• 15 healthy individuals aged ≥ 18 years.
• No history of cardiovascular diseases.
• Current non-smokers.
• All subjects will be informed about the study and consented prior to participation

• Subjects with a history of more significant hypotension (SBP < 90mmHg).
• Subjects who are morbidly obese (BMI > 38).

• Subjects with HAE Type I or II who either have participated in a previous BCX7353 study or, in selected countries, in the opinion of the Investigator are expected to derive benefit from an oral treatment for the prevention of angioedema attacks. 
• Access to appropriate medication for treatment of acute attacks.
• Acceptable effective contraception.
• Written informed consent.

• Pregnancy or breast-feeding.
• Any clinically significant medical condition or medical history that, in the opinion of the Investigator or Sponsor, would interfere with the subject's safety or ability to participate in the study.
• Any laboratory parameter abnormality that, in the opinion of the Investigator, is clinically significant and relevant for this study.
• Discontinuation of study drug due to a hypersensitivity reaction BCX7353 in a prior study.
• Severe hypersensitivity to multiple medicinal products or severe hypersensitivity/ anaphylaxis with unclear etiology.
• Unacceptable noncompliance in a previous BCX7353 study (if applicable) as assessed by the Sponsor or Investigator.
• Investigational drug exposure, other than BCX7353, within 30 days prior to the screening visit (or baseline if no screening visit).

Eligibility last updated 6/1/22. Questions regarding updates should be directed to the study team contact.

• ≥ 8 years old on date of surgery.
• Male or female.
• Diagnosis of idiopathic scoliosis for which surgery is recommended to prevent progression of the curvature or to correct trunk disfigurement and a non-fusion surgery is scheduled within 4 months.
• Thoracic or lumbar primary curves.
• Preop Cobb Angle ≥ 30° and ≤ 65°.
• Skeletally immature: Risser (< 5) and Sanders (< 8).
• Spina bifida Oculta is permitted.
• Spondylolisthesis and Spondylolysis are permitted, as long as non-operative.
• Osseous structure dimensionally adequate to accommodate screw fixation, as determined by radiographic imaging.
• Failed or intolerant to bracing.
• No prior spine surgery.

• Presence of any systemic infection, local infection, or skin compromise at the surgical site.
• Skeletally mature: > 7 Sanders.
• Prior spinal surgery.
• Documented poor bone quality, defined as a T-score -1.5 or less (If DEXA collected as routine care).
• Any other medical or surgical condition which would preclude the potential benefit of spinal surgery, such as coagulation disorders, allergies to the implant materials, and patient’s unwillingness or inability to cooperate with postoperative care instructions.
• MRI abnormalities (including > 4mm of Syrinx and/or Chiari malformation).
• Neuromuscular or other serious co-morbidities.
• Thoracogenic or cardiogenic scoliosis.
• Associated syndrome or developmental delay.
• Unwillingness, inability, or living situation (e.g., custody arrangements, homelessness, detention) that would preclude ability to return to the study site for follow-up visits as described in protocol and Informed Consent.
• Unwillingness to sign Informed Consent Form and participate in study procedure.
• Subjects who are pregnant at the time of enrollment.

• ≥ 8 years old on date of surgery.
• Male or female.
• Diagnosis of idiopathic scoliosis for which surgery is recommended to prevent progression of the curvature or to correct trunk disfigurement and a non-fusion surgery is scheduled within 4 months.
• Thoracic or lumbar primary curves.
• Preop Cobb Angle ≥ 30° and ≤ 65°.
• Skeletally immature: Risser (< 5) and Sanders (< 8).
• Spina bifida Oculta is permitted.
• Spondylolisthesis and Spondylolysis are permitted, as long as non-operative.
• Osseous structure dimensionally adequate to accommodate screw fixation, as determined by radiographic imaging.
• Failed or intolerant to bracing.
• No prior spine surgery.

• Presence of any systemic infection, local infection, or skin compromise at the surgical site.
• Skeletally mature: > 7 Sanders.
• Prior spinal surgery.
• Documented poor bone quality, defined as a T-score -1.5 or less (If DEXA collected as routine care).
• Any other medical or surgical condition which would preclude the potential benefit of spinal surgery, such as coagulation disorders, allergies to the implant materials, and patient’s unwillingness or inability to cooperate with postoperative care instructions.
• MRI abnormalities (including > 4mm of Syrinx and/or Chiari malformation).
• Neuromuscular or other serious co-morbidities.
• Thoracogenic or cardiogenic scoliosis.
• Associated syndrome or developmental delay.
• Unwillingness, inability, or living situation (e.g., custody arrangements, homelessness, detention) that would preclude ability to return to the study site for follow-up visits as described in protocol and Informed Consent.
• Unwillingness to sign Informed Consent Form and participate in study procedure.
• Subjects who are pregnant at the time of enrollment.

