• Between the ages of 18-50 years old.
• Are of moderate to high fitness level and participate in regular physical activity.
• Must have a body mass index (BMI) less than 31 kg/m^2.
• Must be able to provide clear informed written consent.

• History of chronic respiratory, cardiovascular, metabolic disease or neural/cognitive disorders.
• Anemia (< 12 g/dl for males, < 11 g/dl for females).
• Migraines.
• Active smoker (smoke within the past 6 years), or have more than 5 pack-years of smoking history
• Females who are pregnant or trying to become pregnant.

Task 1 Specific:

• History of pneumothorax, functionally limiting barotraumas or any inability to equalize tympanic pressure (e.g., during diving, swimming or flying).
• Current dental abscesses or jaw pain consistent with severe dental caries.
• Prior allergies or serious side effects from vasoconstrictors such as Afrin™ (oxymetazoline hydrochloride) utilized for sinus decongestion.
• Hyperbaric exposure within the last 24 hours (for chamber visits).

• Age 18 and older.
• Willing to provide consent.
• Men or women.
• Stable weight for 3 months prior to study entry.

• Individuals who are unable to sign consent (e.g., mentally challenged, those declared legally incompetent).
• Recent use of weight loss medications (< 6 months).
• History of abdominal GI surgery other than appendectomy.
• Bleeding disorder.
• Pregnancy.
• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption; e.g., orlistat, phentermine.
• Subject has a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder study adherence.
• Any contraindications to MRI.
• Claustrophobia.

• Subjects diagnosed with sleep apnea.
• Self-identify as Somali, African,Asian, or European descent.
• Adult males and females who are older than 18 years of age.

• Minors under 18 years or adults over 100 years.
• Positive pregnancy.

• Ages 65 and older.
• Presenting with type II odontoid fracture confirmed by CT scan to one of the study centers.
• Deemed appropriate by the attending surgeon involved for C1-2 posterior cervical fusion procedure if surgical management were to be indicated.
• Able to independently cooperate in the completion of all study consents, forms and documents.
• Able to speak, read and write English at an elementary school level.

• Those individuals with previously documented type II odontoid fracture.
• Those individuals whose odontoid fracture is related to malignancy or infection.
• Those individuals with associated spinal cord injury.
• Those individuals with other cervical, thoracic or lumbar injuries requiring surgical intervention.
• Those individuals with aberrant/anomalous local anatomy which precludes posterior placement of C1/2 instrumentation.

• Aged ≥ 12 years.
• At least 1 symptomatic stone event (passage or procedural intervention) within 3 years prior to enrollment or a symptomatic stone event within 5 years if the patient also has new stone formation detected on imaging during the last 5 years. Symptomatic stone defined as any of the following:
  • Stone passage;
  • Procedural intervention;
  • Radiographically or ultrasonographically confirmed stone with any of the following:
    • Gross hematuria;
    • Renal colic or atypical abdominal pain attributed to the stone, as determined by a treating provider;
    • A clinical pattern of intermittent symptoms consistent with intermittent obstruction at the ureteropelvic junction, as determined by a treating provider.
• Low 24‐hr urine volume 1. ≥18 years old: <1.8 L/day 2. <18 years old: <20 ml/Kg/day up to 1.8L/day.
• Able to provide informed consent (parental permission for children).
• Owning and willing to use a smartphone or other device (e.g., tablet) compatible with the study‐provided wireless enabled "smart" bottle.

