Cohort 1
•Prospective biospecimens collection from 200 total healthy women and men.

• Healthy male or female over 18 years old.
• All racial and ethnic groups are eligible.
• Able to provide informed consent.

• Incarcerated individuals.
• Pregnant women.

Cohort 2 - banked specimen collection from Mayo Clinic Biobank (50 subjects).
 
Cohort 3 - surgical waste collection. In this case, a waiver of consent will be applied as subjects will not be known before collection to research staff.

• Age ≥ 18 years.
• Provide written informed consent.
• Patients undergoing commercial CAR-T cell therapy in an outpatient setting.

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• Individuals < 18 years of age.
• Non-English speaking.
• Planned initiation of lymphodepleting chemotherapy in the inpatient setting.

• Eligible particiants between the ages of 18 and 90.
• Either a family or personal history of cancer and/or a family or personal history of genetic variants in cancer predisposition genes.
• Participants may also be those who have tested negatively for genetic variants in cancer predisposition genes.

• This project does not involve prisoners or children.

Eligibility last updated 8/16.21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 4/21/23. Questions regarding updates should be directed to the study team contact.

• Parent or LAR has signed information consent.
• Subject weighs between 2.5-10 kg (or 5.5-22 lbs).
• Subject is receiving medical care in an intensive care unit.
• Parental or LAR consent to receive full supportive care through aggressive management utilizing all available therapies for a minimum of 96 hours.
• Subject has a clinical diagnosis of acute kidney injury per Kidney Disease Improving Global Outcomes (KDIGO) criteria or fluid overload requiring CRRT.

• Subject is not expected to survive 72 hours due to an irreversible medical condition, in the opinion of the investigator.
• Subject has irreversible brain damage, in the opinion of the investigator.
• Subject is intolerant to anticoagulation, as documented in the medical record.
• Subject has a Do Not Attempt Resuscitate (DNAR), Allow Natural Death (AND), withdrawal of care or similar order, or anticipated change in status, in the opinion of the investigator, within the next 7 days.
• Subject has pre-existing end-stage renal disease or pre-existing, advanced chronic kidney disease, defined as an estimated Glomerular Filtration Rate (eGRF) < 30 ml/min/1.73m^2.
• Subject has received at least 12 hours of CRRT with another machine (not including ECMO) during the current hospitalization.
• Subject is currently or has chronically been treated with a circulatory support device (i.e., left ventricular assist device (LVAD)) other than ECMO.
• Subject has had prior CRRT treatments using the Carpediem™ system.
• Subject is enrolled in clinical trials or being treated with other investigational therapeutic devices or products for acute kidney injury or fluid overload.
• Subject has any other medical condition that may confound the study objectives, in the opinion of the investigator.

Eligibility last updated 12/9/21. Questions regarding updates should be directed to the study team contact.

• Age: 18-65 years old.
• Willing to provide consent.
• Gender: Men or women.
• Women of childbearing potential will have negative pregnancy tests within 48 hours of enrolment.
• BMI: ≥ 35.
• Individuals who have elected to have RYGB at the Mayo Clinic Bariatric Center of Excellence, and individuals with a BMI ≥ 40 who are otherwise healthy with controlled cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, or endocrine disorders. The RYGB participants will be invited to participate when their surgery is scheduled at the Mayo Clinic Bariatric Center of Excellence.
• The non-RYGB participants (BMI ≥ 40) will be otherwise healthy individuals with no unstable psychiatric disease and no unstable cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, or endocrine disorders.

• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption; e.g., orlistat, phentermine.  
• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), a self-administered alcoholism screening test (AUDIT-C) and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a depression or anxiety score > 11 or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up. The AUDIT-C is a 3-item alcohol screening questionnaire that reliably identifies participants who are hazardous alcohol drinkers or have active alcohol use disorders. In men, a score of 4 or more is above the recommended limits will be reviewed by study personnel.In women, a score of 3 or more is above the recommended limits will be reviewed by study personnel.However when the points are above recommended limits, the provider will review the patient’s alcohol intake over the past few months to confirm accuracy and determine study eligibility.
• Any acute or chronic condition or other disease that, in the opinion of the Investigator, would limit the subject’s ability to complete and/or participate in this clinical study.
• Participant activities: if recruited for the investigation participants will be asked to refrain from donating blood; refrain from participating in other research studies; avoid taking any additional over the counter or prescription medications or herbal supplements that have not been reviewed and approved by the physician or the study coordinator until the study has been completed.

