• Able to provide Informed Consent and follow study instructions.
• 18 years of age or older.
• Pregnant subjects ≥ 32 weeks’ gestation.
• Singleton pregnancy.
• BMI ≥ 15, pre-pregnancy.
• BMI ≤ 45, pre-pregnancy.
• Belly circumference ≥ 80 cm and ≤ 135 cm.
  • NOTE: Subjects admitted for induction of labor and subjects being monitored for premature rupture of membranes (PROM) or other inpatient evaluations can be enrolled in the trial.

• Known major fetal malformation or chromosome abnormality.
• Abdominal medical skin conditions, including surgical incisions, open wounds with or without infections, edema, or irritation.
• Subjects with implanted electronic devices (pacemakers, defibrillator, etc.).
• Involvement in another clinical trial currently or previously in this pregnancy that, in the investigator's opinion, would affect the conduct of this study.
• Medical or obstetric problem that in investigator's opinion would make the subject incapable of taking part in the study.
• In the investigator’s opinion, the subject is not likely to be available for the minimum 60 minutes of the monitoring session.
• History of skin allergies to cosmetics and lotions.
• Known allergies to silver, nylon, or polyester.
  • NOTE: some people with sensitivity to silver jewelry are sensitive to the impurities in silver alloys and not to silver itself.

Eligibility last updated 10/26/22. Questions regarding updates should be directed to the study team contact.

• Male or female and ≥ 18 years-of-age at the time of informed consent.
• ECOG Performance status 0 or 1.
• Locally advanced or metastatic resistant or refractory solid tumors.
• Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible.
• Measurable disease as per RECIST v1.1.
• Ability to swallow and retain oral medications.
• Acceptable hematologic and organ function at screening.
• Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.
• Resolution of all toxicities of prior therapy or surgical procedures.
• Life expectancy ≥ 12 weeks after the start of the treatment.

• Chemotherapy or small molecule antineoplastic agent given within 21 days or < 5 half- lives, whichever is shorter, prior to first dose of study drug.
• History or current condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment.
• Patients who are pregnant or breastfeeding.
• Known sensitivity to any of the ingredients of RP-6306 or gemcitabine.
• Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the participating patient's safety.
• Major surgery within 4 weeks prior to first dose of RP-6306 and gemcitabine.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled hypertension.
• Moderate or severe hepatic impairment.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Eligibility last updated 2/14/22. Questions regarding updates should be directed to the study team contact.

Step 0 Eligibility Criteria

• No age restriction.
• Patient must have a prior or current cancer diagnosis (e.g., solid tumor or hematologic malignancy) that fits into any one of the following categories:
  • Patient is receiving active treatment (defined as current treatment or treatment within the past 6 weeks) or will begin receiving treatment within the next 2 weeks for any CNS or hematologic malignancy or metastatic (Stage IV) solid tumor. Eligible treatment types for hematologic malignancy or metastatic cancer are chemotherapy, immunotherapy, monoclonal antibody therapy (e.g., rituximab, trastuzumab, cetuximab), targeted therapy (e.g., BRAF/MEK inhibitor, EGF-R inhibitor), endocrine therapy, radiation therapy, or targeted radionuclide therapy; or
  • Patient is receiving treatment (defined as current treatment or treatment within the past 6 weeks) or will begin receiving treatment within the next 2 weeks for non-metastatic (Stage I-III) solid tumor. Eligible treatment types for nonmetastatic cancer patients are intravenous chemotherapy, immunotherapy, targeted therapy, radiation therapy, targeted radionuclide therapy, or monoclonal antibody therapy, except trastuzumab/pertuzumab if not accompanied by chemotherapy; or
  • Patient has received an allogenic stem cell transplant or CAR-T cell or other modified cellular therapy at any time; or
  • Patient is currently receiving treatment or prophylaxis for Graft vs. Host Disease.

Testing for SARS CoV-2

• Patient must have a pending or known positive viral test result for SARS-CoV-2:
  • Patients with prior negative viral SARS-CoV-2 test(s) are eligible if they are being tested again;
  • Patients 18 years of age and older with prior positive viral SARS-CoV-2 test(s) more than 14 days prior to enrollment to Step 1 are not eligible.
  • Patient must be undergoing or have undergone testing for SARS CoV-2:
• HIV-infected patients are eligible.
• Patients with CNS metastases are eligible.
• Co-enrollment on other clinical trials (for cancer or for COVID-19) is allowed.