• Adult Employee and Community Health (ECH) patients seen at the Mayo Clinic Rochester practices.
• Patients suffering from one or more cutaneous warts as diagnosed by the examining physician at baseline visit on typical diagnostic characteristics.
• Able to provide consent.
• Both recalcitrant and non-recalcitrant warts will be included.

• Patients with prior use of home or office-based destructive treatments for this wart(s) in the last 1 month with SA or cryotherapy.
• Immunoadjuvant therapy for warts in the last 4 months (e.g Candida).
• History of vitamin D injection of warts ever.
• High-dose vitamin D supplementation (> 4,000 IU daily or equivalent) in the preceding 3 months.
• Pregnancy or lactation.
• Facial or genital warts.
• Lesions not felt by the examining clinician to be a wart (e.g., corns or calluses).
• Immunosuppression (to include immunosuppressive medications or conditions as judged by the physician evaluating the patient at the baseline visit).
• Allergy to sesame oil.

• Age 15-30 years, inclusive.
• Male gender.
• Active participation in competitive baseball as a pitcher.Should be competing at the high school or collegiate level.
• No current musculoskeletal complaints for which the subject is being treated.
• Full pain-free range of motion (ROM) of the bilateral upper and lower limbs.
• Willingness to participate in the study

• Current upper limb, lower limb, or spine musculoskeletal pain complaint for which the subject is taking prescribed medication, has modified activity, or received treatment from a medical care provider.
• History of fracture, dislocation, subluxation, or separation affecting the cervical spine, thoracic spine, rib cage, elbow, or either shoulder girdle.
• History of rotator cuff injury, elbow injury, or shoulder instability for which the subject has been evaluated and/or treated in the past 12 months.
• History of dominant side shoulder or elbow surgery.
• Known neurological, visual, or vestibular disease affecting balance or coordination
• Congenital deformity of the neck, upper extremity, or lower extremity.
• Congenital or acquired scoliosis or significant thoracic kyphosis (> 30 degrees).
• History of connective tissue disease (defined as rheumatoid arthritis, systemic lupus erythematosus, or a seronegative spondylarthropathy).

• Patients who are ≥ 15 years of age at the time of blood draw.
• Received a heart transplant (primary or repeat).
• Patients who have HeartCare initiated within 3 months post-transplant.

• Patients who are pregnant at the time of blood draw.

Inclusion Criteria

• Have disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment
• Any age and either gender
• Using a cord blood product manufactured by the National Cord Blood Program (at least one, if the graft contains more than one unit)

Exclusion Criteria

• Are only receiving licensed cord blood products
• Are only receiving unlicensed cord blood products from other banks
• Are being transplanted at non-US transplant centers
• Are receiving cord blood products that will be "manipulated" post-thaw (e.g., ex vivo expansion, incubation in vitro, etc.)

• Has been diagnosed with PSVT by a medical professional, and reports having at least one previous episode of PSVT. For clarity, PSVT refers to episodic SVT that includes the AV node as a critical part of reentrant circuit. 
• Is at least 18 years of age.
• Signed NODE-303 written informed consent.
• Women of child-bearing potential must be willing to use at least 1 form of contraception during the trial and must be willing to discontinue from the study should they become or plan to become pregnant. Postmenopausal females are defined as having amenorrhea for at least 12 months prior to Screening without an alternative medical cause.
• Willing and able to comply with study procedures.

