• Patients age ≥ 18 years old.
• Either scheduled to receive or have received a kidney transplant (KT) at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida.

• Neuropsychiatric condition causing patient to be unable to provide consent.
• Scheduled to receive a combined organ transplant.

• Healthy, non-obese participants.
• Non-pregnant Caucasian volunteers.
• 18-70 years old.
• Male or female, 1:1.
• BMI < 30kg/m2.

• Diabetes.
• Hypertension.
• BMI ≥ 30kg/m^2.
• Chronic NSAID use (> 3 days/week).

• Patients age ≥ 18 years.
• Have received a kidney transplantation.
• Have a functioning allograft.

• Neuropsychiatric condition causing patient to be unable to provide consent.
• Recipient of a combined organ transplant.

• Self-identifies as Somali.
• Between 18 and 75 years of age.
• Receives primary care at Mayo Clinic ECH.
• Visited the primary care site at least once in the least twelve months.
• Intention to continue receiving care at the clinic for the next six months.
• Diagnosis of T2D in medical record.
• T2D diagnosis for six months or longer.
• Most recent hemoglobin A1c ≥ 8%.

• Not eligible if someone in the same household is participating in the study.

• Age ≥ 18 years old.
• New myocardial infarction within 10 days of enrollment

• Contraindications to MRI scanning including internal defibrillators or pacemakers, cerebral aneurysm clips, or severe claustrophobia.  
• Contraindications to gadolinium-based MRI contrast material; namely, glomerular filtration rate less than or equal to 30mL/min. 
• Patients with no serum creatinine available within 30 days will have a new serum creatinine drawn to calculate glomerular filtration rate. 
• Women who are pregnant or lactating.

• Patients 18-70 years old.
• Patients having ischemic stroke in the past 5 years.
• Diagnosis of ischemic stroke when between 18 and 64 years of age.

• Patients under 18 or over 70 years of age.

• Subject shall have a unilateral amputated lower limb for no less than 12 months. If the amputation needed revision within 12 months, patient could be enrolled if investigator documents that the amputation site has healed and subject’s symptoms have stabilized.
• Post-amputation pain shall be chronic (persistent over 6 months) and resistant to pain medications with a documented history within the subject’s medical records.
• Subject shall have frequent and recurring pain defined as no less than 4 episodes of pain ≥ 5 (NRS) per week on average (to be confirmed with baseline pain diary).
• Subject’s typical pain episode should last no less than 60 minutes.
• Subject shall demonstrate response to two injections, one regional nerve block and the other saline. Response to the regional nerve block is defined as greater than or equal to a 50% pain reduction by NRS at 20 minutes from administration of Lidocaine. An allowable, non-therapeutic response to saline is defined as less than 30% pain reduction by NRS 15 minutes after administration. NRS must be ≥ 5 before first injection.
• Subject’s regimen of drug therapy for pain shall be stable for no less than 4 weeks prior to implant and shall not change without approval of investigator until after their Month- 3 visit. Subject shall sign a pain medication “contract” to confirm acceptance of guidelines for the use of pain medication.
• Subject agrees not to replace or alter their prosthetic (if applicable) until after their Month-3 (primary endpoint) visit.
• Subject is able to independently read and complete all questionnaires provided in English and use electronic diary during study.
• Subject is willing and able to provide informed consent and comply with all procedures and assessments required by study protocol.
• Subject, and caregiver if applicable, is able and willing to be available for study visits throughout the duration of the study; e.g., no planned relocation of residence or extended vacation during the study that would prevent compliance with study visit schedule.
• Subject shall be 21 years of age or older (FDA definition of non-pediatric) and legally able to provide written informed consent.

• Implanted with an active implantable medical device (i.e., pacemaker).
• Confounding source of pain that interferes with reporting of limb pain.
• Uncontrolled diabetes.
• Spasticity preventing full range of motion of involved side .
• Extremely short stump; sits on end.
• Untreated psychological condition (i.e., borderline personality).
• Condition requiring MRI studies or diathermy after device implant.
• Life expectancy of less than 24 months.
• Progressive neurological disease (i.e, multiple sclerosis).
• Subjects with active local or systemic infection or immunocompromised.

