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The goal of this study is to explore the effects of a Mindfulness Based Couples Intervention  on relationship satisfaction with quality of life and immune system function among breast  cancer survivors and their partners. Baseline Visit:  If you are found to be eligible to take part in this research study, you will return to the  clinic about a week later for the Baseline Visit. You will be instructed to fast (eat nothing  and drink only water) for at least 8 hours before this visit.  -  Blood (about 4-5 tablespoons) will be drawn for tests of your immune function, stress  hormone levels, and blood sugar levels. After this blood test, you will be given  breakfast.  -  You will complete a pain assessment which involves you submerging your hand in cold  water. Researchers will use your response to measure your pain tolerance.  -  You will have electrocardiograms (EKGs) to check your heart function. The sensors will  be attached at the beginning of the visit and then removed before you leave. You will be  attached to the machine for several hours, but you will be able to be disconnected to  take bathroom breaks, if needed.  -  You will complete questionnaires about fatigue, mood, stress, social support, marital  satisfaction, depression, and general demographics (age, race and so on). It should take  about 1½ hours total to complete the questionnaires.  -  You will complete a series of traditional neurocognitive tests (for example, tests to  check your memory and thinking abilities). You will take these tests on the computer and  with a pen and paper.  -  Your blood pressure will be measured multiple times throughout the visit.  Study Groups and Interventions:  After the Baseline visit, you will be assigned to one of 2 groups. If you are in Group 1, you  and your partner will take part in an 8-week Mindfulness-Based Relationship Enhancement  (MBRE) intervention course designed to alleviate stress and other symptoms among couples. The  MBRE course will consist of eight sessions taught by a professional Mindfulness instructor.  The sessions will occur 1 time a week and last about 2½ hours each time. The MBRE course will  consist of meditation and yoga techniques and handouts. The sessions will focus on teaching  participants (all female breast cancer survivors and partners) the basics of Mindfulness  Based Relationship Enhancement.  Attendance at these sessions and completion of daily homework assignments requiring up to 45  minutes per day are essential to the program.  If you are in Group 2, you will receive self-help materials that have been previously  developed by MD Anderson's Office of Public Education, the American Cancer Society, and the  National Cancer Institute.  Post-Intervention Follow-Up Visit:  If you are in Group 1, you will have a post-intervention follow-up visit about 12 weeks after  your Baseline visit (4 weeks after you finish your 8-week intervention sessions). If you are  in Group 2, you will have a post-intervention follow-up visit about 8 weeks after the  Baseline Visit. You will fast for 8 hours before a post-intervention follow-up visit.  -  Blood (about 4 to 5 tablespoons) will be drawn to check your immune function, stress  hormone levels, and blood sugar. After the blood is drawn you will be given breakfast.  -  You will complete the cold water pain tolerance test.  -  You will have electrocardiograms (EKGs).  -  You will complete questionnaires about fatigue, mood, stress, social support, marital  satisfaction, depression, and general demographics (age, race and so on). It should take  about 1½ hours total to complete the questionnaires.  -  You will complete a series of traditional neurocognitive tests.  -  Your blood pressure will be measured multiple times throughout the visit.  Cortisol Testing:  After the Baseline and Follow-up Visits, you will be asked to give samples to measure  cortisol, a hormone related to stress. You will place a small cotton tube in your mouth for  about 2 minutes, or until the swab is completely soaked with your saliva. After this, you  will place the swab back in the tube, and freeze the sample. You will be given containers to  hold the samples when you freeze them, as well as to mark which day and time each sample was  collected. You will take these samples 7 times a day (right when you wake up; about 30, 45,  and 60 minutes after waking; and then at noon, 4:00 p.m., and 8:00 p.m.). Researchers will  use these samples to measure the changes in cortisol throughout the day. You will collect  these samples for 2 days during the week, and 2 days on the weekend. After you complete 4  total days of collecting saliva samples after each visit, you will mail them back to MD  Anderson in pre-paid envelopes.  Program Satisfaction Evaluations:  After the follow-up visits, the study staff will conduct individual interviews with a small  group of participants. Interview questions will address participants' overall reactions to  and satisfaction with the mind-body intervention, the impact they felt from social support,  motivation, and their own ability for increasing physical activity and well-being. The study  staff will also ask questions about both positive and negative effects of participating in  the intervention. Interviews will be conducted by the PI or a trained research coordinator.  All interviews will last no longer than 90 minutes and will be audio-taped using a digital  recorder and transcribed. All audio files will be destroyed after they are transcribed.  This is an investigational study.  Up to 30 couples (60 participants) will take part in this research study. All will be  enrolled at MD Anderson. Inclusion Criteria:  1. Stage 0-IIIA breast cancer survivors and their partner  2. All the female breast cancer survivors will be at least two months from receiving  cancer treatment (surgery, adjuvant therapy or radiation) and within three years from  completing cancer treatment, except for tamoxifen/aromatase inhibitors.  3. Are able to read and write in English  4. Are able to pass the Physical Activity Readiness Questionnaire or participant provides  a letter from their physician or nurse practitioner clearing them for study  participation  5. All couples co-habiting for at least 3 years with current partner who is willing to  participate in study  6. Are 21 years of age or older Exclusion Criteria:  1. Male breast cancer survivors;  2. Participants with a diagnosis of diabetes, unless they are able to provide a letter  from a physician who will continue to monitor the participant during the research  study  3. Anti-inflammatory medications (e.g. statins, cholesterol medication)  4. Consume excessive amounts of alcohol (>30 drinks/week)  5. Pregnant or thinking about becoming pregnant during the study period  6. Lactating women  7. Major medical conditions involving the immune system such as autoimmune and/or  inflammatory diseases  8. Pressure readings >/=140/90 mm Hg, as defined by the 7th Report of the Joint National  Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure,  will be deemed ineligible to participate and excluded from the study. They will be  referred to their family physician or community services. Those ineligible based on  their initial blood pressure reading are allowed to participate if they provide a  letter from a physician who will continue to monitor the participant during the  research study.  9. A hemoglobin level < 10g/dl  10. Person less than 21 years of age

Obesity related ailments, such as cardiovascular diseases (CVD) and metabolic disorders are  major causes of death in the Western World. This trial may result in improved prevention,  diagnosis and treatments for obesity and obesity-related disorders. Published data show that  if a weight is carried by a rodent, this animal will lose body weight and gain an improved  glucose control. Recently published data further show comparable results in humans when  carrying an additional weight.  The investigators aim to confirm and further investigate these findings in humans. The  investigators plan to let obese participants carry weight vests and monitor their change in  body weight. The investigators will also measure food intake, physical activity, energy  expenditure, body composition, abdominal fat and heart rate variability. This to further  examine the potential beneficial effects of loading and the mechanism of action. STUDY OBJECTIVES AND ENDPOINTS  Primary objective  To determine if wearing a weight vest with 11 percent of body weight for 8 hours/day for 5  weeks decreases body weight in obese subjects.  Secondary objectives  To determine if wearing a weight vest with 11 percent of an individual's body weight for up  to 5 weeks affects levels of abdominal fat, liver fat, fat mass, fat free mass, physical  activity, energy expenditure, waist circumference, food intake or activity in the autonomic  nervous system in obese subjects.  To determine, exploratory, if wearing a weight vest with 11 percent of an individual's body  weight for up to 5 weeks affects serum concentrations of circulating proteins, metabolites or  electrolytes in obese subjects.  STUDY DESIGN AND PROCEDURES  Overall study design and procedure protocol  The aim of the study is to investigate the effect of adding artificial weights to individuals  suffering from obesity. Enrolled study subjects will be randomized in a 1:1 fashion to either  carry a heavy weight vest with 11 percent of the individual's body weight (intervention  group) or a light weight vest with 1 percent of the individual's body weight (control group).  The weight vests will be worn for a total of 5 weeks.  Body weight, abdominal fat, liver fat, waist circumference, food intake, energy expenditure,  physical activity, activity in the autonomic nervous system, fat mass, bone mass, water mass  and fat free mass together with endpoint blood samples will be measured before the start of  intervention to obtain base line values. New measurements will then be done for comparison  during or after the intervention to determine the effect of added artificial loading on obese  subject.  The study consists of a total of 10 weeks. During the first 3 weeks of the study measurements  will be made which will be used as baseline. The following 5 weeks contains the intervention  and the carrying of a weight vest. The last 2 weeks is a follow up period and at the end of  this period follow up measurements will be done. During or after the intervention period new  measurements will be made to be compared with the baseline measurements to evaluate the study  endpoints.  To avoid the risk of carry-over effects, the investigators have decided to not use a  crossover design. This could have decreased the variation of the measurement values and  increased the power of the study. However, the investigators believe there could be a risk of  a carry-over effect with a cross over design. As this is a completely new effect in clinical  studies, the investigators have no information about the wash-out time needed to avoid this  problem. Inclusion Criteria:  1. Signed informed consent to participate in the study.  2. Consent out of free will.  3. 18-65 years of age.  4. Obesity as defined by a BMI >30 and ≤35. Fat mass > 25 %.  5. Willingness to comply with the study protocol  6. Normal or clinically non-significant screening of blood samples:  1. Hemoglobin (Hb), White Blood Cell Count (WBC), thrombocyte count, sodium (Na),  potassium (K), chloride (Cl), calcium (Ca), creatinine, aspartate transaminase  (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin,  Prothrombin Time (PT-INR), Activated Partial Thromboplastin Time (APTT), human  immunodeficiency viruses (HIV), Hepatitis B, Hepatitis C, glycated hemoglobin  (HbA1c), C-reactive protein (CRP), free thyroxine (fT4), thyroid-stimulating  hormone (TSH).  2. Normal or clinically non-significant aberrations of screening blood samples are  defined as:  i. Normal: Values within the reference interval supplied by the local lab at  Sahlgrenska University Hospital  ii. Clinically non-significant aberration: as judged by investigator (Clinical  significance judged by investigator)  7. Normal or non-clinically significant 12-lead electrocardiography (ECG) recording as  judged by the investigator. Exclusion Criteria:  1. Chronic disease that could interfere with the participation in the study as judged by  the investigator. For example poorly regulated type 1 or 2 diabetes, severe  cardiovascular disease that effect daily life, severe pulmonary disease that affects  daily life or malignancy.  2. Chronic pain such as pain that is constant and impairs quality of life as judged by  the investigator; for example: significant back, hip and knee pain.  3. Regular consumption of medicine or natural supplements that affect weight, inhibit  physical activity or increase the risk of adverse effects as judged by the  investigator. The following drugs will not be accepted:  1. β-blockers, Glucagon-like peptide-1 (GLP-1) agonists, Dipeptidyl peptidase-4  (DPP-IV) inhibitors, SGLT2-inhibitors, sulfonylureas, insulin, orlistat,  anti-obesity drugs, antidepressants, bisphosphonates, β2-agonists, oral  corticosteroids, diuretics, benzodiazepines, or central nervous system  stimulating drugs such as methylphenidate or dextroamphetamine.  2. Any illegal drugs according to local laws and regulation  4. Gastric by-pass surgery or equivalent metabolic surgery in the gastrointestinal tract.  5. Reduced mobility.  6. Pregnancy. Females of childbearing potential must confirm to use reliable  contraception (intrauterine device, oral contraceptives or condom) and not suspect to  be pregnant. Pregnancy test will be taken on all female subjects of fertile age unless  permanently sterile, as judged by the investigator. Permanently sterile women can be  excluded from the pregnancy test. Permanent sterilization methods include  hysterectomy, bilateral salpingectomy and bilateral oophorectomy  7. Change in body weight of 5 kg or greater during the past 3 months or recently started  a strict diet. Also, a greater change in body weight than 4 kg difference between day  -21 and day 0 will not be accepted.  8. Use of any illegal drugs according to local regulations or consuming excessive amounts  of alcohol, tobacco, nicotine.  a. Excessive amounts of above-mentioned substances defined as:  i. Consumption of more than 9 glasses of wine for women, 14 glasses of wine for men  (15 cl/glass 11 % alcohol) or equivalent as judged by investigator during an ordinary  week will not be accepted.  ii. Individuals with a consumption equal or higher than 10 cigarettes or half a packet  of snuff per day.  9. Drastic change in lifestyle during the last 3 months; for example a significant change  in physical activity, dietary habits, nicotine, alcohol or drug use as judged by the  investigator.  10. Apparent risk of not being able to comply with the study protocol for any reason as  judged by the investigator.  11. Having participated in a similar study during the last 6 months.

