Diagnosis of diabetes mellitus Men/women ≥21 years old Foot or ankle wounds sized 5 cm2 -100 cm2 ABI≥0.5 or toe pressures >30 mmHg Active Charcot arthropathy Unable to use NPWT at home Untreated bone or soft tissue infection Unable to keep research appointments Active alcohol or substance abuse

1. Be willing and able to provide written informed consent for the trial. 2. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer. A diagnosis of possible ATC/UTC will be allowed if the clinical presentation is consistent with anaplastic or undifferentiated thyroid cancer. 3. Be ≥ 18 years of age on day of signing informed consent. 4. Have measurable disease based on RECIST 1.1. 5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived sample. 6. Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 7. Demonstrate adequate organ function as defined in the protocol. , 8. Female subject of childbearing potential should have a negative urine or serum pregnancy 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 be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). 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. 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 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 a known history of active TB (Bacillus Tuberculosis). 4. Hypersensitivity to pembrolizumab or any of its excipients. 5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to 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. 6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. Has 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 10. Has known history of, or any evidence of active, non-infectious pneumonitis. 11. Has an active infection requiring systemic therapy. 12. 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. 13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 14. 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 120 days after the last dose of trial treatment. 15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 18. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

• Diagnosis of T2DM in accordance with American Diabetes Association (ADA) guidelines
• Hemoglobin A1c (HbA1c) at the start of study participation of 7.0-10.5% (53-91 mmol/mol)
• On stable allowable anti-hyperglycemic agents (AHA) or on no background AHA for at least 8 weeks prior to the study participation
• Body Mass Index (BMI) > or = to 18.0 kg/m^2
• Evidence or a history of atherosclerosis involving the coronary, cerebral or peripheral vascular systems
• There is adequate documentation of the objective evidence that the participant has established vascular disease such as investigational site's medical records, copies of such records from other institutions, or a letter from a referring physician that specifically states the diagnosis and date of the most recent occurrence of the qualifying event(s) or procedure(s).
• Male, female not or reproductive potential, or female of reproductive potential who agrees to be abstinent from heterosexual activity or agrees to use or have their partner use 2 acceptable methods of contraception
• Previous randomization into a trial of ertugliflozin
• Experiencing a cardiovascular event (myocardial infarction or stroke) or undergoing coronary angioplasty or peripheral intervention procedure between the Screening Visit and randomization
• Undergoing any cardiovascular surgery (valvular surgery) within 3 months of study participation
• Planned revascularization or peripheral intervention procedure or other cardiovascular surgery
• New York Heart Association (NYHA) IV heart failure at study participation
• History of type 1 diabetes mellitus or a history of ketoacidosis

Inclusion criteria :
• Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing (presence of anti-GAD (glutamic acid decarboxylase) or anti-IA2 (islet antigen 2/tyrosine phosphatase) or anti-islet cell antibodies) and/or clinical features (eg, history of ketoacidosis).
• Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from patient. Exclusion criteria:
• Age <6 years and ≥18 years at randomization.
• Less than 1 year on insulin treatment prior to screening visit.
• Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit.
• Patients using premix insulins in the last 3 months before screening visit or patients using human regular insulin as mealtime insulin in the last 3 months before screening visit.
• Use of an insulin pump in the last 6 months before screening visit or plans to switch to pump within the next 6 months after screening visit.
• No willingness to inject insulin glargine (Lantus or HOE901 [U300]) once daily.
• HbA1c <7.5% or >11% at screening.
• Initiation of any glucose-lowering medications in the last 3 months before screening visit.
• Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit.
• Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who are unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse will be considered as an acceptable form of birth control.
• Pregnant or breast-feeding adolescents, or adolescents who intend to become pregnant during the study period, or who are at risk of getting pregnant due to any psychosocial reason during the study period. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Male or female subjects with type 1 diabetes continuously treated with insulin within one year from diagnosis
• Duration of T1D ≥ 8 years
• Age 18-70 years
• History or presence of microalbuminuria or moderate macroalbuminuria, or evidence of declining kidney function regardless of history or presence of albuminuria and/or RAS Blocker treatment. Micro- or moderate macroalbuminuria will be defined as at least two out of three consecutive urinary albumin excretion rates [AERs] or albumin creatinine ratios [ACRs] taken at any time during the two years before screening or at screening in the 30-5000 mg/24 hr (20-3333 ug/min) or 30-5000 mg/g range, respectively, if not on RASB agents, or in the 18-5000 mg/24 hr (12-3333 ug/min) or 18-5000 mg/g range, respectively, if on RASB agents). Evidence of declining kidney function will be defined as an eGFR (CKD-EPI) decline ≥3.0 ml/min/1.73 m2/year, estimated from the slope derived from all the available serum creatinine measurements (including the one at screening assessment) from the previous 3 years. If at least 3 serum creatinine measures are not available in the previous 3 years, then the slope can be derived from creatinine values from the previous 5 years.
• Estimated GFR (eGFR) based on serum creatinine between 40 and 99.9 ml/min/1.73 m2 at screening. The upper and the lower limits should be decreased by 1 ml/min/1.73 m2 for each year over age 60 (with a lower limit of 35 ml/min/1.73m2) and by 10 ml/min/1.73 m2 for strict vegans.
• Serum UA (UA) ≥ 4.5 mg/dl at screening
• History of gout or xanthinuria or other indications for uric acid lowering therapy such as cancer chemotherapy.
• Recurrent renal calculi.
• Use of urate-lowering agents within 2 months before screening.
• Current use of azathioprine, 6-mercaptopurine, didanosine, warfarin, tamoxifen, amoxicillin/ampicillin, or other drugs interacting with allopurinol.
• Known allergy to xanthine-oxidase inhibitors or iodine containing substances.
• HLA B*58:01 positivity (tested before randomization).
• Renal transplant.
• Non-diabetic kidney disease.
• SBP>160 or DBP >100 mmHg at screening or SBP>150 or DBP>95 mmHg at the end of the run-in period.
• Cancer treatment (excluding non-melanoma skin cancer treated by excision) within two years before screening.
• History of clinically significant hepatic disease including hepatitis B or C and/or persistently elevated serum liver enzymes at screening and/or history of HBV/HCV positivity.
• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection.
• Hemoglobin concentration <11 g/dL (males), <10 g/dL (females) at screening.
• Platelet count <100,000/mm3 at screening.
• History of alcohol or drug abuse in the past 6 months.
• Blood donation in the 3 months before screening.
• Breastfeeding or pregnancy or unwillingness to be on contraception throughout the trial.
• Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study.
• Serious pre-existing medical problems other than diabetes, e.g. congestive heart failure, pulmonary insufficiency.

