• ≥ 21 years old.
• Diagnosed cervicogenic headache (CGH) or occipital neuralgia (ON) (in accordance with International Classification of Headache Disorders 3 rd edition [ICHD-3] criteria).
• Average occipital head pain score in the last week ≥4 on a scale of 0-10 (BPISF, question #5) at baseline.
• Average pain interference score in the last week ≥4 on a scale of 0-10 (BPISF, question #9) at baseline.
• Able to understand and willing to take part in study and comply with all study requirements.

Additional inclusion criteria (assessed prior to the PNS lead implant procedure): 

• Moderate-severe baseline pain: Average occipital head pain intensity score of ≥4 (determined by calculating the mean “average pain” scores collected consecutively in a 7-day baseline diary, using Question #5 on the BPI-SF; mean score must be ≥4). Individuals are required to complete all 7 days of the baseline diary consecutively to be eligible to participate in the study because an inability to complete the baseline diary suggests an inability or unwillingness to comply with all study requirements.

• Change of prescribed medications affecting pain within the past 4 weeks as indicated from subject-reported medication history.
• Radiofrequency ablation in the affected area within the last six months.
• Botulinum toxin injection in the affected area within the last three months.
• Steroid injection in the affected area within the last six weeks.
• Other confounding therapies including previous destructive ganglionectomy, rhizotomy section or neurectomy procedure affecting C2/C3/occipital distribution
• Beck Depression Inventory (BDI-II) score of > 20.
• Head pain is attributed to cancerous lesion or a headache condition other than CGH or ON, including (but not limited to) episodic or chronic migraine, tensiontype headache, analgesic medication over-use or withdrawal headache, cluster headache, or vascular and non-vascular intracranial disorders.
• Pain is primarily in the distribution of the lesser occipital nerves.
• ID Migraine screener score of ≥ 2.
• Current daily opioid use ≥ 50 MME (morphine milligram equivalents).
• Diabetes mellitus Type 1 or Type 2.
• Compromised immune system based on medical history (i.e., human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), immunosuppressive therapies such as chemo treatment, radiation, sepsis, active joint or overlying skin infection of the cervical or occipital regions), or other condition that in the opinion of the investigator places the subject at increased risk.
• Implanted electrical stimulation device or metallic implant such as spinal cord stimulator, active cardiac implant (e.g., pacemaker or defibrillator), cochlear implant, cerebrospinal fluid (CSF) shunt, aneurysm clip, or deep brain stimulator.
• Severe traumatic brain injury (TBI) or other central nervous system (CNS) conditions including epilepsy that could be aggravated by the PNS treatment or confound the analysis.
• Allergy to skin-contact materials (stickers, bandages, tape etc.).
• Previous cervical or cranial occipital surgery, such as decompression of the occipital nerve(s), or cervical spine surgery such as laminectomy or fusion at or above the C3 level.
• Participation in any drug or device trial in the past 30 days.
• Any other condition that may interfere with the ability to participate in a clinical trial (e.g., anatomy that may interfere with lead placement or bandaging) as determined by the Investigator.
• Potential secondary gain conflicts of interest (e.g., pending claims or receiving disability).
• .Vulnerable populations (e.g., prisoners, individuals that report to investigators).
• Pregnant (either urine dipstick or serum in females of reproductive potential; to be assessed prior to lead placement procedure).

Eligibility last updated 7/14/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/2/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years
• Willing to provide samples at baseline.
• Cirrhosis
  •where Cirrhosis is defined as:
  • At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis; OR
• If no liver biopsy, the following imaging + laboratory criteria define cirrhosis for the purposes of this protocol:
  • Evidence on imaging, of stiffness, or of varices according to the MOP, AND;
  • Either: FIB-4 > 2.67 OR platelets < 150 (within 180 days prior to consent or during Screening).

• Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Known prior solid organ transplant or bone marrow transplant.
• Current participation in active medication treatment trials at the time of consent for LCN POST.
• Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits.
• Bariatric surgery in the last 180 days prior to consent.
• Known history of fontan procedure-associated liver disease (FALD).
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol.
• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ).
• Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days prior to consent.
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis).
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis with 90 days prior to consent.
• Documented cardiac cirrhosis.
• Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding.
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples).
• Current model for end-stage liver disease (MELD) cut off ≥ 15*.
• Current Child-Turcotte-Pugh (CTP) B or C*.
• Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR).
• Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy*.
• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2X upper limit of normal (ULN) within 60 days prior to consent or during Screening*.
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent or during Screening*.

*Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 60 days prior to consent, it does not need to be re-done for eligibility.  

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.

Healthy Adults

• Healthy participants (≥ 18 years of age) will be recruited from the surrounding community.
• These participants will not have a history of cardiovascular, pulmonary, neurologic, orthopedic, or other diseases affecting the neuromuscular system.
• Additional inclusion criteria include: age, sex, and body mass index matched to the Human Hypertension (HTN) group and those who are able to engage in exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).

Patients with Hypertension

•  ≥ 18 years of age.
• Patients with HTN will have a clinical diagnosis of essential HTN and receiving standard pharmacologic therapy for > 3 months.
• In addition to their primary care physician, Dr. Borlaug, M.D. will provide oversight for all participants throughout the study duration. Patients will be tested while receiving optimized standard pharmacologic optimized therapy. All patients will be managed by their primary care physician or cardiologist with additional review by Dr. Borlaug (Co-Investigator) prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe. Additional inclusion criteria include no history of cardiovascular (except for HTN), pulmonary, renal, and/or muscular related abnormalities and those who are able to engage in exercise (i.e., without significant orthopedic limitations or musculoskeletal disorders limiting their ability to exercise).

Patients with Heart Failure:

• Patients with HF with reduced ejection fraction and HF with preserved ejection fraction. Patients with HF are expected to have a history of ischemic or idiopathic dilated cardiomyopathy (stable > 6 months with a duration of > 1 year) and New York Heart Association class I-III. Although HF medications may influence multiple physiologic systems, we feel it is important, practical, and safe to study these patients under conditions of optimal care. Concurrent withdrawal of ACE-inhibitor, beta-blocker, digoxin, and/or diuretic therapies would likely be associated with moderate decompensation in a high proportion of patients. All patients will be managed by their primary care physician or cardiologist prior to enrollment to ensure inclusion and exclusion criteria have been satisfied and participation in exercise testing is safe.

• ≥ 18 years of age.
• History of dangerous arrhythmias.
• Body mass index > 35 kg/m^2.
• Current smokers and/or smoking history > 15 pack years.
• Pregnant women (testing will be done by research team if requested).
• Uremia, history of allergy to iodides.
• Impaired renal function.
• Creatinine value greater than or equal to 1.3 mg/dL (via clinical record within the past 6 months).
• Diagnosis of liver disease; or (10) individuals who are not able to engage in exercise.
• For individuals agreeing to undergo dual energy x-ray absorptiometry (DEXA) scanning for measurement of body composition as part of their study visit, additional exclusion criteria apply: recently administered gastrointestinal contrast or radionuclides; severe degenerative changes or fracture deformity in measurement areas; or inability to attain correct position and/or remain motionless for the measurement period.

Eligibility last updated 7/26/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/19/22. Questions regarding updates should be directed to the study team contact.

• ≥ 18 years of age. 
• Undergoing Radiofrequency Ablation (RFA) for symptomatic thyroid nodule(s).

• < 18 years of age.
• Decline to participate in research. 

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

• Provide written informed consent.
• Male or female ages 18 or older.
• Evidence of cancer of the colon or rectum that is metastatic to the liver.
  • NOTE:  patients may enroll prior to receiving clinical biopsy results. If they are not confirmed to have adenocarcinoma of the colon or rectum that is metastatic to the liver, they will not be evaluable.
• Treating physician planning to treat CRC liver metastasis with a standard of care therapy.
• Previous adjuvant or neoadjuvant therapies allowed.
• Biopsy may be obtained prior to starting the 2nd cycle of a new standard of care therapy.
• Measurable disease as measured by RECIST 1.1 criteria.
• Life expectancy of ≥ 12 weeks.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2. 
• Adequate coagulation function as evidenced by:
  • Absolute neutrophil count ≥ 1.0 x 10^9/L;
  • Platelets ≥ 50 x 10^9/L;
  • Hemoglobin ≥ 8 g/dL (transfusions are permitted to achieve baseline hemoglobin level);
• ALT/AST (alanine aminotransferase (ALT) / aspartate aminotransferase (AST)) < 2.5 x upper limit of normal (ULN); or
• < 5 x ULN in the presence of liver metastases;
• Total bilirubin < 1.5 x ULN (if total bilirubin ≥ 1.5 x ULN then the subject may participate if the direct bilirubin is ≤ 1.5 x ULN);
• Creatinine clearance > 30 mL/min measured or calculated by Cockcroft-Gault equation or the estimated glomerular filtration rate (GFR) > 30 mL/min/1.73 m^2 using the MDRD;
• INR < 1.5.