Step 1 Eligibility Criteria

• Patient must have a documented positive viral SARS-CoV-2 test:
  • For patients 18 years of age or older, the specimen collection for the positive test must have occurred no earlier than 14 days prior to enrollment to Step 1;
  • For patients under 18 years of age, the specimen collection for the positive test must have occurred after January 31, 2020.
  • The viral test can be either a nucleic acid (PCR) test or an antigen test. Serological or antibody tests are not allowed.
  • The test must have received Emergency Use Approval (EUA) from the FDA and be performed in a CLIA certified lab or patient care setting operating under a CLIA Certificate of Waiver. A full list of tests that have been approved under the EUA can be accessed at:

https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19- emergency-use-authorizations-medical-devices/vitro-diagnostics-euas.

• Any specimen source (e.g., nasopharyngeal swab, oropharyngeal swab, etc.) is allowable for the viral SARS-CoV-2 test.

Step 0 Eligibility Criteria

• No age restriction.
• Patient must have a prior or current cancer diagnosis (e.g., solid tumor or hematologic malignancy) that fits into any one of the following categories:
  • Patient is receiving active treatment (defined as current treatment or treatment within the past 6 weeks) or will begin receiving treatment within the next 2 weeks for any CNS or hematologic malignancy or metastatic (Stage IV) solid tumor. Eligible treatment types for hematologic malignancy or metastatic cancer are chemotherapy, immunotherapy, monoclonal antibody therapy (e.g., rituximab, trastuzumab, cetuximab), targeted therapy (e.g., BRAF/MEK inhibitor, EGF-R inhibitor), endocrine therapy, radiation therapy, or targeted radionuclide therapy; or
  • Patient is receiving treatment (defined as current treatment or treatment within the past 6 weeks) or will begin receiving treatment within the next 2 weeks for non-metastatic (Stage I-III) solid tumor. Eligible treatment types for nonmetastatic cancer patients are intravenous chemotherapy, immunotherapy, targeted therapy, radiation therapy, targeted radionuclide therapy, or monoclonal antibody therapy, except trastuzumab/pertuzumab if not accompanied by chemotherapy; or
  • Patient has received an allogenic stem cell transplant or CAR-T cell or other modified cellular therapy at any time; or
  • Patient is currently receiving treatment or prophylaxis for Graft vs. Host Disease.

Testing for SARS CoV-2

• Patient must have a pending or known positive viral test result for SARS-CoV-2:
  • Patients with prior negative viral SARS-CoV-2 test(s) are eligible if they are being tested again;
  • Patients 18 years of age and older with prior positive viral SARS-CoV-2 test(s) more than 14 days prior to enrollment to Step 1 are not eligible.
  • Patient must be undergoing or have undergone testing for SARS CoV-2:
• HIV-infected patients are eligible.
• Patients with CNS metastases are eligible.
• Co-enrollment on other clinical trials (for cancer or for COVID-19) is allowed.

Step 1 Eligibility Criteria

• Patient must have a documented positive viral SARS-CoV-2 test:
  • For patients 18 years of age or older, the specimen collection for the positive test must have occurred no earlier than 14 days prior to enrollment to Step 1;
  • For patients under 18 years of age, the specimen collection for the positive test must have occurred after January 31, 2020.
  • The viral test can be either a nucleic acid (PCR) test or an antigen test. Serological or antibody tests are not allowed.
  • The test must have received Emergency Use Approval (EUA) from the FDA and be performed in a CLIA certified lab or patient care setting operating under a CLIA Certificate of Waiver. A full list of tests that have been approved under the EUA can be accessed at:

https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19- emergency-use-authorizations-medical-devices/vitro-diagnostics-euas.

• Any specimen source (e.g., nasopharyngeal swab, oropharyngeal swab, etc.) is allowable for the viral SARS-CoV-2 test.

Inclusion Criteria

• An adult with any symptomatic disorder clinically diagnosed as Alzheimer Disease, Lewy Body disease or frontotemporal degeneration

Exclusion Criteria

• An alternative diagnosis likely to be playing a substantial role in the manifestations of the dementia including but not limited to
  • Major head trauma
  • Major psychiatric disorder
  • Major systemic illness
  • Substantial cerebrovascular disease

CASES: Heavy drinkers with alcoholic hepatitis.

