• Age: 18 to 65 years old (inclusive).
• Gender: both males and females.
• Body mass index (BMI): 18.5-34.9 kg/m^2.
• Habitual sleep duration < 7 hours.
• Presence of either:
  • Prehypertension: office systolic BP (SBP) 120-139 mmHg and/or diastolic BP (DBP) 80-89 mmHg;
  • Stage 1 hypertension: office SBP 140-159 mmHg and/or DBP 90-99 mmHg.
• Either on no prescription medications (other than oral contraceptive pills, or intrauterine devices) or on stable medical regimen for at least 1 month, if taking prescription medications for chronic conditions.
• Not pregnant or breast feeding and not intending to become pregnant or breast feed.
• Not a current smoker or tobacco user.
• Ability to provide written informed consent.

• Vulnerable study populations will be excluded.
• Pregnancy.
• Smoking.
• Presence of overt cardiovascular diseases, diabetes, chronic kidney disease, cancer, sleep disorders, psychiatric disorders.
• If taking prescription medications for chronic conditions, change in therapy (type, frequency and/or dosage) over the previous month.
• Habitual sleep duration ≥ 7 hours.
• Excessive alcohol (≥ 15 drinks/week in men and ≥ 8 drinks/week in women) and/or excessive caffeine intake (> 400 mg).
• Currently on a diet and/or actively trying to lose weight.
• Currently or previously (during the past 2 months) participation in any other research study at the discretion of study personnel.
• Blood/plasma donation during the past 2 months.
• Unwillingness or inability to adjust sleep schedule.

• Males or females 60 years of age or older.
• Meet the requirements for one of the four groups (CU A−, CU A+, MCI A+, AD A+).
• Neurologic evaluation procedures with testing in the MCSA or ADRC or Mayo Clinic Behavioral Neurology Practice. Must have had or plan to have at least 2 testing sessions.
• All participants must complete an amyloid PiB PET scan and MRI brain scan within approximately 6 months prior to the ER176 PET/CT scan.
• Capacity to sign consent or have a legally authorized representative to sign the consent.

• Participants unable to lie down without moving for 20 minutes.
• Women who are pregnant or cannot stop breast feeding for 24 hours.
• Actively taking daily anti-inflammatory medications (NSAIDs, corticosteroids, etc.) except for a small control group. Anti-inflammatory creams, eye drops, and nasal sprays are not exclusions.
• Generalized inflammatory condition and treatment with immunosuppressive, corticoid/glucocorticoid, steroidal or non-steroidal anti-inflammatory medication within 2 weeks of scanning (only acute medication use as an exclusion so as to limit medication interaction but preserve possible chronic systemic inflammation interaction).
• Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc., since the quantitative PET data analysis is based on anatomic criteria that are established uniquely for each subject by registration to his/her MRI.

Eligibility last updated 8/20/21. Questions regarding updates should be directed to the study team contact.

• 18 years or older.
• Willing and able to comply with the study procedures and provide written informed consent to participate in the study.
• Scheduled for a clinically indicated ERCP or other duodenoscope-based procedure.

• Potentially vulnerable subjects, including, but not limited to pregnant women.
• Subjects for whom endoscopic techniques are contraindicated.
• Patients who are currently enrolled in another investigational study that would directly interfere with the current study, without prior written approval from the sponsor.
• Investigator discretion.

PRE-REGISTRATION:

• Well- or moderately-differentiated neuroendocrine tumor(s) of bronchial origin (i.e., carcinoid) as assessed by local pathology.
• The pathology report must state ONE of the following:
  • Well- or moderately-differentiated neuroendocrine tumor;
  • Low- or intermediate-grade neuroendocrine tumor.
• Carcinoid tumor (including typical or atypical carcinoid tumors): 
  • Documentation of histology from a primary or metastatic site is allowed.
• Functional (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome) or nonfunctional tumors are allowed.
• Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e., large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e., adenocarcinoid tumor) are not eligible.
• Recurrent or locally-advanced/unresectable or metastatic disease.
• Neuroendocrine tumor of bronchial (i.e., lung) primary site.
• Lesions must have shown radiological evidence of disease progression in the 12 months prior to pre-registration.
• Tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to pre-registration; however, documentation of SSTR positivity in the 6 months prior to pre-registration is preferred. SSTR positivity is defined as uptake greater than background liver in all measurable lesions.
• Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by computer tomography (CT) scan or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or radiotherapy should not be considered measurable unless the lesion has clearly progressed since the procedure.
• Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 1 cm with CT or MRI (or ≥ 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, bone metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.

