• All patients undergoing surgery by Dr. Bakri.
• Any waste tissue will be saved.

• None.

• Provision of signed and dated informed consent form.
• Stated availability and willingness to comply with all study procedures until referred to a clinical trial.
• Age 50-85 (inclusive).
• Global Clinical Dementia Rating (CDR) score of 0 or 0.5 and no diagnosis of dementia.
• Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily function.
• In good general health as evidenced by medical history.
• Adequate visual and auditory acuity to allow neuropsychological testing.
• Fluent in English or Spanish.
• For females who are not surgically sterile or post-menopausal by two years, receiving a Positron Emission Tomography (PET) scan for amyloid biomarker confirmation: negative pregnancy test prior to amyloid PET scan.
• Completed six grades of education or has a good work history.
• Evidence of elevated or intermediate (subthreshold) levels brain amyloid as assessed by central review of amyloid PET or cerebrospinal fluid (CSF) data. Prior amyloid testing results may be used with approval from the Coordinating Center.

• Treatment with another anti-amyloid investigational drug or other intervention within 12 months.
• Enrolled in another interventional clinical trial within the last 12 weeks.
• Any significant neurologic disease such as Alzheimer's disease dementia, Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
• Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol.
• History of schizophrenia (DSM V criteria).
• History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria).
• Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
• History within the last 3 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment.
• Clinically significant abnormalities in B12 or thyroid function tests (TFTs) that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
• Clinically significant abnormalities in screening laboratories or ECG.
• For participants undergoing CSF collection: a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening or if on anti-coagulation (e.g. warfarin).
• Participants whom the Site PI deems to be otherwise ineligible.
  • Site PIs should consult with the Coordinating Center on any issues that may disqualify the participant from participation in future clinical trials to determine whether enrollment into TRC would be appropriate.

Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the Project Director and Coordinating Center.

• Subjects who have received at least one dose of GSK3377794 in the interventional study.
• Subjects who have either completed the interventional study or have withdrawn from it.
• Male or female subjects.
• Capable of giving signed informed consent prior to the study participation.

• None.

• Age 18+ Years Old.
• Diagnosis of Chronic Lymphocytic Leukemia (B-CLL).

• Pregnant.

• Individuals with spinal cord injury who have received an epidural spinal stimulation implant for return of functional return.
• Individuals who have received an epidural spinal stimulation implant but have since had it removed.
• English speaking individuals.

• Individuals with spinal cord injury who have received an epidural spinal stimulation implant for pain.
• Non-English speaking individuals.

Inclusion Criteria (Prostate Cancer Patients):

• ≥ 18 years of age.
• Able to give informed consent.
• Patients with prostate cancer.
• Patients treated with primary prostatectomy.

Inclusion Criteria (Female Control Patients)

• ≥ 18 years of age. 
• Able to give informed consent.                                                        

Exclusion Criteria (Prostate Cancer Patients): 

• Unable or unwilling to provide informed consent.
• Metastatic prostate cancer – defined radiographic evidence of metastatic disease on pre-procedural testing.

Exclusion Criteria (Female Control Patients)

• Unable or unwilling to provide informed consent.

Eligibility last updated 11/17/22. Questions regarding updates should be directed to the study team contact.

• Men and women age 65 years or older.
• Current PD diagnosis with symptoms severity at Hoehn & Yahr (H&Y) stage 1-4 based on an expert assessment (movement disorders neurologist report or telemedicine evaluation).
• Willing and able to continue in follow-up for at least 2 years.
• Willing and able to provide informed consent.

• History of hip fracture.
• Any use of a bisphosphonate drug within the last 12 months.
• Use of any other osteoporosis treatment (such as SERMs and denosumab) within the last 6 months.
• Tooth extraction or invasive dental procedures within the past 30 days or planned/scheduled extraction/procedure in the next 12 months.
• Non-ambulatory; i.e., unable to walk without assistance of another person.
• Undergoing kidney dialysis.
• A diagnosis of multiple myeloma or Paget's disease.
• Unable to speak or read English sufficiently to complete informed consent.
• Any other criteria, which would make the patient unsuitable to participate in this study as determined by the study staff (e.g., an uncontrolled drug and/or alcohol addiction).

