of 18 to 69 years old Working part-time or full-time at the time of the assessment English-speaking Have Internet and computer access Have completed primary treatment and finished with treatment for at last 6 months (hormonal blockade therapy is permitted) Have received a stage I-III diagnosis of cancer for control group Female Between the age of 18 to 69 years old Diagnosis of dementia, history of brain injury and adult attention deficit hyperactivity (ADHD), epilepsy, current drug or alcohol abuse

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Gastric Cancer < age ≤ 70 years old Male or Non pregnant female The Eastern Cooperative Oncology Group (ECOG) status 0-1 T3 or T4 gastric adenocarcinoma (visual determination according to AJCC 2010 7th edition) No distance metastasis, eligible for D2 lymphadenectomy Have not received cytotoxic chemotherapy, radiotherapy or immunotherapy White blood cells > 4,000/mm3 neutrophils ≥ 1,500/mm3 platelets ≥ 100,000/mm3 hemoglobin>9g/l Have other cancer within 5 years Existence of distance metastasis during surgey (M1) Prior malignant tumors with detectable signs of recurrence or distant metastasis Poorly controlled disease e.g. atrial fibrillation, stenocardia, cardiac insufficiency, persistent hypertension despite medicinal treatment, ejection fraction<50% Epileptic seizures patients need medicine control Uncontroled mental disease or mental disorder Drug abuse or psychological or social factors affect the judgment of results Contraindication to any therapy contained in this regimen specific to the study Receiving other chemotherapy, radiotherapy or immunotherapy Without given written informed consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-999.0, Cartilage-hair Hypoplasia genetically confirmed cartilage-hair hypoplasia diagnosis age >12 months no history of chickenpox informed concent of the patient/caregiver positive serum IgG for varicella zoster virus low CD4+ cell counts (<15% or <200 cells/mm3) clinical or laboratory signs of severe immunodeficiency ongoing intravenous or subcutaneous immunoglobulin treatment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Coxarthrosis Unilateral primary osteoarthritis treated with total hip arthroplasty Secondary osteoarthritis Previous spinal, pelvic or lower limb injuries or fractures Bilateral osteoarthritis

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Glioblastoma Multiforme Anaplastic Astrocytoma Subject has given written informed consent 2. Subject is between 18 years old and 75 years old, inclusive 3. Subjects must have histologically proven GBM or AA and: 1. Must have received first-line multimodal therapy with surgery followed by temozolomide (unless MGMT promoter unmethylated) and radiation (subjects with GBM must have received temozolomide and radiation concurrently) 2. Must be in first or second recurrence (including this recurrence) 3. Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI. If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field 4. Subjects must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO 5. Subjects must be at least 4 weeks post last dose of temozolomide 6. Prior gamma knife, stereotactic radiosurgery, or other focal high-dose radiotherapy is allowed but the subject must have either histopathologic confirmation of recurrent tumor, or new enhancement on MRI outside of the radiotherapy treatment field 7. Based on the pre-operative evaluation by neurosurgeon, the subject is a candidate for ≥ 80% resection of enhancing region 8. IDH mutation status of the primary tumor must be available or tumor samples must be available for pre randomization testing 9. Laboratory values adequate for patient to undergo surgery, including Platelet count ≥ 60,000/mm3 Hgb ≥ 10 g/dL Absolute neutrophil count (ANC) ≥ 1,500/mm3 Absolute lymphocyte count (ALC) ≥ 500/mm3 Adequate liver function, including Total bilirubin ≤ 1.5 x ULN (unless has Gilbert's syndrome) ALT ≤ 2.5 x ULN f. Estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft Gault formula 10. Women of childbearing potential (≥12 months of non-therapy-induced amenorrhea or surgically sterile) must have had a negative serum pregnancy test within the past 21 days and must use a birth control method in addition to barrier methods (condoms). 11. Subject or subject's partner is willing to use condoms for 12 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer. 12. The subject has a KPS ≥ 70 13. The subject is willing and able to abide by the protocol History of more than 2 prior recurrences (including this recurrence) of GBM or AA 2. History of other malignancy, unless the patient has been disease free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is acceptable regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment 3. Histologically confirmed oligodendroglioma or mixed glioma 4. Known 1p/19q co deletion 5. A contrast enhancing brain tumor that is any of the following Multi focal (defined as 2 separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid attenuated inversion recovery (FLAIR) or T2 sequences) Associated with either diffuse subependymal or leptomeningeal dissemination; or > 5 cm in any dimension 6. The subject has or had any active infection requiring systemic antibiotic, antifungal or antiviral therapy within the past 4 weeks 7. The subject has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be stopped for surgery 8. The subject is human immunodeficiency virus (HIV) positive 9. The subject has a history of allergy or intolerance to flucytosine 10. The subject has a gastrointestinal disease that would prevent him or her from being able to swallow or absorb flucytosine 11. The subject received cytotoxic chemotherapy within the past 4 weeks (6 weeks for nitrosoureas) of the planned surgery date 12. The subject received any investigational treatment within the past 30 days or prior immunotherapy or antibody therapy within the past 45 days. 13. The subject is pregnant or breast feeding 14. The subject intends to undergo treatment with the Gliadel® wafer at the time of this surgery or has received the Gliadel® wafer < 30 days from W1D1 (surgery) 15. The subject has received bevacizumab for their disease unless in the context of primary therapy for newly diagnosed glioma 16. For subjects planned to potentially receive bevacizumab, they have no evidence of uncontrolled hypertension (defined as a blood pressure of ≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic on medication) or active GI perforation 17. The subject has received systemic dexamethasone continuously at a dose > 8 mg/day for 8 weeks prior to the date of the screening assessment 18. Severe pulmonary, cardiac or other systemic disease, specifically New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or Torsades des pointes), clinically significant pulmonary disease (such as ≥ Grade 2 dyspnea, according to CTCAE 4.03) Subjects who have any other disease, either metabolic or psychological, which as per Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Arthroplasty Any patient scheduled for a primary unilateral TKA Partial knee replacement chronic opioid use history of alcohol or drug abuse preexisting neuropathy in operative limb allergy to local anesthetics ASA Class >3 patients who decline to participate BMI >40 sleep apnea

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Pain participants will all be adults who have been experiencing non-cancer related pain for at least 12 weeks cancer related pain medical "red flags" suggestive of a non-neuromusculoskeletal etiology of symptoms casted fracture within the last 12 weeks related surgery within the last 26 weeks evidence of upper motor neuron lesion

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Arthroplasty, Replacement, Knee Pain, Postoperative The subject is scheduled for elective unilateral TKA 2. The subject is ≥ 18 years and ≤ 80 years; 3. The subject's weight is between 70-120 kg; and 4. The subject's primary anesthesia care team has planned for a neuraxial anesthetic (i.e. spinal, epidural or combined-spinal epidural). 5. The patient agrees to receive an adductor canal block. 6. American Society of Anesthesiologists class 1-3 Subject is < 18 years of age or >80 years of age; 2. Subject is non-English speaking; 3. Subject is known or believed to be pregnant; 4. Subject is a prisoner; 5. Subject has impaired decision-making capacity; per discretion of the Investigator 6. Symptomatic untreated gastroesophageal reflux or otherwise at risk for perioperative aspiration; 7. Any condition for which the primary anesthesia care team deems neuraxial anesthesia inappropriate; 8. Significant pre-existing neuropathy on the operative limb; 9. Significant renal, cardiac or hepatic disease per discretion of the investigator. 10. American Society of Anesthesiologists class 4-5 11. Known hypersensitivity and/or allergies to local anesthetics 12. Chronic Opioid Use (daily or almost daily use of opioids for > 3 months)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Multiple Sclerosis English speakers Relapsing-remitting MS (2010 criteria) Expanded Disability Status Scale (EDSS) ≤6.0 Possession of a smartphone OR of a mobile telephone with text messaging AND an e-mail account AND web access OR willingness to be provided with, and utilize, a smartphone for the duration of the study In the two years before screening: at least two relapses, OR one relapse and two new lesions (unrelated to relapse symptoms) on magnetic resonance imaging (MRI), OR RRMS (MAGNIMS 2010 criteria) onset within the past year with no exposure to disease modifying therapies (DMT) Patient is starting one of the following MS therapies: injectable (subcutaneous interferon beta or glatiramer acetate) or oral (fingolimod, teriflunomide, or dimethyl fumarate) therapies Relapse and MRI activity occurred while untreated or despite one single treatment, and no change in therapy since that activity Lives within 100 miles of Johns Hopkins Medical Center (Baltimore, MD) History of DMT exposure if 2010 used to enroll patients with disease onset in the past year, or change in MS therapy since qualifying relapse/MRI occurred

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Tumors With Aberrations in ALK Anaplastic Large Cell Lymphoma Inflammatory Myofibroblastic Tumor Glioblastoma Patient has a histologically or cytologically confirmed diagnosis of ALK positive (ALK+) tumor other than Non-Small Cell Lung Cancer (NSCLC) Patient must provide an archival or fresh tumor tissue before the first dose of the study drug for ALK testing at a Novartis designated central laboratory Patient has WHO Performance Status (PS) ≤ 2 Patient must have received at least one line of prior systemic treatment for recurrent, locally advanced and/or metastatic disease, and may have discontinued for Disease progression as defined by 1.1 for solid tumors; by RANO for GBM and by Cheson assessment for lymphoma, or Intolerance described as any discontinuation due to an AE of any grade despite appropriate supportive treatment Patient has at least one measurable lesion as defined by appropriate guidelines. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation Patient has received no chemotherapy, immunotherapy or stem cell therapy at least 4 weeks before starting ceritinib Radiotherapy and prior ALK inhibitors must be stopped at least 1 week prior to starting ceritinib Recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (Common Terminology for Adverse Events [CTCAE] v4.03) Patient has ALK+lung cancer Patient with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms Patient with acute or chronic GI disease that may significantly alter the absorption of ceritinib Patient with a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months) Patient has evidence of active viral hepatitis, including Hepatitis A, B or C (testing for viral hepatitis is not mandatory) Patient has known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-999.0, Urinary Retention Stroke, Complication male or female aged over 19 Patients diagnosed with stroke (cerebral hemorrhage or infarction) based on the CT or MRI examination Those whose onset is within 2 years Those who have urinary retention after stroke onset (every PVR result is equal or more than 100ml on the 2 consecutive tests) Those who signed on the informed consent form Patients who have any bleeding disorders based on medical history hearing Patients who have ever had any medical procedures or surgeries for peripheral vascular diseases based on medical history hearing Patients who have any psychiatry disorders based on medical history hearing Patients who have any severe diseases in lower urinary tract symptom based on medical history hearing Patients who have any acute or chronic infectious diseases in lower urinary tract symptom based on medical history hearing Acute stage stroke patients (onset within 1 week) whose Glasgow Coma Scale ≤ 8 Patients who have fear about acupuncture Patients who have changed medications for urinary retention or relevant symptoms, such as urinary incontinence drugs or diuretics, within 3 days Female who diagnosed with pregnancy by urinalysis Those who primary or sub investigators judge not to be suitable for the study

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Spinal Cord Injuries History of spinal cord injury affecting the arm and hand functions, at least 6 months prior to enrollment Upper extremity weakness as measured on a standard clinical scale No active major psychiatric problems, or neurological/orthopedic problems affecting the training upper extremity No active major neurological disease other than the spinal cord injury Absence of pain in the affected upper extremity Severe tone at the affected upper extremity as measured on a standard clinical scale Severe sensory/proprioception deficit at the affected upper extremity as measured on a standard clinical scale Difficulty in understanding or complying with instructions given by the experimenter Inability to perform the experimental task that will be studied Increased pain with movement of the training upper extremity