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
• Clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of start of therapy, New York Heart Association Class II, III or IV congestive heart failure, and arrhythmia requiring therapy.
• Presence of significant concurrent, uncontrolled medical condition including but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, active infection, non-healing wound, or psychiatric disease that excludes them from receiving chemotherapy.
• Pregnant or actively breastfeeding women (Pregnant or breastfeeding women are not candidates for chemotherapy).

Eligibility last updated 7/20/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

Healthy Volunteer

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

Eligibility last updated 5/8/23. Questions regarding updates should be directed to the study team contact.

• Patients self-report as being > 1 year postmenopausal.
• Patients are able to walk without a walking aid.
• Patients own and know how to operate a smart phone or tablet.
• Patients are willing and able to complete the activity monitoring.
• Patients are self-reportedly underactive.

• Patients are < 1 year postmenopausal.
• Patients require a walking aid for daily mobility.
• Patients do not own a smartphone or table, or are unwilling to use such a device for the purposes of the study.
• Patients' primary form of exercise is swimming (the activity monitors are not waterproof).
• Patients are unable or unwilling to complete activity monitoring.
• Patients are unable to provide informed consent independently.

Eligibility last updated 7/22/22. Questions regarding updates should be directed to the study team contact.

• Age 3 to < 9 years.
• IXT meeting all of the following criteria:
  • Intermittent or constant XT at distance (mean distance control 2.0 or more) with at least 1 control measure of 3, 4 or 5 (i.e., indicating spontaneous tropia);
  • Either IXT, exophoria, or orthophoria at near (cannot have control score of 5 on all 3 near assessments);
  • Distance exodeviation between 15Δ and 50Δ by PACT;
  • Near exodeviation between 0Δ and 50Δ by PACT;
  • Near exodeviation does not exceed distance by more than 10Δ by PACT (convergence insufficiency-type IXT excluded).
• Age-normal visual acuity in both eyes:
  • 3 years: 20/50 or better (≥ 63 letters);
  • 4 years: 20/40 or better (≥ 68 letters);
  • 5-6 years: 20/32 or better (≥ 73 letters);
  • 7
    •< 9 years: 20/25 or better (≥ 78 letters).
• Interocular difference in distance VA of 2 logMAR lines or less (10 letters or less on E-ETDRS for patients ≥ 7 years old). Testing by ATS HOTV for participants 3 to < 7 years old and by E-ETDRS for participants ≥ 7 years old.
• Cycloplegic refraction within the last 7 months.
• Refractive error between -6.00 D SE and +2.00 D SE (inclusive) based on a cycloplegic refraction within 7 months.
• Participants with refractive error meeting any of the following based on a cycloplegic refraction within 6 months must be wearing spectacles for at least 2 weeks:
  • Myopia > -0.50 D spherical equivalent (SE) in either eye;
  • Anisometropia > 1.00 D SEl;
  • Astigmatism in either eye > 1.00 D.
• Any refractive correction worn at enrollment (required or not) must meet the following guidelines based on a cycloplegic refraction within 7 months:
  • Anisometropia SE must be within 0.50 D of the full anisometropic difference correction;
  • Astigmatism must be corrected within 0.50 D;
  • Axis must be within ±10 degrees if cylinder power is ≤1.00 D and within ± 5 degrees if cylinder power is >1.00 D;
  • For hyperopia, the spherical component can be reduced at investigator discretion provided the reduction is symmetrical and does not meet the definition of deliberate overminus (see below);
  • For myopia, the intent is to fully correct, but the spherical component can be  undercorrected at investigator discretion provided the reduction is symmetrical and results in no more than -0.50 D SE residual (i.e., uncorrected) myopia;
  • Deliberate overminus is not allowed;
  • Deliberate overminus is defined for this protocol as any refractive correction prescribed to yield lenses that are overminused by more than -0.50D SE than cycloplegic refraction SE;
  • Less than the full cycloplegic hyperopic correction (i.e., prescribing reduced plus) is not considered the same as overminusing for this protocol (because most patients without IXT but with hyperopic SE refractions up to +2.00 D SE would not typically be prescribed a refractive correction);
  • For refractive errors with an emmetropic or myopic SE, the intent is to fully correct, but the spherical component can be undercorrected at investigator discretion provided the reduction is symmetrical and results in no more than -0.50 D SE residual (i.e., uncorrected) myopia. Prescribing a correction that yields more than 0.50 D more minus SE than the cycloplegic refraction SE is considered deliberate overminus and is not allowed.
  • Note that the refractive correction guidelines and the requirement to wear refractive correction for at least 2 weeks apply not only to participants who require refractive correction under the above criteria but also to any other participant who is wearing refractive correction.
• Gestational age > 30 weeks.
• Birth weight > 1500 grams.
• Patient and/or parent understands protocol, is willing to enroll, and is willing to accept that other (i.e., nonrandomized) treatment for IXT will not be offered by the investigator for 3 months.
• Parent has phone and is willing to be contacted by Jaeb Center staff.
• Relocation outside of area of an active PEDIG site within 3 months not anticipated.

