• Metastatic, histologically confirmed well-differentiated neuroendocrine tumor with positive gallium 68 Dotatate scan within 6 months. Lesions on gallium 68 Dotatate scan will be considered positive if the SUVmax is > 2 times SUV mean of normal liver parenchyma.
• Failure of at least one prior systemic cancer treatment, including somatostatin analogs.
• Patients must have progressive disease based on RECIST Criteria, Version 1.1 evidenced with CT scans/MRI obtained within 24 months from enrollment.
• Patients must have measurable disease per RECIST 1.1.
• No prior exposure to peptide receptor radionuclide therapy.
• Recovered from adverse events of previously administered therapeutic agents to Grade 1 or less toxicity according to CTCAE version 5.0.
• Archival tissue no longer than 6 months old should be present, otherwise baseline research biopsy is needed for WES.
• Age ≥ 18 years.
• Because no dosing or adverse event data are currently available on the use of triapine in combination with Lutetium Lu 177 Dotatate in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status 0,1, or 2 (Karnofsky ≥ 60%).
• Patients must have adequate organ and marrow function as defined below:
  • leukocytes                                     ≥ 2,000/mcL;
  • absolute neutrophil count              ≥ 1,500/mcL;
  • platelets                                         ≥ 75,000/mcL;
  • total bilirubin                                  ≤ 3 × institutional upper limit of normal (ULN);
  • AST(SGOT)/ALT(SGPT)               ≤  3 × institutional ULN;
  • glomerular filtration rate (GFR)     ≥ 50 mL/min using Cockroft-Gault method;
  • hemoglobin                                   ≥ 8.0 g/dL.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen, in the opinion of the enrolling physician, are eligible for this trial.
• Pregnancy Precaution: Men and women should avoid pregnancy for seven months after the date of their last treatment with Lutetium Lu 177 Dotatate. It is noteworthy that β- HCG may be secreted by a small percentage of NETs, such that, in addition to being a pregnancy marker, it also is a tumor marker. Consequently, NET female patients with positive β-HCG (>5 mIU/mL) at baseline can be eligible to enter the study and receive treatment if pregnancy can be excluded by lack of expected doubling of β-HCG and negative pelvic ultrasound. Normally, in pregnant subjects β-HCG doubles every 2 days during the first 4 weeks of pregnancy and every 3.5 days by Weeks 6 to 7. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral ovariectomy) or is not postmenopausal (defined as amenorrhea > 12 consecutive months, and for women on hormone replacement therapy, only with a documented plasma follicle-stimulating hormone (FSH) level > 35 mIU/mL). Even women who are using oral, implanted, or injected contraceptive hormones, an intrauterine device (IUD), or barrier methods (diaphragm, condoms, spermicidal) to prevent pregnancy, are practicing abstinence or where the partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential. Postmenopausal women who have fertilized eggs implanted are also considered to be of childbearing potential. Acceptable methods of contraception may include total abstinence at the discretion of the Investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance.
• Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception (hormonal or barrier method of birth control; abstinence) should be maintained throughout the study and for 7 months after study treatment discontinuation. All women of childbearing potential and male partners must use a double-barrier method of birth control or practice continuous abstinence from heterosexual contact throughout the study and for seven months after the end of the last treatment.
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally- authorized representative (LAR) and/or family member available will also be eligible.

• Individuals < 18 years old.
• Patients who have had major surgical procedures in the prior 6 weeks.
• Patients with an inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents.
• Patients who have received prior external beam radiotherapy to more than 50% of bone marrow, as determined by a radiation medicine physicist who will calculate the volume of bone marrow exposure in prior radiotherapy portals divided by the volume of total bone marrow harboring tissues. This ratio must be less than 50 percent.
• Uncontrolled congestive heart failure (NYHA III, IV).
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or Lutetium Lu 177 Dotatate.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection; symptomatic decompensated congestive heart failure; unstable angina pectoris; cardiac arrhythmia; and known inadequately controlled hypertension.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because triapine is an RNR inhibitor and Lutetium Lu 177 Dotatate is a peptide receptor radionuclide therapy with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine and Lutetium Lu 177 Dotatate, breastfeeding should be discontinued if the mother is treated with triapine and Lutetium Lu 177 Dotatate and for 2.5 months following the last treatment.
• Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating Lutetium Lu 177 dotatate. Long-acting somatostatin analog will be allowed to continue if patient has history of carcinoid syndrome and requires long- acting somatostatin analog for control of his/her functional syndrome.

• 18 years of age or older at the time of consent.
• Healthcare Professional at Mayo Clinic.
• Not pregnant by participant self-report at time of consent.
• Have the ability to provide informed consent.
• Have no contraindicated comorbid health conditions as determined by the clinical investigators.

• Currently (within the past 3 weeks) been practicing mindfulness training on a weekly/regular basis.
• Currently (within the past 3 weeks) been undergoing an additional program (e.g., Complementary and Alternative Medicine [CAM]) to improve quality of life.
• Currently (within 3 weeks) been enrolled in another clinical or research program (e.g., CAM) which impacts the patients’ quality of life (QOL), stress or anxiety.
• Currently has photosensitivity.
• Cannot tolerate virtual reality experiences.
• An unstable medical or mental health condition as determined by the physician investigator (e.g., pre-existing eye strain, seizures, dizziness, nausea).