• Patients with only a history of atrial arrhythmia that does not involve the atrioventricular (AV) node as part of the tachycardia circuit (e.g., atrial fibrillation, atrial flutter, intra-atrial tachycardia) are not eligible. Patients with a history of these tachycardias who are also diagnosed with PSVT are eligible.
• History of allergic reaction to verapamil.
• Current therapy with digoxin, or any Class I or III antiarrhythmic drug. Patients may be eligible if these drugs are stopped at least five half-lives before the administration of etripamil NS. The only exception is oral amiodarone which must be stopped 30 days before enrollment.
• History or evidence of ventricular pre-excitation; e.g., delta waves, Wolff-Parkinson-White syndrome.
• History or evidence of a second- or third-degree AV block.
• History or evidence of severe ventricular arrhythmia (e.g., torsades de pointes, ventricular fibrillation, or sustained ventricular tachycardia).
• Symptoms of congestive heart failure New York Heart Association Class II to IV.
• SBP < 90 mmHg at Screening, Baseline or any Follow-up Visit.
• Severe symptoms of hypotension experienced during PSVT episodes.
• Significant physical or psychiatric condition including alcoholism or drug abuse, which, in the opinion of the Investigator, could jeopardize the safety of the patient, or impede the patient’s capacity to follow the study procedures.
• History of syncope due to an arrhythmic etiology at any time, or history in last 5 years of unexplained syncope.
• Is pregnant or breastfeeding.
• Previously enrolled in a clinical trial for etripamil and received study drug or participation in any clinical trial for other investigational products or medical devices within 30 days of Screening.
• History of ACS or stroke within 6 months of Screening.
• Evidence of renal dysfunction as determined by an estimated glomerular filtration rate assessed at the Screening Visit as follows:
  • < 60mL/min/1.73m^2 for patients < 60 years of age;
  • < 40mL/min/1.73m^2 for patients ≥ 60 and < 70 years of age;
  • < 35mL/min/1.73m^2 for patients ≥ 70 years of age.

• Currently in the ED seeking treatment for suicidal behavior.
• Medically and clinically stable, as deemed by ED medical personnel/patient’s care team.
• Access to a computer or other device (smartphone, tablet) with Internet connection.
• Currently has and regularly uses an Apple or Android smartphone.
• Stable address and housing for the last 30 days.

Exclusion Criteria:

• Acutely psychotic, severely agitated, and patients with significant intoxication or other impairment (as deemed by medical providers) that may interfere with providing consent and meaningful feedback (as determined by their care team).
• No access or way to access phone or computer (or other device) with Internet connection.
• homeless or unstable housing in the past 30 days.
• Severely agitated patients are those who are perceived by medical personnel as highly distressed and likely to become more agitated (e.g., yelling, throwing objects, engaging in self-harming behaviors) and/or distressed if approached by medical personnel and/or research staff about research-related activities, from inquiring about their interest to participate and obtaining informed consent to providing feedback to researchers.

• Signed and dated written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, after the nature of the trial has been explained according to local regulatory requirements.
• Females ≥ 40 up to ≤ 65 years of age at randomization.
• For hysterectomized subjects: documented hysterectomy must have occurred at least 6 weeks prior to the start of screening. Hysterectomy can be total or subtotal (i.e., cervix was not removed).
• For non-hysterectomized subjects: uterus with bi-layer endometrial thickness ≤ 4 mm on TVUS (Amendment 3, 08 October 2019 and Amendment 4, 03 February 2020).
• For non-hysterectomized subjects: endometrial biopsy taken during screening that reveals no abnormal results; i.e., presence of hyperplasia (simple or complex, with or without atypia), presence of carcinoma, and presence of disordered proliferative findings. The screening biopsy should have sufficient endometrial tissue for diagnosis. Biopsies without tissue or with insufficient tissue may be repeated once.
• Seeking treatment for relief of VMS associated with menopause:
  • For the Efficacy Study part: at least 7 moderate to severe bothersome VMS per day or at least 50 moderate to severe bothersome VMS per week in the last 7 consecutive days during the Screening period;
  • For the Safety Study part: at least 1 moderate to severe VMS per week.
• Body mass index ≥ 18.0 kg/m² to ≤ 38.0 kg/m².
• A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening.*
• Post-menopausal status defined as any of the following:
• For non-hysterectomized subjects:
  • or at least 6 weeks postsurgical bilateral oophorectomy;
  • or at least 6 months of spontaneous amenorrhea with serum FSH > 40 mIU /mL and E2 < 20 pg/mL (value obtained after washout of estrogen/progestin containing drugs;
  • or at least 6 weeks postsurgical bilateral oophorectomy.
• For hysterectomized subjects:
  • serum FSH > 40 mIU/mL and E2 < 20 pg/mL (values obtained after washout of estrogen/progestin containing drug;
  • or at least 6 weeks post-surgical bilateral oophorectomy.
• Good physical and mental health, in the judgement of the Investigator as based on medical history, physical and gynecological examination, and clinical assessments performed prior to Visit 1.
• Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions.
• Able and willing to complete trial daily diaries and questionnaires.

* Subjects must have a Breast Imaging-Reporting And Data System (BI-RADS) score of 1 or 2 to enroll in the study. An incomplete mammogram result, i.e., BI-RADS 0, is not acceptable. and requires further assessment (Amendment 5, 23 September, 2020). The site must obtain a copy of the official report for the subject's study file. A digitalized imaging should be obtained if mammography is done as part of this study.

