• Male or female subjects age 18 years or older.
• Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
• EGPA diagnosis based on history or presence asthma and eosinophilia (> 1.0x10^9/L and/or >10% of leucocytes) and at least 2 of; biopsy with eosinophilic vasculitis or perivascular/granulomatous inflammation; mono-or polyneuropathy, non-fixed pulmonary infiltrates, sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar haemorrhage; palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positivity (Myeloperoxidase or proteinease 3).
• History of relapsing (at least 1 confirmed EGPA relapse within last 2 years and > 12 weeks prior to screening, or refractory (failure to attain remission, defined as BVAS=0 and oral corticosteroid (OCS) dose ≤ 7.5 mg/day of prednisolone or equivalent, following standard induction regimen for at least 3 months and within 6 months prior to screening, or recurrence of symptoms upon OCS tapering at any dose of ≥ 7.5 mg/day prednisolone or equivalent. If induction with glucocorticoidsalone, patient must have failed to attain remission after 3 months and the glucocorticoid dose must be ≥ 15 mg/day prednisolone or equivalent for the 4 weeks prior to randomization.
• Must be on a stable dose of oral prednisolone or prednisone of ≥ 7.5 mg/day (but not > 50mg/day) for at least 4 weeks prior to randomization.
• If receiving immunosuppressive therapy (excluding cyclophosphamide) the dose must be stable for the 4 weeks prior to randomization and during the study (dose reductions for safety reasons will be permitted).
• QTc(F) < 450 msec or QTc(F) < 480 msec for patients with bundle branch block.
• Females of childbearing potential must use an acceptable method of birth control from signing the informed consent until 4 months after the last study drug administration.

• Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
• Organ-threatening EGPA: organ-threatening EGPA as per the European League against Rheumatism criteria (Yates et al 2016); i.e., organ failure due to active vasculitis, creatinine > 5.8 mg/dL (> 513 μmol/L) within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
• Life-threatening EGPA: imminently life-threatening EGPA disease defined as any of the following within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
• Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
  • Intensive care required;
  • Severe alveolar haemorrhage or haemoptysis requiring transfusion or ventilation or haemoglobin < 8 g/dL (< 80 g/L) or drop in haemoglobin > 2 g/dL (> 20 g/L) over a 48-hour period due to alveolar haemorrhage;
  • Rapidly progressive glomerulonephritis with creatinine > 2.5 mg/dL (> 221 μmol/L) or rise in creatinine > 2 mg/dL (> 177 μmol/L) over a 48-hour period;
  • Severe gastrointestinal involvement, for example, gangrene, bleeding requiring surgery;
  • Severe central nervous system involvement;
  • Severe cardiac involvement, for example, life-threatening arrhythmia, cardiac failure: ejection fraction < 20%, NYHA Class III/IV (NYHA 2012), acute myocardial infarction.
• Patients who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to screening (Visit 1).
• Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
• Patients who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to:
  • Known ejection fraction < 30%, OR
  • Severe heart failure that meet NYHA Class IV (NYHA 2012), OR
  • Hospitalised in the 12 months prior to screening (Visit 1) for severe heart failure meeting NYHA Class III (NYHA 2012), OR
  • Angina diagnosed within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
• Chronic or ongoing active infectious disease requiring systemic treatment.
• A helminth parasitic infection diagnosed within 6 months prior to screening (Visit 1) and through randomisation (Visit 2) that has not been treated with or has failed to respond to standard of care therapy.
• Chronic stable hepatitis B and C (including positive testing for HBsAg or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
• A history of known immunodeficiency disorder including a positive HIV test.
• History of known allergy, intolerance, or anaphylaxis to any biologic therapy or vaccine.
• Known history of allergy or reaction to any component of the IP formulation.
• Patients who have known, preexisting, clinically significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal, hepatic, haematological, respiratory or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk, because of his/her participation in the study, or may influence the results of the study, or the patients’ ability to complete entire duration of the study.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
• Previous randomisation in the present study.
• Participant is currently participating in any other interventional clinical study.
• For women only: Currently pregnant, breastfeeding, or lactating. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A serum pregnancy test will be done for WOCBP at screening (Visit 1) and a urine pregnancy test must be performed for WOCBP at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test, before proceeding with further IP dosing. If serum test is positive, the patient should be excluded.
• Other laboratory parameter exclusions at screening (Visit 1) and on repeat testing (if applicable) prior to Visit 2: 
  • Creatinine > 2.5 mg/dL (221 µmol/L);
  • WBC < 4 × 10^9 /L;
  • Platelet count < 120000/mm^3;
  • Haemoglobin < 8 g/dL (< 80 g/L).
• Alcohol/substance abuse: a history (or suspected history) or alcohol misuse or substance abuse within 2 years prior to screening (Visit 1).
• Other investigational non-biologic product: receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to screening (Visit 1), whichever is longer.
• Adherence: patients who have known evidence of lack of adherence to prescribed medications and/or ability to follow physician's recommendations.
• ALT or AST level ≥ 3 times the ULN confirmed during screening period, confirmed by repeated testing (if applicable) during screening period. Transient increase of AST/ALT level that resolves by the time of randomisation is acceptable if, in the Investigator’s opinion, the patient does not have an active liver disease and meets other eligibility criteria.
• Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk, because of his/her participation in the study, or may influence the results of the study, or the patients’ ability to complete entire duration of the study. Any other medical illness that precludes study involvement.
• Receipt of blood products within 30 days prior to screening (Visit 1).
• Receipt of live attenuated vaccines 30 days prior to screening (Visit 1).

• Individuals 18 years or older.
• Individuals able and willing to give consent to under PET/CT.

• Age < 18 years old.
• Women who are pregnant, or breast-feeding.
• Unable or unwilling to give consent to undergo PET/CT.

