• Females, 18 to 35 years of age (pregnancy assessed by self-report).
• Non-pregnant.

• Male.
• Known pregnancy (by self-report.
• Known genetic disorder (by self-report).
• Cancer history (including any form of skin cancer).
• Diabetes.
• Failure to meet 21 CFR 1271 donor eligibility criteria based on responses to a donor eligibility questionnaire.
• Positive infectious disease result on any test in the infectious disease screening panel (including HBsAg Screen, HBc Total Ab, HBV NAT, HCV NAT, HIV-1 NAT, HCV Ab Screen, HIV-1/-2, plus O Ab Screen, HTLV-I/-II Ab Screen, T. cruzi Total Ab, Syphilis Ab Screen, CMV Total Ab, West Nile Virus NAT).
• Medical records review.
• Physical exam.    

Eligibility last updated 1/12/23. Questions regarding updates should be directed to the study team contact. 

• Signed informed consent.
• Between 40 to 75 years old (inclusive).
• Have PSP diagnosed for less than 5 years with a current classification of probable PSP Richardson syndrome, a Progressive Supranuclear Palsy Rating scale (PSPRS, Golbe and Ohman-Strickland 2007) score < 40 and MOCA score > 17 at screening.
• Able to ambulate independently or to take at least 5 steps with minimal assistance (Participant requires no more help than touching, providing at least 75% of total effort.  Participant is able to assume all of his body weight, but requires guidance for initiation, balance and/or stability) as performed at screening visit.
• At least a 12-month history of postural instability or falls within 3 years from disease onset as per medical history.
• Able and willing to meet all study requirements including:
  • Have a study partner who is reliable, competent, and at least 18 years of age, able to accompany the participant to study visits, knowledgeable of the participant's ongoing 
    condition during the study to provide study related information to study site when required both 
    in person and via a phone;
  • Reside in a proximity to the study site to allow an unscheduled  visit to happen timely (ideally less than 2 hours);
  • Able to undergo LP, CSF draws, and blood draws.
• If the participant is receiving benzodiazepines, levodopa/carbidopa, levodopa/benserazide, dopamine agonist,  catechol-o-ethyltransferase (COMT)  inhibitor,  rasagiline, CoQl0, or other Parkinson's medications, acetylcholinesterase inhibitors, antipsychotics, memantine, or other non-tau modifying Alzheimer's medication, the doses must have been stable for at least  30 days prior to the screening visit and must remain stable for the duration of the study. No such medication can be initiated during the study.

• Live in a skilled nursing facility or dementia care facility.
• Evidence of motor neuron disease, or any other neurological disease that could explain symptoms.
• Any clinically significant laboratory abnormality, with the exception of these usually found in PSP patients; e.g., lower cholesterol, that may adversely and critically affect a patient's safety or protocol required clinical assessments in the study in the judgement of the investigator.
• Attempted suicide, suicidal ideation with a plan that required hospital admission within 12 months prior to Screening. For patients with (i) a suicide ideation score ≥ 4 on the Columbia Suicide Severity Rating Scale (C-SSRS) within the last 12 months, (ii) suicidal behaviors within the last 12 months (as measured by the answer “Yes” on any of the C-SSRS Suicidal Behavior Items), a risk assessment should be done by an appropriately-qualified mental health professional (e.g., a Psychiatrist or licensed Clinical Psychologist) to assess whether it is safe for the patient to participate in the study. In addition, patients deemed by the Investigator to be at significant risk of suicide, major depressive episode, psychosis, confusion state or violent behavior should be excluded.
• A clear and robust benefit from levodopa at the time of screening defined as improvement of the MDS-UPDRS motor scale by > 30%.
• Use of lithium, methylene blue or other putative disease modifying drugs for PSP within 30 days of screening.
• Any previous use of experimental therapy within 30 days or 5 half-lives prior to Day 1, whichever is greater.
• History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
• Any  condition that increases risk of meningitis unless patient is receiving appropriate prophylactic treatment.
• History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch.
• Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study.
• Have any other conditions which, in the opinion of the Investigator, would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.
• Patient is unable to undergo magnetic resonance imaging (MRI) due to for example claustrophobia or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
• Pregnant  women, breast feeding women, and women of childbearing  potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of investigational drug and for 15 weeks after stopping study medication. Highly effective contraception methods include:
  • Total abstinence from heterosexual intercourse (when this is in line with the preferred and usual lifestyle  of  the participant).  Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had   surgical bilateral oophorectomy   with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 months prior to screening). For female participants on the study, 
    the vasectomized male partner should be the sole partner for that participant;
  • Use of oral (estrogen  and progesterone), injected or implanted hormonal methods  of 
    contraception or other forms of hormonal contraception that have comparable efficacy (failure   
    rate < 1%), for example   hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should be stable on the same pill for a minimum of 3 months before taking study drug.
• If local regulations deviate from the contraception  methods listed above and require more extensive measures to prevent pregnancy, local regulations apply and will be described in the ICF.
• Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age   
  appropriate, history of vasomotor symptoms)   or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six 
  weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.
• Sexually active males unless they always use condoms during intercourse while taking study drug and for 15 weeks(= 5 times the expected plasma terminal half-life of study medication. Plasma is considered  to be the relevant compartment to provide indirect measurement of NI0752 in seminal fluid) after stopping study medication and should not father a child in this period. A condom is required  to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
• Patients with other significant brain MRI abnormalities by history or at screening.
• Any contraindications to LP including, but not limited to:
  • Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance  of the LP, or increase the risk of the procedure for the participant;
  • Presence  of risk  for  increased  or uncontrolled  bleeding  including,  but  not  limited  to, 
    vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count;
  • Participants  on  anticoagulants  (e.g.,  warfarin)  or  antiplatelets  [except  for  low-dose 
    aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable], are not eligible to   participate, unless temporal   suspension of the anticoagulant  
    or antiplatelet treatment for the purpose of the LP is considered  safe for the patient, feasible, and guided by a hematologist.