• Individuals meeting any of the following criteria at baseline will be excluded from study participation:
  • Prior strabismus, intraocular, or refractive surgery (including BOTOX injection);
  • Prior nonsurgical treatment for IXT (e.g., patching, vergence therapy, vision therapy/orthoptics, base-in prism, or deliberate overminus (more than 1.00 D) spectacles of > 1 week duration within the past year.
• Previous amblyopia treatment other than refractive correction.
• Diplopia more than 2 times per day by parental assessment.
• Paretic or restrictive strabismus.
• Craniofacial malformations affecting the orbits.
• Ocular disorders which would reduce VA (except refractive error).
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities or ADHD are not excluded.
• Neurological anomaly that could affect ocular motility (e.g., cerebral palsy, Down syndrome).
• Immediate family member (child or sibling) of any investigative site personnel directly affiliated with this study.
• Known allergy to adhesive patches.
• Known allergy to silicone.

Eligibility last updated 8/9/22. Questions regarding updates should be directed to the study team contact.

• Patients seen in Oncology or surgery with a diagnosis of a solid tumor malignancy,.

• < 18 years of age. 

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

• 18 to 90 years of age
• Diagnosed with Eosinophilic esophagitis ≥ 15 eosinophils per HPF
• Going through or completed the six-food elimination diet, with milk only or milk plus one additional food identified as a trigger

• Patients with conditions known to be associated with esophageal eosinophilia, including Crohn’s disease, Churg-Strauss, achalasia, and hypereosinophilic syndrome
• Topical swallowed steroids within 8 weeks of study enrollment
• Inability to read due to: Blindness, cognitive dysfunction, or English language illiteracy

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

1. Patients with cirrhosis admitted to hospital for the treatment of a complication of liver disease (ascites, gastrointestinal bleeding, hepatic encephalopathy, bacterial infections, jaundice, etc.).

1. Age < 18 years old.

2. Pregnancy.

3. Hepatocellular carcinoma outside Milan criteria (i.e., a single lesion < 5 cm or multiple lesions [maximum of three], the largest of which measures ≤ 3 cm).

4. Extrahepatic malignancy other than non-melanoma skin cancer within last 5 years.

5. Previously known severe extrahepatic diseases (e.g., chronic renal failure requiring hemodialysis, severe congestive heart disease [NYHA class ≥ 3]; severe chronic obstructive pulmonary disease [GOLD class ≥ 3], psychiatric disorders).

6. Previous solid organ transplantation.

7. HIV infection with CD4 ≤ 250/µL.

8. Patients who cannot provide prior informed consent and no legal surrogate decision maker.

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

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

• Subjects ≥ 18 years age who will undergo clinically indicated stress or non-stress cardiac MRI (CMR) imaging with contrast on a GE scanner in Rochester, MN.