• A clinical diagnosis of alcoholic hepatitis.
• Serum total bilirubin >3 mg/dL.
• Subject or guardian ability to understand and willingness to provide written consent.
• Age greater or equal to 21 years.
• Re-enrolment of an alcoholic hepatitis donor is permissible up to 4 times if the donor presents with a new episode of alcoholic hepatitis 24 weeks or longer after the most recent enrolment in the study.

• Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, and acute viral hepatitis.
  • NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to participation).
• Pregnant or breast feeding.
• Based on the judgment of the investigator, subject is not capable of understanding or complying with the study requirements.

CONTROLS: Heavy drinkers without significant liver disease Inclusion criteria

• History of chronic alcohol consumption sufficient to cause liver damage. Generally, this is considered to be >40 g/day or >280g/week on average for women and >60 g/day or >420 g/week on average for men, for many years (usually decades). Judgement about chronic alcohol consumption will be made by the site investigator. 
• Subject or guardian ability to understand and willingness to provide written consent.
• Age greater or equal to 21 years.

• Past evidence of alcoholic liver disease, defined as a bilirubin > 2.0 mg/dL, an AST > 1.5 ULN, and any hospital admission for liver disease, or the presence of esophageal varices or ascites (at any time in the past).
• Liver disease significantly caused by hemochromatosis, autoimmune liver disease, Wilson disease, NAFLD, and acute viral hepatitis.
  • NOTE: The presence of chronic hepatitis C, hepatitis B, or HIV is not exclusion to participation.
• Alcohol intake at less than 40 g/day or 280g/week on average for women and 60 g/day or 420 g/week on average for men for longer than the past 28 days.
• If liver stiffness has been assessed within the prior 90 days, then stiffness suggesting fibrosis of F1 or greater is excluded. For Fibroscan, this is a fibrosis score >7.0 kPa.
• Pregnant or breast feeding.
• Any of the following laboratory abnormalities within 90 days prior to signing the consent:
  • Total bilirubin: >ULN* 2.
  • INR: > 1.4 5
    • *Individuals with a diagnosis of Gilbert's can have total bilirubin up to 3.0 mg/dL and still be eligible for participation.

HEALTHY CONTROLS

• AUDIT-C scores of <4 for men and <3 for women (signifying no alcohol misuse).
• Abstinent (consumption of less than one standard drink/week) during the 6 months prior to enrolment.
• Ability to understand and willingness to provide written consent.

• Clinical history or laboratory evidence of liver disease including alcoholic liver disease, NAFLD, hemochromatosis, alcoholic hepatitis, autoimmune liver disease, Wilson disease, hepatitis C, or hepatitis B. 
• Presence of diabetes (requiring treatment with oral agents or insulin). 
• Significant heart disease (prior history of heart disease, other than hypertension).
• Chronic lung disease (requiring chronic treatment).
• Immune related conditions (such as Crohn's disease, rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, severe psoriasis, etc.).
• Known infection with HIV.
• Presumed infection, or use of antibiotics or other medications (e.g., corticosteroids) that would affect immune function, within the past 14 days.
• BMI>35.
• Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment.
• Pregnant or breast feeding.
• Any of the following laboratory abnormalities within 90 days prior to signing the consent:
  • Hemoglobin: <10 g/dL;
  • Conjugated bilirubin: > ULN;
  • INR: > 1.4;
  • AST: >40 IU/mL;
  • ALT: >40 IU/mL.
• Based on the judgment of the investigator, subject is not capable of complying with the study requirements.

• Age 18 or older.
• Scleral lens wearers with a history of 6 months of at least 5 hours of scleral lens wear at least 5 days/week are invited to participate.

• Patients with active infections or unstable inflammation of the eyes are not eligible to participate.
• Patients who have been refit into a different scleral lens design during the past 6 months.
• Patients who are actively participating in the scleral lens fitting process.

