• TIA with ABCD2 ≥ 4 or ischemic stroke, within the prior 14 days.

• Pre-event inability to perform all of own basic ADLs.
• Unable to obtain informed consent from subject or legally authorized representative.
• Incarcerated.
• Known pregnancy.
• Current mechanical ventilation (can enroll later if this resolves) or tracheostomy.
• Current use of positive airway pressure, or use within one month prior to stroke.
• Anatomical or dermatologic anomaly that makes use of CPAP interface unfeasible.
• Severe bullous lung disease.
• History of prior spontaneous pneumothorax or current pneumothorax.
• Hypotension requiring current treatment with pressors (can enroll later if this resolves).
• Other specific medical circumstances that conceivably, in the opinion of the site PI, could render the patient at risk of harm from use of CPAP.
• <assive epistaxis or previous history of massive epistaxis.
• Cranial surgery or head trauma within the past 6 months, with known or possible CSF leak or pneumocephalus.
• Recent hemicraniectomy or suboccipital craniectomy (i.e., those whose bone has not yet been replaced), or any other recent bone removal procedure for relief of intracranial pressure.
• Current receipt of oxygen supplementation > 4 liters per minute.

• Male and female volunteers > 18 years old.
• Male and female volunteers with symptom of claudication and suspected peripheral arterial disease (PAD) who are scheduled for vascular testing.

• Patients with gangrene.
• Patients with lower leg amputation.
• Having ulcer and any health condition that does not allow proper use of ultrasound scanning.
• People considered in “vulnerable” populations.

• Male and female patients with liver cancers.
• Undergoing medical therapy.
• Age 18 or greater.
• Body mass index (BMI) below 40.

• Patients with unreliable ultrasound images due to conditions such as fatty liver or poor ultrasound imaging window.
• Adults lacking capacity to consent.
• Vulnerable subjects such as prisoners, pregnant women, nursing mothers, patients with known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts.
• Patients with history of hypersensitivity allergic reactions to ultrasound contrast agents.

• All participants will be 50 years of age or older and younger than 85 years of age. 
• All participants will be stratified into those with or without gastroesophageal reflux disease (defined as symptoms of heartburn or acid regurgitation more than once a week, or taking proton pump inhibitors for more than 3 months, or those with the diagnosis of gastroesophageal reflux disease in the diagnostic index, or those with endoscopic evidence of esophagitis).
• Other risk factors considered would include:
  • Caucasian race;
  • History of ever smoking (current or prior history of smoking);
  • BMI greater than equal to 30;
  •  Family history of Barrett's esophagus or esophageal adenocarcinoma;
  •  Male sex.

• History of Barrett's esophagus or esophageal adenocarcinoma.
• Prior endoscopy in the last 10 years.
• Pregnant or lactating females.
• Patients who are unable to consent.
• Patients with current history of uninvestigated dysphagia
• History of eosinophilic esophagitis, achalasia.
• Patients on oral anticoagulation including Coumadin, Warfarin.
• Patients on antiplatelet agents including Clopidogrel (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients with history of known varices or cirrhosis.
• Patients with history of esophageal or gastric resection.
• Patients with congenital or acquired bleeding diatheses.
• Patients with a history of esophageal squamous dysplasia or esophageal squamous carcinoma.
• Identification of patients meeting inclusion and exclusion criteria was done using two institutional EMR search tools (i2b2 and ACE) using ICD and CPT codes listed below along with NLP for some terms.

• All participants will be 50 years of age or older and younger than 85 years of age. 
• All participants will be stratified into those with or without gastroesophageal reflux disease (defined as symptoms of heartburn or acid regurgitation more than once a week, or taking proton pump inhibitors for more than 3 months, or those with the diagnosis of gastroesophageal reflux disease in the diagnostic index, or those with endoscopic evidence of esophagitis).
• Other risk factors considered would include:
  • Caucasian race;
  • History of ever smoking (current or prior history of smoking);
  • BMI greater than equal to 30;
  •  Family history of Barrett's esophagus or esophageal adenocarcinoma;
  •  Male sex.