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-90.0, Stomach Diseases Treatment by esomeprazole 40mg since 4 weeks or more Esomeprazole withdrawal decided by the clinician Male and female aged 18-90 years Volunteers to participate to the study Must understand and read French language Must be able to give a written informed consent Impairment of cognitive status Current indication to continue PPI treatment History of erosive and ulcerative esophagitis, Barrett esophagus, Zollinger-Ellison syndrome Short-term treatment of documented ulcer disease, as part of a combination regimen for Helicobacter pylori (HP) eradication Prevention of ulcers due to non-steroidal anti-inflammatory drugs Hepatic impairment (TP<60%) Hypersensitivity to omeprazole (CYP2C19 activity) or esomeprazole Current pregnancy or current breastfeeding

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Anaplastic Astrocytoma Gender: Male and Female Age: Patients must be at least 18 years of age Race: Minorities will be recruited. No to this study will be based on race Patients must have histologically confirmed high grade astrocytoma, WHO grade III or IV, by pathology Patients' proposed post-operative treatment plan must standard focal brain irradiation and temozolomide Patients must have a Karnofsky Performance Status > 60 % (i.e. the patient must be able to care for himself/herself with occasional help from others) Patients must have normal bone marrow function, with a baseline total lymphocyte count > 1000 Patients must be able to provide informed consent Glucocorticoid use is allowed Women of childbearing potential should use effective contraception during and for two months after stopping fingolimod Patients must not have received prior radiation therapy, chemotherapy, immunotherapy, therapy with biologic agents or hormonal therapy for their brain tumor Patients must not have recent (within six months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III/IV heart failure Patients must not have history of or presence of Mobitz Type II 2nd degree or 3rd degree atrioventricular block or sick sinus syndrome, unless patient has a pacemaker Patients must not have baseline QTc interval > 500 ms Patients must not be on treatment with Class Ia or Class III antiarrhythmic drugs Patients must not have a history of macular edema, uveitis or diabetes mellitus Patients must not have elevated liver transaminase levels. Adequate liver function is defined as total bilirubin < 1.5 times upper limit of normal, SGPT (ALT) < 5 times upper limit of normal and serum albumin > 2 g/dL Patients must not have an active infection Patients with known HIV will be excluded Patients with collagen vascular disease are excluded

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Colorectal Cancer Histologically confirmed metastatic colorectal adenocarcinoma, 2. Curative-intent resection (or ablation) R0 of at least 4 CRLM, 3. Preoperative oxaliplatin and/or irinotecan-based chemotherapy (successively or concomitantly) +/ non experimental biological therapy, e.g., anti-EGFR or antiangiogenic antibody, 4. Confirmed radiological tumor control before surgery (i.e., objective response or stable disease according to criteria), 5. WHO performance status of 0 or 1, 6. Age ≥ 18 years, 7. Adequate hematological function: absolute neutrophil count (ANC) > 2 x 109/L; platelets > 100 x 10^^9/L, hemoglobin (Hb) > 9 g/dL. 8. Adequate liver function: serum bilirubin </= 1.5 x ULN; 9. Aminotransferases levels </= 2.5 ULN (</= 5 ULN if liver metastases in place), and alkaline phosphatase level ≤ 5 ULN 10. Creatinin clearance ≥ 30 ml/min 11. Informed consent signed by the patient or his/her legal representative. 12. Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment Extrahepatic metastatic disease (except ≤3 lung nodules (≤10 mm on chest CT scan) deemed amenable to curative-intent resection/ablation), 2. Symptomatic primary tumor requiring urgent surgery, asymptomatic primary colorectal tumor is not a non-inclusion if its 3. Contraindication to fluoropyrimidines or oxaliplatin, as mentioned in the SMPC of investigational medicinal products 4. Known dihydropyrimidine dehydrogenase (DPD) deficiency 5. Disease progression during, or early hepatic relapse (< 6 months) after the end of, oxaliplatin-based adjuvant chemotherapy following primary tumor resection 6. History of hepatic arterial infusion with any treatment (chemotherapy, radioembolisation), 7. Peripheral neuropathy> grade 1, 8. History of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix 9. Concomitant administration of cimetidine 10. Concomitant medications/comorbidities that may prevent the patient from receiving study treatments, 11. Patient already included in another clinical trial with an experimental molecule, 12. Pregnancy or lactation, 13. Patients deprived of liberty or under guardianship, 14. Patients unable to undergo medical monitoring test for geographical, social or psychological reasons. 15. Patients must not have any uncontrolled concurrent illness including, but not limited to, severe active or uncontrolled infection, symptomatic congestive heart failure, unstable, angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus or psychiatric illness/social situations that would limit compliance with study requirements resection is planned (REVERSE strategy authorized)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Tumor High Grade Glioma Histologically confirmed diagnosis of supratentorial WHO Grade III or IV Glioma (High Grade Glioma) that has undergone surgical biopsy or resection followed by adjuvant chemoradiotherapy, that has evidence of recurrence or progression based on imaging studies and surgical resection of the enhancing tumor is clinically indicated Karnofsky Performance Status 70-100 MRI demonstration of an enhancing mass of more than 1 cm^3 and less than 100 cm^3 Patient understands the procedures and agrees to comply with the study requirements by providing written informed consent; and Laboratory values within the following ranges Absolute neutrophil count (ANC) ≥ 1,500 / μL Platelet count ≥ 100,000 / μL Hemoglobin ≥ 10 g / dL Estimated glomerular filtration rate (eGFR) of at least 50 mL/min Patient is mentally or legally incapacitated at the time of the study Known HIV(+) or has been diagnosed with AIDS Participation in another investigational drug study in the prior 4 weeks Positive pregnancy test in a female Patient, in the opinion of the investigator, is likely to be poorly compliant Diffuse subependymal or CSF disease Tumors involving the cerebellum Active infection requiring treatment Unexplained febrile illness Radiation or chemotherapy within 4 weeks of enrollment

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-75.0, Pain American Society of Anesthesiologists (ASA) Physical Status I-II Without history of urethral or prostatic surgery Without respiration or circulation disorders Without chronic pain Allergy to local anesthetics Coagulation disorder or usage of antiplatelet drugs Infection at the site of puncture point Severe urethral stenosis

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Stroke chartered physiotherapists physiotherapists in training working with stroke patients other languages than German

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Osteoarthritis, Knee Clinical diagnosis of knee osteoarthritis Must have waist circumference >35 inches for women and >40 inches for men Cancer Heart disease Smoking Berry allergy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-80.0, Pancreatic Ductal Adenocarcinoma Older than 20 years old and younger than 80 years old Pathologically confirmed pancreatic ductal adenocarcinoma (metastatic or locally advanced stage) ECOG Performance status ≤2 Scheduled fot concurrent chemoradiation Adequate liver function (total bilirubin < 1.5 X the upper limits of normal (ULN), AST and ALT <3 X UNL, and alkaline phosphatases < 3 X ULN or < 5 x ULN in case of liver involvement) Adequate BM function (WBC ≥ 3,500/µl, absolute neutrophil cell count ≥ 1,500 /µl, platelet count ≥ 100,000/µl) Not remarkable coagulation profile (PT < 1.5 international normalized ratio(INR), aPTT <35 sec) Subjects who given written informed consent after being given a full description of the study Coexisting of other malignancies within 5 years, except squamous cell carcinoma and basal cell carcinoma of the skin Evidence of distant metastasis, such as liver, peritoneum and brain history of receiving the chemoradiation for pancreatic cancer in the other hospital History of receiving the operation which affect the anatomy of upper gastrointestinal tract Any trouble for examination of upper endoscopy Evidence of GI ulcers (A1~H2) on endoscopy before start of chemoradiotherapy Use of aspirin, anti-platelet agent, anticoagulation agent, NSAIDs, or glucocorticoid within 1 week or enable to stop the administration (including start during chemoradiation) Use of PPI, Histamine-2 receptor antagonist, antacid, prostaglandin, sucralfate within 2 weeks or enable to stop the administration Patients who are unwilling or unable to provide informed consent, such as those with psychiatric problem, drug abuse or alcoholism

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Wound Burn Wound Diabetic Foot Ulcers Pressure Ulcers Venous Leg Ulcers Chronic Wound Age ≥ 18 Willing to comply with protocol instructions, including all biopsies, study visits and study activities One of the following: 1. Chronic wound of multiple etiologies and open for at least 30 days, including: 1. Diabetic foot ulcers, Wagner grade 1-3 2. Pressure ulcers, stage 2-3 3. Venous leg ulcers, confirmed by venous duplex 4. Burn wounds open 5. Other etiology, deemed appropriate for biopsy 2. Wounds not appropriate for biopsy due to either: 1. Almost healed at the time of enrollment (per physician) 2. Healed within 10 days prior to enrollment visit 3. Clinical contraindication to biopsy in the opinion of the wound care provider Adequate arterial blood flow as evidenced by at least one of the following (for subjects receiving tissue biopsy, if would is located on a lower extremity below the knee): 1. Transcutaneous oxygen measurement (TcOM) > 30 mmHg 2. Ankle-brachial index ≥0.7 3. Toe pressure > 30 mmHg Individuals who are deemed unable to understand the procedures, risks and benefits of the study, (i.e. unable to provide informed consent) Diabetics with Hemoglobin A1c > 10% Subjects with marked immunodeficiency (HIV/AIDS, organ transplant patients and cancer patients and patients with autoimmune disease on immunosuppressive medications) Wounds closed or to be closed by flap or graft coverage including stage 4 pressure ulcers and Wagner grade 4 or 5 diabetic foot ulcers Prisoners Patients with allergies to petrolatum Patients who are currently enrolled in another research study which includes investigational treatment and/or medication

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Urinary Calculi Adult male patients presenting with acute urinary retention due to urethral or urinary bladder stones. 2. with a stone size not more than 2 centimeters in greatest diameter. 3. No more than 2 stones Bladder cancer. 2. Bladder replacement of any type. 3. Infravesical obstruction, due to marked benign prostatic hyperplasia, prostate cancer, stricture urethra or external urethral meatal stenosis

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Cytomegalovirus Infections brain tumours (glioblastoma or anaplastic astrocytoma) brain metastases from diagnosed primary tumours legal age planned chemoradiation and adjuvant chemotherapy [metastases] planned chemoradiation and adjuvant chemotherapy with temodal (according to Stupp et. al.) [brain tumors] fertile patients who refuse effective contraception during study treatment persistent drug and/or alcohol abuse patients not able or willing to behave according to study protocol patients in care patients that are not able to speak German patients with claustrophobia patients with artificial joint or any metal parts in the body patients with pacemakers

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Glioma Neoplasms Among the patients with high-grade glioma (glioblastoma multiforme or anaplastic astrocytoma), who received concurrent chemoradiation (CCRT) with temozolomide, the patients show the measurable enhancing portion (1 cm in the long diameter according to the RANO criteria) in the immediate f/up MRI after CCRT Among the patients with high-grade glioma (glioblastoma multiforme or anaplastic astrocytoma), who received concurrent chemoradiation (CCRT) with temozolomide, the patients do not show the measurable enhancing portion (1 cm in the long diameter according to the RANO criteria) in the immediate f/up MRI after CCRT