Inclusion Criteria for Patients:
• African-American or White
• age 65 or greater
• English-speaking
• residing in non-institutional setting
• cognitively able to participate in advance care planning
• Serious or chronic illness including: metastatic cancer; end stage renal disease; advanced liver disease, heart disease or lung disease; amyotrophic lateral sclerosis, severe Parkinson's disease; 2 or more unplanned hospitalizations in the last year; requiring assistance with any basic activity of daily living
• Serious illness based on the following: Clinician answers "no" to the surprise question: "Would you be surprised if this person died in the next 12 months?" Exclusion Criteria for Patients:
• residence in nursing home or assisted living facility
• diagnosis of dementia or unable to consent
• documented advance care plan (living will, health care proxy, MOST form, provider note)
• current or prior use of hospice
• current or prior use of non-hospice palliative care except inpatient palliative care consultation

• ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)
• Women of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration; patients that are pregnant or breast feeding are excluded; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of study; should a woman become pregnant or suspect while she or her partner is participating in this study, she should inform her treating physician immediately
• Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:
• Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR
• Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
• NOTE: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage I or II cancer from which the patient is currently in complete remission; any other cancer from which the patient has been disease-free for 5 years
• Patients must have measurable disease
• Patients must meet the criteria below and have received results from one of the designated outside laboratories indicating a "rare variant" that is an actionable Mutation of Interest (aMOI) for specific select subprotocols.
• The following requirements apply:
• The outside laboratory specifically notified the site that patient may be a potential candidate for MATCH due to a detected "rare variant"; the outside lab reports are NOT sufficient for this purpose
• NOTE: The content and format of these specific notifications for the Outside Assay process will vary depending on the designated outside lab in question, as they are each responsible for their own outreach efforts; it is strongly recommended that the designated outside laboratory be contacted to confirm the format and receipt of this notification prior to registering any patients to Step 0
• Patients with an applicable "rare variant" must be able to meet the eligibility criteria for the appropriate subprotocols within 4 weeks following notification of treatment assignment
• NOTE: The receipt of this notification (and the start of the associated deadline for Step 1 registration) may occur shortly after Step 0 registration, since these patients will not be submitting tissue for screening purposes; however, for certain "rare variant" arms, submission of archival tissue for central immunohistochemistry (IHC) testing may be required
• Registration to Step 0 must occur after stopping prior systemic anti-cancer therapy; there is no specific duration for which patients must be off treatment prior to registration to Step 0, as long as all eligibility criteria are met
• There is no particular window of time after notification of potential eligibility from an outside lab in which the patient must be registered to Step 0, but treatment slots will be assigned on a first come, first serve basis to those who do register to Step 0, and are not held for those notified of potential eligibility who do not register to Step 0
• Patients may have received other non-targeted, immunotherapy or targeted treatment between the prior genetic testing at the outside lab and registration to Step 0; the decision to stop such treatment in favor of participation in MATCH, if no further clinical benefit is expected, is per the treating physician's discretion; documentation of a lack of response to the prior treatment is not required in these cases
• NOTE: Other potential aMOIs that would be eligibility criteria for "NON RARE" arms, as determined by the designated laboratories, are not applicable for this process in MATCH
• NOTE: Tumor tissue for the confirmation of "rare variant" by the MATCH assay is to be submitted, preferably from the same time of collection as that evaluated by the designated outside laboratory
• Patient must not require the use of full dose coumarin-derivative anticoagulants such as warfarin; low molecular weight heparin is permitted for prophylactic or therapeutic use; factor X inhibitors are permitted
• NOTE: Warfarin may not be started while enrolled in the EAY131 study
• Stopping the anticoagulation for biopsy should be per site standard operating procedure (SOP)
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 and a life expectancy of at least 3 months
• Patients must not currently be receiving any other investigational agents
• Patients must not have any uncontrolled intercurrent illness including, but not limited to:
• Symptomatic congestive heart failure (New York Heart Association [NYHA] classification of III/IV)
• Unstable angina pectoris or coronary angioplasty, or stenting within 6 months prior to registration to Step 0, 2, 4, 6
• Cardiac arrhythmia (ongoing cardiac dysrhythmias of National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4 grade >= 2)
• Psychiatric illness/social situations that would limit compliance with study requirements
• Intra-cardiac defibrillators
• Known cardiac metastases
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram (ECHO) (as clinically indicated); (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study
• NOTE: To receive an agent, patient must not have any uncontrolled intercurrent illness such as ongoing or active infection; patients with infections unlikely to be resolved within 2 weeks following screening should not be considered for the trial
• Patients must be able to swallow tablets or capsules; a patient with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible
• Patients who are human immunodeficiency virus (HIV)-positive are eligible if:
• CD4+ cell count greater or equal to 250 cells/mm^3
• If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; for experimental cancer therapeutics with CYP3A/4 interactions, protease inhibitor therapy is disallowed; suggested regimens to replace protease inhibitor therapy include dolutegravir given with tenofovir/emtricitabine; raltegravir given with tenofovir and emtricitabine; once daily combinations that use pharmacologic boosters may not be used
• No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
• Probable long-term survival with HIV if cancer were not present
• Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy] or less), or major surgery must have been completed >= 4 weeks prior to start of treatment; all adverse events due to prior therapy have resolved to a grade 1 or better (except alopecia and lymphopenia) by start of treatment; palliative radiation therapy must have been completed at least 2 weeks prior to start of treatment; the radiotherapy must not be to a lesion that is included as measurable disease
• NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing hormone (LHRH) agonist
• NOTE: For patients entering the study via the original screening process, patients may receive non-protocol treatment after biopsy (if clinically indicated) until they receive notification of results; however, lack of response must be documented prior to registration to Step 1; new non-protocol treatment will NOT be permitted as intervening therapy after registration to Step 0; the only intervening treatment permitted is prior therapy that the patient already received prior to Step 0 registration; the decision to stop the intervening non-protocol treatment will be left up to the treating physician if patient has an aMOI; however, patients will need to be off such therapy for at least 4 weeks before receiving any MATCH protocol treatment
• NOTE: For patients entering the study via a designated outside laboratory, no intervening systemic non-protocol treatment is permitted after Step 0 registration; all other eligibility requirements still apply to these patients, including the washouts for prior therapy noted above in this section, the time restrictions outlined, and the eligibility criteria for the intended subprotocol
• Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to start of treatment
• Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and remain off steroids thereafter, except as permitted (see below); patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration to treatment (Step 1, 3, 5, 7)
• NOTE: The following steroids are permitted (low dose steroid use is defined as prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):
• Temporary steroid use: e.g. for computed tomography (CT) imaging in setting of contrast allergy
• Low dose steroid use for appetite
• Chronic inhaled steroid use
• Steroid injections for joint disease
• Stable dose of replacement steroid for adrenal insufficiency or low doses for non-malignant disease
• Topical steroid
• Steroids required to manage toxicity related to study treatment, as described in the subprotocols
• Steroids required as pre- or post-chemotherapy medication for acceptable intervening chemotherapy
• NOTE: Steroids must be completed alongside last dose of chemotherapy
• Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• NOTE: Patients with documented bone marrow involvement by lymphoma are not required to meet the above hematologic parameters, but must have a platelet count of at least 75,000/mcL and neutrophil count of at least 1,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to screening step and must meet the following cardiac criteria:
• Resting corrected QT interval (QTc) =< 480 msec
• NOTE: If the first recorded QTc exceeds 480 msec, two additional, consecutive ECGs are required and must result in a mean resting QTc =< 480 msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs
• The following only need to be assessed if the mean QTc > 480 msec
• Check potassium and magnesium serum levels
• Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG to confirm exclusion of patient due to QTc
• For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual read of QTc is required
• For patients with baseline HR < 60 or > 100 bpm, manual read of QT by trained personnel is required, with Fridericia correction applied to determine QTc
• Patient must not have hypokalemia (value < institutional lower limit of normal)
• No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• NOTE: Patient must be taken off prohibited medication prior to registration to the screening step (Step 0, 2, 4, 6) and remain off these medications thereafter, unless permitted on a subprotocol for the management of treatment related toxicity; patient must be off the drug for at least 5 half-lives prior to registration to the treatment step (Step 1, 3, 5, 7); the medication half-life can be found in the package insert for Food and Drug Administration (FDA) approved drugs
• ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)
• If patients have been biopsied or submitted archived tumor tissue obtained within the last 6 months for assessment with the MATCH assays, patients may receive non-protocol treatment after biopsy/tissue submission (if clinically indicated) until they receive notification of results however, lack of response must be documented prior to registration to step 1; new non-protocol treatment will NOT be permitted as intervening therapy after registration to Step 0; for pat