• History of Barrett's esophagus or esophageal adenocarcinoma.
• Prior endoscopy in the last 10 years.
• Pregnant or lactating females.
• Patients who are unable to consent.
• Patients with current history of uninvestigated dysphagia
• History of eosinophilic esophagitis, achalasia.
• Patients on oral anticoagulation including Coumadin, Warfarin.
• Patients on antiplatelet agents including Clopidogrel (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients with history of known varices or cirrhosis.
• Patients with history of esophageal or gastric resection.
• Patients with congenital or acquired bleeding diatheses.
• Patients with a history of esophageal squamous dysplasia or esophageal squamous carcinoma.
• Identification of patients meeting inclusion and exclusion criteria was done using two institutional EMR search tools (i2b2 and ACE) using ICD and CPT codes listed below along with NLP for some terms.

Aim 1

• All participants will be 50 years of age or older and younger than 85 years of age. 
• All participants will be stratified into those with or without gastroesophageal reflux disease (defined as symptoms of heartburn or acid regurgitation more than once a week, or taking proton pump inhibitors for more than 3 months, or those with the diagnosis of gastroesophageal reflux disease in the diagnostic index, or those with endoscopic evidence of esophagitis).
• Other risk factors considered would include:
  • Caucasian race;
  • History of ever smoking (current or prior history of smoking);
  • BMI greater than equal to 30;
  •  Family history of Barrett's esophagus or esophageal adenocarcinoma;
  •  Male sex.

• History of Barrett's esophagus or esophageal adenocarcinoma.
• Prior endoscopy in the last 10 years.
• Pregnant or lactating females.
• Patients who are unable to consent.
• Patients with current history of uninvestigated dysphagia
• History of eosinophilic esophagitis, achalasia.
• Patients on oral anticoagulation including Coumadin, Warfarin.
• Patients on antiplatelet agents including Clopidogrel (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients with history of known varices or cirrhosis.
• Patients with history of esophageal or gastric resection.
• Patients with congenital or acquired bleeding diatheses.
• Patients with a history of esophageal squamous dysplasia or esophageal squamous carcinoma.
• Identification of patients meeting inclusion and exclusion criteria was done using two institutional EMR search tools (i2b2 and ACE) using ICD and CPT codes listed below along with NLP for some terms.

Aim 2:

 Inclusion criteria:

1. Subjects with known BE (cases).

1. Patient between the ages 18 – 90.
2. Patients with a BE segment ≥ 1cm in maximal extent endoscopically.
3. Histology showing evidence of intestinal metaplasia with or without presence of dysplasia.
4. Undergoing clinically indicated endoscopy.

1. Subjects without known history of BE (controls).

1. Undergoing clinically indicated diagnostic endoscopy.

Exclusion criteria:

a. Subjects with known BE.

1. Patients with prior history of ablation (photodynamic therapy, radiofrequency ablation, cryotherapy, argon plasma coagulation). Patients with history of endoscopic mucosal resection alone will not be excluded.
2. Patients with history of esophageal or gastric resection. 

b. Subjects with or without known evidence of BE (on history or review of medical records).

1. Pregnant or lactating females.
2. Patients who are unable to consent.
3. Patients with current history of uninvestigated dysphagia (this does not apply to the brushings only portion of the study).
4. History of eosinophilic esophagitis, achalasia.
5. Patients on oral anticoagulation including Coumadin, Warfarin.
6. Patients on antiplatelet agents including Clopidogrel, unless discontinued for three to five days prior to the sponge procedure.
7. Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban, unless discontinued for three to five days prior to the sponge procedure.
8. Patients with history of known varices or cirrhosis.
9. Patients with history of esophageal or gastric resection. 
10. Patients with congenital or acquired bleeding diatheses.
11. Patients with a history of esophageal squamous dysplasia.