• Subject is age 18
  •80 years at the time of screening.
• Subject has type 1 diabetes for more than one year Study specific inclusion criteria.
• Subject is on the MiniMed™ 670G insulin pump therapy within 1 year prior to screening and willing to utilize Auto Mode and CGM with Guardian™ Sensor (3) during the study.
• Subject is willing and able to perform study procedures as per investigator discretion.
• Subject is willing to take one of the following insulins and can financially support the use of either of the 2 insulin preparations throughout the course of the study (i.e., co-payments for insulin with insurance or able to pay full amount):
  • Humalog™* (insulin lispro injection);
  • NovoLog™* (insulin aspart).

• Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks.
• Subject is female and has a positive pregnancy screening test.
• Subject is female of child bearing age and who is sexually active should be excluded if she is not using a form of contraception deemed reliable by investigator.
• Subject is female and plans to become pregnant during the course of the study.
• Subject has Glycosylated hemoglobin (HbA1c) > 8.5 % at time of screening.
  • Note: All HbA1c blood specimens will be sent to and tested by a NGSP certified Central Laboratory. HbA1c testing must follow National Glycohemoglobin Standardization Program (NGSP) standards.
• Subject has had a history of 1 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening:
  • Medical assistance (i.e., Paramedics, Emergency Room [ER] or Hospitalization);
  • Coma;
  • Seizures.
• Subject has taken any oral, injectable, or IV glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study.
• Subject is unable to tolerate tape adhesive in the area of infusion set.
• Subject has any unresolved adverse skin condition in the area of infusion set placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection).
• Subject has infection in the area of infusion set placement at time of screening.
• Subject has had Diabetic Ketoacidosis (DKA) in the 12 months prior to screening visit.
• Subject is currently abusing illicit drugs.
• Subject is currently abusing alcohol.
• Subject is on dialysis (for renal failure).
• Subject has history of adrenal disorder.
• Subject has a history of inpatient psychiatric treatment in the past 6 months prior to screening.
• Subject has any condition that the Investigator believes would interfere with study participation
• Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator.
• Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening.
• Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation.
• Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, biguanides, DPP-4 inhibitors or sulfonylureas more than 2 weeks from time of screening.
• Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting in chronic anemia.
• Subject has history of cardiovascular disease defined as any ischemic related event or clinically significant arrythmia.
• Subject has hypothyroidism and has out of reference range thyroid-stimulating hormone (TSH) on screening visit (prior labs in the last 3 months are sufficient). Subject may repeat TSH draw to verify eligibility if not in range.

General

• Subjects must be ≥18 years of age, must be able to read, understand, and provide written informed consent on the Institutional Review Board (IRB)‑approved ICF and are able and willing to comply with all treatment and follow-up/study procedures.
• Females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must agree to use an acceptable method of contraception throughout their participation in the study.

Ocular

• Subjects must have a diagnosis of OHT in both eyes (IOP ≥ 22 mmHg prior to starting treatment with IOP-lowering medication) without evidence of glaucomatous optic neuropathy or visual field loss and have been receiving IOP-lowering medication for ≥ 3 months prior to Visit 1.
• Subjects must undergo a washout of any existing ocular hypotensive medications in order to determine eligibility. Washout period will vary with the class of medication used (2-6 weeks).
• Subjects must meet the following IOP requirements at Visit 3 (Eligibility Visit at End of Washout):
  • Intraocular pressure ≥ 22 mmHg and ≤ 32 mmHg in both eyes;
  • An increase in IOP of ≥ 20% over the screening visit (Visit 1) IOP in both eyes;
  • A difference in IOP between eyes ≤ 4 mmHg.
• Subjects must have a BCVA in each eye of 20/50 (LogMAR +0.4) or better.

General

• Subjects participating in any drug or device clinical investigation within 30 days prior to Visit 1 (Screening) or who anticipate participating in any other drug or device clinical investigation within the duration of this study. 
• Subjects with a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the results of the study.
• Female subjects who are pregnant or breastfeeding.
• Subjects with Body Mass Index (BMI) ≥ 40.0. Subjects with BMI 35.0-39.9 may be excluded at the discretion of the PI.

Ocular

Diseases

• Participants who are unable to discontinue contact lens use during and for 15 minutes following instillation of study drug and for 24 hours before check-in and during each study visit.
• Participants with a central corneal thickness less than 480 μm or greater than 600 micrometer (μm) in either eye.
• Participants with any condition that prevents reliable applanation tonometry (for example, significant corneal surface abnormalities) in either eye. 
• Participants who are monocular. 
• Participants with ocular conditions, which, in the opinion of the Investigator, will impact the study measurements, such as:
  • Active optic disc hemorrhage in either eye;
  • Current or a history of central/branch retinal vein or artery occlusion in either eye;
  • Current or a history of macular edema in either eye;
  • Very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and participants with angle closure, congenital, and secondary glaucoma, and with history of angle closure in either eye;
  • Diagnosis of a clinically significant or progressive retinal disease (for example, diabetic retinopathy, exudative or severe non-exudative macular degeneration) in either eye.
• Participants with any intraocular infection or inflammation in either eye within 3 months prior to Visit 1 (Screening). 
• Myopia greater than -4.00 diopter (D), or hyperopia greater than +2.000 Surgery.
• Participants with a history of ocular laser surgery in either eye within the 3 months (90 days) prior to Visit 1 (Screening).
• Participants with a history of laser trabeculoplasty, cyclophotocoagulation or glaucoma surgical procedures at any time prior to Visit 1 (Screening). 
• Participants with a history of incisional ocular surgery other than routine uncomplicated cataract surgery or severe trauma in either eye within the 3 months (90 days) prior to Visit 1 (Screening).

Eligibility last updated 2/28/22. Questions regarding updates should be directed to the study team contact.