• Subject is currently implanted with any active implantable device including but not limited to: pacemaker, implantable cardiac defibrillator, implantable neurostimulator (e.g., peripheral or spinal cord stimulator), or implantable drug pump.
• Subject has a source of pain other than post-amputation pain (incl. dysesthesia, cancer- related, visceral, angina, migraine, causalgia) which in the opinion of the investigator may interfere with the reporting of post-amputation pain.
• Subject has medical contraindications to surgery, including but not limited to cardiovascular, pulmonary, renal, liver or hematological disorders, active inflammation, medical contraindication for general anesthesia (e.g., severe cardiopulmonary disease), compromised immune state (due to concomitant disease or medications such as chemotherapy or immunosuppressants), or anticoagulant medication that cannot be discontinued for perioperative period.
• Uncontrolled diabetes as defined by HbA1c > 8.0.
• Spasticity in their residual limb such that the subject cannot achieve volitional full range of motion (ROM) of joints on involved side.
• Subject has skin graft or severe scarring over targeted implant site or any anatomical conditions that would prevent placement of the Altius System components.
• Subject demonstrates an inability to discern differences in pain severity, report pain intensity and related information, or complete a pain diary.
• Subject has a suspected or known allergy to any materials of the Altius System in tissue contact or Lidocaine (necessary for injection screen).
• Subject has received therapeutic regional nerve block (e.g., anesthetic with steroid, and/or opioids) for post-amputation pain within 30 days prior to baseline visit.
• Subject’s usual seated posture includes sitting on the end of their stump.
• Subject is a woman who is not using adequate contraception, is pregnant or breastfeeding, or intends to become pregnant during the course of the study.
• Subject is currently participating or intends to participate in another investigational drug or device clinical study that may influence or interfere with the data that will be collected for this study.
• Subject has a condition requiring MRI studies or diathermy after device implantation.
• Subject has a history of any alcohol or substance abuse or dependence which has required prior medical treatment or intervention. Subject has active alcohol or substance abuse.
• Subject has a condition that, in the opinion of the investigator, would interfere with study compliance (incl. unresolved issues of secondary gain) or subject’s safety.
• Subject has a life expectancy of less than 24 months.
• Subject is diagnosed with or has untreated psychological conditions: borderline personality disorder, major depression disorder characterized by hospitalization within the prior year for a major depressive episode.
• Subject has current diagnosis of any progressive neurological disease such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive diabetic peripheral neuropathy, or any tumor of the nervous system.
• Subjects with active local or systemic infection, prior recurrent bacterial infection, those who are immunocompromised or have high risk of infection due to other comorbidities.

• Adult male and non-pregnant women 18 years old or older.
• Subject has suspected temporal arteritis.
• Subject is scheduled for TAB based on clinical diagnostic protocol.
• Subject is able to understand the study procedure and provide informed consent.

• Subject has an established prior diagnosis of temporal arteritis/giant cell arteritis.
• Subject is pregnant or breast feeding.
• Subject is unable to provide informed consent.

• Aged 18 or older who are the primary caregivers of patients listed (active, deferred, or temporarily inactive) for lung, heart/lung, or heart transplantation at Mayo Clinic in Rochester, MN and Jacksonville, FL.

• Individuals younger than 18.
• Those who are non-English speaking, non-verbal, or extremely hard of hearing.

• Age 18 and older.
• Aneurysmal subarachnoid hemorrhage (SAH) in anterior/middle posterior circulation  cerebral compartment.
• Aneurysm must be secured endovascular with coiling.
• The patient or patient’s surrogate should be able to give informed consent and understand the risks of this study.
• Pain NRS ≥ 5/10 in severity.