• Age 13-18 years old
• Diagnosed with Type 1 Diabetes Mellitus >1 year ago with at least one positive diabetes autoantibody
• Patient on multiple daily injections of insulin, with no change to insulin type within the past 3 months
• ≥2 separate HbA1c values (at least 60 days apart) ≥10.0% in the past year, with the most recent HbA1c value ≥10.0%
• English-Speaking (patient and at least 1 parent)
• Patient or parents must own a smart phone or other device compatible with Glooko
• Patients on Continuous Subcutaneous Insulin Infusion
• Diagnosed with Type 2 Diabetes or taking metformin
• Other chronic medical condition that would be likely to affect blood glucose. Exceptions include:
• Hypothyroidism on treatment with normal thyroid function tests
• Asthma with no oral steroids within past 3 months
• Unstable social situation that could compromise diabetes management or study follow-up in the judgment of the investigators

Key
• Advanced solid tumor for which, in the opinion of the Investigator, no other standard therapy offers greater benefit.
• A solid tumor diagnosis in the setting of: 1. a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor 2. a documented NTRK fusion unresponsive to a prior TRK inhibitor 3. a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
• NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 (age ≥16) or Lansky Performance Score (LPS) ≥40% (age<16). If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Status (KPS) (age ≥16) or LPS (age<16) ≥ 50%
• Life expectancy > 4 weeks
• Adequate hematologic, hepatic and renal function.
• Patients with stable CNS primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms and steroid use (if applicable) have been stable for 7 days prior to the first dose of LOXO-195
• Ability to receive study drug orally or by enteral administration Key
• Required treatment with certain strong CYP3A4 inhibitors or inducers.
• Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195 or prolongation of the QT interval corrected (QTcF) > 480 msec within the past 6 months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection
• Pregnancy or lactation.
• Known hypersensitivity to any of the components of LOXO-195 or Ora-Sweet® SF and OraOlus, for patients receiving liquid suspension

• Age > 18 years
• Presumed AJCC (American Joint Committee on Cancer) tumor Stage I or II
• Planned total or near-total thyroidectomy
• Planned goal TSH suppression 0.1-0.5 mU/L for at least 18 weeks postoperatively
• Normal serum TSH within 12 months preceding surgery
• AJCC Stage III or greater
• Undifferentiated, Anaplastic or Medullary Thyroid Cancer
• Planned postoperative TSH goal other than 0.1-0.5 mU/L
• History of gastrointestinal malabsorption or gastric bypass surgery
• Pregnancy
• Use of medications that alter the absorption or metabolism of levothyroxine
• Prior use of levothyroxine