Phase 1
•App Refinement

• Health care provider (physician, registered nurse, physician assistant) at one of the two FQHCs.
• Patient receiving primary care at one of the two partnering FQHCs:
  • AA race/ethnicity.
  • Men and women aged ≥ 18 years old.

Phase 2
•App Implementation

• Receiving primary care at one of the two partnering FQHCs and intent to continue care there for next 6 months.
• AA race/ethnicity.
• Men and women aged ≥ 18 years old.
• Uncontrolled HTN (defined as BP ≥ 140/90 mmHg [as per JNC7 Hypertension Guidelines] at most recent outpatient evaluation, with or without BP medications).
• Documented diagnosis of HTN in EHR.
• At least 1 office visit at one of the two partnering FQHCs in prior year.
• Smartphone ownership (supporting iOS or Android Systems).

Phase 1

• Unable to commit to participating in both focus groups (pre- and post-app refinement).
• Diagnosis of a serious medical condition or disability that would make participation difficult; i.e., visual or hearing impairment, mental disability that would preclude independent use of the app.

Phase 2

• Diagnosis of a serious medical condition or disability that would make participation difficult; i.e., visual or hearing impairment, mental disability that would preclude independent use of the app.

Inclusion Criteria
•Clinicians:

• Prescribing clinicians in the areas of, family medicine, primary care internal medicine, and cardiology will be included. The following providers are eligible: physicians, residents, fellows, physician assistants, and nurse practitioners.

• Clinicians who are non-prescribers (e.g. nurses, dietitians) and pediatricians will be excluded.

Inclusion Criteria
•Patients:

• Minimum age of 18.
• Known or suspected condition(s) of interest who present  with a  medical diagnosis, treatment, and/or management decision needing to be made.

Exclusion Criteria 

• Patients who have, in their clinician's best judgment, major communication barriers such as visual or hearing impairment or dementia that would compromise their ability to give written informed consent.

• Healthy adult (> 18) men and women of all races and ethnic backgrounds.
• Recruited from faculty and staff of the Mayo Medical Center and from Rochester, MN and surrounding communities. 

• Children under the age of 18 years old.

• Age > 18 years old.
• Primary total knee performed, 2000-2019.
• Development of knee stiffness requiring manipulation under anesthesia.
• Primary surgery and manipulation performed at Mayo Clinic Rochester, MN.

• Age < 18 years old.
• Pregnant women.

• Early-onset osteoarthritis diagnosis.

• Lack of early-onset osteoarthritis diagnosis.

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

- Any patient considered to be vulnerable

• Participants will be enrolled for this study from patients attending the Mayo Clinic Depression Center, Mayo Clinic Family Medicine clinics at Rochester and Kasson, MN;, Behavioral Health and Primary Care Clinic at Mayo Clinic Health System, Austin and Albert Lea, MN, with a diagnosis of major depression with a current moderate episode, with PHQ-9 scores 10-23.
• Participants will be required to be between 25 and 80 years old.
• Able to speak English.
• Able to provide written informed consent to participate in the study.
• Participants must have DSM-V diagnostic confirmation of major depressive disorder (MDD) (American Psychiatric Association 2013). 
• Participants will continue taking any prescribed medications from their clinical treatment team. 
• Participants with co-morbid secondary diagnoses of persistent depressive disorder and generalized anxiety disorders will be included in the study.
• Participants must consent to audio recording of random group sessions which will be disclosed at the final study session.
• Participants are willing to use the Mayo Clinic Patient Portal for communication purposes during the study.

• Participants with bipolar disorder, active psychosis, active suicidal ideations, and active substance abuse meeting criteria for substance use disorders except nicotine, obsessive compulsive disorder, active panic disorder with agoraphobia or other phobic disorder, active posttraumatic stress disorder, active severe personality disorders will be excluded.
• Participants with a severe major depressive episode- HAM-D scores ≥ 23.
• Pregnant women – because of time duration of the study.

• Participants will be enrolled for this study from patients attending the Mayo Clinic Depression Center, Mayo Clinic Family Medicine clinics at Rochester and Kasson, MN;, Behavioral Health and Primary Care Clinic at Mayo Clinic Health System, Austin and Albert Lea, MN, with a diagnosis of major depression with a current moderate episode, with PHQ-9 scores 10-23.
• Participants will be required to be between 25 and 80 years old.
• Able to speak English.
• Able to provide written informed consent to participate in the study.
• Participants must have DSM-V diagnostic confirmation of major depressive disorder (MDD) (American Psychiatric Association 2013). 
• Participants will continue taking any prescribed medications from their clinical treatment team. 
• Participants with co-morbid secondary diagnoses of persistent depressive disorder and generalized anxiety disorders will be included in the study.
• Participants must consent to audio recording of random group sessions which will be disclosed at the final study session.
• Participants are willing to use the Mayo Clinic Patient Portal for communication purposes during the study.

• Participants with bipolar disorder, active psychosis, active suicidal ideations, and active substance abuse meeting criteria for substance use disorders except nicotine, obsessive compulsive disorder, active panic disorder with agoraphobia or other phobic disorder, active posttraumatic stress disorder, active severe personality disorders will be excluded.
• Participants with a severe major depressive episode- HAM-D scores ≥ 23.
• Pregnant women – because of time duration of the study.

• Participants will be enrolled for this study from patients attending the Mayo Clinic Depression Center, Mayo Clinic Family Medicine clinics at Rochester and Kasson, MN;, Behavioral Health and Primary Care Clinic at Mayo Clinic Health System, Austin and Albert Lea, MN, with a diagnosis of major depression with a current moderate episode, with PHQ-9 scores 10-23.
• Participants will be required to be between 25 and 80 years old.
• Able to speak English.
• Able to provide written informed consent to participate in the study.
• Participants must have DSM-V diagnostic confirmation of major depressive disorder (MDD) (American Psychiatric Association 2013). 
• Participants will continue taking any prescribed medications from their clinical treatment team. 
• Participants with co-morbid secondary diagnoses of persistent depressive disorder and generalized anxiety disorders will be included in the study.
• Participants must consent to audio recording of random group sessions which will be disclosed at the final study session.
• Participants are willing to use the Mayo Clinic Patient Portal for communication purposes during the study.