• Age ≥ 18 years old
• Histological confirmation of melanoma of any mucosal site including (but not limited to) anus/rectum, vulvar/vaginal, sinonasal.
  • NOTE: Melanomas of cutaneous origin and/or ocular origin are ineligible.
• R0 or R1 resection of primary melanoma tumor (no gross disease can be left behind, but microscopically positive margins are acceptable).
• Surgery within ≤ 90 days of registration.
• ECOG Performance Status (PS) ≤ 1.
• The following laboratory values obtained ≤ 14 days prior to registration:
• Hematological
  • Absolute Neutrophil Count (ANC) ≥ 1500/mm^;3
  • Hemoglobin (Hgb) ≥ 9 g/dL (may be transfused);
  • Platelet (Plt) 100,000/mm^3.
• Renal
  • Serum Creatinine ≤ 1.5 x ULN.
• Hepatic
  • Alkaline Phosphatase (Alk Phos) ≤ 1.5 x upper limit of normal (ULN);
  • Total and Direct Bilirubin ≤ 1.5 × (ULN);
  • Aspartate aminotransferase (AST) ≤ 1.5 × ULN.
• Negative pregnancy test done within 7 days prior to registration, for women of childbearing potential only.
  • NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• Written informed consent and HIPAA authorization for release of personal health information prior to registration.
  • NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Willing to return to enrolling institution for follow-up.
• Willing to provide archival tissue prior to C1D1 if available and blood samples for correlative research purposes

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and subjects known to be HIV positive and currently receiving antiretroviral therapy.
  • NOTE: Subjects known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 3 years prior to registration.
  • EXCEPTIONS: Malignancies with a very low (< 5%) risk of recurrence such as non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Active autoimmune disease -including but not limited to:
  • Subjects with a history of inflammatory bowel disease, including ulcerative colitis and Crohn’s Disease;
  • Subjects with a history of symptomatic autoimmune disease requiring systemic treatment within the past 2 years with the use of disease modifying agents, corticosteroids, or immunosuppressive drugs:
  • rheumatoid arthritis;
  • systemic progressive sclerosis (scleroderma);
  • systemic lupus erythematosus;
  • psoriasis;
  • autoimmune vasculitis (e.g., Wegener’s Granulomatosis);
  • CNS or motor neuropathy considered of autoimmune origin (e.g., GuillainBarre Syndrome and Myasthenia Gravis, multiple sclerosis).
    • EXCEPTION: autoimmune conditions that are only requiring replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Any radiation within 2 weeks prior to study initiation. Neoadjuvant and adjuvant radiation are allowed, but must be completed > 2 weeks prior to registration.
• Any prior systemic therapy for melanoma (chemotherapy, immunotherapy, targeted therapy).
• Women of childbearing potential (WOCBP) must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent until 5 months after the last dose of study drug. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Examples include: intrauterine device (IUD), vasectomy of a female subject’s male partner, contraceptive rod implanted into the skin, or use of two of the following: diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide), cervical cap with spermicide (nulliparous women only), contraceptive sponge (nulliparous women only), male condom or female condom (cannot be used together), hormonal contraceptive.

*Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• NOTE: Male subjects are not required to utilize contraception. The study regimen is not genotoxic and systemic concentrations sufficient to produce a risk of fetal toxicity are not expected in WOCBP partners from exposure to a male participant’s seminal fluid.
• Pregnant or breastfeeding.
  • NOTE: breast milk cannot be stored for future use while the mother is being treated on study.