Aim 3:

Inclusion and exclusion criteria will be those outlined under Aims 1 and 2.

• All participants will be 50 years of age or older and younger than 85 years of age. 
• All participants will be stratified into those with or without gastroesophageal reflux disease (defined as symptoms of heartburn or acid regurgitation more than once a week, or taking proton pump inhibitors for more than 3 months, or those with the diagnosis of gastroesophageal reflux disease in the diagnostic index, or those with endoscopic evidence of esophagitis).
• Other risk factors considered would include:
  • Caucasian race;
  • History of ever smoking (current or prior history of smoking);
  • BMI greater than equal to 30;
  •  Family history of Barrett's esophagus or esophageal adenocarcinoma;
  •  Male sex.

• History of Barrett's esophagus or esophageal adenocarcinoma.
• Prior endoscopy in the last 10 years.
• Pregnant or lactating females.
• Patients who are unable to consent.
• Patients with current history of uninvestigated dysphagia
• History of eosinophilic esophagitis, achalasia.
• Patients on oral anticoagulation including Coumadin, Warfarin.
• Patients on antiplatelet agents including Clopidogrel (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients on oral thrombin inhibitors including Dabigatran and oral factor X a inhibitors such as rivaroxaban, apixaban and edoxaban (Visit 1), unless discontinued for three to five days prior to the sponge procedure (Visit 2 and 3).
• Patients with history of known varices or cirrhosis.
• Patients with history of esophageal or gastric resection.
• Patients with congenital or acquired bleeding diatheses.
• Patients with a history of esophageal squamous dysplasia or esophageal squamous carcinoma.
• Identification of patients meeting inclusion and exclusion criteria was done using two institutional EMR search tools (i2b2 and ACE) using ICD and CPT codes listed below along with NLP for some terms.

• Subjects over the age of 18 able to provide consent or have a legally authorized consent in the event the subject is unable to consent due to a transient clinical condition.
• Subject scheduled to undergo a TIPS procedure.

• Minors under the age of 18 at the time of enrollment.
• Prisoners.
• Pregnant women.
• Subjects undergoing TIPS placement as part of an investigational study outside of usual clinical care.

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• Patient is an adult (18 years of age or older).

• Treatment with Envarsus XR® or immediate-release, twice-daily tacrolimus has been indicated by patient’s transplant care team. 

• Patient is a recipient of a deceased or living donor kidney transplant.
• Patient is able to comply with study procedures for the entire length of the study.
• Patient has been informed about the study survey and has signed an informed consent form.

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Patient is unable or unwilling to complete study patient reported outcome questionnaires.
• Patient is currently receiving azathioprine
• Patient is currently receiving an mTOR inhibitor (sirolimus, everolimus)
• Patient is currently receiving belatacept .
• Patient has received investigational immunosuppression 1 month prior to transplant or post-transplant.
• Patient is in a setting where a professional care taker is responsible for dispensing subject’s medication.

• Histologically confirmed pancreatic adenocarcinoma with vascular involvement, either borderline/potentially resectable or locally advanced.
• Borderline resectable is defined by the NCCN as tumors (based on cross sectional imaging) with venous involvement of the SMV/portal vein demonstrated tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall. Tumors involving retroperitoneal structures that can be surgically removed (i.e., kidney), will also be included.
• Locally advanced unresectable disease is defined by the NCCN as: Tumors of the head that have greater than 180 degrees of SMA encasement or any celiac abutment, unreconstructable SMV or portal occlusion, or aortic invasion or encasement. Tumors of the body with SMA or celiac encasement of greater than 180 degrees, unreconstructable SMV or portal occlusion, or aortic invasion. Tumors of the tail with SMA or celiac encasement of greater than 180 degrees. Irrespective of location, all tumors with evidence of nodal metastasis outside of the resection field are deemed unresectable.
• Age ≥ 18 years old.
• ECOG Performance Status 0-1.
• Previous completion of at least three (3) months of EITHER gemcitabine plus nab-paclitaxel OR FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan and leucovorin)
• Previous completion of either stereotactic-body radiation therapy (SBRT) (minimum 24 Gy) or external beam irradiation (EBRT) (minimum 45 Gy or 36 Gy in 15 fractions).
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment is PERMITTED.
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months after IORT.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after IORT. Women who are not of childbearing potential; i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
• Ability to understand and the willingness to sign a written informed consent document.