The present study will evaluate the concomitant administration of a Quadrivalent Inactivated  Influenza Vaccine with the highest dose level of OVX836 (480µg) tested in the clinic to date,  for which the likelihood for interference with Quadrivalent Inactivated Influenza Vaccine is  considered the highest. This trial is a Phase 2a, randomized, double-blind, controlled study in 180 adult subjects to  compare the immunogenicity and the safety of the concomitant administration (given  intramuscularly, in healthy subjects, as 2 separate injections in the same arm) of:  -  OVX836 influenza vaccine and a Quadrivalent Inactivated Influenza Vaccine  -  Quadrivalent Inactivated Influenza Vaccine and placebo  -  OVX836 influenza vaccine and placebo Inclusion Criteria:  1. Written informed consent.  2. Healthy male or female subjects, as determined by medical history and medical  examination.  3. Between the age of 18 and 55 years, inclusive.  4. Subjects who have fully been vaccinated with licensed Severe Acute Respiratory  Syndrome Coronavirus-2 (COVID-19) vaccine(s) according to national recommendations for  the corresponding population group, in vigor at the moment the study starts.  5. Reliable and willing to make themselves available for the duration of the study, and  willing and able to follow study procedures.  6. Ability and technical possibility for completing an e-diary and ePRO. Exclusion Criteria:  1. Subjects with a body mass index ≤19 kg/m² or ≥35 kg/m² on the day of vaccination.  2. Previous influenza vaccination within 6 months before the day of vaccination or  planned to receive during the study duration.  3. Any known or suspected immunodeficient conditions.  4. Past or current history of significant autoimmune diseases, as judged by the  Investigator.  5. Current history of uncontrolled medical illness such as diabetes, hypertension, heart,  renal or hepatic diseases.  6. Known or suspected infection with human immunodeficiency virus, hepatitis C virus, or  hepatitis B virus, based upon medical history or physical examination findings.  7. Female subjects: pregnant, breast-feeding or of childbearing potential without  appropriate contraceptive methods in place for 2 months before enrolment, or with  positive pregnancy test on the day of vaccination. Appropriate contraceptive methods  are to be maintained until the end of the trial. Appropriate contraceptive methods are  defined by the Clinical Trial Facilitation Group as follow: "Contraceptive methods  that can achieve a failure rate of less than 1% per year when used consistently and  correctly are considered as highly effective birth control methods. Such methods  include: combined (estrogen- and progestogen-containing) hormonal contraception  associated with inhibition of ovulation (oral, intravaginal, transdermal),  progestogen-only hormonal contraception associated with inhibition of ovulation (oral,  injectable, implantable intrauterine device, intrauterine hormone-releasing system),  bilateral tubal occlusion, vasectomized partner and/or sexual abstinence (refraining  from heterosexual intercourse)."  8. Having received another vaccination within 3 months prior to the day of study  vaccination with live attenuated vaccines, or within 1 month prior to the day of study  vaccination with inactivated vaccines, except COVID-19 vaccine.  9. Planning to receive other vaccines during the first 28 days following the study  vaccine administration, except COVID-19 vaccine.  10. Having received a COVID-19 vaccination within 2 weeks prior to the day of study  vaccination.  11. Planning to receive COVID-19 vaccine during the first week (within 7 days) following  the study vaccine administration. An interval of preferably 14 days is recommended. If  for scheduling reasons, COVID-19 vaccine has to be given on Day 8, the vaccination  should be administered after completion of the study procedures.  12. Administration of any investigational or non-registered drug or vaccine within 3  months prior to the administration of study vaccines, or planned administration of any  such product during the whole study period.  13. History of receiving blood, blood components or immunoglobulins within 3 months prior  to the day of vaccination, or planned to receive such product during the whole study  period.  14. Presence of an acute febrile illness on the day of vaccination (oral temperature  >38.0°C, temporary exclusion criterion).  15. Past or current history of any progressive or severe neurological disorder, seizure  disorder or Guillain-Barré syndrome.  16. Behavioral or cognitive impairment, or psychiatric disease that, in the opinion of the  Investigator, may interfere with the subject's ability to participate in the study.  17. Past (stopped less than 6 months before enrolment) or current history of alcohol or  drug abuse, or current smoking habit above 10 cigarettes per day, or current vaping.  18. Treatment that can affect immune response such as systemic or high dose inhaled  corticosteroids (>800μg/day beclomethasone or equivalent; occasional inhaled  corticosteroids for asthma therapy are allowed), radiation treatment, cytotoxic drugs,  or current or recent (within 30 days before study entry) chronic or prolonged (>10  days) use of systemic non-steroidal anti-inflammatory drugs, interferon,  immunomodulators, allergy shots, as judged by the Investigator.  19. History of severe allergic reactions and/or anaphylaxis, or serious adverse reactions  to vaccines or allergy to any component of either of the study vaccines, including to  egg protein or to kanamycin.  20. Any contraindication to IM administration, as judged by the Investigator, including  bleeding disorders such as hemophilia or anticoagulant therapy.  21. Individuals with history of any illness that, in the opinion of the Investigator,  might interfere with the results of the study or pose additional risk to the subjects  due to participation in the study.  22. Subjects with tattoos in the deltoid region bilaterally, which might interfere with  observation of local signs and symptoms or other adverse events at the injection  sites. In case of tattoos on one side, injections of study vaccines should be  performed in the contralateral arm.  23. Sponsor employees or Investigator site personnel directly affiliated with this study,  and their immediate families. Immediate family is defined as a spouse, parent, child  or sibling, whether biological or legally adopted, including children of newly  composed families.

This phase 3, 12-week, randomized, double-blind, placebo-controlled, multi-center study will evaluate the safety and efficacy of tenapanor in subjects with constipation-predominant irritable bowel syndrome (IBS-C) as defined by the ROME III criteria and who have active disease as determined after a two-week screening period. Subjects who qualify and are randomized into the study will either receive 50mg BID of tenapanor or placebo BID for 12 week treatment period and then undergo a 4 week placebo controlled randomized withdrawal. During the 12-week treatment period, subjects will record daily assessments including: frequency and timing of bowel movements; sensation and complete bowel emptying; consistency of bowel movements; degree of straining, worst abdominal pain, abdominal discomfort, abdominal bloating, abdominal fullness and abdominal cramping. Subjects will also record weekly assessments including: adequate relief of IBS severity, and constipation severity. At the end of the 12-week treatment period, there will be a 4-week randomized withdrawal period in which subjects who complete the study in Tenapanor group will be randomized to either Tenapanor 50mg BID or placebo BID (1:1) and subjects who complete the study in the placebo group will be assigned to receive Tenapanor 50mg BID. Inclusion Criteria:   -  18 to 75 years old   -  Females must be of non-childbearing potential; If of child-bearing potential, must have negative pregnancy test and confirm the use of one of the appropriate means of contraception.   -  Males must agree to use an appropriate method of barrier contraception or have documented surgical sterilization   -  Subject meets definition of IBS-C using Rome III Criteria for the Diagnosis of IBS   -  A colonoscopy based on AGA guidelines; every 10 years at ≥ 50 years old, or the occurrence of any warning signs Exclusion Criteria:   -  Functional diarrhea as defined by Rome III criteria   -  IBS with diarrhea (IBS-D), mixed IBS (IBS-M), or unsubtyped IBS as defined by Rome III criteria   -  Diagnosis or treatment of any clinically symptomatic biochemical or structural abnormality of the GI tract within 6 months prior to screening, or active disease within 6 months prior to screening; including but not limited to cancer, inflammatory bowel disease, diverticulitis, duodenal ulcer, erosive esophagitis, gastric ulcer, pancreatitis (within 12 months of screening), cholelithiasis, amyloidosis, ileus, non-controlled GERD, gastrointestinal obstruction, ischemic colitis or carcinoid syndrome.   -  Subject has a history or current evidence of laxative abuse (in the clinical judgment of the physician)   -  Hepatic dysfunction (ALT [SGPT] or AST [SGOT] >2.5 times the upper limit of normal) or renal impairment (serum creatinine > 2mg/dL)   -  Any evidence of or treatment of malignancy (other than localized basal cell, squamous cell skin cancer or cancer in situ that has been resected) within the previous year   -  Any surgery on the stomach, small intestine or colon, excluding appendectomy or cholecystectomy (unless within 60 days of screening visit)

This study will evaluate safety, tolerability, and preliminary efficacy of a single  intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy,  4D-110, in male patients with genetically-confirmed Choroideremia (CHM). This is an open-label, Phase 1 study to evaluate safety and tolerability as well as  preliminary efficacy of a single IVT injection of 4D-110 at two dose levels in male patients  with genetically-confirmed CHM. Inclusion Criteria: None Exclusion Criteria: None

