• Adult woman aged 18 or older.
• Diagnosis of biopsy-proven invasive breast cancer at Mayo Clinic Health System, Austin and Albert Lea, MN.

• Concomitant 2nd malignancy.
• Recurrent malignancy.
• Pregnancy.
• Age over 80 years.

Inclusion Criteria

1. Provision of the signed and dated written informed consent of the patient or the
patient's legally authorised representative, and informed assent from the patient (per
local regulations) prior to any mandatory study-specific procedures, sampling, and
analyses.

2. Males and females 12 years of age and older at the time of signing the ICF.

3. Documented diagnosis of HES (history of persistent eosinophilia >1500 cells/?L without
secondary cause on 2 examinations [interval ≥1 month; Valent et al 2012] and evidence
of end organ manifestations attributable to the eosinophilia).

4. Documented negative testing for the FIP1L1-PDGFRA fusion tyrosine kinase gene
translocation.

5. Stable HES treatment dose(s) and regimen for ≥4 weeks at the time of Visit 1

6. Signs or symptoms of HES worsening/flare and/or laboratory abnormalities indicative of
HES worsening/flare (other than isolated eosinophilia) at Visit 1.

7. AEC ≥1000 cells/?L at Visit 1 (assessed by local laboratory).

8. Corticosteroid responsiveness defined as an AEC <1000 cells/?L after a 2-day course of
OCS 1 mg/kg/day at Visit 2 (assessed by local laboratory).

9. Women of childbearing potential (WOCBP) must agree to use a highly effective method of
birth control (confirmed by the Investigator) from enrolment, throughout the study
duration, and within 12 weeks after last dose of IP and have a negative urine dipstick
pregnancy test result on Visit 1

Exclusion Criteria

1. Life-threatening HES and/or HES complication(s) as judged by the Investigator:

1. Medical intervention for HES-related life-threatening event(s) within 12 weeks
prior to randomisation OR

2. History of thrombotic complications, stroke, or significant cardiac damage
related to HES, if the respective events were life threatening and currently
represent a risk of life-threatening disease complications. Events that occurred
in the past but considered resolved or stable, can be accepted if, as per
Investigator's judgment participation in the study will not put the patient at
risk

3. Disease severity that, in the opinion of the Investigator, makes the patient
inappropriate for inclusion in the study.

2. Presence of FIP1L1-PDGFRA fusion tyrosine kinase gene translocation or other known
imatinib-sensitive mutation.

3. Definitive diagnosis of eosinophilic granulomatosis with polyangiitis.

4. Known, pre-existing, clinically significant endocrine, autoimmune, metabolic,
neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any
other system abnormalities that are not associated with HES and are uncontrolled with
standard treatment which, in the opinion of the Investigator, may put the patient at
risk because of his/her participation in the study, or may influence the results of
the study, or the patient's ability to complete the entire duration of the study.

5. Hypereosinophilia of unknown significance.

6. Cardiovascular: Documented history of any clinically significant cardiac damage,
clinically significant echocardiography (if available) or ECG findings within 12
months prior to Visit 1 or clinically significant ECG findings at screening that, in
the opinion of the Investigator, may put the patients at risk.

7. Known currently active liver disease.

1. Chronic stable hepatitis B and C (including positive testing for hepatitis B
surface antigen or hepatitis C antibody) or other stable chronic liver disease
are acceptable if patient otherwise meets eligibility criteria. Stable chronic
liver disease should generally be defined by the absence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or
persistent jaundice, or cirrhosis.

2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3× the
upper limit of normal (ULN) during the screening period (AST or ALT >5×ULN if
documented HES with liver manifestations). Transient increase of AST/ALT level
that resolves by the time of randomisation is acceptable if, in the
Investigator's opinion, the patient does not have an active liver disease and
meets other eligibility criteria.

8. Current malignancy, or history of malignancy, except:

1. Patients who have had basal cell carcinoma, localised squamous cell carcinoma of
the skin, or in situ carcinoma of the cervix are eligible provided the patient is
in remission and curative therapy was completed at least 12 months prior to the
date that informed consent, and assent when applicable, was obtained.

2. Patients who have had other malignancies are eligible provided the patient is in
remission and curative therapy was completed at least 5 years prior to the date
informed consent, and assent when applicable, was obtained.

9. Diagnosis of systemic mastocytosis.

10. Chronic or ongoing active infections requiring systemic treatment, as well as
clinically significant viral, bacterial, or fungal infection within 4 weeks prior to
Visit 1.

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

Eligibility last updated 11/3/22. Questions regarding updates should be directed to the study team contact.