• Evidence of disease progression or distant metastases.
• Pregnant or lactating women.
• Treatment for other invasive carcinomas within the last five years who are at greater than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/ squamous cell carcinoma of the skin are allowed.
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• An active infection requiring systemic therapy.
• Other serious medical conditions that the investigator feels might compromise study participation.

• > 18 years old.
• AO classification Type 44 A, B, C.
• posterior malleolus fragment measuring < 25% of the maximal A-P diameter of the tibial plafond as measured on pre-operative CT.

• Previous surgery about the ankle.
• Non-ambulatory status preoperatively.
• Ipsilateral lower extremity injury which would be expected to affect mobility status’.
• Contraindication to prone positioning during surgery.

Inclusion Criteria (for 0169 Completers Group): 

• Subject has completed 4 weeks of double blind treatment in Study 0169 (V6) and, in the opinion of the Investigator, could benefit from continued treatment with TD-9855. No minimum score of OHSA#1 is required to enter V1 of Study 0170. 
• Subject has a minimum of 80% study medication compliance in Study 0169.
• The subject must be able to understand the nature of the study and must provide written informed consent prior to the conduct of any study procedures (including an understanding that entry to Study 0170 may result in changes occurring in the subject’s current therapeutic regimen).
• The subject must be willing to continue on treatment regardless of the possibility of randomization to either TD-9855 or PBO during the randomized withdrawal phase and must continue to meet the inclusion criteria for the preceding study (Study 0169) with the exception that tilt-table test, ESC review and approval of eligibility are not required for entry into Study 0170.

Inclusion Criteria (For De Novo Group): 

• Subject is male or female and at least 30 years old;
• Subject must meet the diagnostic criteria of snOH, as demonstrated by a ≥ 20 mm Hg (systolic) or ≥10 mm Hg (diastolic) within 3 min of being tilted-up ≥ 60o from a supine position as determined by a tilt-table test;
• Subject must score at least a 4 on the OHSA#1 at V1. 
• 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 impaired autonomic reflexes, as determined by absence of Phase IV BP overshoot after release of the Valsalva strain. 
• Subject has plasma Norepinephrine (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 understand clinic staff, understands the expectations of the study and is able to comply with the study procedures, requirements, and restrictions.

Exclusion Criteria (for 0169 Completers Group): 

• Subject may not be enrolled in another clinical trial (other than exiting Study 0169).
• Subject has psychiatric, neurological, or behavioral disorders that may interfere with the ability of subjects to give informed consent or interfere with the conduct of the study.
• Medical, laboratory, or surgical issues deemed by the Investigator to be clinically significant. 
• Uncooperative attitude or reasonable likelihood of non-compliance with the protocol.
• 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.

Exclusion Criteria (For De Novo Group): 

• 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 serotonin norepinephrine reuptake inhibitors (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 V1 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 V1:
  • Midodrine and droxidopa (if applicable) must be tapered off at least 7 days prior to V1. 
• Subject has known or suspected alcohol or substance abuse within the past 12 months (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR®] definition of alcohol or substance abuse).
• Subject has a clinically unstable coronary artery disease or has had a major cardiovascular or neurological event in the past 6 months.
• Subject has used any monoamine oxidase inhibitor (MAO-I) within 14 days prior to V1.
• 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 had 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 drug that is not approved by a regulatory agency (e.g., Food and Drug Administration [FDA]).
• Subject has a clinically significant abnormal laboratory finding(s) (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/1.73 m^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
  • 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.
• At V3 (Week 4), following the initial 4-week OL treatment, subjects must demonstrate a reduction in OHSA#1 of at least 2 points compared to the baseline value, as determined in Study 0169 for subjects entering from Study 0169 and from V1 for de novo subjects, in order to continue in Study 0170.