• Spinal cord injury.
• Currently undergoing active treatment for cancer except basal cell skin cancer, or patients with a history of cancer who completed their initial therapy <1 year before screening. 
• Known infectious (struvite), monogenic or other causes of stone disease for which therapies are likely to significantly alter course of stone disease:
  • Cystinuria;
  • Primary hyperoxaluria;
  • Primary xanthinuria;
  • Primary hyperparathyroidism;
  • Sarcoidosis;
  • Medullary sponge kidney.
• History or presence of hyponatremia (serum sodium <130 mmol/L) or hypo‐osmolality (serum osmolality <275 mosm/kg).
• Study participants with comorbidities that preclude high fluid intake or prior surgery precluding high fluid intake or leading to GI fluid losses:
  • History of or current Crohn's disease, ulcerative colitis, short gut syndrome (e.g. ileostomy, bowel bypass surgery to treat obesity, small bowel resection), chronic diarrhea, or GI tract ostomy.
  • History of malabsorptive (e.g., Roux‐en‐Y gastric bypass) or restrictive (e.g., sleeve gastrectomy) bariatric surgery procedures.
  • Congestive heart failure:
    • NYHA class II or greater; and/or
    • Hospital admission in the past year for heart failure.
  • Lung disease with a home oxygen requirement.
  • Chronic kidney disease (eGFR <30 ml/min/1.7 m2 over a 3‐month period):
    • For adults (age ≥18), we will use the CKD‐Epi equation which requires the measurement of serum creatinine only;
    • For children (age <18), we will use the bedside Schwartz (CKiD) formula.
  • Nephrotic syndrome (>3.5 grams of protein per 24 hours) g. Cirrhosis with ascites.
• Women who are currently pregnant or planning pregnancy within 2 years.
• Renal transplant recipient.
• Bedridden study participants (ECOG ≥ 3).
• Uncorrected anatomical obstruction of the urinary tract.
• History of recurrent urinary tract infections (> 3 UTI/year proven by urine culture).
• Exclusions due to medication use:
  • Chronic use of lithium'
  • Long‐term glucocorticoid use (> 7.5 mg prednisone daily for > 30 days prior to enrollment)'
  • Intake of narcotic medication on a daily basis for >30 days prior to enrollment'
  • Supplemental Vitamin C (> 1 g daily).
• Individuals with stones that have developed after the initiation of medications that are strongly associated with USD such as carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide), high dose vitamin C (> 1 g daily), high dose calcium supplementation (> 1,200 mg daily) AND who have discontinued or plan to discontinue these medications.
• Individuals with stones composed of medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir) AND who have discontinued or plan to discontinue these medications.
  • Note: Individuals who are on long‐term medications that increase the risk of stone disease, who cannot stop these medications due to other chronic conditions (e.g., HIV) and who may reduce their risk for stone recurrence through increased fluid intake, will be eligible to participate in the trial. Examples of these medications include:
    • Carbonic anhydrase inhibitors (acetazolamide, topiramate, zonisamide);
    • Medications that may crystallize in the urine (guaifenesin, sulfonamides, triamterene, and the protease inhibitors indinavir and nelfinavir).
• Study participants <2 yrs life expectancy.
• Non‐English Speakers.
• History of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
• Anatomical urologic abnormalities including ileal conduits, horseshoe kidney, megaureter or solitary kidney.
• Psychiatric conditions impairing compliance with the study.
• Vulnerable population (prisoner and/or cognitive impairment that the investigator feels will impact the study participant's ability to participate in the protocol).
• Individual who will be unable to participate in the protocol in the judgment of the investigator.

• Young, healthy adults will be sought out for recruitment in the present study.
• The experimental design of this study requires at 1-2 visits to the laboratory.
• Participants will be within the age range of 18 and 45 years.
• Non-smokers.
• no current or past history of cardiovascular, pulmonary or neuromuscular disease.  
• As per the American College of Sports Medicine’s (ACSM) Guidelines for Exercise Testing and Prescription, we will consider patient as “low risk” for participating in exercise, if they have:
  • No family history cardiovascular disease;
  • Have a BMI <30kg∙m-2;
  • Participate in at least 30 minutes of moderate exercise a minimum of 3 times a week;
  • No diagnoses of hypertension;
  • No diagnosis of dyslipidemia;
  • No diagnosis of prediabetes.

• Participants must also pass the Physical Activity Readiness Questionnaire (PAR-Q) to be included in the study.

• None.

• Resident of the United States.
• Age 18 years or older.
• Able to provide informed consent.
• Able to complete surveys in English or Spanish.
• Valid order for Cologuard screening.

• Provisions for inclusion of minorities:
  • Subjects will be included based upon a random selection from among all recipients of a Cologuard test.
  • Minorities will be invited without discrimination by this random process.

• Patients who are 18-65 years old.
• Patients who present to the ED with a blunt head injury within the past 24 hours.
• Patients determined to be low risk by the CCHR.
• Patients being considered for a head CT by the treating provider.

• Patients who are pregnant.
• Patients who are non-English speaking.
• Patients who are in police custody.
• Patients who are undergoing psychiatric evaluation.
• Patients found to have drug or alcohol intoxication.