• Patients are eligible under ONE of the following criteria:
• Patients must have histologically confirmed rare cancer and must be able to submit specimens; NOTE: Subsequent to site's Institutional Review Board (IRB) approval of revision 3, patients are NOT required to participate in EAY131 "National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" to register to this study
• FOR PATIENTS ENROLLED IN EAY131 "NCI-MATCH" PRIOR TO EAY131 ADDENDUM 10 ONLY: Patients must have histologically confirmed rare cancer that did not have a match to a molecularly-guided therapy on EAY131 "NCI-MATCH" protocol or who are off protocol treatment on EAY131, "NCI-MATCH" and have no further molecularly-matched treatment recommendations per EAY131, "NCI-MATCH" or who are otherwise unable to receive EAY131, "NCI-MATCH" therapy
• Patients that do not qualify for one of the histologic cohorts may be considered for registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation of at least one of the study chairs via email
• Patients that are determined to have a rare cancer with unknown primary site are eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated cross-sectional imaging of the chest, abdomen, and pelvis
• Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR
• Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
• Patients must have a diagnostic quality computed tomography (CT) scan or magnetic resonance imaging (MRI), performed within 28 days prior to registration, which demonstrates measurable disease, as defined in RECIST v. 1.1; all disease must be assessed and documented on the S1609 Baseline Tumor Assessment Form
• No other prior malignancy is allowed except for the following:
• Adequately managed stage I or II cancer from which the patient is currently in complete remission
• Any other cancer from which the patient has been disease free for one year
• Adequately managed stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission
• Patients may have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >= 4 weeks prior to registration
• Patients who had prior grade 3 or higher immune-related adverse event (e.g. pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.) are not eligible
• Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
• Patients are not eligible if they have had or are planned for solid organ transplant; patients who have received allogeneic hematopoietic stem cell transplant are eligible if:
• The transplant occurred at least 90 days prior to registration,
• Patient has no prior acute graft versus host disease (GVHD), and
• Within 48 hours of registration, patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count (ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl, or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment
• Patients with autoimmune disease who are otherwise eligible must not have received steroid and immunosuppressive therapy within 28 days prior to registration
• Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 28 days prior to registration and have stable disease at time of registration; metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration; patients must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to registration
• Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation, excluding RANKL inhibitors and bisphosphonates); in event patient recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; any planned radiation therapy must be completed before enrollment onto S1609
• Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab
• Patients must have a Zubrod performance status of 0-2
• Within 28 days prior to registration: ANC >= 1,000/mcL
• Within 28 days prior to registration: Platelets >= 75,000/mcL
• Within 28 days prior to registration: Hemoglobin >= 8 g/dL
• Within 28 days prior to registration: Total bilirubin =< 2.0 x institutional upper limit of normal (IULN) or for documented/suspected Gilbert's disease, total bilirubin =< 3.0 x IULN
• Within 28 days prior to registration: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN
• Within 28 days prior to registration: Serum creatinine =< 2.0 x IULN
• Within 28 days prior to registration: Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault formula; estimated creatinine clearance is based on actual body weight
• Patients must have adequate thyroid function, as evidenced by either thyroid-stimulating hormone (TSH) or, free thyroxine (T4) serum tests demonstrating values within the normal range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable if per institutional standard; otherwise, both TSH and free-T4 must be obtained
• Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic hormone (ACTH) values within the institutional normal ranges OR cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days prior to registration
• Females of childbearing potential must have negative serum or urine pregnancy test 7 days prior to registration and agree to use birth control throughout study and for 23 weeks after completion of protocol therapy; patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
• Men of reproductive potential must have agreed to use birth control throughout the study and for 31 weeks after completion of protocol therapy; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (vasectomy); however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures
• Patients must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV) infection at time of registration; patients with HBV or HCV that have an undetectable viral load, or in the opinion of the treating investigator is well-controlled, are eligible
• Patients who are known to be human immunodeficiency virus (HIV)-positive at registration are eligible at the time of registration: 1. Cluster of differentiation (CD)4+ cell count greater or equal to 250 cells/mm^3 2. If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; once daily combinations that use pharmacologic boosters may not be used 3. No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
• Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10mg or equivalent); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Chron's disease), as well as symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or glomerulonephritis); vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 2 years is permitted; short-term steroid premedication for contrast allergy is permitted
• Patients must not have any uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= grade 3)
• Note: Patients with history of CHF or patients who are deemed at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs should have an electrocardiogram (EKG) and echocardiogram (ECHO), as clinically indicated, at baseline and at the start of each cycle; patients who have evidence at baseline (or subsequently) of CHF, myocardial infarction (MI), cardiomyopathy, or myositis cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist, including review of EKG, creatine phosphokinase (CPK), troponin, echocardiogram, as clinically indicated
• Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
• Patients must not have symptomatic interstitial lung disease or pneumonitis
• Patients must have fully recovered from any adverse effects of major surgery (to =< grade 1) at least 14 days prior to registration

1. Age 11
•17 years 2. Male and Female subjects 3. BMI >= 95th percentile according to CDC body mass index chart for age and gender 4. Must be willing to participate and undergo "willingness to change" evaluation 5. Metabolic Syndrome(MetS) which is defined when 3 of the following are met:
• Central adiposity (waist circumference ≥90th% for age and sex)
• Hypertriglyceridemia (triglycerides ≥ 110mg/dl)
• Low HDL cholesterol ≤40mg/dl
• Elevated blood pressure systolic or diastolic blood pressure > 90th % adjusted for age, sex and height or ≥ 130/85
• IFG (Impaired fasting glucose ≥ 100mg/dl or elevated HOMA‐ IR ≥3.16) 6. ALT greater than 60 U/L and Non Alcoholic Fatty Liver Disease based on histologic confirmation on liver biopsy (minimum of 5% of hepatocytes with macrovesicular fat) obtained within 6 months before randomization 1. Those patients with a history of poor compliance or adherence to energy restriction diets 2. Patients on medications that could alter appetite including glucocorticoids, psychostimulants (Vyvanse, Adderall), psychotropic medications (Zoloft, Risperdal), and antihyperglycemic medications (metformin, sulfonylurea) 3. Patients with the following illnesses:
• Type 2 diabetes
• Renal disease
• Mental diseases (mood, psychotic and anxiety disorders)
• Developmental delay
• Autism and autism spectrum disorders
• Any liver disease except for non alcoholic fatty liver (NAFLD)
• Metabolic disorders (tyrosinemia, glycogen storage disease, lysosomal disorders)
• Congenital heart disease
• Myopathies or muscular disorders/disability 4. Patients who follow a (cultural or religious) vegetarian lifestyle as this would not be compatible with Carbohydrate Restriction (need for high quality protein) 5. Prepubertal patients defined by a tanner stage of 1 6. Current or history of significant alcohol consumption

Men or women ≥50 years of age with type 2 diabetes mellitus on treatment with a glucose lowering medication since at least 6 months, and either documented coronary artery occlusive disease or previous revascularization of a coronary artery. Key History of myocardial infarction or any stroke; planned treatment with agents inhibiting blood clotting; planned use of ASA/Aspirin at doses above 150 mg daily; planned coronary, cerebrovascular, or peripheral arterial revascularization; patients with known bleeding disorders and patients who need chronic oral anticoagulant therapy or chronic low-molecular-weight heparin; history of intracranial bleeding at any time, or a history of bleeding from the gastrointestinal tract within the last 6 months or a major surgery within the last 30 days; patients with known severe liver disease or with kidney failure requiring dialysis