REGISTRATION:

• Confirmation of SSTR positivity by Alliance Imaging Core Lab (ICL) at Imaging and Radiation Oncology Core (IROC) Ohio central radiographic review.
• Patients with treatment-naive or previously-treated disease are allowed. Patients with previously-treated disease must have demonstrated radiographic disease progression on the prior therapy.
• No prior treatment with peptide receptor radionuclide therapy (PRRT) (e.g. < lutetium Lu 177 dotatate).
• No prior treatment with mammalian target of rapamycin (mTOR) inhibitors (e.g., deforolimus, everolimus, sirolimus, temsirolimus, etc.).
• Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective radioembolization) or ablative therapies (i.e., cryoablation, radiofrequency ablation, etc.) is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site. Prior liver-directed or other ablative treatment must be completed at least 28 days prior to registration.
• Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to registration.
• Radiation therapy (conventional fractionated or stereotactic ablative) to the lung and/or mediastinum must be completed at least 28 days prior to registration.
• Prior treatment with systemic anticancer therapy must be completed at least 28 days prior to registration (except for somatostatin analogs in patients with functional tumors). Continuation of treatment with somatostatin analogs while on protocol therapy is allowed provided that the patient:
  • Has functional tumors (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome);
  • Has been on a stable dose of somatostatin analog therapy for at least three months;
  • Has previously demonstrated radiographic disease progression while on somatostatin analog therapy.
• Patients must have completed any major surgery at least 28 days prior to registration. Complete wound healing from major surgery should occur prior to registration.
• Patients should have improvement of any toxic effects of prior therapy (except alopecia, fatigue, and other non-reversible toxic effects such as neuropathy from cisplatin) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, grade 1 or less.
• Not pregnant and not nursing, because this study involves:
  • An investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown;
  • An agent that has known genotoxic, mutagenic, and teratogenic effects.
  • Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to registration is required.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Hemoglobin ≥ 8.0 g/dL.
• Platelet count ≥ 75,000/mm^3.
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 40 mL/min.
• Calculated by the Cockcroft-Gault equation -ION:
• Total bilirubin ≤ 2.0 x ULN.
• In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be =< 2.0 x ULN.
• Albumin ≥ 2.8 g/dL.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN.
• No known central nervous system metastases unless adequately treated, stable, and off steroid support for at least 14 days prior to registration.
• No other currently active malignancy that requires therapy or is expected to require therapy during the study (excluding non-melanoma skin cancers or in situ carcinomas, such as breast or cervical).
• No uncontrolled diabetes mellitus, defined as fasting glucose > 200 mg/dL, despite optimal medical therapy.
• No known uncontrolled hypercholesterolemia (defined as fasting cholesterol > 300 mg/dL OR > 7.75 mmol/L) or hypertriglyceridemia (defined as fasting triglycerides > 2.5 x ULN), despite optimal medical therapy -
• No known active hepatitis B (defined as hepatitis B surface antigen [HbsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) Patients with human immunodeficiency virus (HIV) positivity are allowed if CD4 count > 500 cells/uL.
• No known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to registration.
• No receipt of live attenuated vaccines in the 7 days prior to registration.
• No known liver cirrhosis.
• No known prior drug-induced pneumonitis that was symptomatic or required treatment
• No known medical condition causing an inability to swallow and no known impairment of gastrointestinal function that may significantly alter the absorption of an oral agent.
• No known hypersensitivity to everolimus or other rapamycin analogs (e.g., sirolimus, temsirolimus, etc.).
• Concurrent somatostatin analog use while on protocol therapy is allowed provided that the patient:
  • has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome);
  • has been on a stable dose of somatostatin analog therapy for at least three months;
  • has previously demonstrated radiographic disease progression while on somatostatin analog therapy. For subjects receiving lutetium Lu 177 dotatate, there should be a minimum of 14 days between long-acting somatostatin analogue and lutetium Lu 177 dotatate dosing. Short-acting somatostatin analogs should not be administered within 24 hours of lutetium Lu 177 dotatate dosing. Following lutetium Lu 177 dotatate dosing, long-acting somatostatin analogs may be administered between 4 and 24 hours after each dose.
• Chronic concomitant treatment with strong inhibitors or inducers of CYP3A4 is not allowed on this study. Patients on strong inhibitors or inducers of CYP3A4 must discontinue the drug(s) 7 days prior to registration.
• Chronic concomitant treatment with strong inhibitors or inducers of P-glycoprotein (PgP) is not allowed on this study. Patients on strong inhibitors or inducers of PgP must discontinue the drug(s) 7 days prior to registration.