Surgery Cohort

• Maternal age ≥ 18 years old.
• Pregnant with a congenital anomaly diagnosis.
• Undergoing endoscopic in utero fetal intervention.
• Singleton pregnancy
• Delivery planned at Mayo Clinic.

Control Cohort

• Maternal age ≥ 18 years old.
• Pregnant with normal ultrasound findings.
• Singleton pregnancy
• Delivery planned at Mayo Clinic.

• Delivery planned elsewhere.
• Abnormal fetal karyotype.
• Multiples (i.e. twins/triplets, etc)
• Undergoing open in utero fetal intervention

• Patients with diagnosis of mitral annular calcification (MAC) (case group) and patients coming to the Valve Clinic without MAC diagnosis (control group).
• Patients who will undergo surgery, either standard surgical MVR or trans-atrial TMVR, with diagnosis of MAC (case group) or without diagnosis of MAC (control group).

• Subjects unwilling to participate or to provide consent.

• Adults, ≥ 18 years old.
• Adults with lung disease undergoing lung resection surgery.

• < 18 years old.

• Male or female aged 18 years and older.
• Females of childbearing potential must have a negative pregnancy test prior to receiving the study drug and will agree to use adequate contraception (hormonal/barrier method or abstinence) from the time of screening to a period of 1 year following completion of the drug treatment cycle.  Females of childbearing potential are defined as premenopausal and not surgically sterilized, or post-menopausal for fewer than 2 years. If the urine pregnancy test is positive, the study drug will not be administered and the result will be confirmed by a serum pregnancy test. Serum pregnancy tests will be performed at a central clinical laboratory, whereas urine pregnancy tests will be performed by qualified personnel using kit.
• Females becoming pregnant during the study will continue to be monitored for the duration of the study or completion of the pregnancy, whichever is longer.  Monitoring will include perinatal and neonatal outcome.  Any SAEs associated with pregnancy will be recorded. 
• AIS grade A or B of SCI at the time of injury with or without subsequent improvement within 1 year of injury that has progressed to a higher AIS grade with a plateau in functional improvement
• SCI must be traumatic, blunt/non-penetrating in nature and not degenerative.
• Full understanding of the requirements of the study and willingness to comply with the treatment plan, including fat harvesting, laboratory tests, diagnostic imaging, complete physical and neurologic examination and follow-up visits and assessments.
• Full understanding of the requirements of home exercise program prescribed by physical and occupational therapists.
• Once the nature of the study is fully explained and prior to any study-related procedure is initiated the subject is willing to provide written, informed consent and complete HIPAA documentation.

• Pregnant or nursing, or planning on becoming pregnant during the study period.
• AIS grade of SCI other than A or B at the time of injury.
• Non-traumatic SCI.
• History of receiving mesenchymal stem cell, gene or exosome therapy for any indications.
• History of intra-spinal infection
• History of superficial infection in the index spinal level within 6 months of study.
• Evidence of current superficial infection affecting the index spinal level at the time of enrollment.
• On chronic, immunosuppressive transplant therapy or having a chronic, immunosuppressive state, including use of systemic steroids/corticosteroids.
• Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment.
• Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis.
• Fever, defined as temperature above 100.4 F/38.0 Celsius, or mental confusion at baseline.
• Significant improvement between the time of adipose tissue harvest and the time of injection, defined as improvement from AIS grade A or B to AIS grade C or greater.
• Clinically significant cardiovascular (e.g. history of myocardial infarction, congestive heart failure or uncontrolled hypertension > 90 mmHg diastolic and/or 180 mmHg systolic), neurological (e.g. stroke, TIA) renal, hepatic or endocrine disease (e.g. diabetes, osteoporosis).
• History of malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
• History of blood dyscrasia, including but not limited to anemia, thrombocytopenia, and monoclonal gammopathy.
• Participation in a study of an experimental drug or medical device within 3 months of study enrollment.
• Known allergy to local anesthetics of other components of the study drug.
• Any contraindication to MRI scan according to MRI guidelines, or unwillingness to undergo MRI procedures.
• History of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or use of medical marijuana within 30 days of study entry.
• Patients with baseline depression, diagnosed by the Beck Depression Inventory Assessment.