• Age 18 to 70 years old.
• Chronic lumbar spine pain or other non-spine pain for ≥ 3 months duration.
• Scheduled for elective lumbar spine surgery or other non-spine surgery.
• Daily morphine equivalent dose between 50 mg and 200 mg.

• Cancer-related pain.
• Medical or surgical conditions that could be adversely impacted by opioid tapering or use of lofexidine including, but not exclusively limited to, cardiac disease, inflammatory bowel disease, renal or hepatic impairment, vascular disease, and history of anaphylaxis.  Patients may be excluded for other comorbid medical or surgical conditions based on the physician investigator’s discretion.
• History of schizophrenia or other chronic psychiatric disorder that could be adversely impacted by opioid tapering or use of lofexidine. Patients may be excluded for other comorbid mental health conditions based on the physician investigator’s discretion.
• Neurological condition that impair functioning in an ambulatory setting or could be adversely impacted by opioid tapering or use of lofexidine including, but not exclusively limited to, Parkinson’s disease, amyotrophic lateral sclerosis, or a dementing illness.  Patients may be excluded for other neurological conditions based on the physician investigator’s discretion.              
• Active substance abuse disorder.
• Inability to function in an ambulatory care setting due to severe deconditioning requiring use of supportive gait aids including a cane or walker.  Patients may be excluded for other functional problems based on the physician investigator’s discretion.      
• History of adverse effects attributed to opioid tapering or lofexidine use.
• Use of medications from drug classes known to have adverse interactions with lofexidine including, but not exclusively limited to, beta-blockers, calcium channel blockers, alpha 1 and 2 receptor antagonists, tricyclic antidepressants, benzodiazepines, and selective serotonin reuptake inhibitors.  Patients may be excluded for use of other medications based on the physician investigator’s and research pharmacy’s discretion.

• Any patient undergoing surgery or biopsy for malignancy in the kidney, bladder, prostate.
• Any patient undergoing resection or biopsy of tumor recurrence after surgery for malignancy in the kidney, bladder, prostate.
• Any patient undergoing resection or biopsy of tumor metastatic site after surgery for malignancy in the kidney, bladder, prostate.

• Inability to provide consent.
• Specimen and data related to this pilot study will be retained for future use in case we wish to perform further related studies and include these pilot patients in ensuing analyses. In that case, re-consent of patients will be required when they turn 18.   

• Patients from both genders and all ethnic backgrounds will be allowed with no reservation.

• Patients who do not consent to the study will be excluded despite being sequential.

• Displaced 3- and 4-part proximal humerus fractures.
• Age ≥ 65 years old and < 90 years old.

• < 65 years old or ≥ 90 years old.
• Medical comorbidities precluding surgical treatment or anesthesia.
• Dementia or inability to provide adequate follow up.
• Pathologic fractures.
• Open fractures.
• Associated injuries: fracture dislocations, multiple or complex injuries of the ipsilateral limb, complete brachial plexopathy, vascular injury and polytrauma.

• Subjects between 18-55 years of age. 
• Non-obese (BMI < 30).
• Non-smokers.
• Free of any systemic diseases including hypertension, diabetes, coronary artery disease, neurologic disease, or any other major medical co-morbidity. 
• Women will be either surgically sterilized or non-pregnant as determined by a urine pregnancy test.  Urine pregnancy tests will be completed within 48 hours of any study intervention. If the test is positive they will not be able to participate in the study.
• All inclusion/exclusion criteria will be at the discretion of the Principal Investigator.    

• None.

• Neurologic Surgery, ENT, plastic surgery, orthopedic surgery, urology resident, fellow and staff surgeons.