• Participants with bipolar disorder, active psychosis, active suicidal ideations, and active substance abuse meeting criteria for substance use disorders except nicotine, obsessive compulsive disorder, active panic disorder with agoraphobia or other phobic disorder, active posttraumatic stress disorder, active severe personality disorders will be excluded.
• Participants with a severe major depressive episode- HAM-D scores ≥ 23.
• Pregnant women – because of time duration of the study.

• Male or female, age above or equal to 18 years at the time of signing informed consent.
  • Japan: Male or female, age above or equal to 20 years at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus.
• HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol).
• Renal impairment defined either by:
  • serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g; or 
  • serum creatinine-based eGFR greater than or equal to 25 and less than 50 mL/min/1.73 m^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g.
• Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening.

• Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations.
• Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening.
• Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening.
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure.
• Planned coronary, carotid or peripheral artery revascularisation.
• Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

• Adult patients, 18 years of age or older.
• Renal transplant recipients undergoing renal biopsy to evaluate for graft function

• Patients under 18 years of age.

• Age 14
  •40 years.
• Skeletally Mature.
• Failure of 6 weeks of conservative treatment.
• Primary surgery (Hip Arthroscopic Treatment) a. Surgical treatment of FAI with hip arthroscopy.
• Tonnis 0 -1 OA, with greater than 2 mm of joint space.
• Clinical diagnosis of femoroacetabular impingement (FAI) (cam or combined; alpha > 50 degrees).

• Not a surgical candidate.
• Skeletally Immature.
• Acetabular Dysplasia (LCEA < 20).
• Tonnis 2+ OA.
• Previous ipsilateral hip surgery.
• Previous major hip trauma (hip fractures, hip dislocations).
• Additional disease processes (e.g., Avascular Necrosis (AVN), synovial disease, Ehlers-Danlos Syndrome (EDS), neuromuscular disorders).
• Unable to consent due to mental faculty.
• Pregnant women.
• Non-English speaking patients.
• Prisoners or other vulnerable populations.

• Subjects with target disease ONFH and OA.

• ONFH and OA subjects taking the medications statins, steroids, or TZDs will be excluded. 

• Patients will be recruited who are undergoing MR Imaging studies as part of their routine clinical care for untreated intracranial aneurysms where no interventional treatment is planned.
• Consent to research.

• Unable to undergo MRI or have gadolinium (patients are already having these studies as part of routine clinical exam, so don’t foresee this being pertinent).
• Atypical cause of aneurysm (e.g. infectious, related to atrial myxoma, dissecting, etc.).
• Unable to remain still enough for diagnostic examinations.

• Understands the requirements of the study and provides written informed consent.
• prior to undergoing any study-related procedures.
• Subject is between the ages of 18 to 85 years old, inclusive.
• Has had and agrees to submit the results and images of a CT that shows some disease of the bowel or disease adjacent to bowel (e.g., peritoneal disease, carcinomatosis, omental caking or bowel inflammation), such that there is a reasonably high chance that the study CT scan could also show disease and which was:
  • conducted within 6 months prior to study entry;
  • conducted with IV and either positive or neutral oral contrast.
• Is willing and able to comply with protocol-specified CT scanning and visits to the clinic.
• Is able to lie flat with arms above head for 15 minutes and hold breath for 15 seconds.
• Is able to drink 1.2 liters of fluid within 45 minutes.
• Has good venous access as determined by the Investigator at screening.
• Is an outpatient who is able and willing to come to the clinic for study visits.

• Has any co-morbidity that the Investigator judges will interfere with their ability to complete the study or undergo a quality CT scan; e.g., high risk of aspiration.
• Has a history of or is currently suffering from a known gastrointestinal motility disorder; e.g., severe constipation / gastroparesis, achalasia, pseudo-obstruction, etc.
• Has symptoms of a possible current bowel obstruction.
• Has a moderate to high risk of current bowel perforation.
• Subject should not schedule a GI diagnostic surgery or hospitalization for any procedure until after the Study follow-up on Day 14 day. However, if at the time of study entry, the subject has pre-planned a surgery or hospitalization, it may be allowed at the discretion of the PI provided it does not take place until after the subject completes the Day 3 ± 2 days visit.
• Has a contraindication (i.e. allergy) to IV or Oral CT contrast.
• If of child-bearing potential, has a confirmed pregnancy or a high probability of pregnancy at the time of screening.
• Has received an investigational therapeutic or diagnostic agent or been treated with an investigational device within the 30 days prior to enrollment.

• Discharged from hospital in the past 7 days or observation status.
• Age ≥ 18 years.
• LACE+ score ≥ 59 and at least two chronic conditions.
• Index hospitalization with discharge directly to community dwelling (home, assisted living).
• English speaking.
• Discharge to home (residential dwelling) or assisted living, as appropriate and determined by the study coordinator.
• Normal cognitive function. Mild dementia or mild cognitive impairment is allowed if a caregiver is able to work with the care coordinator and patient during program enrollment.
• Mayo Clinic or Mayo Clinic Health System provider managing the patient’s care (e.g. primary care).  Patient is paneled to a Mayo Clinic MD/NP/PA.
• Access to and ability to communicate via telephone and/or video (either patient or caregiver).