• Non aneurysmal, traumatic subarachnoid hemorrhage (SAH).
• Transcranial Doppler velocities suggestive of or approaching vasospasm.
• Pregnancy.

• Patients with Barrett's Esophagus (BE) undergoing endoscopic surveillance.

• Patients with contraindications to endoscopic resection and/or volumetric laser endomicroscopy (VLE) imaging.

• Individuals between the ages of 18-30 years old.
• No current cervical spine pain or condition that would compromise the ability to perform a maximal isometric contraction of the cervical musculature. 
• No pain with screening evaluation consisting of active flexion, extension, side bending and negative Spurling’s compression test.
• No disability based on NDI scores (less than 4 points out of 50 possible points).

• Current neck pain or diagnoses cervical pathology.
• Past history of cervical spine surgery or pain with cervical screening.

• Subjects from 18 to 99 years of age.
• Aims 1 and 4
  •subjects from daily schedules of those scanners for the brain or MSK studies.
• Aims 2 and 3 - collaboration with the Departments of Neurology, Neurosurgery, and Physical Medicine and Rehabilitation for recruitment of subjects that may be identified by clinical colleagues or via the log of patients that are potential candidates to receive an implanted MR conditional device and passed on to the study team for screening. 

• The subject has an MR unsafe implanted device. Similarly subjects who have foreign metallic objects which contraindicate having an MRI exam (e.g., shrapnel).
• If all the labeled conditions cannot be met at the location of the device for a particular subject (e.g., due to the location of their device, no x-ray available, or other some other reason), that subject will not be scanned on the Compact 3T as part of this protocol. As described above in Methods (step 5), this may result in a screen failure.
• Pregnant or nursing subjects.

• Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines, or ESC guidelines. 
• Patient is at least 18 years of age and meets age requirements per local law. 
• Patient is geographically stable and willing and able to complete the study procedures and visits for the duration of the follow-up.

• Patient is unwilling or unable to personally provide Informed Consent. 
• Patient has indications for bradycardia pacing or Cardiac Resynchronization Therapy (CRT) (Class I, IIa, or IIb indication). 
• Patient with an existing pacemaker, ICD, or CRT device implant or leads. 
• Patients with these medical interventions are excluded from participation in the study: 
  • Prior sternotomy;
  • Any prior medical condition or procedure that leads to adhesions in the anterior mediastinal space (i.e., prior mediastinal instrumentation, mediastinitis);
  • Prior abdominal surgery in the epigastric region;
  • Planned sternotomy;
  • Prior chest radiotherapy Or any other prior/planned medical intervention not listed that precludes their participation in the opinion of the Investigator.
• Patient has previous pericarditis that:
  • Was chronic and recurrent; or
  • Resulted in pericardial effusion; or
  • Resulted in pericardial thickening or calcification. 
• Patients with these medical conditions or anatomies are excluded from participation in the study: 
  • Hiatal hernia that distorts mediastinal anatomy;
  • Marked sternal abnormality (e.g., pectus excavatum);
  • Decompensated heart failure;
  • COPD with oxygen dependence;
  • Gross hepatosplenomegaly.
• Or any other known medical condition or anatomy type not listed that precludes their participation in the opinion of the Investigator.
• Patients with a medical condition that precludes them from undergoing defibrillation testing: 
  • Severe aortic stenosis;
  • Intracardiac LA or LV thrombus;
  • Severe proximal three-vessel or left main coronary artery disease without revascularization;
  • Hemodynamic instability;
  • Unstable angina;
  • Recent stroke or transient ischemic attack (within the last 6 months);
  • Known inadequate external defibrillation; 
  • LVEF < 20%;
  • LVEDD > 70 mm.
• Or any other known medical condition not listed that precludes their participation in the opinion of the Investigator. 
• Patient with any evidence of active infection or undergoing treatment for an infection. 
• Patient is contraindicated from temporary suspension of oral/systemic anticoagulation.
• Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body. 
• Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months). 
• Patient is enrolled or planning to enroll in a concurrent clinical study that may confound the results of this study, without documented pre-approval from a Medtronic study manager. 
• Patient with any exclusion criteria as required by local law (e.g., age or other).
• Pregnant women or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth regulation method or abstinence.