• Unable to give informed consent.

• Age ≥ 18 years old (HCC is rare in US children).
• Diagnosis of HCC with cross-sectional imaging or histology.
• 3D MRE of the liver was performed within 1 month of diagnosis.

• History of secondary hepatic malignancy.
• Any medical condition that, in the opinion of the Principal Investigators, would serve as exclusion criteria.

• Diagnosis of large duct PSC.
• Liver biopsy at screening that is deemed acceptable for interpretation and demonstrates stage F0. 
• F3 fibrosis in the opinion of the central reader. 
• Individual has the following laboratory parameters at the screening visit, as determined by the central laboratory: 
  • Platelet count ≥ 150,000/mm^3; 
  • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation;
  • ALT ≤ 8 x upper limit of the normal range (ULN);
  • Total bilirubin < 2 mg/dL, unless the individual is known to have Gilbert's syndrome or hemolytic anemia; 
  • International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation;
  • Negative anti-mitochondrial antibody.

Current or prior history of any of the following:

• Cirrhosis; 
• Liver transplantation; 
• Cholangiocarcinoma or hepatocellular carcinoma (HCC); 
• Ascending cholangitis within 30 days of screening; 
• Presence of a percutaneous drain or biliary stent;
• Other causes of liver disease; 
• Current or prior history of unstable cardiovascular disease;
• Current moderate to severely active inflammatory bowel disease (IBD).

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

• At least 18 years of age, at the time of signing the informed consent. 
• Signs and symptoms of CDI including diarrhea such that in the Investigator's opinion CDI antimicrobial therapy is required. Diarrhea is defined as a change in bowel habits, with ≥ 3 Unformed Bowel Movements (UBMs) (5, 6 or 7 on the Bristol Stool Chart) in the 24 hours prior to randomization. 
• The presence of either toxin A and/or B of C. difficile in the stool determined by a positive free toxin test, produced within 72 hours prior to randomization. 
• Male or Female
  •Male must agree to use contraception as detailed in the protocol during the treatment period and for at least 5 days after study treatment and refrain from donating sperm during this period.
• Female patient is eligible to participate if she is not pregnant, not breastfeeding, and either:
• Not a woman of childbearing potential (WOCBP). A WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and for at least 5 days after study treatment. 
• Documented signed informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI]).

• More than one prior episode of CDI in the previous 3 months or more than 3 episodes in the past 12 months.
• A history of chronic diarrheal disease including inflammatory bowel disease (Crohn's disease or ulcerative colitis). 
• Positive diagnostic test for other gastro intestinal (GI) pathogens within 2 weeks of randomization. 
• Major gastrointestinal (GI) surgery (e.g., significant bowel resection) within 3 months of randomization (except appendectomy). Presence of a colostomy or ileostomy or likely requirement of an ostomy during the study. 
• Life threatening or fulminant CDI with evidence of hypotension, septic shock, peritoneal signs or absence of bowel sounds, or toxic megacolon. 
• Current history of significantly compromised immune system:
  • HIV positive with a CD4<200 cells/mm3 within 6 months of randomization;
  • Severe neutropenia with neutrophil count < 500 cells/mL;
  • Concurrent immunosuppressive therapy for recent (within previous 6 months) or anticipated solid organ transplant or bone marrow transplant;
  • Concurrent chemotherapy, radiotherapy or biologic for active malignancy. Or active malignancy with ablative chemotherapy within the past 3 months or anticipated during the study;
  • More than one day (24 hours) of dosing of antimicrobial treatment active against CDI for the current episode of CDI prior to randomization;
  • Prior or current use of anti-toxin antibodies including bezlotoxumab;
  • Unable to discontinue products used to affect bowel movement or disease progression;
  • Involved in a clinical trial and received an IMP for indications other than CDI within 1 month or five half-lives (whichever is longer) or within 3 months if the IMP was for CDI;
  • Received an investigational vaccine against C.difficile;
  • Patients that the Investigator feels are inappropriate for the study for any other reason; e.g., have any conditions that would make the patient unsuitable for inclusion, patients not likely to complete the study for whatever reason, known hypersensitivity or intolerance to study IMPs, patients unwilling or unable to comply with protocol requirements.