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Carpal Tunnel Syndrome The diagnosis of CTS will signs and symptoms of CTS: nighttime numbness and tingling or numbness and tingling in a median nerve distribution with a positive phalen or tinel or forearm compression test as well as a nerve conduction test and electromyography (NCT and EMG) that is positive for CTS The normal subjects: individuals that do not have any signs and or symptoms of CTS Patients or individuals that have a known history of peripheral neuropathy or other condition in the hand including recent significant trauma Patients with incomplete or unclear evaluation and tests Individuals unwilling to sign a consent form to participate in the study

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 40.0-999.0, Post-Operative Urinary Retention Any male age 40 or older Scheduled to undergo one of the planned surgeries (thoracic, general, or urologic) Ability to give informed consent Current use of alpha blocker Current use of a strong CYP 3A4 inhibitors Any allergy to tamsulosin, alpha-blocker medication class, or anaphylaxis allergy to sulfate containing medications Patients with any upcoming surgery for cataracts Currently enrolled in a clinical trial Inability to give informed consent

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Prostatic Hypertrophy, Benign AUR Patients presenting with a first episode of AUR related to BPH (no matter if previously known or not) AND Failure of at least one TWOC AND Prostate size > or = 50 ml (ultrasound measurement) Known hypocontractile bladder AUR related to other causes (Acute prostatitis or documented Prostate cancer) Severe iodine allergy Known prostate cancer Known ongoing acute or chronic prostatitis On-going acute pyelonephritis or septicemia from urinary origin Patient refusing PAE Severe renal failure (creatinine Clearance < 20 ml/min (MDRD) Contra-indication to AR blockers (postural hypotension micturition syncope) Contra-indication to anticoagulants

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Anaplastic Oligodendroglioma Breast Cancer With Recurrent Brain Metastases Leptomeningeal Carcinomatosis Neurologically stable 2. Karnofsky performance status (KPS) ≥ 80 3. Adequate laboratory results Radiotherapy within 3 months. 2. Evidence of significant intracranial hemorrhage 3. NCI Common Toxicity for Adverse Effects (CTCAE) v4.0 Grade ≥ 2 neuropathy 4. Inadequate bone marrow reserve 5. Any evidence of severe or uncontrolled disease

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-75.0, Glioblastoma Recurrence Progression Histologically proven diagnosis of glioblastoma (including giant cell glioblastoma and gliosarcoma) by WHO2007 criteria. 2. For patients who did not undergo surgery for recurrent disease; pre-registration contrast MRI should confirm; (i)progressive or recurrent glioblastoma; (ii)no evidence of acute or subacute cerebral hemorrhage at enrolment; (iii)presence of a measurable lesion. 3. For patients who underwent surgery for recurrent disease; (i)progressive or recurrent glioblastoma must be confirmed on contrast MRI before reoperation; (ii)glioblastoma or anaplastic astrocytoma must be histologically identified in the tissue resected at reoperation; (iii)presence of measurable lesions is not mandatory on pre-registration contrast MRI (more than 4 days after reoperation); (iv)no MRI evidence of aggravating cerebral hemorrhage. 4. No evidence of tumors in the cerebellum, brain stem, optic nerve, olfactory nerve, and pituitary gland. 5. No evidence of meningeal dissemination or gliomatosis cerebri. 6. Prior treatment for newly-diagnosed glioblastoma (or diffuse astrocytoma (Grade II) or anaplastic astrocytoma (Grade III)) with postoperative TMZ administered concomitantly with radiotherapy (>=54 Gy for <=69 years old; >=30 Gy for >=70 years old) and at least for two cycles (5/28d) as an adjuvant treatment have been given. 7. No history of prior treatment with stereotactic radiotherapy (ex. Gamma-knife/Cyberknife), proton beam irradiation, neutron capture therapy, and chemotherapies except standard dose TMZ and immunotherapy (vaccines, immune checkpoint inhibitors, antibodies etc.), bevacizumab (12 weeks or more after termination of prior upfront bevacizumab use) that were combined with TMZ, and intraoperative placement of carmustine wafers, for glioblastoma (including diffuse astrocytoma (Grade II) and anaplastic astrocytoma (Grade III) at onset) diagnosed with WHO2007 criteria. Time periods required from the last day of the prior treatment indicated at registration. ①Peptide vaccination, immune checkpoint inhibitors, antibodies: 4 weeks. ②Bevacizumab: 12 weeks. 8. More than 90 days after completion of radiotherapy. For those who underwent reoperation, between 21 and 28 days postoperatively. 9. Age between 20 and 75 years at enrolment. 10. Karnofsky Performance Status >= 60 within 14 days before enrolment. 11. No prior treatment with chemotherapy, molecular targeted therapy, or radiotherapy to head and neck area for other malignancies. 12. Adequate organ function. 13. Written informed consent Synchronous or metachronous (within 5 years) malignancy, except for carcinoma in situ or mucosal tumors curatively treated with local therapy 2. Active infection requiring systemic therapy 3. Body temperature >= 38 degrees Celsius at registration 4. Women during pregnancy, possible pregnancy, within 28 days after delivery, or breast-feeding 5. Psychosis or with psychotic symptom 6. Continuous systemic use of immunosuppressant except for steroid 7. Uncontrolled diabetes mellitus or routine administration of insulin 8. Unstable angina within 3 weeks, with a history of myocardial infarction within 6 months, or New York Heart Association (NYHA) class II or greater congestive heart failure 9. Inadequately controlled hypertension (cannot be controlled to a systolic pressure of >= 150 mmHg and a diastolic pressure of >= 100 mmHg) 10. History of symptomatic cerebrovascular disorder (including subarachnoid hemorrhage, cerebral infarction and transient ischemic attack) within 6 months or history of vascular disorder requiring intervention (including venous/arterial thrombosis or embolism and aortic aneurysm) within 6 moths 11. History of grade >= 2 hemoptysis within 28 days 12. History of hemorrhagic tendency (e.g., coagulation disorder) or any grade >= 3 hemorrhage within 28 days 13. History of gastrointestinal perforation, fistula, abdominal abscess or uncontrolled peptic ulcer within 6 months 14. Interstitial pneumonia, pulmonary fibrosis, or severe lung emphysema 15. Severe non-healing wound or traumatic fracture at enrolment 16. Hypersensitivity to Chinese Hamster Ovary-derived drugs or other recombinant antibodies 17. Gadolinium allergy 18. Positive HIV antibody 19. Positive Hepatitis B (HB)s antigen

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Low Back Pain, Mechanical Spinal Stenosis Nerve Root Disorder Radiculopathy, Cervical Benign Hypermobility Syndrome Clinical diagnosis of axial back pain (neck, mid-back, lower back) or pain radiating to the extremity, with suspected diagnosis of a specific pain generator amenable to a pain procedure, including disorders of the nerves, joints, and muscles as listed immediately below Clinical decision to schedule patient for a pain procedure, including procedures targeting the following disorders Facet arthropathy: intra-articular facet joint injection, medial branch block, medial branch radiofrequency ablation Sacroiliac joint dysfunction: sacroiliac joint injection, lateral branch block, lateral branch radiofrequency ablation Myofascial pain syndrome: trigger point injection Radiculopathy, spinal stenosis, or herniated nucleus pulposus: epidural steroid injection, selective nerve root block Piriformis syndrome: piriformis injection Greater trochanteric bursitis: greater trochanteric bursa injection Able to provide HIPAA authorization to share prior medical records/imaging Previous diagnosis of cancer Currently pregnant Previously enrolled for the same procedure or the same pain generator site. (For example, this would a patient who had an intra-articular facet joint injection at the right L5/S1 if: 1) he had the same injection 3 months ago and was enrolled at that time, or 2) the patient was already enrolled for a medial branch block at the right L5 and sacral ala, as this targets the same facet joint.) Inability or unwillingness of subject or legal guardian/representative to give informed consent (e.g., ward of the state)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 20.0-60.0, Spinal Neoplasms The patient should meet the diagnostic of intra-spinal canal tumors and the indications for surgery. Meanwhile, the length of tumor should no more than 5 cm, and the cross-sectional area should be less than 2/3 of the respective area of the spinal canal The patient was never be treated with any spinal surgery There was no cognitive impairment before onset of diseases or other diseases which can cause cognitive dysfunction The patient should sign the informed consent forms The patient is diagnozed as non intra-spinal canal tumors, spinal degenerative diseases, or other spinal diseases The patient received spinal surgery previously The patient suffered from serious heart, lung, liver, or kidney insufficiency The patient has other spinal and spinal cord diseases rather than intra-spinal canal tumor, such as disc herniation, vertebral fractures The patient has severe diabetes, coronary heart disease, coagulation disorders, difficult to correct before operation, or cannot tolerate surgery The patient has other surgical contraindications The patient is pregnant or breast-feeding The patient is unable to sign the informed consent voluntarily

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Peripheral Arterial Disease (PAD) Subject is at least 18 years of age 2. Subject or authorized representative, signed a written Informed Consent form to participate in the study, prior to any study related procedures 3. Subject is willing to comply with the protocol requirements and return to the treatment center for all required clinical evaluations 4. Rutherford classification 2-4 5. Has moderate to severe calcification visualized on angiogram in the femoropopliteal arteries 6. Planned atherectomy of the native femoropopliteal arteries 7. Reference vessel diameter for intended filter location must be visually estimated to be ≥3.5mm and ≤6.0mm 8. An adequate "landing zone" for placement of the device distal to the target lesion of at least 30mm 9. A female subject is eligible if not of child bearing potential or has a negative pregnancy test within the previous 7 days and agrees to remain on birth control throughout the study Any planned surgical or endovascular intervention within 30 days before or after the index procedure 2. A lesion deemed not accessible by the EPS 3. Inability to take aspirin or ADP receptor antagonists 4. History of bleeding diathesis or coagulopathy or will refuse blood transfusion if deemed necessary 5. Has perforation, dissection, or other injury of the access or target vessel requiring additional stenting or surgical intervention before enrollment 6. Subject is enrolled in another drug or device study protocol that has not reached its primary endpoint (participating in registry studies is not excluded) 7. Life expectancy less than 12 months 8. Known severe renal insufficiency (eGFR <30 ml/min/1.72m2). 9. ≤1-vessel tibial run-off status

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Anaplastic Astrocytoma Recurrent Anaplastic Astrocytoma Patients must meet all of the following to be eligible for participation in this study Surgical or biopsy-proven diagnosis of WHO grade 3 AA First AA tumor progression or recurrence ≤ 6 months prior to randomization based on MRI using T2 hyperintesity, gadolinium (Gd)-contrast enhancement, or both. To avoid enrollment of patients with glioblastoma, patients with Gd-contrast enhancing tumors will be eligible if there is no necrosis seen on MRI and any of the following is true: 1. Gd-contrast lesion margins are not clearly defined, 2. Gd-contrast lesions are only measurable in one dimension, 3. Gd-contrast lesion has two perpendicular diameters less than 10 mm, 4. Gd-contrast lesion has two perpendicular diameters greater than 10 mm but less than 20 mm and lesion does not demonstrate central necrosis, 5. Recent histopathological confirmation of WHO grade 3 AA Received EBRT and temozolomide chemotherapy prior to first tumor progression or recurrence of WHO Grade 3 AA Completion of EBRT ≥ 6 months prior to randomization A patient whose AA tumor has progressed or recurred and has had another surgical resection prior to randomization will be eligible if a) pathology review confirms AA, and b) post-surgical MRI demonstrates measurable tumor on T2 FLAIR Karnofsky Performance Status (KPS) score of ≥ 70 Patients who meet any of the following are not eligible for study participation MRI defining progression is consistent with a diagnosis of glioblastoma or radiation necrosis Patients who are considered to be refractory to EBRT and temozolomide but who have not progressed Prior systemic therapy for recurrence of AA Presence of extracranial or leptomeningeal disease Prior lomustine use Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study Pregnant or breastfeeding