• Adult patients with non-traumatic hemispheric brain lesions deemed at risk for progression of mass effect and possible subfalcine and/or uncal herniation.
• Patients admitted the Neuroscience ICU for serial neurological monitoring.
• Patients whose care is not expected to include immediate surgical decompression.

• Patients under the age of 18.
• Patients who are unable to provide consent due to neurologic deficit and does not have a surrogate decision maker available to provide consent.

• Age ≥ 18 years of age.
• Precapillary pulmonary hypertension with mean PA pressure > 20 mmHg and planned initiation of pulmonary arterial hypertension therapy.
• No active treatment for precapillary pulmonary hypertension.
• Ambulatory (not wheelchair / scooter dependent).
• Presence of any risk factor for left heart disease will qualify for inclusion (either atrial fibrillation, body mass index > 30 kg/m^2, arterial hypertension, diabetes, coronary artery disease or age > 60 years).

• Significant chronic obstructive pulmonary disease that is a primary contributor to symptoms in the opinion of the investigator.
• Ischemia thought to contribute to dyspnea in the opinion of the investigator.
• Obstructive hypertrophic cardiomyopathy.
• Known infiltrative cardiomyopathy (amyloid).
• Constrictive pericarditis or tamponade.
• Active myocarditis.
• Complex congenital heart disease.
• More than mild aortic or mitral stenosis.
• Intrinsic (prolapse, rheumatic) valve disease with more than moderate mitral, tricuspid or aortic regurgitation.
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR > 1.7 in the absence of anticoagulation treatment.
• Terminal illness (other than HF) with expected survival of less than 1 year.
• Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
• Inability to comply with planned study procedures.
• Pregnancy or breastfeeding mothers.

• Adults, ≥ 18 years of age.
• Patients who were diagnosed with hypertrophic cardiomyopathy with systolic cavity obliteration and underwent transapical septal myectomy to enlarge the left ventricular (LV) cavity.

• Individuals < 18 years of age.

• All patients seen by Doctor Rafael Sierra and Robert Trousdale in clinic.
• Between the ages of 12 and 65 years of age.

• Individiuals under the age of 12 and over the age of 65 years.

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 who are implanted with a brain stimulation device per Mayo Clinic standard of care.

• Patients for whom clinical follow-up is not expected during the initial 6-8 months following implant.

Inclusion Criteria:

• Age 18 years or older.
• Consenting to research.
• Chronic kidney disease (stages 1-5).
• An SPPB score ≤ 10 or considered frail or pre-frail according to the Fried Frailty Phenotype.

Exclusion Criteria: 

• Younger than 18 years.
• Patients being evaluated for combined organ transplantation.
• Significant comorbidities that limit rehabilitation potential including pulmonary disease requiring continuous oxygen supplementation, active angina, critical aortic sclerosis, decompensated heart failure, or known ventricular arrhythmia.
• An SPPB score > 10 or not considered frail or pre-frail by the Fried Frailty Phenotype.
• Non-English speaker without availability of adequate interpreter services (safety concern).
• Failure to pass submaximal exercise test in pateints not approved for kidney transplantation at our center.

• Adults and adolescents (aged ≥ 12 years.
• Children 6 to 11 years of age.
• Children 2 to 5 years of age.
• Infants and newborns from birth to < 2 years of age.
• Documented diagnosis of PH1 or PH2, confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
• Estimated GFR at Screening < 30 mL/min normalized to 1.73 m^2 BSA.  For infants aged less than 12 months, serum creatinine above the 97th percentile of a healthy population (Boer et al., 2010).
• Median of 3 plasma oxalate values > 30 µmol/L during Screening.
• Less than 20% variation from the median Screening period Pox value.
• For participants receiving hemodialysis or peritoneal dialysis, total duration of hemodialysis or peritoneal dialysis must be less than or equal to 18 months and hemodialysis or peritoneal dialysis regimen must have been stable for at least 3 months prior to Screening.
• Body weight of:
  • Adults and adolescents aged ≥ 12 years: ≥ 31.0 kg;
  • Children 6 to 11 years of age: to be determined;
  • Children 2 to 5 years of age: to be determined;
  • Infants and newborns from birth to < 2 years of age: to be determined.
• Male participants: A male participant with a female partner of childbearing potential must agree to use contraception during the treatment period and for at least 12 weeks after the last dose of study intervention and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP);OR
  • A WOCBP who agrees to follow the contraceptive guidance for the 4 weeks prior to randomization, during the treatment period, and for at least 12 weeks after the last dose of study intervention and agrees to refrain from harvesting/freezing eggs during this period. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Participant (and/or participant’s parent or legal guardian if participant is a minor [defined as patient < 18 years of age, or younger than the age of majority according to local regulations]) is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  • Adolescents (12 to < 18 years of age, or older than 12 years but younger than the age of majority according to local regulations) must be able to provide written assent for participation;
  • For children younger than 12 years of age, assent will be based on local regulations.
• Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations).

• Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Renal transplantation planned in the 6 months from Day 1. Prior renal transplantation is allowed.
• Known history of severe systemic oxalosis.
• Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact patient safety including, but not restricted to:
  • Severe intercurrent illness;
  • Known causes of active liver disease/injury (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis);
  • Non-PH related conditions contributing to renal insufficiency;
  • Physician concerns about intake of drugs of abuse or excessive alcohol intake, or history of excessive alcohol intake in the 2 years prior to enrollment (defined as ≥ 21 units of alcohol per week in men and ≥ 14 units of alcohol per week in women; where a “unit” of alcohol is equivalent to a 12-ounce beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor).
• Use of an RNAi drug, other than DCR-PHXC, within the last 6 months.
• History of one or more of the following reactions to an oligonucleotide-based therapy:
  • Severe thrombocytopenia (platelet count ≤ 100,000/µL);
  • Hepatotoxicity, defined as alanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the upper limit of normal (ULN) and total bilirubin > 2 × ULN or international normalized ratio (INR) >1.5;
  • Severe flu-like symptoms leading to discontinuation of therapy;
  • Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy;
  • Coagulopathy/clinically significant prolongation of clotting time.
• Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening.
• Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender.
• Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody test at Screening.
• Known hypersensitivity to DCR-PHXC or any of its ingredients.
• Inability or unwillingness to comply with the specified study procedures, including lifestyle considerations.

• Written informed consent by subject or legally authorized representative.
• At least 18 years of age.
• Cirrhosis and ascites.
• No sustained improvement in renal function (less than 20% decrease in SCr) at least 48 hours after diuretic withdrawal and after plasma volume expansion with albumin (given daily for two days
  •48 hours minimum from 1st dose).If SCr improves by ≥ 20 % but plateaus ( ≤ 10 % fluctuation in sCr) and remains above 1.5 mg/dl for ≥another 48 hrs and there are no features of acute tubular necrosis.
• Increase in SCr by at least ≥ 0.3 mg/dl OR 1.5-2 fold above baseline (AKI stage 1 and above), to a SCr of ≥ 1.5 mg/dl at the time of initiating treatment. Baseline SCr is defined as the most recent, lowest SCr within last 6 months before date of current admission.
• On liver transplant wait list or liver transplant eligible with anticipation of being placed on the liver transplant wait list.
• Patients not on the transplant waitlist or transplant eligible are also eligible for the trial (maximum 25 subjects)

• Serum creatinine level greater than 5.0 mg/dL. Subjects with value greater than 5.0 mg/dL may be enrolled with Sponsor prior approval.
• MELD score of ≥ 35.
• Acute on Chronic Liver Failure (ACLF) grade 3 (according to the CLIF Consortium grading system).
• Uncontrolled sepsis and/or uncontrolled bacterial infection (e.g., persisting bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with vasomotor instability).
• Shock.
• Current or recent (within 4 weeks) treatment with or exposure to nephrotoxic agents; e.g., aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen, diclofenac), significant exposure to radiographic contrast agents (large doses or multiple injections of iodinated contrast media; e.g., during coronary or abdominal angiogram).
• Estimated life expectancy of less than 7 days.
• Advanced hepatocellular Carcinoma with expected life expectancy of < 6 months.
• Superimposed acute liver injury due to drugs (e.g., acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins (e.g., Amanita toxin with mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic hepatitis.
• Evidence of obstructive uropathy or parenchymal renal disease. Renal ultrasound or other imaging not required but should be taken if suspicious.
• Tubular epithelial casts, heme granular casts (range of 1-3 granular casts acceptable), hematuria or microhematuria on urinalysis that is indicative of acute tubular necrosis and/or intrinsic renal disease.
• Subjects known to be pregnant; all women of child-bearing age and potential must have a negative pregnancy test.
• Severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure, or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the investigator to be severe and creates a risk to subject with concurrent terlipressin use.
• Current or recent (within 4 weeks) renal replacement therapy (RRT) or anticipation of RRT within 3 days on enrollment.
• Participation in other clinical research involving investigational medicinal products within 30 days of starting study drug that would adversely affect participation in this or the current trial.
• Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of starting study drug.
• For the Prospective Group: All vasopressors must be stopped prior to treatment with terlipressin. Use of vasopressors (e.g., norepinephrine, epinephrine or vasopressin dopamine or other vasopressors) of ≥ 3 consecutive days within the prior 14-day screening period are excluded. Patients receiving a vasopressor other than midodrine within 24 hours of qualifying SCr are excluded; i.e, a 24-h washout is required prior to enrollment.
  • Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to enrollment.
• Known allergy or sensitivity to terlipressin.

Eligibility last updated 8/11/21.  Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

• Patients with unilateral or bilateral cochlear implantation or auditory brainstem implantation that were implanted at Mayo Clinic, Rochester.

• Not able to provide consent for self to participate.
• Patients that declined MN research authorization.

• Adults age 18 and over
• Patients with an endoprosthesis.

• Patients without an endoprosthesis.

Inclusion Criteria
•Stroke Survivors:

• Age ≥ 18 years old.
• Admitted to Mayo Clinic Rehabilitation Unit with diagnosis of stroke or brain tumor.
• English fluency.
• No diagnosed severe cognitive impairment (determined through clinician report and/or medical record documentation).
• Provide written (paper or electronic) informed consent.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Have ability to utilize the technology to watch online modules.

Inclusion Criteria
•Caregivers:

• Age ≥ 18 years old.
• English fluency.
• Identifies as a caregiver for a stroke survivor or person with BT and lives with the care recipient at least 50% of the time.
• No diagnosed severe cognitive impairment (determined through self report).
• Have ability to utilize the technology to watch online modules.

• Individuals < 18 years old.
• As determined through self-report, those diagnosed with a history of a psychotic episode.
• Documented psychological comorbidities such as untreated schizophrenia, bipolar disease.

• Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.
• Age ≥ 18 years at the time of informed consent.
• Satisfy the following:
  • Females: must be non-pregnant and non-lactating and either:
    • surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
    • post-menopausal (defined as 12 months of spontaneous amenorrhea in females > 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved)
    • abstinent*; or
    • if engaged in sexual relations and of child-bearing potential, agree to use highly effective contraceptive methods from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug (ION251).
  • Males: Surgically sterile or if engaged in sexual relations with a female of child-bearing potential, either the patient or their female partner is utilizing a highly effective contraceptive method from the time of signing the informed consent form until at least 13 weeks after the last dose of Study Drug (ION251).

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

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Measurable multiple myeloma (MM) et al. defined as at least one of the following: serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours or serum free light chain level ≥ 10 mg/dL (provided the serum free light chain ratio was abnormal).
• In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM.  Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose of treatment (Rajkumar et al. 2011).
• Has an estimated life expectancy of at least 12 weeks.
• Have recovered from all toxicities of prior therapy to ≤ Grade 1 (or baseline) by Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (exceptions: peripheral neuropathy ≤ Grade 2 and any toxicities that in the view of the Investigator is not a clinically significant (CS) safety risk for further therapy administration, such as but not limited to: alopecia, fatigue, erectile dysfunction, hot flashes, cough, and urinary incontinence).
• Termination from prior line of multiple myeloma therapy at least 14 days before first administration of ION251 (i.e., Cycle 1 Day 1).

• Clinically significant abnormalities in medical history (e.g., acute coronary syndrome within 6 months of Screen, major surgery within 3 months of Screen) or physical examination.
• Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a patient unsuitable for inclusion:
  • ALT or AST > 2 × ULN;
  • Total bilirubin > 1.3 × ULN (patients with Gilbert’s Syndrome may be eligible if direct bilirubin < 1 × ULN and results reviewed with the Medical Monitor);
  • Absolute neutrophil count ≤ 1.0 k/mm^3;
  • Platelet count < 50 k/mm^3;
  • Hemoglobin < 8.0 g/dL;
  • Estimated glomerular filtration rate (eGFR, by CKD-EPI equation < 50 mL/min/1.73 m^2 );
  • Urine albumin creatinine ratio > 100 mg/g.
• Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.
• Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
• Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B. Antibody positivity for HCV is allowed if patient is below detection limit for plasma or serum HCV RNA, is not currently receiving antiHCV therapy, and has not received such therapy for > 6 months.
• History of or current plasma cell leukemia defined as > 2.0 × 10^9 /L circulating plasma cells by standard differential, clinically significant light chain amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm.
• History of atypical hemolytic uremic syndrome.
• Blood or platelet transfusion during the 6 days prior to Screen.
• Treated or untreated parenchymal brain metastases or leptomeningeal disease. Current active malignant epidural disease is also excluded. Previously treated epidural disease does not exclude the patient from study as long as disease is inactive.
  • Note: CT or magnetic resonance imaging (MRI) of brain is not needed to rule these out unless the patient has clinical symptoms suggestive of CNS metastases.
• Uncontrolled hypertension (systolic pressure ≥ 160 mm Hg and/or diastolic pressure ≥ 100 mm Hg).
• Presence or history of malignancies other than multiple myeloma, except non-melanoma skin cancers or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 3 years may also be eligible.
• Treatment with another investigational drug, biological agent, or device within 14 days before first administration of ION251 (i.e., Cycle 1 Day 1).
• Previous treatment with an oligonucleotide (including small interfering ribonucleic acid [siRNA]) within 4 months of Screen if single dose received, or within 12 months of Screening if multiple doses received.
• Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
• Recent history of, or current drug or alcohol abuse.
• QTc interval > 470 msec during Screen.
• Concurrent treatment with anti-myeloma drugs or biologicals (exception: ongoing treatment with bisphosphonates and RANK-ligand inhibitors is allowed provided dose regimen has been stable for the ≥ 4 weeks before first administration of ION251).
• Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the patient unsuitable for inclusion, or could interfere with the subject participating in or completing the Study.

Eligibility last updated 8/31/21. Questions regarding updates should be directed to the study team contact.

• Patients with a locally advanced or metastatic malignancy, that has progressed following systemic therapy for their disease, if available, or for which the patient is not a candidate or refuses.
• Tumors harboring a MEK or atypical BRAF alteration.
• Provide signed and dated informed consent prior to initiation of any study-related procedures that are not considered standard of care (SoC).
• Male or female patients, aged ≥ 18 years.
• Patients must have measurable disease by RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0
  •2.
• Adequate renal function [creatinine ≤ 1.5 times ULN (upper limit of normal)] or a glomerular filtration rate (GFR) of ≥ 50 mL/min (using Cockcroft-Gault).
• Adequate hepatic function [total bilirubin ≤ 1.5 times ULN; AST (aspartate transaminase) and ALT (alanine transaminase) ≤ 3 times ULN or ≤ 5 times ULN if the elevation is due to liver involvement by tumor].
• Adequate bone marrow function:
  • Hemoglobin ≥ 9.0 g/dL;
  • Platelets ≥ 100 x 10^9 cells/L;
  • Absolute neutrophil count ≥ 1.5 x 10^9 cells/L).
• Adequate cardiac function:
  • Left ventricular ejection fraction (LVEF) of > 50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and a corrected QT interval (QTc) < 480ms by the Fridericia method (QTcF).
• Contraception
  •women:
  • Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal (no menstrual cycle for at least 12 consecutive months), or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug. Abstinence is not considered an adequate contraceptive regimen.
• Contraception
  •men:
  • Must be surgically sterile, or compliant with a medically approved contraceptive regimen during and for 3 months after the last administration of study drug.
• Willing and able to participate in the trial and comply with all trial requirements.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational agent may be included after consultation with the medical monitor.