• Patients who would fall outside of the range for normal operating mode. Examples include patients with retained implantable electronic device leads, or those with a legacy device requiring active monitoring by a physicist (with limitation of the whole-body specific absorption rate ‘SAR’ exposure to less than 2W/kg), and patients with a cardiac implantable electronic device (CIED).

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

Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 5/1/23. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 8/1/22. Questions regarding updates should be directed to the study team contact.

• Transgender and gender diverse (TGD) identifying patients.
• Patients ≥ 18 years old.
• Patients who are seeking or have sought gender-affirming care or fertility preservation.
• Willingness to provide informed consent and allow recording of the interview.
• Speaks and understand English language proficiently.

• Patients who are not transgender or gender diverse or have not received gender-affirming care or counseling.
• Participants under 18 years old.

Eligibility last updated 8/3/22. Questions regarding updates should be directed to the study team contact.

Study participants taking  the role as circulating clinical personnel and scrub personnel must have the following:

• A high school diploma, or equivalent, minimum level of education.
• Professional working proficiency, or higher, in English.
• Experience working in the OR and trained in aseptic technique.
• The role of circulating clinical personnel can be undertaken by the following people: doctor, surgeon, surgical trainee, surgical technician, or other adequately trained personnel.
• The role of scrub personnel can be undertaken by the following people: surgical technician, surgeon, surgical trainee, or other adequately trained personnel.

Study participants taking the role of the surgeon must have the following:

• A good working knowledge of ENT anatomy.
• Have worked with cadaveric tissue or live patients in the past.

• < 18 years of age. 
• The role of surgeon can be undertaken by the following people: surgeon or surgical trainee. Individuals may take on multiple roles throughout the study, but not during the same test session.

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

Eligibility last updated 8/4/22. Questions regarding updates should be directed to the study team contact.

• Infants born via vaginal delivery at Mayo Clinic Rochester.
• Infants must be followed by the Division of Pediatrics with follow-up routine prenatal care to be completed at Baldwin Building.
• 25 infants will be at high risk for development of atopic dermatitis. High risk for development of atopic dermatitis is determined by an immediate family history (parent or sibling) of one of the following: atopic dermatitis, asthma, allergic rhinitis, or food allergy.
• 25 infants will be at low risk for development of atopic dermatitis. Low risk for development of atopic dermatitis is determined by an immediate family history (parent or sibling) without the presence of any of the following medical conditions: atopic dermatitis, asthma, allergic rhinitis, or food allergy.
• No underlying medical conditions at birth including underlying congenital medical conditions.

• Infants born via cesarean section delivery.
• Infants followed by the Division of Family Medicine with routine follow-up prenatal care to be completed outside of Baldwin Building.
• Presence of underlying medical conditions at birth including congenital medical conditions.

Eligibility last updated 9/2/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Females ≥ 25 and ≤ 60 years of age.
• Appointment at Mayo Clinic Rochester in Gynecology Colposcopy Clinic or ICS (integrated community specialty) Colposcopy Clinic (will always include a speculum exam).
• Appointment at Mayo Clinic Rochester in Gynecology Clinic for indication that will already include a speculum exam (e.g., cervical cancer screening or IUD insertion). 

• Excluded if pregnant.
• Excluded if no cervix (history of total hysterectomy).
• Excluded if moderate to heavy vaginal bleeding on the day of the visit.
• Excluded if reason for visit in Gynecology Clinic is abnormal vaginal discharge.

Eligibility last updated 8/11/22. Questions regarding updates should be directed to the study team contact

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

Eligibility last updated 3/28/23. Questions regarding updates should be directed to the study team contact.

• Adult 21 years and older.
• English speaking.
• Able to provide consent.
• Clinically diagnosed stable heart failure with NYHA Class I-III symptoms.

• Patients who are unable to engage in a regularly structured exercise training program.
• History of dangerous arrhythmias.
• BMI > 40 kg/m^2
• Current smokers or smoking history of > 20 pack years
• Pregnant women, implanted pacemaker and/or ICD, cochlear implants, drug infusion pump, or any other implanted metal objects.

Eligibility last updated 8/8/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Childre:

• Ages 3-7.
• Outpatients.
• Any gender, race, or ethnicity.
• Able to provide developmentally appropriate informed assent, and legal guardians able to provide informed consent.
• EBP Severity rated above the clinically significant range (≥120; T-score ≥ 60) (Eyberg Child Behavior Inventory- ECBI; Eyberg & Pincus, 1999).
• Families approached for participation will be asked to commit to complete the treatment:
• At least one primary caregiver and the identified child will have to be able to speak and understand English;
• Must have the ability, technology, and internet access for remote therapy/research visits.   