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Glioma Brain Neoplasm Brain Cancer Brain Tumor Brain Tumor, Recurrent Brain Neoplasm, Malignant Male or female patients of ≥18 years of age Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic oligoastrocytoma (AOA) Patients with pathology confirmed histologic EGFR overexpression Patients must have at least one confirmed and evaluable tumor site.∗ *A confirmed tumor site is one in which is biopsy-proven Patients must have a Karnofsky performance status ≥60% and an expected survival of ≥ three months No chemotherapy for two weeks prior to treatment under this research protocol and no external beam radiation for eight weeks prior to treatment under this research protocol Patients must have adequate hematologic reserve with WBC≥3000/mm3, absolute neutrophils ≥1500/mm3 and platelets ≥100,000/ mm3. Patients who are on Coumadin must have a platelet count of ≥150,000/ mm3 Pre-enrollment chemistry parameters must show: bilirubin<1.5X the institutional upper limit of normal (IUNL); AST or ALT<2.5X IUNL and creatinine<1.5X IUNL Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5X the IUNL Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study Women who are pregnant or lactating Women of childbearing potential and fertile men will be informed of the potential unknown risk of conception while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring Patients with radiological evidence of leptomeningeal disease Patients with history of allergic reaction to CTX Patients who completed chemo/RT less than 6 months prior to enrollment Patients who have not failed standard Stupp protocol

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Lumbar Intervertebral Disc Displacement Cervical Intervertebral Disc Displacement Lumbar and/or cervical disc herniation patients with baseline MRI and follow-up results after receiving treatment at Jaseng Hospital of Korean Medicine visiting between February 2012 and December 2015 Participants giving informed written consent to use of medical records for academic means Participants refusing to participate in study or to respond to phone interview

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-90.0, Osteoarthritis Patients with indication of Osteoarthritis, grade 2 or more. Can be from degeneration or chronic injury. 2. Patients range from 18-90 years of age. 3. Patients must be able to comply with treatment plan, laboratory tests and periodic interviews. 4. Patients with adequate renal function, Creatinine ≤ 1.5 mg/dl. 5. Patients with adequate cardiac and respiratory function. 6. Patients with adequate blood coagulation activity, PT(INR) < 1.5, APTT 7. Patients must have adequate immune system function, with no known immunodeficiency disease. 8. Greater than 6 months knee pain on the index side (left or right knee) Neoplastic cancer within 5 years prior to screening, except for cutaneous basal cell or squamous cell cancer resolved by excision 2. Presence of clinically significant acute or unstable cardiovascular and cerebrovascular (stroke). 3. Diagnosis of a transient ischemic attack in the 6 months prior to screening. 4. Patients infected with hepatitis B, C or HIV. 5. Patients with Body Mass Index (BMI) > 40kg/m2 6. Presence of active infection. 7. Any other illness, psychiatric disorder, alcohol or chemical dependence that in the opinion of the investigator would render a patient unsuitable to participate in the study. 8. Conditions/therapies/factors which could confound or interfere with the evaluation of pain/mobility including, but not limited to: 1. Knee instability. 2. A varus/valgus deformity of more than 10o, a deformity requiring osteotomy or complex surgery. 3. Gout or pseudo gout 4. Treatments with strong opioid drugs in the previous 4 weeks for other pain rather than knee osteoarthritis 5. Corticosteroid injection at treatment site within 1 month 6. Consistent use of NSAIDs within 48 hours of procedure

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-25.0, Severe Aplastic Anemia Confirmed diagnosis of idiopathic SAA, defined as Bone marrow cellularity <25%, or <30% hematopoietic cells Two out of three of the following (in peripheral blood): neutrophils <0.5 x109/L, platelets <20 x109/L, reticulocyte count <60 x109/L with hemoglobin <8g/dL. 2. Age ≤25 years old. 3. No suitable fully matched related donor available (minimum 6/6 match for Human Leukocyte antigen (HLA) -A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing). 4. At least two unrelated donors noted on National Marrow Donor Program (NMDP) search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution). 5. Signed informed consent for the randomized trial by patient and/or legal guardian. 6. Adequate organ function defined as in the judgment of the investigator, there is not irreversible organ damage that would preclude the patient from meeting the organ function for HSCT listed in section 2.3.4 by the intended time of HSCT (6-8 weeks after randomization) or preclude patients from receiving horse ATG Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to Dyskeratosis congenita, but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman Diamond syndrome, this syndrome must be excluded by pancreatic isoamylase testing or gene mutation analysis. Note: pancreatic isoamylase testing is not accurate in children less than 3 years. 2. Clonal cytogenetic abnormalities or fluorescence In Situ Hybridization (FISH) pattern consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (see section 4.2.3.1 for details of the required MDS FISH panel). 3. Known severe allergy to horse ATG. 4. Prior allogeneic stem cell transplant. 5. Prior solid organ transplant. 6. Infection with human immunodeficiency virus (HIV). 7. Active Hepatitis B or C. This should be excluded in patients where there is clinical suspicion of hepatitis (e.g. elevated LFTs). 8. Female patients who are pregnant or breast-feeding. 9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-31.0, B Acute Lymphoblastic Leukemia Central Nervous System Leukemia Ph-Like Acute Lymphoblastic Leukemia Testicular Leukemia Patients must be enrolled on APEC14B1 and consented to Screening on the Part A consent form prior to enrollment on AALL1131 White Blood Cell Count (WBC) Age 1-9.99 years: WBC >= 50 000/uL Age 10-30.99 years: Any WBC Age 1-30.99 years: Any WBC with Testicular leukemia CNS leukemia (CNS3) Steroid pretreatment Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131 With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131 Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction DS HR B-ALL patients with Induction failure or BCR-ABL1 Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs Lactating females are not eligible unless they have agreed not to breastfeed their infant Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Urinary Tract Infections Admission to one of three hospital units at the University of Virginia (5 Central, 6 West, or the Short Stay Unit) Patient has a Foley urethral catheter in place The physician has ordered the Foley urethral catheter to be discontinued Age less than 18 years Prisoners Women who are pregnant

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, Neoplasm, Trophoblastic Gestational Trophoblastic Disease Hydatidiform Mole Hydatidiform Mole, Invasive Patients are eligible if they have a histologically proven trophoblastic disease, or a diagnosis of gestational trophoblastic neoplasia done on an abnormal evolution of hCG none

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Pain Subject has been implanted with a commercially available SJM spinal cord stimulator for controlling chronic intractable pain associated with back and/or leg pain Subject has been exclusively using burst stimulation for at least three months Subject is 18 years of age or older Subject's pain-related medication regimen was stable in the 4 weeks prior to the screening evaluation Subject agrees not to add or increase pain-related medication from enrollment through the study duration Subject is willing to cooperate with the study requirements including compliance with the regimen and completion of all office visits Subject is currently participating in a clinical investigation study that includes an active treatment arm Subject is currently receiving, applying or considering seeking workers compensation, or is involved in disability litigation Subject has a non SJM neuromodulation device

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 65.0-999.0, Frail Elderly Exercise Therapy Physical Therapy Techniques volunteers above the age of 65 who are community residents and classified as frail according to the established by Fried et al. will be selected for in the study previous lower extremities orthopedic surgery, a history of fractures within the past year, an inability to walk unaided, carriers of neurological diseases, diagnosed acute inflammatory disease that could interfere in the assessments and the program, tumor growth in the last five years and cognitive impairment based on the mini-mental state examination [4]. Moreover, will be excluded volunteers who are absent more than three consecutive training and / or more than 25% of the sessions, and / or present the course of the physical program changes or decompensation and / or disease injury

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-50.0, Intervertebral Disc Displacement Indication for monosegmental anterior cervical discectomy with implantation of a disc prosthesis Radiologic signs of extensive bone degeneration in the affected segment Necessity of implantation of a device smaller in height than 5 mm (as predicted with teh use of the Vertaplan (TM) software Transversal spine cord lesion Cervical myelopathy Preceding surgery on the cervical spine Traumatic lesions of the cervical spine Radiographic instability in the affected segment: flexion / extension: shift sagittal plane> 3.5 mm or 20% and rotation in the sagittal plane > 20 °, OR in static X-ray examinations: shift in the sagittal plane 3.5 mm or 20% of the vertebral body width and relative sagittal plane angulation > 11º signs of instability (Olisthesis) in another segment of the cervical spine Active systemic infection diseases of the rheumatic type and all autoimmune diseases

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-50.0, Intervertebral Disc Displacement Indication for monosegmental anterior cervical discectomy with implantation of a disc prosthesis Radiologic signs of extensive bone degeneration in the affected segment Necessity of implantation of a device smaller in height than 5 mm (as predicted with teh use of the Vertaplan (TM) software Transversal spine cord lesion Cervical myelopathy Preceding surgery on the cervical spine Traumatic lesions of the cervical spine Radiographic instability in the affected segment: flexion / extension: shift sagittal plane> 3.5 mm or 20% and rotation in the sagittal plane > 20 °, OR in static X-ray examinations: shift in the sagittal plane 3.5 mm or 20% of the vertebral body width and relative sagittal plane angulation > 11º signs of instability (Olisthesis) in another segment of the cervical spine Active systemic infection diseases of the rheumatic type and all autoimmune diseases

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Brain Tumor Astrocytoma Astroglioma Glioblastoma Gliosarcoma are same in both Phase I and Phase II parts, except for the number of prior disease relapses Patients must have pathologic diagnosis of anaplastic astrocytoma defined as WHO grade III or glioblastoma/gliosarcoma, WHO grade IV, which are confirmed by NCI Laboratory of Pathology. If the pathology diagnosis is anaplastic glioma or anaplastic oligoastrocytoma, evidence of either intact 1p/19q chromosomes or molecular features suggesting astrocytic tumor must be present. (including, but not limited to ATRX, TP53) Patients must have recurrent disease, histologically proven or imaging suggestive of recurrent disease as determined by PI. Prior implantation of Gliadel wafers is acceptable, if tumor recurrence is confirmed by histologic examination of the recurrent tumor Patients must have the ability to understand and the willingness to sign a written informed consent document Patients must be greater than or equal to 18 years old No more than two prior disease relapses to be eligible for the phase I portion of the study and no more than one prior relapse to be eligible for phase II Patients must have undergone prior standard therapy for their primary disease. For patients with glioblastoma, this would surgical resection, or biopsy, if safe resection was not permitted due to the tumor location, radiation and adjuvant temozolomide. For patients with anaplastic astrocytoma, this would surgical resection, radiation and adjuvant chemotherapy PCV or temozolomide Tumor tissue must be available for review to confirm histological diagnosis Tumor block or unstained slides must be available for molecular profiling Karnofsky > 60 percent Patients who are receiving any other investigational agents. However, prior enrollment on a study using investigational agents is acceptable Patients with prior bevacizumab use for tumor treatment. Patients who received bevacizumab for symptom management, including but not limited to cerebral edema, pseudoprogression can be included in the study(To date, there have been no effective regimens developed for recurrent malignant gliomas that are refractory to bevacizumab. of this patient population may impact the ability to determine the efficacy of Zotiraciclib (TG02) with TMZ.) Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent Any condition, including the presence of clinically significant laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. These would Active infection (including persistent fever) including known history of HIV or Hepatitis C infection, because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy Diseases or conditions that obscure toxicity or dangerously alter drug metabolism Serious concurrent medical illness e.g. symptomatic congestive heart failure History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide and/or Zotiraciclib (TG02) Patients with a history of any other cancer (except non-melanoma skin cancer or melanoma in-situ following curative surgical resection; or carcinoma in-situ of the cervix or bladder), unless in complete remission and off all therapy for that disease for a minimum of 3 years, are ineligible Zotiraciclib (TG02) is primarily metabolized by CYP1A2 and CYP3A4. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP1A2 and/or CYP3A4 are ineligible