1. Pre-pubescent girls (age 2 years [12 kg minimum] to 8 years inclusive; skeletal age <10 years) or boys (age 2 years [12 kg] to 9 years inclusive; skeletal age <11 years). 2. Confirmed classic 21-hydroxylase deficiency evident by genotype groups A, A1 or B or clinical course (e.g., adrenal crisis with documented hyperkalemia and hyponatremia, at diagnosis or during a later evaluation; ambiguous genitalia in females). Documentation of one or both parents' genotypes may be required to confirm the subject's genotype. 3. Requirement for standard of care fludrocortisone (any dose) and ≥10 mg/m2/day of hydrocortisone for at least 1 month prior to the study consent. 4. Morning serum androstenedione concentrations >1.5 x ULN after 7 days of dosing with doses of hydrocortisone required for physiologic replacement. 5. At least one parent (or other legally acceptable representative) must sign the informed consent form before the performance of any study procedures, but both parents must sign if both have parental rights. Children who are capable of providing assent (typically 10 years of age and older) must sign an assent form before the performance of any study procedures 1. Evidence of central puberty: Tanner Stage >2 for breast development in girls or testicular volume >4 mL in boys, or random LH >0.3 mIU/mL. Subjects with pubic and/or axillary hair as the only sign of puberty onset will be allowed. 2. Current or history of hepatitis from any etiology, including history of active viral hepatitis A, B, or C. 3. Patients with baseline hepatic impairment are excluded from this trial. To be eligible for this protocol, patients must meet all of the following criteria: AST, ALT and Total bilirubin < ULN Albumin > LLN No evidence of ascites No evidence of encephalopathy 4. Abnormalities of liver function developing during the study 5. Abnormal renal function tests, defined as BUN or creatinine >1.5 ULN for age. 6. Significant anemia (hemoglobin < 12 g/dl). If documented to be due to iron deficiency, subjects may be rescreened 3 months after this has been treated. 7. Clinically significant abnormality in the 12-lead electrocardiogram (ECG) 8. A history of a malabsorption syndrome. 9. Evidence of active malignancy. 10. Serious or uncontrolled co-existent disease, including active or uncontrolled infection. Subjects may be rescreened after resolution of any such condition. 11. Concurrent medical condition or disease other than 21-hydroxylase deficiency that may interfere with linear growth or that requires concomitant therapy that is likely to interfere with study procedures or results. 12. Asthma or other condition requiring treatment with systemic corticosteroids within the past 3 months. Asthma treatment with inhaled corticosteroids is permitted. 13. Treatment with potentially hepatotoxic medications (statins); strong inhibitors of CYP3A4 (ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), or CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). CYP2C8 substrates (rosiglitazone, pioglitazone, rapaglinide) and CYP2D6 substrates (dextromethorphan, thioridazine) should be avoided 14. Treatment with medications to affect puberty or synthesis of sex steroids, including gonadotropin releasing hormone agonists, aromatase inhibitors, or androgen receptor blockers (e.g., flutamide, spironolactone). However, a gonadotropin releasing hormone agonist may be started during the study for treatment-emergent central puberty without disqualifying the subject 15. Treatment with growth hormone at enrollment or during the course of the study. 16. Known allergies, hypersensitivity, or intolerance to abiraterone acetate or its excipients (refer to United States Prescribing Information). 17. Has received an investigational drug within 4 weeks of the planned first dose of study drug or is currently enrolled in an investigational interventional study. 18. Any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments. 19. Presence or history of cataracts.

Inclusion Criteria
• CKD Inclusion Criteria (present at least ≥ 3 months apart) 1. There will be two or more Estimated Glomerular Filtration Rate (eGFRs) calculations less than 60ml/minute (corrected for BSA) or 2. Two or more positive tests for albuminuria and/or proteinuria Albuminuria/proteinuria can be defined by quantitative criteria with albumin/creatinine ratio greater than 30mg/g, urine protein creatinine ratio greater than 200mg/g or positive dipstick with protein detection (adjusted for urinary concentration/specific gravity).
• Diabetes Inclusion Criteria Only patients with type 2 diabetes will be enrolled in this study. 1. Random blood glucose greater than 200mg/dL 2. Hemoglobin A1C greater than 6.5% 3. Use of hypoglycemic agents or 4. Type 2 diabetes included in problem list
• Hypertension Inclusion Criteria 1. Systolic blood pressure greater than 140 mmHg on two different occasions at least one week apart 2. Diastolic blood pressure greater than 90 on two occasions at least more than one week apart 3. Use of antihypertensive agents except thiazide diuretics or 4. Hypertension included in problem list
• Exclusion criteria will be minimal in this pragmatic trial. The collaborative model of care will not be implemented in patients younger than 18 years or older than 85 years of age or patients who have CKD stage 5/End Stage Renal Disease(ESRD.
• Primary care practitioners have the option of not implementing the intervention on any of their patients if they believe benefit to be minimal or risk too high due to patient comorbidities

• Male or female subjects of all races and ethnicities, age 18-89
• Diagnosis of diabetes mellitus
• Has a diabetic foot ulcer
• End-stage renal disease (ESRD)
• Has untreated foot ulcer at time of study
• HIV, hepatitis, autoimmune disease, Systemic lupus erythematous (SLE), Raynaud's disease
• Ankle-Brachial Index (ABI) < 0.4
• Unable or unwilling to provide informed consent

• Diagnosis of glucose transporter type I deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory or by PET scan.
• Stable diet on no dietary therapy (i.e., no dietary therapy for 1 month).
• Males and females 30 months to 17 years 11 months old, inclusive.
• Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
• Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis that could increase the subject's risk of developing diarrhea or stomach pain.
• Subjects with a BMI (body mass index) greater than or equal to 30.
• Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride supplemented diets, Atkins diet and versions of it, low glycemic index diet, and related diets).
• Subjects with no evidence of abnormal EEG (spike wave discharges) in the last 12 months.
• Women who are pregnant or breast-feeding may not participate. Women who plan to become pregnant during the course of the study, or who are unwilling to use birth control to prevent pregnancy (including abstinence) may not participate. Females age 10 and over will be asked to provide a urine sample for a pregnancy test via dipstick. Subjects will be asked to agree to abstinence or another form of birth control for the duration of the study.
• Allergy/sensitivity to C7.
• Previous use of triheptanoin in the past 1 month. Subjects who participate in Protocol 1 of this study are thus eligible.
• Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain disorder (such as Alzheimer's disease) that would confound assessment of cognitive changes, in the opinion of the investigator.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent, or assent for children age 10-17.
• Addition of a new antiseizure drug in the previous 3 months.