Inclusion Criteria
•Adults:

• Agree to wear Garmin watch.
• Ages 18-99.
• Any gender, race, ethnicity.
• Able to provide informed consent.
• Able to speak and understand English.
• Has the ability, technology, and internet access for remote therapy/research visits.

Exclusion Criteria
•Children: 

• Formal diagnosis of Severe Intellectual disability, Autistic Spectrum Disorder Level 3, or a psychotic disorder for the child.
• Parents not consenting to the study.
• Parents or child is not able to adhere to the study protocol.
• A Child who is reasonable expected to be unable to tolerate wearing the Garmin device for at least 70% of the time during the day and night 70% of the days during the treatment (12 weeks). This is based on the principal investigator’s discretion.
• Unable to speak and understand English.
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.
• Children in foster care.
• Does not have the ability, technology, and/or internet access for remote therapy/research visits.
• Need for more intensive behavioral treatments such as ER visit for behavioral dyscontrol or hospitalization will not be exclusionary or exit criteria.

Exclusion Criteria
•Adults:

• Unable to speak and understand English. 
• Refusal or withdrawal of consent, inability, or unwillingness to adhere to study procedures.

Eligibility last updated  10/19/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•General: 

• The subject (or, when applicable, the subject’s legally acceptable representative) signs an informed consent form indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
• The subject is an outpatient of either sex, at least 40 years old, at the time of consent.
• Subjects must, in the opinion of the investigator, be able to participate in all scheduled evaluations, likely to be compliant, and likely to complete all required tests, including neuroimaging brain scans and lumbar punctures.
• The subject has a body mass index (BMI) ≥ 18 and ≤ 35 kg/m^2 at screening.

Inclusion Criteria
•Diagnostic:

• The subject has a diagnosis of possible or probable MSA using the modified Gilman et al, 2008 diagnostic criteria (Gilman et al. 2008).
• The subject’s onset of first MSA symptoms (including parkinsonism, cerebellar symptoms, orthostatic or urinary symptoms) occurred ≤ 4 years before screening, as assessed by the investigator.
• The subject’s anticipated life expectancy is ≥ 3 years, per investigator judgment.
• The subject has an UMSARS Part I score of ≤ 21 (excluding Item #11, sexual function), and additionally has:
  • Severity score ≤ 2 on the swallowing item (#2);
  • Severity score ≤ 2 on the ambulation item (#7);
  • Severity score ≤ 2 on the falling item (#8).
• The subject has an UMSARS Part IV disability score ≤ 3.
• Subject has a MoCA ≥ 18. Additionally, subject has sufficiently intact cognition to complete study assessments and follow study instructions, per investigator's judgment.
• A male subject who is nonsterilized and sexually active with a female partner of childbearing potential is eligible to participate if he agrees to use a barrier method of contraception (i.e., condom with or without spermicide) from the signing of informed consent throughout the study and for 90 days plus 5 half-lives (total of 190 days) after the last dose.
• Female subjects are eligible to participate if:
  • they are not pregnant or nursing; and
  • they are of nonchildbearing potential or agree to use highly effective contraception from the signing of informed consent throughout the study and for 30 days plus 5 half-lives (total of 130 days) after the last dose of study drug.

Exclusion Criteria
•Medical History:

• The subject has serious or unstable clinically significant illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic or autoimmune (e.g., multiple sclerosis), hematologic, or other major disease, which, in the judgment of the investigator, is poorly controlled or otherwise likely to deteriorate, compromises the subject’s safety or ability to complete the study, or compromises the interpretation of the study results.
• The subject has other medical problems (neurological, visual, orthopedic, psychiatric) that, in the opinion of the investigator, may significantly interfere with completion of the study or interpretation of study endpoints.
• The subject has a disorder that is likely to interfere with drug disposition and elimination.
• In the opinion of the investigator, the subject has a diagnosis of depression or other psychiatric disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), AND this disorder is poorly controlled AND of sufficient severity to interfere with completion of the study or interpretation of the endpoints.
• The subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the subject has attempted suicide within the past year before screening. Subjects who have positive answers on Item 4 or 5 on the C-SSRS (based on the past year) before randomization are excluded.
• The subject has a history of alcohol or substance use disorder (except tobacco use disorder), as defined by the DSM-5, within 1 year before screening or between screening and randomization, or, in the opinion of the investigator, the subject’s current or past use of substances may interfere with performance on the assessments.
• The subject has a positive finding on an alcohol or illicit drug screen. A positive result for cannabis or prescription medications does not require exclusion.
• The subject has undergone surgery for the treatment of MSA (e.g., pallidotomy, deep brain stimulation, fetal tissue transplantation).
• The subject has a history of epilepsy or seizures, except self-limited febrile childhood seizures.
• The subject has any contraindication to lumbar puncture including but not limited to thrombocytopenia or other coagulation disorders (including subjects who are receiving anticoagulants and cannot safely stop them), the absence of cutaneous or soft-tissue infection overlying or adjacent to the site of lumbar puncture, previous spinal surgery that could complicate access to the subarachnoid space, or conditions associated with raised intracranial pressure such as a closed head injury within 3 months or benign intracranial hypertension, or any spinal abnormality or other aspects (e.g., tattoos in the midline lumbar area) or other clinical findings (papilledema seen with ophthalmoscopy) that may complicate or contraindicate lumbar puncture, as judged by the investigator. Subjects who are using low-dose aspirin, low molecular weight heparin, coumadin, or other anticoagulants may still participate if use of these medications can be safely suspended before lumbar puncture, per investigator judgment and local medical practices.

Exclusion Criteria
•Diagnostic Assessments:

• Any clinically significant abnormality as determined by investigator at screening or between screening and randomization in physical examination findings, vital signs, ECGs, or clinical laboratory test results that may compromise the subject’s safety or ability to complete the study or compromise the interpretation of the study results.
• Presence of any of the following contraindications to MRI:
  • claustrophobia that would contraindicate brain MRI or the presence of a pacemaker;
  • cardiac defibrillator; spinal cord or vagus nerve stimulator;
  • aneurysm clip;
  • artificial heart valve; recently placed (within 1 year) coronary or carotid stent; ear implant;
  • CSF shunt; other implanted medical device (e.g., insulin pump); or
  • metal fragments or foreign objects in the eyes, skin, or body.
• Ophthalmic abnormalities. The following are considered exclusionary:
  • Ophthalmic abnormalities and conditions that, in the judgment of the investigator and/or ophthalmologist, would affect subject safety and/or impair the ability to perform a quality ophthalmological evaluation;
  • Congenital or acquired ophthalmic conditions (primary or secondary) that are considered poorly controlled within the last 12 months before screening, with or without treatment, or otherwise expected to lead to significant deterioration in visual acuity in the next 12 months after randomization;
  • Any ocular opacities that may prevent quality fundus assessment;
  • Neovascular or exudative (wet) form of age-related macular degeneration.
• The subject has any of the following at the screening visit:
  • estimated glomerular filtration rate (determined with the Chronic Kidney Disease Epidemiology Collaboration equation) < 50 mL/min; QT interval with Fridericia correction method > 450 ms for male subjects and > 470 ms for female subjects;
  • a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value > 1.5 × the upper limit of normal (ULN).
• Clinically significant vital sign abnormalities at screening, defined as:
  • Systolic blood pressure ≥ 160 mm Hg;
  • Diastolic blood pressure ≥ 90 mm Hg (blood pressure assessed with the subject at rest in the seated position; may be repeated up to 3 times), or;
  • Pulse rate 100 beats per minute (subject at rest in the seated position).
• The subject has a positive hepatitis B surface antigen test result, known or suspected active hepatitis C infection, or known history of HIV infection:
  • Note: Subjects with positive hepatitis C virus (HCV) serology results may be enrolled if results from a quantitative polymerase chain reaction for HCV RNA is negative, to exclude active hepatitis C infection, and if the investigator agrees that the subject can safely participate in the study.
• The subject has a brain MRI that shows clinically significant evidence of malignant, ischemic, demyelinating, structural, or degenerative brain disease (other than MSA) that may confound diagnosis or subject safety during the study, or the subject has findings that compromise the safety of lumbar puncture per investigator judgment.
• The subject has a current blood clotting or bleeding disorder, including clinically significant abnormal findings in laboratory tests of coagulation.