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Urinary Retention Hospitalized patients in Ramathibodi Hospital who developed first-time AUR from June 2014 to May 2015 Patients under 18 years of age History of urinary retention Urinary tract infection Poor compliance

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-60.0, Spinal Cord Injuries Obesity Insulin Resistance SCI only: 1. Lower extremity weakness or paralysis at C5 or below resulting from spinal cord injury for at least one year. 2. ASIA Classification A-D Overweight or obese as classified by a Body Mass Index (BMI) (kg/m2) of ≥ 25.0 (CON) and ≥ 22.0 (SCI). SCI and non injured control: Resting SaO2 ≥ 95% (SCI and non injured control): 1. Currently hospitalized 2. Resting heart rate ≥120 BPM 3. Resting systolic blood pressure >180 mm Hg 4. Resting diastolic Blood Pressure >100 mmHg 5. Self-reported history of unstable angina or myocardial infarction within the previous month 6. Previous cardiac surgery or condition that evidences ischemic heart disease 7. Cardiopulmonary complication such as COPD 8. Pregnancy determined by urine testing in sexually active females

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chemo-radiation Induced Nausea and Vomiting Patients must have histologically-confirmed, newly-diagnosed malignant glioma (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, or anaplastic oligodendroglioma) and are scheduled to receive radiotherapy (for a total of 54-60 Gy) and concomitant daily temozolomide therapy (at a dose of 75 mg/m^2 for one complete 6-week cycle) Age ≥ 18 years Karnofsky ≥ 60% or ECOG 0-2 Hematocrit >29%, Absolute Neutrophil Count >1,000 cells/mm^3, platelets >100,000 cells/mm^3 Serum creatinine <1.4 mg/dl, bilirubin <1.5 times upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 2.5 x ULN. For subjects with known liver metastases ≤ 5 x ULN, and alanine aminotransferase (ALT) ≤ 2.5 x ULN. For subjects with known liver metastases ≤ 5 x ULN For patients on higher than physiological level of corticosteroids, they must have been on a stable dose for 1 week prior to initiating study drug, and the dose should not be escalated over entry dose level, if clinically possible Ability and willingness to give informed consent Female patients of childbearing potential must have a negative pregnancy test at Screening Female patients of childbearing potential must agree to use an acceptable method of birth control from the signing of informed consent and to continue its use during the study and for at least 90 days after the final dose Co-medications that may interact with rolapitant as reviewed by Duke Preston Robert Tisch Brain Tumor investigator pharmacist Co-medications that are contraindicated in patients on rolapitant including pimozide, thioridazine, carbamazepine, colchicine, dabigatran (Pradaxa), edoxaban (Savaysa), fosphenytoin, metoprolol, phenobarbital, phenytoin, primidone, and warfarin Inability or unwillingness to cooperate with the study procedures Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of radiation therapy through the full course of radiation therapy is prohibited, with the exception of the study drug. Corticosteroids will be allowed for treatment of cerebral swelling Previous participation in any clinical trial involving rolapitant Any vomiting, retching, dry heaves, or clinically significant nausea (i.e., NCI Common Toxicity version 4.0 grade 2-4 nausea) caused by any etiology in the 24 hrs. preceding day 1 of the study intervention (ondansetron or ondansetron with rolapitant) as scheduled to begin on day 1 of radiation and chemotherapy. Or a patient who has a history of anticipatory nausea and vomiting Ongoing vomiting from any organic etiology Received rolapitant within 21 days prior to study enrollment Prior cancer chemotherapy or radiotherapy Any current treatment, medical history, or uncontrolled condition, other than malignancy, (e.g., alcoholism or signs of alcohol abuse, seizure disorder, medical or psychiatric condition) that, in the opinion of the investigator, would confound the results of the study or pose any unwarranted risk in administering study drug to the subject

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Patient Adherence • Non-specific low back pain Patients physical active in accordance with the Dutch Standard Healthy Physical Activity (NNGB) (Hildebrandt et al., 2007) Patients with specific low back pain Onset of the low back pain after age 50 years Continuous pain regardless of posture or movement Nocturnal pain General malaise History of malignancy Unexplained weight loss Elevated erythrocyte sedimentation rate (ESR) Previous vertebral fracture

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, IDH Family Wildtype Recurrent Anaplastic Astrocytoma Recurrent Glioblastoma Patients must have histologically-proven, recurrent supratentorial grade IV glioblastoma (or grade III IDH-wildtype anaplastic astrocytoma), for which a complete surgical resection is unsafe due to location, shape, or size of the tumor. Diagnosis of recurrence will be established by biopsy and frozen section immediately prior to initiating LITT procedure. If findings on frozen section are not consistent with recurrence (glioblastoma or recurrent IDH-wildtype anaplastic astrocytoma), decision to proceed with LITT procedure will be at the discretion of the neurosurgeon (only patients with histologically-proven recurrent tumor will be evaluable for efficacy) All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information. Patients must be registered prior to treatment on study Patients must have a Karnofsky performance score (KPS) > 60 Patients must have received standard of care therapy with chemoradiation with temozolomide followed by adjuvant chemotherapy with temozolomide. Patients may have received one additional chemotherapy regimen (other than lomustine) in addition to adjuvant temozolomide prior to study entry (patients at either first or second recurrence are eligible) In the context of this clinical trial, a lesion suitable for LITT is single, enhancing, supratentorial, at least 2 cm from inner table of skull over the hemispheric convexity, and > 1 cm, but < 4 cm in cross-sectional dimension, including thalamic tumor (=< 3 cm) Patients must have stable cardiovascular, neurovascular and neurological status, and be considered surgical candidates, as determined by any relevant pre-operative assessments, at the neurosurgeon's discretion Patients must not be receiving concurrent anti-tumor treatment and must have recovered from toxicity of prior treatment. Minimum interval required: 1) > 6 weeks following nitrosourea chemotherapy; 2) > 4 weeks after recovering from any non-nitrosourea drug or systemic investigational agent; 3) > 2 weeks after receiving any non-cytotoxic anti-tumor drug; 4) > 4 weeks after receiving radiation therapy (> 12 weeks following upfront concurrent chemoradiation); 5) > 2 weeks following Optune device use Patients must not have previously undergone an intracranial LITT procedure White blood cell (WBC) > 3,000/ul (performed within 14 days (+ 3 working days) prior to registration) Absolute neutrophil count (ANC) > 1,500/mm^3 (performed within 14 days (+ 3 working days) prior to registration) Patients must not have received prior treatment with bevacizumab Patients must not have had prior treatment of glioblastoma with stereotactic radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel) Patients must not have symptoms attributed to mass effect of the tumor (despite corticosteroid treatment) that would be better treated with debulking surgery, or wherein surgical debulking in the first 30 days following LITT procedure would be anticipated for symptom management Patients unable to undergo MRI are not eligible Patients with progression of multifocal tumors or tumors involving the posterior fossa (brainstem and cerebellum) will be excluded, as will patients where the anticipated treatment margin will be within 5 mm of critical intracranial structures (e.g., primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves) Patients may not have undergone previous treatment with lomustine Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible Patients must not have active infection or serious intercurrent medical illness Patients must not be pregnant/breast feeding and must agree to practice adequate contraception

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Aortic Valve Stenosis Subject has provided written informed consent prior to uploading CT scan to core lab. 2. Subject is ≥ 18 years of age or legal age in host country. 3. Subject's aortic annulus diameter meets the range indicated in the Instructions for Use as measured by multislice CT conducted within 180 days prior to the index procedure. 4. Subject has senile degenerative aortic stenosis seen by echocardiography within 90 days of index procedure as measured by: 1. mean gradient >40 mmHg 2. Peak velocity ≥ 4.0 m/s 3. Doppler Velocity Index <0.25 4. Aortic valve area (AVA) of ≤ 1.0 cm2 or indexed EOA ≤ 0.6 cm2/m2). 5. Subject has symptomatic aortic stenosis as demonstrated by NYHA Functional Classification of Class II, or greater or other symptoms of aortic stenosis (e.g. syncope). 6. Subject is deemed high operable risk and preferred TAVI delivery route is alternate access (subclavian/axillary or direct aortic) per the medical opinion of the center's heart team and confirmed by SSC High risk is defined as an STS mortality > 8% or documented heart team agreement ≥ high risk for SAVR due to frailty or co-morbidities Subject is unwilling or unable to comply with all study-required follow-up evaluations. 2. Subject has a documented history of a cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6 months (less than or equal to 180 days) prior to the index procedure. 3. Subject has carotid artery disease requiring intervention. 4. Subject has evidence of a myocardial infarction (MI) within 30 days prior to patient index procedure. 5. Subject has a native aortic valve that is congenitally unicuspid, bicuspid, quadricuspid or non-calcified as seen by echocardiography. 6. Subject has severe mitral valvular regurgitation. 7. Subject has severe mitral stenosis. 8. Subject has a pre-existing prosthetic cardiac device, valve, or prosthetic ring in any position. 9. Subject refuses any blood product transfusion. 10. Subject has resting left ventricular ejection fraction (LVEF) less than 20%. 11. Subject has documented, untreated symptomatic coronary artery disease (CAD) requiring revascularization. 12. Subject has had a percutaneous interventional or other invasive cardiovascular or peripheral vascular procedure less than or equal to 14 days prior to index procedure. 13. Subject has severe basal septal hypertrophy that would interfere with transcatheter aortic valve placement. 14. Subject has a history of, or is currently diagnosed with, endocarditis. 15. There is imaging evidence of intracardiac mass, thrombus, or vegetation. 16. Subject is considered hemodynamically unstable (requiring inotropic support or mechanical heart assistance). 17. Subject is in acute pulmonary edema or requiring intravenous diuretic therapy to stabilize heart failure. 18. Subject with severe pulmonary disease as determined by STS score. 19. Subject is on chronic oral steroid therapy. 20. Subject has a documented hypersensitivity or contraindication to anticoagulant or antiplatelet medication. 21. Subject has renal insufficiency as evidenced by a serum creatinine greater than 3.0 mg/dL (265.5 µmol/L) or end-stage renal disease requiring chronic dialysis. 22. Subject has morbid obesity defined as a BMI greater than or equal to 40. 23. Subject has ongoing infection or sepsis. 24. Subject has uncontrolled blood dyscrasias as defined: leukopenia (WBC<3000 mm3), acute anemia (Hb<9 mg/dL), thrombocytopenia (platelet count <50,000 cells/mm3,). 25. Anatomy falling outside the recommended values in the IFU, unless specifically approved by the Subject Selection Committee. 26. Subject has an active peptic ulcer or has had gastrointestinal (GI) bleeding within 90 days prior to the index procedure. 27. Subject is currently participating in another investigational drug or device study, unless approved by the Sponsor. 28. Subject has/had emergency surgery for any reason within 30 days of the index procedure. 29. Subject has a life expectancy less than 1 year. 30. Subject has other medical, social or psychological conditions that, in the opinion of the Principal Investigator or the Subject Selection Committee, preclude the subject from study participation. 31. Subject is diagnosed with a state of dementia which would fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits. 32. Subject has a documented allergy to contrast media that cannot adequately be treated, nitinol alloys, porcine tissue, or bovine tissue. 33. Significant aortic disease including abdominal aortic or thoracic aneurysm defined as maximal luminal diameter 5cm or greater 34. Subjects with severe pulmonary hypertension and severe RV dysfunction 35. Subjects with hypertrophic cardiomyopathy Transaortic Subject Cohort Specific Subjects are not eligible for participation in the TAo access arm if they meet any of the following Subject has a chest condition (anatomical or otherwise) that prevents TAo access. 2. Subject has pre-existing patent RIMA graft that would preclude access. 3. Subject has a porcelain aorta, defined as an extensive circumferential calcification of the ascending aorta that would complicate TAo access. Subclavian/Axillary Subject Cohort Specific Subjects are not eligible for participation in the subclavian/axillary access arm if they meet any of the following Subject's access vessel (subclavian/axillary) diameter will not allow for introduction of the 18/19 Fr delivery system. 2. Subject's subclavian/axillary arteries have severe calcification and/or tortuosity. 3. Subject has a history of LIMA/RIMA graft that would preclude access