Inclusion Criteria
•Aim 1:

• Patient volunteers, ages ≥ 18 years.
• Having suspicious breast masses scheduled for breast biopsy.
• At least two weeks or more after breast biopsy.

Inclusion Criteria
•Aim 2:

• Patient volunteers, ages ≥ 18 years.
• Suspicious breast masses scheduled for breast biopsy.
• At least two weeks or more after breast biopsy.

Exclusion Criteria
•Aims 1 and 2: 

• Patients with breast implants, mastectomy or any condition that does not allow proper use of U.S.

   

   

   

   

• Age 18-99 years old.
• Diagnosis of cancer and undergoing cancer therapy or scheduled to start cancer therapy or undergoing stem cell transplant for any hematological condition.

• Unable to provide informed consent.
• Vulnerable adults.

• Women > 35 years old and < 75 years old with at least one of the following:
  • A NCI-BCRAT 5 year risk of ≥ 3% which corresponds to the level in which there is moderate evidence of treatment benefit outweighing risk according to the US Preventative Services Task Force; or
  • IBIS (Tyrer-Cuzik) score for the 10 year risk of breast cancer of ≥ 5%;
  • History of atypical ductal hyperplasia or atypical lobular hyperplasia with a BCRAT ≥ 3% or IBIS ≥ 5%; OR
• Women ≥ 18 years old or ≤ 75 years old with a:
  • BRCA 1 or 2  mutation;
  • CHEK 2;
  • PALB 2;
  • ATM; or
  • Other hereditary breast mutation carrier per investigator; AND
• Able to participate in all aspects of the study.
• Understand and sign the study informed consent. 

• 1. 1.  
• Women whose BCRAT falls below the threshold (< 3% 5 year risk) of moderate benefit according to the US Preventative Task Force AND Women whose IBIS score is < 5% for the 10 year risk.
• Women with known contra-indications to Tamoxifen, raloxifene ,exemestane, or anastrazole.
• Current or prior use of Tamoxifen, raloxifene, exemestane or anastrazole for ≥ 6 months.
• Unable to give informed consent.
• Prior history of invasive breast cancer, ductal carcinoma in situ or other breast cancers.
• History of ovarian cancer within the last 2 years.
• Recurrence of ovarian cancer at any timepoint.
• Prior bilateral  prophylactic mastectomy.
• Women who are currently pregnant.

Eligibility last updated 2/24/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 12/20/22. Questions regarding updates should be directed to the study team contact.

• Documented diagnosis of UC at least 12 weeks prior to screening.
• Active UC with an an adapted Mayo score of 5 to 9 points, endoscopic subscore of ≥ 2. 
• Demonstrated an inadequate response, loss of response, or intolerance to at lease one of the following treatments including, 5-aminosalicylic acids (ASAs), corticosteroids, immunosuppressants, anti-tumor necrosis factor (TNF)-α agents, integrin inhibitor.

• Participant with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC), ischemic colitis, pseudomembranous colitis.
• Current evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation. 
• History or evidence of any extensive colonic resection, subtotal or total colectomy, with or without presence of a stoma or ileoanal pouch.

• Diagnosis of HCV infection with laboratory test and verified by histological examination.
• Liver MRE was performed within 3 months of histological analysis.
• Age ≥ 18 years old.

• Patients with HBV coinfection (10% a high risk of parenteral transmission).
• Perinatal transmission (because of the immature immunity system, the infection becomes chronic much easily; cause delayed virus clearance).
• Patients with HIV infection (lower immune activity).
• Patients have alcohol abuse.
• Patients have antiviral treatment between liver biopsy and MRE examination.
• Any medical condition that, in the opinion of the Principal Investigator, would serve as exclusion criteria for study enrollment.