Eligibility last updated 2/10/22. Questions regarding updates should be directed to the study team contact.

• All individuals who present for a routine elective, clinically indicated, diagnostic echocardiogram at the echocardiography laboratory at Mayo Clinic.

• Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
• Patients under the age of 18 years.
• Pregnancy.

• Patients referred for our pelvic floor rehabilitation program.
• Patients with the following diagnosis will be offered participation in our study:
  • urinary urgency or frequency;
  • urinary incontinence (urgency, stress or mixed);
  • defecatory dysfunction;
  • fecal incontinence;
  • pelvic pain;
  • pelvic dysfunction (spasms, pain or weakness); or
  • dyspareunia.

• Patients with implanted electrical devices.

Eligibility last updated 10/18/21. Questions regarding updates should be directed to the study team contact.

• Individuals, ≥ 18 years of age.
• Previously registered to A151216.
• Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation.
• Central and/or local testing of ALK with no ALK rearrangement (failed testing is  considered negative).
• Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the  following assays: DAKO 22C3, DAKO 28-8, or SP263.
  • Note: Local testing results of EGFR and ALK by a local Clinical Laboratory Improvement Act (CLIA) certified laboratory is acceptable. The report must indicate the result as well as the CLIA number of the laboratory that performed the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, or SP263 are acceptable for enrollment on A081801.
• Patients with local results for EGFR, ALK and PD-L1 still need to be registered to A151216 and follow all the submissions requirements but do NOT need to wait for the results to proceed to A081801 registration.
• Completely resected stage IB (≥ 4 cm), II or IIIA non-small cell lung cancer (NSCLC)  with negative margins (complete R0 resection).
• Patients will be staged according to  the 7th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2010.
  • Note: Patients with pathologic N2 disease, completely resected, are eligible; however, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population.
• Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery.
• No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis.
• No prior allogeneic tissue/solid organ transplant.
• Patients must NOT have uncontrolled intercurrent illness including, but not limited  to, serious ongoing or active infection, symptomatic congestive heart failure,  uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements.
• No current pneumonitis or history of (non-infectious) pneumonitis that required steroids.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral  therapy with undetectable viral load within 6 months are eligible for this trial.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1.
• No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs).  Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release  therapy for adrenal or pituitary insufficiency) is not considered a form of systemic  treatment.
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required. 
• No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin  cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that  have undergone potentially curative therapy are eligible
• No hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
• No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella,  varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG),  and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed  virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. 
• No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]  reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA]  [qualitative] is detected) infection.
• Required initial laboratory values:
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3; 
  • Platelet count ≥ 100,000/mm^3;
  • Hemoglobin ≥ 8 gm/dl;
  • Calculated (Calc.) creatinine clearance ≥ 45 mL/min;
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 x upper limit  of normal (ULN).

• Individuals < 18 years of age.

​​​​​​

• Adults ≥ 18 years of age.
• Patients with post-Fontan palliative surgery status with heart failure or have congenital heart disease or are family members of congenital heart disease patients.
• Subjects with no history of congenital heart defects.
• Able to provide informed consent.

• Individuals < 18 years of age.
• Inability to speak English.
• Inability or unwilling to provide informed consent.

Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 6/21/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 11/29/22. Questions regarding updates should be directed to the study team contact.

• Age 45 years and greater.
• Receiving primary care services at any of the 3 main Mayo Clinic sites and Mayo Clinic Health system in Northwest Wisconsin.

• Lack of consent for use of medical records for research.

• Male or female aged 18 through 70 years.
• Physician-diagnosed asthma requiring continuous treatment with medium- or high-dose ICS plus LABA with or without additional controller medication for at least 12  months prior to Visit 1, and current treatment with high-dose ICS plus LABA for at least 3 months prior to Visit 1 with or without additional asthma maintenance medication.
• Morning pre-BD FEV1 ≥ 50 to < 80% of predicted normal value (PNV) and ≥ 1 liter (L) or morning pre-BD FEV1 ≥ 50 to < 90% of PNV, if historical pre-BD FEV1 value (within 12 months prior to screening visit) was < 80% of PNV.
• A blood eosinophil count of: ≥ 300 cells/µL during screening or ≥ 150 to < 300 cells/µL during screening plus one of the following: presence of nasal polyps or pre-BD FVC < 65% predicted at Visit 2 or sputum eosinophil count of ≥ 2% at Visit 2.
• Negative pregnancy test.
• Asthma control questionnaire (ACQ-6) > 1.5.
• Fewer than 12 exacerbations within the 6 months prior to Visit 3.