• Adult participants (≥ 25 years of age).
• PLS diagnosis is based on the new PLS diagnostic criteria.
• Symptom onset was no more than 15 years prior to baseline.
• Ability to independently walk with or without an assistive device (e.g., walker) at the baseline evaluation.
• In cases where a molecular test has been done prior to enrollment in this study, HSP or HSP- related mutations are negative.
• Expected to have at least some bulbar symptoms (dysarthria, dysphagia, drooling or pseudobulbar affect); however, the absence of these symptoms will not exclude participants when molecular testing is negative for known HSP.
• UMN symptoms and signs in a region other than the legs.
• Normal brain and spinal cord neuroimaging except for changes expected for PLS.
• No active major neurological diseases other than PLS and no history of major neurological diseases.
• No major unstable medical diseases that require treatment (e.g., active cancer, dialysis) in the past 6 months.
• Participant is residing within a commutable distance to the study site and is willing to visit the study site as required.
• No history of ALS or PLS in immediate family and no family history of hereditary spastic paraplegia (HSP).
• gia (HSP) If disease duration is less than 5 years, no significant lower motor neuron (LMN) degeneration upon the EMG examination within 12 months before enrollment (evident entrapment neuropathy or radiculopathy are acceptable). If EMG tests were not done in this period, an EMG test should be obtained through regular patient care (through insurance) in order to make a diagnosis of PLS (this cost will not be covered by this research study). If disease duration is more than 5 years and at least one EMG was performed post-diagnosis, an EMG examination 12 months prior to enrollment is not required.
• Participant understands the study’s purpose, has capacity to consent, and is willing to sign the informed consent form.

• Unwilling or unable to give informed consent.
• UMN symptoms and signs only in the legs.
• Unwilling or unable to visit the study site as required.
• Clinically obvious cognitive impairment that precludes obtaining informed consent, as determined by the site PI.
• Participating in clinical treatment trials.

Eligibility last updated 5/3/22. Questions regarding updates should be directed to the study team contact.

• Female, 18 years of age or older.
• Women treated for breast cancer with radiation with a curative intent

• Non breast cancer.
• Children under 18-years of age.
• Non curative intent.

Eligibility last updated 4/19/22.  Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• The patient must meet all of the below criteria to be eligible for enrollment in the study:
  • The participant is less than 18 years of age at the time of transplant
  • The participant received a liver-only, a combined liver-kidney, or a combined liver-pancreas transplant at a participating SPLIT Registry Center

Exclusion Criteria

• The participant previously received a solid-organ transplant other than a liver-only, kidney-only, a combined liver-kidney, or a combined liver-pancreas transplant.

• 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.

• Ability to understand and provide written informed consent
• Age ≥ 50 years
• Current or Former Smoker
• ≥ 20 pack-years (pack years = number of packs per day X number of years smoked)

Inclusion Group 1: High Risk Patients that meet criteria 5 and 6 below:

• Prior thoracic imaging (computed tomography (CT)) within 12 months of enrollment OR Planned thoracic imaging (CT) as part of standard of care within 6 weeks of enrollment AND
• Meet one of the criteria below: a) No suspected or confirmed lung cancer diagnosis as defined by:
  • No clinical and/or radiological findings that indicate suspicion of lung cancer diagnosis (i.e., no lung nodules, <6mm lung nodules, ≥6mm lung nodules with no significant change from prior CT scan); OR
  • Suspected of lung cancer as defined by:
  • Radiological finding and/or clinical evaluation that indicates suspicion of lung cancer diagnosis (i.e., suspicious lung nodule(s) ≥6mm or Lung-RADS 3/4 for first-time CT scan patients and newly suspicious lung nodule(s) ≥ 6mm or Lung-RADS 3/4 identified within 6 months prior to enrollment for follow-up and surveillance CT scan patients). Subjects must have not received therapy prior to blood collection; OR
  • Confirmed, untreated lung cancer as defined by:
  • Pathologic diagnosis of lung cancer with no prior systemic therapy, definitive therapy, radiation, or surgical resection for any lesion.

Inclusion Group 2: High Risk Patients that meet the following criteria:

• Pathologic confirmed, invasive non-lung cancer diagnosis, originating from esophagus (upper), colon or rectum, pancreas, stomach (including lower esophagus), head and neck, bladder, kidney, or liver, with no prior systemic therapy, definitive therapy, radiation, or surgical resection; OR
• Clinically confirmed invasive non-lung cancer diagnosis originating from the pancreas, kidney, or liver, based on imaging and clinical judgement with planned treatment and no prior systemic therapy, definitive therapy, radiation, or surgical resection.