RE-REGISTRATION:

• Confirmation of disease progression by RECIST v1.1 by real-time Alliance ICL at IROC Ohio central radiographic review.
• Not pregnant and not nursing.
• Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 14 days prior to re-registration is required.
• ECOG performance status 0-2.
• Hemoglobin ≥ 8.0 g/dL.
• Platelet count ≥ 75,000/mm^3.
• Absolute neutrophil count (ANC) ≥ 1,500/mm^3.
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 40 mL/min.
• Calculated by the Cockcroft-Gault equation.
• Total bilirubin ≤ 2.0 x ULN.
• In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be ≤ 2.0 x ULN.
• Albumin ≥ 2.8 g/dL.
• AST/ALT ≤ 3.0 x ULN.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

• 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.

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.

• Subjects with chronic kidney disease (estimated glomerular filtration rate < 60).
• Recruitment will primarily focus on patients with end stage renal disease who are being considered for renal transplantation or initiation of hemodialysis.
• Minorities will be included.

• Individuals < 18 years of age.
• Subjects not diagnosed with chronic kidney disease.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.

• Patients who have non-sustained or sustained VA (VA ≥ 30s or receiving appropriate ICD therapies).
• The causes of VA are associated with structural heart diseases including ischemic or nonischemic cardiomyopathy (idiopathic cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis or amyloidosis, and arrhythmogentic right ventricular dysplasia) and nonstructural heart diseases.
• Subjects 18 years of age and older.

• Female patients who are pregnant or of childbearing potential and not on a reliable form of birth control.
• Individuals allergic to skin patch electrodes.
• Vulnerable populations (fetuses, neonates, pregnant women, prisoners, institutionalized individuals).

• 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.

• Demographic characteristics: ≥ 18 and ≤ 65 years of age.
• Required laboratory results: negative pregnancy test for those with female sex assigned at birth (contraception will not be required to participate in the study).
• Health status: Schizophrenia spectrum disorder (as defined by the DSM-5; Delusional Disorder, Brief Psychotic Disorder, Schizophreniform Disorder, Schizophrenia, Schizoaffective Disorder, Catatonia, Other Specified Schizophrenia Spectrum Disorder, Unspecified Schizophrenia and Other Psychotic Disorder; but NOT Substance/Medication-Induced Psychotic Disorder or Psychotic Disorder Due to Another Medical Condition) for case group; control group can have any non-schizophrenia spectrum psychiatric illness with exceptions listed below  
• Ability to understand study procedures and to comply with them for the entire length of the study.
• Has an established mental health provider (e.g. ,integrated behavioral health, Mayo W11 psychiatric longitudinal clinic) or a follow up appointment with a new mental health provider within 2 weeks of study appointment.

