• Diagnosis of advanced retinitis pigmentosa.
• Subjects must have an Argus II device implanted to be eligible for this study.
• Subjects must be familiar with using their Argus II device.

• No Argus II implant.

• 65 years of age or older at time of randomization.
• Severe AS defined as:
  • AVA ≤ 1.0 cm^2 or AVA index ≤ 0.6 cm2/m^2; AND
  • Peak jet velocity ≥ 4.0 m/s or Mean gradient ≥ 40 mmHg.
• Patient is asymptomatic defined as:
  • Negative treadmill stress test. To be considered asymptomatic, the patient must not demonstrate any of the following during and/or after the test:
    • Syncopal or pre-syncopal episode, including severe dizziness;
    • Angina;
    • Limiting dyspnea or decreased exercise tolerance, defined as inability to reach 60% of age and sex adjusted metabolic equivalents of task (METs);
    • Drop in systolic blood pressure (defined as a progressive drop of at least 20 mmHg and sustained for 1 minute or an acute drop of 40 mmHg);
    • Significant ventricular arrhythmias (≥ 4 consecutive ventricular premature beats); OR
    • Per physician after thorough assessment of patient history if the patient is unable to perform a stress test.
• LV ejection fraction ≥ 50%.
• Society of Thoracic Surgeons (STS) risk score ≤ 10.
• The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the institutional review board (IRB) of the respective clinical site.

• Patient is symptomatic (e.g., NYHA Functional Class ≥ 2, history of syncopal episode, or CCS angina score > 1, hospitalization for heart failure within the last 12 months).
• Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV based on 3D imaging analysis.
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak (PVL) post TAVR.
• Evidence of an acute myocardial infarction ≤ 30 days before randomization.
• Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR (e.g., aneurysmal ascending aorta; i.e., > 4.0 cm; severe or bulky calcification of the LVOT or raphe that would increase the risk of annular injury or significant PVL post TAVR; coronary anatomy that increases the risk of coronary artery obstruction post TAVR), or is non-calcified.
• Severe aortic regurgitation (> 3+).
• Severe mitral regurgitation (> 3+) or ≥moderate mitral stenosis.
• Pre-existing mechanical or bioprosthetic valve in any position. (Of note, mitral ring is not an exclusion) .
• Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization.
• Leukopenia (WBC < 3000 cell/mL), anemia (Hgb < 9 g/dL), thrombocytopenia (Plt < 50,000 cell/mL), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization.
• Hypertrophic cardiomyopathy with obstruction.
• Cardiac imaging (echo, Computed Tomography (CT), and/or Magnetic Resonance Imaging (MRI)) evidence of intracardiac mass, thrombus or vegetation.
• Inability to tolerate or condition precluding treatment with anti-thrombotic therapy.
• Stroke or transient ischemic attack (TIA) within 90 days of randomization.
• Renal insufficiency (estimated glomerular filtration rate (eGFR) <30 mL/min per the Cockcroft-Gault formula) and/or renal replacement therapy.
• Active bacterial endocarditis within 180 days of randomization.
• Severe lung disease (FEV1 <5 0% predicted) or currently on home oxygen.
• Severe pulmonary hypertension (e.g., pulmonary artery (PA) systolic pressure ≥ 2/3 systemic pressure).
• History of cirrhosis or any active liver disease.
• Significant frailty as determined by the Heart Team (after objective assessment of frailty parameters).
• Significant abdominal or thoracic aortic disease (such as aneurysm, severe calcification, aortic coarctation, etc.) that would preclude safe passage of the delivery system.
• Patient refuses blood products.
• BMI > 50 kg/m^2.
• Estimated life expectancy < 24 months .
• Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication.
• Currently participating in an investigational drug or another device study.
  • Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials. Observational studies are not considered exclusionary.
• Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments (as assessed by Case Review Board).

Eligibility last updated 10/20/21. Questions regarding updates should be directed to the study team contact.

• Consented adult patients taking daily opioids at the time of admission to the Pain Rehabilitation Center will be included
• Consented adult patients here for opioid tapering therapy
• Patients with or without pre-existing history of RLS/WED can be enrolled

• Research authorization not provided
• Pediatric patients (<18 years of age) and patients who are unable to provide consent or have significant language barrier (limiting understanding of the questionnaire) will be excluded from the study

• Adults with obesity (BMI >30Kg/m2); these will be otherwise healthy individuals with no unstable psychiatric disease and controlled comorbidities or other diseases.
• Age: 18-75 years old.
• Gender: Men or women. Women of childbearing potential will have negative pregnancy tests within 48 hours of enrolment and before each radiation exposure.
• Participant must have an abnormal phenotype based on testing done in visit 2.

• Abdominal bariatric surgery.
• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption; e.g., orlistat, within the last 6 months.
• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by an anxiety or depression score >11 or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up.
• Hypersensitivity to any of the study medications.
• No contraindications to the FDA-approved medications: Phentermine-Topiramate Extended Release; Phentermine; ; Oral naltrexone extended-release/bupropion extended-release (NBSR; Contrave®, Mysimba™); and Liraglutide (Saxenda®).
• Participants with >1 phenotype based on the following criteria:
  1. No match to any phenotype based upon 90th and 75th percentile criteria; or
  2. Matches 2 or more phenotype based upon 90th percentile criteria; or
  3. No match to phenotype based on 90th percentile criteria and 2 or more match to phenotype based upon 75th percentile criteria

• Healthy endurance trained individuals participating in the Ultra Trail du Mont Blanc (UTMB) and/or Hong Kong 100 ultramarathons

• > 65 years age

• Aged 18 years or older.
• Able and willing to consenting to research.
• Listed (active and temporarily inactive) or deferred for lung or heart transplantation at Mayo Clinic in Rochester, MN.

• Under 18 years of age.
• Non-English speaking, non-verbal or extremely hard of hearing.