• Psychiatric hospital admission.
• Patients with a serious and persistent mental health disorder or severe treatment interfering behavior that require a higher level of service than is available at the patient’s clinic.
• Untreated active substance or alcohol abuse.
• Dementia or moderate to severe cognitive impairment.
• Discharged to one of the following:
  • Rehabilitation unit;
  • Skilled nursing facility;
  • Assisted living memory unit;
  • Group home;
  • Transitional care unit.
• Pregnancy.
• Active treatment for cancer.
• Receiving dialysis or transplant services.
• Life expectancy < 6 months or enrolled in hospice or palliative care programs.
• Patient is unwilling to sign a Release of Information (ROI) – (ROI allows those providing care, internal and external to be actively involved in patient’s care coordination).
• Patients with active tuberculosis (TB).
• Violent patient flag noted in Epic.
• Patient is already enrolled in Remote Patient Monitoring or the Care Transitions Program (CTP), Palliative Care Homebound Program (PCHP), or Primary Care House Calls Program (PCHP), Advanced Care at Home (ACH) Program (NW WI).
• Recent or active COVID patient (i.e., discharged from COVID admission, active COVID event)
• Religious Sisterhood living at Mayo Clinic Hospital
  •St. Mary’s Campus or Assisi Heights (Rochester only).
• Permanently living in a long-term care facility or a memory unit of an assisted living facility.
• Chronic pain syndrome if chronic pain is the only diagnosis and no chronic medical condition exists.

• Subject is 18 years or older of any gender or race. 
• Subject is undergoing pars plana vitrectomy due to recurrent retinal detachment due to proliferative vitreoretionapthy or open globe injury. 
• Subject is willing and able to provide written informed consent, comply with clinical trial procedures, and return for all clinical trial visits. 
• Subjects of childbearing potential must agree to use two forms of birth control for the duration of the clinical trial. 

• History of severe non-proliferative or proliferative diabetic retinopathy. 
• Other planned eye surgery during the course of the trial. 
• Participation in a clinical trial with an investigational medicinal product or investigational device within 90 days of subject enrollment.

• ≥ 35 years of age.
• Either gender.
• Any self-declared ethno-racial category.
• Subjects with two healthy eyes with the crystalline lens, without glaucoma or any other clinically significant eye diseases.
• Open angles in both eyes.
• Intraocular pressure less than 24 mmHg in either eye.
• Be able and willing to provide signed informed consent and follow study instructions.
• Ability to cooperate for the examinations required for study and be able to attend all study visits.
• Contact lenses removed before the study visit.
• Best-corrected visual acuity (BCVA) in each eye of 20/50 or better.

• Female subjects who are pregnant or breastfeeding.
• Narrow angle of < Shaffer grade 2, peripheral synechiae, or peripheral iridotomy in either eye
• Subjects with a central corneal thickness less than 480 µm or greater than 620 µm in either eye.
• Chronic or recurrent inflammatory eye diseases.
• Ocular infection or ocular inflammation in the past 3 months.
• Ocular trauma other than corneal abrasion within the past 6 months.
• Clinically significant retinal disease (e.g., diabetic retinopathy, exudative or severe non-exudative macular degeneration).
• Cornea pathologic changes preventing reliable measurement (e.g., scarring, opacity) in either eye.
• Previous intraocular surgery or laser procedure in either eye.
• Previous corneal refractive surgeries.
• Myopia greater than -6.00D, or hyperopia greater than +2.00D.
• Moderate to severe dry eye in either eye.
• Serious hypersensitivity to topical anesthetic eye drops.
• Use of any topical ophthalmic medications other than lubricants and artificial tears within the past 30 days.
• For healthy subjects cohort: Subjects with a history or presence of chronic generalized systemic disease (such as hypertension, diabetes) that may confound the results of the study.
• Systolic blood pressure > 145 mmHg or/and diastolic blood pressure > 95 mmHg.
• For healthy subjects cohort: Subjects who are currently using or have a history of using medications (systemic or topical) that are known to affect IOP or blood pressure within the past 30 days (e.g., systemic/inhaled steroids, α-adrenergic agonists and antagonists, β-adrenergic antagonists, calcium channel blockers, angiotensin converting enzyme [ACE] inhibitors, and  angiotensin II receptor blockers).
• Subjects with a history or presence of any systemic condition (e.g., heart failure or kidney disease) for which drinking the water volumes proposed in this study could be harmful (for water drinking test visit).
• For hypertensive subjects cohort: Subjects who are currently using or have a history of using systemic/inhaled steroids within the past 30 days.
• Use of any products of cannabis (THC or CBD compounds) within the past 30 days.
• Lack of suitable episcleral vein for EVP measurement.
•  Subjects who are not fully vaccinated against COVID-19.

Eligibility last updated 12/16/21. Questions regarding updates should be directed to the study team contact.

• Patients undergoing deep brain stimulation (DBS) surgery.

• Patients not undergo DBS surgery.

• Age 1-65 years at the time of kidney transplant.
• Biopsy proven diagnosis of primary FSGS or minimal change disease.
• History of nephrotic syndrome (proteinuria, edema, hypoalbuminemia).
• First kidney transplant OR second or third kidney transplant with a history of recurrent FSGS in the first or second transplant
• The patient (if  ≥ 18 years old) or the child's parent or guardian must be able and willing to give written informed consent and comply with the requirements of the study protocol. Patient assent if < 18 years old will be required per local IRB requirements. 
• Negative urine pregnancy test prior to randomization (for females who are post-menarche). 
• Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment with rituximab. An individual who meets any of the following criteria will be excluded from participation in this study: 
  • Known genetic cause of FSGS;
  • Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.);
  • Received rituximab within 1 year prior to transplant;
  • Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins;
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
  • Known active bacterial, viral (e.g., HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit;
  • Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer);
  • ANC < 1.5 x 10^3;
  • Hemoglobin: < 8.0 gm/dL;
  • Platelets: < 100,000/mm;
  • AST or ALT > 2.5 x Upper Limit of Normal at the local institution's laboratory;
  • History of drug, alcohol, or chemical abuse within 6 months prior to screening visit;
  • Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential;
  • Concomitant malignancies or previous malignancies; 
  • History of psychiatric disorder that would interfere with normal participation in this protocol;
  • History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease);
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
  • Inability to comply with study and follow-up procedures.