Exclusion Criteria
•Other:

• The subject has poor venous access such that IV drug delivery or PK/safety blood sampling would be difficult.
• The subject has participated in another study investigating active or passive immunization against αSYN for PD or MSA, or has had immunoglobulin G therapy, within 6 months before screening.
• The subject’s participation in a previous study of a disease-modifying therapy (with proven receipt of active treatment) will compromise the interpretability of the data from the present study, per consultation with medical monitor or designee. For example, subjects who participated in a study of gene therapy and antisense oligonucleotides (or other disease-modifying treatment) and received active treatment would be excluded.
• The subject has received any investigational compound that, in the opinion of the investigator or sponsor, may not have completely washed out before the screening visit or may affect the safety or efficacy evaluations.
• The subject has a positive pregnancy test result at screening.
• The subject is an immediate family member, is a study site employee, or is in a dependent relationship (e.g., as a spouse, parent, child, or sibling) with a study site employee who is involved in the conduct of this study.
• The subject has donated 400 mL or more of his or her blood volume within 90 days before the start of the screening visit.  

Eligibility last updated 8/10/22. Questions regarding updates should be directed to the study team contact.

• Individuals carrying the OSTEOCALCIN SNP gene and age, sex, and race matched controls.

• Participants with a known diagnosis of type 1 or type 2 diabetes mellitus or those individuals on lipid lowering drugs, as these conditions may alter FGF21 and/or apolipoprotein B levels.

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

Eligibility last updated 10/25/22. Questions regarding updates should be directed to the study team contact.

• Wrestlers on roster from Rochester Community and Technical College.
• ≥ 18 years of age. 

• Any athlete with a known cardiac condition will be excluded.

Eligibility last updated 8/23/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 and < 70 years.
• Any gender.
• Patients with physician-diagnosed AERD (including a physician diagnosis of bilateral nasal polyposis, and at least one NSAID-induced reaction that caused respiratory symptoms).
• Patients with nasal polyps and no AERD (with and without asthma).
• Patients who require endoscopic sinus surgery (ESS) for treatment of chronic rhinosinusitis and sinonasal polyposis as part of their standard of care treatment.

• Patients under the age of 18 years and above 70 years.
• Patients who are or intend to get pregnant during the course of the study or those who are breastfeeding.
• Patients with mental or legal incapacitation.
• Patients with acute of chronic kidney or liver disease either self-reported or physician-diagnosed.
• Patients with anemia requiring work-up up (hemoglobin < 10 mg/dL).
• Patients with an active peptic ulcer disease.
• Patients with bleeding-disorder or G6PD deficiency.
• Patients with a planned surgical procedure during the 1-year study period.

Eligibility last updated 8/16/22. Questions regarding updates should be directed to the study team contact.

Adult Patients With Two or More Chronic Conditions

• Members of Mayo Clinic Connect, the online community of patients facilitated by the Mayo Clinic Center for Social Media, who have received care in multiple settings and organizations.

People Living With One or More Chronic Conditions

•  Individual with one of more chronic conditions.

International Experts in Shared Decision Making (SDM)

• Participants will be adults that have published, peer reviewed, SDM related manuscripts.
• Affiliated with institutions eligible to support a research collaborator status with Mayo Clinic and willing to become Mayo Clinic research collaborators for the duration of their participation in this study.

Primary and Specialty Care Clinicians

• Clinicians included in the KER Unit database as having expressed interest in SDM, having participated in prior focus groups, or contributed to our work as clinical content experts in developing SDM tools.

Adult Patients With Two or More Chronic Conditions

• Minors, those with cognitive issues and/or non-English speaking.

People Living With One or More Chronic Conditions

• Minors, those with cognitive issues and/or non-English speaking.

International Experts in Shared Decision Making (SDM)

• No expertise in SDM or ability to enter into research collaborator status with Mayo Clinic , Minors, those with cognitive issues and/or non-English speaking.

Primary and Specialty Care Clinicians

• Minors, those with cognitive issues and/or non-English speaking.

Eligibility last updated 8/17/22. Questions regarding updates should be directed to the study team contact.