• Type 2 diabetes mellitus.
• Refractory predominantly lower extremity neuropathic pain for > 1 year.
• Presence of length dependent peripheral neuropathy on sudomotor testing (Q-SWEAT).
• Completed spinal cord stimulation trial with 40% or greater pain reduction from baseline.
• Failed medication trials or contraindication to gabapentinoid medications (gabapentin, pregabalin) and/or serotonin/norepinephrine reuptake inhibitors (tricyclic antidepressant (TCA) or duloxetine or venlafaxine).
• Average pain score on a visual analog scale (VAS) of ≥ 5 (with 0 representing no pain and 10 the worst pain imaginable).
• Appropriate surgical candidate for SCS56.

• Severe Autonomic Neuropathy as measured by the composite autonomic scoring scale (10 point scale) with a score ≥ 752.
• History of sympathectomy.
• Uncontrolled arterial hypertension (Systolic Blood Pressure >160).
• Baseline Foot TcPO2 < 10 mmHg to exclude patients with severe peripheral arterial disease.
• Hemoglobin A1c > 8%.
• Stable opioid regimen with oral morphine equivalent ≥ 100 mg/day.
• Alternative principle cause for peripheral neuropathy or lower extremity neuropathic pain.
• Disruptive psychiatric disorder (screened for during preoperative psychiatric evaluation).
• Pending litigations.
• Women of child bearing potential unwilling to use contraception or found to be pregnant as part of perioperative screening.
• Patients unable to hold medications that would impact autonomic testing.

• Men and women between the ages of 20-35 years
• Men and women between the ages of 65-85 years

• Regular use of omega-3 nutritional supplements
• Diabetes or fasting plasma glucose > or equal to 126 mg/dL
• Anemia (female subjects hemoglobin of <11 g/dl and male subjects hemoglobin <12 g/dl)
• Active coronary artery disease or history of unstable macrovascular disease (unstable angina, myocardial infarction, stroke, and revascularization of coronary, peripheral or carotid artery within 3 months of recruitment)
• Renal failure (serum creatinine > 1.5mg/dl)
• Chronic active liver disease (AST>144 IU/L or ALT>165 IU/L)
• Oral warfarin group medications or history of blood clotting disorders.
• international normalized ratio (INR) >2.01.5
• Smoking
• Pregnancy or breastfeeding
• Alcohol consumption greater than 2 glasses/day or other substance abuse
• Untreated or uncontrolled hypothyroidism
• Debilitating chronic disease (at the discretion of the investigators)
• Fish or shellfish allergy

• Adult patients over the age of 18 who have a clinical suspicion of an actively bleeding soft-tissue hematoma as determined by the treating emergency provider. Enrollment will be for one year or until a target of 20 patients is enrolled.

• The investigators will exclude persons under the age of eighteen, vulnerable populations (pregnant patients and prisoners), need for immediate procedural intervention and those with known hypersensitivity to sulfur hexafluoride lipid containing microspheres as well as those who have a soft-tissue hematomas that are in an unfavorable anatomical location for ultrasound imaging.

• Individuals over the age of 1 year old with a clinical diagnosis of C3 glomerulopathy or idiopathic MPGN.
  • We do not want to exclude anyone on the grounds of age, but it is very unusual to see patients diagnosed at ages older than 60 and in very early life.

• Patients who lack the capacity to give informed consent
• Individuals who do not wish to participate in the study
• Individuals whose first language is not English and an appropriate interpreter is not available.
• Inability to obtain informed consent.
• Individuals with incomplete clinical datasets and/or renal biopsy tissue that is unavailable for analysis

Patients must meet the following inclusion criteria to participate in this registry.

1. Patient is between the ages of 12 and 65 years old at the time of surgery
2. Has at least one cartilage defect present in the knee joint
3. Has a defect as determined by a medical professional
4. Is a candidate for the surgical use of fresh osteochondral allografts for a primary or revision procedure
5. Has the ability to understand the requirements of the registry, to provide written informed consent and to comply with the registry protocol

Patients must not meet any of the following criteria to be considered for this clinical trial.

1. None

• Male and female.
• Aged 18
  •80 years old.
• Biopsy confirmed CD diagnosis (Pathology report confirmation by principal investigator).
• Self-reported adherence to a gluten-free diet for ≥ 12 months (documented by medical history).
• TG2 IgA antibody negative.
• Agree to maintain dosing of approved prescribed and OTC medications throughout the course of the study.
• Willing to take study treatment with each daily evening meal (e.g., dinner).
• Willing to take gluten foodstuff with each daily evening meal (e.g., dinner).
• If using a statin, willing to withhold statin therapy for 48 hours prior to in-clinic simvastatin ingestion and testing.
• Willing to maintain GFD for entire study duration.
• Willing to undergo multiple esophagogastroduodenoscopy procedures during the course of the trial.
• Access to a reliable telephone that would allow MSM dosing compliance telephone calls.
• Access to the internet via smartphone, tablet or computer device or equivalent to facilitate daily (end-of-day) symptom reporting.
• Willing to agree to minimal ingestion outside of three main daily meals.
• Willing to limit snacks outside the daily evening meal (e.g., dinner) to gluten-free snacks.
• Willing to not ingest grapefruit in any form (i.e., whole fruit, pulp, juice, etc.) during the 48 hour period prior to and during study visits 3 & 4.
• Willing and able to comply with all study procedures.
• Must read and understand English.
• Must sign informed consent.