Inclusion Criteria (Group A and B):

• Patient with either GM1 gangliosidosis, GM2 gangliosidoses (Tay-Sachs, Sandhoff, AB Variant), or GD2.
• Diagnosis confirmed by either biochemical (enzyme activity) or genetic testing, or both.
• Date of birth on or after 1 January 2000.
• Onset of the first neurological symptom within the first 24 months of age.
• Informed consent of parent or legal guardian as required by local law.

• Any diversion from the above Inclusion Criteria.

• Patients fulfilling the inclusion criteria will be eligible for enrollment in this study.
• Of those who consent, only patients who lack a suitable HLA-identical or 1 allele or antigen mismatched related donors are evaluable.
• Patients with an HLA-identical sibling or 1 allele or antigen mismatched family member donor are evaluable as long as the center deems the family member donor as unsuitable for other reasons.
• Patients may co-enroll with other interventional or observational studies.
• Patients of all ages with AML, ALL, MDS, NHL, HL, AA, or SCD are eligible. 
• Any planned conditioning regimen and GVHD prophylaxis approach is eligible. 
• Patients must be considered suitable allogeneic transplant candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used by the treating physician to judge transplant suitability. 
• Patient and physician must intend to proceed with allogeneic HCT within the next 6 months if a suitable donor is identified. 
• Center plans to follow the algorithm for alternative donor identification:
  • for subjects who are Very Likely to find a MUD, attempt to identify a matched unrelated donor; 
  • for a subjects who are Very Unlikely to find a MUD, proceed expeditiously to a haploidentical, cord blood or mismatched unrelated donor.
• Signed informed consent, and assent if applicable. Consent may be signed prior to completion of family typing but patients will only be considered evaluable upon confirmation that there is no suitable HLA-identical or 1 allele or antigen mismatched related donor available.

• Prior allogeneic HCT (prior autologous transplant is allowed).
• Previous formal unrelated donor search.

• Diagnosis of Alzheimer’s Dementia according to NIA-AA Criteria for dementia.
• MMSE ≤ 15.
• Cohen-Mansfield Agitation Inventory Nursing Home Version (CMAI) score of >5 on at least one item of aggression or a physical nonaggressive item that holds potentially dangerous consequences including hitting (including self), kicking, grabbing onto people, pushing, throwing things, biting, scratching, spitting, hurting self or other, tearing things or destroying property, making physical sexual advances, trying to get to a different place, intentional falling, screaming, making verbal sexual advances, and cursing or verbal aggression (items 1-11, 14, 15, 22-24).
• At least three failed pharmacological interventions from different drug classes (including antidepressants, antipsychotics, anticonvulsants, prazosin, and cannabinoids) at therapeutic doses (to be determined by clinical judgment) and duration of at least two weeks each to manage behavioral symptoms. These interventions may also include medications discontinued after 1 week due to tolerability concerns. Furthermore, medication trials that occur prior to admission to the hospital may count towards the three failed trials. The trials can be inpatient and/or outpatient. These trials can also be concurrent, such as using two medications from different classes for at least one week  at the same time (i.e., polypharmacy).
• Medically stable for safe administration of ECT verified by standard physical examination, urinalysis and serum chemistries.
• Comprehension of English language.
• Authorized legal representative able and willing to give informed consent.
• Age 55
  •89 years old (inclusive).

• Current diagnosis of co-morbid delirium, measured by the Confusion Assessment Method (CAM) and by clinical diagnosis.
• Diagnosis of Non-AD Dementia.
• Lifetime or current diagnosis of Schizophrenia, Bipolar Disorder or Schizoaffective Disorder.
• Active substance use disorder within past 6 months.
• Treatment with ECT or other neurostimulation therapies (e.g., TMS or vagal nerve stimulation) within the past 3 months.