• Age ≥ 50 years old OR primary healthcare professional (defined as having a job that has had direct patient contact during the COVID-19 pandemic) and ≥ 18 years old.
• No symptoms of COVID-19 (a fever of 100.0 degrees F or greater, OR a new cough, OR new shortness of breath, OR new sore throat, OR new diarrhea, OR new fast breathing (respiratory distress), OR new chills, OR new muscle aches (myalgias), OR new loss of smell, OR new change or loss of taste sensation) in the past 7 days.
• Have a negative Elecsys Anti-SARS-CoV-2 immunoassay antibody test at screening .
• Have not had close contact with a person with a LABORATORY CONFIRMED case of COVID-19 (Close contact is defined by CDC as:  being within approximately 6 feet of a COVID-19 patient for a prolonged period of time (more than 5 minutes) or having direct contact with infectious secretions of a COVID-19 patient (e.g., being coughed on)) in the last 14 days.
• Mayo Clinic patient who has a patient online account set up or is willing to set up an online account.
• Must have a valid email address and internet service

• History of positive or indeterminate COVID PCR test prior to screening or positive or indeterminate Elecsys Anti-SARS-CoV-2 immunoassay antibody test at screening.
• Active symptoms of COVID ((a fever of 100.0 degrees F or greater, OR a new cough, OR new shortness of breath, OR new sore throat, OR new diarrhea, OR new fast breathing (respiratory distress), OR new chills, OR new muscle aches (myalgias), OR new loss of smell, OR new change or loss of taste sensation)) in past 7 days.
• Known intolerance to Centrum multivitamins or Zinc supplement from prior exposure.
• Inability to complete follow-up questions or grant access to electronic health record for surveillance.
• Have had close contact with a person with a LABORATORY CONFIRMED case of COVID-19 in past 14 days.
• Current or former smoker less than 5 years ago.
• Pregnant or breastfeeding.
• Prisoner.
• Any subject with known immunosuppressed state, including:
  • A history of solid organ or bone marrow transplantation;
  • Subjects currently receiving chemotherapy;
  • Current rheumatologic or autoimmune illness requiring treatment with glucocorticoids, antimetabolite agents (methotrexate, azathioprine, mercaptopurine, fluorouracil, mycophenolate, leflunomide), IMIDs (lenalidomide, thalidomide, pomalidomide), calcineurin inhibitors (tacrolimus, cyclosporine), mTOR inhibitors (sirolimus, everolimus), or any monoclonal antibody drugs (including any drug given intravenously or subcutaneously) for the purpose of immunosuppression;
  • Subjects with HIV or primary immunodeficiency syndromes.

• Patients with T2DM prior to transplant who are followed in our kidney transplant clinic at Mayo Clinic Rochester
• Age ≤ 70 at the time of transplant
• Positive C peptide (>2.0 ng/ml)at any time  and/or clinically verified T2DM
• Time post transplant 1- 4 years
• On insulin  ± other antihyperglycemic agents (study group N=15) and on single non-insulin based agent (control group N=15)
• 2 groups : BMI >35 kg/m2 (N=15) and <35 kg/m2 (N=15)

Exclusion Criteria:

• Patients on no anti-hyperglycemic treatment
• Unable to give a consent
• Non-english speaking, unable to fill the questionnaires

• Dysfunctional right ventricular outflow tract (RVOT) conduit or previously implanted surgical valve.
• RVOT/PV (Pulmonic Valve) with ≥ moderate regurgitation and/or a mean RVOT/PV gradient of ≥ 35 mmHg.

• Inability to tolerate an anticoagulation/antiplatelet regimen.
• Active bacterial endocarditis or other active infections.

Eligibility last updated 5/13/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Primary Care Patient Cohort:

• All adult patients ≥ 18 years of age currently in the panel for participating Family Medicine providers within the Mayo Clinic Family Practice.
• Valid MN research authorization.

• Age < 18 years of age.

Inclusion Criteria
•Family Practice Provider Cohort:

• Mayo Clinic Family Practice providers.

• Not willing to provide consent.

Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.

• Subjects with ventricular tachycardia that require an epicardial ablation approach.
• Subjects with atrial fibrillation who require the deployment of left atrial appendage occluder device (LARIAT).
• Subjects with frequent ventricular ectopic activities that require an epicardial ablation approach.
• Subjects with coronary artery disease undergoing CABG with a history of atrial fibrillation.
• Subjects with coronary artery disease who require coronary bypass surgery
• Subjects with aortic valve disease who require aortic valve replacement surgery
• Subjects who have hypertrophic cardiomyopathy who require surgical septal myomectomy.