• Any disease or concomitant medication which could affect study results or safety of study participants, including:
  • current smokers;
  • history of cancer;
  • life-threatening asthma;
  • clinically important pulmonary disease other than asthma.
• Use of chronic immunosuppressive medication or receipt of immunoglobulin (or blood products) within 30 days prior to the date informed consent is obtained.
• Previously received:
  • benralizumab;
  • live attenuated vaccines 30 days prior to the date of  randomization;
  • bronchial thermoplasty in the last 24 months prior to Visit 1;
  • any investigational non-biologic within 22 days (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer; 
  • any marketed or investigational biologic within 4 months (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.
• Currently pregnant, breastfeeding or lactating women.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/28/23. Questions regarding updates should be directed to the study team contact.

• Signed Informed Consent Form.
• Age 18 to 75 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol, in the investigator's judgment.
• Diagnosis of pMN according to renal biopsy prior to or during screening.
  • Diagnosis should be based on light and immunofluorescence microscopy, and if possible, electron microscopy.
• UPCR ≥ 5 g from 24-hour urine collection despite best supportive care for ≥ 3 months prior to screening or UPCR ≥ 4 g despite best supportive care ≥ 6 months prior to screening.
  • Best supportive care comprises renin-angiotensin system blockade with ACE inhibitor and/or ARB at maximally tolerated approved dose.
• Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening
• eGFR ≥ 40 mL/min/1.73m^2 or qualified endogenous creatinine clearance ≥ 40 mL/min based on 24-hour urine collection during screening. eGFR is calculated using the CKD-EPI equation (Levey, et al. 2009).
• Patients who previously responded to CNIs (CsA or tacrolimus), rituximab, or alkylating agents with either a CR or PR and subsequently relapsed are eligible but require discontinuation of CNIs or alkylating agents for ≥ 6 months and rituximab for ≥ 9 months prior to screening.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 18 months after the final dose of obinutuzumab and for 28 days after the final dose of tacrolimus.
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
  • The following are examples of adequate contraceptive methods: bilateral tubal ligation; male sterilization; hormonal contraceptives; hormone-releasing intrauterine devices; copper intrauterine devices; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
• For men receiving tacrolimus:  agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, as defined below:
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.
  • With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 28 days after the final dose of tacrolimus to avoid exposing the embryo.
  • For patients enrolled in the extended China enrollment phase at NMPA-recognized sites: current resident of mainland China and of Chinese ancestry.

• Patients with a secondary cause of MN (e.g., hepatitis B, SLE, medications, malignancies).
• Uncontrolled blood pressure, in the opinion of the investigator, during 3 months prior to screening.
• Evidence of ≥  50% reduction in proteinuria during the previous 6 months prior to randomization.
• Receipt of renal replacement therapy (e.g., renal transplantation, chronic dialysis).
• Type 1 or 2 diabetes mellitus (to exclude proteinuria secondary to diabetic nephropathy).
• Patients who have recent history of steroid-induced diabetes but no evidence on renal biopsy for diabetic nephropathy performed within 6 months of entry into the study are eligible.
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or 28 days after the final dose of tacrolimus.
• Women of childbearing potential, including those who have had a tubal ligation, must have a negative pregnancy test result within 1 day prior to each obinutuzumab infusion.
• History of resistance (no response) to CNIs or B-cell depleting antibodies.
• Patients with non-response to rituximab due to development of human anti-chimeric antibodies will be eligible.
• Receipt of previous therapies as follows:
  • Treatment with MMF or oral, intramuscular, or intravenous corticosteroids within 1 month prior to screening;
  • Any B-cell depleting therapy such as rituximab, ocrelizumab, or ofatumumab within 9 months prior to screening;
  • Treatment with cyclophosphamide or CNI within 6 months prior to screening;
  • Treatment with any biologic therapy (other than B-cell depleting agents) such as belimumab, ustekinumab, or anifrolumab (investigational) within 6 months prior to screening;
  • Treatment with an inhibitor of Janus-associated kinase, Bruton’s tyrosine kinase, or tyrosine kinase 2, including but not limited to tofacitinib, baricitinib, upadacitinib, filgotinib (investigational), ibrutinib, or fenebrutinib (investigational) within 3 months prior to screening;
  • Treatment with any investigational agent within 28 days of screening or 5 drug-elimination half-lives of the investigational drug, whichever is longer;
  • Receipt of a live vaccine within 28 days prior to screening or during screening.
• Thrombocytopenia, anemia, and/or coagulopathy with high risk for clinically significant bleeding or organ dysfunction or requiring plasmapheresis, IVIg, or acute blood product transfusions.
• Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation.
• Known HIV infection. 
• Tuberculosis (TB) infection:
  •  Testing for latent TB will be performed at screening if required by local regulations or in accordance with local clinical practice;
  •  Latent TB after completion of appropriate treatment is not exclusionary.
• Known active infection of any kind, excluding fungal infection of the nail beds.
• Any major episode of infection requiring hospitalization or treatment either with IV anti-infective treatments during the 2 months prior to or during screening or with oral anti-infective treatments during the 2 weeks prior to or during screening.
• History of serious recurrent or chronic infection.
• History of progressive multifocal leukoencephalopathy (PML).
• History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, except non-melanomatous carcinomas of the skin that have been treated or excised and have resolved.
• Major surgery requiring hospitalization within the 4 weeks prior to screening.
• Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening.
• Intolerance or contraindication to study therapies, including:
  • Evidence of intolerance or toxicity associated with tacrolimus prior to screening;
  • History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion;
  • Intolerance or contraindication to oral or IV corticosteroids and premedications;
  • Intolerance or hypersensitivity to tacrolimus and its excipients;
  • Lack of peripheral venous access. 
• Laboratory parameters:
  • AST or ALT 2.5 > the upper limit of normal (ULN);
  • Amylase or lipase > 2 x ULN;
  • Neutrophils < 1.5 x 10^3 /µL;
  • CD19+ B cells < 5/µL;
  • Positive for hepatitis B surface antigen (HBsAg) at screening.
  • Patients who are HBsAg negative and hepatitis B core antibody positive with no detectable hepatitis B virus (HBV) DNA will be allowed into the study but will require regular HBV DNA monitoring;
  • Positive hepatitis C virus (HCV) antibody at screening.
  • Patients with positive hepatitis C antibody test result with no detectable HCV RNA for at least 12 months after completion of antiviral therapy are eligible but will require regular HCV RNA monitoring;
  • Hemoglobin < 9 g/dL;
  • Platelet count < 75,000/µL;
  • Positive serum human chorionic gonadotropin measured at screening.