• Demographic characteristics: < 18 or  ≥ 65 years of age.
• This exclusion criterion is implemented primarily to keep research team and patient safe. It is common for patients with psychosis to be agitated and sometimes violent in acute settings. It is also common for hostility/violence to be completely resolved with adequate treatment. Hence, a patient with recent violence while unmedicated, can have very low risk of violence once adequately treated. Risk of violence will be assessed on case-by-case basis for this study, taking into account legal history, documented history of hostility/violence in medical records, response to medications, medication non-compliance. Clinical judgment will be used to identify and exclude patients who pose significant risk of violence.
• Any active movement disorder that would interfere with quality TMS-EEG.
• Any confirmed or suspected history of a seizure.
• Any major neurocognitive disorder.
• Current diagnosis of Bipolar Disorder with psychotic features or Major Depressive Disorder with psychotic features.
• Current diagnosis of Autism Spectrum Disorder.
• No follow up appointments with a primary care physician or mental health provider.
• Positive pregnancy test
• Positive or presumptive positive urine drug screen test for alcohol or any illicit substance (with the exception of cannabis) at time of recruitment.
• Those with female sex assigned at birth with negative pregnancy test actively trying to become pregnant. Women who are lactating will be included, as long as the infant/toddler can be away from mother for the duration of the study (per mother’s judgement).
• Use of benzodiazepines; any antiepileptic drugs (including gabapentin, valproate, topiramate, carbamazepine, lamotrigine, etc.), opioids, and opioid antagonists.
• TMS or electroconvulsive treatment within the past 12 months, and any past significant adverse events with TMS exposure.
• Any past neuroanatomic findings of gross structural abnormalities; or such findings detected on the MRI. Gross structural abnormalities of the brain include aneurysms, tumors, encephalomalacia and other anatomic sequalae of trauma, infarcts, etc. Of note, in routine clinical practice significant anatomic abnormalities are rarely discovered in patients undergoing workup for psychosis.
• Any active substance use disorder, apart from cannabis and nicotine use disorder.
• Claustrophobia and inability to tolerate MRI (including MRI non-compatible implants, and movement disorders that would interfere with obtaining a quality MRI image).
• Inability or unwillingness of individual to give written informed consent.
• Current involuntary hospitalization as evidenced by active 72h hold; any type of ongoing commitment process (including provisional discharge, stay of commitment, awaiting commitment hearing, etc.).
• Insufficient knowledge of English.
• Any metal, electronic, or other implant that is incompatible with TMS or MRI technology.

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

Eligibility last updated 12/12/23. Questions regarding updates should be directed to the study team contact. 

• Patients with myeloid neoplasms including MDS, MDS/MPN overlap syndromes and CMML

• Any patients not meeting the above mentioned disease criteria.
• Any patient who has declined participation in research activity.
• For quarterly samples if hemoglobin is <8 gm/dl and/or HCT < 30%

• Children diagnosed with autism spectrum disorder (ASD).
• Between 2 years, 0 months to 4 years, 11 months of age.
• With less than phrased speech.
• Child must have at least one caregiver willing to participate in the study.

• Children and parents if they do not meet the above inclusion criteria.

   

• Obese men and women ≥ 20 and ≤ 45 years of age. 

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

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

Eligibility last updated 11/28/22. Questions regarding updates should be directed to the study team contact.

• Ability to provide informed consent.
• 40 patients:
  • 20 preoperative THA, 20 postoperative THA;
  • Sex: 20 men, 20 women;
  • Age: 20 patients ≥ 70 years, 10 patients 50-70 years, 10 patients 18-50 years.

• Patients with lumbosacral hardware, contralateral THA.

Eligibility last updated 11/5/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• Age ≥ 18 years.
• Histological confirmation of AL amyloidosis with adequate typing (mass spectrometry, immunohistochemistry, immunofluorescence, immunogold).
• AL amyloidosis with organ disease requiring therapy.
• NOTE: Disease requiring therapy is referred to the time of diagnosis. There are no limitations in baseline measurable disease parameters.
• Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum MASS-FIX) obtained at time of diagnosis before induction therapy initiated and available for review to be enrolled.
• NOTE: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained.
• Patients must have completed 6 cycles of Dara-CyBorD-based induction treatment ≤84 days prior to registration.
• Patients must have achieved a hematological CR (irrespective of organ response achievement) or hematological VGPR (irrespective of organ response           achievement) or hematological low-dFLC PR (irrespective of organ response             achievement) or hematological PR with at least one organ response after receiving Dara-CyBorD-based induction.
• NOTE: Patients with. baseline dFLC <5 mg/dL, must have achieved hematological CR, or dFLC <1 mg/dL or achieved organ response prior to randomization.
• Patients in whom bortezomib and/or cyclophosphamide were omitted from induction due to toxicity concerns or adverse effects are allowed. Patients must receive at least daratumumab and dexamethasone at induction to qualify for the study.
• NOTE: Dexamethasone use does not need to be carried to end of induction for eligibility consideration.
• ECOG Performance Status (PS) 0, 1, 2 or 3. 
• The following laboratory values obtained ≤28 days prior to registration:
  • Hemoglobin ≥ 8.0 g/dL;
  • Absolute neutrophil count (ANC) ≥1000/mm^3;
  • Platelet count ≥ 50,000/mm^3.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
• NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent. NOTE: Informed consent required ≤90 days prior registration.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