Patients with the following genotypes and/or clinical diagnosis:

• POMC/PCSK1/LEPR heterozygous;
• POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity;
• POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity;
• Smith-Magenis Syndrome (SMS);
• SH2B1 deficiency obesity;
• Chromosomal rearrangement of the 16p11.2 locus causing obesity;
• CPE compound heterozygous or homozygous deficiency obesity;
• Leptin deficiency obesity with loss of response to metreleptin;
• SRC1 deficiency obesity;
• MC4R deficiency obesity;
  • Note: The specific genotype for all patients must be reviewed by the Sponsor prior to study enrollment to confirm that the patient meets Inclusion Criterion #1. In addition, enrollment of patients in some subgroups may be prioritized by the Sponsor in order to ensure enrollment of patients with (1) well described, loss of function genetic mutations, (2) a variety of genetic variants, or (3) genetic variants likely to respond to setmelanotide.
• Age 6 years and above.
• Obese, defined as Body Mass Index (BMI) ≥ 30 kg/m^2 for patients ≥ 16 years of age or BMI ≥ 95th percentile for age and gender for patients 6 up to 16 years of age.
• Study participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study, and is able to understand and sign the written informed consent/assent.
• Female participants of child-bearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening Follicle Stimulating Hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study.
• Female participants of child-bearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening Follicle Stimulating Hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study.
• Male participants with female partners of childbearing potential must agree to a double-barrier method if they become sexually active during the study. Male patients must not donate sperm during and for 90 days following their participation in the study.

• Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in > 2% weight loss.
• Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).Note: Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose  approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as:
  • is it not being prescribed for the treatment of obesity;
  • the dose has been stable for at least three months prior to enrollmen;
  • the patient has not experienced weight loss during the previous three months; AND
  • the patient intends to keep the dose stable throughout the course of the study.
• Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in > 10% weight loss durably maintained from the baseline pre-operative weight  with no evidence of weight regain. Specifically, patients may be considered if surgery was  not successful, or resulted in < 10% weight loss compared to pre-operative baseline weight or clear evidence of weight regain after an initial response to bariatric surgery. All patients with a history of bariatric surgery must be discussed with and receive approval from the Sponsor prior to enrollment.
  • Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be enrolled in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
• Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.
• HbA1c > 9.0% at Screening
• .Diagnosis of schizophrenia, bipolar disorder, personality disorder, or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance. Neurocognitive disorders affecting ability to consent will not be disqualifying as long as an appropriate guardian able to give consent has been appointed.
• A PHQ-9 score of ≥ 15 or any suicidal ideation of type 4 or 5 on the C-SSRS during Screening, any lifetime history of a suicide attempt, or any suicidal behavior in the last month.
• History of significant liver disease or abnormal liver tests on Screening (i.e., > 1.5 x upper limit of normal [ULN] for alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin).
  • Note: Patients entering the study with SRC1 haploinsufficiency obesity must be evaluated during the Screening Period for hepatic fibrosis by appropriate imaging techniques (e.g., transient elastography or magnetic resonance elastography). Any patient with moderate or greater fibrosis (e.g., the equivalent of a METAVIR score ≥ 2) will be excluded from the study.
  • Note: A patient with a diagnosis of non-alcoholic fatty liver disease (NAFLD) or non- alcoholic steatohepatitis (NASH) may be allowed to enroll in the study, after consultation with the Sponsor. Other significant liver disease, such as cirrhosis, are exclusionary.
• Glomerular filtration rate (GFR) < 30 mL/min at Screening.
• History or close family history (parents or siblings) of skin cancer or melanoma (not   including non-invasive/infiltrative basal or squamous cell lesion), or patient history of ocular- cutaneous albinism.
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by a qualified dermatologist during Screening. Any concerning lesions identified during the Screening Period will be biopsied and results known  to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study.
• Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
• Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
• Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
• Significant hypersensitivity to any excipient in the study drug.
• Inability to comply with QD injection regimen.
• Females who are breastfeeding or nursing.

• Subject must be > 18 years of age.
• Subjects will be undergoing routine endarterectomy to remove culprit atheromas in either the carotid, aortoiliac, or femoral arterial beds.
• All eligible subjects regardless of race or gender or ethnicity will be eligible and included in the study.

• None.

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

Eligibility last updated 2/23/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older.
• Subjects who are able and willing to sign the informed consent.
• Subjects who are able to follow verbal commands.
• A negative urine pregnancy test within 48 hours prior to PET imaging procedures in females of childbearing potential.
• Subjects who are scheduled for a PET/CT study under Mayo Clinic Rochester IRB research protocol 08-005553 (Aim 1 cohort only).
• A positive 18F-FDG oncology PET/CT exam in the last six months (Aim 2 cohort only).

• Patients who are unable to lay still for an additional 15 minutes (for Aim 1 cohort).
• Patients who are unable to lay still for 90 min for 18F-FDG scans or 100 min for 18F-AV1451 scans (for Aim 2 cohort).
• Patients who cannot follow the prep instructions.

• Patients who are > 18 years old.
• Patients who require a pharyngeal and/or rectal swab for CT/NG NAAT as part of their routine care.

• Patients who can not physically obtain a self-collected swab due to either mental or physical disability.
• Patients who cannot give informed consent.
• Planned Parenthood site Mayo Clinic Employees or participant in other Mayo Studies

• Age ≥ 18 years old.
• May be on oral therapy (including metformin) or insulin.
• Most recent HgbA1c level measuring between 6.5 -10 within the last 3 months.
• May be on stable (> 4 weeks) statin dose or no statin therapy.
• Willing to sign informed consent and stay on current medical regimen.
• Does not use regular dietary fiber supplements; has not had any psyllium containing products in the previous 30 days; is willing to refrain from taking any other fiber containing supplement products during the study.
• Has not used systemic steroid agents in the last 30 days.
• Able to participate fully in all aspects of the study.
• Have access and ability to utilize text messaging or email.