• Prior systemic therapy, definitive therapy, radiation, or surgical resection for cancer within one year prior to enrollment (with the exception of organ biopsies or surgery for non-melanoma skin cancer).
• Any history of hematologic malignancies or myelodysplasia.
• Any history of organ tissue transplantation.
• History of blood product transfusion within 120 days prior to enrollment.
• Current pregnancy.
• Any condition that in the opinion of the Investigator should preclude the subject’s participation in the study.
• Prior systemic therapy.
• Prior systemic therapy, definitive therapy, radiation, or surgical resection for the enrollment cancer diagnosis (with the exception of organ biopsies or surgery for non-melanoma skin cancer are not exclusionary).
• Enrollment in the DELFI-L201 study.

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

Eligibility last updated 12/15/23. Questions regarding updates should be directed to the study team contact.

• Only patients who completed studies UT001 or TC-BC-12 with a status of CR at the final FU visit.

• None.

• Subjects will be sampled from the 997 subjects who underwent neuropsychological testing in the current funding period.
  • Most are still resident in Olmsted County, MN or environs.

• Claustrophobia or other condition which precludes the subject from lying quietly in the MRI scanner 
• Standard MRI contraindications such as an implanted device, and
• Oral braces or other head and neck metal implants that significantly degrade MRI image quality

• The individual must have received an infusion of gene-modified cells in a completed Kite-sponsored parent study, has not withdrawn full consent, and has discontinued or completed the post-treatment follow-up period in the parent study, as applicable.
• The individual must understand and voluntarily sign an Informed Consent Form (ICF) or an Informed Assent Form prior to any study-related assessments or procedures being conducted.
• In the investigator's judgment, the individual is willing and able to complete the protocol-required follow-up schedule and comply with the study requirements for participation.

• None.

Eligibility last updated 1/12/22. Questions regarding updates should be directed to the study team contact.

Inclusion Critereia:

150 total patients with suspected portopulmonary hypertension in the biorepository, with approximately 75 patients with confirmed portopulmonary hypertension as defined by pulmonary hemodynamics at the time of right heart catheterization

• An individual who has previously consented to the Biospecimen Resource for Pancreas Research (Substudy #1 – Pancreatic Disease Cases) – IRB 354-06 who does not have pancreas disease but does have a family history of pancreas disease or (Substudy #2 Family Studies) – IRB 355-06.
• Individual who does not have a personal history of pancreatic cancer and meets one of the following:
  • Has relatives in family that contains pancreatic cancer, and carries a known germline mutation in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53; OR
  • Is a first- or second-degree blood relative of an individual with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) and this PDAC patient has a germline mutation in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53; OR
  • Is a first- or second-degree blood relative of an individual with a germline mutation in one of these genes and where the mutation carrier is also a first-degree relative to a PDAC case; OR     
  • Is a blood relative to a PDAC patient in a family that contains three blood relatives (all maternal side or all paternal side) with PDAC;
  • Age 50 or older; OR
  • Or within 10 years of the age of diagnosis of the youngest PDAC blood relative.
• Individual with a valid United States mailing address.

• Individual who has a personal history of PDAC.
• Individual who has received a bone marrow transplant, who has had a blood transfusion within the last 7 days, or who has an active hematologic malignancy (i.e., leukemia or lymphoma).
• Individual who is unable to sign the informed consent because of mental incompetency or psychiatric illness.
• Individual who is non-English speaking
• Individual who is a prison inmate.

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

• Capable and willing to provide informed consent.
• Confirmed or suspected physician diagnosis of Primary Immunodeficiency.

• Not willing to provide consent.
• Not diagnosed with Primary Immunodeficiency.

Eligibility last updated 9/10/21. Questions regarding updates should be directed to the study team contact.

• Adult postmenopausal women, aged 45-60 years.
• Menopause symptoms (hot flashes/night sweats) rated moderate or greater or total MRS score ≥ 14.

• Current use of hormone therapy.

Eligibility last updated 3/10/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years
• Radiographic evidence or histopathologic confirmation of CNS malignancy, with or without prior resection. 
• Provide written informed consent for the current study.
• Willing to undergo at least one MRI (at most two) with proton and/or phosphorus magnetic resonance spectroscopy analysis.