• Active dermatitis herpetiformis lesions at the time of screening.
• History of any form of colitis.
• History of IgE-mediated reactions to wheat (i.e., “wheat allergy”).
• Any clinical contraindications to performing an endoscopy with intestinal biopsy.
• Received any systemic biologics (such as monoclonal antibodies or other protein therapeutics where the half-life overlaps with study start) within 6 months prior to study start.
• Taking any oral probiotic supplements (not including probiotics contained in commercially available food preparations) 6 months prior to entry.
• Use of any immunosuppressive medications (i.e., for chronic treatment of autoimmune disease or transplant-rejection prophylaxis) 6 months prior to entry.
• Use of systemic cortisone-like medications within 28-days prior to and during study treatment.
• History of alcohol abuse, illegal drug use (e.g. amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, and opiates) or medical and recreational cannabinoid use within the past 12 months.
• Laboratory values:
  • Elevated liver function tests (Alanine Aminotransferase [ALT], Aspartate Transaminase[AST],Alkaline Phosphatase [Alk Phos], or Gamma-Glutamyl Transferase [GGT]) > 2.5 times the upper limit of normal (ULN);
  • Total bilirubin > 1.5x ULN;
  • Serum creatinine > 1.5x ULN;
  • Hemoglobin < 10 g/dL or 100 g/L;
  • Calcium  < 8.0 mg/mL;
  • Platelet count< 75.0 x 109/L or 75,000/mm3;
  • Partial thromboplastin time (PTT) or prothrombin time (PT/INR) > 1.5 ULN;
  • Serum potassium < 3.0 mmol/L, > 5 mmol/L;
  • Total white blood cell count (WBC)  < 3.0 x 109/L or 3000/mm3;
  • Total lymphocyte < 1.0 x 109/L or 1000/mm3.
• Current untreated or active peptic ulcer disease, Grade B or greater esophagitis, motility disorders such as irritable bowel syndrome, functional dyspepsia, inflammatory bowel disease, and symptomatic GERD (gastroesophageal reflux disease) other than celiac disease.
• Women of Child Bearing Potential (WOCBP): positive urine pregnancy test.
• Unwilling to practice highly effective birth control (unless surgically sterilized or post-menopausal).
• Other than oral contraceptives, use of prescribed medications or over-the-counter medications that, in the opinion of the investigator might interfere with study results.
• Current use of anticoagulants (warfarin sodium, heparin, full-dose aspirin [325 – 650 mg/dose] or clopidogrel) during the 7-day period prior to randomization.
• Currently taking any medication(s) contraindicated for use with simvastatin that cannot be stopped 48 hours prior to visits 3 & 4 and restarted after visits 3 & 4, respectively.
• Received any experimental drug within 30 days of randomization, in the case of experimental biologics at least 6 months prior to randomization.
• The existence of any uncontrolled chronic disease or condition [for example HIV-AIDS, hepatitis, Type 1 or 2 diabetes, or cancer (other than skin cancer)], other than celiac disease.
• Uncontrolled complications of celiac disease, which, in the opinion of the investigator, could affect immune response or pose an increased risk to the patient (e.g. Type 1 diabetes or other autoimmune disease).
• Known allergy or hypersensitivity to any of the components of the placebo, IMGX003 (including sulfites), E. coli, or E. coli-derived proteins and simvastatin.
• Known adverse respiratory effects caused by sulfites.
• Inability to give informed consent.
• Any medical condition, other than celiac disease, which, in the opinion of the investigator, could adversely affect the patient’s participation in the trial.

• Adult patients with fibrotic interstitial lung disease (defined by the presence of fibrosis on chest computed tomography (CT)) and evidence of disease progression based on worsening reported symptom burden, decline in forced vital capacity, or degree of radiologic scarring.
• Patients with emphysema but present fibrosis are also included.

• Stable or unchanged lung fibrosis (post-inflammatory, radiation induced), non-fibrotic ILD (organizing pneumonia), or non-ILD but chronic lung disease (severe asthma, COPD).

Field test 1:

• Diagnosed NMIBC
• Adult (>18yrs)
• Able to read and understand English
• Undergoing active treatment (i.e. one week after tumour resection or intravesical therapy) or completed final treatment for NMIBC within the last week

Field test 2:

• Diagnosed NMIBC
• Adult (>18yrs)
• Able to read and understand English
• After imaging or flexible cystoscopy but before endoscopic resection (i.e. before active treatment)

Field test 1:

• Unconscious or confused
• Have cognitive impairment
• Unable to speak, read and/or write in English
• Diagnosed with muscle invasive disease
• Unable to provide informed consent

Field test 2:

• Unconscious or confused
• Have cognitive impairment
• Unable to speak, read and/or write in English
• Diagnosed with muscle invasive disease
• Unable to provide informed consent
• Currently undergoing active treatment

1. Male or female 18 years of age or older with a primary diagnosis of atrial fibrillation
2. Willing and able to provide informed consent and follow the study protocol
3. Clinically indicated planned restoration of normal rhythm

1. Unable to provide informed consent
2. Unable to follow the study protocol
3. Women who are pregnant
4. Subjects with implantable devices (only if participating in phase 2-BodyGuardian processes/testing)

• Nondiabetic subjects in whom genotype at rs7903146 is known
• Have no history of diabetes and reside within a 100 mile radius of Mayo Clinic, Rochester, MN
• Subjects will have no known systemic illness, or be taking any medication that could affect glucose metabolism and no history of abdominal surgery (other than appendectomy or tubal ligation).
• Subjects who do not have diabetes (fasting glucose <100mg/dL and 2hr glucose after a 75g OGTT < 200mg/dl)

• Subjects < 25 years of age or > 70 years of age will not be studied
• Subjects taking medications that affect glucose metabolism (to be determined by PI)   
• Individuals with a BMI < 19 or > 40 kg/m2 will be excluded

• Adults ages 18-70 years of age
• Diagnosis of EoE, i.e. symptoms of esophageal dysfunction with histologic finding of 15 or more eosinophils per high power field on esophageal biopsy despite 8 weeks of high dose proton pump inhibitor therapy.
• All Subjects diagnosed with Eosinophilic Esophagitis pre and pose therapy