• Unwilling/unable to participate.
• Comorbid inflammatory bowel disease, celiac sprue, nephrotic syndrome, severe cholestasis (e.g., primary biliary cirrhosis), or history of bariatric surgery/bowel resection.
• Alcohol use in excess of 14 drinks/week.
• Allergic reactions to psyllium or wheat dextrin.
• Has participated in a clinical drug study or used an investigational new drug during the previous 30 days.
• Self-Report of known or suspected pregnancy or immediate plans (within 3 months) of becoming pregnant.
• Currently breastfeeding.
• Has a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence.
• Anticipated or recent major changes in diet or exercise routine.
• Anticipated colonoscopy prep during 3 months of study period.

Inclusion Criteria
•Patients Undergoing Parathyroidectomy:

• ≥ 21 years of age
• Undergoing first parathyroidectomy procedure.
• Able to provide a minimum of 10 mL blood per collection timepoint, with a maximum of 20 mL blood per collection timepoint.

Exclusion Criteria
•Patients Undergoing Parathyroidectomy:

• Known HIV or Hepatitis C infection.

Inclusion Criteria
•Patients with Hypoparathyroidism:

• ≥ 21 years of age.
• Clinical diagnosis of Hypoparathyroidism.
• Able to provide a minimum of 10 mL blood with a maximum of 70 mL blood.

Exclusion Criteria - Patients with Hypoparathyroidism:

• Known HIV or Hepatitis C infection.
• Treatment with NATPARA < 18 hours prior to study blood collection.

Inclusion Criteria
•Patients with Primary Hyperparathyroidism:

• ≥ 21 years of age.
• Clinical diagnosis of Primary Hyperparathyroidism.
• Able to provide a minimum of 10 mL blood with a maximum of 70 mL blood.

Exclusion Criteria - Patients with Primary Hyperparathyroidism:

• Known HIV or Hepatitis C infection.

Inclusion Criteria
•Patients with Secondary Hyperparathyroidism:

• ≥ 21 years of age.
• eGFR of less than 20 mL/min/1.73 m^2 (can be from Standard of Care result).
• Clinical diagnosis of Secondary Hyperparathyroidism.
• Able to provide a minimum of 10 mL blood with a maximum of 70 mL blood.

Exclusion Criteria
•Patients with Secondary Hyperparathyroidism:

• Known HIV or Hepatitis C infection.

Inclusion Criteria
•Patients with Hypercalcemia from Malignancy:

• ≥ 21 years of age.
• Calcium level of 10.3 mg/dL or higher (can be from recent Calcium result).
• Clinical diagnosis of Hypercalcemia resulting from malignancy.
• Able to provide a minimum of 10 mL blood with a maximum of 70 mL blood.

Exclusion Criteria
•Patients with Hypercalcemia from Malignancy:

• Known HIV or Hepatitis C infection.
• Treatment with calcitonin.
• Treatment with bisphosphonates (zoledronic acid, pamidronate) or Denosumab > 3 hours prior to study blood collection.

Inclusion Criteria
•Patients with Tertiary Hyperparathyroidism:

• ≥ 21 years of age.
• Clinical diagnosis of Tertiary Hyperparathyroidism.
• Able to provide a minimum of 10 mL blood with a maximum of 70 mL blood.

Exclusion Criteria
•Patients with Tertiary Hyperparathyroidism:

• Known HIV or Hepatitis C infection.

• Males, 18 years of age or older.
• Metastatic Prostate Cancer (lymph node-positive metastatic prostate cancer).

• Life expectancy of less than 3 months.

Inclusion Critieria:

• Adults ( ≥ 18 years).
• Critically ill patients admitted to medical, surgical, cardiac, neuro or mixed ICU at Mayo Clinic.
• Has a family member available.
• > 24.00 hours in ICU length of stay.
• Get to Know Me board was used in the ICU.

• If patient unable to communicate and has no family members or friends available.
• Patients without research authorization.

• Must have diagnosis of SOD1-ALS, and must have completed the End of Study Visit for either Parts A, B, or C of Study 233AS101 (NCT02623699) (i.e., were not withdrawn).
• If taking riluzole, must be receiving a stable dose for ≥ 30 days prior to Day 1. 
• For participants of childbearing potential must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment. 
• Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator. 
• Participants from Study 233AS101 Parts A and B must have a washout ≥ 16 weeks between the last dose of study treatment received in Study 233AS101 and the first dose of BIIB067 received in the current Study 233AS102.
• If taking edaravone, participant must have initiated edaravone ≥ 60 days (2 treatment cycles) prior to Day 1.
  • Edaravone may not be administered on dosing days during this study.

• History of allergies to a broad range of anesthetics. 
• Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for bleeding during or after a Lumbar Puncture (LP) procedure. These risks could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter. 
• Prior or current treatment with small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy. 
• Treatment with another investigational drug, biological agent (excluding BIIB067), or device within 1 month or 5 half-lives of study agent, whichever is longer.
• Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period. 
• Female participants who are pregnant or currently breastfeeding. 
• Current enrollment in any other interventional study. 
• Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) or pyrimethamine. 
• Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive anti-HBs) are eligible to participate in the study. 
• Presence of an implanted intravenous port/catheter.
  • NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

• Patients 18-95 years old.
• Diagnosed with sellar and suprasellar masses.
• Undergo neurosurgical procedure at Mayo Clinic Rochester.