• Vulnerable populations:  pregnant or nursing women (Arm B exempt), prisoners, mentally handicapped.
• Cardiac pacemaker or artificial heart valve.
• Metal plate, pin, or other metallic implant.
• Intrauterine device, such as Copper-7 IUD.
• Insulin or other drug pump.
• Non-titanium aneurysm clips.
• Previous gunshot wound.
• Cochlear implant or other hearing device.
• Employment history as a metalworker (had metal in eye).
• Permanent (tattoo) eye-liner.

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

Eligibility last updated 11/16/23. Questions regarding updates should be directed to the study team contact.

• Over 18 years of age.
• Able to provide consent.

• Individuals < 18 years of age.
• Any subjects with head size circumference greater than 56 cm will be excluded in studies to assess positional brain shift.
• History of epilepsy.
• Pregnant.
• Present of ferromagnet objects or non-MR-safe medical devices or implants.

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

Eligibility last updated 12/11/23. Questions regarding updates should be directed to the study team contact.

• 18 years of age or older.
• Male or nonpregnant, nonlactating females.
• Diagnosis of ulcerative colitis (UC) for at least 3 months prior to screening.
• Moderately to severely active ulcerative colitis (UC) (total MCS ≥ 6), with objective evidence of inflammation defined by a Mayo endoscopic subscore (MES) ≥ 2 and disease extending > 15 cm from the anal verge.
• Physician plans to administer Janus Kinase Inhibitor Therapy for at least 8 weeks as part of standard of care (SOC).
• Documentation of a negative test result for latent tuberculosis within the last 12 months, or according to routine clinical practice.
• Able to participate fully in all aspects of this clinical trial, including collection of tissue biopsies.
• Written informed consent must be obtained and documented.

• Diagnosis of Crohn’s disease or indeterminate colitis.
• An active, serious infection, including localized infections.
• Concomitant administration of biological therapies for UC or potent immunosuppressants, such as azathioprine and cyclosporine. Subjects with previous exposure to these treatments should undergo an appropriate washout period according to local practice prior to starting tofacitinib, in keeping with routine clinical practice.
• Hematology laboratory results that meet the following:
  • absolute lymphocyte count < 500 cells/mm3.
  • absolute neutrophil count < 1000 cells/mm3.
  • hemoglobin < 9 g/dL.
• Interval between live vaccinations and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
• Serious underlying disease other than UC that in the opinion of the investigator may interfere with the subject’s ability to participate fully in the study.
• Prior enrollment in the current study and having received tofacitinib.

Subjects must meet ALL of the following criteria:

• Signed and dated informed consent form.
• At least 18 years of age at time of implant.
• Good health and absence of significant morbidity.
• Ability to read, write, comprehend, and speak fluently in English.
• Post-lingually deafened.
• Pure-tone thresholds indicate at least a bilateral moderate-to-severe sensorineural hearing loss:
  • Low frequency pure-tone average greater than or equal to 40 dB HL at 250, 500, 750, and 1,000 Hz; and
  • Severe or profound hearing loss greater than or equal to 70 dB HL at 2 KHz and above.
• Limited benefit from amplification, defined by aided CNC word recognition ≤ 40% in the ear to be implanted and ≤ 60% in the best aided condition.
• Normal middle ear function based on otoscopy and tympanometry (Type A, AS, or AD).
• An accessible cochlear lumen and intact cochlear nerve, and no known lesions on the auditory nerve or acoustic areas of the central nervous system.
• Ability to undergo surgery and post-implant rehabilitation.

Subjects will be excluded if any of the following are present:

• More than ten years of documented severe-to-profound hearing loss.
• Air-bone gap greater than 10 dB at two of the four following frequencies: 500, 1000, 2000, and 4000 Hz.
• Prior surgery in the middle ear, inner ear, neck, or infraclavicular region that is anticipated to prevent proper placement or function of the Acclaim CI.
• Ossification, malformation, or any other cochlear anomaly that might prevent complete insertion of the electrode array.
• Hearing impairment due to retrocochlear pathology.
• Diagnosed auditory neuropathy.
• Unwillingness or inability of the candidate to comply with all required investigational testing and follow-up visits, in the opinion of the Investigator.
• Known hypersensitivity or contraindication to procedural or post-procedural medications that cannot be adequately managed medically.
• Known hypersensitivity to silicone rubber, polyurethane, stainless steel, titanium, or platinum.
• Currently using other active implants that are expected to interfere with the Acclaim CI positioning or function.
• Participation or planned participation in an investigational drug or another device study within the three months prior to screening. Participation in clinical trials or registries where only measurements and/or samples are taken (e.g., no test device or test drug) is allowed.
• Pregnancy at the time of implant or plans to become pregnant within two (2) years of enrollment.