• Subjects not requiring one of the above ablative or surgical procedures.
• Subjects not willing to provide consent.
• Subjects with concomitant mitral valvular heart disease, or congenital heart disease.
• Subjects who has mitral or tricuspid valve disease who require surgical replacement or repair

Inclusion Criteria 

• Phase 1 and 2
  • Females aged 18-80 years with urge predominant or combined urge plus passive fecal incontinence for at least 1 year, as defined by questionnaire
• Phase 3
  • Completion of at least 5 out of 7 days of the diary in the preceding week and 10 out of 14 in the preceding 2 weeks
  • At least 1 episode of fecal incontinence per week averaged over 2 weeks
  • Average Bristol stool score of 3 or higher
  • Average stool frequency of ≥ 1/day
• Phase 4
  • All patients who complete at least 1 week of treatment with study drugs or placebo

Exclusion Criteria

• Phase 1
  • History of clinically serious cardiovascular or pulmonary disease or EKG showing 2nd degree atrioventricular block or higher
  • Current or past history of
    • Rectal cancer
    • Scleroderma
    • Inflammatory bowel disease
    • Small bowel obstruction
    • Congenital anorectal abnormalities
    • Grade 2 rectal prolapse
    • History of rectal resection 
    • Pelvic irradiation
  • Neurological disorders
    • Spinal cord injuries
    • Dementia (Mini-Mental status score <21)
    • Multiple sclerosis
    • Parkinson's disease
    • Peripheral neuropathy
  • Conditions precluding safe use of clonidine, i.e., symptomatic hypotension, or systolic blood pressure of <100 mm Hg on initial visit 
  • Currently pregnant or nursing
  • Prior history of intolerance to clonidine or colesevelam
  • Medications
    • Absolute- opioid analgesics
    • Relative- other antihypertensive agents (i.e. if there is concern about synergistic effects and hypotension)
    • Patients using drugs with anticholinergic effects will be excluded if they are used at high doses (e.g. nortriptyline greater than 50 mg/day or amitriptyline greater than 25 mg/day)
    • Patients who use lower doses will be eligible to participate provided the dose will be stable during the study 
• Phase 2
  • Positive urine pregnancy screen 
• Phase 3 (if any one is satisfied)
  • Missing data in bowel diaries, i.e. if patient did not record bowel symptoms data for more than 2 days in 1 week or 4 days over 2 weeks
  • Greater than 6 liquid [Bristol 6 or 7]) stools daily
  • Average of less than 1 bowel movement daily
  • Average Bristol stool score < 3 as assessed from analysis of bowel diaries
• Phase 4
  • Patients who completed less than 1 week of treatment with study drugs or placebo

• Patients with idiopathic cytopenias of unclear significance (ICUS).
• Patients with clonal hematopoiesis of indeterminate significance (CHIP).
• Patients with clonal cytopenias of unclear significance.
• Marrow failure syndromes with myeloid malignancy predisposition – telomere dysfunction, chromosomal breakage disorders.
• Germ line inherited syndromes with risk for malignant transformation – GATA2, CEBPA, ETV-6, RUNX1, JAK2, PF6 etc.
• Low Risk MDS (idiopathic dysplasia of unclear significance).
• Family member of a patient with one of the above conditions.

• Patients under 18 years of age.
• Reconsenting of participants may be made by a telephone call with an IRB approved telephone script from the Rochester, Arizona, or Florida location, electronic remote, electronic digital in person, or a mail out consent form so we will not add undo stress to participants.

Eligibility last updated 3/23/22. Questions regarding updates should be directed to the study team contact.

• Generally healthy adults aged 18-80 years
• Able to play a harmonica

• History of respiratory, cardiovascular, or metabolic disease.

• Known diagnosis of inflammatory skin disease (e.g., lichen planus);
• No current systemic immunosuppression therapy;
• Willingness and ability to participate and consent.

• Ambiguous diagnosis;
• Latent disease activity;
• Insufficient area of uninvolved (control) skin;
• Relative contraindication to skin biopsy (e.g., serum platelets <10; allergy to lidocaine).