• Patients under 18 or over 95 years old.
• Patients with preexisting central diabetes insipidus (CDI).

• An individual who has previously consented to the Biospecimen Resource for Pancreas Research (Substudy #1 – Pancreatic Disease Cases) – IRB 354-06 who does not have pancreas disease but does have a family history of pancreas disease or (Substudy #2 Family Studies) – IRB 355-06.
• Individual who does not have a personal history of pancreatic cancer and meets one of the following:
  • Has relatives in family that contains pancreatic cancer, and carries a known germline mutation in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53; OR
  • Is a first- or second-degree blood relative of an individual with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) and this PDAC patient has a germline mutation in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53; OR
  • Is a first- or second-degree blood relative of an individual with a germline mutation in one of these genes and where the mutation carrier is also a first-degree relative to a PDAC case; OR     
  • Is a blood relative to a PDAC patient in a family that contains three blood relatives (all maternal side or all paternal side) with PDAC;
  • Age 50 or older; OR
  • Or within 10 years of the age of diagnosis of the youngest PDAC blood relative.
• Individual with a valid United States mailing address.

• Individual who has a personal history of PDAC.
• Individual who has received a bone marrow transplant, who has had a blood transfusion within the last 7 days, or who has an active hematologic malignancy (i.e., leukemia or lymphoma).
• Individual who is unable to sign the informed consent because of mental incompetency or psychiatric illness.
• Individual who is non-English speaking
• Individual who is a prison inmate.

Eligibility last updated 10/6/21. Questions regarding updates should be directed to the study team contact.

• Adults, 20
  •45 years old, inclusive.
• Body mass index (BMI) of > 24 kg/m^2.
• Fasting serum glucose < 126 mg/dl.

• BMI ≤ 24 kg/m^2.
• Fasting serum glucose ≥ 126 mg/dl.
• Currently taking calcium and/or vitamin D supplements and unwilling to stop for study duration.
• Serum total calcium > 10.2 mg/dL.
• Serum inorganic phosphorus > 4.5 mg/dL.
• Pregnancy or breastfeeding.
• Diagnosis of Diabetes Mellitus.
• Diagnosis of Rheumatoid Arthritis.
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD).
• Renal insufficiency/failure (serum creatinine >1.5 mg/dl men; >1.3 mg/dl women).
• Chronic active liver disease (bilirubin > 1.2 mg/dL, AST > 144 IU/L, or ALT > 165 IU/L).
• History of chronic hepatitis.
• History of depression, anxiety or psychiatric disease.
• Active coronary artery disease (unstable angina, myocardial infarction, stroke, and revascularization of coronary, peripheral or carotid artery within 3 months of recruitment).
• Oral warfarin or history of blood clotting disorders.
• Platelet count < 100,000 per uL within the last 7 days.
• Alcohol consumption greater than 2 glasses/day or other substance abuse.
• Untreated or uncontrolled thyroid disorders (outside a TSH range of 0.5 to 10 mIU/L).
• Debilitating chronic disease (at the discretion of the investigators).
• The presence of infections, highly communicable diseases (AIDS, active tuberculosis, venereal disease, hepatitis).
• Any malignancy.

• Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally acceptable representative must provide informed consent on his/her behalf.
• Males or females ≥ 18 years of age.
• Established mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken ≤ 4 days (96 hours) before randomization defined as:
  • ≥ 1 blood culture positive for yeast or Candida; OR
  • Positive test for Candida from a Sponsor-approved rapid IVD; OR
  • Positive gram stain (or other method of direct microscopy) for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site.
• Presence of one or more systemic signs attributable to candidemia or invasive candidiasis appearing from ≤ 12 hours prior to the qualifying positive culture through time of randomization.
• Willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required.
• Female subjects of childbearing potential (all female subjects between 18 years < 2 years post-menopausal unless surgically sterile) must agree to and comply with using one barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control, or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception, and also agree not to donate sperm while participating in the study and for 90 days thereafter (and at least 120 days from the last dose of study drug).
• For Candidemia only subjects, drawing of a set of blood cultures within 12 hours prior to randomization in the study. The result of these blood cultures is not required for inclusion in the study.

• Any of the following forms of invasive candidiasis at baseline:
  • Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed;
  • Osteomyelitis;
  • Endocarditis or myocarditis;
  • Meningitis, endophthalmitis, chorioretinitis, or any central nervous system infection;
  • Chronic disseminated candidiasis;
  • Urinary tract candidiasis due to ascending Candida infection secondary to obstruction or surgical instrumentation of the urinary tract. 
• Received systemic treatment with an antifungal agent at approved doses for treatment of candidemia for > 48 hours (e.g., > 2 doses of a once daily antifungal agent or > 4 doses of a twice daily antifungal agent) ≤ 4 days (96 hours) before randomization.
  • Exception: Receipt of antifungal therapy to which any Candida spp. isolated in culture is not susceptible.
• Alanine aminotransferase or aspartate aminotransferase levels > 10-fold the upper limit of norma.
• Severe hepatic impairment in subjects with a history of chronic cirrhosis (Child-Pugh score > 9).
• Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or invasive candidiasis.
• Known hypersensitivity to Rezafungin for Injection, caspofungin, any echinocandin, or to any of their excipients.
• Meets National Cancer Institute Common Terminology Criteria for Adverse Events, version 5, criteria for ataxia, tremor, motor neuropathy, or sensory neuropathy of Grade 2 or higher.
• History of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's Disease or Huntington's Disease).
• Planned or ongoing therapy at Screening with a known neurotoxic medication.
• Previous participation in this or any previous rezafungin study.
• Current participation in another interventional treatment trial with an investigational agent.
• Recent use of an investigational medicinal product within 28 days of the first dose of study drug or presence of an investigational device at the time of screening.
• Pregnant or lactating females.
• The Principal Investigator (PI) is of the opinion the subject should not participate in the study