• Clinical evidence of infectious process potentially contributing to dysphagia (e.g. candidiasis, CMV, herpes)
• Other cause of dysphagia identified at endoscopy or esophagram (e.g. reflux esophagitis, stricture, web, ring, achalasia, esophageal neoplasm)
• Esophageal minimal diameter < 13 mm on structured barium esophagram
• Inability to read due to: Blindness, cognitive dysfunction, or English language illiteracy
• Pregnant women
• Presence of body metallic fragments or devices that prohibit use of MRI
• History of renal disease
• eGRF <30

• Patients with cancer without evidence of primary disease relapse
• Able to speak and read English  
• Able to provide informed consent 

• Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be available.
• SES-CD (excluding the presence of narrowing component) ≥ 6 (or ≥ 4 for subjects with isolated ileal disease), as confirmed by a central reader.
• Average daily liquid/very soft SF ≥ 4.0 AND/OR average daily AP score ≥ 2.0 at Baseline.
• Demonstrated an inadequate response or intolerance to one or more conventional and/or biologic therapies, in the opinion of the investigator, as defined below:
  • Oral locally acting steroids
  • Signs and symptoms of persistently active disease during or after a course of at least 4 weeks of treatment with 9 mg/day budesonide or 5 mg/day beclomethasone; OR
  • Inability to taper oral budesonide at or below 6 mg/day without recurrent active disease; OR
  • Intravenous or oral corticosteroids
  • Signs and symptoms of persistently active disease despite a history of at least one induction regimen consisting of a dose equivalent to prednisone (or equivalent) ≥ 40 mg/day orally for at least 3 weeks or intravenously for 1 week; OR
  • Inability to taper corticosteroids at or below a dose equivalent to prednisone 10 mg/day without recurrent active disease; OR
  • Immunosuppressants
  • Signs and symptoms of persistently active disease despite a history of at least one 12 weeks regimen of the following:
    • AZA: ≥ 2.0 mg/kg/day (≥ 1 mg/kg/day for subjects in Japan, Korea, Taiwan, Singapore, Hong Kong, or China), rounded to the nearest available tablet or half tablet formulation, OR a documented 6-thioguanine nucleotide (6-TGN) level of > 235 pmol/8 × 108 RBC at a dose < 2 mg/kg/day OR documentation that a dose reduction was required due to elevated 6-MP levels (> 5700 pmol/8 ×108  erythrocytes); OR
    • 6-MP: ≥ 1 mg/kg/day (≥ 0.6 mg/kg/day for subjects in Japan, Korea, Taiwan, Singapore, Hong Kong, or China), rounded to the nearest available tablet or half tablet formulation, (or a 6-TGN level of > 235 pmol/8 ×  108 RBC); OR
    • MTX (≥25 mg/week subcutaneous [SC] or intramuscular); OR
    • Tacrolimus (for subjects in Australia, Japan or Taiwan only): documented trough level of ≥5 ng/mL.
    • Note: Oral MTX use is allowed during the study, however prior or current use of oral MTX is not sufficient for inclusion into the study.
  • Biologic therapies for CD
    • At least one 6-week induction regimen of infliximab (≥5 mg/kg intravenous [IV] at Baseline and Weeks 2, and 6); OR
    • At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous [SC] dose at Baseline, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Baseline, followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is approved]); OR
    • At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Baseline and Weeks 2, and 4); OR
    • At least one 6-week induction regimen of vedolizumab (300 mg IV at Baseline and Weeks 2, and 6); OR
    • At least one 8-week induction regimen of ustekinumab [260 mg (≤55 kg) or 390 mg (> 55 to ≤85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8]; OR
    • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit of the above biologics.
    • Intolerance to corticosteroids may include depression, severe insomnia, osteopenia, cushingoid features, etc. Intolerance to AZA/6-MP should include elevations of liver enzymes, pancreatitis, etc., and may include subjects with known thiopurine methyltransferase (TPMT) genetic mutation or low activity. Intolerance to a biologic may include, but not be limited to infusion-related reaction, rash, serum sickness, anaphylaxis,  elevated liver enzymes, demyelination, congestive heart failure, infection, etc. Demonstration of intolerance requires no minimum dose or duration of use.
    • Note: Non-bio-IR subjects who have received prior biologic for up to 1 year but have not failed may be enrolled; however, subjects must have discontinued the biologic for reasons other than  inadequate response or intolerance (e.g., change of insurance, well controlled disease), and must meet the criteria for intolerance or inadequate response to oral locally acting steroids, systemic steroids (prednisone or equivalent), and/or immunosuppressants as defined above.