• Any of the following because this study involves an agent that has possible genotoxic, mutagenic and teratogenic effects:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential {and persons able to father a child} who are unwilling to employ adequate contraception.
• Received > 1 cycle of daratumumab maintenance after end of induction therapy and prior to registration.
• Multiple myeloma at time of diagnosis as defined by any of the following:
• • Hypercalcemia: Serum calcium > 1 mg/dL higher than upper limit of normal or > 11 mg/dL;
  • Renal insufficiency: Creatinine clearance < 40 mL per min or serum creatinine > 2 mg/dL attributed to high circulating light chains (i.e., cast nephropathy) or hypercalcemia;
  • Anemia: Hemoglobin > 2 g/dL below lower limit of normal, or < 10 g/dL, attributed to high marrow myeloma infiltration;
  • Bone lesions: ≥1 osteolytic lesion on skeletal x-ray, CT, or PET-CT (bone imaging is not mandatory but based on clinical suspicion);
  • Clonal bone marrow plasma cells ≥ 60%;
  • >1 focal lesion on MRI (MRI is not mandatory but based on clinical suspicion);
  • If bone imaging (CT, MRI, PET-CT) was not done at time of diagnosis it is not needed to be performed at registration to rule out bone disease;
  • ≥ 40% BMPCs irrespective of the above;
  • The study will allow patients with Involved: uninvolved sFLC ratio ≥ 100 if this is the only criteria that defines amyloidosis if all the above criteria are not met.
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]).
• NOTE:  Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
• EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy. 
• NOTE: Patients 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;
  • unstable angina pectoris;
  • psychiatric illness/social situations that would limit compliance with study requirements.

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

Eligibility last updated 12/5/23.   Questions regarding updates should be directed to the study team contact.

• Neonates with myelomeningocele who are cared for at a study center NICU are eligible to participate after myelomeningocele repair.

• Born at < 30 weeks gestation.
• Congenital anomalies that would predispose to sleep-disordered breathing (e.g., micrognathia).
• Confirmed or suspected genetic syndromes that alter developmental outcomes.

• Adult patients ≥ 18 years old.
• Willing and able to consent.
• Admitted to a hospital ward or ICU for greater than 24 hours with cirrhosis.
• Patients with cirrhosis admitted to the general ward or intensive care unit may be enrolled.
• Patient must undergo 1 or more invasive non-surgical procedures at admission or during the hospitalization.

• Age < 18 years old.
• Prisoner.
• Pregnant.
• Previously enrolled in this study.
• Unable to consent.

• Adult patients with presence of NAFLD associated cirrhosis.
• Cirrhosis: biopsy confirmed or Agile F (F4) score > 0.45.
• NAFLD as the etiology of cirrhosis (any of the following below) NAFLD as an etiology of liver disease will be determined based on presence of any of the following:
  •Biopsy showing > 5% steatosis or
  •CAP > 280 dB/m or MR-PDFF> 5%
  •If CAP < 280 dB/m or MR-PDFF < 5%, then must have type 2 diabetes and or 2 or more features of metabolic syndrome for 5 years (cryptogenic cirrhosis)
• Rationale for Study
  Inclusion Criteria:
  The study will focus on stage 4 fibrosis (i.e. cirrhosis) because they have the highest unmet need. The F4 score is based on LSM, platelets, AST:ALT ratio, diabetes status and sex; many of these parameters are accepted by regulatory standards to represent a non-invasive diagnosis of cirrhosis (54). The attribution of NAFLD as cause of cirrhosis and criteria for cryptogenic cirrhosis meet regulatory standards and are accepted for inclusion in clinical trials (55). NIT-based diagnosis of cirrhosis is included to ensure that data are generalizable to populations seen in routine practice where biopsies are not done and diagnoses made with NIT.