• Must be ≥ 18 years of age and, in selected countries, adolescents aged 12 years and greater and weighing ≥ 30 kilogram (kg) at time of randomization.
• Must undergo deoxyribose nucleic acid (DNA)-based human leukocyte antigen (HLA) matching and be 8 of 8 or 7 of 8 HLA-matched (singe allele or antigen mismatch at HLA-A, -B, and -C, and HLA-DRB1 is allowable) unrelated hematopoietic stem cell transplantation (HSCT) from either peripheral blood or bone marrow stem cells for a hematologic malignancy or myeloproliferative disorder.
• For whom a myeloablative conditioning or reduced intensity conditioning (RIC) is planned.
• Allo-HSCT eligible (meeting institutional criteria)-participants planned medical care should include aGvHD prophylaxis with a combination of calcineurin inhibitor (CNI) (cyclosporine [CYS] or tacrolimus [TAC]) and methotrexate (MTX) or CNI and mycophenolate mofetil (MMF). With the exception of antithymocyte globulin (ATG) (antithymocyte globulin-Fresenius [ATG-F] or thymoglobulin), all other therapies, approved or investigational, for GvHD prophylaxis are excluded.
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (<=) 2 for participants aged ≥ 18 years at randomization or ≥ 60 percent (%) using the Karnofsky performance status for adolescent subjects aged ≥ 16 years at randomization or the Lansky performance status for adolescent participants aged 12 to ≤ 16 years at randomization.

• Had prior allo- HSCT.
• Planned umbilical cord blood transplant or planned to receive posttransplant cyclophosphamide, in-vivo or ex-vivo T cell-depleted hematopoietic stem cells (HSCs) with the exception of ATG (ATG-F or thymoglobulin).
• Planned allo-HSCT for nonmalignant hematological disorders (example; aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia or immunodeficiency).

• Patients must have histologically or cytologically confirmed papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), or Hurthle cell thyroid cancer (HTC). Follicular variant of PTC or any of the above mixed histology will be allowed, as well as tall cell, insular, or poorly-differentiated thyroid cancers. Patients with anaplastic thyroid cancers (ATC) or medullary thyroid cancers (MTC) are not eligible.
• Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Patients must have radioactive iodine (RAI)-refractory/resistant disease as defined by one or more of the following criteria: 
  • One or more measurable lesions that do not demonstrate RAI uptake;
  • Progressive disease (PD) (new lesion or progression of previously known lesions), as defined by RECIST v1.1, within 12 months of prior RAI therapy;
  • One or more measurable lesion present after cumulative RAI dose of > 600 mCi; or 
  • Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan-positive disease (SUV ≥ 5 in tumor lesion).
• The patient's disease must have progressed on one line of VEGFR-targeted therapy (including, but not limited to, sorafenib, sunitinib, vandetanib, pazopanib, or lenvatinib, etc.) as defined by PD per RECIST v1.1 while receiving VEGFR-targeted therapy. Patients who have received more than one line of prior VEGFR-targeted therapy will not be eligible.
• Prior external beam radiation to extra-osseous disease, systemic cytotoxic chemotherapy or BRAF- or non-VEGFR-targeted therapies will be allowed, provided that > 4 weeks has elapsed since receiving prior treatment. Radiation to bone metastases is allowed up to 2 weeks prior to initiation of study treatment.
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status  ≤ 2 (Karnofsky ≥ 60%).
• Patients must have recovered to baseline or ≤ Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 1 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy .
• Absolute neutrophils ≥ 1,500/mcL.
• Platelets ≥ 100,000/mcL.
• Hemoglobin ≥ 9 g/dL.
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); ≤ 3.0 x ULN for patients with Gilbert's syndrome.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3.0 x institutional ULN .
• Alkaline phosphatase ≤ 3.0 x institutional ULN; ≤ 5.0 x ULN with documented bone metastases.
• Creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) ≥ 50 mL/min (if using the Cockcroft-Gault formula).
• Serum albumin ≥ 2.8 g/dL.
• Lipase < 2.0 x ULN and no radiologic or clinical evidence of pancreatitis.
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg.
• Serum phosphorus, calcium, magnesium, and potassium within institutional normal limits.
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) test < 1.3 x ULN.
• Patients with a history of human immunodeficiency virus (HIV) infection must be on an effective anti-retroviral regimen utilizing agents that do not strongly induce or inhibit cytochrome P450 (CYP) 3A4, and must have an undetectable viral load measured within 6 months prior to study registration.
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
• The effects of XL184 (cabozantinib), nivolumab, and ipilimumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of study therapy. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity: 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study therapy. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of < 1% per year. Men who receive study therapy and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of study therapy. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
• WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level < 40 mIU/mL.
• WOCBP and men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 5 and 7 months, respectively, after the last dose of study therapy. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) must inform the treating physician immediately.
• Patients must be able to swallow tablets.
• Patients must be able to understand be willing to sign a written informed consent document.
• Patients with impaired decision-making capacity (IDMC) will be eligible if they have a legally authorized representative (LAR) or caregiver available to assist them.