Eligibility last updated 12/2/21. Questions regarding updates should be directed to the study team contact.

• Patient and caregiver willing to participate as a dyad (patients will need a legally authorized representative to consent on their behalf given the requirement for at least moderate dementia, but patients who resists participating in the study will not be enrolled).
• U.S. residents (i.e., individuals accessing the LBDA from outside the U.S. will be excluded).
• Patient with a clinical diagnosis of Dementia with Lewy Bodies (DLB).
• Patient with moderate severity dementia as assessed by the Quick Dementia Rating System (QDRS, with a score of > 12 suggestive of moderate dementia), and caregiver modified telephone interview for cognitive status (TICS-m) score of > 31 to ensure that the caregiver is able to reliably complete study visits. Diagnosis of DLB will be confirmed using the Lewy Body Composite Risk Score (LBCRS, score ≥ 3 consistent with DLB). The QDRS and LBCRS were chosen for inclusion criteria as they are validated caregiver-reported scales and can be used for both the clinical and the virtual cohorts.
• The participating caregiver must be the person providing the majority of the patient’s informal care (whether the individual with DLB is living at home or in a facility) and attending the majority of the patient’s clinical visits.
• The carepartner can represent any relationship with the individual with DLB (e.g., spouse, child).
• The type of relationship will be captured in demographic details to assess the impact of this relationship/role on end of life for the individual with DLB and the caregiver.
• The participating caregiver must remain the same throughout the study.
• If the primary caregiver changes (e.g., due to caregiver death), that dyad will drop out of the study.
• The location of the person with DLB (e.g., home, facility) will be monitored throughout the study for its influence on outcomes and its relationship with informal caregiver responsibilities.

• Individuals < 18 years of age.

• Patients who have 2 or more of following:
  • hypertension (systolic blood pressure ≥ 130mmHg);
  • dyslipidemia (triglyceride ≥ 150mg/dl);
  • hyperglycemia (fasting glucose ≥ 100mg/dl);
  • obesity (body mass index > 30kg/m^2);
  • dyslipidemia 2 (high density lipoprotein <40 mg/dl (male) and < 50mg/dl (female);
  • moderate exercising (i.e., fast walking) less than 100 minutes a week.

• Patients who have cardiovascular or pulmonary disease.
• Patients who arer unable to participate in a regular exercise program.

• Postmenopausal women with or without history of BSO.
• Willing and able to complete informed consent for this study.
• Already enrolled in IRB#18-008476.

• Ongoing exogenous glucocorticoid therapy.

STEP 0

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (PS 3 allowed if secondary to pain). 
• Patient must have newly diagnosed multiple myeloma (MM) by International  Myeloma Working Group (IMWG) criteria.
• Patient must agree to register to the mandatory REVLIMID Risk Evaluation and  Mitigation Strategy (RevREMS) program and be willing and able to comply with the  requirements of RevREMS.
• Patient must be able to undergo diagnostic bone marrow aspirate following  preregistration.
  • NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies for clonoSEQ Assay.  
  • NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from the Clonality (ID) test within fourteen (14) days of receipt and reconciliation of fresh bone marrow specimen to the submitting institution.