• Patients who are > 18 years of age.
• Patients who are either known to be HIV seropositive or have a positive syphilis serology or who require HIV or syphilis serologic testing as part of their routine care.

• Unable due to cognitive or physical limitations to understand dried blood spot collection instructions or to safely perform finger-stick for DBS self-collection.
• Patients who are unable to give informed consent.

• Males and females, age ≥ 18 years.
• Newly diagnosed, histological confirmation of soft tissue sarcoma of the extremities (including limb girdle) or superficial trunk that present as either:
  • Deemed a candidate for complete macroscopic resection of the primary sarcoma; OR
  • Having had non-oncologic excisional procedure with positive or uncertain resection margins and still be eligible if the evaluating sarcoma surgeon recommends oncologic re-resection of the surgical bed to obtain negative margins after a course of preoperative radiation therapy.
• No evidence of nodal or distant metastases as determined by clinical examination on any form of imaging.
• Eastern Cooperative oncology Group (ECOG) Performance Status (PS) ≤ 3.
• Life expectancy greater than 6 months.
• Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only. Patients capable of childbearing must use adequate contraception.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Ability to provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

• Previous radiation therapy to the site of the sarcoma or area surrounding it such that it would be encompassed by the radiation field needed to treat the current sarcoma.  In other words, treatment on this trial would require re-irradiation of tissues.
• Patients with nodal or distant metastases.
• Rhabdomyosarcoma, soft tissue osteosarcoma, soft tissue Ewing sarcoma, and benign histologies.
• Any of the following:
• • •  
  • Pregnant women;
  • Nursing women;
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.

• Healthy participants above the age 18 years old.
• Participants capable of performing submaximal exercise.

• Participants less than the age of 18 years and older than 65.
• Participants with compromised cardiovascular or pulmonary function.
• Unable to pedal an exercise ergometer.

• Severe Pneumonia defined as hospitalization for acute (< 14 days) onset of symptoms (cough, sputum production, or dyspnea) and radiographic evidence of pneumonia by chest radiograph or CT scan and evidence of systemic inflammation (temperature < 35oC or > 38oC or WBC < 4000 or > 11,000 or procalcitonin > 0.5 mcg/L), OR known current immunosuppression preventing inflammatory response.
• Hypoxemia defined as new requirement for supplemental oxygen with SpO2 < 90% on room air, ≤ 96% on ≥ 2 L/min oxygen, or > 6L/min or NIV (regardless of SpO2) at enrollment.

• A condition requiring inhaled corticosteroids or beta-agonists, or chronic systemic steroid therapy equivalent to a dose >10 mg prednisone (this does not include patients receiving inhaled beta-agonists in the Emergency Department without an established indication if treating clinician is willing to discontinue subsequent treatments).
• Contraindication or known allergy to inhaled corticosteroids or beta-agonists.
• Inability to obtain consent within 24 hours of presentation to enrolling hospital (up to 12 hours allowed at transferring ED for maximum of 36 hours from presentation).
• Intubation (or impending intubation) prior to enrollment.
• This does not include those patients receiving High flow nasal cannula (HFNC) oxygen or Noninvasive ventilation (NIV) prior to enrollment.
• Do Not Intubate order but does not include a "Do Not Resuscitate" order.
• Chronic lung or neuromuscular disease requiring daytime oxygen or mechanical ventilation other than for obstructive sleep apnea (OSA) or obesity hypoventilation syndrome.
• Not anticipated to survive > 48 hours or not expected to require > 48 hours of hospitalization.
• Patients with heart rate > 130 bpm, ventricular tachycardia or new supraventricular tachycardia within last 4 hours, or K+ < 3.0 will be potentially eligible for enrollment after the condition has resolved.
• Younger than 18 years of age.
• Pregnancy.