The double-blinded and randomized study evaluated the effectiveness and side effects of a  novel non-invasive treatment, Schumann resonance (SR), in treating insomnia. The objective of  this study is (1) to evaluate the improvement of sleep quality of patients with insomnia  disorder by SR and (2) to be the basis for the future development of physical magnetic  therapy. Insomnia is a common sleep disturbance that affects the health and quality of life of  individuals and accounts for considerable utilization of medical resources. The prevalence of  insomnia is approximately 30%; in Asia, the prevalence of insomnia is approximately 4% in  Japan, 9.9% in South Korea, 10.3% in Taiwan. Based on the statistic of Taiwan BNHI office in  a 2013 report, there is worth of 1.3 billion prescriptions of hypnotic drug in one year. In  addition, the reimbursement expenditure pays up more than 1 billion New Taiwan Dollars (NTD)  with increasing expense rate of 15% every year, showing insomnia causes great distress to  Taiwanese.  The characteristics of insomnia are difficulty with initiating or maintaining sleep, early  morning waking, or non-restorative sleep. In DSM-5, the diagnosis of primary insomnia has  been renamed insomnia disorder to avoid the differentiation between primary and secondary  insomnia.  The most common treatment for insomnia is pharmacological therapy with hypnotics such as a  benzodiazepine, zolpidem, or zopiclone. However, treatment with hypnotics includes the risk  of adverse effects, drug tolerance and dependence . Some past reports on different  non-pharmacological treatment strategies, such as Cognitive-Behavioral Therapy (CBT), muscle  relaxation training, stimulus control, sleep restriction, and sleep hygiene, have  demonstrated the effectiveness of most of these non-pharmacological treatments. However, the  poor compliance and inconvenience for CBT is always a big issue.  Except the traditional treatment of insomnia, some folk therapies' clinical effect does not  been confirmed, such as aromatherapy, music therapy, etc. Nowadays, due to development of  technology for medical devices, some sleep devices were launched, aim to prolong the  slow-wave sleep and enhances the sleeping quality.  The investigational device in this study is a sleep device with SRF (Sleep Restore  Frequency), the principle is to integrate the bio-energy generated Schumann resonances,  native from Earth, and the shocks from the Earth's magnetic field. Through the non-contact  method with bio-energy waves, SRF are coupled to the sleep center of the brain, inducing and  adjusting the electrical activities of the sleep center. It prolongs the in-depth sleep and  enhances the sleeping quality.  The objective of this study is (1) to evaluate the improvement of sleep quality of patients  with insomnia disorder by sleep device and (2) to be the basis for the future development of  physical magnetic therapy.  Sample Size Approximately 60 subjects who meet the inclusion and exclusion criteria will be  enrolled into the trial and averagely separated two arms for statistical analysis.  Statistical Analysis Efficacy evaluation statistics will be conducted with independent t-test  or Fisher's exact test for testing the differences and conducted with Pearson correlation  coefficient for the association between variables. Inclusion Criteria:  -  (1) participants are between 20 and 70 years old;  -  (2) participants must meet the DSM-5 diagnostic criteria for insomnia and have been  diagnosed for more than three months;  -  (3) participants must be willing to sign an informed consent form;  -  (4) participants who took sleep aiding pills must cooperate not to change any  medication and dosage during the study. Exclusion Criteria:  -  (1) participants using pacemakers or cardiac monitors;  -  (2) participants with severe physical illness or after surgery, such as heart disease,  metabolic diseases, or cancer;  -  (3) participants with severe mental disorders, such as schizophrenia, severe major  depression, severe anxiety, bipolar disorder, dementia, substance use disorder; or  severe neurological diseases such as a seizure, stroke or Parkinson's disease;  -  (4) participants with other serious sleep disorders, such as severe sleep obstructive  apnea, severe periodic limb movement syndrome or narcolepsy;  -  (5) participants who are unable to attend regular follow-up evaluations;  -  (6) participants who are unable to keep good sleep hygiene and cannot stop using  electronic products before going to bed.

Evaluation of microneedling vs injectable -platelet rich fibrin on gingival phenotype in thin  periodontal phenotype. INTRODUCTION The gingival phenotype and different parts of the masticatory mucosa have become  the subject of considerable interest in Periodontics, especially from an aesthetic and  therapeutic perspective. The periodontal phenotype has been defined as the combination of  gingival phenotype and buccal bone plate thickness (bone morphotype). Gingival phenotype  refers to gingival thickness (GT) and keratinized tissue width (KTW).  Gingival phenotypes can be classified as scalloped and thin or flat and thick gingiva. A  gingival thickness of ≥1 mm is defined as thick phenotype and a gingival thickness of ≤1 mm  as thin phenotype1. Thin gingival phenotype are very friable and might be prone to recede in  response to traumatic insults, such as plaque-related inflammation and traumatic  toothbrushing. Gingival recession is usually observed in the presence of trauma and  inflammation in individuals with thin phenotypes, whereas pocket formation has been reported  in individuals with thick phenotypes.  Soft tissue grafting in areas of thin phenotypes can enhance the quality of the gingival  tissue. The best way to convert a thin soft tissue to a thick phenotype is through  subepithelial connective tissue grafting Various other soft tissue augmentation procedures  include: - modified roll technique and use of acellular dermal matrix. There were many  drawback of these techniques such as were not cost effective, complications, second surgical  site creation, healing and time consuming, etc.  Therefore marked transformation in the field of periodontics has led to the development of  newer, less invasive therapeutic approaches, which allows proper management of surrounding  tissues to provide best outcome of periodontal therapy. Minimally invasive treatment  approaches help to achieve satisfactory therapeutic results with minimum trauma to tissues.  Recent study has shown i-PRF (injectable Platelet Rich Fibrin) and Microneedling procedures  to be effective in increasing gingival tissue thickness.  I-PRF prepared according to low-speed centrifugation concept can provide a significant  advantage for the regeneration process, as it is rich in platelets, leucocytes and growth  factors. I-PRF clots and forms a gel form after approximately 10-15 min and preserves its  content in the tissue for sustained release. Recent studies have shown that in comparison to  PRP and the blood clot even though there is slight or no increases in blood cell  concentrations and growth factors; i- PRF was capable of inducing higher cell migration and  mRNA expression of TGF- β, PDGF, osteocalcin and significant increase in type I collagen gene  expression. It has been suggested that i- PRF provides a three- dimensional fibrin clot  network embedding platelets, leucocytes, type I collagen, osteocalcin and growth factors  acting as a dynamic gel with additional release of growth factors up to 10 days. Hence  studies have documented that i-PRF results in increased gingival thickness.  Microneedling (MN) is also known as "percutaneous collagen induction therapy." Microinjuries  created by MN result in minimal superficial bleedings and create a wound- healing cascade  from which various growth factors, such as platelet-derived growth factors, transforming  growth factors, connective tissue growth factor and fibroblast growth factors, are released.  In MN, the tissue responds as if experiencing tissue trauma and the body's own collagen  production is induced to preserve skin integrity. Study has shown a statistically significant  increase in gingival thickness when microneedling was performed along with i- PRF in  comparison to standalone i-PRF.  Only one study have evaluated effect of i-PRF alone and with microneedling on thin phenotype  . To the best of our knowledge no studies have been conducted till now using microneedling  alone to observe its effect on gingival thickness on thin periodontal phenotype. Considering  the effects of MN and i-PRF on the biological potential, neoangiogenesis, neocollagenesis and  wound, the present Randomized clinical trial is designed to compare and evaluate the effects  of MN and i-PRF alone in thin periodontal phenotype. The null hypothesis is that there is no  significant difference in the clinical outcome in microneedling and i-PRF on thin periodontal  phenotype.  MATERIALS AND METHODOLOGY  SETTINGS: The present prospective, analytical, split mouth clinical trial will be conducted  in the Department of Periodontics, Post Graduate Institute of Dental Sciences, Rohtak STUDY  DESIGN: Interventional study. TIME FRAME: 12-14 months STUDY  Written and verbal consent will be taken from the willing participants. This Split mouth  clinical trial will include 20 systemically healthy patients, with thin periodontal phenotype  in mandibular anteriors.  Test group I : microneedling Test group II : i-PRF METHOD OF RECRUITMENT  In power analysis, it was found that a minimum of 18 cases will be required for each group at  a 95% confidence level and 80% power when analysed with a mean difference of 0.5 mm and a  standard deviation of 0.47 using the soft tissue thickness as a reference.  Estimating a 10% drop-out rate, the study includes 20 individuals with thin periodontal  phenotypes who will consult to the Department of Periodontology, Post Graduate Institute of  Dental Sciences, Rohtak .  BLINDING/MASKING Single blinding will be adopted where the investigator analysing the results  will be unaware to which group the patient belongs.  PHASE I THERAPY All the participants will undergo phase-I therapy with a combination of hand  scalers and curettes and ultrasonic scaler. Oral hygiene instructions will be imparted and  will be reinforced at each appointment.  INTERVENTION Local anaesthesia will be administered. TEST GROUP I Thin periodontal phenotype  will be treated with microneedling. A total of 4 sessions will be done with an interval of 10  days each. And all the parameters will be measured.  TEST GROUP II Thin periodontal phenotype will be treated with i-PRF procedure. A total of 4  sessions will be done with an interval of 10 days each. And all the parameters will be  measured.  DATA COLLECTION METHODS To measure GT from the apical 1.5 mm of the gingival margin, a No:15  endodontic spreader with a 3-mm-diameter silicone disc will be placed in the centre and will  be measured on Vernier caliper.  Keratinised tissue width will be measured with the help of UNC 15 probe with silicon disc  stopper from the mucogingival junction to the free gingival margin and will be measured on  Vernier caliper.  PPD will be measured using UNC 15 periodontal probe at six sites (mesiobuccal, distobuccal,  mesiolingual , distolingual , and median points at buccal and lingual aspect).  GI, PI will be measured using UNC 15 periodontal probe at four sites (distofacial,  mesiofacial, facial, lingual gingival margin).  All clinical parameters will be measured at baseline, 3 months and 6 months and 1 year.  DATA MANAGEMENT AND STATISTICAL ANALYSIS Data recorded will be processed by standard  statistical analysis. The normality of distribution of data will be examined by Shapiro Wilk  test. Statistical analysis will be performed according to distribution of data. If it is in  normal distribution inter group comparison will be done by using Independent T test and  paired t test will be use for intragroup comparison and if non-normal distributionof data,  inter group comparison will be done by Mann-Whitney U test and intragroup by signed rank  test. The Chi square test will be applied to analyze categoric data. Correlation and  association between predictors and dependent variables will be analyzed by correlation  analysis and regression analysis. Inclusion Criteria:  -  GT of the mandibular and maxillary anterior teeth < 1 mm, gingival index (GI) of < 1  -  Age 18-40 years and otherwise systemically healthy  -  Patients who had completed etiological periodontal therapy with Plaque index <1,  gingival index <1 and showing adequate compliance and willing to participate in the  study. Exclusion Criteria:  -  Patients having systemic diseases such as hypertension, diabetes, hyperthyroidism or  on medications that influence the outcome of periodontal procedure  -  Pregnant and lactating women  -  Smokers, tobacco users  -  Previous periodontal surgery  -  No haematological disorders  -  Use of blood thinners  -  Use of any drugs that might lead to gingival enlargement  -  Stress, bruxism.