• Upper age limit of =< 18 years of age for medullary thyroid carcinoma (MTC), renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC)
• Patients must have a body surface area >= 0.35 m^2
• Patients must have recurrent or refractory disease, or newly diagnosed disease with no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse:
• Ewing sarcoma
• Rhabdomyosarcoma (RMS)
• Non-rhabdomyosarcoma soft tissue sarcomas (STS) including microphthalmia transcription factor associated STS (alveolar soft part sarcoma [ASPS] and clear cell sarcoma [CCS])
• Osteosarcoma
• Wilms tumor
• Rare tumors
• Medullary thyroid carcinoma (MTC)
• Renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Hepatoblastoma
• Adrenocortical carcinoma
• Pediatric solid tumors (including central nervous system [CNS] tumors) with known molecular alterations in the targets of XL184 (i.e., MET amplification, overexpression, activating mutation, MET translocation, MET exon skipping mutations, activating RET mutations, RET rearrangement, overexpression or activation of AXL); documentation of the alteration from a Clinical Laboratory Improvement Act (CLIA) certified laboratory will be required
• Note: Documentation of any known tumor molecular alterations and RET mutation status for patients with MTC (germline) must be uploaded via the RAVE system
• Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
• Note: The following do NOT qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans)
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement parameters noted above
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
• At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of M-Iodobenzylguanidine (MIBG); >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total-body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
• Subjects should not have any clinically relevant ongoing complications from prior radiation therapy (i.e., radiation esophagitis or other inflammation of the viscera)
• No evidence of active graft versus (vs.) host disease and >= 2 months must have elapsed since transplant
• Not previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib); there are no limits on number of prior therapeutic regimens; patients who have been treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligible
• Peripheral absolute neutrophil count (ANC) >= 1000/uL for patients with solid tumors without bone marrow involvement
• Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment) for patients with solid tumors without bone marrow involvement
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) for patients with solid tumors without bone marrow involvement
• Peripheral absolute neutrophil count (ANC) >= 750/uL for patients with solid tumors and known bone marrow metastatic disease
• Platelet count >= 50,000/uL for patients with solid tumors and known bone marrow metastatic disease
• Hemoglobin >= 8.0 g/dL for patients with solid tumors and known bone marrow metastatic disease
• Transfusions are permitted to meet both the platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• 2 to < 6 years of age
• Male and female: 0.8 (maximum serum creatinine [mg/dL])
• 6 to < 10 years of age
• Male and female: 1 (maximum serum creatinine [mg/dL])
• 10 to < 13 years of age
• Male and female: 1.2 (maximum serum creatinine [mg/dL])
• 13 to < 16 years of age
• Male 1.5 (maximum serum creatinine [mg/dL])
• Female: 1.4 (maximum serum creatinine [mg/dL])
• >= 16 years of age
• Male: 1.7 (maximum serum creatinine [mg/dL])
• Female: 1.4 (maximum serum creatinine [mg/dL])
• Urine protein: =< 30 mg/dl in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour (h) urine sample
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3 x ULN) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2.8 g/dL
• No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) class III or IV congestive heart failure (CHF)
• No clinically significant cardiac arrhythmias, stroke or myocardial infarction within 6 months prior to enrollment
• QTc =< 480 msec; Note: Patients with grade 1 prolonged QTc (450- 480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
• Patients with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures may be enrolled
• CNS toxicity =< grade 2 with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible
• A blood pressure (BP) =< the 95th percentile for age, height, and gender for pediatric patients < 18 years old and =< 140/90 mmHg for patients >= 18 years old; patients should not be receiving medication for treatment of hypertension (except patients with Wilms tumor and RCC who may be eligible if on stable doses of no more than one anti-hypertensive medication with a baseline BP =< ULN for pediatric patients and =< 140/90 for adult patients); please note that 3 serial blood pressures should be obtained and averaged to determine baseline BP
• International normalized ratio (INR) =< 1.5
• Serum amylase =< 1.5 ULN
• Serum lipase =< 1.5 ULN
• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use two methods of birth control- a medically accepted barrier method of contraceptive method (e.g., male or female condom) and a second effective method of birth control-during protocol therapy and for at least 4 months after the last dose of XL184; abstinence is an acceptable method of birth control
• Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if pegfilgrastim)
• Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib)
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) are prohibited
• Note: Low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen
• Patients must not have received enzyme-inducing anticonvulsants within 14 days prior to enrollment
• Patients who are receiving drugs that prolong QTc are not eligible
• Patients who are unable to swallow intact tablets are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment; patients with evidence of an acute intracranial or intratumoral hemorrhage on CT or MRI are not eligible (patients with evidence of resolving hemorrhage will be eligible); in patients with CNS tumors, an MRI with ECHO gradient sequences would be required to exclude presence of petechial hemorrhages
• Patients who have had or are planning to have the following invasive procedures are not eligible:
• Major surgical procedure, laparoscopic procedure, or open biopsy within 28 days prior to enrollment
• Central line placement or subcutaneous port placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines (e.g., Hickman or Broviac catheter, peripherally inserted central catheter [PICC]) and at least 7 days prior to enrollment for a subcutaneous port
• Core biopsy within 7 days prior to enrollment
• Fine needle aspirate within 7 days prior to enrollment
• Surgical or other wounds must be adequately healed prior to enrollment
• NOTE: For purposes of this study, bone marrow aspirate and biopsy are not considered surgical procedures and therefore are permitted within 14 days prior to start of protocol therapy
• Patients who have had significant traumatic injury within 28 days prior to enrollment are not eligible
• Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of the study drug are not eligible

• Men or women (non pregnant) 18 years old or above
• Diagnosed for Diabetes Mellitus (type 2)* and ADA criteria Diabetes
• Evidence of peripheral neuropathy on neurologic examination
• Identified by our clinical staff examination and based on the criteria explained in -ADA statement
• Agreed to participate in this study and comply with instruction
• Amputation and active ulcers or infection
• Cognitive deficits
• MMSE score of 24 or lower
• Unable to stand for more than 5 minutes (including symptomatic orthostatic hypotension or pain)
• Any clinically significant orthopedic, muscular, or peripheral vascular disorders that affect balance
• Alcohol or substance abuse within 6 months or major psychiatric disorder

• Children and adolescents between the ages of 10-16 years. Subjects cannot turn 17 years and 11 months before the end of treatment (52 weeks)
• Diagnosis of type 2 diabetes mellitus and treated for at least 30 days with: diet and exercise alone, diet and exercise in combination with metformin monotherapy, diet and exercise in combination with metformin and a stable (Stable is defined as basal insulin adjustments up to 15%) dose of basal insulin, diet and exercise in combination with a stable (Stable is defined as basal insulin adjustments up to 15%) dose of basal insulin
• HbA1c: 7.0-11% (inclusive) if diet and exercise treated or 6.5-11% (inclusive) if treated with metformin as monotherapy, basal insulin as monotherapy or metformin and basal insulin in combination
• Body mass index (BMI) above 85% percentile of the general age and gender matched population
• Type 1 diabetes
• Maturity onset diabetes of the young (MODY)
• Use of any antidiabetic agent other than metformin and/or basal insulin within 90 days prior to screening
• Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator
• History of chronic pancreatitis or idiopathic acute pancreatitis
• Any clinically significant disorder, except for conditions associated with type 2 diabetes history which in the investigator's opinion could interfere with results of the trial
• Uncontrolled hypertension, treated or untreated above 99th percentile for age and gender in children
• Known or suspected abuse of alcohol or drugs/narcotics

• A participant in the Diabetes Control and Complications Trial (DCCT)(N01-DK-6-2204-A).

Inclusion criteria:
• Male or female, age above or equal to 18 years at the time of signing informed consent.
• Subjects fulfilling at least one of the below criteria (For this inclusion criterion the aim is to include minimum 80% of individuals with a previous episode of hypoglycaemia (criterion e). The remaining subjects will have to fulfil at least one of criteria a-d.):
• a) Experienced at least one severe hypoglycaemic episode within the last year (according to the ADA definition, April 2013 (An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.).
• b) Moderate chronic renal failure, defined as glomerular filtration rate 30
•59 mL/min/1.73 m^2 per CKD-EPI by central laboratory analysis.
• c) Hypoglycaemic symptom unawareness (History of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger) during hypoglycaemia).
• d) Treated with insulin for more than 5 years.
• e) Episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (equal to or below 70 mg/dL [equal to or below 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening).
• Subjects diagnosed (clinically) with type 2 diabetes mellitus.
• Treated with basal only insulin (once daily or twice-daily insulin (insulin detemir; insulin glargine 100 U/mL, biosimilar of insulin glargine 100 U/mL or insulin Neutral Protamine Hagedorn)) equal to or above 90 days prior to the day of screening with or without any of the following anti-diabetic drugs with stable doses for equal to or above 90 days prior to screening:
• a) Metformin
• b) Dipeptidyl peptidase -4 inhibitor
• c) Sodium-glucose co-transporter 2 inhibitor
• d) Alpha-glucosidase-inhibitors (acarbose)
• e) Thiazolidinediones
• f) Marketed oral combination products only including the products listed in criteria 5a-5e
• HbA1c equal to or below 9.5% (80 mmol/mol) at screening by central laboratory analysis.
• BMI equal to or below 45 kg/m^2.
•Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening

1. Men or women diagnosed with diabetes at age ≥ 30 years (≥ 20 for American Indians) 2. Duration of diagnosed diabetes < 10 years 3. HbA1c criteria (at final run-in visit, ~2 weeks prior to randomization): 6.8-8.5% 4. Taking a daily dose of ≥ 1000 mg metformin for a minimum of 8 weeks at final run-in 5. Willingness to administer daily subcutaneous injections, take a second diabetes drug after randomization, potentially initiate insulin and intensify insulin therapy if study metabolic goals are not met, perform self-monitoring of blood glucose 6. Fluent in either English or Spanish 7. A negative pregnancy test for all females of childbearing potential (i.e. pre-menopausal, and not surgically sterile) 8. Provision of signed and dated informed consent prior to any study procedures 1. Suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin) or "secondary" diabetes due to specific causes (e.g. previously diagnosed monogenic syndromes, pancreatic surgery, pancreatitis) 2. Current or previous (within past 6 months) treatment with any diabetes drug/glucose-lowering medication other than metformin (limited use of no longer than seven days is allowed, for example during hospitalization) 3. More than 10 years of treatment with metformin at time of randomization screening 4. History of intolerance or allergy or other contraindications to any of the proposed study medications 5. Resides in the same household with another GRADE study participant 6. Current need for any specific glucose-lowering medications solely for other conditions, for example for polycystic ovary syndrome 7. Symptomatic hyperglycemia requiring immediate therapy during screening or run-in, in the judgment of the physician 8. A life-threatening event within 30 days prior to screening or currently planned major surgery 9. Any major cardiovascular event in previous year, including history of myocardial infarction, stroke, or vascular procedure such as coronary artery or peripheral bypass grafting, stent placements (peripheral or coronary) or angioplasty. 10. Plans for pregnancy during the course of the study for women of child-bearing potential 11. History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass (if banding removed, may be considered eligible after 1 year) 12. History of congestive heart failure (NYHA 3 or greater) 13. History of pancreatitis 14. History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization 15. Personal or family history of MEN-2 or family history of medullary thyroid cancer 16. Estimated GFR (eGFR) <30 ml/min/1.73 m2 or end stage renal disease requiring renal replacement therapy 17. History of severe liver disease or acute hepatitis or ALT > 3 times upper limit of normal 18. Current alcoholism or excessive alcohol intake 19. Previous organ transplant 20. Treatment with oral or systemic glucocorticoids (other than short-term treatment, for example for poison ivy) or disease likely to require periodic or regular glucocorticoid therapy (inhaled steroids are allowed) 21. Treatment with atypical antipsychotics 22. History of hemolytic anemia, chronic transfusion requirement, or other condition rendering HbA1c results unreliable as indicator of chronic glucose levels, or hematocrit <35 for males and <33 for females 23. Clinically or medically unstable with expected survival <1 year 24. Unwillingness to permit sites to contact the PCP to communicate information about the study and the participant's data 25. No non-study PCP or inability to identify such a PCP (who will provide non-study care) by the time of final run-in 26. Participation in another interventional clinical trial 27. Previous randomization in the GRADE study 28. In the opinion of the principal investigator (PI), any other factor, including language barrier, likely to limit compliance with the protocol

• Individuals 1 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
• Individuals 1-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling) To be eligible a person must not:
• Have diabetes already
• Have a previous history of being treated with insulin or oral diabetes medications.
• Currently be using systemic immunosuppressive agents (topical and inhaled agents are acceptable)
• Have any known serious diseases

• Age 3-5.5 years old (+/- 2 months) at the date of first camp session they are eligible to join.
• Child and Parents fluent in either English or Spanish.
• Type 1 diabetes mellitus diagnosed for at least 10 months previous to date of first camp they are eligible to join.
• Taking insulin
• Custodial parent or guardian (preferable both parents or guardians) willing to attend both session of camp and the activities scheduled for them.
• Parent or guardian must sign consent before any study procedures are performed.
• Neonatal diabetes (diagnosis in the first 3 months of life) or documented MODY; i.e., a likely genetic form of diabetes rather than an autoimmune etiology.
• Post-surgical diabetes (e.g., pancreatectomy for congenital hyperinsulinism). Such patients often cannot secrete glucagon, leading to a particularly severe inability to defend against hypoglycemia.
• Other severe chronic disease (e.g., cancer, cystic fibrosis) which in the judgment of the investigator is likely to significantly affect glycemic control.
• Patients cannot be taking systemic corticosteroids at enrollment because of adverse effects on glycemic control, but we will not disqualify subjects who require such therapy during the study. Inhaled or topical corticosteroids are permissible.
• Patients with hypothyroidism or hyperthyroidism must be clinically euthyroid and have free T4 and TSH within age-appropriate reference ranges at last medically indicated testing. Patients with out of range values may be retested after medication dose adjustment.
• Developmental delay or behavioral disorder in the patient of sufficient severity, in the judgment of the investigator, to interfere with group activities.
• Medical or psychiatric disorder in a parent of sufficient severity, in the judgment of the investigator, to interfere with group activities.
• Celiac disease is not an exclusion criterion.

• Prepubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage 1 (Tanner 1982) aged:
• Boys: 3-12 years, inclusive
• Girls: 3-11 years, inclusive
• Impaired height (HT) defined as at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS ≤ -2.0) according to the 2000 CDC Growth Charts for the United States Methods and Development, available at http://www.cdc.gov/growthcharts/
• Diagnosis of GHD confirmed by 2 different GH stimulation tests, defined as a peak GH level of ≤10 ng/mL, determined with a validated assay
• Bone age (BA) at least 6 months less than chronological age
• Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age and sex (IGF-1 SDS ≤-1)
• Written, signed informed consent of the parent(s) or legal guardian(s) of the subject and written assent of the subject (if the subject is able to read, understand, and sign)
• Children with a body weight below 12 kg
• Prior exposure to recombinant hGH or IGF-1 therapy
• Children with past or present intracranial tumor growth as confirmed by a sellar MRI scan (with contrast) at Screening (MRI results from up to 6 months prior to Screening may be accepted)
• Children with psychosocial dwarfism
• Children with idiopathic short stature
• History or presence of malignant disease; any evidence of present tumor growth
• Closed epiphyses
• Major medical conditions and/or presence of contraindication to hGH treatment
• Participation in any other trial of an investigational agent within 3 months prior to Screening

• Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on tumor histopathology or elevated urine catecholamines with typical tumor cells in the bone marrow, OR pheochromocytoma or paraganglioma not amenable to curative surgery
• Age ≥ 12 months and able to cooperate with radiation safety restrictions during therapy period with/without pharmacologic anxiolysis.
• Disease status: Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any time (any new lesion or an increase in size of > 25% of a pre-existing lesion). Disease evaluation must be completed within 8 weeks of study entry. If possible, the disease evaluation should take place subsequent to any intervening therapy; if intervening therapy does occur, evaluations should be done as clinically indicated. If patient has received prior treatment with MIBG, they must have a response or stable disease after the most recent MIBG infusion. Patient may have PD after showing an initial response to MIBG therapy (at [or around] the day 35-63 post-MIBG therapy evaluation).
• Stem cells: Patients must have a hematopoietic stem cell product available for re-infusion after 131I-MIBG treatment at doses of ≥ 12 mCi/kg. If no stem cells are available, then the dose of 131I-MIBG should be < 12 mCi/kg.
• The minimum quantity for purged or unpurged peripheral blood stem cells (PBSC) is 1.5 x 106 viable CD34+ cells/kg (recommended 2 x 106 viable CD34+ cells/kg).
• The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum > 2.0 x 108 mononuclear cells/kg).
• Prior Therapy: Patients may enter this study with or without re-induction therapy for recurrent tumor. Patients must have fully recovered from the toxic effects of any prior therapy, meeting the following criteria: At least 2 weeks should have elapsed since any anti-tumor therapy and the patient must meet hematologic criteria below. Three-months should have elapsed in the case of completing radiation to any of the following fields: craniospinal, total abdominal, whole lung, total body irradiation (spot irradiation to skull-based metastases is NOT considered craniospinal radiation for the purposes of this study. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued a minimum of 24 hours prior to 131I-MIBG therapy.
• Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit of normal
• Kidney function: Serum Creatinine ≤ 2x upper limit of normal OR 24-hr creatinine clearance OR GFR ≥ 60 ml/min/1.73m2(For example, a patient would meet this criteria if GFR < 60 ml/min/1.73m2 but serum creatinine ≤ 2x upper limit of normal.)
• Hematologic Criteria: ANC ≥ 750/µL; Platelets ≥ 50,000/µL without transfusion if stem cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells available). Patient must be off myeloid growth factors for at least 24 hours. If the patient has received prior treatment with MIBG, they may be thrombocytopenic, but requiring no more than 2 platelet transfusions per week to maintain counts above 20,000. Hemoglobin must be ≥ 10 gm/dL (transfusion allowed) regardless of stored stem cell availability.
• Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no oxygen requirement
• No clinically significant cardiac dysfunction
• Signed informed consent/assent: The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent/assent to become a study subject has been obtained, in accordance with institutional policies approved by the U.S. Department of Health and Human Services.
• Patients with disease of any major organ system that would compromise their ability to withstand therapy. Any significant organ impairment should be discussed with the Principal Investigator prior to patient entry.
• Because of the teratogenic potential of the study medications, no patients who are pregnant or lactating will be allowed. Patients of childbearing potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is an effective method of birth control.
• Patients who are on hemodialysis
• Proteinuria, in the absence of urinary infection, within 4 weeks prior to the planned treatment date is a relative contraindication to receiving therapy for patients with pheochromocytoma/paraganglioma. Patients with pheochromocytoma/paraganglioma with any proteinuria must have a 24-hr urine protein determination. If proteinuria is confirmed as being above the institutional upper limit of normal, the patient is ineligible for MIBG therapy.
• Patients with active infections that meet grade 3-4 according to the NCI CTCAE v3.0.
• Patients with known MIBG-avid parenchymal brain metastases are not eligible. (Patients with leptomeningeal or skull-based metastases are eligible.)

• Able to provide informed consent
• 18-90 years of age
• Chronic foot ulceration below the ankle
•persistent for 30 days or longer
• Ankle Brachial Index (ABI) >0.5 (Bedside ABI is acceptable for screening purposes as the formal imaging ABI may not be resulted prior to surgery)
• Unable to provide informed consent
• <18 or >90 years of age
• History of poor compliance with follow-up visits
• Gangrene
• Untreated Osteomyelitis
• Widespread malignancy
• Active alcohol or substance abuse such as cocaine, heroin, or methamphetamines
• Currently Pregnant or planning pregnancy during the course of intended participation in the study
• Is nursing or actively lactating

1. Pre-diabetes ("at increased risk for diabetes") defined by meeting 2-out-of-3 of the following glycemic criteria at the baseline visit: 1. Fasting plasma glucose (FPG) 100-125 mg/dL 2. 2-hour plasma glucose (2hPG) 140-199 mg/dL 3. Hemoglobin A1c (HbA1c) 5.7-6.4% 2. Age ≥ 30 years .(≥25 years for people of the following races: American-Indian, Alaska Native, Native Hawaiian or Other Pacific Islander). 3. Body Mass Index 22.5 to 42 kg/m2 4. Provision of signed and dated written informed consent prior to any study procedures. Major 1. Diabetes based on either of the following criteria: 1. History (past 1 year) of hypoglycemic pharmacotherapy (oral or injectable medication approved by the FDA for type 2 diabetes), used for any condition (e.g. pre-diabetes, diabetes, polycystic ovarian syndrome. 2. Meeting the diagnosis criteria for diabetes 2. History (past 3 years) of hyperparathyroidism, nephrolithiasis or hypercalcemia. 3. Pregnancy (past 1 year by report or positive pregnancy test at screening), intent to become pregnant in the next 4 years or unprotected intercourse. History of gestational diabetes is not an exclusion criterion. 4. Currently breastfeeding.

• Type I hyperlipoproteinemia.
• Fasting serum triglyceride levels of greater than 1000 mg/dL.
• Age > 12 years
• Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-protease inhibitors, retinoic acid derivatives and interferons.
• Pregnant or lactating women
• Significant liver disease (elevated transaminases > 2 times upper limit of normal)
• Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks for men or 168 g per week for men)
• Drug use (cocaine, marijuana, LSD, etc.)
• Major surgery in the past three months
• Congestive heart failure
• Serum creatinine greater than 2.5 mg/dL
• Cancer within the past five years
• Gastrointestinal surgery in the past
• Current therapy with anti-coagulants, digoxin and anti-arrhythmics
• Chronic malabsorption syndromes
• Cholestasis
• Acute illnesses such as acute pancreatitis in the last 8 weeks