• Known genetic cause of FSGS.
• Patients with FSGS secondary to another condition (obesity, viral infection, medications, etc.).
• Received rituximab within 1 year prior to transplant.
• Known hypersensitivity to rituximab, to any of its excipients, or to murine proteins.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Known active bacterial, viral (e.g. HIV, hepatitis B, hepatitis C), fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening visit.
• Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug (whichever is longer)
  • ANC < 1.5 x 10^3;
  • Hemoglobin:  < 8.0 gm/dL;
  • Platelets:  < 100,000/mm;
  • AST or ALT  > 2.5 x Upper Limit of Normal at the local institution’s laboratory.
• History of drug, alcohol, or chemical abuse within 6 months prior to screening visit.
• Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential.
• Concomitant malignancies or previous malignancies.
• History of psychiatric disorder that would interfere with normal participation in this protocol.
• History of significant cardiac (including arrhythmias) or pulmonary disease (including obstructive pulmonary disease).
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Inability to comply with study and follow-up procedures.

• Age 18 (or age of legal consent per local regulations, whichever is older) to 85 years, inclusive.
• Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy:
  • Hereditary ATTR (hATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
  • Documentation of a TTR pathogenic mutation consistent with hATTR amyloidosis;
  • Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm (based on central echocardiogram reading at Screening);
  • Amyloid deposits in cardiac or noncardiac tissue (e.g., fat pad aspirate, salivary gland, median nerve connective sheath) confirmed by Congo Red (or equivalent) staining OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc] or 99Tchydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if monoclonal gammopathy of undetermined significance (MGUS) has been excluded;
  • If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains,  documentation of TTR protein in tissue with immunohistochemistry or mass spectrometry is required.
  • Wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy diagnosed based on meeting all of the following criteria:
    • Documentation of absence of pathogenic TTR mutation;
    • Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12mm (based on central echocardiogram reading at Screening);
    • Amyloid deposits in cardiac tissue with TTR protein identification by IHC, mass spectrometry, OR technetium (99mTc) scintigraphy (99mTc-3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99mTc-pyrophosphate [PYP-Tc], or 99Tchydroxymethylene diphosphonate [HMDP]) with Grade 2 or 3 cardiac uptake, if MGUS has been excluded;
    • If the patient has evidence of a MGUS based on serum and urine protein electrophoresis and serum free light chains, the following is required: documentation of TTR protein in cardiac tissue with immunohistochemistry or mass spectrometry OR documentation of TTR protein in noncardiac tissue (e.g., fat pad aspirate, salivary gland, median nerve connective sheath) with immunohistochemistry or mass spectrometry; AND Grade 2 or 3 cardiac uptake on technetium scintigraphy.
• Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that currently requires treatment with a diuretic.
• Patient meets one of the following criteria: a. Tafamidis-naïve and not actively planning to commence treatment with tafamidis during the first 12 months following randomization.
  • Note: in addition to patients who have never taken tafamidis, those who have previously been on tafamidis and have not received any tafamidis for at least 30 days before the Screening Visit will be considered tafamidis-naïve for purposes of this study); or
  • On tafamidis.  Note: must be on-label use of commercial tafamidis per an approved cardiomyopathy indication and dose in the country of use.
• Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator.
• Screening NT-proBNP > 300 ng/L and 600 ng/L and < 8500 ng/L.
• Able to complete ≥ 150 meters on the 6-MWT at Screening.
• Have a Karnofsky performance status of ≥ 60%

• Has known primary amyloidosis (AL amyloidosis) or leptomeningeal amyloidosis.
• NYHA Class IV heart failure; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP > 3000 ng/L and eGFR < 45 ml/min).[Gillmore 2018].
• Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk due to polyneuropathy, or is wheelchair bound) at the Screening visit.
• Has any of the following laboratory parameter assessments at Screening:
  • AST or ALT levels > 2.0 × ULN;
  • Total bilirubin > 2.0 × ULN;
  • International normalized ratio (INR) > 1.5 (unless patients were on anticoagulant therapy in which case excluded if INR ˃ 3.5).
• Has eGFR < 30 mL/min/1.73 m^2 (using the modification of diet in renal disease [MDRD] formula) at Screening.
• Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
• Tafamidis-naïve patients for whom the Investigator actively plans or anticipates commencing treatment with tafamidis either during the Screening Period or the first 12 months following randomization, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis.
• Received prior TTR-lowering treatment (including revusiran, patisiran or inotersen) or participated in a gene therapy trial for hATTR amyloidosis.
• Is currently taking diflunisal; if previously on this agent, must have at least a 30-day wash-out prior to dosing (Day 1).
• Is currently taking doxycycline, ursodeoxycholic acid, or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1).
• Unwilling to avoid any concurrent treatment with diflunisal, ursodeoxycholic acid/tauroursodeoxycholate/doxycycline, or TTR lowering agents (e.g., patisiran, inotersen)
• Current or future participation in another investigational device or drug study, scheduled to occur during this study, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline.
• Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem).
• 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline.
• Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem).
• Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzymes and ECG changes) that the Investigator feels is a significant contributor or the predominant cause of the patient’s heart failure.
• Unstable congestive heart failure (CHF) (including patients who require adjustment of existing diuretics or addition of new diuretics at time of Screening for purposes of achieving optimal management of CHF).
• Had acute coronary syndrome or unstable angina within the past 3 months.
• Has history of sustained ventricular tachycardia or aborted ventricular fibrillation.
• Has history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker is indicated but will not be placed.
• Has persistent elevation of systolic (˃ 170 mmHg) or diastolic (˃ 100 mmHg) blood pressure that is considered uncontrolled by physician.
• Has untreated hypo- or hyperthyroidism.
• Has an active infection requiring systemic antiviral, antiparasitic or antimicrobial therapy that will not be completed prior to dosing (Day 1).
• Prior or anticipated (during the first 12 months after randomization) heart, liver or other organ transplant or implantation of left-ventricular assist device.
• History of multiple drug allergies or history of allergic reaction to any component of or excipient in the study drug.
• History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability.
• Has other medical conditions or comorbidities (e.g., malignancy, neuropsychiatric disorder etc…) which, in the opinion of the Investigator, would interfere with study compliance or data interpretation.
• Is not willing to comply with the contraceptive requirements during the study period.
• Female patient is pregnant, planning a pregnancy, or breast-feeding.
• Unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol intake of > 2 units/day is excluded during the study (unit: 1 glass of wine [approximately 125 mL] = 1 measure of spirits [approximately 1 fluid ounce] = ½ pint of beer [approximately 284 mL]).
• History of alcohol abuse, within the last 12 months before Screening, in the opinion of the Investigator.
• History of illicit drug abuse within the past 5 years that in the opinion of the Investigator would interfere with compliance with study procedures or follow-up visits.

• Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
• 18 to 90 years of age (inclusive).
• Females: must be non-pregnant and non-lactating and either:
  • surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
  • post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and folliclestimulating hormone (FSH) levels in the post-menopausal range for the laboratory involved);
  • abstinent*; or
  • if of child-bearing potential and engaged in sexual relations, agree to use 1 highly effective contraceptive method from the time of signing the informed consent form until at least 24 weeks after the last dose of Study Drug (ION‑682884 or placebo).
• Males must be surgically sterile or abstinent*; if engaged in sexual relations with a female of child-bearing potential, the patient must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 24 weeks after the last dose of Study Drug.

*Abstinence is only acceptable as true abstinence; i.e., when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.

• Willing to be genetically tested for mutations in the TTR gene during screening, if it was not done before.
• Amyloid deposits in cardiac or non-cardiac tissue confirmed by Congo Red (or equivalent) staining OR technetium scintigraphy (99mTc -3,3-diphosphono-1,2- propanodicarboxylic acid [DPD-Tc], 99m Tc-pyrophosphate [PYP-Tc], or 99mTc-hydroxymethylene-diphosphonate [HMDP-Tc]) with Grade 2 or 3 cardiac uptake in the absence of abnormal light chains ratio, centrally confirmed.
• End-diastolic interventricular septum thickness of > 12 mm on Screening echocardiogram.
• Medical history of HF secondary to hereditary or wild-type ATTR-CM with at least:
  • 1 prior hospitalization for HF, which may include hospitalization for arrhythmia or pacemaker/ICD (implantable cardioverter defibrillator) placement; OR
  • symptoms and signs of volume overload or elevated intracardiac pressure that either requires or required treatment with diuretics for clinical stabilization.
• Screening N-terminal prohormone of brain natriuretic peptide (NT-proBNP) ≥ 600 pg/mL by central lab. For patients in atrial fibrillation at Screening the eligibility NT-proBNP value is ≥ 1200 pg/mL.
• New York Heart Association (NYHA) class I-III.
• 6MWT ≥ 150 meters.
• If on medical treatment for HF, stable medication regimen for at least 2 weeks prior to randomization.
• Willingness to adhere to vitamin A supplementation per protocol.

• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening.
• Hospitalization or urgent visit to emergency department/emergency room (ED/ER) for worsening of HF within 4 weeks prior to or during Screening.
• Uncontrolled hypertension (systolic blood pressure [BP] > 160 or diastolic BP > 100 mmHg).
• Uncontrolled clinically significant cardiac arrhythmia, per Investigator’s assessment (e.g., no pacemaker, although indicated).
• Severe, uncorrected, cardiac valvular disease.
• Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease.
• Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a patient unsuitable for inclusion:
  • Alanine aminotransferase/aspartate aminotransferase (ALT/AST) > 2.0 × upper limit of normal (ULN);
  • Total bilirubin ≥ 1.5 × ULN (patients with total bilirubin ≥ 1.5 × ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN, and known to have Gilbert’s disease);
  • Platelets < lower limit of normal (LLN; central laboratory);
  • Urine protein creatinine ratio (UPCR) ≥ 750 mg/g. In the event of UPCR above this threshold, ineligibility may be confirmed by a repeat random spot UPCR ≥ 750 mg/g;
  • Positive test (including trace) for blood on urinalysis. In the event of a positive test ineligibility may be confirmed with urine microscopy showing > 5 red blood cells per high power field in women, this exclusion criterion must be assessed outside of menstrual period;
  • Estimated glomerular filtration rate (eGFR) < 30 mL /min/1.73 m^2 at Screening [CKD-EPI formula; (Levey et al. 2009)]. If the eGFR is thought to be underestimated, the CKD-EPI creatinine-cystatin C equation can be used for confirmation (Inker et al. 2012);
  • Abnormal thyroid function tests with clinical significance per Investigator judgement;
  • Serum retinol level at Screening < LLN (this criterion does not apply to hATTR-CM patients with mutation at the position 84 [e.g., Ile84Ser]);
  • Hemoglobin A1c (HbA1c) > 9.5%.
• Monoclonal gammopathy of undetermined significance (MGUS) and/or immunoglobulin free light chain ratio < 0.26 and/or > 1.65, unless fat, bone marrow, or heart biopsy confirming the absence of light chain and the presence of TTR protein by mass spectrometry or immunoelectron microscopy.
• Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.
• Known history of or positive test for human immunodeficiency virus (HIV), (as evidenced by positive tests for HIV antibody and HIV RNA), hepatitis C (as evidenced by positive tests for HCV antibody and HCV RNA) or hepatitis B (as evidenced by a positive test for hepatitis B surface antigen).
• History of bleeding, diathesis or coagulopathy (e.g., liver cirrhosis, hematologic malignancy, antiphospholipid antibody syndrome, congenital disorders such as hemophilia A, B, and Von Willebrand disease).
• If receiving oral anticoagulants (except vitamin K antagonists), the dose must have been stable for 4 weeks prior to the first dose of Study Drug and regular monitoring must be performed, per clinical practice during the study. If the patient is receiving vitamin K antagonists (e.g., warfarin) INR should be in therapeutic range, as established by the Investigator, for 4 weeks prior to the first dose.
• Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies who have been treated with curative intent and without recurrence within 5 years may also be eligible per Investigator judgment 14. Prior liver or heart transplant, and/or Left Ventricular Assist Device (LVAD) or anticipated liver transplant or LVAD within 1 year after randomization.
• Karnofsky performance status of ≤ 50%.
• Contraindication for immunosuppressive therapy, per Investigator’s discretion.
• Known Light chain/Primary Amyloidosis (AL).
• Known leptomeningeal amyloidosis.
• Known history of multiple myeloma.
• Treatment with another investigational drug and/or biological agent within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer.
• Current or previous treatment with Tegsedi™ (inotersen) or Onpattro™ (patisiran) or other oligonucleotide or RNA therapeutic (including siRNA).
• Current treatment with diflunisal, doxycycline, non-dihydropyridine calcium-channel blocker (e.g., verapamil, diltiazem). Patients receiving any of these agents must respect a wash-out period of 14 days before randomization.
• Unwillingness or inability to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
• Other physical, social, or psychological conditions including illicit drug or alcohol use, which, in the opinion of the Investigator would make the patient unsuitable for inclusion, or could interfere with the patient participating in or completing the study.