• Patients must not have had prior treatment with XL184 (cabozantinib), any MET-targeting tyrosine kinase inhibitor (TKI), or any MET-targeting monoclonal antibody (MetMAb), such as onartuzumab.
• Patients must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• Patients must not have a tumor invading or encasing any major blood vessels, and must not have evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum, or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of XL184 (cabozantinib).
• Patients must not have a diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Adjuvant hormonal therapy for history of prostate or breast cancer is allowed.
• Patients must not have received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 4 weeks, or nitrosoureas/ mitomycin C within 6 weeks, before the first dose of study treatment. Patients may continue on bone-modifying agents (denosumab or bisphosphonates) with caution.
• Patients must not have received radiation therapy:
  • o the thoracic cavity, abdomen, or pelvis within 4 weeks before the first dose of study treatment; 
  • To bone metastases within 14 days before the first dose of study treatment;
  • To any other sites within 4 weeks before the first dose of study treatment.
• Patients must not have clinically relevant, ongoing complications from prior radiation therapy. Palliative (limited-field) radiation therapy is permitted as long as the patient does not have disease progression according to RECIST v 1.1.
• Patients must not have received any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 4 weeks before the first dose of study treatment.
• Patients must not have received any other type of investigational agent within 4 weeks before the first dose of study treatment.
• Patients must not have a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 msec by electrocardiogram (EKG) within 28 days before the first dose of study treatment.
  • Note: if a single EKG shows a QTcF with an absolute value > 500 msec, two additional EKGs at intervals of approximately 3 min must be performed within 30 min after the initial EKG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Patients should not have known, untreated brain metastases or leptomeningeal metastases because of poor prognosis and concerns that progressive neurologic dysfunction could confound the evaluation of neurologic and other adverse events. However, patients will be eligible if metastases have been treated, and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment for metastases is complete and within 28 days prior to the first dose of study treatment.
• Patients must not require concomitant treatment with oral anticoagulants (e.g., warfarin, direct thrombin, and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel). The following anticoagulants are allowed: 
  • Low-dose aspirin for cardioprotection (per local applicable guidelines);
  • Low-dose low molecular weight heparins (LMWH);
  • Therapeutic doses of LMWH are allowed in patients without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before the first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Patients must not require systemic corticosteroids treatment (≥ 10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg/day prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if ≥ 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted, as is steroid pre-medication for contrast allergy.
• Patients must not have a history of severe hypersensitivity reactions to any monoclonal antibodies.
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study.
• Patients must not require concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, or St. John's wort). Because lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list. Medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, patients will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
• Patients must not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders: 
    • Congestive heart failure New York Heart Association (NYHA) class 3 or 4;
    • Unstable angina pectoris;
    • Serious cardiac arrhythmias;
    • Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment within seven days prior to the first dose of study treatment;
    • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis [DVT], pulmonary embolism [PE]) within 6 months before first dose.
  • GI disorders including those associated with a high risk of perforation or fistula formation: 
    • The patient has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction;
    • Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Complete healing of an intra-abdominal abscess must be confirmed before first dose.
  • Clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.
  • Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
  • Lesions invading or encasing any major blood vessels.
  • Other clinically significant disorders that would preclude safe study participation:
    • Serious non-healing wound/ulcer/bone fracture;
    • Uncompensated/symptomatic hypothyroidism;
    • Moderate-to-severe hepatic impairment (Child-Pugh B or C).
• Patients must not have had major surgery (e.g., GI surgery or removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment and from minor surgery (e.g., simple excision or tooth extraction) at least 10 days before the first dose. Patients with clinically relevant ongoing complications from prior surgery are not eligible.
• Pregnant women are excluded from this study because XL184 (cabozantinib) has the potential for teratogenic or abortifacient effects, and the effects of nivolumab and ipilimumab on the developing fetus are not well known. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued if the mother is treated with XL184 (cabozantinib), nivolumab, or ipilimumab.
• Patients with ac

• Provision of signed and dated informed consent form.
• Stated availability and willingness to comply with all study procedures until referred to a clinical trial.
• Age 50-85 (inclusive).
• Global Clinical Dementia Rating (CDR) score of 0 or 0.5 and no diagnosis of dementia.
• Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily function.
• In good general health as evidenced by medical history.
• Adequate visual and auditory acuity to allow neuropsychological testing.
• Fluent in English or Spanish.
• For females who are not surgically sterile or post-menopausal by two years, receiving a Positron Emission Tomography (PET) scan for amyloid biomarker confirmation: negative pregnancy test prior to amyloid PET scan.
• Completed six grades of education or has a good work history.
• Evidence of elevated or intermediate (subthreshold) levels brain amyloid as assessed by central review of amyloid PET or cerebrospinal fluid (CSF) data. Prior amyloid testing results may be used with approval from the Coordinating Center.