• White Earth Health Center clinic staff; and/or White Earth area early childhood educator; and/or
• Caregivers of children age 6 months to 5 years presenting for well visits at White Earth Health Center

• Written informed consent must be obtained prior to any screening procedures or treatment assignment.
• Has a patient specific batch of CTL019 which is out of specification either due to out of specification incoming apheresis or final product not meeting commercial release.
• Not excluded from commercial manufacturing under the prescribing guidelines for their country.
• Out of specification material has not been deemed to pose an undue safety risk to the patient.
• Is suffering from a serious or life-threatening disease or condition.
• Repeat leukapheresis is not feasible per the treating physician assessment.
• Does not have access to a comparable or satisfactory alternative treatment.
• Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options, the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient..
• Many other relevant medical criteria for compassionate use of the investigational product.
• Is not being transferred from an ongoing clinical trial for which they are still eligible.

• Product can be commercially manufactured per the specification of the country in which treatment will occur. 
• Patients who are able to repeat leukapheresis. 
• Evidence of CD19 negative disease. 
• HIV positive patients. 
• Patients with active replication of Hep B or active or latent Hep C.
• History of hypersensitivity to any drugs or metabolites of similar chemical classes as tisagenlecleucel. 
• Uncontrolled active infection or inflammation.
• History of unstable angina or MI within 6 months prior to screening. 
• Any medical condition identified by the investigator that may impact the assessment of the safety or efficacy outcomes in relation to study treatment.

• Patients admitted to Saint Mary’s Hospital for EEG monitoring or inpatient psychiatric treatment;
• Patients aged 18 or above;
• Patients possessing written and spoken English language proficiency; and
• Patients able to provide consent will be invited to participate. Patients that are anticipated to be implanted with intracranial EEG electrodes may be prioritized for this study, including patients implanted with depth electrodes and/or subdural neocortical strips or grids.

• Patients with an inability to provide informed consent;
• Patients with an inability to complete study materials secondary to cognitive, psychiatric, or other medical impairment; and/or
• Patients with secondary-to-limited English language fluency as determined by EMU or Generose staff and Dr. Greg Worrell.

• Adolescents between the ages of 14 and 19 years of age.
• Existing or newly diagnosed epilepsy.
• Currently receiving continued care within the Mayo Clinic Pediatric Neurology Department.
• Participants must live within approximately 70 miles of the Mayo Clinic Rochester campus.

• Adolescents with a history of severe intellectual disability based on chart review and/or prior neuropsychological testing (e.g., nonverbal, non-ambulatory).

• Adult patients > 18 years.
• BMI over 30 kg/m^2.
• Participants can give consent to the procedure.
• Participants have no contraindications to LSG. (gastric ulceration).

• Participants who have LA grade C or D esophagitis, Barrett mucosa or peptic stricture.
• Patients who have evidence of a major motility abnormality defined by the Chicago classification version 3.0 (achalasia, absent contractility, esophagogastric junction outflow obstruction, distal esophageal spasm, or hypertensive peristalsis).
• Patients with hiatal hernia > 3 cm.
• Patients with previous esophageal or stomach surgery.

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

• Failure to respond to at least two trials of anti-seizure drugs with different mechanisms of action;
• Normal MRI.

• Active immunomodulatory therapy;
• Autoimmune disorder;
• Signs or symptoms consistent with comorbid infection;
• ncological comorbidity.

• Hospitalized hematology-oncology patients, age 18 – 80 years old.
• Able to speak English and complete surveys.
• Able to read, understand and sign inform consent.

• Patient unwilling for reiki therapy.
• Unable to give written consent.
• Already having received or receiving other reiki treatment.
• Pregnant women. (as verbalized by participant)/

• Subjects older than 18.

• Vulnerable subjects such as prisoners and adults lacking capacity to consent.
• Subjects with low B-mode ultrasound image quality due to factors such as narrow rib gap space or excessive body fat.

RETROSPECTIVE COHORT
•COHORT 1A: T1D

• Adult pregnant females with type 1 diabetes mellitus.

• Adult pregnant female with type 2 diabetes or gestational diabetes mellitus.

PROSPECTIVE COHORT
•COHORT 2A: T1D

• Adult pregnant females with type 1 diabetes mellitus.

• Adult pregnant female with type 2 diabetes or gestational diabetes mellitus.