• Adults more than 18 years old.
• Adults presenting with ST elevation myocardial infarction.
• Able to consent.

• Unable to provide consent.

• Adults >18 years old.
• Adults with chronic lung disease undergoing lung resection surgery.

• Patients < 18 years old.

• >18 and <45 years of age.
• Asymptomatic individuals who have vaped at least once a week for the past 6 months or longer OR individuals with non-urgent symptoms possibly related to vaping whose symptom onset occurred after at least weekly vaping use for 3 months or longer (non-urgent is defined as following: in the opinion of the investigator or primary care physician, the patient does not require urgent/emergent medical care for symptom management).
• Current vapers or those vapers who have quit within the past 30 days.
• If subject is referred by a physician as a symptomatic patient, his or her health history, medications, review of symptoms, and physical exam are available in Epic EMR and would have been updated within the past 30 days.
• Subject is a never smoker
  •defined as having used less than 100 cigarettes in their lifetime.
• Able to fully participate in all aspects of the study.
• Able to understand and sign the consent.
• Mayo Clinic patient with a primary care physician who can be contacted if medical attention to CT findings is needed.

Exclusion criteria

• Smoked one or more cigarettes within the past 30 days.
• With the exception of asthma, has a known medical condition that causes or can cause lung findings, including but not limited to heart disease, liver or kidney failure, amyloidosis, cancer (excluding non-melanoma skin cancer), HIV, immunosuppression, bleeding disorders, cystic fibrosis, emphysema, or any interstitial lung disease.
• An upper respiratory infection (includes nasal congestion with cough), pneumonia or influenza within the past 30 days.
• Chronic respiratory symptoms prior to the start of vaping.
• With the exception of vaping marijuana and THC products, participant must have NO  history of IV drug abuse, not used non-THC illicit drugs within the past 6 months, and not smoked marijuana within the last 3 months.
• Has an unstable or urgent medical condition as determined by the physician investigator.
• Expired air carbon monoxide > 8 ppm.

Eligibility last updated 9/28/22. Questions regarding updates should be directed to the study team contact.

• Subject is male or female, ≥ 40 years of age at the time of enrollment. 
• Subject presents for a screening colonoscopy per standard of care. 
• Subject has no symptoms or signs that require immediate, or near term, referral for diagnostic or therapeutic colonoscopy. 
• Subject understands the study procedures and can provide informed consent to participate in the study and authorization for release of relevant protected health information (PHI) to the Study Investigator.

• Subject has a personal history of CRC or advanced precancerous lesions.
• Subject has a diagnosis or medical / family history of any of the following conditions, including:
  • Familial adenomatous polyposis (also referred to as "FAP", including attenuated FAP and Gardner’s syndrome);
  • Hereditary non-polyposis CRC syndrome (also referred to as "HNPCC" or "Lynch Syndrome");
  • Other hereditary cancer syndromes including but are not limited to Peutz–Jeghers Syndrome, MYH-Associated Polyposis (MAP), Turcot's (or Crail’s) Syndrome, Cowden's Syndrome, Juvenile Polyposis, Neurofibromatosis, or Familial Hyperplastic Polyposis.
• Subject has a diagnosis or personal history of inflammatory bowel disease (IBD) including chronic ulcerative colitis and/or Crohn’s disease.
• Subject has a diagnosis of Cronkhite-Canada Syndrome.
• Subject has had a positive Cologuard within the previous 2 years, or fecal occult blood test or FIT within the previous 6 months.
• Subject has undergone a colonoscopy within the previous 9 years, with the exception of a failed colonoscopy due to poor bowel preparation. Failed colonoscopy must have been within the past year and without therapeutic intervention.
• Subject has had overt rectal bleeding within the previous 30 days.
• Subject has any condition that in the opinion of the Investigator should preclude participation in the study.