1. To assess the value of 18F-FDG PET/CT in the initial staging and detection of recurrent  cases of endometrial cancer.  2. To determine correlation between PET/CT derived parameters including SUVmax, TLG and MTV  and clinic-pathological patient characteristics.  3. To detect local and distant recurrence after therapy. Endometrial cancer (EC) is one of the most common gynaecological malignancies worldwide.The  incidence rate of uterine cancer in Egypt was 4.1 per 100,000.  The standard surgery consists of laparotomy, hysterectomy, and bilateral  salpingo-oophorectomy. Maximal surgical cytoreduction is recommended for advanced EC.  Prognostic impact of complete lymphadenectomy remains controversial, especially in early-  stage disease.  With the aim of predicting extrauterine disease pre-operatively and optimizing surgical  planning, several techniques have been evaluated, including 18F-fluoro-2-deoxyglucose  (18F-FDG) positron emission tomography/computed tomography (PET/CT). PET /CT can be used to  effectively and accurately diagnose EC pelvic lymph node metastasis and distant metastasis.  It has great value in clinical staging, judging prognosis, diagnosing recurrence.  Radiomics analysis of the uterine primary tumor on pre-operative 18F-FDG PET images may help  predict the presence of metastatic nodes, thus reducing false-negative results and increasing  the sensitivity of the technique. The maximum standard uptake value (SUVmax), metabolic tumor  volume (MTV) and total glycolysis (TLG) of primary lesions are significantly correlated with  pathological tissue grading. Previous studies on metabolic parameters of primary lesions  examined by 18F-FDG PET/CT for endometrial cancer mainly focused on SUVmax, However, SUVmax  can only reflect the functional metabolic degree of the point. It cannot assess the overall  metabolic situation of tumor. MTV and TLG can more comprehensively measure the glucose  metabolic activity of tumor cells with more clinical value in reflecting the malignancy  degree of tumor. Inclusion Criteria:  -  Patients proved to have endometrial cancer by curettage or hysteroscopy.  -  Patients accepted surgery treatment, without anti-tumor and hormone therapy before  surgery.  -  Ability to stay still for the duration of the PET/CT scan (~15 minutes).  -  Ability of the patient (or his/her guardian) to sign informed consent. Exclusion Criteria:  -  Patients who recieved neoadjuvant therapy before PET/CT.  -  Patients with tumors other than endometrial cancer.  -  Pregnancy.  -  Inability to give informed consent.  -  Inability to stay still for the duration of the scan.  -  Claustrophobia

Study introduction: this is a multicenter, randomized controlled study of patients with  histopathologically confirmed hepatocellular carcinoma (HCC) who have not previously received  systematic treatment for HCC, all the patients are Chinese stage IIb/IIIa (BCLC stage B/C),  and have not developed extrahepatic metastases. Follow-up, data collection and analysis will  be performed for patients who meet the study inclusion criteria and will be treated with  lenvatinib plus toripalimab and TACE (on demand) or TACE alone, so as to compare the  objective response rate (ORR), overall survival (OS), progression-free survival (PFS), ratio  of conversion resection, and safety between the two cohorts. The study includes two groups:  Treatment group: patients with potentially resectable HCC who meet the study inclusion  criteria will be treated with lenvatinib in combination with toripalimab and TACE (on  demand). Tumor response will be regularly evaluated, data will be collected, and complete  surgical resection will be evaluated by an independent review committee, the conversion  resection rate will be calculated, and patient survival will be assessed.  Control group: patients with potentially resectable HCC who meet the study inclusion criteria  will be treated with TACE. Tumor response will be regularly evaluated, data will be  collected, and complete surgical resection will be evaluated by an independent review  committee, the translational resection rate will be calculated, and patient survival will be  assessed.  The maximum duration of study treatment for each subject is expected to be 48 weeks, with  efficacy evaluation by the MDT after 2 TACE treatments to determine whether subjects meet the  surgical criteria.  This study is a multicenter, randomized controlled study. The primary endpoint is the  objective response rate (ORR). Historical data showed that the objective response rate of  patients in the TACE group was about 40%. The objective response rate of lenvatinib in  combination with toripalimab and TACE is expected to reach 60%. Using a two-sided Z test of  pooled variance, α is set to 0.05, power is set to 0.8, and patients will be assigned at a  1:1 ratio. The required sample sizes are 98 (treatment group) and 98 (control group), and a  total of 220 subjects are planned to be prospectively observed, taking into account a dropout  rate of 10%. Inclusion Criteria:  1. Male or female patients of 18-75 years old;  2. Clinical or histopathological diagnosis of hepatocellular carcinoma;  3. ECOG PS score of 0-1, Child-Pugh grade A;  4. Chinese stage IIb/IIIa (equal to BCLC B/C) patients with portal vein tumor thrombus  (according to the Japanese PVTT grading criteria Vp3-Vp4) or more than 3 tumor  nodules, without extrahepatic metastasis;  5. According to the evaluation by the site multi-disciplinary team (MDT), surgical  resection is not the current preferred treatment;  6. No previous systemic treatment for hepatocellular carcinoma; no previous use of PD-1  inhibitor, PD-L1 inhibitor, lenvatinib or sorafenib;  7. Previous TACE treatment for 0-2 times  8. The patients in the treatment group voluntarily and have decided to receive treatment  of lenvatinib in combination with toripalimab and TACE, and sign an informed consent  form. Additional identification of qualified subjects: subjects who have received at  least one combination medication enter the safety evaluation; subjects who have  received at least one imaging evaluation after treatment enter the efficacy  evaluation. The patients in the control group treated with TACE alone have at least  one imaging evaluation.  9. Patients with HBV infection (characterized by hepatitis B surface antigen [HBsAg]  positive and/or hepatitis B core antibody [anti-HBcAb], with detectable HBV DNA [>10  IU/mL]) should be treated with antiviral therapy according to clinical routine, so as  to ensure adequate viral suppression (HBV DNA≤2000 IU/mL or 104) before enrollment.  Patients must maintain antiviral therapy during the study period and within 6 months  after the last study drug administration; patients with positive hepatitis B core  antibody (HBc) and undetectable HBV DNA (<10 IU/mL) will be not required to receive  antiviral therapy before enrollment; these patients will be checked every cycle to  monitor HBV DNA levels; if HBV DNA is detected (> 10 IU/mL), antiviral therapy will be  initiated; patients with detectable HBV DNA must continue to receive antiviral therapy  during the study Exclusion Criteria:  1. Clinical or pathological diagnosis of mixed liver cancer, fibrolamellar hepatocellular  carcinoma or other non-hepatocellular malignant tumor components;  2. Hematological examination: PLT<50×109/L, WBC<3.0×109/L or not meet the requirements of  TACE treatment;  3. Coagulation function: international normalized (prothrombin time) ratio (INR) > 1.2;  4. Liver function indicators: serum albumin (ALB) < 2.8 g/dl, serum total bilirubin  (TBIL) > 1.5 times the upper limit of normal (excluding those with biliary  obstruction), serum transaminase (ALT and AST) > 3 times the upper limit of normal;  5. Renal function indicators: serum creatinine (CR) > 1.5 times the upper limit of  normal;  6. Uncontrollable hypertension (defined as diastolic blood pressure > 90 mmHg or systolic  blood pressure > 150 mmHg);  7. Patients with bile duct tumor thrombi, superior mesenteric vein tumor thrombi and  diffuse portal vein tumor thrombi;  8. Participated in other clinical trials 30 days before screening;  9. Accompanied by hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc.;  10. Acute gastrointestinal bleeding recorded within the last 3 months;  11. Have a history of allogeneic transplantation (such as liver transplantation);  12. Patients with acute or chronic active hepatitis B or C infection, hepatitis B virus  (HBV) DNA > 2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA > 103 copies/ml;  those who are positive for both hepatitis B surface antigen (HbsAg) and anti-HCV  antibodies.  13. Patients who have autoimmune diseases or a history of autoimmune diseases or syndromes  requiring systemic use of steroids / immunosuppressants, including hypophysitis,  pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism etc.  14. Be suspected of being allergic to study drugs;  15. Patients with other organ dysfunction who are expected to be unable to tolerate  general anesthesia or hepatectomy;  16. Other conditions in which the investigators deem the patients unsuitable for the  clinical trial

This is a three-year project funded by a Cancer Research UK Multidisciplinary Award and  brings together a team from UCL Division of Medicine, Computer Science and University College  London Hospital. The aim is to develop Magnetic Resonance (MR) sequences and mathematical  algorithms to reduce the distortions in MR images, especially of the prostate. This is a three-year project funded by a Cancer Research UK Multidisciplinary Award and  brings together a team from UCL Division of Medicine, Computer Science and University College  London Hospital. The aim is to develop Magnetic Resonance (MR) sequences and mathematical  algorithms to reduce the distortions in MR images, especially of the prostate. Current NICE  guidelines include a type of MR imaging called Diffusion Weighted MRI for the detection of  tumour within the prostate, and for active surveillance of low risk confirmed disease.  However, approximately 40% of prostate diffusion images suffer from severe localised  distortions and this is most marked in the peripheral zone of the prostate where 75% of  prostate cancers occur. The source of these distortions is magnetic field imperfections due  to the presence of rectal gas or metallic hip implants.  The research study will ask both healthy volunteers and patients to undergo research MR scans  and use the acquired data for analysis. For patients, the scans may be either additional  sequences acquired during an extended clinical session, or a separate additional session  entirely for research.  The output from the research will be modified ways to run an MR scanner and compute the final  images.  The work should lead to improved diagnostic accuracy and a reduced number of non-diagnostic  studies. It will have broader impact through application to diffusion imaging of other body  sites, including whole-body diffusion MRI and non-cancer applications. If successful, the  results would provide evidence for a larger trial with the eventual outcome being  manufacturers incorporating modified MR sequences and data processing into clinical systems  worldwide. Inclusion Criteria:  -  For the development and testing phases, there are no specific inclusion criteria.  Assessment of the primary outcome measure (reduced distortions) also does not require  specific inclusion criteria. The intended application of our methods is to prostate  cancer and this is reflected in some of the secondary outcome measures. Recruitment  will come from the UCLH imaging bookings system. This list will include many men  having prostate scans and many of these will subsequently be found to have at least a  suspicion of cancer. Note there is no requirement for a suspicion of cancer to be  recruited for the study. Exclusion Criteria:  -  Subjects unable to have an MRI scan due to contraindications for MRI, for example,  pacemaker and certain other implants, severe claustrophobia.  -  Subjects unable to give informed consent.  -  Children and vulnerable populations.