• Age ≥ 18 years.
• Able to provide written consent.
• Patient has given permission to give tumor/blood sample for research testing.
• Histological confirmation of squamous cell carcinoma or adenosquamous carcinoma.
• Known HPV status defined as positive staining for p16 on IHC or DNA ISH for HPV.
• Willingness to return to enrolling institution (Mayo Clinic Rochester or the University of Minnesota) for follow-up (during the Active Monitoring Phase of the study) or complete blood draws locally using study mail-in kits.
• Consent to allow blood specimens to be shared with potential external collaborators.
• Definitive Chemoradiotherapy for Locally Advanced Disease (FIGO Stage IB2-IIIC):
  • FIGO 2019 Stage IB2-IIIC or not a surgical candidate;
  • Plan to undergo definitive chemoradiotherapy including external beam radiotherapy, brachytherapy, and chemotherapy.

• Other active malignancy ≤ 2 years prior to registration. 
  • EXCEPTIONS:  Non-melanotic skin cancer.
  • NOTE:  If there is a history or prior malignancy, they must not be receiving other specific treatment for cancer.
• Pregnancy or lactation.
• Inability on the part of the patient to understand the informed consent to be compliant with the protocol.

Eligibility last updated 3/24/22. Questions regarding updates should be directed to the study team contact.

A subject must meet all of the following inclusion criteria to participate in this study:

• Has radiographic evidence (i.e., CT or MRI within 12 months of enrollment*) of degenerative disease of the lumbosacral spine in one or two adjacent levels (L2 to S1) that results in radiculopathy secondary to nerve root compression, manifested by:
  • History of radiating leg or buttock pain, paresthesia, numbness or weakness; or
  • History of neurogenic claudication.
  • *If a subject hasn’t had a CT or MRI in the last 12 months, a CT/MRI will need to be obtained.
• Has a history of low back pain.
• Has radiographic evidence (i.e., CT or MRI within 12 months of enrollment*) of degenerative disease of the lumbosacral spine including at least one of the following:
  • Instability up to and including Grade 2 spondylolisthesis/retrolisthesis based on the Meyerding classification (Meyerding, HW, 1932), or lateral listhesis demonstrated by coronal plane translation (slippage) of the superior (cranial) vertebral body lateral to the inferior (caudal) vertebral body less than or equal to 3mm; or
  • Stenosis, or narrowing, of the lumbar spinal canal and/or intervertebral foramen requiring significant decompression leading to segmental instability; or
  • Recurrent disc herniation.
  • *If a subject hasn’t had a CT or MRI in the last 12 months, a CT/MRI will need to be obtained.
• Has preoperative Oswestry Disability Index score ≥ 35.
• Has preoperative back pain and leg pain scores of (back pain ≥ 4 and leg pain ≥ 1) based on the Preoperative Back and Leg Pain Questionnaire.
• Has preoperative back and leg pain scores of (back pain ≥ 1 and leg pain ≥ 4) based on the Preoperative Back and Leg Pain Questionnaire.
• Is at least 18 years of age and skeletally mature at the time of surgery.
• Has not responded to non-operative treatment (e.g., bed rest, physical therapy, medications, spinal injections, manipulation, and/or TENS) for a period of six months.
• Is willing and able to comply with the study plan and able to understand and sign the subject Informed Consent Form.

A subject will be excluded from participating in this study for any of the following reasons:

• Prior surgical procedure at the involved or adjacent spinal levels (e.g., bony decompression, fusion, arthroplasty, and/or other non-fusion procedures). Prior discectomy and/or laminectomy at the target or adjacent levels is allowed.
• Significant lumbar instability defined as sagittal listhesis greater than Grade 2 at any involved level using the Meyerding Classification or lateral listhesis greater than 3 mm at any involved level.
• Planned use of an internal or external bone growth stimulator.
• Lumbar scoliosis > 30 degrees.
• Patients who had a previous diagnosis of osteoporosis with a T-score of -2.5 or below in the last 12 months existing together with a prevalent fragility fracture. If subject has a prevalent fragility fracture and a T-score hasn’t been assessed in the last 12 months, a DEXA will need to be obtained.19/
• Morbidly obese, as defined by a Body Mass Index (BMI) > 40.
• Presence of active malignancy or prior history of malignancy (non-invasive basal cell carcinoma of the skin and non-invasive squamous cell carcinoma localized only to the skin is allowed).
• Overt or active bacterial infection, either local to surgical space or systemic.
• Has undergone administration of any type of corticosteroid, anti-neoplastic, immunostimulating, or immunosuppressive agents, or medications known to inhibit the healing of bone or soft tissue within 30 days prior to implantation of the assigned treatment.
  • This includes patients ≥ 65 years of age taking warfarin with documented diagnosed osteoporosis. All other patients taking warfarin should washout for at least 5 days prior to treatment;
  • Use of steroidal inhalers, short-term NSAID use, and short-term steroidal use (e.g., Medrol Dosepak) is allowed pre and post-operatively. For this clinical study, short-term use is defined as ≤ two weeks;
  • Use of NSAIDs and/or steroids for longer than two weeks post-operatively through the 24 Month Follow-Up Visit is prohibited.
• Co-morbidities, which in the investigator’s opinion, precludes the subject from being a surgical candidate.
• Autoimmune disease, which in the investigator’s opinion, is known to affect bone metabolism or the spine (e.g., spondyloarthropathies, juvenile arthritis, rheumatoid arthritis, Graves’ disease, Hashimoto’s thyroiditis).
• Any endocrine or metabolic disorder, which in the investigator’s opinion, is known to affect osteogenesis (e.g., Paget’s disease, renal osteodystrophy, Ehlers-Danlos syndrome, or osteogenesis imperfecta).
• Known exposure to any recombinant proteins used for bone formation (e.g., Infuse™ Bone Graft, OP1 Putty, OP-1 Implant, AUGMENT Bone Graft, GEM21S, i-FACTOR Peptide Enhanced Bone Graft, or PepGen P-15 Synthetic Bone Graft).
• Known hypersensitivity or allergy to any components of the study treatments including, but not limited to bone morphogenetic proteins (BMPs); injectable collagen; protein pharmaceuticals (e.g., monoclonal antibodies or gamma globulins); bovine collagen products; and/or instrumentation materials (e.g., titanium, titanium alloy, cobalt chrome, cobalt chrome alloy, or PEEK).
• History of any allergy resulting in anaphylaxis.
• Is a prisoner.
• Is mentally incompetent. If questionable, obtain psychiatric consult.
• Treatment with an investigational therapy (drug, device, and/or biologic) targeting spinal conditions within 3 months prior to implantation surgery, treatment with any other investigational therapies within 30 days prior to implantation surgery, or such treatment is planned during the 24-month period following implantation of the study treatment.
• Pregnant or nursing.
• Females of child-bearing potential must agree not to become pregnant for 24 months following surgery.
• A documented diagnosis of substance use disorder as defined by the DSM-5. (Nicotine use is allowed.)
• Pursuing worker’s compensation or active litigation for spinal fusion procedure.
• Any condition, which in the investigator’s opinion, would interfere with the subject’s ability to comply with study instructions, which might confound data interpretation.

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

• Able to understand the goals of the study and provide informed consent.
• Any hospitalized patient scheduled for a first-time sternotomy or thoracotomy under the care of Mayo Clinic cardiovascular inpatient service or thoracic inpatient service admitted after 1 February 2020, who is not excluded due to criteria listed below.
• Between the ages of 21 and 80 years old.
• English speaking.

• Unable to consent to study due to cognitive difficulty.
• Current diagnosis of epilepsy, dementia, or other neurological disease that may prevent use of virtual reality (VR) hardware and software.
• Sensitivity to flashing light or motion.
• Patients who received anxiolytic drugs or sedatives within the preceding 24 hours.
• Recent stroke.
• Post-transplant patient, or pre-transplant patient with severe illness.
• At the time of in-room virtual reality (VR) administration, patient on ventilator, is receiving BiPAP or CPAP, or other breathing assistance equipment.
• Injury to the eyes, face, neck, or arms that prevents comfortable use of VR hardware or software, or safe use of the hardware (e.g., open sores, wounds, or skin rash on face).
• Non-English speaking.