STEP 1

• Patient must meet all eligibility criteria in STEP 0 with exception of  allergy requirement.
• Institution must have received the Clonality (ID) test results from Adaptive  Biotechnologies and dominant sequences were identified.
• Patient must have standard risk MM as defined by the Revised International  Staging System (RISS) stage I or II. 
  • NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH). Presence of del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these, including any other findings, are standard risk.
  • R-ISS stage - Stage I: ISS stage I [beta2 macroglobulin < 3.5 mg/L, albumin > 3.5 g/dL]  AND standard-risk CA AND normal LDH
• Stage II: Not R-ISS stage I or III
• Stage III: ISS stage III [beta2 macroglobulin > 5.5 mg/L] AND high-risk CA  OR high LDH (> upper limit of normal) [patients with stage III are  ineligible].
• Patient must have measurable or evaluable disease as defined by having one or  more of the following, obtained within 28 days prior to registration:  
  • ≥ 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis;
  •  ≥ 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis.
• Involved free light chain ≥ 10 mg/dL or ≥ 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65).
• Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease).
• Patients must have a serum protein electrophoresis (SPEP), urine protein  electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28  days prior to registration. In addition, a bone marrow biopsy and/or aspirate is  required within 28 days if bone marrow is being followed for response.
  • NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr. Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response.
  • NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine. Measurable disease in the serum is defined as having a serum M-spike ≥ 1 g/dL. Measurable disease in the urine is defined as having a urine M-spike ≥ 200 mg/24 hr.
• Calculated creatinine clearance > 30 mL/min (obtained ≤ 14 days prior to Step 1 registration).
• Absolute neutrophil count (ANC) ≥ 1000/mm^3 (obtained ≤ 14 days prior to Step 1 registration).
• Untransfused platelet count ≥ 75,000/mm^3 (obtained ≤ 14 days prior to Step  1 registration).
• Hemoglobin ≥ 8.0 g/dL (obtained ≤ 14 days prior to Step 1 registration).
• Total bilirubin ≤ 1.5 x ULN (institutional upper limit of normal) (obtained  ≤ 14 days prior to Step 1 registration).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x  ULN (obtained ≤ 14 days prior to Step 1 registration).
• Patient must have received no more than one cycle (28 days or less) of prior  chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed  to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to  symptomatic lesions is allowed provided there are no residual toxicity related to radiation and blood counts meet the study requirements. Radiation treatment must be  completed at least 14 days prior to Step 1 registration.
• Human immunodeficiency virus (HIV)-infected patients on effective  anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the  HBV viral load must be undetectable on suppressive therapy, if indicated. 
• Patients with a history of hepatitis C virus (HCV) infection must have been  treated and cured. For patients with HCV infection who are currently on treatment,  they are eligible if they have an undetectable HCV viral load.
• Patients with a prior or concurrent malignancy whose natural history or  treatment does not have the potential to interfere with the safety or efficacy  assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or  history of treatment with cardiotoxic agents, should have a clinical risk assessment  of cardiac function using the New York Heart Association Functional Classification. To  be eligible for this trial, patients should be class 2B or better. Patients must not have evidence of current uncontrolled cardiovascular conditions, including  hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or  myocardial infarction within 6 months prior to Step 1 registration.
• Patient may have a history of current or previous deep vein thrombosis (DVT)  or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
• Patients with a history of chronic obstructive pulmonary disease (COPD) must  have FEV1 testing done within 28 days prior to Step 1 registration and the forced expiratory volume in 1 second (FEV1) must be > 50% of predicted normal.

STEP 2

• Institution must have received Tracking (MRD) test results from Adaptive  Biotechnologies.
• Patient must have completed the Step 1 Induction phase of this protocol  without experiencing progression.
• Patient must be registered to Step 2 within 8 weeks of completing Step 1  Induction Treatment, counting from last day of completion of last cycle.
• Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if  secondary to pain).  
• Any adverse event(s) related to Step 1 Induction Treatment must have resolved  to grade 2 or less.
• Hemoglobin ≥ 8 g/dL (obtained within 14 days prior to Step 2 randomization).
• Platelet count ≥ 50,000/mm^3 (obtained within 14 days prior to Step 2  randomization).
• Absolute neutrophil count (ANC) ≥ 1000/mm^3 (obtained within 14 days prior  to Step 2 randomization).
• Calculated creatinine clearance ≥ 30 mL/min (obtained within 14 days prior  to Step 2 randomization).
• Total bilirubin ≤ 1.5 x ULN (Institutional upper limit of normal) (obtained within 14 days prior to Step 2 randomization).
• ALT and AST < 3 x ULN (obtained within 14 days prior to Step 2 randomization).

STEP 0

• Patient must not have any known allergies, hypersensitivity, or intolerance  to corticosteroids, monoclonal antibodies or human proteins, or their excipients  (refer to respective package inserts or Investigator's Brochure), or known sensitivity  to mammalian-derived products.