To demonstrate the efficacy of sabizabulin in the treatment of ER+HER2- metastatic breast  cancer (MBC) as measured by progression free survival (PFS) by RECIST v1.1. This study is a multicenter, randomized, open-label, two treatment arm, efficacy and safety  study. Subjects will be randomized to the two treatment arms in a 1:1 fashion.  The primary efficacy endpoint of the study will be the median PFS by RECIST v1.1.  Subjects will continue study treatment until disease progression confirmed by blinded  independent central reader (BICR) is observed. A safety follow up visit will occur  approximately 30 days after last dose of study drug. Inclusion Criteria:  -  Provide informed consent  -  Be able to communicate effectively with the study personnel  -  Aged ≥18 years  -  For Female Subjects Menopausal status  -  Be postmenopausal as defined by the National Comprehensive Cancer Network as  either:  -  Age ≥55 years and one year or more of amenorrhea  -  Age <55 years and one year or more of amenorrhea, with an estradiol assay  <20 pg/mL  -  Age <55 years and surgical menopause with bilateral oophorectomy  -  Be premenopausal or perimenopausal with a negative urine pregnancy test.  -  If subject is of child bearing potential, the subject must agree to use  acceptable methods of contraception:  -  If female study participant could become pregnant, use acceptable methods of  contraception from the time of the first administration of study medication  until 6 months following administration of the last dose of study  medication. Acceptable methods of contraception are as follows: Condom with  spermicidal foam/gel/film/cream/suppository [i.e., barrier method of  contraception], surgical sterilization of male partner (vasectomy with  documentation of azoospermia) and a barrier method {condom used with  spermicidal foam/gel/film/cream/suppository}  -  If female study participant has undergone documented tubal ligation (female  sterilization), a barrier method (condom used with spermicidal  foam/gel/film/cream/suppository) should also be used  -  If female study participant has undergone documented placement of an  intrauterine device (IUD) or intrauterine system (IUS), a barrier method  (condom with spermicidal foam/gel/film/cream/suppository) should also be  used  -  For Male Subjects  Subject must agree to use acceptable methods of contraception:  -  If the study subject's partner could become pregnant, use acceptable methods of  contraception from the time of the first administration of study medication until 6  months following administration of the last dose of study medication. Acceptable  methods of contraception are as follows: Condom with spermicidal  foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical  sterilization (vasectomy with documentation of azoospermia) and a barrier method  {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner  uses oral contraceptives (combination estrogen/progesterone pills), injectable  progesterone or subdermal implants and a barrier method (condom used with spermicidal  foam/gel/film/cream/suppository)  -  If female partner of a study subject has undergone documented tubal ligation (female  sterilization), a barrier method (condom used with spermicidal  foam/gel/film/cream/suppository) should also be used  -  If female partner of a study subject has undergone documented placement of an  intrauterine device (IUD) or intrauterine system (IUS), a barrier method (condom with  spermicidal foam/gel/film/cream/suppository) should also be used  -  For premenopausal and perimenopausal women where exemestane monotherapy or  exemestane plus everolimus is chosen as the active control treatment or the  patient is randomized to receive sabizabulin, the patient must be already on  ovarian suppression or be candidates for this treatment: e.g., luteinizing  hormone release hormone agonist or ovariectomy  -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2  -  Documented evidence of ER+/HER2- metastatic breast cancer (NOTE: patients HER2+  metastatic breast cancer are excluded from participation in this study)  -  Measurable disease is required as per RECIST 1.1 as confirmed by BICR (NOTE: Bone  only metastatic disease is acceptable but requires a measurable component)  -  Received a nonsteroidal AI (monotherapy or combination therapy) either for  adjuvant or metastatic breast cancer and a SERD, such as fulvestrant (monotherapy  or combination therapy) for MBC; at least one of the non-steroidal AI or SERD  must have been given in combination with a CDK 4/6 inhibitor.  -  Previously responded (without disease progression for at least 6 months) to one  of the following treatments: SERD monotherapy or SERD plus CDK 4/6 inhibitor or  nonsteroidal aromatase inhibitor monotherapy or nonsteroidal aromatase inhibitor  plus CDK 4/6 inhibitor for metastatic breast cancer.  -  Subject is willing to comply with the requirements of the protocol through the  end of the study Exclusion Criteria:  -  Women of childbearing potential or fertile men with a female partner of childbearing  potential not willing to use effective contraception during the study and 6 months  after last dose of study drug for the women of childbearing potential participating in  the study and for 3 months after last dose of study drug in fertile men with a female  partner of childbearing potential.  -  Known hypersensitivity or allergy to sabizabulin or colchicine  -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 X upper limit  of normal (ULN) or total bilirubin >ULN (an elevated total bilirubin up to 1.5 X ULN  attributed to a previously confirmed diagnosis of Gilbert's disease is acceptable if  all other eligibility criteria are met). In patients with documented metastases to the  liver, the limits for inclusion are ALT or AST >5.0 X ULN or total bilirubin >1.5 X  ULN.  -  Patients with biliary catheter  -  Creatinine clearance < 60 mL/min as measured using the Cockcoft Gault formula  (patients with mild and moderate renal failure are not excluded from participation in  this study)  -  QT interval corrected by Fridericia's formulation >480 ms  -  Patients with history of Tosade de Pointe  -  Patients taking QT-prolonging drugs  -  Previously received >1 course of systemic chemotherapy (not including immunotherapies  or targeted therapies) for the treatment of metastatic breast cancer.  NOTE: A course of systemic chemotherapy is defined as a line of prior chemotherapy.  Chemotherapy received in the neoadjuvant or adjuvant setting will not count as a prior line  of chemotherapy.  -  Subjects with radiographic evidence of central nervous system (CNS) metastases as  assessed by CT or MRI that are not well-controlled (symptomatic or requiring control  with continuous corticosteroid therapy [e.g., dexamethasone]) NOTE: Subjects with CNS  metastases are permitted to participate in the study if the CNS metastases are  medically well-controlled and stable for at least 30 days after receiving local  therapy (irradiation, surgery, etc.)  -  Radiotherapy within 14 days prior to randomization except in case of localized  radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can  then be completed within 7 days prior to randomization. Subjects must have recovered  from radiotherapy toxicities prior to randomization  -  Any comorbid disease or condition (medical or surgical) which might compromise the  hematologic, cardiovascular, endocrine, pulmonary, severe renal impairment,  gastrointestinal, hepatic, or central nervous system; or other conditions that may  interfere with the absorption, distribution, metabolism or excretion of study drug, or  would place the subject at increased risk  -  Treatment with any investigational product within < 5 half-lives for each individual  investigational product OR within 30 days prior to randomization whichever is shorter.  -  Major surgery within 30 days prior to randomization  -  Treatment with testosterone, methyltestosterone, oxandrolone (Oxandrin®),  oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such  as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including  herbals), or antiandrogens (enzalutamide, abiraterone, bicalutamide, apalutamide, or  darolutamide). Previous therapy with testosterone and testosterone- like agents is  acceptable with a 30-day washout (if previous testosterone therapy was long term depot  within the past 6 months, the site should contact the Medical Monitor) or any other  androgenic agent.  -  Treatment with any of the following hormone replacement therapies for metastatic  breast cancer. Prior use in the adjuvant or neoadjuvant setting is allowed if the  treatment is discontinued greater than 30 days prior to randomization  -  Estrogens  -  Megestrol acetate  -  Testosterone  -  All other concurrent anticancer treatments (including, but not limited to, all SERMs  unless randomized to the Control Treatment Group with a SERM as the control treatment,  AIs unless randomized to Control Treatment Group (exemestane or exemestane plus  everolimus) with the AI containing treatment as the control treatment, and all CDK 4/6  inhibitors)  -  An abnormal ECG result which, based on the investigator's clinical judgment, would  place the subject at increased risk  -  Has a known additional, invasive, malignancy that is progressing or required active  treatment in the last 5 years [note: subjects with basal cell carcinoma of the skin,  squamous cell carcinoma of the skin, ductal breast carcinoma in situ, bladder cancer  (superficial treated), or cervical carcinoma in situ that have undergone potentially  curative therapy are not excluded]  -  Pregnant, lactating, or breastfeeding, or intending to become pregnant during the  study or within 60 days after the final dose of study treatment

Acute pain is one of the complications after cardiothoracic surgeries . It can delay  patients´recovery and may increase patients´morbity and mortality. This study intends to  evaluate Dexmedetomidine, a highly selective α- 2 receptor agonist, that is currently applied  safely and efficiently in intraoperative cardiac surgery. It has analgesic, sedative,  anxiolytic and sympatholytic properties, without respiratory- depressant effect. The aim of  this study is to investigate whether the intraoperative use of dexmedetomidine is better than  the standard analgesia used in the intraoperative period to reduce pain and the consequences  of it. This project is a prospective, double-blinded and randomized clinical trial. Eligible  participants are assigned in a 1:1 ratio to either the intervention group (Group  Dexmedetomidine) or control group (Group Saline 0,9%), after written informed consent to be  obtained. The patients will undergo elective cardiac surgery, with extracorporeal  circulation.  In the operating room, patients will be monitored for pulse oximetry, invasive blood  pressure, electrocardiograms, capnography, central venous pressure and nasopharyngeal  temperature probe. Induction of anesthesia is performed with intravenous midazolam, fentanyl,  etomidate and neuromuscular blocking agent. Anesthesia is maintained with sevoflurane.  Dexmedetomidine, at the rate of 0,3μg/ kg/h, or placebo will be infused from the initiation  of the anesthesia up to the end of the procedure, except during the cardiopulmonary by-pass.  Placebo is a 0,9% saline. The follow up of the assessment of the groups will extend to the  postoperative ICU, where data will be collected, during the first 24 hours after surgery. Inclusion Criteria:  -  Patients at least 18 years old and who are undergoing cardiac procedures (coronary  artery bypass, valve replacement or combined procedure), with cardiopulmonary by-  pass. Exclusion Criteria:  -  Congenital heart disease  -  Infective endocarditis  -  Acute myocardial infarction (<two weeks)  -  Pregnancy  -  Cancer  -  Left ventricle ejection fraction < 40%  -  Cardiogenic shock  -  Emergent procedure  -  Use of vasopressor and/or inotrope, in the preoperative  -  Liver disfunction  -  Renal replacement therapy  -  Nephrectomy  -  Previous renal transplantation  -  Patients who are participating in another clinical research

This pilot clinical trial studies how well imetelstat sodium works in treating participants  with primary or secondary myelofibrosis and other myeloid malignancies. Imetelstat sodium may  stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PRIMARY OBJECTIVES:  I. To evaluate overall response rate.  SECONDARY OBJECTIVES:  I. To evaluate the safety and tolerability of imetelstat (imetelstat sodium) in myelofibrosis  (MF).  II. To evaluate the efficacy of imetelstat in the reduction of spleen size, as measured by  physical examination (palpable distance from the left costal margin).  III. To evaluate the efficacy of imetelstat in improving anemia or inducing red blood cell  transfusion-independence in previously transfusion-dependent participants (per International  Working Group for Myelofibrosis Research and Treatment [IWG-MRT] criteria).  IV. To evaluate onset and durability of response as defined in primary and secondary  endpoints  EXPLORATORY OBJECTIVES:  I. To evaluate the effect of imetelstat on bone marrow histology, karyotype and JAK2V617F  allele burden II. To evaluate the effect of imetelstat on leukocytosis, circulating blast  count, circulating immature myeloid cell count and thrombocytosis.  OUTLINE: Participants receive imetelstat sodium intravenously (IV) over 2 hours on day 1.  Participants may continue to receive imetelstat study treatment for as long as they derive  clinical benefit or until study end. The study end when all participants discontinued study  drug, the last participant enrolled has been treated for approximately 5.7 years, or  imetelstat is commercially available in the United States, whichever occurs first.  Maximum duration of study was approximately 5.7 years. Arm C was never initiated, and  participants allocated to Arm C (Imetelstat 9.4 mg/kg [with MF]) were reassigned to Arms A  and B. Inclusion Criteria:  -  Diagnosis of one of the following:  -  Primary myelofibrosis (PMF) per the revised World Health Organization (WHO) criteria.  -  Post-polycythemia vera/essential thrombocythemia myelofibrosis (Post-ET/PV MF) per the  International Working Group for Myeloproliferative Neoplasms Research and Treatment  (IWG-MRT) criteria.  -  High-risk or Intermediate-2 risk MF (as defined by the Dynamic International  Prognostic Scoring System [DIPSS-plus]).  -  Life expectancy of greater than or equal to (>=) 12 weeks.  -  Able to provide informed consent and be willing to sign an informed consent form.  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.  -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])  =<2.5 x upper limit of normal (ULN) (or =<5 x ULN if in the investigator's opinion the  elevation is due to extramedullary hematopoiesis).  -  Serum glutamic pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =<2.5 x ULN  (or =<5 x ULN if in the investigator's opinion the elevation is due to extramedullary  hematopoiesis).  -  Total bilirubin =<3.0 mg/dL (or direct bilirubin < 1 mg/dL).  -  Creatinine =<3.0 mg/dL.  -  Absolute neutrophil count >=1000/microliter (mcL).  -  Platelet count >=50,000/mcL.  -  Absence of active treatment with systemic anticoagulation and a baseline prothrombin  time (PT) and activated partial thromboplastin time (aPTT) that does not exceed 1.5 x  ULN.  -  Females of childbearing potential must have a negative pregnancy test =<7 days prior  to registration, unless they are surgically sterile for at least 3 months (i.e.,  hysterectomy), OR postmenopausal for at least 12 months (follicle-stimulating hormone  [FSH] >30 U/mL).  -  Females of childbearing potential must agree to take appropriate precautions to avoid  pregnancy (with at least 99% certainty) from screening through end of study; permitted  methods for preventing pregnancy must be communicated to study participants and their  understanding confirmed.  -  Males must agree to take appropriate precautions to avoid fathering a child (with at  least 99% certainty) from screening through follow-up; permitted methods for  preventing pregnancy should be communicated to the participants and their  understanding confirmed. Exclusion Criteria:  -  Females who are pregnant or are currently breastfeeding.  -  Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g.,  thalidomide), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or  equivalent, growth factor treatment (e.g., erythropoietin) or Janus kinase (JAK)  inhibitor therapy =<14 days prior to registration.  -  Participants with another active malignancy.  -  Note: participants with early stage squamous cell carcinoma of the skin, basal cell  carcinoma of the skin or cervical intraepithelial neoplasia are eligible for  enrollment.  -  Known positive status for human immunodeficiency virus (HIV).  -  Any unresolved toxicity greater or equal to grade 2 from previous anticancer therapy,  except for stable chronic toxicities not expected to resolve.  -  Incomplete recovery from any prior surgical procedures or had surgery =<4 weeks prior  to registration, excluding the placement of vascular access.  -  Presence of acute active infection requiring antibiotics.  -  Uncontrolled intercurrent illness or any concurrent condition that, in the  Investigator's opinion, would jeopardize the safety of the participant or compliance  with the protocol.