COHORT 2B: AGE MATCHED HEALTHY CONTROLS

• Adult pregnant female without diabetes.

• BMI greater than 35.

• Non-Infectious Active Uveitis of the posterior segment of the eye.

• Females who are pregnant, nursing, or planning a pregnancy.
• Confirmed or suspected infectious uveitis.

Inclusion Criteria
•All Cohorts:

• Age 18 years old or above.
• Consents to participate.

Inclusion Criteria
•Group I PAH Cohort:

• Documented group I PAH based upon these hemodynamic criteria: (mPAP > 20, PCW 18 or less, PVR > 3 Wood units.
• Exclusion criteria for group I PAH:
  • Left sided heart disease (LVEF<50%, PAWP>18).

• Additional exclusion criteria

  • Patients who have been seen or evaluated by palliative care in the past

  • Current or planned participation in investigational clinical trial of a drug or device

Inclusion Criteria
•Group III PH Cohort:

• Mean PAP > 20, PCW 18, PVR > 3 Wood units.
• Parenchymal lung disease that in the opinion of the investigator qualifies patient as group III PH.

Inclusion Ccriteria
•Group IV PH Cohort::

• Documented chronic thromboembolic pulmonary hypertension or chronic thromboembolic disease with intent to treat with surgery, balloon pulmonary angioplasty, and/or PH medication.

Exclusion Criteria - All Groups:

• Any other known concomitant life-threatening disease with a life expectancy <12 months.
• Any other clinically relevant and/or serious chronic medical condition that would affect study participation in the opinion of the investigator.
• Non English speaking.

• Individuals who received results of predictive genomic testing through the SL3 clinic from 1/1/2017 to 6/30/2019.

• Center for Individualized Medicine employees.
• Non-English speaking patients.
• Patients with no available email address.

• Children aged 5-10 years at the time of enrollment.
• Those who receive medical care from Mayo Clinic.
• Those born either:
  • preterm (< 37 weeks of gestation) who received supplemental oxygen within 2 weeks after birth with (n=12) and without asthma (n=12); or term (>= 37 weeks of gestation) without asthma (n=12).
• Those with a weight of 17 kgs or greater.

• Those who have a history of chronic lung diseases such as cystic fibrosis, pulmonary fibrosis, lung cancer, or bronchopulmonary dysplasia.
• Those who do not receive primary medical care from Mayo Clinic.  

• Male participant.
• Age ≥ 18 years old.
• Histological confirmation of prostate adenocarcinoma.
• Recurrent prostate cancer after prior receipt of primary radiotherapy to the prostate (can also include treatment of SVs and LNs) or salvage RT to the prostate fossa (can also include prior pelvic RT).
• Oligometastatic extent of disease.
• Recurrent disease involving lymph nodes as diagnosed with choline  PET/CT or other advanced PET imaging (PSMA or flucyclovine).
• Limited to pelvic and/or retroperitoneal/para-aortic lymph nodes.
• Zubrod performance score (PS) ≤ 1.
• Signed informed consent.

• Bone or visceral metastases present.
• Lymph node metastases beyond the pelvis and/or retroperitoneum.
• Contraindications to RT (e.g., uncontrolled inflammatory bowel disease).
• Contraindications to androgen suppression.
• Concurrent antineoplastic agents (chemotherapy).
• Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer.
• Inability to start the protocol treatment within 6 months after study enrollment.
• Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up.

• Patients 18 years old or older.
• Referred for 7T brain MRI with seizure protocol as well as normal controls.
• A subset of patients will be recruited for repeat scanning, using FDA approved T1- and T2-weighted volumetric pulse sequences, to evaluate the repeatability and validity of the results.

• Patients less than 18 years of age.
• Pregnant patients
• Patients with major brain structural lesions likely to interfere with post-processing software, including large infarcts, major congenital malformations, brain tumors and patients that have previously undergone craniotomies.
• Any patient implanted devices would be evaluated for MR safety at 7T with the standard safety protocol implemented in our 7T clinical practice.  More specifically, those individuals with safety contraindications as follows, would be excluded from research:
  • any ‘undefined’ metallic implants or foreign bodies inside the body;
  • implanted active devices such as cardiac defibrillators/pacemakers, deep brain stimulators, vagus nerve stimulators, intrathecal pumps, cochlear implants;
  • devices, or residual parts thereof left in the body such as cardiac pacer wires, which provide life assist, bone growth or pain management;
  • structural support devices, screws, or wires in bone that are near the spinal cord or temperature sensitive organs;
  • reconstructive metallic implants near the orbits;
  • external devices, medicinal patches, piercings, jewelry, clothing or hair accessories (such as wigs, weaves and extensions) within to the radiofrequency coil that cannot be removed from the body;
  • tattoos located within the radiofrequency coil;
  • permanent facial makeup;
  • metallic fragment in the eye;
  • colored contact lens;
  • fever / elevated temperature.