• Subject on CD-related antibiotics who:
  • has not been on stable doses of these medications for at least 14 days prior to Baseline, or
  • has discontinued these medications within 14 days of Baseline.
• Subject on oral aminosalicylates who:
  • has not been on stable doses of these medications for at least 14 days prior to Baseline, or
  • has discontinued these medications within 14 days of Baseline.
• Subject on corticosteroids who meets the following:
  • prednisone or equivalent dose > 30 mg/day; or
  • budesonide > 9 mg/day; or
  • has not been on the current course for at least 14 days prior to Baseline and on a stable dose for at least 7 days prior to Baseline.
• Subject on MTX who:
  • has not been on the current course for ≥ 42 days prior to Baseline, and
  • has not been on a stable dose for ≥ 28 days prior to Baseline;
• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral/intramuscular (IM) anti-infectives within 14 days prior to the Baseline Visit
• Subject requiring or receiving any parenteral nutrition and/or exclusive enteral nutrition.
• Subject who received oral or parenteral traditional Chinese medicines within 30 days prior to Baseline.
• Subject who received any live vaccination within 30 days (or longer, if required locally [e.g., 8 weeks for Japan]) prior to Baseline, or who is expected to need live vaccination during study participation including at least 30 days (or longer, if required locally [e.g., 8 weeks for Japan]) after the last dose of study drug. 
• Subject who received cyclosporine, tacrolimus, mycophenolate mofetil, or thalidomide within 30 days prior to Baseline.
• Subject who received azathioprine (AZA) or 6-mercaptopurine (6-MP) within 10 days of Baseline.
• Subject who received fecal microbial transplantation within 30 days prior to Baseline.
• Subject who received nonsteroidal anti-inflammatory drugs (NSAIDs) within 7 days prior to Baseline, except topical NSAIDs and low dose aspirin for cardiovascular protection. 
• Systemic use of known strong cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers from Screening through the end of the study (refer to Table 1 for examples of commonly used strong CYP3A inhibitors and inducers).
• Subject who received any of the following agents:
  • adalimumab, certolizumab, golimumab, infliximab, natalizumab, vedolizumab, within 8 weeks prior to Baseline; or 
  • ustekinumab within 12 weeks prior to Baseline;
  • Note: If there is proper documentation of an undetectable drug level measured by a commercially available assay for any of the approved biologics above, there is no minimum washout prior to Baseline.
• Any investigational agent within 30 days or 5 half-lives prior to Baseline, whichever is longer, or is currently enrolled in another interventional study.
• Subject with previous exposure to a JAK inhibitor (e.g., tofacitinib, baricitinib, filgotinib) within 30 days from Baseline.
  • Note: Subjects who received a JAK inhibitor prior to study entry may be enrolled if they have not had inadequate response or loss of response.
•  Subject has been taking both oral budesonide (or oral beclomethasone) and oral prednisone (or equivalent) simultaneously, with the exception of topical or inhalers within 14 days prior to Screening or during the Screening Period.
• Subject received IV corticosteroids within 14 days prior to Screening or during the Screening Period.
• Subject has received therapeutic enema or suppository (i.e., rectal aminosalicylates/corticosteroids), other than required for endoscopy, within 14 days prior to endoscopy used for Screening or during the Screening period.
• Subject who received apheresis (e.g., Adacolumn apheresis) within 60 days prior to Screening or during the Screening Period. 
• Subject has cannabis use either recreational or for medical reasons within 14 days prior to Baseline or any history of clinically significant (per investigator's judgment) drug or alcohol abuse in the last 6 months.
• Subject who previously received stem cell transplantation except for local stem cell therapy for complex perianal fistula.
• Subject has been a previous recipient of an organ transplant which requires continued immunosuppression.
• Subject with the following ongoing known complications of CD:
  • abscess (abdominal or peri-anal);
  • symptomatic bowel strictures;
  • > 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum;
  • Confirmed COVID-19: the Baseline visit must be at least 14 days from onset of signs/symptoms or positive SARS-CoV-2 test, symptomatic subjects must have recovered, defined as resolution of fever without use of anti-pyretics and improvement in symptoms;
  • Suspected COVID-19: subjects with signs/symptoms suggestive of COVID-19, known exposure, or high risk behavior should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure;
  • fulminant colitis,
  • toxic megacolon;
  • or any other manifestation that might require surgery while enrolled in the study;
  • Subject with ostomy or ileoanal pouch;
  • Subject diagnosed with conditions that could interfere with drug absorption including but not limited to short gut or short bowel syndrome; 
  • Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of > 3 bowel resections.
  • Subject with positive Clostridium difficile (C. difficile) toxin stool assay during Screening. 
• Any active, chronic or recurrent infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study, including hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, disseminated (even a single episode) herpes simplex, or HIV infection. Active HBV, HCV and HIV are defined as:
  • HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for hepatitis B core antibody (HBc Ab) positive (+) subjects;
• HCV: HCV ribonucleic acid (RNA) detectable in any subject with anti-HCV antibody (HCV Ab); 
  • HIV: confirmed positive anti-HIV antibody (HIV Ab) test;
  • Confirmed COVID-19: the Baseline visit must be at least 14 days from onset of signs/symptoms or positive SARS-CoV-2 test, symptomatic subjects must have recovered, defined as resolution of fever without use of anti-pyretics and improvement in symptoms;
  • Suspected COVID-19: subjects with signs/symptoms suggestive of COVID-19, known exposure, or high risk behavior should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure.
  • Subject has active TB or meets TB exclusionary parameters. 
  • History of any malignancy except for successfully treated nonmelanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.
  • Prior or current gastrointestinal dysplasia, other than completely removed low-grade dysplastic lesions in any biopsy performed during or before the Screening endoscopy.
  • History of gastrointestinal perforation (other than appendicitis or mechanical injury), diverticulitis or significantly increased risk for gastrointestinal perforation per investigator judgment.
  • Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or within 30 days after the last dose of study drug.
  • History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same.
  • Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug:
    • Serum AST or ALT > 2.0 × upper limit of normal (ULN); 
    • Total WBC count < 2500/µL;
    • Estimated glomerular filtration rate (eGFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m^2;
    • Hemoglobin < 9 g/dL;
    • Platelet count < 100,000/µL; 
    • Absolute neutrophil count (ANC) < 1200/µL;
    •  Absolute lymphocyte count (ALC) < 750/µL. 37. Any of the following cardiovascular conditions or thrombotic conditions:
    • recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting;
    • current uncontrolled hypertension as defined by a confirmed systolic blood pressure (BP) > 160 mmHg or diastolic BP > 100 mmHg;
    • prior history of thrombotic events including deep venous thrombosis and pulmonary embolism;
    • known inherited conditions that predispose to hypercoagulability. 
• History of clinically significant medical conditions or any other reason that in the opinion of the investigator would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug or would put the subject at risk by participating in the study.
• For Japan subjects only: positive result of beta-D-glucan or 2 consecutive indeterminate results of beta-D-glucan during the Screening Period.

• Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, as determined by the investigator, must be available.
• SES-CD (excluding the presence of narrowing component) ≥ 6 (or ≥ 4 for subjects with isolated ileal disease), as confirmed by a central reader.
• Average daily very soft or liquid SF ≥ 4.0 AND/OR average daily AP score ≥ 2.0 at Baseline.
• Demonstrated an inadequate response or intolerance to one or more of the following biologic agents:
  • At least one 6-week induction regimen of infliximab (≥ 5 mg/kg intravenous [IV] at Baseline and Weeks 2, and 6);
  • At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous [SC] dose at Baseline, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Baseline, followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is approved]);
  • At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Baseline and Weeks 2, and 4);
  • At least one 6-week induction regimen of vedolizumab (300 mg IV at Baseline and Weeks 2, and 6);
  • At least one 8-week induction regimen of ustekinumab [260 mg (≤ 55 kg) or 390 mg (> 55 to ≤ 85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8];
  • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit of the above biologics;
  • Intolerance to a biologic may include, but not limited to infusion-related reaction, rash, serum sickness, anaphylaxis, elevated liver enzymes, demyelination, congestive heart failure, infection. Demonstration of intolerance requires no minimum dose or duration of use.

• Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
• Subject on CD related antibiotics who:
  • has not been on stable doses of these medications for at least 14 days prior to Baseline; or
  • has discontinued these medications within 14 days of Baseline.
• Subject on oral aminosalicylates who:
  • has not been on stable doses of these medications for at least 14 days prior to Baseline; or
  • has discontinued these medications within 14 days of Baseline.
• Subject on corticosteroids who meet the following:
  • prednisone or equivalent dose > 30 mg/day; or
  • budesonide > 9 mg/day; or
  • has not been on the current course for at least 14 days prior to Baseline and on a stable dose for at least 7 days prior to Baseline.
• Subject on MTX who:
  • has not been on the current course for ≥ 42 days prior to Baseline, and has not been on a stable dose for ≥ 28 days prior to Baseline;
• Subject with the ongoing following known complications of CD:
  • abscess (abdominal or peri-anal);
  • symptomatic bowel strictures,;
  •  > 2 entire missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum;
  • Confirmed COVID-19: the Baseline visit must be at least 14 days from onset of signs/symptoms or positive SARS-CoV-2 test, symptomatic subjects must have recovered, defined as resolution of fever without use of anti-pyretics and improvement in symptoms; 
  • Suspected COVID-19: subjects with signs/symptoms suggestive of COVID-19, known exposure, or high risk behavior should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection or must be asymptomatic for 14 days from a potential exposure;
  • fulminant colitis;
  • toxic megacolon;
  • or any other manifestation that might require surgery while enrolled in the study.
• Subject with ostomy or ileoanal pouch.
• Subject diagnosed with conditions that could interfere with drug absorption including but not limited to short gut or short bowel syndrome. 
• Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of > 3 bowel resections.
• Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug:
  • Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 2.0 × upper limit of the reference range (ULN);
  • Total white blood cell count < 2500/µL;
  • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m^2 ;
  • Hemoglobin < 9 g/dL;
  • Platelet count < 100,000/µL;
  • Absolute neutrophil count < 1200/µL;
  • Absolute lymphocyte count < 750/µL.

For Substudy 1:

• Subject achieved clinical response in Study M14-431 or Study M14-433.
• Subject completed Week 12 (in subjects who achieve response at Week 12) or Week 24 (in subjects who achieve response at Week 24) visit and procedures in Study M14-431 or Study M14-433.
  • Note: Subjects completing Part 3/Cohort 3 of Study M14-431, who received open-label Extended Treatment, should enroll in Substudy 2.

For Substudy 2:

• Subject completed Week 52 of the maintenance period of Study M14-430 (Substudy 1).  Completion includes the Week 52 endoscopy of Substudy 1.
• Subject achieved clinical response at Week 24 and completed Week 24 visit and procedures in Part 3/Cohort 3 of Study M14-431.

Substudy 1 and 2:

• Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an AE during Study M14-431, M14-433, or Substudy 1 of Study M14-430 that in the investigator's judgment makes the subject unsuitable for this study.
• Subject with any active or chronic recurring infections based on the investigator's assessment that makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed, and the infection is resolved, based on the investigator's assessment.
• Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Study M14-431, M14-433, or Substudy 1 of Study M14-430 (Week 52).

Substudy 1 and 2

• Subject is  considered by the  investigator, for any reason, to be an unsuitable candidate for the study.
• Subject who has a known hypersensitivity to upadacitinib or its excipients, or had an AE during Studies M14-431, M14-433, or Substudy 1 of Study M14-430 that, in the investigator's judgment, makes the subject unsuitable for this study.
• Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.
• Female subjects with a confirmed positive pregnancy test at the final visit in Studies M14-431, M14-433, or Substudy 1 of Study M14-430, or who is considering becoming pregnant during the study.
• Subject is not in compliance with prior and concomitant medication requirements throughout Studies M14-431, M14-433, or Substudy 1 of Study M14-430.
• Subject with any active or chronic recurring infections based on the investigator's assessment makes the subject an unsuitable candidate for the study. Subjects with serious infections undergoing treatment may be enrolled BUT NOT dosed until the infection treatment has been completed, and the infection is resolved, based on the investigator's assessment.
• Current evidence of active or untreated latent tuberculosis.
• Subjects with high grade colonic dysplasia or malignancy diagnosed at the endoscopy performed at the final visit of Studies M14-431, M14-433, or Substudy 1 of Study M14-430 (Week 52).
• Current or history of malignancy or lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly; except for successfully treated non-metastatic cutaneous squamous cell, basal cell carcinoma, and/or localized carcinoma in situ of the cervix.
• Subject with a poorly controlled medical condition, such as uncontrolled diabetes, unstable ischemic heart disease, moderate or severe congestive heart failure, recent cerebrovascular accidents, and any other condition which, in the opinion of the investigator or sponsor, would put the subject at risk by participation in this study.
• Laboratory values from the visit immediately prior to the Week 0 Visit meeting the following criteria:
  • AST or ALT > 3 × upper limit of normal (ULN);
  • Estimated glomerular filtration rate (eGFR) by simplified 4-variable;
  • Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m2;
  • Total WBC count < 2,000/μL;
  • Absolute neutrophil count (ANC) < 1,000/μL;
  • Platelet count < 50,000/μL;
  • Absolute lymphocyte count < 500/μL;
  • Hemoglobin < 8 g/dL.
• Enrollment in another interventional clinical study while participating in this study.