Eligibility last updated 7/1/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated10/11/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 8/24/22. Questions regarding updates should be directed to the study team contact.

• Adult patients, ≥ 18 years of age.
• Patients with histopathologic or molecular confirmation of either IDH-mutant diffuse astrocytoma or IDH-mutant anaplastic astrocytoma.
• Patients who will be proceeding to receive routine standard of care treatment (radiation with concurrent oral temozolomide) at Mayo Clinic, Rochester.

• Patients who have previously received any adjuvant therapy (radiation, chemotherapy, investigational) directed towards the glioma.
• Patients who have been previously treated with Gliadel wafers.

• Solid organ transplant candidates (18 years or older) on deferred, active, or inactive transplant waiting lists.
• Nominated adult caregivers (18 years or older) of solid organ transplant patients listed for deceased donor solid organ transplantation.
• CG identified in the electronic medical record.

• Individuals unwilling to provide consent.
• Patients or CG unable to complete questionnaires or consents due to limited English proficiency.

• Patients with either an imaging diagnosis of HCC by CT or MRI (LI-RADS 5) confirmed by a board-certified abdominal radiologist, or with biopsy-proven HCC.
• Subjects who may undergo hepatic surgical resection, liver transplant, hepatic locoregional therapy (ablation, embolization, etc.) or systemic therapy.
• No prior treatment for index HCC lesion (surgical resection, liver transplant, hepatic locoregional therapy arm).
• For the systemic therapy arm, patients who have had unequivocal progression after prior LRT and/or those undergoing de novo systemic therapy in view of advanced HCC at diagnosis.
• Male or female with age greater than 18 years, with the capacity and willingness to provide a written informed consent.

• Subjects requiring emergent surgery for a ruptured/bleeding HCC.
• Bilirubin > 3.0 mg/dL, which is a contraindication for Gadoxetate, the MRI contrast agent (relevant to PET/MRI).
• Pregnant and/or breast-feeding subjects. A negative pregnancy test within 48 hours of the PET scan.
• Subjects with higher than the weight/size limitations of PET/MRI or PET/CT scanner.
• Subjects with contraindication to MRI (relevant to PET/MRI):
  • Subjects who have a heart pacemaker;
  • Subjects who have a metallic foreign body (metal sliver) in their eye, or who have an aneurysm clip in their brain;
  • Subjects who have implanted devices with magnets;
  • Subjects who have other implanted electronic devices;
  • Subjects who have deep brain stimulator;
  • Subjects who have vagal nerve stimulator;
  • Subjects with cochlear (ear) or auditory implants.

We propose recruiting a total of 150 subjects with ages ranging from 18 to 99 including 3 groups: (1) mTBI+/RHI+: 50 patients with diagnosed mild traumatic brain injury (mTBI) and with the history of organized contact-sports; (2) mTBI-/RHI+: 50 age (by decades) /sex-matched participants that has a history of organized contact-sports but without diagnosed mTBI; (3) mTBI-/RHI-: 50 age (by decades)/sex-matched control participants with no history of organized contact-sports and no diagnosis of mTBI. It is not anticipated that these subjects will have mild cognitive impairment (MCI) from the TBI. MCI is a syndrome defined as a cognitive decline greater than expected for an individual’s age and education level but that does not interfere with activities of daily living.

Group 1 recruitment mTBI+/RHI+:

Residents of Olmsted County, Minnesota who were diagnosed with mTBI will be identified by using the medical-records linkage system of the Rochester Epidemiology Project (REP) between 2017 and 2020. The REP indexes all medical information of individuals residing and receiving care in Olmsted County, Minnesota. Individuals will be identified if they had a diagnostic code in the medical records suggestive of a potential head injury (Table 1),then the medical records will be reviewed for the dates of the specific codes and determined whether a mTBI occurred based on the Mayo Classification System for TBI severity (Definite, Probable, and Possible). By this definition, a “Definite” TBI had to have at least one of the following: loss of conscious of ≥30 minutes, post-traumatic anterograde amnesia of ≥24 hours, intracerebral hematoma, subdural hematoma, epidural hematoma, cerebral contusion, hemorrhagic contusion, penetrating TBI (dura penetrated) or subarachnoid hemorrhage; a “Probable” TBI had to have at least one of the following: loss of consciousness of momentary to <30 minutes, post-traumatic anterograde amnesia of momentary to <24 hours, or depressed, basilar, or linear skull fracture; a “Possible” TBI had to have at least two of the following: blurred vision, confusion (mental state changes), dazed, dizziness, focal neurologic symptoms, headache, or nausea.