• History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin if diagnosed more than 1 year prior to the Screening visit.
• Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (however, simple cysts confirmed by ultrasound are allowed).
• Papanicolaou (PAP) test with atypical squamous cells undetermined significance (ASC-US) or higher (low-grade intraepithelial lesion [LSIL], atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion [HSIL] [ASC-H], HSIL dysplastic or malignant cells) in sub-totally hysterectomized and non-hysterectomized subjects.
  • Note: ASC-US is allowed if a reflex human papilloma virus (HPV) testing is performed and is negative for high risk oncogene HPV.
• For non-hysterectomized subjects:
  • History or presence of uterine cancer, endometrial hyperplasia, disordered proliferative findings;
  • Presence of endometrial polyp;
  • Undiagnosed vaginal bleeding;
  • Endometrial ablation;
  • Enlarged uterus with myoma.
• Systolic blood pressure (BP) higher than 130 mmHg, diastolic BP higher than 80 mmHg during screening.
• History of venous or arterial thromboembolic disease (e.g., superficial or deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, angina pectoris, etc.), or first degree family history of venous thromboembolism (VTE).
• History of known acquired of congenital coagulopathy or abnormal coagulation factors, including known thrombophilias.
• Diabetes mellitus with poor glycemic control in the last 6 months assessed by laboratory values of fasting glucose outside the normal ranges and glycated hemoglobin above 7%.
• Dyslipoproteinaemia (LDL > 190 mg/dL and triglycerides > 300 mg/dL).
• Smoking:
  • Efficacy Study part: subjects smoking > 5 cigarettes per day or > 2 packs per week;
  • Safety Study part: subjects smoking > 15 cigarettes per day or > 6 packs per week.
• Presence or history of gallbladder disease, unless cholecystectomy has been performed.
• Systemic lupus erythematosus.
• Any malabsorption disorders including gastric by-pass surgery.
• History of acute liver disease in the preceding 12 months before the start of screening or presence of chronic liver disease [alanine transaminase (ALT) or aspartate transaminase (AST) >2 x upper limit of normal (ULN), bilirubin >1.5 ULN].
• Chronic or current acute renal impairment (estimated glomerular filtration rate <60 ml/min).
• Porphyria.
• Diagnosis or treatment of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, etc.) in the judgement of the Investigator.
• Use of estrogen/progestin containing drug(s) up to:
  • 1 week before screening start for vaginal non systemic hormonal products (rings, creams, gels).
  • 4 weeks before screening start for vaginal or transdermal estrogen or estrogen/progestin products.
  • 8 weeks before screening start for oral estrogen and/or progestin products and/or selective estrogen receptor modulator therapy.
  • 8 weeks before screening start for intrauterine progestin therapy.
  • 3 months before screening start for progestin implants or estrogen alone injectable drug therapy.
  • 6 months before screening start for estrogen pellet therapy or progestin injectable drug therapy.
  • Use of androgen/ dehydroepiandrosterone (DHEA) containing drugs:
    • 8 weeks before screening start for oral, topical, vaginal or transdermal androgen;
    • 6 months before screening start for implantable or injectable androgen therapy.
• Use of phytoestrogens or black cohosh for treatment of VMS up to 2 weeks before the start of screening.
• For the women participating in the Efficacy Study part: use of prescription or over-the-counter products used for the treatment of VMS; e.g., anti-depressants: paroxetine, escitalopram, methyldopa, opioid and clonidine up to 4 weeks before the start of screening, and venlafaxine and desvenlafaxine up to 3 months before the start of screening , and not willing to stop these during their participation in the trial.
• Inadequately treated hyperthyroidism at screening.
• History or presence of allergy/intolerance to the investigational product or drugs of this class or any component of it, or history of drug or other allergy that, in the opinion of the Investigator contraindicates subject participation.
• For non-hysterectomized subjects: history or presence of allergy to peanuts.
• History of alcohol or substance abuse (including marijuana, even if legally allowed) or dependence in the previous 12 months before the start of screening as determined by the Investigator, based on reported observations.
• Sponsor or contract research organization (CRO) employees or employees under the direct supervision of the Investigator and/or involved directly in the trial.
• Subjects with known or suspected history of a clinically significant systemic disease, unstable medical disorders, life-threatening disease or current malignancies that would pose a risk to the subject in the opinion of the Investigator.
• Participation in another investigational drug clinical trial within 1 month (30 days) or having received an investigational drug within the last 1 month (30 days) before the start of screening.
• Is judged by the Investigator to be unsuitable for any reason.

• 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.

• 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.

• 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.

• 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.