• Chronic functional tricuspid regurgitation (moderate or greater). 
• Symptomatic despite medical therapy.
• The local site Heart Team determines that the patient is appropriate for transcatheter tricuspid reconstruction.

• Unsuitable anatomy.
• Primary tricuspid valve disease.
• Previous tricuspid valve repair or replacement.

Co-morbid condition(s) that, in the opinion of the investigator, could limit the patient's ability to participate in the study, including compliance with follow-up. requirements, or that could impact the scientific integrity of the study.

Inclusion Criteria
•Early ADPKD Patients:

• ADPKD (based on Ravine, et al. criteria).
• Class 1 according to our imaging classification.
• Male and female subjects, 18 - 64 years of age, inclusive.
• Estimated GFR > 45 mL/min/m^2 (CKD-EPI equation) within the last 2 years.
• Systolic BP ≤ 130mmHg without taking HTN medications (average of last 3 readings).
• Ability to provide written, informed consent.

Inclusion Criteria
•Late ADPKD Patients:

• ADPKD (based on Ravine, et al. criteria).
• Class 1 according to our imaging classification.
• Male and female subjects, 18
  •64 years of age, inclusive.
• Estimated GFR > 45 mL/min/m^2 (CKD-EPI equation) within the last 2 years.
• Systolic BP ≤ 130mmHg; can be taking HTN medications (average of last 3 readings).
• Ability to provide written, informed consent.

Inclusion Criteria
•Normal Volunteers:

• Male and female subjects, 18
  •64 years of age, inclusive.
• Estimated GFR > 45 mL/min/m^2 (CKD-EPI equation) within the last 2 years.
• Systolic BP ≤ 130mmHg without taking HTN medications (average of last 3 readings).
• Ability to provide written, informed consent.

Exclusion Criteria - Early ADPKD Patients:

• Class 2 according to our imaging classification.
• Concomitant systemic disease in the kidney (e.g., lupus, hepatitis B or C, amyloidosis, glomerular disease).
  • Diabetes mellitus trea  tment with insulin or oral hypoglycemics).
• Patients that are receiving anticoagulants (i.e., blood thinners) to prevent complications of skin biopsy.

Exclusion Criteria - Late ADPKD Patients:

• Class 2 according to our imaging classification.
• Concomitant systemic disease in the kidney (e.g., lupus, hepatitis B or C, amyloidosis, glomerular disease).
• Diabetes mellitus treatment with insulin or oral hypoglycemics).
• Patients that are receiving anticoagulants (i.e., blood thinners) to prevent complications of skin biopsy.

Exclusion Criteria
•Normal Volunteers:

• Previous personal or family history of kidney disease.
• Concomitant systemic disease in the kidney (e.g., lupus, hepatitis B or C, amyloidosis, glomerular disease).
• Diabetes mellitus treatment with insulin or oral hypoglycemics).
• Patients that are receiving anticoagulants (i.e., blood thinners) to prevent complications of skin biopsy.

• Subjects are scheduled for a clinically indicated cardiac ultrasound examination at the site.
• Subjects are over the age of 18.

Exclusion Criteria:

• Subjects under the age of 18.
• Women who are currently pregnant.
• Subjects with any known contraindications for ultrasound scanning.
• Philips employees and their family members.

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

Eligibility last updated 9/2922. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years old.
• At least one ambulatory visit in one of the participating study sites during the past year.
• SBP > 145 mmHg at most recent clinic visit (may be treated with BP meds already or not), as reported by the participant.
• A self-reported commitment to “work on lowering your blood pressure by 10 points or more to reduce your risk of heart attack and stroke."
• Owns a Smartphone (Android or iOS) and has an email address.
• Willing to receive text messages from the study.
• Can read/write English well enough to use English-based Smartphone apps and fill out online surveys in English.

• Has an arm circumference < 22 cm or > 42 cm.
• Owns a functioning Home Blood Pressure Monitor (HBPM) and has used it in the last 3 months.