STEP 1

• Women must not be pregnant or breast-feeding due to the potential harm and  teratogenic effects to an unborn fetus and possible risk for adverse events in nursing  infants with the treatment regimens being used. All females of childbearing potential  must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 1 registration to rule out pregnancy and again within 24  hours prior to the first dose of lenalidomide. Females of childbearing potential must  also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or  whether they have undergone tubal ligation, who meets the following criteria:  
  • Has achieved menarche at some point;
  • Has not undergone a hysterectomy or bilateral oophorectomy; or  
  • Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential must not expect to conceive children by using  accepted and effective method(s) of contraception (for this protocol defined as the use of TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for:
  • at least 28 days before starting  protocol treatment;
  • while participating in the study;
  • during dose interruptions; and
  • for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation,  symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of  contraception). Men must not expect to father children by practicing true abstinence  from sexual intercourse for the duration of their participation in the study (periodic  abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and  withdrawal are not acceptable methods of contraception) OR use a latex condom during  sexual contact with a female of child bearing potential while participating in the  study and for at least 3 months after the last dose of protocol treatment even if they  have had a successful vasectomy. Men must also agree to abstain from donating sperm  while on study treatment and for 3 months after the last dose of protocol treatment  even if they have had a successful vasectomy. Both women and men must both agree to  abstain from donating blood during study participation and for at least 28 days after  the last dose of protocol treatment.
• Patient must not have peripheral neuropathy ≥ grade 2 on clinical  examination or grade 1 with pain at time of Step 1 registration.
• Patient must not have any serious medical or psychiatric illness that could,  in the investigator's opinion, potentially interfere with the completion of treatment  according to this protocol.
• Patient must not have moderate or severe persistent asthma within the past 2  years, or uncontrolled asthma of any classification.
  • NOTE: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to register.
• Patient must not receive any other concurrent chemotherapy, or any ancillary  therapy considered investigational while on this protocol.
  • NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.

STEP 2

• Patient must not have received any non-protocol therapy outside of the  assigned Step 1 Induction treatment including stem cell transplant.
• Women must not be pregnant or breast-feeding due to the potential harm and  teratogenic effects to an unborn fetus and possible risk for adverse events in nursing  infants with the treatment regimens being used. All females of childbearing potential  must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24  hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or  whether they have undergone tubal ligation, who meets the following criteria:  
  • Has achieved menarche at some point;
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential must not expect to conceive children by using  accepted and effective method(s) of contraception (for this protocol defined as the  use of TWO acceptable methods of birth control, one highly effective method and one  additional effective method AT THE SAME TIME for:
  • at least 28 days before starting  protocol treatment;
  • while participating in the study;
  • during dose interruptions; and
  • for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of  contraception).  Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment.

Inclusion Criteria - Longhaulers Cohort:

Subject population: 100 men and women who have been diagnosed with Post-COVID syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject or LAR to read and speak the English language.
• Positive PCR or antibody test within 18 months of initial study visit.
• Patient of the Long-Hauler Syndrome clinic and differential diagnosis of Long-Hauler Syndrome.

• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.
• Patient is unfit to participate at the discretion of the Principal Investigator.

Inclusion Criteria - Control Cohort:

Subject population: 50 men and women who have not had a known case of COVID or Longhauler’s syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject or LAR to read and speak the English language.

• Known case of COVID-19.
• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.
• Patient is unfit to participate at the discretion of the Principal Investigator.

Inclusion Criteria - COVID-19 Control Cohort:

Subject population: 50 men and women who have had a known case of COVID, but not Longhauler’s syndrome.

• Ability to give informed consent or LAR.
• At least 18 years old.
• Ability of subject to read and speak the English language.
• Known case of COVID-19.

• Known Longhauler’s syndrome/Post-COVID
• Any potential participant who refuses medical record review.
• Pregnant females.
• Incarcerated individuals.
• Inability to cooperate or any medical condition that, in the opinion of the investigator, interferes with the evaluation of the study objectives or increases the subject’s risk by participating in the study.

Eligibility last updated 11/19/21. Questions regarding updates should be directed to the study team contact.

• Biopsy proven cutaneous mastocytosis with or without evidence of systemic disease.
• Male and female patients, 18 to 80 years of age.
• No UVB treatment of the skin for 6 months prior to study entry.
• No use of topical or systemic corticosteroids for 1 month prior to study entry.
• Good general health as confirmed by medical history.
• Female patients of child-bearing potential with negative urine pregnancy test who agree to use effective methods of birth control or remain abstinent during treatment. Participants must use birth control for the entire study and for at least 1 week after the last application of the study formulation. Acceptable methods of birth control include ongoing hormonal contraception methods, (such as birth control pills, patches, injections, vaginal ring, or implants), barrier methods (such as a condom (for men) or diaphragm used with a spermicide), intrauterine devices, tubal ligation, or abstinence.
• Patients who are willing and capable of cooperating to the extent and degree required by the protocol.
• Patients who read and sign an approved informed consent for this study.

• Vulnerable study population.
• Exposure to ultraviolet B (UVB) radiation to any region of the skin surface for 6 months.
• Regular use of skin lightening agents within 1 month of study entry, including:
  • Topical corticosteroids;
  • Topical bleaching products;
  • Topical retinoids.
• Use of systemic preparations within 1 month of study entry, including:
  • Systemic corticosteroids;
  • Systemic cyclosporine, interferon;
  • Systemic acitretin, etretinate, isoretinoin;
  • Systemic methotrexate;
  • Systemic photoallergic, phototoxic and/or photosensitizing drugs.
• UV light therapy and sunbathing.
• Inability to communicate or cooperate with the Principal Investigator and/or Investigators due to language problems, poor mental development or impaired cerebral function.
• Pregnant or nursing women.
• Women planning a pregnancy within the study period.

Cohort 1
•Prospective biospecimens collection from 200 total healthy women and men.

• Healthy male or female over 18 years old.
• All racial and ethnic groups are eligible.
• Able to provide informed consent.