Our study aims to describe the effect of the intrauterine adminstration of HCG versus the  endometrial injury by pipelle on the ongoing pregnancy rate and the biochemical pregnancy  rate in women with unexplained infertility undergoing ovulation induction. Also to describe  the effect on the first trimester miscarriage rate, ectopic pregnancy rate, and multiple  pregnancy.This study is an open-label, prospective, controlled study, multi-center study.  The study participants' relevant medical records will be collected and reviewed after  obtaining informed consent for the participants. The study materials that will be used will  include blood tests, and ultrasound. The study will involve three study arms. Our study aims to describe the effect of the intrauterine adminstration of HCG versus the  endometrial injury by pipelle on the ongoing pregnancy rate and the biochemical pregnancy  rate in women with unexplained infertility undergoing ovulation induction. Also to describe  the effect on the first trimester miscarriage rate, ectopic pregnancy rate, and multiple  pregnancy.This study is an open-label, prospective, controlled study, multi-center study.  The study participants' relevant medical records will be collected and reviewed after  obtaining informed consent for the participants. The study materials that will be used will  include blood tests, and ultrasound. The study will involve three study arms:  Arm 1: Women with unexplained infertility undergoing ovulation induction following  intrauterine adminstration of HCG on the day of trigger Arm 2: Women with unexplained  infertility undergoing ovulation induction following endometrial injury by pipelle on day 8-9  of the same cycle of ovulation induction Arm 3: Women with unexplained infertility undergoing  ovulation induction following intrauterine adminstration of placebo on the day of trigger  Primary and secondary key measurements will be used in the study.  The primary measures will include:  -  Signs of ongoing pregnancy Presence of intrauterine gestational sac at 12 weeks Presence  of fetal heart pulsation at 12 weeks  -  Two serum β-HCG levels in 48hrs interval to emphasis biochemical pregnancy  The secondary key measures will include:  -  Occurance of abortion in the 1st trimester  -  Appearance of ectopic pregnancy diagnosis by:  Ultrasound Serum β-HCG level Symptoms of pain and bleeding  -  Signs of multiple pregnancy Number of intrauterine gestational sacs Number of fetal  poles Number of fetal heart pulsations  -  Recording the the baseline characteristics of the study participants Inclusion Criteria:  1. Women with primary or secondary infertility due to unexplained infertility  2. The age group of these women was 25-35 years  3. BMI 18.5-29.9 kg/m2  4. Normal hormone profile (FSH <10 mIU/ml on day 2-3 and AMH more than 1)  5. Euthyroid state or controlled thyroid state  6. Bilateral free spill on HSG Exclusion Criteria:  1. Patients with severe male factor infertility; serum analysis count < 10 million sperms  /mL - sperm motility<15% - 96%<abnormal morphology)  2. Stage III or IV endometriosis  3. Bilateral tubal factor infertility  4. Premature ovarian failure  5. Polycystic ovary syndrome  6. Uterine cavity abnormality  7. Recurrent spontaneous abortion

Advances in the medical service and public health increased longevity; hence, more elderly  patients (>65 years) are encountered by the anesthetists for variety of surgical  interventions. Even with the absence of comorbidity, older patients represent a challenge to  the anesthetist in comparison to the younger patients due to their limited physiologic  reserve and their aberrant response to the varies perioperative medications.  Intraoperative hypotension increases the risk of postoperative kidney injury, myocardial  injury, cerebral ischemia, and perioperative mortality. Postinduction hypotension is mainly  caused by anesthetic drugs. Hence, developing a technique for induction of anesthesia that  provide adequate hypnosis with stable hemodynamics during surgery is critical, especially for  elderly patients. The elderly patients are at increased risk of post-induction hypotension  due to increased drug sensitivity.  Propofol is the most commonly used drug for anesthesia induction; however, its use is usually  associated with hypotension through vasodilation and direct myocardial depression. Opioid  drugs are usually added as analgesics to propofol during induction of anesthesia. However,  addition of opioids to propofol potentiates the risk of postinduction hypotension.  Furthermore, opioids increase the risk of postoperative delirium in elderly patients and this  risk is further increased with intraoperative hypotension.  Lidocaine is a local anesthetic drug with multiple systemic uses. Lidocaine was proposed to  have an anesthetic sparing effect. Lidocaine was previously reported to enhance the hypnotic  effect of thiopentone, propofol, and midazolam during procedural sedation. Lidocaine/ketamine  combination showed favorable hemodynamic profile following rapid-sequence induction of  anesthesia in septic shock patients. Therefore, the use of lidocaine as an adjuvant to  propofol might provide a stable cardiovascular profile during induction of anesthesia in  elderly compared to fentanyl. To the best of our knowledge, there is no previous data  comparing the efficacy of adding lidocaine versus fentanyl to the induction of anesthesia  with propofol in elderly Upon arrival to the operating room, patient's airway will be assessed by trained anesthetist  (modified Mallampati test, mouth opening, jaw protrusion, thyromental height, neck extension,  dentation). If the patient is considered to be difficult and alternative device other than  endotracheal tube is considered, the patients will be excluded. Routine monitors  (electrocardiogram, pulse oximetry, and non-invasive blood pressure monitor) will be applied;  intravenous line will be secured, and routine pre-medications {ranitidine 50 mg,  dexamethasone 4 mg (0.5 mg/ml slow I.V injection)} will be administrated. Baseline  preoperative blood pressure will be recorded form the preoperative visit in the supine  position as average of 3 readings with difference less than 5 mmHg.  Before induction of anesthesia for all study patients, Electrical cardiometry device (ICON;  Cardiotonic, Osypka; Berlin, Germany) will be applied to the patient through 4 electrodes at  the following sites: Below the left ear, Above the midpoint of the left clavicle, Left  mid-axillary line at level of the xiphoid process and 5 cm inferior to the third electrode.  Stroke volume variability (SVV) was measured while patient maintaining standard calm  breathing at 8 breath/minute for one-minute. Patients with SVV ≥ 13% will be considered fluid  responder and will receive a fluid bolus of 8 mL/kg Ringer acetate over 10 minutes. The fluid  bolus will be repeated until the SVV is less than 13%.  Patients will be allocated into two groups: lidocaine group and fentanyl group. In all  patients, propofol will be injected slowly in 0.25 mg/kg increments every 20 s till clinical  loss of consciousness or reaching a maximum dose of 1-1.5 mg/kg in addition to the study  drug. Clinical loss of consciousness (defined as no response to auditory command and  disappearance of a patient's eyelash reflex) will be assessed by asking the patients  repeatedly every 10 s to open their eyes, when there is no response to auditory commands, the  eyelid reflex will be tested. After loss of consciousness, rocuronium (0.6 mg/kg) will be  administered, and anesthesia will be maintained by isoflurane (0.9-1% end-tidal).  Endotracheal tube will be inserted after 2-minutes of mask ventilation. Ringer lactate  solution will be infused at a rate of 2 mL/kg/hour. If the patient did not achieve adequate  hypnosis, an additional bolus of propofol (0.5 mg/kg) will be administered.  Any episode of hypotension (defined as mean arterial pressure ≤ 70% of the baseline reading  and/or mean arterial pressure <60 mmHg) will be managed by 5 mcg norepinephrine (which can be  repeated if hypotension persisted for 2 minutes).  Severe post-induction hypotension defined as mean arterial pressure ≤60% of baseline, will be  managed by 5 mcg norepinephrine and the blood pressure will be measure at 1-min interval.  Norepinephrine bolus will be repeated if severe hypotension persisted for 1-minute.  If bradycardia occurred (defined as heart rate less than 45 bpm), it will be managed by IV  atropine bolus (0.5 mg).  After skin incision, hemodynamic and anesthetic management will be according to the attending  anesthetist discretion.  Postoperative Confusion assessment method (CAM) assessment will be performed by trained  research member at and 24- and 48-hours after surgery. CAM will be assessed through a  four-step algorithm identifying the following: 1) acute onset of mental status changes or a  fluctuating course, 2) inattention, 3) disorganized thinking, 4) an altered level of  consciousness. Patients will be diagnosed to be delirious if both features {(1) and (2)} will  be present plus either feature (3) or (4)} Inclusion Criteria:  -  American society of anesthesiologists I-III,  -  scheduled for elective non-cardiac surgery under general anesthesia Exclusion Criteria:  -  Patients with severe cardiac morbidities (impaired contractility with ejection  fraction < 50%, heart block, arrhythmias, tight valvular lesions, metabolic equivalent  less than 4),  -  patients on angiotensin converting enzyme inhibitors and angiotensin receptor blockers  medications,  -  patients with uncontrolled hypertension,  -  patients with body mass index <18 or > 35 Kg/m2,  -  patient with allergy of any of the study drugs