1. Hypertension, defined as a mean supine blood pressure greater than 140/90 mmHg and taking at least one (1) standard of care therapies (including a diuretic, angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a calcium channel blocker)
2. MDRD estimated GFR > 30 mL/min to be calculated at the screening visit by available serum creatinine
3. Male or female African Americans
4. Between the ages of 20 and 70 years
5. Have a body mass index (BMI) within the range of 18–40 kg/m2
6. Be able to communicate effectively with the study personnel
7. Be adequately informed of the nature and risks of the study and give written informed consent prior to receiving study medication

1. Known hypersensitivity or allergy to MANP or other natriuretic peptides
2. Women of child bearing age
3. Having received any investigational drug or device within 30 days prior to entry into the study; 4) A history (within the last 2 years) of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction
4. A history of difficulty with donating blood or donated blood or blood products within 45 days prior to enrollment
5. Clinically significant new illness in the 1 month before screening in the opinion of the investigator
6. History of severe allergies
7. History of coronary artery disease, cerebrovascular disease, or syncope
8. History of epilepsy or other seizure disorder
9. History of organ transplantation
10. Malignancy within 5 years
11. Clinically significant intrinsic renal disease, renal artery stenosis, or history of fibromuscular dysplasia of the renal arteries and
12. Consumption of a phosphodiesterase-5 inhibitor

• Patients undergoing isolated coronary artery bypass graft (CABG) surgery 
• Must be undergoing the procedure at Mayo Clinic in Rochester, MN
• Must be greater than or equal to 40 years of age

• Under 40 years of age
• Concomitant additional surgical procedure (e.g., CABG + valve replacement)
• Patients with implantable pacemakers/defibrillators
• Patients that find the device too uncomfortable to wear for 48 hours

• Patients who understand the conditions of the study and are willing to participate in a single two-hour visit to the clinical site.
• Patients who are male and female, 30 years of age or older.
• Patients with a pre-primary THR diagnosis of osteoarthritis or avascular necrosis.
• Patients with a 32mm or 36mm diameter THR bearing.
• For Group 1, Patients who have had a single or first episode of dislocation beyond 6 weeks following their primary THR.
• For Group 1, Patients who have had a single episode or multiple episodes of dislocation following their primary THR, but have not been revised.
• For the Group 2, Patients who are beyond 1 year post-operative following their primary THR and have had no incidence of hip dislocation following their primary THR.
• For the Group 2, Patients who are asymptomatic based upon their pain, feeling of "popping out", and range of motion in the primary THR hip.
• Patients who have been deemed eligible for the study as determined by a blinded radiograph reviewer.
• Patients who have consented to participate in the study.

• Patients who aren’t able to clearly describe the activity in which their dislocation occurred (applicable to "dislocator group").
• Patients with a lipped polyethylene liner.
• Patients who are reluctant to flex as far forward as possible during the seated x-ray with their legs abducted.
• Patients with abductor insufficiency.
• Patients whose index hip is short by >5mm, or have offset reduced by >10mm in comparison to the contralateral side as measured on radiographs.
• For the Group 1, Patients who had a spinal fusion or spinal surgery post-dislocation.
• For the Group 2, Patients with evidence of hip joint instability (e.g., pain, feeling of "popping out", and limited range of motion, ball and socket joint laxity) of the joint.
• Patients who have a neurological disorders which may interfere or adversely affect gait or weight bearing (e.g., Parkinson’s, muscular dystrophy, multiple sclerosis).
• Patients who have cerebral dysfunction (e.g., stroke).
• Patients who have a medical history of femoral neck fracture, hip fracture.
• Patients who have a medical history of rheumatoid arthritis.
• Patients who are a known drug or alcohol abuser, or have a psychological disorder.
• Patients who are currently involved in any personal injury litigation, medical-legal or worker’s compensations claims.
• Patients who are unable to provide informed consent.
• Patients who are unable to comply with all the required study procedures.

FINAL EXCLUSIONS - following consent to participate in the study:

• If the subject isn’t flexed enough in the picture taken by radiology to achieve the positioning specified in the Imaging Protocol, or if the subject answers to being "apprehensive" or "significantly apprehensive" in the flexed seated position on the Apprehension Questionnaire
• A combined anteversion5 (CT measured supine cup anteversion + stem anteversion to the posterior condyles) that is outside of the range of 25 – 50.