• Incarcerated individuals.
• Pregnant women.

Cohort 2 - banked specimen collection from Mayo Clinic Biobank (50 subjects).
 
Cohort 3 - surgical waste collection. In this case, a waiver of consent will be applied as subjects will not be known before collection to research staff.

• Women ≥ 25 years of age.
• Women who had previously undergone salpingectomy or salpingo oophorectomy for any indication, including risk reduction, independent of final pathology including:
  • Morphologically unremarkable FTs;
  • STIC, pure (isolated) or concurrent with:
  • Histologic diagnosis of STIC has been confirmed by the GYN pathologist.
  • OHGSC.
• FFPE block is available for research.
• IRB approved informed consent for banking remnant tissue (taken during the course of routine care) for future use in research or waivers of consent and HIPAA Authorization for the release of information and biospecimens.
• Assessment of risk for ovarian cancer will be based on criteria derived from the inclusion criteria for the United Kingdom Familial Ovarian Cancer Screening Study (UKFOCSS).

• Patients who don’t satisfy the inclusion criteria listed above.
• Subjects with history of other malignancies, except:
  • Adequately treated non-melanoma skin cancer;
  • Curatively treated in-situ cancer of the cervix;
  • Other solid tumors curatively treated with no evidence of disease for > 5 years.

Eligibility last updated 7/17/23. Questions regarding updates should be directed to the study team contact.

• Participants from an existing IRB approved protocol (#18-008476, #14-004401, #712-98)

• Unable to complete study activities.
• Unable to read and speak English.

Pre-Registration
•

• Age ≥ 18 years.
• Currently have or have had in the past the diagnosis of any type of lymphoma.
• If previously treated, the patient must be off myelosuppressive chemotherapy with no planned chemotherapy for ≥2 months. Patients with lymphoproliferative disorders being observed (i.e., never treated) or those on rituximab (or equivalent) maintenance or chronic oral therapies such as BTK inhibitors, venetoclax, tazemetostat, or corticosteroids are also eligible.
• Able to eat a full range of solid food and liquids and tolerate seeds/nuts.
• ECOG Performance Status (PS) 0, 1, or 2).
• Provide written informed consent.
• Able to recollect dietary intake for the prior 24 hours in order to complete a one-day food record with assistance from a dietitian at each study visit.
• Willing to be seen at the enrolling institution at baseline, and at 4 weeks and 8 weeks (end of treatment) in person or by video/phone.
• Willing to have a blood magnesium checked every 2 weeks x 4 at any Mayo Clinic site.
• Ability to complete questionnaire(s) by themselves or with assistance.

Pre-Registration
•

• Cannot eat normal table food by mouth. 
  • Note: Patients with any form of feeding tube or a swallowing disorder are not eligible.
• Have taken dedicated magnesium supplements (i.e., magnesium oxide) or IV magnesium ≤ 28 days prior to pre-registration.
  • Note: If patient is already on a multivitamin containing -magnesium, they may be enrolled, but the brand should not be changed during the 8 weeks on study.
• Co-morbid systemic illnesses such as active infection or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Patients with significant gut malabsorptive conditions (such as inflammatory bowel disease or others at the discretion of the investigator) will be excluded as well as patients with chronic kidney disease stage 3b or greater (eGFR < 45).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent for lymphoma or any other disease.
• Active other malignancy requiring treatment that would interfere with the assessments of this study.
• Major surgery other than diagnostic surgery ≤ 4 weeks prior to pre-registration.
• Have an allergy to nuts.
• Patients with active skin lymphoma or rashes that would preclude lotion testing.
• Have taken antibiotics ≤ 7 days prior to pre-registration.

Registration -

• The following laboratory value obtained ≤ 5 days prior to registration:
  • Magnesium level of 1.5 – 1.9 mg/dL.

Registration
•

• None.

Eligibility last updated 11/16/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 12/23/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 12/23/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 12/23/22. Questions regarding updates should be directed to the study team contact.

• Age 16-55 years old.
• Medial, lateral, vertical longitutdinal, oblique, or radial meniscal tear.
• Complex tears may be included (investigator discetion) if the patient has one of the tear patterns listed in incluse as the predominant finding.
• No other concomitant procedures unless (one of the following):
  • Chondroplasty;
  • Synovectomy;
  • Loose body removal;
  • “Contralateral” menisectomy (i.e., medial meniscus repair with a lateral menisectomy or lateral meniscus repair with a medial menisectomy) would be permitted for inclusion;
  • Any other procedure that does not include drilling, requires prior approval of the study sponsor for each procedure.

• Patients requiring cartilage restorative or repair procedures (i.e., OCD fixation, micro-fracture repair, or others).
• Patients with meniscus root tears.
• Patients undergoing repair for horizontal cleavage tears.
• Kellgren-Lawrence scale > 2.
• Patients undergoing lateral release.
• Ipsilateral chondral lesion with Outerbridge classification of 3-4.
• Use of prednisone or other steroids, any immunosuppressant, or chemotherapy 1-week before surgery or expected use within six weeks after surgery.
• Cortisone use within the six weeks prior to surgery.
• Utilizing worker’s compensation at the time of screening.
• Any previous ligament surgery on the index limb. Any previous meniscal surgery on the index meniscus.
• Concomitant ligamentous insufficiency.
• Inflammatory rheumatic disease or other rheumatic disease.
• Immune compromised patients (hepatitis, HIV, etc.).
• Any nicotine based products within the three months prior to surgery (including cigarettes, cigars, vaping, nicotaine patch, etc.).
• History of distal femur, proximal tibia, or patellar fracture that was treated operatively.
• Non English-speaking patients.