Inclusion Criteria
•Healthy Cohort:

• Adults over the age of 18 and who are willing and able to give informed consent.
• Willing to participate in all activities related to this study, including trimming chest hair and wearing a reference device and the CPM wearable device.
• Volunteers of any race, any gender.
• Range of physiques.

Inclusion Criteria
•Pathologic Cohort: 

• Adults over the age of 21 and who are willing and able to give informed consent.
• Willing to participate in all activities related to this study, including wearing a capnography device, thoracic impedance reference device, and the CPM wearable device.
• Those who:
  • Are taking diuretic medication;
  • Are living with heart failure;
  • Have chronic obstructive pulmonary disorder (COPD);
  • Are recovering from a coronary-artery disease related event.
• Volunteers of any race, any gender.
• Range of physiques.

Exclusion Criteria
•Healthy Cohort: 

• Injury or skin disturbance in the area of the test device.
• Pregnant.
• Currently smokes cigarettes.
• Has known respiratory conditions such as:
  • Flu;
  • Pneumonia/bronchitis;
  • Shortness of breath/respiratory distress;
  • Respiratory or lung surgery;
  • Emphysema, COPD, lung disease.
• Has self-reported heart or cardiovascular conditions such as chest pain, AFib, CHF, cardiomyopathy, or other conditions that could interfere with cardiopulmonary function.
• Has other self-reported health conditions that could interfere with the breathing patterns and exercises detailed in the protocol (including wearing a capnography mask).

 Exclusion Criteria
•Pathologic Cohort: 

• Under the age of 21.
• Cognitive or physical impairment sufficient enough to interfere with informed consent or successful completion of the protocol.
• Injury or skin disturbance in the area of the test device.
• Pregnant.
• Have life-threatening arrhythmias which require hospital admission and constant monitoring.
• Has other self-reported health conditions that could interfere with wearing a capnography mask.

• Patients over the age of 18 years.
• Ability to provide informed consent.
• Patients scheduled for gastrointestinal endoscopy and clinically indicated resection through our advanced endoscopy practice at Mayo Clinic Saint Mary Hospital, Alfred 6 Endoscopy Unit; or
• Patients undergoing clinically indicated surgical resection of the gastrointestinal tract (esophagus, stomach, small bowel, colon).

• Patients in who endoscopic or surgical resection is contraindicated.
• Patients who are pregnant.

Eligibility last updated 8/25/21. Questions regarding updates should be directed to the study team contact.

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, 18 years of age or older.
• In good general health as evidenced by medical history but may include a diagnosis of epilepsy.
• Volunteers who are confirmed to have temporal lobe epilepsy based on established medical history and have established outpatient epilepsy care within the Mayo Clinic Health System.

• Participants with a contraindication to MRI. Such contraindications include, but are not limited to: pacemaker, metallic cardiac valve(s), magnetic material such as surgical clips, tattoos, implanted electronic infusion pumps or any other condition that would interfere with the MRI, a stent somewhere in the body, a history of allergic reaction to any metals.
• Participants who have structural anatomical legions outside the medial temporal lobe.
• Pregnancy or lactation.
• Participants who report previous experience with claustrophobia, anxiety and/or vertigo when moved inside the scanner.
• Febrile illness within the last thirty days.
• Treatment with another investigational drug or other intervention within the last thirty days.
• Subjects incapable of giving informed written consent.
•  Participants in the prisoner population.

Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.

• Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF). If over the age of 65, patient must have a family history of Chronic Kidney Disease (CKD) or clinical suspicion of genetic disorder.
• Able to read, understand, and provide written informed consent.
• Willing and able to comply with the study-related procedures.
• Diagnosis of kidney disease, and/or one of the following without any kidney biopsy (note: can be newly diagnosed or existing patient):
  • Nephropathy associated with Diabetes Mellitus (DM)*;
  • Nephropathy associated with Hypertension*;
  • Cystic nephropathy*;
  • Congenital nephropathy;
  • Tubulointerstitial disease of unknown etiology;
  • Proteinuric disease suggestive of a primary glomerulopathy by clinical evaluation;
  • Early onset, severe or familial hypertension;
  • Thrombotic microangiopathy;
  • Electrolyte and acid base disorder;
  • Nephrolithiasis with family history;
  • CKD of unknown cause after standard nephrological evaluation;
  • End stage kidney disease (ESRD).
  • * Total number of patients in each of these categories will not exceed 10% of total cohort.