Aging is the number one risk factor for the majority of chronic diseases. There are no  pharmaceutical treatments to slow aging and prolong healthspan. The anti-diabetic drug  metformin is considered a likely pharmaceutical candidate to slow aging. In this study, the  investigators hypothesize that metformin treatment in subjects free of type 2 diabetes will  improve insulin sensitivity and glucoregulation in insulin resistant individuals, but will  decrease insulin sensitivity and glucoregulation in insulin sensitive subjects. Further, the  investigators hypothesize that long-term metformin treatment will remodel mitochondria in a  way that decreases mitochondrial function in subjects that are insulin sensitive, but  improves mitochondrial function in subjects that are insulin resistant. The investigators  will use a dual-site, 12- week drug intervention trial performed in a double-blind,  placebo-controlled manner on 148 subjects recruited from two separate sites (Oklahoma Medical  Research Foundation (OMRF) and University of Wisconsin-Madison (UWM)). After consent and  initial subject screening for chronic disease, subjects will be stratified to insulin  sensitive (IS) or insulin resistant (IR) groups. Over a 12- week intervention, half of each  group will take metformin and half will take a placebo. Pre- and post--intervention, subjects  will complete a series of procedures to assess insulin sensitivity, glucose regulation, and  biomarkers of aging. The same subjects will provide a skeletal muscle biopsy pre-- and  post-intervention to assess the change in mitochondrial function and mitochondrial remodeling  with and without metformin treatment. By completion of this project, the investigators expect  to provide evidence that helps further delineate who may benefit from metformin treatment to  slow aging. Although there is epidemiological support for health benefits of metformin in patient  populations, it is not clear if these protective effects extend to those free of disease.  Therefore, there is a need to perform human studies determining which subjects free of  chronic disease benefit from metformin treatment. Retrospective analysis of a randomized,  double-blinded clinical trial in our lab revealed that subjects who were insulin sensitive  had no effect or negative effects on insulin sensitivity when taking metformin during an  exercise training program. These data suggest that in some subjects, metformin has  detrimental metabolic outcomes that could accelerate aging. There are data both in support of  and refuting that metformin inhibits mitochondrial complex I action and/or mitochondrial  remodeling. The overall objective of this trial is to determine if subjects currently free of  disease benefit from metformin treatment. There are two critical questions that remain  unanswered in human subjects: 1) does antecedent metabolic health influence responses to  metformin, and 2) does long-term treatment with metformin lead to mitochondrial remodeling  and changes in function. To better understand the translational potential of a clinically  relevant dose of metformin for the prevention of chronic conditions, this proposal aims to  determine how antecedent metabolic health affects the response to metformin treatment, and  identify the relationship between skeletal muscle mitochondrial remodeling and mitochondrial  function with metformin treatment. The hypotheses are that: 1) metformin treatment in  subjects free of Type 2 diabetes will improve insulin sensitivity and glucoregulation in  insulin resistant individuals, but will decrease insulin sensitivity and glucoregulation in  insulin sensitive subjects, and 2) long-term metformin treatment will remodel mitochondria in  a way that decreases mitochondrial function in subjects that are insulin sensitive, but  improves mitochondrial function in subjects that are insulin resistant. To test these  hypotheses, a 12-week randomized, double-blind clinical trial will be performed in subjects  40-75 yrs of age, free of disease, and stratified by insulin sensitivity (insulin sensitive  and insulin resistant). Pre- and post-training assessments include the hyperinsulinemic-  euglycemic clamp to measure hepatic and peripheral insulin sensitivity, continuous glucose  monitoring to determine glucoregulation, and proposed blood-based biomarkers of aging.  Further, the use of novel stable isotope labeling with proteomic analysis will determine  individual and complex-specific mitochondrial remodeling. This approach will be combined with  analysis of protein modification and turnover to comprehensively analyze mitochondrial  effects of metformin treatment in skeletal muscle. By completion of this project, it is  expected that there will be evidence that helps further delineate who may benefit from  metformin treatment to slow aging. Inclusion Criteria:  -  40-75 years of age (inclusive)  -  Free of chronic disease  -  Comprehension of the protocol as indicated by an ability to respond to questions about  the study after reading the consent form.  -  Able to use and be contacted by telephone.  -  Able to speak, read, and understand English, and complete a questionnaire in English  -  Independently mobile Exclusion Criteria:  -  Pregnancy  -  Heart disease (history, abnormal ECG, abnormal stress ECG)  -  Cerebrovascular disease (history)  -  Cancer (history)  -  Chronic respiratory disease (history, forced expiratory volume at one second/forced  vital capacity [FEV1/FVC] < 70, FEV1 < 80% predicted)  -  Chronic liver disease (history, alanine transaminase [ALT] > 52 IU/L)  -  Diabetes (history, HbA1C ≥ 6.5, fasting blood glucose≥126 mg/dl, oral glucose  tolerance test [OGTT] ≥ 200 mg/dl at 2 hrs)  -  Impaired kidney function (eGFR ,45 mL/min)  -  B12 lab values outside of normal range (<193 or >982 pg/mL)  -  Alzheimer's (history)  -  Chronic kidney disease (history, abnormal blood kidney panel including serum  creatinine > 1.4)  -  Problems with bleeding, on medication that prolongs bleeding time (if subject cannot  safely stop prior to biopsy)  -  Those on glucose lowering drugs  -  Those planning to have imaging that requires intravenous contrast dye (within 6 weeks)  or are on any of the following medications since they are contraindicated with the use  of metformin: Dofetilide, Lamotrigine, Pegvisomant, Somatropin, Trimethoprim,  Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine  -  Tobacco use  -  Allergies to lidocaine or metformin

Since its recent marketizing in France, the cannabidiol (CBD), a major component of cannabis,  is used in many over-the-counter products in France. Some painful patients or patients  suffering from addiction seem to use the CBD in search of therapeutic effects. Yet, there are  no data available for patients in algology and addictology, particularly with regard to the  prevalence of the use of CBD, the effects sought and felt. Faced with the emergence of the  use of a substance with a therapeutic purpose but outside a medical framework and without  monitoring of adverse effects, it becomes essential to characterize the use of CBD. The main  objective of the study is therefore to assess the prevalence of CBD users in algology and  addictology departments. Secondary objectives are to characterize the use of CBD as well as  the users of CBD, and to evaluate the impact of the use of CBD on other psychoactive  substances use or current drug treatments and the drug liking of CBD. Physicians from algology and addictology departments will propose the study to all patients  who meet the inclusion criteria during a medical consultation (in hospitalization or  ambulatory care). If the patient agrees to participate, the non-opposition will be collected  and the physician will complete a short form with sociodemographic data, medical history and  contact details of the patient.  The form will be transmitted securely to the research staff that will perform a unique  research evaluation face to face (when the patient is still hospitalized and available) or by  phone (when the patient is not available during hospitalization or no longer hospitalized or  in case of ambulatory care). The research evaluation includes data about the frequency and  the duration of the use of all substances (CBD included) in the last 12 months and the  frequency of current drug treatments. For patients with CBD use in the last 12 months,  additional data regarding the use of CBD will be collected: the form, the route of  administration, the effects sought and felt, the method of obtaining, the impact on other  drugs and/or substances use and the drug liking of CBD.  A descriptive analysis will be carried out. The CBD user group and the CBD non-user group  will be compared on all the variables collected. A multivariate analysis will be carried out  in order to identify factors associated to CBD use in algology and addictology patients. Inclusion Criteria:  -  Minimum age of 18 years  -  Patients for whom hospital specialists in algology or addictology have been requested  (for hospitalized or ambulatory cares) during the inclusion period.  -  Giving oral non opposition to participate. Exclusion Criteria:  -  Adults under guardianship or curator  -  Patients unable to respond to the research evaluation (cerebral function disorder,  difficulty to understand, read or write French language).

The purpose of this study is to determine whether tart cherry supplementation effects  thermotolerance and heat acclimation in human subjects exposed to exercise/heat stress.  Specific Aim I. To determine if tart cherry in combination with repeated bouts of thermally  stressful exercise will impact the gut microbiome & inflammation measured via stool sample &  blood samples for plasma endotoxin, inflammatory cytokines and HSP.  Specific Aim II. To determine whether whole body hyperthermia causes changes in bacterial  populations in the gut microbiome, and if these changes are affected by washout or  re-acclimation.  Specific Aim III. To determine whether tart cherry supplementation suppresses the ability of  human subjects to acclimate to exercise/heat stress. This will be assessed via body  temperature, heart rate, sweat and plasma volume responses, and exercise performance during  standardized heat tolerance tests. 10 recreationally trained cyclists will be recruited and will complete the study in  counter-balanced randomized order (5 will start with placebo and 5 will start with tart  cherry juice, then have a 4 week washout and complete the other intervention). Participants  will complete 15 total sessions in the exercise physiology lab including: a VO2max test, 4  heat stress tests (pre- and post-acclimation) and 5 consecutive days of heat acclimation  sessions (twice).  The VO2max test will be an incremental cycling test, starting at 80 Watts and increasing 25  Watts per minute until fatigue. The maximal Wattage will be used to determine exercise  intensity during the heat stress test and heat acclimation sessions.  The heat stress test and heat acclimation sessions will occur in a controlled environment of  38C and 25% humidity. Airflow will be provided with a fan at 1 m/s. Prior to entering the  controlled environment, participants will provide a mid-stream urine sample to assess  hydration status via urine specific gravity (USG) and osmolality (Vapro, ELITech), then empty  their bladder, measure their nude body mass on a scale (in a private bathroom in the lab),  and self-insert a rectal thermometer 10cm past the anal sphincter. If the participant is  dehydrated, they will be instructed to drink 500 ml of water and wait to start exercise until  their hydration level is normal (USG<1.020, urine osmolality 500 800 mOsm). Researchers will  then affix skin temperature sensors to the participants chest, arm, thigh, and calf and a  heart rate monitor to their chest. Participants will the enter the heat chamber and sit on  the bicycle for 5 minutes to get acclimated to the environment and to obtain resting levels  of thermal sensation and perceived effort. Following these 5 minutes, the participant will  commence exercise (described below). Participants will be provided water kept in the  controlled environment (to avoid cooling) to consume ad libitum throughout all exercise  sessions. Following the exercise session, participants will exit the controlled environment  and void their bladder, collecting all urine in a cylinder and towel dry and assess their  nude body mass. These will be used along with volume of water consumed during exercise to  assess body mass changes and sweat rate.  Heat stress test:  The heat stress test will consist of cycling at 40% of their maximal Watt output for 45  minutes, followed by a 5k time trial, where they will cover the 5k in as fast a time as  possible.  Heat acclimation sessions Heat acclimation sessions will be 60 minutes and will utilize an  isothermic heat acclimation modality where individuals will exercise at a self-selected  cadence to reach a core temperature of 38.5C. Once 38.5C has been reached, they will stop  exercising and rest. Typical time to reach a core body temperature of 38.5C is 30-50 minutes,  so the individual will exercise for this time, and rest for the remainder of the 60 minutes.  During this rest time, body temperature will continue to rise because of metabolic heat and  heat produced from exercises. However if their temperature reduces below 38.5C, they will  begin exercise again to maintain temperature above 38.5C. These sessions will occur daily for  5 days.  Supplementation Participants will begin supplementation 24 hours prior to their first heat  stress test and throughout their heat acclimation sessions until the final heat stress test  has been completed (7 days of supplementation total). Supplementation will consist of  consuming an 8 oz bottle of tart cherry juice or placebo twice daily, once in the morning and  once in the evening, at least 2 hours before bed. Following a 4 week washout period,  participants will complete the opposite condition (placebo or polyphenol).  The investigators will assess the impact of hyperthermia on the gut microbiome before and  after heat acclimation. Participants will provide a stool sample at pre-supplementation and  24 hours post each of the heat stress tests (pre- and post-acclimation) for each of the  interventions (tart cherry and placebo). Participants will collect a stool sample using a  toilet hat and aliquot three small samples. They will be provided with a toilet hat, a pair  of gloves, a sterile spatula, and three sterile eppendorf tubes. They will be asked to put  approximately a nickle sized sample in each of these tubes. These will be placed in the  freezer and brought to the lab on ice (they will be provided with a biohazard cooler bag and  ice pack for transport), where they will be stored at -80C until analysis. Inclusion Criteria:  -  Male  -  18-55 years old  -  Recreational cyclists (>150 minutes per week of cycling exercise)  -  VO2max >60th percentile according to ACSM Exclusion Criteria:  -  Previous episode of heat illness, such as heat syncope, heat exhaustion or heat stroke  -  Known cardiopulmonary disease, metabolic disorders, Parkinsons Disease, or multiple  sclerosis or other autonomic nervous system conditions  -  diagnosed with or being treated for arthritis or any inflammatory condition (such as  Lupus, gout, or Sjogrens syndrome)  -  Known or suspected orthostatic hypotension or low blood pressure  -  Known issues with cooling or sweating  -  currently smoke or quit smoking less than one year ago  -  not willing to self-insert a flexible, thin (3 mm) vinyl rectal probe and maintain  this position throughout all exercise sessions.  -  not willing to have blood drawn pre-supplementation and 4 times during heat stress  test trials (a total of 10 times during the study).  -  not willing to provide a stool sample pre- and post-heat stress tests (4 total  samples).  -  allergy to cherries or food dyes