Inclusion Criteria
•Aim 1 Tissue:

• Adults, age >18 years old.

Cases

• Patient has a biopsy confirmed diagnosis of target histology.
• Tissue samples from synchronous or metachronous primary cancers may be used as long as they are clearly of a different target organ.
• Tumors from patients with an underlying genetic disorder pre-disposing to cancer may be included as long as they are stratified from those without.

Controls

• Patient does not have the diagnosis of target histology.

Exclusion Criteria
•Aim 1 Tissue:

• Individuals under 18 years of age.

Cases and Controls:

• Patient has had any transplants prior to tissue collection.
• Patient has received chemotherapy class drugs within 5 years prior to tissue collection.

Cases:

• Patient has had radiation to the current target lesion prior to tissue collection.
• Patient has multi-centric/multi-focal breast cancer with differing genetic profiles (ER/HER2/PR status differ; if multiple masses are present and not all are tested then exclude patient).
• Patient has bilateral breast cancer/DCIS.

Inclusion Criteria
•Aim 2 Blood:

Cases

• Patient has a biopsy confirmed diagnosis of target histology or radiographic criteria that are unequivocal for diagnosis (example, meets radiographic criteria for hepatocellular carcinoma)

Controls

• Patient does not have a diagnosis of the target histology.

Exclusion Criteria
•Aim 2 Blood:

Cases and Controls

• Patient has known cancer outside of the target cancer 5 years prior to blood collection (not including basal cell or squamous cell skin cancers).
• Patient has had any transplants prior to blood collection.
• Patient has had any prior radiation therapy to the target lesion prior to blood collection.
• Patient has had a biopsy to the target organ and/or lesion within 3 days before blood collection.

Cases

• Patient has had an intervention to completely remove current target pathology.
• The current target pathology is a recurrence.
• Patient has multi-centric/multi-focal breast cancer with differing genetic profiles (ER/HER2/PR status differ; if multiple masses are present and not all are tested then exclude patient).
• Patient has bilateral breast cancer/DCIS.

Inclusion Criteria: Aim 3 Urine

Cases:

• Patient has a biopsy confirmed diagnosis of target histology or radiographic criteria that are unequivocal for diagnosis (example, meets radiographic criteria for hepatocellular carcinoma).

Controls:

• Patient does not have a diagnosis of the target histology.

• Patient has known cancer outside of the target cancer 5 years prior to urine collection (not including basal cell or squamous cell skin cancers).
• Patient has received chemotherapy class drugs in the 5 years prior to urine collection.
• Patient has had any prior radiation therapy to the target lesion prior to urine collection.
• Patient has had a biopsy to the target organ and/or lesion within 3 days before urine collection.
• The current target pathology is a recurrence.
• Patient has chronic indwelling urinary catheter.
• Patient has had a urinary tract infection within the 14 days prior to sample collection.
• If patient does not have a primary bladder , ureter or urethral cancer, patient has a history of bladder ureter, or urethral cancer.

Cases:

• Patient has had an intervention to completely remove current target pathology.
• The current target pathology is a recurrence.
• Patient has multi-centric/multi-focal breast cancer with differing genetic profiles (ER/HER2/PR status differ; if multiple masses are present and not all are tested then exclude patient).
•  Patient has bilateral breast cancer/DCIS.

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

Eligibility last updated 6/16/23. Questions regarding updates should be directed to the study team contact.

• Subjects with an ocular tumor.
• Subjects with a family history of an ocular tumor.
• Subjects without an ocular tumor and no family history of ocular tumor who would serve as a control in specific case-control experiments.
• Subjects within the United States who are not currently Mayo Clinic patients.
• Ability to understand and willingness to sign the informed consent documents.