• Gastrointestinal (GI) condition that could impair absorption of study medication (specific cases; e.g., remote history of GI surgery, may be enrolled after discussion with the medical monitor) or inability to ingest study medication.
• Uncontrolled or severe intercurrent medical condition.
• Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change in the previous 4 weeks, can be allowed.
• Having received any cancer-directed therapy (chemotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. Patients previously treated with radiotherapy must have recovered from the acute toxicities associated with such treatment.
• Major surgery within 4 weeks prior to first dose.
• Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 10 days between termination of the prior investigational drug and administration of study drug is required. In addition, any drug-related toxicity except alopecia should have recovered to Grade 1 or less.
• Prior therapy with any ERK inhibitor (e.g., LY3214996, LTT462).

Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g., encorafenib, dabrafenib, vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior BRAF and/or MEK inhibitor therapy is permitted for Groups 5 and 6.

• For Part B, agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician's choice.
• Pregnant or breast-feeding women.
• Any evidence of serious active infections. Patients are allowed to enroll if they have been fever-free for at least 48 hours and are on an active treatment that is not prohibited in the protocol.
• Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study (based on the investigator's judgment).
• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
• Concurrent therapy with any other investigational agent.
• Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, and CYP3A4.

• 18 years of age or older.
• Severe mitral annular calcification with severe mitral stenosis defined as mitral valve area (MVA) of ≤ 1.5 cm^2, or moderate to severe or severe mitral regurgitation.
• NYHA Functional Class ≥ II.
• The heart team agrees that valve implantation will likely benefit the patient.
• High or prohibitive risk for standard mitral valve surgery as determined by the heart team (at least one site cardiac surgeon must personally examine the subject to determine operative risk).
• The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
• The study patient agrees to comply with all required post-procedure follow-up visits including annual visits through 5 years and analysis close date visits, which will be conducted as a phone follow-up.

• The heart team considers the patient is a surgical candidate.
• Mitral annulus is not calcified.
• Myocardial infarction requiring revascularization within 30 days from procedure.
• Clinically significant untreated coronary artery disease requiring revascularization.
• Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease). Implantation of a permanent pacemaker is not excluded.
• Any patient with a balloon valvuloplasty (BMV) within 30 days of the procedure (unless BMV is a bridge to procedure after a qualifying Echo).
• Severe tricuspid regurgitation requiring surgery.
• Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), Thrombocytopenia (Plt < 50,000 cell/mL), history of coagulopathy or hypercoagulable state.
• Hypertrophic obstructive cardiomyopathy (HOCM) with mean LVOT gradient of ≥ 20 mm Hg at rest or ≥ 50 mmHg with Valsalva.
• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of screening evaluation.
• Need for emergency surgery for any reason.
• Severe left ventricular dysfunction with LVEF < 20%.
• Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
• Active upper GI bleeding within 90 days prior to procedure.
• A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be anticoagulated for the study procedure.
• Cardiac anatomy that would preclude appropriate delivery and deployment of a SAPIEN 3 or SAPIEN 3 Ultra valve in MAC via transseptal access, including but not limited to:
  • Native neo mitral annulus size < 275 mm^2 or > 810 mm^2 as measured by CT scan;
  • Significant risk of LVOT obstruction or valve embolization as assessed by CT core lab.
• Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 90 days of the procedure.
• Estimated life expectancy < 12 months due to non-cardiac conditions.
• Expectation that patient will not improve despite treatment of mitral valve dysfunction.
• Active bacterial endocarditis within 180 days of procedure.
• Severe right ventricular dysfunction as assessed by Echo core lab 22.
• Active infection requiring antibiotic therapy (subject may be a candidate after 2 weeks of antibiotic discontinuation.
• Female who is pregnant or lactating.
• Participating in another investigational device study.
• Aortic valve disease requiring intervention.
• Severe fixed pulmonary hypertension (PASP ≥ 70 mmHg).
• Severe chronic obstructive pulmonary disease requiring continuous home oxygen.

• Age, 18-65 years.
• Diagnosis of BD-I or BD-II, or SCZ-BD by DSM-IV (SCID confirmed). Participants of the Bipolar Biobank (IRB # 08-008794) are patients with existing SCID results and participants enrolling to the MoStGEN protocol (IRB # 20-001658) are required to complete a SCID; thus they will not be required to repeat the SCID assessment. Only patients without a previous SCID will be interviewed to complete it.
• Subjects willing to provide consent to be blood-tested for SARS-CoV-2 IgG/IgM on each of the three visits.

• Inability to understand English.
• Inability or unwillingness to provide informed consent or scoring less than 80% on the comprehension assessment (CA) form.
• Unwilling to consent to providing bio-specimens to be stored in the biobank for an indefinite amount of time and to be used in future research studies of as yet unknown design.
• Actively psychotic (i.e., paranoia, perceptual disturbances, delusional ideas, impaired judgment) or active suicidal behavior (including suicidal ideation or planning).
• Involuntary patients.
• Women with known pregnancy. (Due to the lack of conclusive data regarding the quality of antibody response during pregnancy, we considered it appropriate the exclusion of women with known pregnancy from this study).