• Treatment with another anti-amyloid investigational drug or other intervention within 12 months.
• Enrolled in another interventional clinical trial within the last 12 weeks.
• Any significant neurologic disease such as Alzheimer's disease dementia, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
• Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol.
• History of schizophrenia (DSM V criteria).
• History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria).
• Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
• History within the last 3 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment.
• Clinically significant abnormalities in B12 or thyroid function tests (TFTs) that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Clinically significant abnormalities in screening laboratories or ECG.
• For participants undergoing CSF collection: a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening or if on anti-coagulation (e.g. warfarin).
• Participants whom the Site PI deems to be otherwise ineligible.
  • Site PIs should consult with the Coordinating Center on any issues that may disqualify the participant from participation in future clinical trials to determine whether enrollment into TRC would be appropriate.

Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the Project Director and Coordinating Center.

• Subjects who have received at least one dose of GSK3377794 in the interventional study.
• Subjects who have either completed the interventional study or have withdrawn from it.
• Male or female subjects.
• Capable of giving signed informed consent prior to the study participation.

• None.

Inclusion Criteria
•Aim 1:

• Clinical diagnostic testing via laboratory or home-based sleep study indicates diagnosis of obstructive sleep apnea.
• Currently use an appropriate Apple (iOS9 or higher) or Android (4.2 or higher) smartphone device.
• Able to read and understand English.
• Prescribed continuous or auto-titrated PAP treatment for obstructive sleep apnea.
• Stroke diagnosis with stroke event occurring within 36 months.

Inclusion Criteria
•Aim 2: 

• Clinical diagnostic testing via laboratory or home-based sleep study indicates diagnosis of obstructive sleep apnea.
• Currently use an appropriate Apple (iOS9 or higher) or Android (4.2 or higher) smartphone device.
• Able to read and understand English.
• Prescribed continuous or auto-titrated PAP treatment for obstructive sleep apnea.
• Stroke diagnosis with stroke event occurring no more than 10 years prior to referral to Center for Sleep Medicine.
• Functional and cognitive  ability to manage smartphone application and PAP device with minimal to no assistance.
• Agree to using a smartphone application and wearable wrist sensor.

Inclusion Criteria
•Aim 3:

• Health care provider (MD, APRN, PA, RN) providing care to patients with OSA and history of stroke.
• Sleep Medicine.
• Primary Care.

• Communication or cognitive impairments that limit ability to read and/or follow directions.
• Currently participating in other lifestyle programs (e.g., active, formal weight loss program or research study; smoking cessation program, etc.).
• Has lost 10lb or 4.5kg or more over the past 4 weeks.
• Other acute or severe health, cognitive, or psychological conditions that prevent participation.
• Self-report of pregnant, lactating, or trying to become pregnant.
• Decide to use different PAP device than ResMED Airsense 10.
• Prescribed high-dose benzodiazepines (equivalent to > 1 mg lorazapam/night).
• Daily opioid medication use at night.
• Unwilling to discontinue use of any current wearable sensor for the duration of the trial.
• Previous documented history of treatment/referral for claustrophobia.
• Previous PAP use.
• Other conditions determined by a sleep medicine team member that may interfere with full participation in the trial.
• Planning to travel for more than seven consecutive nights during the trial.
• Currently engaging in shiftwork defined as night shift or rotating day and night shifts.
• Unwilling to have an in-person follow-up appointment at the Center for Sleep Medicine in Rochester.

• Age 18+ Years Old.
• Diagnosis of Chronic Lymphocytic Leukemia (B-CLL).

• Pregnant.

• Individuals with spinal cord injury who have received an epidural spinal stimulation implant for return of functional return.
• Individuals who have received an epidural spinal stimulation implant but have since had it removed.
• English speaking individuals.

• Individuals with spinal cord injury who have received an epidural spinal stimulation implant for pain.
• Non-English speaking individuals.

Inclusion Criteria (Prostate Cancer Patients):

• ≥ 18 years of age.
• Able to give informed consent.
• Patients with prostate cancer.
• Patients treated with primary prostatectomy.

Inclusion Criteria (Female Control Patients)

• ≥ 18 years of age. 
• Able to give informed consent.                                                        

Exclusion Criteria (Prostate Cancer Patients): 

• Unable or unwilling to provide informed consent.
• Metastatic prostate cancer – defined radiographic evidence of metastatic disease on pre-procedural testing.

Exclusion Criteria (Female Control Patients)

• Unable or unwilling to provide informed consent.

Eligibility last updated 11/17/22. Questions regarding updates should be directed to the study team contact.

• Men and women age 65 years or older.
• Current PD diagnosis with symptoms severity at Hoehn & Yahr (H&Y) stage 1-4 based on an expert assessment (movement disorders neurologist report or telemedicine evaluation).
• Willing and able to continue in follow-up for at least 2 years.
• Willing and able to provide informed consent.

• History of hip fracture.
• Any use of a bisphosphonate drug within the last 12 months.
• Use of any other osteoporosis treatment (such as SERMs and denosumab) within the last 6 months.
• Tooth extraction or invasive dental procedures within the past 30 days or planned/scheduled extraction/procedure in the next 12 months.
• Non-ambulatory; i.e., unable to walk without assistance of another person.
• Undergoing kidney dialysis.
• A diagnosis of multiple myeloma or Paget's disease.
• Unable to speak or read English sufficiently to complete informed consent.
• Any other criteria, which would make the patient unsuitable to participate in this study as determined by the study staff (e.g., an uncontrolled drug and/or alcohol addiction).