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-80.0, Glioma Patients with high-grade gliomas confirmed by pathology and have not been treated with concurrent chemoradiotherapy; 2. Written informed consent is obtained Patients not suitable for enhanced MRI scanning of patients; 2. Patients who have not finished follow-up concurrent chemoradiotherapy or MR scanning

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Chronic Pain Adult patients who have experienced chronic pain for at least 6 months Do not have any of the following conditions: substance abuse or dependence, psychosis, suicidal ideation in the last 2 months, high levels of trauma symptoms plans to have a permanent change of station or deploy in the coming 6 months, or pregnancy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Skin Squamous Cell Carcinoma Appendix Adenocarcinoma Rare Lesion Locally Advanced Malignant Neoplasm Locally Advanced Skin Squamous Cell Carcinoma Metastatic Malignant Neoplasm Metastatic Skin Squamous Cell Carcinoma Metastatic Small Intestinal Adenocarcinoma Rare Neoplastic Syndrome Refractory Malignant Neoplasm Stage IV Small Intestinal Adenocarcinoma AJCC v8 Unresectable Malignant Neoplasm Patients must be informed of the investigational nature of this study and must be willing to give written informed consent in accordance with institutional and federal guidelines. Patients must be able to comply with the requirements and assessments of the study protocol Must have histologically or cytologically documented rare tumor as defined per protocol that is metastatic or locally advanced and unresectable. Patients with locally advanced cutaneous squamous cell carcinoma that are technically resectable but in whom surgery is expected to lead to substantial function impairment or disfigurement are eligible Must be refractory or intolerant to standard lines of therapy Must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to start of treatment and all toxicity must be resolved to Common Terminology for Adverse Events (CTCAE) v4.0 grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to start of treatment Presence of radiographically evaluable disease Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Tissue Parameters: a. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 4 unstained slides, with an associated pathology report, for testing of tumor PD-L1 expression (tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable). b. Tumor tissue should be of good quality based on total and viable tumor content. Fine needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable. For core-needle biopsy specimens, at least three cores should be submitted for evaluation. c. Patients who do not have tissue specimens meeting requirements must be willing to undergo a biopsy during the screening period Absolute neutrophil count (ANC) >= 1,000/mcL (obtained within 14 days prior to enrollment) Platelets >= 75,000/mcL (obtained within 14 days prior to enrollment) Hemoglobin >= 9 g/dL (obtained within 14 days prior to enrollment) Presence of brain metastases (unless they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to enrollment provided patient is neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to enrollment) Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, severe infection, severe malnutrition, unstable angina, class III-IV New York Heart Association (NYHA) congestive heart failure, ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within 6 months prior to enrollment History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration Patients will be excluded from study participation if they currently are known to have any of the following risk factors for RVO: a. Glaucoma with intraocular pressure >= 21 mmHg b. Grade >= 2 serum cholesterol c. Grade >= 2 hypertriglyceridemia d. Grade >= 2 or symptomatic hyperglycemia (fasting) e. Grade >= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to grade =< 1 are eligible) Active malignancy (other than colorectal carcinoma [CRC]) or a history of prior malignancy within the past 3 years. Adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade lesions such as incidental appendix carcinoid, or any other cancer from which the patient has been disease and treatment free for two years are allowed. Prostate cancer patients on active surveillance are eligible Pregnant or nursing patients due to risk of fetal or nursing infant harm. Women/men of reproductive potential who do not agree to use an effective contraceptive method while on study and for at least 6 months after study treatment related to study medication (any cancer immunotherapy including CD137 agonists, anti-PD-1, anti-PD-L1, or anti-CTLA4 or any MEK or ERK inhibitor) Left ventricular ejection fraction (LVEF) < institutional lower limit of normal or < 50% History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis a. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. b. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. c. Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-50.0, Hip Joint Muscle Weakness Individuals with a lower extremity pathology volunteered for this study Being greater than 18 years of age decrease in muscle strength in symptomatic side compared to healthy side Absence of medical precautions that would prevent a maximal effort strength test Included individuals with a history lower extremity arthroplasty Recent muscle or tendon ruptures (within the past 6 months) Unhealed fractures Neurological diseases Malignant cancer Osteoporosis Active infections processes Early postoperative knee, hip and ankle surgery with range of motion and weight bearing restrictions

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 14.0-999.0, Stress Fracture Ultrasound Therapy Musculoskeletal Ultrasound age 14 years and up suspected acute stress fracture of the lower extremity symptoms < 4 weeks x-ray ordered by clinician to which subjects originally present with suspected stress fracture age < 14 unable to provide consent unable to undergo MRI (implantable pacemaker or other device not compatible for MRI) previous diagnosis of acute stress fracture in the location of interest previous XR or MRI obtained at an outside clinic/facility prior to presentation previously implanted hardware (ex. orthopedic screws or plates) at location of interest symptoms > 8 weeks depth from skin surface to bone surface that exceeds the capability of ultrasound for visualization Pregnant (self-reported) Subject is known to all clinicians who would be completing the diagnostic ultrasound component of the study

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 19.0-70.0, Urinary Tract Infection Men or non-pregnant women over 18 years of age with cUTI in One or more clinical symptoms and signs of a lower UTI: fever (> 38°C, orally), chills, frequency of micturition, dysuria, urge sensation One or more of the following underlying conditions suggestive of cUTI Indwelling urinary catheter Neurogenic bladder Obstructive uropathy due to lithiasis, tumor or fibrosis Acute urinary retention in men History of allergy to quinolones Are unable to take oral medication Have an intractable infection requiring > 14 days of therapy Have a requirement for concomitant administration of sucralfate or divalent and trivalent cations such as iron or antacids containing magnesium, aluminum or calcium Have prostatitis or epididymitis Have had a renal transplant Have ileal loop or vesica urethral reflux Have significant liver or kidney impairment Have a history of tendinopathy associated with fluoroquinolones

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Postoperative Pain patients who require major lower extremity amputations less than 18 years old, pregnant, emergency amputation, staged amputation, amputations performed by non-vascular surgeons, patients who are allergic to bupivacaine, patients who are unable to communicate symptoms of pain

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-70.0, Severe Acute Pancreatitis Age of 18 years to 70 years; and 2. Pain characteristic of pancreatitis; and 3. Elevated serum lipase or amylase (≥3-fold upper normal range); and 4. Persistent organ failure >48 hours; and 5. Organ dysfunction occurred within 7 days after onset of pain; and 6. Presentation with a width of ≥2cm of APFCs in the peripheral tissues of the pancreas, the cyst of lesser omentum , or the paracolic sulci on CT image History diseases of chronic organ dysfunction; or 2. Traumatic pancreatitis; or 3. Post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis; or 4. Severe coagulopathy (INR>2); or 5. Severe thrombocytopenia (PLT≤50×109/L); or 6. No suitable route for puncturing; or 7. Pregnancy; or 8. Absent of informed consent from patient or representative

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 10.0-18.0, Diabetes Mellitus, Type 2 Signed Written Informed Consent Target Population Previously diagnosed with Type 2 Diabetes Mellitus by World Health Organization/ADA HbA1c between 6.5% and 10.5% obtained at screening Currently on diet and exercise and stable dose of at least 1000 mg metformin (IR or XR) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of at least 1000 mg metformin (IR or XR) and insulin for a minimum of 8 weeks prior to randomization. For those children on insulin, investigators will confirm that attempts at removing insulin from the subject's therapeutic regimen had been previously made but had not been successful Age and Reproductive Status Male and female patients eligible if 10 years of age, up to but not including 18 years of age at the time of enrollment/screening. At least 30% of total subjects will be between the ages of 10 and 14 years and at least one third, but no more than two thirds, female subjects Women of childbearing potential must have a negative pregnancy test within 24 hours prior to the start of study drug Women must not be breastfeeding Women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs: saxagliptin, and dapagliflozin, plus 5 half-lives of study drugs or 30 days (whichever is longer), plus 30 days (duration of ovulatory cycle) for a total of 60 days post treatment completion Target Disease Exceptions Presence of Type 1 diabetes, as demonstrated by Preexisting diagnosis of Type 1 diabetes Previous diagnosis of monogenic etiology of Type 2 diabetes Diabetes ketoacidosis (DKA) within 6 months of screening Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics, other antidiabetes medications not otherwise specified Sixteen weeks: thiazolidinediones, DPP-4 inhibitors (with no reported medication related AEs related to DPP-4 inhibitors), sodium glucose cotransporter-2 (SGLT-2) inhibitors (with no reported medication related AEs related to SGLT-2 inhibitors) Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study Medical History and Concurrent Diseases Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Obesity Edema For in the study, subjects must fulfil the following 1. Healthy volunteers 2. Signed informed consent 3. Willingness to comply with study restrictions of not using alcohol, coffee etc during the hours specified below prior to each study day Subjects must not enter the study if any of the following are present: 1. Chronic disease requiring continuous medication or harden the participation in the study as judged by the investigator 2. High blood pressure (>140/90 mm Hg) 3. Chronic pain such as pain that is constant and impairs quality of life 4. Consumption of medications during the last 7 days prior the study day, not including contraceptives 5. Consumption of nature medicine or supplements that results in a increased intake of a specific compound that isn't a nutrient during the last 7 days prior the study day 6. Smoking, snuff use or intake of drugs during the last 7 days prior the study day 7. Intake of alcohol during the last 24 hours prior the study day 8. Intake of coffee and tea during the last 12 hours prior the study day 9. Strenuous physical activity before the study during the last 6 hours prior the study day 10. Pregnancy: Females of childbearing potential must confirm to use reliable contraception and not suspect to be pregnant