If the “Probably” or “Possible” TBI criteria apply to the trauma event, the event will be considered as a mTBI.

The participation of organized contact-sport will be self-reported. Potential participants will be approached with the phone script and/or the letter. If the patient expresses willingness to participate, we will send him/her the follow-up letter or email with a tentative study visit date according to his/her preference. The consent form will be enclosed with the letter/email for his/her review. The questionnaire about the history of contact-sports play will also be enclosed.

Table 1- Codes for traumatic brain injury-related emergency department visits and hospitalizations as recommended by Center for Disease Control and Prevention

Description

ICD-9-CM Codes

Concussion

850

Cerebral laceration and contusion

851

Intracranial injury of other and unspecified nature

854

Injury to optic nerve and pathways

950.1-950.3

Head injury, unspecified

959.01

Inclusion Criteria for Group 1 (mTBI+/RHI+):

1. A history of “Possible” or “Probably” TBI as defined above.
2. A history of participating in at least one organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 1 (mTBI+/RHI+):

1. A history of “Definite” TBI as defined above.
2. A history of chronic neurological disease;
3. Pregnancy or breastfeeding;
4. Inability to provide consent.

Group 2 and Group 3 recruitment:

Recruitment of these paid, groups 2 and 3 participants will be conducted (1) through established Mayo Clinic Rochester research study advertisements, and (2) through Mayo Clinic Study of Aging (MCSA) that provides a list of Olmsted County, MN residents who enrolled in MCSA, from whom matched control will be drawn. The participation of organized contact-sport will be self-reported.

Inclusion Criteria for Group 2 (mTBI-/RHI+):

1. A history of participating in at least one organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
2. No history of “Definite”, “Possible” or “Probably” TBI as defined above.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 2 (mTBI-/RHI+):

1. A history of chronic neurological disease;
2. Pregnancy or breastfeeding;
3. Inability to provide consent.

Inclusion Criteria for Group 3 (mTBI-/RHI-):

1. No history of participating in any organized contact-sport (e.g., football, hockey, soccer, rugby, lacrosse, martial art, etc.) featuring officiated competition.
2. No history of “Definite”, “Possible” or “Probably” TBI as defined above.
3. Able to understand the goal of the project and give informed consent/assent;
4. Age ≥18 years;

Exclusion Criteria for Group 3 (mTBI-/RHI-):

1. A history of chronic neurological disease;
2. Pregnancy or breastfeeding;
3. Inability to provide consent.

The 3 groups will be age- (by decades) and sex-matched. We will start by recruiting the 3 groups together for the efficiency of data collection. During the recruitment process, if we notice a certain age range or sex is lacking, we will focus on targeting this particular age group or sex group to ensure the maximum matching. For example, if we particularly looking for 18-25-year-old male volunteers with no history of contact-sports participation in group 3, we will have a 2nd advertisement focusing on this particular age group and/or sex group.

Remuneration of $75 will be provided for each participant. If the participant were asked to return for additional imaging, remuneration of $75 will be provided for each visit.

All subjects will be carefully screened by MRI personnel to be certain that they do not have any contraindication to an MRI exam such as foreign bodies in the brain or eye or an incompatible device such as a cardiac pacemaker. This safety screening is part of the routine clinical practice and is performed before any subject is permitted to enter the scanning room. The patients and parents will be given the option of withdrawing from the study at any point in the project without jeopardizing their medical care at Mayo Clinic. Patients requiring sedation to complete the MRI will be excluded from the study.