• Provide written informed consent.
• Male or female aged ≥ 18 and < 80 years at the time of signing the informed consent for entry.
• Baseline endoscopic biopsy with ≥ 30 eosinophils/hpf in 5 hpf in the stomach and/or ≥ 30 eosinophils/hpf in 3 hpf in the duodenum, as determined by central histology assessment of biopsies collected during the screening EGD, without any significant cause for the eosinophilia.
• Prior EGD may be used for eligibility as long as the EGD occurred within 30 days of the first screening visit for the AK002-016 study and was performed and centrally assessed as for the AK002-016 study.
• Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
• A weekly average score of abdominal pain, nausea, and/or diarrhea ≥ 3 on the PRO questionnaire (score from 0–10) and a weekly average TSS of ≥ 10 for at least 2 weeks of screening.
• Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EG/EoD symptoms which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
• If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
• Willing and able to comply with all study procedures and visit schedule including follow-up visits.
• Female patients must be either post-menopausal for at least 1 year with FSH level > 30 mIU/mL at screening or surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test and agree to use dual methods of contraception, or abstain from sexual activity from screening until the end of the study, or for 120 days following the last dose of study drug, whichever is longer.

Male patients with female partners of childbearing potential must agree to use a highly effective method of contraception from screening until the end of the study or for 120 days following the last dose of study drug, whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual period) at any time during study participation.

• Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
• Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to screening.
• Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
• Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
• Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and histology per repeat EGD and symptoms still qualify for enrollment after treatment.
• Confirmed history of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
• History of bleeding disorders and/or esophageal varices considered to be clinically significant by the Investigator.
• Other significant causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
• Confirmed diagnosis of Hypereosinophilic Syndrome (HES).
• Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
• Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
• Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.
• History of malignancy, except carcinoma in situ, early stage prostate cancer, or non-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled.
• Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
• Positive helminthic infection on Ova and Parasite (O&P) test.
• Seropositive for Strongyloides stercoralis at screening, except for patients with past but resolved disease.
• Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved disease.
• Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. All types and formulations of vaccines (including live attenuated vaccines) authorized by FDA or other regulatory authority for the prevention of COVID-19 may be administered before, during, or after this study. The vaccine should not be administered within 7 days prior to and within 7 days after the administration of AK002 so that any side effects caused by either of the 2 medications can be more easily determined.
• Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration or 90 days or 5 half-lives, whichever is longer, for biologic products.
• Known history of alcohol, drug, or other substance abuse or dependence that is considered by the Investigator to be ongoing and clinically significant.
• Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

Surgery Cohort

• Maternal age ≥ 18 years old.
• Pregnant with a congenital anomaly diagnosis.
• Undergoing endoscopic in utero fetal intervention.
• Singleton pregnancy
• Delivery planned at Mayo Clinic.

Control Cohort

• Maternal age ≥ 18 years old.
• Pregnant with normal ultrasound findings.
• Singleton pregnancy
• Delivery planned at Mayo Clinic.

• Delivery planned elsewhere.
• Abnormal fetal karyotype.
• Multiples (i.e. twins/triplets, etc)
• Undergoing open in utero fetal intervention

• Patients with diagnosis of mitral annular calcification (MAC) (case group) and patients coming to the Valve Clinic without MAC diagnosis (control group).
• Patients who will undergo surgery, either standard surgical MVR or trans-atrial TMVR, with diagnosis of MAC (case group) or without diagnosis of MAC (control group).

• Subjects unwilling to participate or to provide consent.

• Male and female patients aged 18 years or more.
• Patients with IBD, Celiac disease, and a history of receiving a liver transplant, or potential conditions or on drugs that may predispose them to osteoporosis.
• Ability to undergo a research DEXA scan on Gonda 2.
• Patients able and willing to sign informed consent.

• Patients not meeting inclusion criteria will be excluded.
• Patients unable or unwilling to provide informed consent.
• Patients with metal artifacts affecting the regions of interest.
• Pregnancy.
• Body mass index of more than 30.

Inclusion Criteria
•Patients:

• Age  ≥ 18 years old.
• English fluency.
• No diagnosed severe cognitive impairment.
• Diagnosis of advanced, incurable solid tumor cancer.
• Expected prognosis > 6 months.
• Provide informed consent (written or electronic).
• Ability to complete questionnaire(s) by themselves or with assistance.
• Patient baseline distress score ≥ 4/10 OR identified as having distress that would benefit from program by care team or provider.
• Ability to do first Resilient Living session in person.

Inclusion Criteria - Caregivers:

• Self-identifies as a caregiver of a patient that meets the above cancer diagnosis criteria, and who also participates in the study.
• Provide informed consent (written or electronic).
• Ability to complete questionnaire(s) by themselves or with assistance.
• Age ≥ 18 years old.
• English fluency.
• No diagnosed severe cognitive impairment.
• Ability to do first Resilient Living session in person.

• As determined through self-report, those diagnosed with a history of a psychotic episode will be excluded.
• Other psychological co-morbidities such as untreated schizophrenia, bipolar disease.
• Participated in the Mayo Clinic study entitled “Feasibility and Acceptability of a Stress Management and Resilience Training (SMART) Intervention for Family Caregivers of Individuals with Advanced Cancer Undergoing Outpatient Chemotherapy."