Eligibility last updated 11/16/21. Questions regarding updates should be directed to the study team contact.

• Patient must be ≥ 2.5 years of age.
• Patient and/or authorized representative must be willing and able to give informed consent/assent and any authorizations required by local law for participation in the study.
• Patient and their caregiver must be willing and able (in the Investigator’s opinion) to comply with all protocol requirements.
• Patient must have completed dosing with STK-001 and the End of Study Visit in Study STK-001-DS-101, with an acceptable safety profile per Investigator judgment.
• Patient must have satisfactory compliance with study visits and procedures in Study STK-001-DS-101 per Investigator and Sponsor judgment.
• Patient must meet age-appropriate institutional standard practices for intrathecal (IT) drug administration procedures.
• Patient and/or family (or caretaker) must be sufficiently fluent in English or Spanish to be able to complete questionnaires relevant to this study.
• Patient must have completed Study STK-001-DS-101 within 4 weeks of the start of their participation in Study STK-001-DS-501, unless approved by the Sponsor.

• Patient has met any withdrawal criteria from Study STK-001-DS-101.
• Patient is currently being treated as maintenance therapy with an antiepileptic drug acting primarily as a sodium channel blocker including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide, or rufinamide.
• Patient has clinically significant unstable medical conditions other than epilepsy.
• Patient has had clinically relevant symptoms or a clinically significant illness (in the judgment of the Investigator) at Screening or prior to dosing on Day 1, other than epilepsy.
• Patient has a spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt.
• Patient has clinically significant (in the judgment of the Investigator) abnormal laboratory values at baseline or prior to dosing on Day 1.
• Patient has aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3-fold upper limit of normal (ULN), serum creatinine > ULN or platelet count < lower limit of normal at baseline and upon repeat testing.
• Patient has clinically significant abnormalities (in the judgment of the Investigator) in the 12-lead ECG measured at Screening/Baseline (This includes 12-lead ECG from STK-001-DS-101 [Visit 6 or Visit 9], if STK-001-DS-101 Visit 6 or Visit 9 and STK-001-DS-501 Visit 1 are the Same Day).
• Patient has a psychiatric or behavioral disorder which, in the opinion of the Investigator, may interfere with the patient’s participation in the study.
• Patient is currently taking, or within 4 weeks prior to Screening/Baseline has taken any anticoagulant (including but not limited to heparins, warfarin and other vitamin K antagonists, dabigatran, rivaroxaban and apixaban), or within 7 days prior to Screening/Baseline, has taken any antiplatelet (including but not limited to aspirin, non-steroidal anti-inflammatory drugs, clopidogrel, ticlopidine. and dipyridamole).
• Patient is a female of childbearing potential, or patient is a fertile male with female partner(s) of childbearing potential, unless willing to ensure that they or their partners use effective contraception throughout the duration of the study and for at least 6 months after their last dose of STK-001.
• . Patient is a female who is lactating or planning pregnancy during the duration of the study and for at least 6 months after their last dose of STK-001.
• Patient has any other significant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, may influence the results of the study, or may affect the patient’s ability to participate in the study.
• Patient has been treated (or is being treated) with an investigational product (other than STK-001) since participating in Study STK-001-DS-101.
• Patient is participating in an observational study, unless approved by the Sponsor.

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

Eligibility last updated 4/25/23. Questions regarding updates should be directed to the study team contact.

• Subjects must have a malignancy 
• Under the age of 21

• Men and women age ≥ 18 years.
• Diagnosis of intracranial aneurysm secured by magnetic resonance angiography (MRA), computed tomographic angiography (CTA), or catheter-based cerebral angiography.
• Diagnosis of subarachnoid hemorrhage diagnosed by head CT, brain MRI or lumbar puncture.
• Provides written informed consent.

• Individuals < 18 years of age.
• No known diagnosis of aortic aneurysm.
• No history of prior screening for aortic aneurysm.
• No condition like recent abdominal surgical scar that would preclude abdominal ultrasonography.
• No therapy like abdominal hypothermia pads that would preclude abdominal ultrasonography.