• Subjects between the ages of 30 days (non-inclusive) and 99 years (inclusive).
• Patients with a new diagnosis of sinonasal cancer.
• Patients undergoing treatment at Mayo Clinic, Rochester, MN.

• Healthy individuals.
• Unwilling to sign the informed consent.

Key Inclusion Criteria:

• Patients that receive brain stimulation for evaluation or treatment of neurological diseases including intractable epilepsy, chronic pain syndromes and brain tumors.

Key Exclusion Criteria: 

• Patients that do not receive brain stimulation for evaluation or treatment of neurological diseases including intractable epilepsy, chronic pain syndromes, and brain tumors.

   

• Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Is between the ages of 18 and 80 years, inclusive.
• Has had RCC (including unexplained chronic cough) for at least 1 year prior to screening, defined as follows:
  • insufficient improvement in cough after treatment for the underlying condition causing the cough; OR
  • unexplained cough for which an underlying condition has not been determined.
• Has had a chest radiograph or CT thorax within the 5 years before screening and following the onset of chronic cough that does not show any abnormality considered to be significantly contributing to the chronic cough, as per the investigator opinion.
• Has an awake cough frequency of ≥25 coughs/hour at screening and at Day –6. For the low-cough cohort, awake cough frequency of ≥ 10 to < 25 coughs/hour at screening and at Day -6.
• Has a score of ≥4 0 mm on the Cough Severity VAS at screening and at Day 1.
• If a woman of childbearing potential has a negative serum β-HCG pregnancy test conducted during screening.
• Highly effective methods of birth control in this study include:
  • combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation;
  • intrauterine device;
  • intrauterine hormone-releasing system;
  • bilateral tubal occlusion;
  • vasectomized partner.
• If a male, agrees to make no donation of sperm from screening until 3 months after the last dose of study treatment and agrees to use condoms during intercourse from screening to the follow-up visit.

• Female participants who are pregnant, trying to become pregnant, or lactating.
• Current smoker/vaper or current use of the following inhaled substances (e.g., tobacco or cannabis smoke, nicotine vapors).
• Individuals who have given up smoking or vaping within the past 6 months, or those with a > 20 pack-year smoking history.
• Diagnosis of COPD, bronchiectasis, or idiopathic pulmonary fibrosis based on clinician assessment.
• Uncontrolled asthma defined as one or both of the following:
  • ≥ 1 exacerbation in the last 6 months or ≥ 2 exacerbations in the last 12 months;
  • Use of rescue medication ≥ 3 days per week or night waking >1 time per week (Pre-exercise prophylactic medication use will not be considered rescue medication).
• Pre-bronchodilator FEV1/FVC <60% at screening or on spirometry testing performed within the 2 years before screening and following the onset of chronic cough.
• Participants who fail to use the cough monitor or who are confirmed to have incorrectly recorded 24-hour cough frequency at screening or baseline visits.
  • Note: A single retest will be allowed for the purpose of eligibility at screening or Day -6 in the event that insufficient recording time is captured to assess cough frequency. If insufficient time is recorded at baseline, a retest may be performed only if retesting will occur within the protocol-defined window for the Day -6 visit. Incorrectly recorded 24-hour cough frequencies are defined as recordings where less than 20 hours of the recording can be assessed for cough frequency. 
• History of upper and/or lower respiratory tract infection or recent significant change in pulmonary status within 28 days of screening.
• Current active tuberculosis or nontuberculous mycobacterial infection, a history of latent untreated tuberculosis, or a history of incompletely treated tuberculosis.
• Laboratory-confirmed SARS-CoV-2 infection at screening or Day -6.
• History of SARS-CoV-2 infection or COVID-19 within 3 months of screening or known exposure to someone with SARS-CoV-2 infection or COVID-19 within 1 month of screening.
• Medical history of hypogeusia/dysgeusia/ageusia or known presence of a dysfunction in the ability to taste, including loss of taste secondary to SARS-CoV-2 infection.
• Screening SBP > 160 mm Hg or a DBP > 90 mm Hg.
• Clinically significant abnormal ECG at screening, per investigator discretion.
• Prolonged corrected QT (QTcF) interval (Men: > 450 ms; Women: > 470 ms) at screening.
• Clinically significant abnormal laboratory tests at screening, including the following:
  • Alkaline phosphatase, ALT/SGPT, AST/SGOT > 1.50 × the ULN;
  • GGT > 2.0 × ULN;
  • Total bilirubin above ULN;
  • Creatinine > 2.0 × ULN;
  • Unexplained creatine kinase concentration > 3 × ULN, per investigator discretion;
  • Hemoglobin < 10 g/dL, WBC count < 2500 mm^3;
  • Neutrophil count < 1500 mm^3;
  • Platelet count < 100 × 10^3/mm^3.
  • Note: One repeat laboratory test may be permitted following discussion with the medical monitor.
  • Note: Participants with neutrophil count >1000 mm^3 and a diagnosis of benign ethnic neutropenia will be eligible.
• Positive serological test for HIV, hepatitis B (hepatitis B surface antigen), or hepatitis C.
  • Note: Participants with positive hepatitis B or C serology will have confirmatory testing with hepatitis B or C RNA PCR.
• Acutely ill or febrile 24 hours prior to or at the screening visit. Fever is defined as a body temperature ≥ 38.0°C/100.4°F.
• Medical history of malignancy ≤ years prior to screening, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, in the opinion of the investigator.
• History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years, per investigator assessment or a positive urine drug result at screening. If urine drug screen at screening is positive for cannabinoids the patient should be asked about route of administration, as smoking is an exclusion criterion however oral use is acceptable.
• Has a known allergy/sensitivity or contraindication to BLU-5937 or any of its excipients.
• Previous participation in an investigational study of BLU-5937.
• Any current usage of biologics. Previous use that ended > 90 days prior to screening may be allowed if approved by the medical monitor.
• Treatment with any other investigational products within the 3 months before first dose of study treatment.
• Participants who are considered ineligible to participate in the study for any other reason, based on the investigator’s judgment.
• Noncompliance (< 80%) with single-blind, placebo, run-in medication up to Day 1.