Pregnant or nursing women are not eligible to participate in this study.  If the participant wishes to participate with the study she will be asked about her pregnancy status.  If she thinks she may be pregnant or if she is unsure of her pregnancy status, she will be offered a no-charge urine pregnancy test before proceeding with any study visit imaging.

We will attempt to recruit an equal number of men and women, but the final proportions will be dependent upon the available subjects in the disease group. Although we will make every effort to include minority subjects, most of the subjects enrolled in Rochester will be of Caucasian background which is a reflection of the regional demographics.

If there is a question on whether or not the subject has the capacity to provide informed consent, the investigator or a member of the study team will assess the patient by reviewing questions regarding the study such as:

1. Can you tell me the purpose of this study?
2. Do you have to be in this study?
3. Can you tell me what will happen if you agree to take part in this study?
4. What will happen to you if you choose not to be in the study?

If it is determined that the subject does not have the capacity to provide informed consent, the subject will then be excluded from the study.

The investigator or coordinator will meet with the potential participants in a private consult room to review and discuss the details of the study using the informed consent document as a guide. The discussion will include all of the elements of informed consent. Potential participants will be given an opportunity to ask questions and we be provided a copy of the informed consent document.

• ≥ 18 years of age.
• Female patients with confirmed IBD diagnoses who are pregnant and taking immunosuppressants and/or biologic therapy.

• Pregnant female patients younger than 18 years of age.
• Confirmed multiple gestation.

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

• Age ≥ 18 years old.
• Capable of giving consent.
• Established diagnosis of Multiple Sclerosis according to McDonald Criteria (2018). Patients may be diagnosed with any of the conventional phases of MS, primary progressive, relapsing remitting, secondary progressive etc.
• Willing to participate in a 7T MRI examination within a few days of their clinical 3T or 1.5T examination.

• Age < 18 years old.
• Any metallic implant, device implant, ventriculoperitoneal shunt, cardiac valve, pacemaker which would constitute a contraindication to 7T imaging.
• Previous craniotomy.
• Permanent facial makeup (for brain scanning).
• Suffer from claustrophobia.
• Pregnancy.
• Fever / elevated temperature.

• Age ≥ 18.
• Blood cancer diagnosis (including B-ALL, multiple myeloma, and lymphoma).
• Receiving a CAR-T product.
• Able to complete a written questionnaire in English either at home or with assistance at an appointment.
• Able to perform a verbal interview either in person or via phone teleconference.

• Severe cognitive deficit of neuropsychiatric condition that would prevent person from being able to provide informed consent or complete survey or interview questions.

Eligibility last updated 6/3/22. Questions regarding updates should be directed to the study team contact.

• Adults, age ≥ 40 years old.
• Clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD).
• At least 10 pack years of smoking.

• Unable to do mild exercise (orthopedic-neurologic problems or confined to a bed).
• Unable to follow commands (cognitive impairment).
• Have a high likelihood of being lost to follow-up (active alcohol or drug abuse).
• Live in an area that does not have cellular service (Verizon).

Eligibility last updated 8/27/21. Questions regarding updates should be directed to the study team contact.

• Males and females, age ≥ 18 years.
• Patients with tumors of the head and neck, thorax, abdomen, pelvis, and extremities.
• Histological confirmation of oncologic diagnosis.
• Completed oncologic imaging (per discretion of treating physician).
• ECOG Performance Status 0-3.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Provide informed written consent.

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
  • Pregnant women;
  • Nursing women;
  • Women of childbearing potential who are unwilling to employ adequate contraception.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.  NOTE:  Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Uncontrolled inter-current 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.

• Adults self-referred or referred by their physicians starting a senotherapeutic intervention.
• Any individual with senescence-associated medical conditions as defined above, refractory to current standards or care, or without known treatments.
• Any individual taking senotherapeutic agents or performing dietary restriction for any reason.

• Absolute contraindications to indicated senotherapeutic agents due to drug-drug or other interactions.
• Pregnancy or breast-feeding.
• Clinically significant dehydration, infection, renal or hepatic insufficiency.
• Excessive acute or chronic alcohol use.
• Acutely ill individuals requiring hospitalization, emergency, or urgent care.