• Age less than 18, or greater than 65 without a family history of CKD or clinical suspicion of genetic disorder.
• History of renal transplant.
• Clinical features and a kidney biopsy diagnosis strongly indicative of a secondary nephropathy (e.g., diabetic nephropathy, lupus nephritis, acute kidney injury).
• Previously confirmed diagnosis of a hereditary kidney disease via genetic testing.
• Received a blood transfusion within that last 30 days of study blood draw.

Eligibility last updated 10/6/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Overactive Bladder:

• 18 years of age or older.
• Candidate for or undergoing Medtronic InterStim lead implant for labeled indication* requiring an advanced evaluation.
• Willing and able to provide signed and dated informed consent.
• Willing and able to independently and accurately complete diaries, questionnaires, attend visits, and comply with the study protocol.
• Willing to maintain current regimen (dosage and frequency) of any OAB medication from baseline diary through the end of therapy evaluation.
• For subjects with urinary urge incontinence, have a diagnosis of OAB as demonstrated on a voiding diary by having a minimum of 3 episodes of urinary urge incontinence in 72 hours (Episodes must have a mild, moderate, or severe degree of urgency to meet this criterion).
• For subjects with urinary frequency, have a diagnosis of OAB as demonstrated on a voiding diary with greater than or equal to 8 urgency frequency episodes per day.
• *Candidate for or undergoing a Medtronic InterStim lead implant for labeled indication means that a clinical decision has already been made between a physician and the patient to undergo Medtronic Interstim lead implant to treat the subject’s condition. This decision is to be made prior to discussing with the patient whether to enroll in the study.

Inclusion Criteria
•Non-Obstructive Urinary Retention:

• 18 years of age or older.
• Candidate for or undergoing Medtronic InterStim lead implant for labeled indication* requiring an advanced evaluation.
• Willing and able to provide signed and dated informed consent..
• Willing and able to independently and accurately complete diaries, questionnaires, attend visits, and comply with the study protocol.
• Willing to maintain current regimen (dosage and frequency) of any NOUR medication from baseline diary through the end of therapy evaluation.
• Have a diagnosis of non-obstructive urinary retention as demonstrated by a urinary voiding diary with a minimum of 5 clean intermittent self-catheterizations in a 7-day period; and chronic non-obstructive urinary. retention with an elevated postvoid residual (PVR) that has persisted for at least six months and is documented on two or more separate occasions.
• *Candidate for or undergoing a Medtronic InterStim lead implant for labeled indication means that a clinical decision has already been made between a physician and the patient to undergo Medtronic Interstim lead implant to treat the subject’s condition. This decision is to be made prior to discussing with the patient whether to enroll in the study.

Inclusion Criteria - Fecal Incontinence:

• 18 years of age or older.
• Candidate for or undergoing Medtronic InterStim lead implant labeled indication* requiring an advanced evaluation.
• Willing and able to provide signed and dated informed consent.
• Willing and able to independently and accurately complete diaries, questionnaires, attend visits, and comply with the study protocol.
• Willing to maintain current regimen (dosage and frequency) of any FI medication from baseline diary through the end of therapy evaluation.
• Have a diagnosis of fecal incontinence as demonstrated by a bowel diary as greater than or equal to 2 incontinent episodes of more than staining (i.e., either slight, moderate, or severe soiling) per week.
• *Candidate for or undergoing a Medtronic InterStim lead implant for labeled indication means that a clinical decision has already been made between a physician and the patient to undergo Medtronic Interstim lead implant to treat the subject’s condition. This decision is to be made prior to discussing with the patient whether to enroll in the study.