​​​​​​

• Ability to understand and willingness to provide informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged ≥ 18 years.
• Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent.
• FDG-PET/CT scan available to serve as baseline; the archived scan date must be within 30 days prior to date of enrollment (date initial ICF signed); images from external facilities are allowed. If no archived FDG-PET/CT scan in window, the baseline scan must be obtained at Screening.
• Complete blood count with differential, within 14 calendar days prior to enrollment, demonstrating the following:
  • White blood cells (WBC) > 2500/mm^3;
  • Hemoglobin (Hgb) > 9.0 g/dL;
  • Platelets > 60,000/mm^3;
  • Absolute Neutrophil Count (ANC) > 1,250/mm^3
    • If no differential is available in the SOC results for enrollment, a subject may be enrolled without the ANC level. Following enrollment, however, this criterion must be met to proceed in the study.
• Comprehensive metabolic panel, within 14 calendar days prior to enrollment, demonstrating values within the site’s upper limit of normal (ULN), with the following exceptions:
  • Alanine aminotransferase (ALT) ≤ 3 x ULN;
  • Aspartate aminotransferase (AST) ≤ 3 x ULN;
  • Alkaline phosphatase (ALP) ≤ 2.5 x ULN.
• Ability to lie flat and still for a minimum of two hours for the SPECT scan.
• For females of reproductive potential: use of highly effective contraception for at least one month prior to screening, and agreement to use such a method during study participation and for an additional four weeks after the end of last investigational imaging agent administration.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional four weeks after the end of last investigational imaging agent administration.
• Agreement to adhere to Lifestyle Considerations throughout study duration.
• Documented life expectancy of at least 3 months.
• Access to most recent biopsy is requested (if tissue is available) at screen or if it is obtained through SOC during an expanded window of acceptability; i.e., throughout entire conduct of study at this site. (An updated consent will be obtained.) If a biopsy is completed as part of routine clinical care prior to IRB closure, the study may request access to this sample for tissue MC1R staining and analysis.

• Active secondary malignancy.
• Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable.
• Pregnancy.
• Lactation.
• Febrile illness within 48 hours of scheduled imaging procedure.
• Uncontrolled infection.
• Treatment with another investigational drug within 30 days prior to enrollment date.
• Subjects initiating BRAFi drugs between baseline FDG scan and enrollment. Subjects receiving consistent, stable therapy with BRAFi for ≥ 3 months prior to enrollment and who have persistent FDG positive malignant lesions on PET imaging are eligible.
• eGFR < 50 mL/min/1.73m^2.
• BMI > 50 kg/m^2.
• Previous medical history of a condition resulting in anaphylaxis or angioedema.
• Planned treatment while on study with concomitant investigative agents that do not have disclosed safety profiles in the melanoma population (peer-reviewed publications and investigator’s brochures for phase 2 or 3 trials will be accepted as disclosed safety profiles).

Eligibility last updated 11/10/21. Questions regarding updates should be directed to the study team contact.

• Patients positive for rheumatoid factor and/or anti-CCP antibodies.
• Patients with CAD documented by prior bypass surgery, prior placing of coronary stents of prior documentation of myocardial infarction
• Healthy Controls:
  • > 60 years of age;
  • No history of cardiovascular disease based on evaluation of a physician.

• Chronic viral infection.
• History of chemo/radiotherapy.
• History of cancer.
•  
• Healthy Controls:
  • Hx of autoimmune disease;
  • Hx of chemo/radiotherapy.
• History of cancer (with the exception of basal cell carcinoma of the skin).

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

Eligibility last updated 1/18/23. Questions regarding updates should be directed to the study team contact.

• 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.