• Scholars and former scholars of the Mayo Clinic Cancer Center’s “Paul Calabresi Clinical Oncology (K12) Training Program.”

• None.

• Non-treatment seeking male or females ages 18 to 65 years, inclusive.
• DSM-5 diagnosis of cocaine use disorder in sustained remission as confirmed by the PI’s review of the medical record.
• Are motivated to abstain from cocaine use during the period of the study, as evidenced both by the judgment of the Investigator or designee and by compliance with the requirement to make regular clinic visits.
• In the opinion of the PI, be in good general health as determined by medical and psychiatric history, general clinical examination, vital signs, and laboratory tests.
• Have provided written informed consent. Subjects should be cooperative, willing and able to participate and adhere to the protocol requirements.
• Have hematology, chemistry, kidney and liver function laboratory tests that are within (+/- 10%) of the current Mayo Clinic standardized normal values.
• Show a baseline EKG that demonstrates normal sinus rhythm and conduction without clinically significant abnormalities or arrhythmias.
• Are willing to return to research area for follow-up.

• They show detectable pre-existing immunity to the AAV8 capsid as measured by AAV8 transduction inhibition and AAV8 total antibodies.
• Evidence of HIV or hepatitis of any etiology.
• Creatinine ≥ 1.5 mg/dL.
• Any disease or mental health condition at the physician’s discretion that would prevent the subject from fully complying with the requirements of the study. The physician may exclude subjects with active alcohol abuse, other substance abuse or positive urine toxicology screen for substances of abuse.
• Pregnant &/or lactating. All lactating women will be excluded from study participation. Women of child-bearing potential must have a negative pregnancy test performed at screening visit, agree to use birth control throughout the study period, refrain from getting pregnant within the study period and consent to pregnancy testing throughout the study period. Men must agree to use barrier methods of birth control and refrain from fathering children within the next year.
• Morbid obesity (BM > 40).

• Adult patients with brain metastases, for whom gamma knife radiosurgery recommended.

• Patients unable to tolerate/obtain MRI brain.

• Adults, age ≥ 18 years old.
• of Home Enteral Nutrition (HEN) patient receiving at least 90% of energy needs from enteral nutrition.
• BMI > 30.
• History of stroke.
• Weight stable over the past month.

• Diagnosis of cancer undergoing active treatment (chemotherapy, radiation, immunotherapy).
• Life expectancy of less than 6 months.
• Stage IV or higher kidney disease (GFR < 30).

Healthy Adults

• Healthy women (≥ 18 years of age).
• Participants will be categorized by menopausal status using the STRAW+10 guidelines36:
  • Premenopausal women will be experiencing regular menstrual cycles; 
  • Perimenopausal women will be experiencing irregular cycles (i.e., early perimenopause) or 2-11 mo of amenorrhea (i.e., late perimenopause). Postmenopausal women will have been > 5 years without menstruation and have undergone natural menopause.
• No history of cardiovascular, pulmonary, neurologic, orthopedic, or other diseases affecting the neuromuscular system.
• Undergoing treatment for menopausal symptoms (e.g., hormone replacement therapy).
• Having taken oral contraceptives in the past > 6 months.
• BMI ≤ 35kg/m^2.
• Current non-smokers with smoking history < 15 pack years.
• Able to engage in exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).

Patients with Hypertension

• (≥ 18 years).
• No history of dangerous arrhythmias.
• Not pacemaker dependent.
• Undergoing treatment for menopausal symptoms (e.g., hormone replacement therapy).
• Having taken oral contraceptives in the past > 6 months.
• Body mass index ≤ 35 kg/m^2.
• Currently non-smokers with < 15 pack year history.
• Able to exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).
• Patients will be tested while receiving optimized standard pharmacologic optimized therapy.
• All patients will be managed by their primary care physician or cardiologist with additional review by Dr. Borlaug (Co-Investigator) prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe.

• History of dangerous arrhythmias.
• Undergoing treatment for menopausal symptoms (e.g., hormone replacement therapy.
• Having taken oral contraceptives in the past > 6 months.
• Body mass index > 35 kg/m^2.
• Current smokers and/or smoking history > 15 pack years.
• Pregnant women.
• Uremia, history of allergy to iodides.
• Impaired renal function.
• Creatinine value than or equal to 1.3 mg/dL (via clinical record within the past 6 months).
• Diagnosis of liver disease.
• Individuals who are not able to engage in exercise.
• For individuals agreeing to undergo dual energy x-ray absorptiometry (DEXA) scanning for measurement of body composition as part of their study visit, additional exclusion criteria apply:
• Recently administered gastrointestinal contrast or radionuclides;
• Severe degenerative changes or fracture deformity in measurement areas; or
• Inability to attain correct position and/or remain motionless for the measurement period.