• Unable or unwilling to sign or understand the informed consent documents.
• Unwilling to participate in the research.
• Unwilling to allow genetic testing.
• Unwilling to allow samples to be sent to other institutions for testing.
• Not meeting the inclusion criteria.

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

Eligibility last updated 11/2/23. Questions regarding updates should be directed to the study team contact.

• Subject is male or female.
• Subject is at least 30 years old.
• Subject is female and must be nonpregnant and nonlactating. A woman of childbearing potential must have a documented negative pregnancy test at screening.
  • NOTE: A woman is considered to be of childbearing potential unless she is postmenopausal (amenorrheic for at least 2 years) or documented to be surgically sterile (bilateral tubal ligation or total hysterectomy). A female subject may be admitted to the study on the basis of a negative urine pregnancy test. If the urine bHCG (beta human chorionic gonadotropin) test is positive, a serum bHCG test must be performed. The pregnancy test must be confirmed negative for a subject to be eligible for this study.
• During the study and for 30 days after receiving the last dose of the study drug, females of childbearing potential or males capable of fathering children must agree to use highly effective birth control measures (failure rate <1% when used consistently and correctly) or agree to abstain from sexual intercourse.
• Subject must meet the diagnostic criteria of nOH, as demonstrated by a sustained reduction in BP of ≥ 20 mmHg (systolic) or ≥ 10 mmHg (diastolic) within 3 min of being tilted up to ≥ 60° from a supine position as determined by a tilt-table test.
• Subject must score at least a 4 on the Orthostatic Hypotension Symptom Assessment Question #1 at randomization visit.
• For subjects with PD only: Subject has a diagnosis of PD according to the United Kingdom Parkinson’s Disease Society (UKPDS) Brain Bank Criteria (1992).
• For subjects with MSA only: Subject has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008).
• For subjects with PAF only: Subject has documented impaired autonomic reflexes, including the Valsalva maneuver performed within 24 months from the date of randomization.
• Subject has plasma NE levels >100 pg/mL after being in seated position for 30 minutes.
• Subject is willing and able to provide signed and dated written informed consent to participate prior to initiation of any study related procedures.
• Subject is able to communicate well with the investigator and clinic staff, understands the expectations of the study and is able to comply with the study procedures, requirements, and restrictions.

• Subject has a known systemic illness known to produce autonomic neuropathy, including but not limited to amyloidosis and autoimmune neuropathies. Subject has diabetes mellitus and diagnosis of PAF. Subject with diabetes mellitus and either MSA or PD, will be evaluated on a case by case basis by the medical monitor and considered ineligible unless they meet all of the following criteria:
  • Well controlled type-2 DM in treatment with only oral medications and diet;
  • HgbA1C of ≤ 7.5% performed during screening or up to 12 weeks before screening;
  • No clinically evident peripheral neuropathy (e.g., normal sensory examination on peripheral extremities);
  • No known retinopathy (e.g., annual ophthalmic exam is sufficient);
  • No nephropathy (e.g., absence of albuminuria and GFR > 60).
• Subject has a known intolerance to other NRIs or SNRIs.
• Subject currently uses concomitant antihypertensive medication for the treatment of essential hypertension.
• Subject has used strong CYP1A2 inhibitors or inducers within 7 days or 5 half-lives, whichever is longer, prior to randomization or requires concomitant use until the follow-up visit.
• Subject has changed dose, frequency, or type of prescribed medication for orthostatic hypotension within 7 days prior to randomization visit.
  •  Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to randomization.
• Subject has a known or suspected alcohol or substance abuse within the past 12 months (DSM-IV-TR® definition of alcohol or substance abuse).
• Subject has a clinically unstable coronary artery disease, or major cardiovascular or neurological event in the past 6 months.
• Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to randomization.
• Subject has a history of untreated closed angle glaucoma, or treated closed angle glaucoma that, in the opinion of an ophthalmologist, might result in an increased risk to the subject.
• Subject has any significant uncontrolled cardiac arrhythmia.
• Subject has a Montreal Cognitive Assessment (MoCA) ≤ 23.
• Subject is unable or unwilling to complete all protocol specified procedures including questionnaires.
• Subject had a myocardial infarction in the past 6 months or has current unstable angina. 
• Subject has known congestive heart failure (New York Heart Association [NYHA] Class 3 or 4).
• Subject has any malignant disease other than carcinoma in situ of the cervix or basal cell carcinoma within the past 2 years prior to screening.
• Subject has a known gastrointestinal (GI) condition, which in the investigator’s judgment, may affect the absorption of study medication (e.g., ulcerative colitis, gastric bypass).
• Subject has psychiatric, neurological, or behavioral disorders that may interfere with the ability of the subject to give informed consent or interfere with the conduct of the study.
• Subject is currently receiving any investigational drug or has received an investigational drug within 30 days of dosing. An investigational drug is defined as nonregulatory agency approved drug (e.g., Food and Drug Administration).
• Subject has a clinically significant abnormal laboratory findings (e.g., alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >3.0 x upper limit of normal [ULN]; blood bilirubin [total] > 1.5 x ULN; estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2, or any abnormal laboratory value that could interfere with safety of the subject).
• Subject has demonstrated a history of lifetime suicidal ideation and/or suicidal behavior, as outlined by the C-SSRS (Baseline/Screening Version) subject should be assessed by the rater for risk of suicide and the subject’s appropriateness for inclusion in the study.
• Subject has a concurrent disease or condition that, in the opinion of the investigator, would confound or interfere with study participation or evaluation of safety, tolerability, or pharmacokinetics of the study drug.
• Subject has known hypersensitivity to TD-9855 (ampreloxetine hydrochloride), or any excipients in the formulation.
• Subject has:
  • confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented with coronavirus disease 2019 [COVID-19] positive test result, OR (ii) is suspected of SARS-CoV-2 infection (clinical features without documented test results two weeks after resolution of symptoms and remains asymptomatic until Day 1); OR
  • has been in close contact with a person with known (or suspected) SARS-CoV-2 infection and remains asymptomatic until Day 1.