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Astrocytoma, Grade III Glioblastoma Specifics for groups A and B Newly diagnosed glioblastoma or anaplastic astrocytoma, IDH1R132H-non-mutant by immunohistochemistry locally assessed, with FFPE tissue available for central MGMT testing and optional biomarker studies (treatment allocation will be performed based on centrally assessed MGMT result) Tumor debulking surgery, including partial resection Age > 65 and considered non-eligible for combination therapy (TMZ/RT→TMZ) in Investigator's opinion No prior RT with overlap of radiation fields with the planned RT in this study (Group A) No prior therapy for glioblastoma or anaplastic astrocytoma before surgery Brain MRI within 14 days before the first dose of TG02 Specifics for group C IDH1R132H-non-mutant glioblastoma or anaplastic astrocytoma at first relapse with tissue available from first surgery. [Per 2016 WHO classification, in patients older than 55 years of age at diagnosis with a histological diagnosis of glioblastoma, without a pre-existing lower grade glioma and with non-midline tumor location, immunohistochemical negativity for IDH1R132H suffices for classification as glioblastoma. In all other instances of diffuse gliomas, lack of IDH1R132H immunopositivity should be followed by IDH1 and IDH2 sequencing to detect or other less common IDH mutations.] Brain MRI at the time of progression or 14 days before the first dose of TG02 and availability of last brain MRI before progression diagnosis for upload to the EORTC Imaging Platform for post-hoc central review of progression Diagnosis of recurrence more than 3 months after the end of RT for initial treatment

2

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 0.0-999.0, BPH With Urinary Obstruction Patients having first attack of acute urinary retention secondary to BPH Renal impairment Suspected urethral stricture Neurogenic bladder Cancer prostate Medically induced retention Previous use of alpha blockers History of drug hypersensitivity or allergy to Tamsulosin

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 41.0-80.0, Urinary Retention Inguinal Hernia Males of 41 to 80 years old who are going for elective inguinal hernia repair (laparoscopic or open) under general anesthesia Patient whom has any of the following will be excluded Contraindication to tamsulosin : known allergy, known orthostatic hypotension, significant cardiac co-morbidities ( New york heart association functional classification >2) or heart failure End stage renal failure More than two anti-hypertensive use/long term alpha blockers/beta blockers/anticholinergic (eg : buscopan) Previous urological or pelvic surgery Known benign prostatic hyperplasia on medications Long term indwelling catheters Concurrent neurologic disease such as stroke, poliomyelitis, cerebral palsy, multiple sclerosis, spinal lesions, diabetic and alcoholic neuropathy

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 50.0-999.0, Lumbar Spinal Stenosis Fulfilment of International Society for the Study of Lumbar Spine clinical diagnosis for lumbar spinal stenosis with the presence of at least 6 out of the 7 following "pain in the buttocks or legs while walking"; "flex forward to relieve symptoms"; "feel relief when using a shopping cart or bicycle"; "motor or sensory disturbance while walking"; "normal and symmetric foot pulses"; "lower extremity weakness"; and "low back pain" Lumbar spinal stenosis qualitatively detected on MRI or CT-scan Inability to speak or read French Impossibility or refusal to have an ergometric bicycle at home Ongoing lumbar-flexion-based endurance training History of spinal surgery Cognitive impairment Neurological or vascular disorder involving the lower limbs Contraindication to cycling

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-85.0, Glioblastoma Multiforme Anaplastic Astrocytoma Male or female ≥ 18 years of age 2. Diagnosis of advanced solid tumor or hematologic malignancy (limited to lymphoma) that has failed or become intolerant to standard therapy (Component 1 single agent PAC-1) Note: Gliomas are excluded from Component 1 (see #19) 3. Diagnosis of high grade glioma: glioblastoma multiforme (GBM) or anaplastic astrocytoma after progression following treatment with standard first line therapy (Component 2 PAC-1 in combination with temozolomide). 4. Has measurable disease, defined as at least 1 tumor that fulfills the for a target lesion according to 1.1 (Component 1). 5. For patients in study Component 2 measurable disease RANO will be used. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see Appendix 4) 7. Has adequate hepatic function defined as total bilirubin < 1.5 mg/dL, serum albumin > 3.0 gm/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 × upper limit of normal (ULN) or < 3 x ULN for subjects with known hepatic metastases 8. Has adequate renal function defined as serum creatinine < 1.5 × ULN 9. Has adequate bone marrow function defined as a hemoglobin ≥ 10 g/dL, absolute neutrophil count (ANC) ≥ 1.5 × 109/L, and platelet count ≥ 100 × 109/L 10. Patients taking antiepileptic drugs (AED) must be on stable doses of AED for at least two weeks prior to registration and have no episode of seizures for at least 14 days prior to registration. Because some AEDs enhance or inhibit enzymes that may affect PAC-1 metabolism, those AEDs will not be permitted in this study. The AEDs that are and are not permissible are in Appendix 6. 11. Patient must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after capsule(s) administration 12. Must be willing and able to comply with study visits and procedures 13. Has read, understood and signed the informed consent form (ICF) approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC) 14. Women of childbearing potential (WOCP) must not be pregnant (confirmed by a negative pregnancy test, with a serum B-HCG with a sensitivity of 50 mL U/L within 7 days of study treatment) or breast-feeding. In addition, a medically acceptable method of birth control must be used such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence during the study participation and for one month after last dose of study drug(s). Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP. 15. Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least one month after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative. 16. Prior systemic treatments for metastatic disease are permitted but may not be ongoing, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy (see #20). 17. Willingness to donate blood for biomarker studies related to the type of therapies used in this trial and the tumor types being treated Had surgery within 4 weeks prior to study treatment except for minor procedures (hepatic biliary stent placement is allowed) 19. For Component 1 (PAC-1 alone), gliomas are excluded, as well as any history of brain metastases, seizures or underlying brain injury (e.g., traumatic brain injury, or hemorrhagic or ischemic stroke) 20. Patients may not have received cytotoxic chemotherapy, targeted therapies, biologic response modifiers, chemotherapy, and hormonal therapy within the last 3 weeks, or nitrosureas within the last 6 weeks prior to study treatment. 21. Has a known hypersensitivity to temozolomide (this criterion applies only in Component 2) 22. Has a history of blood clots, pulmonary embolism, or deep vein thrombosis unless controlled by anticoagulant treatment (patient must be on stable dose for 2 weeks) 23. Has a history of an arterial thromboembolic event within the prior six months including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina. 24. Has uncontrolled human immunodeficiency virus (HIV) (defined as HIV RNA >500 copies/ml and CD4+ count<200/mm3 on antiretroviral therapy) infection or hepatitis B (defined as ALT > 1 x ULN, and HBV DNA >2000 IU/ml) or hepatitis C (defined as ALT > 1 x ULN, persistent viremia on antiviral therapy) infections. 25. Has any clinically significant infection, i.e., any acute viral, bacterial, or fungal infection that requires specific treatment (anti-infective treatment has to be completed ≥ 7 days prior to study entry) 26. Has any other severe, uncontrolled medical condition, including uncontrolled diabetes mellitus (defined as a Hemoglobin A1C≥ 9% in patients with a prior history of diabetes, 28 days prior to study ) or clinical signs of unstable congestive heart failure (Stage III-IV of the New York Heart Association Functional Classification) (Appendix 5). 27. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%. 28. Prior allogeneic bone marrow or organ transplantation. 29. > Grade 1 peripheral neuropathy within 14 days before enrollment. 30. Pregnant or breastfeeding temozolomide is Pregnancy Category D can cause fetal harm. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 31. Patient has received other investigational drugs within 14 days prior to study treatment. 32. Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study. 33. Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant (such as acute ischemia, left bundle branch block, ventricular arrhythmias) or baseline prolongation of the rate-corrected QT interval (e.g., repeated demonstration of QTc interval > 480 milliseconds). 34. Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug. 35. Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance 36. Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial

1

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, High Risk Superficial Upper Urinary Tract Transitional Cell Carcinoma Endoscopic Surgical Procedure Transitional Epithelial Cells Be willing and able to provide written informed consent for the trial. 2. Be at least18 years of age on day of signing informed consent. 3. Have pathologically documented high grade (CIS, Ta, T1) that could be completely ablated with ureteroscopy or through antegrade percutaneous access. 4. Subject must also unwilling or unfit to undergo treatment with radical nephroureterectomy 5. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Tissue must be obtained from the most recent upper urinary tract biopsy. 6. Have a performance status of 0-1 on the ECOG Performance Scale (Appendix A). 7. Demonstrate adequate organ function, all screening labs should be performed within 28 days of treatment initiation. 8. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. 10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 11. Patients who received prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for are allowed into the study as long as there is confirmed recurrence of the disease after previous treatment and the patient is unwilling or unfit to undergo radical surgery Currently has active or progressive metastatic disease. (Chest X-ray, Computerized Tomography [CT] urogram or Magnetic Resonance Imaging [MRI], and urogram are allowed to ascertain the superficial nature of the disease when indicated, but not required. If urogram protocol is not available or contrast allergy/poor renal function precludes such imaging, then non-contrast CT or MRI of the abdomen/pelvis within 90 days of study entry will suffice.) 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has had a prior monoclonal antibody within 4 weeks before study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4. Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for 5. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions basal cell carcinoma of the skin, squamous cell carcinoma of the skin, localized prostate cancer with no recurrence after curative surgery or radiation, or in situ cervical cancer that has undergone potentially curative therapy. Lower urinary tract transitional cell carcinoma is also allowable on study as high risk transitional cell carcinoma is commonly multifocal, and intraluminal BCG therapy is also used for treatment of lower urinary tract lesions in a manner similar to that of 7. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 8. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease, or active , non-infectious pneumonitis. 9. Has an active infection, including a concurrent febrile illness, requiring systemic therapy. 10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 12. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 4 months after the last dose of trial treatment. 13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) including anti-CD40 and anti-OX40 antibodies. 14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 15. Has known active Hepatitis B (e.g., HBs Ag reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 16. Has known active tuberculosis. Subjects will not be specifically tested for the study; however, subjects that are tested within 28 days of beginning study or while on study and test positive with the PPD test before treatment should have active tuberculosis ruled out before therapy begins for their superficial renal pelvis cancer. 17. Has received a live vaccine within 30 days prior to the first dose of trial treatment. 18. Has an active urinary tract infection, gross hematuria, or known broken mucosal barrier of the renal pelvis. 19. Less than 14 days post renal pelvis biopsy, TUR, or traumatic catheterization. 20. Evidence of muscle invasive renal pelvis cancer, or transitional cell carcinoma of the upper urinary tract

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Sciatica Age ≥ 18 years Radiating pain below the knee with a severity score of ≥4 on a 0-10 (NRS) in the previous 24 hours Signs of nerve root/spinal nerve involvement as indicated by at least one of the following features; myotomal weakness, dermatomal sensory disturbances (e.g. sensory loss, self-reported tingling/numbness), diminished reflexes, radiating pain exacerbation by SLR Not able to read or speak Norwegian Unlikely to adhere to treatment and/ or complete follow-up (e.g ongoing serious psychiatric disease, drug abuse, plans to move) Sciatica of known cause other than disc herniation or degenerative stenosis Neurogenic claudication, i.e. pain in the legs on walking or standing that resolves with sitting down or lumbar flexion Symptoms indicating immediate surgery: cauda equina syndrome or a progressive large paresis Women who attempt to conceive, are pregnant or breastfeeding Previous episodes of asthma, urticaria or allergic-type reactions after taking aspirin or other NSAIDs Active or history of peptic ulceration, gastrointestinal bleeding, or perforation Use of drugs known to increase upper gastrointestinal adverse events in combination with Naproxen: anticoagulants, aspirin (acetyl salicylic acid), serotonin reuptake inhibitors and systemic corticosteroids Hepatic enzyme (ASAT/ALAT) values above 1,5 x upper limit of normal (ULN)