• Patient must provide written or verbal informed assent and the parent/guardian/LAR must provide written informed consent before the initiation of any study-specific procedures.
• Patient is a male or female outpatient, 12 to 17 years of age inclusive, at the time the patient provides assent for the study and parent/guardian/LAR has provided signed consent.
• Patient is able to read and understand the assessments in the eDiary.
• Female patients of childbearing potential must have a negative serum pregnancy test at Visit 1 (screening) and a negative urine pregnancy test at Visit 3 (randomization) prior to dosing.
• Female patients who have had their first menstrual period and are sexually active must agree to use a reliable form of contraception. Reliable contraception is defined as:
  • Hormonal contraception (eg, oral contraceptive, contraceptive implant, or injectable hormonal contraceptive).
  • Double-barrier method (eg, condom plus intrauterine device, diaphragm plus spermicide).
• Patient has a diagnosis of IBS-D as defined by the modified Rome IV child/adolescent criteria*: Must include all of the following:
  •  Abdominal pain at least 4 days per month over at least 2 months associated with one or more of the following:
    •  Related to defecation
    •  A change in frequency of stool
    •  A change in form (appearance) of stool
  • After appropriate evaluation, the symptoms cannot be fully explained by another medical condition
  • Patient has predominantly diarrheal stool symptoms defined as Bristol stool types 6 or 7 for more than 25% of bowel movements and Bristol stool types 1 or 2 for less than 25% of bowel movements that occur in the absence of laxatives
• All criteria fulfilled for at least 2 months prior to Visit 1 (screening). 
• Patient has been compliant with the eDiary by completing both the morning and evening assessments for at least 8 out of the 14 days immediately preceding Visit 3 (randomization).
• Patient has an average daytime abdominal pain scoreless than or equal to 2.0 over the 2 weeks prior to randomization. 
• Patient has at least 1 daytime bowel movement with a consistency of Type 6 or Type 7 on the pediatric Bristol Stool Form Scale (p-BSFS) on at least 2 days per week during the 2 weeks prior to randomization that occurs in the absence of laxatives. 
• Patient has no clinically significant findings on a physical examination, vital sign assessment, electrocardiogram (ECG), and clinical laboratory tests (clinical chemistry panel, complete blood count, urine drug screen, urinalysis) after providing informed assent and after written consent is obtained, but before receiving the first dose of study treatment. (A central laboratory will be used to evaluate all urine [except urine pregnancy tests] and blood samples and will utilize reference ranges specific to a patient's age and gender. ECGs will be performed and electronically transmitted to a central ECG laboratory for analysis by a pediatric cardiologist in accordance with the instructions provided by the central ECG laboratory. The Investigator will determine if a particular finding is clinically significant. [In making this determination, the Investigator will consider whether the particular finding could represent a condition that would exclude the patient from the study, could represent a safety concern if the patient participates in the study, or could confound the study-specific assessments of safety or efficacy.])

• Patient has no gallbladder, (ie, agenesis of the gallbladder or cholecystectomy). 
• Patient has had any of the following surgeries:
  • Any abdominal surgery within the 3 months prior to Screening; or
  • A history of major gastric, hepatic, pancreatic, or intestinal surgery.  (Note: appendectomy, hemorrhoidectomy, or polypectomy greater than 3 months post-surgery are allowed. For the purposes of this study, laparoscopic surgeries without complication are considered minor and non-exclusionary, provided the condition for which the surgery was performed was not exclusionary.)
• Patient has a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical GI obstruction or pseudo obstruction. 
• Patient has a history or current diagnosis of constipation with encopresis. 
• Patient meets the child/adolescent Rome IV criteria of IBS with constipation, IBS with constipation and diarrhea (mixed), unspecified IBS, or Patient has a history of intestinal obstruction, stricture, toxic megacolon, GI perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation. 
• Patient has a documented history of hepatic impairment as defined by Child-Pugh Classification Grade A, B or C. 
• Patient has a history or current diagnosis of inflammatory or immune-mediated GI disorders including inflammatory bowel disease (ie, Crohn's disease, ulcerative colitis, microscopic colitis). 
• Patient has celiac disease, or a positive serological test for celiac disease and the condition has not been ruled out by endoscopic biopsy.
• Patient has any congenital and/or acquired malabsorption syndrome (eg, Shwachman-Diamond syndrome). 
• Patient has a history of a microbiologically documented (ie, stool culture or medical history) GI infection within 3 months prior to Screening. 
• Patient has a known lactose or fructose intolerance that is associated with diarrhea, abdominal pain or discomfort, and that could confound assessments in the study. 
• Patient has a history of diverticulitis within 3 months prior to Screening.

• Age ≥ 18 years.
• Diagnosis of TBI.
• Less than or equal to 18 months post-injury.
• Minnesota resident.
• Access to a telephone, active email account, and device (smart phone, tablet, computer) for internet access.
• Enrolled in MN BIA Resource Facilitation program during study recruitment window.

• Non-English speaking individuals (funding limits preclude a multilingual intervention).
• Individuals under a civil commitment order.
• Active patient in Mayo’s Brain Rehabilitation Clinic in Rochester, MN.
• Acquired (vs. traumatic) brain injury.

Inclusion Criteria
•Family:

• Age > 18 years.
• Access to at least a telephone.

Exclusion Criteria
•Family:

• Non-English speaking individuals (funding limits preclude a multilingual intervention).

Inclusion Criteria
•Primary Care Provider:

• Doctor or a midlevel provider (NP, PA) in primary care practice.

Exclusion Criteria
•Primary Care Provider:

• Non-English speaking individuals (funding limits preclude a multilingual intervention).

Inclusion Criteria

• Clinical diagnosis of COPD
• Age ≥40 years
• Current or previous smoker (≥10 packs per year)
• Confidence in using the proposed PR system
• English or Spanish language fluency

Exclusion Criteria

• Unable or unwilling to do Rehabilitation due to physical conditions

• Suspected glioma patient undergoing neurosurgery

• Patients without a diagnosis of glioma

• Aged 18 years or older.
• Consenting to research.
• Varying level of kidney function
• An SPPB score ≤ 10 or considered frail or pre-frail by frailty phenotype (FP).

• Younger than 18 years of age.
• Patients listed for heart or lung transplants.
• Terminal illness with a prognosis of less than 6 months.
• Significant comorbidities that limit rehabilitation potential including pulmonary disease requiring continuous oxygen supplementation, active angina, critical aortic sclerosis, decompensated heart failure, or known ventricular arrhythmia.
• Kidney transplant candidates without cardiac clearance for transplant.
• An SPPB score > 10 or not considered frail or pre-frail by FP.
• Non-English speaker without availability of adequate interpreter services (safety concern).
• Failure to pass submaximal exercise test.

• Age 18-40 years
• Female  
• Member of the WNBA team the Lynx

• Failure to meet all inclusion criteria 
• Unwilling to participate in study