• Tapestry patients who have received genetic results, regardless of positive or negative testing results.
• Age of 18 and older.
• Patients with an established Mayo Clinic provider prior to their enrollment in Tapestry.

• Individuals less than 18 years old.
• Patients without capacity to consent (i.e., needing legal authorized representatives).
• Prisoners.
• Subjects eligible for chart review, without a Minnesota Research Authorization on record.

• Participants will be adults 60 years old and older.
• Have requested a home safety evaluation from Family Service Rochester and are willing to participate in the Build Better Balance exercise program.
• Participants will be included if they are 60 years old and older.
• Can speak conversational English.
• Able to complete interviews and questionnaires over the phone or video chat
• Read workbook materials (English translation is only available) and ambulate independently with or without a gait aide. Inclusion criteria will further include any risk factors for falling (such as fear of falling, history of falls within the last 12 months or polypharmacy).
• These inclusion criteria are broad in order to reflect older adults that are aging and have a fall risk potential.

• Individuals will be excluded if they are unable to answer “yes” to all questions on the Mayo Clinic IRB’s Informed Consent for Research A Guide to Assessing a Participant’s Understanding.
• Individuals will also be excluded if they have vision, hearing or cognitive impairment preventing the participants from reading workbook materials, hearing or verbally communicating over the telephone or following through on an exercise program.
• Further exclusion criteria will include living in a skilled nursing facility or assisted living facility, non-ambulatory or bedridden, report of being hospitalized more than 3 times in the last year, needs physical assistance to transfer or walk, recent history of acute illness including stroke or severe neurologic impairment. Individuals who are unable to participate due to high fall risk potential or other complications will be referred back to FSR or their primary care provider for appropriate services.

• Pathologically (histologically or cytologically) proven diagnosis of NPC that has recurred at locoregional and/or distant sites. The following histological types are accepted:
  • Keratinizing
    •squamous cell carcinoma;
  • Non-keratinizing;
  • Undifferentiated or poorly differentiated.
• Measurable disease by the RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression has been demonstrated prior to enrollment.
• Age ≥ 18.
• History/physical examination by medical oncologist or clinical oncologist within 14 days prior to registration.
• Zubrod/Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days prior to registration.
• Contrast enhanced magnetic resonance imaging (MRI) or computed tomography (CT) of the nasopharynx and neck within 30 days prior to registration.
• Contrast enhanced CT scan of the chest, abdomen and pelvis within 30 days prior to registration.
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3 (within 14 days prior to registration).
• Platelets ≥ 100,000 cells/mm^3 (within 14 days prior to registration).
• Hemoglobin ≥ 9.0 g/dL (transfusion is accepted. Erythropoietin dependency not accepted) (within 14 days prior to registration).
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN.
• Patients with known Gilbert's syndrome are not excluded (within 14 days prior to registration).
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN (≤ 3 x ULN for patients with liver metastases) (within 14 days prior to registration).
• Serum creatinine ≤ 1.5 x ULN OR calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation ≥ 30 mL/min for patients with serum creatinine levels > 1.5 x ULN. In this protocol, cisplatin or carboplatin may be used at the discretion of the investigator
  •except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be used instead of cisplatin (within 14 days prior to registration).
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable and patients must be receiving anti-viral therapy at enrollment. Patients must agree to continue anti-viral therapy throughout the study period as directed by their treating physicians -Known positive test for hepatitis B virus surface antigen (HBsAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on anti-viral therapy.
• Patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (i.e., patients immunized against hepatitis B).
• In some centers, hepatitis B core antibody (anti-HBc) are done routinely before chemotherapy for some cancer patients. This is because patients who are HBsAg-negative but positive for anti-HBc should have undetectable HBV viral load at enrollment and receive prophylactic anti-viral therapy throughout the study (American Society of Clinical Oncology 2015 guideline, Hwang 2015). In this protocol anti-HBc should be performed based on institutional standards.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy.
• For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 14 days prior to registration. For WOCBP randomized to Arm 2, an additional negative serum or urine pregnancy is required within 24 hours prior to starting nivolumab treatment.
• Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception during and after treatment.
• The patient or a legally authorized representative must provide written informed consent prior to study entry.