• Refusal to consent.
• Alcohol use > 14/21 gm/week cutoff.
• Other causes of chronic liver disease.
• MELD > 12.
• Hepatic and extrahepatic cancers expected to limit life expectancy < 2 yrs.
• Prior hepatic resections, TIPS, splenic embolization.
• Prior decompensation events.
• Inability to fit in to MRI (failed hula-hoop test).
• Contraindications for MRI.
• General contraindication for MRI contrast (GFR < 30 ml/min).
• Pregnancy.

Rationale for exclusion criteria: The exclusion criteria are designed to meet ethical (refusal to consent), etiology (alcohol and other etiologies), clinical (factors likely to lead to death before a liver event e.g. cancers) and MRI-related (hula-hoop, GFR that precludes MRI) factors.

Eligibility last updated 7/27/22. Questions regarding updates should be directed to the study team contact.

• Mayo Clinic patients with a previously confirmed infection with the novel SARS-CoV-2 virus who have been seen in the PCCOC, CARP, Pulmonary for post COVID clinic, Neurology, or approval by MAGPIES research group.
• Aged 5 years and older.
• All racial and ethnic groups are eligible.

• Lacking the capacity to consent.
• Prisoners and institutionalized individuals.

Eligibility last updated 9/8/21. Questions regarding updates should be directed to the study team contact.

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Eligibility last updated 4/27/23. Questions regarding updates should be directed to the study team contact.

Affected subjects, healthy family members, and healthy unrelated subjects will be recruited to the study.  In many cases in data analysis the healthy unrelated subjects will be used as the “control” population

Study subjects will inform their family and friends of this type of research.  If those unaffected individuals would like to participate the study subjects will inform their treating physician or the PI.

Subject population - Cardiothoracic transplant patients (pretransplant and follow-up), heart failure patients and patients prior to and on mechanical circulatory support take part in this study.

• Those who have signed informed consent. 

• Those who have not signed informed consent.

Inclusion Criteria for Controls.

• Healthy male (N=30) and female (N=30) volunteers aged 18-80 years.

• Having capacity to provide written informed consent before participating in the study.

• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Inclusion Criteria for Constipated Patients.

• Male and female volunteers aged 18-80 years.

• Individuals with chronic constipation for 1 year, with 2 or more of the following symptoms for 3 months or longer: <3 bowel motions/week, straining ≥ 25% of time, hard or lumpy stools ≥ 25% of time, incomplete evacuation ≥ 25% of time, feeling of anorectal blockage ≥ 25% of time.

• Having capacity to provide written informed consent before participating in the study.

• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

Exclusion Criteria for Controls (Items indicated with an asterisk are also exclusion criteria for patients).

• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns.*

• Current symptoms of a functional gastrointestinal disorder assessed by questionnaire [2, 16].

• Putative risk factors for pelvic floor trauma: i.e. six or more vaginal deliveries, birthweight >4500gms (macrosomia), or known 3rd or 4th degree perineal tear.

• Medications that are likely to alter gastrointestinal motility: e.g., opiates, anticholinergic medications, serotoninergic agents, alpha adrenergic agonists, calcium channel or b blockers; a stable dose of thyroxine will be permitted (i.e. no alterations in dose for the preceding three months).

• Active rectal inflammation, cancer; perianal sepsis; history of pelvic radiation, rectosigmoid surgery or inflammatory bowel disease.*

• Anxiety or depression as assessed by the Hospital Anxiety and Depression Questionnaire [17].

• Contraindications for MR imaging: i.e. pacemakers, aneurysm clips, cochlear implants.*

• Pregnant women, prisoners and institutionalized individuals.*

   

• All patients who have undergone arthroscopic shoulder surgery between 1996-2015.

• Arthritis, Infection