0

Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-75.0, Lumbar Disc Herniation Annular Disc Tear Annular Tear of Lumbar Disc Age 18 to 75 years old (male or female) Patients with posterior or posterolateral disc herniations at one level between L1 and S1 with radiographic confirmation of neural compression using CT and/or MRI At least six (6) weeks of failed, conservative treatment prior to surgery, or requires immediate surgery to prevent permanent disability Minimum posterior disc height of 5mm at the index level(s) Lower back pain and/or sciatica with or without spinal claudication Oswestry Questionnaire score of at least 40/100 at baseline VAS leg pain of at least 40/100 at baseline Psychosocially, mentally and physically able to fully comply with the clinical protocol and willing to adhere to follow-up schedule and requirements Spondylolisthesis Grade II or higher Subject requires uni or bilateral facetectomy to treat leg/back pain Subject has back or non-radicular leg pain of unknown etiology Prior surgery at the index lumbar level Subject requiring a spine DEXA (i.e., patients with SCORE of ≥ 6) with a T Score less than -2.0 at the index level. For patients with a herniation at L5/S1, the average T score of L1-L4 shall be used Subject has clinically compromised vertebral bodies at the index level(s) due to any traumatic, neoplastic, metabolic, or infectious pathology Subject has sustained pathologic fractures of the vertebra or multiple fractures of the vertebra or hip Subject has scoliosis of greater than ten (10) degrees (both angular and rotational) Any metabolic disease bone disease that has not been stabilized for at least three months (e.g., Paget's disease, osteomalacia, osteogenesis imperfecta, thyroid and/or parathyroid gland disorder, etc.) Subject has an active infection either systemic or local

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Glioblastoma Multiforme Anaplastic Astrocytoma Radiotherapy Years or older Histologically confirmed newly diagnosed glioblastoma or anaplastic astrocytoma Patients must have undergone surgery with macroscopic complete resection or incomplete resection with residual disease less than 5 cm on MRI An MRI or a scan 48h after surgery should be available WHO ≤ 2 Indication for adjuvant radiotherapy Surgery must have been performed 45 days before the start of radiotherapy Ability to understand and to give consent Age < 18 Years Prior radiation therapy to the brain Any usual formal indication against MRI (claustrophobia, metallic objects or implanted medical devices in body: pacemaker, clips, prostheses ...) Allergic reaction to FET Pregnant women or nursing mothers Refusal to use effective contraception at study entry and throughout the study if patient is of childbearing age

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 21.0-80.0, Aphasia Stroke Stroke, Ischemic Aphasia, Broca Aphasia, Global Aphasia, Mixed Aphasia, Jargon Aphasia, Expressive Aphasia, Conduction Aphasia, Fluent Aphasia, Anomic Experienced a left hemisphere ischemic or hemorrhagic stroke At least 12 months post-stroke Primarily English speaker for the past 20 years Ability to provide informed written or verbal consent MRI-compatible (e.g., no metal implants, not claustrophobic) History of a right hemisphere stroke (Bilateral stroke) Clinically reported history of dementia, alcohol abuse, psychiatric disorder, traumatic brain injury, or extensive visual acuity or visual-spatial problems Severely limited speech production and/or auditory comprehension that interferes with adequate participation in the therapy provided

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 1.0-39.0, Anaplastic Astrocytoma Anaplastic Ependymoma Anaplastic Ganglioglioma Anaplastic Meningioma Anaplastic Oligodendroglioma Pleomorphic Xanthoastrocytoma, Anaplastic Atypical Teratoid/Rhabdoid Tumor Brain Cancer Brain Tumor Central Nervous System Neoplasms Choroid Plexus Carcinoma CNS Embryonal Tumor With Rhabdoid Features Ganglioneuroblastoma of Central Nervous System CNS Tumor Embryonal Tumor of CNS Ependymoma Glioblastoma Glioma Glioma, Malignant Medulloblastoma Medulloblastoma; Unspecified Site Medulloepithelioma Neuroepithelial Tumor Neoplasms Neoplasms, Neuroepithelial Papillary Tumor of the Pineal Region (High-grade Only) Pediatric Brain Tumor Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only) Pineoblastoma Primitive Neuroectodermal Tumor Recurrent Medulloblastoma Refractory Brain Tumor Neuroblastoma. CNS Glioblastoma, IDH-mutant Glioblastoma, IDH-wildtype Medulloblastoma, Group 3 Medulloblastoma, Group 4 Glioma, High Grade Neuroepithelial Tumor, High Grade Medulloblastoma, SHH-activated and TP53 Mutant Medulloblastoma, SHH-activated and TP53 Wildtype Medulloblastoma, Chromosome 9q Loss Medulloblastoma, Non-WNT Non-SHH, NOS Medulloblastoma, Non-WNT/Non-SHH Medulloblastoma, PTCH1 Mutation Medulloblastoma, WNT-activated Ependymoma, Recurrent Glioma, Recurrent High Grade Glioma, Recurrent Malignant Embryonal Tumor, NOS Glioma, Diffuse Midline, H3K27M-mutant Embryonal Tumor With Multilayered Rosettes (ETMR) Ependymoma, NOS, WHO Grade III Ependymoma, NOS, WHO Grade II Medulloblastoma, G3/G4 Ependymoma, RELA Fusion Positive Potential participants will first be screened using the screening inclusion/exclusion shown below. If they meet the requirements of the screening phase, they will then be evaluated for enrollment based on the overall study's as well as the stratum-specific inclusion/ for the applicable stratum, all of which are shown below ALL Participants with recurrent, progressive, or refractory brain tumors Age ≥ 1 year and < 25 years at the time of screening. Exception: Participants with recurrent, progressive, or refractory Medulloblastoma and are ≥ 1 and < 40 years of age at the time of study screening are eligible for screening Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines ALL Participants with a diagnosis of recurrent, progressive, or refractory low grade glioma (LGG) Previous exposure to a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib) Participants with a history of clinically significant, uncontrolled heart disease and/or repolarization abnormalities Participants with any history of QTc prolongation (i.e. QTc interval of > 450 msec). Participants who meet the requirements of the screening phase will then be evaluated for enrollment based on the overall study's as well as the stratum-specific inclusion/

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 22.0-999.0, Astrocytoma, Grade III Understand and voluntarily sign and date an informed consent document before any study related assessments/procedures are conducted. 2. Males and females of age ≥18 years at the time of the signing of the informed consent document. 3. All subjects must have histologic evidence of G3 MG and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bi-dimensional product of enhancement, a new enhancing lesion or a significant increase in T2 FLAIR). 4. Subjects with archival tumor tissue suitable for genetic testing must give permission to access and test the tissue; subjects without archival tumor tissue are eligible. 5. No prior treatment with BEV or any anti-angiogenesis agents. 6. At least 4 weeks from surgical resection and 12 weeks from end of radiotherapy prior to enrollment in this study, unless relapse is confirmed by tumor biopsy or new lesion outside of radiation field, or if there are two MRIs confirming progressive disease that are 8 weeks apart. 7. All AEs resulting from prior chemotherapy, surgery or radiotherapy must have resolved to NCI-CTCAE (v. 4.03) Grade ≤1 (except for laboratory parameters outlined below). 8. Laboratory results within 7 days prior to administration (transfusions and/or growth factor support may be used at the discretion of the Investigator during Screening) Hemoglobin ≥9 g/dL Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelet count ≥100 × 109/L Serum bilirubin ≤1.5 × upper limit of normal (ULN) or ≤3 × ULN if Gilbert's disease is documented Aspartate transaminase (AST) ≤ 2.5 ULN Serum creatinine ≤1.5 × ULN. 9. Karnofsky Performance Status (KPS) score ≥70%. 10. Willing and able to adhere to the study visit schedule and other protocol requirements The presence of any of the following will a subject from enrollment: 1. The presence of 1p19q LOH which is diagnostic for anaplastic oligodendroglioma (AO). 2. Co-medication that may interfere with study results, e.g., immunosuppressive agents other than corticosteroids. (Steroid therapy for control of cerebral edema is allowed at the discretion of the investigator. Subjects should be on a stable dose of steroids for at least 1 week prior to study beginning.) 3. Chemotherapy administered within 4 weeks (6 weeks for an IV nitrosoureas and 12 weeks for an implanted nitrosoureas wafer) prior to Day 1 of study treatment. 4. Pregnancy or breastfeeding. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit adherence with study requirements, or disorders associated with significant immunocompromised state. 6. Known previous/current malignancy requiring treatment within ≤ 3 years except for cervical carcinoma in situ, squamous or basal cell skin carcinoma and superficial bladder carcinoma. 7. Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Peripheral Arterial Disease Patients with symptomatic LEAD (Fontaine stage ≥ IIa) ABI ≤ 0.9 TBI ≤ 0.6 if incompressible arteries (diabetes and renal insufficiency) Signed written informed consent form Neurological and neuromuscular disorders which can limit balance and walking Any history of altitude-related sickness Any health risks (assessed during clinical history) linked to hypoxia exposure Acclimatization or exposure to hypoxia of more than 2000 m for more than 48 h during a period of 6 months before the study Medication required for the treatment of migraines, claustrophobia that may interfere with the interpretation of the results Obstructive sleep apnea (> 25 Apnea-Hypopnea Index) Prior leg/foot amputation Pregnant women Cardiac contraindication to exercise

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Patient is a 45-year-old man with a history of anaplastic astrocytoma of the spine complicated by severe lower extremity weakness and urinary retention s/p Foley catheter, high-dose steroids, hypertension, and chronic pain. The tumor is located in the T-L spine, unresectable anaplastic astrocytoma s/p radiation. Complicated by progressive lower extremity weakness and urinary retention. Patient initially presented with RLE weakness where his right knee gave out with difficulty walking and right anterior thigh numbness. MRI showed a spinal cord conus mass which was biopsied and found to be anaplastic astrocytoma. Therapy included field radiation t10-l1 followed by 11 cycles of temozolomide 7 days on and 7 days off. This was followed by CPT-11 Weekly x4 with Avastin Q2 weeks/ 2 weeks rest and repeat cycle.

eligible ages (years): 18.0-999.0, Lumbar Spinal Stenosis Mild-severe lumbar central canal stenosis identified by MRI or CT scan Symptoms Lower extremety symptoms consistent with neurogenic claudication Pain, weakness and/or numbness triggered by standing or walking, and relieved by sitting Must be able to read English and complete assessment instruments Cognitive impairment that renders the patient unable to give informed consent or provide accurate data Clinical co-morbidities that could interfere with the collection of data concerning pain and function Severe vascular, pulmonary, or coronary artery disease that limits ambulation including recent myocardial infarction (within 6 months) Spinal instability requiring surgical fusion Severe osteoporosis as defined by multiple compression fractures or a fracture at the same level as the stenosis Metastatic cancer Excessive alcohol consumption or evidence of non-prescribed or illegal drug use Pregnancy Concordant pain with internal rotation of the hip (or known hip joint pathology) Active local or systemic infection

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