• Patient scheduled for open or laparoscopic liver surgery. 
• Age ≥ 18 years old. 

• Severe anemia (hemoglobin (Hgb) levels <90 g/l).
• Documented arterial or venous thrombosis at screening or in past three months (not including therapeutic portal vein embolization). 
• Anticoagulants (other than low-molecular-weight heparin (LMWH) or heparin in prophylactic doses to prevent deep vein thrombosis), direct thrombin inhibitors or thrombolytic therapy administered or completed within last week. 
• Known disseminated intravascular coagulation. 
• Severe renal insufficiency (creatinine clearance (CrCl) <30 ml/min).
• History of seizure disorder. 
• Pregnant or lactating (a negative urine pregnancy test must be obtained for women of child bearing potential during the pretreatment evaluation). 
• Acquired disturbance of colour vision
  •Hypersensitivity to TXA or any of the ingredients. 
• Unable to receive blood products (i.e., difficulty with cross matching, refuses blood transfusion, or a past history of unexplained severe transfusion reaction). 
• Previously enrolled in this study.

• Currently be 55 years of age or older.
• 50 participants:
  • Have a history of premenopausal bilateral salpingo-oophorectomy.
• 50 participants:
  • Have no history of premenopausal bilateral salpingo-oophorectomy.
• Participants for both cohorts must also be enrolled in another study on premenopausal bilateral salpingo-oophorectomy (IRB #18-008476).
• Must be willing and able to complete all study activities.
• Have provided written informed consent.

• They are younger than 55 years of age.
• They are < 6 months post-chemotherapy.
• They are < 6 months post-major surgery requiring general anesthesia.

• Adult patients (age ≥ 18 years)
• Adult patients with diagnosis of Congenital Heart Disease (i.e., Tetralogy of Fallot (TOF), Pulmonary Atresia, Coarctation of Aorta, etc.).

• Patients without research authorization.

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

• Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained.
• Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma.
• An FA severity score of 2 or 3 on the IGA scale.
• Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation.
• Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator.

• Patients who cannot carry out the treatment plan or follow-up assessment.
• Patients with serious skin lesions such as erosions or ulcers.
• Patients with known hypersensitivity to any component of the study product.
• Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment.
• Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment.
• Patients who participated in any other clinical trial within 3 months prior to the day of enrolment.
• Patients judged unsuitable for this clinical trial by the investigator or sub-investigator.
• Pregnant or lactating females.
• Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception.
• Patients with immune dysfunction or receiving any form of immunosuppression.
• Patients with severe FA, with a score of 4 on the IGA scale.
• Patients with an FA severity score of less than 2 on the IGA scale.