Exclusion Criteria
•Overactive Bladder:

• Currently enrolled or planning to enroll in an interventional clinical study that could potentially confound the study results (co‐enrollment in an interventional study is only allowed when documented pre‐approval is obtained from the Medtronic study manager or designee).
• Implanted with a neurostimulator, pacemaker or defibrillator.
• Pelvic floor muscle dysfunction due to surgical intervention or injury.
• Have neurological conditions such as multiple sclerosis, clinically significant peripheral neuropathy or spinal cord injury (e.g., paraplegia).
• History of diabetes unless the diabetes is well‐controlled through diet and/or medications.
• Have symptomatic urinary tract infection (UTI).
• Have primary stress incontinence or mixed incontinence where the stress component overrides the urge component.
• Treatment of voiding behavior with botulinum toxin in the past 9 months or any plan to have botulinum toxin treatment during the study.
• Treatment of symptoms with tibial neuromodulation therapy in the last 3 months.
• Have knowledge of planned magnetic resonance imaging (MRIs) during the therapy evaluation portion of the study.
• Have knowledge of planned shortwave diathermy, microwave diathermy, or therapeutic diathermy.
• Women who are pregnant or planning to become pregnant.
• Current urinary tract mechanical obstruction (e.g., benign prostatic enlargement or urethral stricture).
• Characteristics indicating a poor understanding of the study or characteristics that indicate the subject may have poor compliance with the study protocol requirements.

Exclusion Criteria - Non-Obstructive Urinary Retention:

• Currently enrolled or planning to enroll in an interventional clinical study that could potentially confound the study results (co‐enrollment in an interventional study is only allowed when documented pre‐approval is obtained from the Medtronic study manager or designee).
• Implanted with a neurostimulator, pacemaker or defibrillator.
• Pelvic floor muscle dysfunction due to surgical intervention or injury.
• Have neurological conditions such as multiple sclerosis, clinically significant peripheral neuropathy or spinal cord injury (e.g., paraplegia).
• History of diabetes unless the diabetes is well‐controlled through diet and/or medications
• Have symptomatic urinary tract infection (UTI)
• Treatment of symptoms with tibial neuromodulation therapy in the last 3 months
• Have knowledge of planned magnetic resonance imaging (MRIs) during the therapy evaluation portion of the study
• Have knowledge of planned shortwave diathermy, microwave diathermy, or therapeutic diathermy
• Women who are pregnant or planning to become pregnant
• Current urinary tract mechanical obstruction (e.g., benign prostatic enlargement or urethral stricture).
• Characteristics indicating a poor understanding of the study or characteristics that indicate the subject may have poor compliance with the study protocol requirements.

Exclusion Criteria
•Fecal Incontinence:

• Currently enrolled or planning to enroll in an interventional clinical study that could potentially confound the study results (co‐enrollment in an interventional study is only allowed when documented pre‐approval is obtained from the Medtronic study manager or designee).
• Implanted with a neurostimulator, pacemaker or defibrillator.
• Pelvic floor muscle dysfunction due to surgical intervention or injury.
• Have neurological conditions such as multiple sclerosis, clinically significant peripheral neuropathy or spinal cord injury (e.g., paraplegia).
• Have uncorrected high grade internal rectal prolapse.
• Treatment of symptoms with tibial neuromodulation therapy in the last 3 months.
• Have knowledge of planned magnetic resonance imaging (MRIs) during the therapy evaluation portion of the study.
• Have knowledge of planned shortwave diathermy, microwave diathermy, or therapeutic diathermy.
• Women who are pregnant or planning to become pregnant.
• Characteristics indicating a poor understanding of the study or characteristics that indicate the subject may have poor compliance with the study protocol requirements.

Eligibility last updated 10/22/21. Questions regarding updates should be directed to the study team contact.

• Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
• Normal Controls:
  • Age ≥ 18 years;
  • Able to provide informed written consent documenting permission to give saliva sample for research testing;
  • Ability to complete questionnaire(s) by themselves or with assistance.

• Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
• Normal Controls:
  • Any personal history of head or neck cancer including head or neck skin cancer;
  • Other active malignancy ≤ 5 years prior to registration. 
  • EXCEPTIONS:  Non-melanotic skin cancer, non-metastatic prostate cancer. 
  • NOTE:  If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
  • Dry mouth (xerostomia) caused by any chronic (> 30 days) condition (known or unknown) or medication;
  • Recent (within 30 days) or active upper aerodigestive tract or anogenital infections.