• Diagnosed with another invasive malignancy (except non-melanomatous skin cancer) unless disease free for more than 3 years.
  • Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded).
• Any prior systemic anti-cancer agents (including chemotherapy and investigational agents) for the purpose of treating locoregional and/or distant recurrence of NPC.
• Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary NPC with chemotherapy (any drug regimens including those containing platinum and/or gemcitabine) at or within 6 months prior to registration are excluded (counting from the last day of the chemotherapy for the primary NPC, prior to enrolling into the current study). The following subgroups of patients are NOT excluded:
  • Patients who have received neoadjuvant (induction) and/or adjuvant chemotherapy for primary (non-metastatic/non-recurrent) NPC more than 6 months prior to registration, counting from the last day of the chemoradiotherapy for the primary NPC, prior to enrolling into the current study;
  • For prior RT with radical intent: Patients who have prior radiotherapy (RT) to the primary and locoregional disease (i.e., non-recurrent disease) with or without concurrent cisplatin or carboplatin monotherapy are not excluded as long as they have not received any neoadjuvant/adjuvant chemotherapy within 6 months prior to registration (counting from the last day of the chemotherapy), and that the last RT fraction (with radical intent) has been given more than 3 months prior to registration;
  • For RT with palliative intent: Prior radiotherapy (RT) at or within 30 days prior to registration, this includes RT given with palliative intent (with or without concurrent cisplatin or carboplatin alone) to recurrent/ metastatic sites in patients with recurrent/metastatic NPC. The re-irradiated sites must not be the only sites of measurable recurrent disease;
  • Prior chemotherapy for cancers other than NPC is allowed as long as the last course of chemotherapy was administered more than 3 years prior to registration and the patient has remained disease-free for more than 3 years;
• Prior therapy for any indication, with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137) -History of severe (grade 3-4) hypersensitivity reaction to any monoclonal antibody including nivolumab and/or any of its excipients.
• Severe, active co-morbidity defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  • Myocardial infarction within the last 6 months;
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
  • History of (non-infectious) pneumonitis that required steroids or has current pneumonitis requiring steroids and/or immunosuppressive therapy;
  • History of active TB (Bacillus tuberculosis, not known to be multi-drug resistant) as defined by the need to receive systemic treatment within the last 2 years or any known history of multi-drug resistant TB.
    • Note: Patients who had a distant history of treated TB (not known to be multi-drug resistant) at 5 or more years from enrollment and have no current symptoms suggestive of active TB, are not excluded from this study.
    • Note: Testing for prior exposure to TB is not required in this study since TB is endemic in parts of Asia.
  • Prior solid organ transplant or bone marrow transplant.
  • History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current CDC definition; Note: HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive.
  • Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid premedication for the prophylaxis of CT contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic premedication prior to chemotherapy is also allowed.
  • Active autoimmune disease requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn’s, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.
• Prior solid organ transplant or bone marrow transplant.
• History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition.
  • Note: Human immunodeficient virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive.
• Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid premedication for the prophylaxis of CT contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic premedication prior to chemotherapy is also allowed.
• Active autoimmune disease requiring systemic treatment (i.e. ,disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.
  • Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
• Patients who are pregnant or breastfeeding and unwilling to discontinue breastfeeding.
• Known history of grade 3-4 allergic reaction and/or hepatic toxicity to cisplatin, carboplatin, or gemcitabine.
  • Note: For patients with known history of grade 3-4 renal toxicity to cisplatin or known history of clinically significant hearing loss (grade 2 or above) attributed to cisplatin, or other intolerances to cisplatin that are of clinical significance, carboplatin can be used in this study and therefore these patients are NOT excluded from enrollment.
• Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Patients with base of skull involvement by NPC are not excluded unless their disease is directly invading the brain parenchyma and is associated with clinical symptoms (headaches, nausea and vomiting, neurological abnormalities on physical examination) and/or cerebral edema on radiological imaging.
• Patients who have received a live vaccine within 30 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

• Patients with a clinical and imaging diagnosis of a vascular anomaly.
• No prior treatment for the vascular anomaly.
• Subjects undergoing clinically indicated sclerotherapy, embolization and/or ablation.
• Male or female with age greater than or equal to 18 years.
• Capacity and willingness to provide a written informed consent..

• Subjects with prior treatment for their vascular anomaly.
• Uncorrectable coagulopathy.
• Pregnant and/or breast-feeding subjects. A negative pregnancy test within 48 hours of the procedure.

• All individuals who present for a routine elective, clinically indicated, diagnostic echocardiogram at the echocardiography laboratory at Mayo Clinic.

• Known history of voice disorder either primary or secondary to neuromuscular or other pathology.
• Patients under the age of 18 years.
• Pregnancy.

• Patients referred for our pelvic floor rehabilitation program.
• Patients with the following diagnosis will be offered participation in our study:
  • urinary urgency or frequency;
  • urinary incontinence (urgency, stress or mixed);
  • defecatory dysfunction;
  • fecal incontinence;
  • pelvic pain;
  • pelvic dysfunction (spasms, pain or weakness); or
  • dyspareunia.

• Patients with implanted electrical devices.

Eligibility last updated 10/18/21. Questions regarding updates should be directed to the study team contact.

• Adults ≥ 18 years of age.
• Asymptomatic subjects presenting for SARS-CoV-2 screening as part of their routine pre-procedural testing.

• Individuals < 18 years of age.
• Symptomatic subjects.
• Subjects who are not undergoing routine SARS-CoV-2 PCR screening.

• Adult males and females age 18 or greater.
• Undergoing COVID-19 testing by PCR.
• Willing and able to provide informed consent.
• Pregnant females (minimal risk study, no risk from ECG).

• Unwilling or unable to provide informed consent.