The aim of this study is to investigate the effect of kinesio-tape application and stretching  exercise on calf muscle cramp during pregnancy Up to 30% to 50% of pregnant women suffered from leg cramps, especially in the third  trimester. Almost two-thirds of these women experience leg cramps twice per week and they can  occur at any time, particularly at night.In mild and moderate cases, calf cramps may last for  seconds, but in severe cases, leg cramps in pregnancy may last for minutes .In many cases  calf cramps are very painful , which can affect daily activities, restrict exercise and  performance, motive sleep disturbance and reduce the quality of life.Non-drug treatments are  found to being effective for the treatment of muscle cramps. Non-drug treatments such as  muscle stretching, physical exercise, avoidance of physical fatigue, massage, relaxation,  heat therapy, weight loss, sensory nerve stimulation, ankle splints worn while sleeping, and  changes to sleeping and sitting positions.This study has two groups; one recieved  kinesio-tape application and stretching exercises and the second one recieved instructions  about dealing with cramps with self low sustained stretch Inclusion Criteria:  -  pregnant women who are suffering from calf cramps.  -  Their age range from 25 to 35 years.  -  Their body mass index range from 25 to 29.9 kg/m2 . Exclusion Criteria:  -  Skin abnormalities (skin malignancy in the treated area or burned).  -  History of previous back surgery.  -  Neuromuscular diseases like multiple sclerosis.  -  Sensory disturbances.  -  Evidence of previous vertebral fractures or major spinal structural abnormality,  spondylolisthesis or spinal stenosis.  -  Systemic disease of musculoskeletal system.  -  Viscerogenic cause of back pain.  -  Also, women who have eclampsia or pre-eclampsia.

FThis NIDA-funded research study, entitled, PrEP2Prevent: An Online PrEP Navigation and  Activation Intervention for YMSM, will develop and pilot test a PrEP activation, navigation  and support intervention for young men who have sex with men (YMSM); this population not only  has the highest annual incidence of HIV, but also is the least likely to have ever used PrEP.  Our own data with a large cohort of YMSM indicates that while 90% have heard about PrEP and  86% meet CDC's eligible criteria for PrEP, only 23% have ever used PrEP and 8% are currently  on PrEP. In this same cohort, 26% tested positive for one or more sexually transmitted  infections (STIs) and the HIV seroconversion rate was 4.3% during a 2 years period. Thus, it  is very clear that there is an urgent need for interventions that specifically target PrEP  uptake while also addressing a complex array of individual (e.g. substance use, depression),  sociocultural (e.g., PrEP-related stigma), and structural (e.g., medication costs) barriers  to PrEP uptake. The investigators are proposing an intervention that includes PrEP  navigation; patient activation to reduce PrEP-related stigma and increase PrEP self-efficacy;  and peer/social support. The intervention will be delivered using mobile health (mHealth) or  similar technology. The U.S. Department of Health and Human Services (HHS) has set a goal to end the HIV epidemic  by the year 2030, which is well within reach given the availability of antiretrovirals that  effectively prevent and treat HIV. But success can only be achieved if targeted approaches  are implemented with at-risk populations to address known barriers of engagement along the  pre-exposure prophylaxis (PrEP) and HIV care continua. In response, obtained funding from  NIH, using the R34 mechanism, with the goal of the research being to develop and pilot test a  PrEP activation, navigation and support intervention for YMSM, including young Black and  Latino YMSM (B-YMSM, L-YMSM), who not only have the highest annual incidence of HIV but who  are also the least likely to have ever used PrEP. There is very clear evidence demonstrating  that while YMSM have high levels of knowledge about and intentions to use PrEP, few have ever  used PrEP. Our own research demonstrate the urgent need for interventions that specifically  target PrEP uptake while also addressing a complex array of individual (e.g., side effect  concerns, substance use, depression), sociocultural (e.g., internalized homophobia,  PrEP-related stigma), and structural (e.g., access to care, medication costs) barriers to  PrEP uptake. Our research also demonstrates that such an intervention should include four  components: 1) inclusion of PrEP and other service navigation; 2) provision of skills to  address patient activation, reduce PrEP-related stigma, and increase PrEP self-efficacy; 3)  peer/social support; and 4) utilize a mobile health (mHealth) platform or similar technology  that supports both in-person and virtual intervention delivery (text and live video chat).  Based on these findings, the investigators propose to conduct research with the following  specific aims  Specific Aim 1: Conduct formative research to inform the development of a PrEP activation,  navigation and support intervention, which the investigators call PrEP2Prevent. Qualitative  data will be collected using structured guides from working/focus groups with YMSM, Trans,  and gender non-conforming youth and during Key Informant Interviews (KII) with existing PrEP  care providers/navigators. These data will inform intervention content and  activation/navigation services.  Specific Aim 2: Develop and then conduct usability testing of PrEP2Prevent, including both  the intervention content and mHealth delivery platform. Data from Aim 1 will inform the  content and structure of intervention components to be included. During intervention  development, two rounds of usability testing will be conducted with 8-10 YMSM, Trans, and  gender non-conforming youth to ensure features are usable and the content is understood.  Internal beta testing will be performed to assess for full technical functionality.  Specific Aim 3: Evaluate the feasibility, acceptability and preliminary efficacy of  PrEP2Prevent with a racially/ethnically diverse sample of 150 (50 Non-Hispanic Whites, 50  Blacks/African American, 50 Latino/Hispanic) YMSM, Trans, gender non-conforming youth, ages  16-26 years. Participants will be randomly assigned in a 1:1 ratio to the intervention app  (PrEP2Prevent) or control app (standard of care). Primary outcomes are feasibility,  acceptability and preliminary efficacy. Feasibility data will include sources and rates of  recruitment/retention, barriers and facilitators to recruitment/retention, engagement with  PrEP navigator both in-person and via mHealth platform, as well as paradata on the mHealth  platform use (e.g., number of log-ins, time spent, chatroom/text-based discussions).  Acceptability will be assessed using a survey with validated measures at intervention  completion. Preliminary efficacy will include linkage to PrEP services and PrEP uptake, these  data will be collected at baseline and at 3- and 6-months following completion of the  intervention. Mediators/moderators will include PrEP self-efficacy, PrEP stigma, and patient  activation. The findings from this research will inform further refinements to the  intervention and provide estimates of possible intervention effect sizes (group means, SDs)  for a future randomized controlled trial (RCT). The funded research is highly significant,  timely and innovative. Its innovation lies in the fact that it: a) targets an intervention  for YMSM where it is most needed - e.g., on PrEP uptake; b) recognizes that YMSM require  tools and support to successfully navigate PrEP services; and c) uses mHealth to deliver the  intervention. Moreover, the intervention can be used for both engagement and re-engagement in  PrEP uptake for YMSM who cycle in and out of PrEP care. Further, the intervention is  potentially easily adaptable and transferable to address other critical PrEP and HIV needs  (e.g., uptake of long-acting PrEP and antiretroviral therapy [ART]). Inclusion Criteria:  1. PrEP providers serving YMSM from healthcare and community-based organizations located  in Los Angeles County or PrEP Navigators similarly employed by healthcare and  community-based organizations that deliver PrEP services to YMSM.  2. >18 years of age  1. 16-26 years old  2. cisgender male, Trans, gender non-conforming, or identify differently from the gender  picked for you at birth  3. identify as gay, bisexual, or some other same-sex identity, and/or report having had  sex with anyone with a penis during the previous 12 months  4. identify as White/Caucasian, Black/African American, Latinx, Asian-Pacific Islander,  Indigenous, Native American or mixed-race  5. living in the Los Angeles metro area  6. have daily access to an iOS/Android smartphone and/or tablet with internet access  7. know their HIV status and are HIV negative at time of enrollment.  1. 16-26 years old  2. cisgender male, Trans, gender non-conforming, or identify differently from the gender  picked for you at birth  3. identify as gay, bisexual, or some other same-sex identity, and/or report having had  sex with anyone with a penis during the previous 12 months  4. identify as White/Caucasian, Black/African American, Hispanic/Latino/Latinx, or  mixed-race  5. living in the Los Angeles metro area  6. have daily access to an iOS/Android smartphone and/or tablet with internet access  7. report having insertive and/or receptive anal sex in the previous 6 months or report a  positive STI result in the previous 6 months  8. not currently on PrEP and no plan to start/restart PrEP in the following 7 days  9. not currently enrolled in another HIV prevention study Exclusion Criteria:  1. Not a PrEP provider or navigator serving YMSM from healthcare and community-based  organizations located in Los Angeles County  2. under 18 years of age  Phase 1B and Phase 2:  1. is younger than or older than 16- to 26-years  2. not cisgender male, Trans, gender non-conforming, or identify differently from the  gender picked for you at birth  3. does not identify as gay, bisexual, or some other same-sex identity, and/or report  having had sex with anyone with a penis during the previous 12 months  4. does not identify as White/Caucasian, Black/African American, Latinx, Asian-Pacific  Islander, Indigenous, Native American or mixed-race  5. does not report living in the Los Angeles metro area  6. is non-English speaking  7. does not have daily access to an iOS/Android smartphone and/or tablet with internet  access  8. is a person living with HIV  9. for Phase 2 only, participants will be excluded if they participated in the Phase 1B  focus groups  Phase 3:  1. is younger than or older than 16- to 26-years  2. not cisgender male, Trans, gender non-conforming, or identify differently from the  gender picked for you at birth  3. does not identify as gay, bisexual, or some other same-sex identity, and/or does not  report having had sex with anyone with a penis during the previous 12 months  4. does not identify as White/Caucasian, Black/African American, Hispanic/Latino/Latinx,  or mixed-race  5. does not report living in the Los Angeles metro area  6. is non-English speaking  7. is a person living with HIV (self-reported)  8. does not report insertive and/or receptive anal sex in the previous 6 months or does  not report a positive STI result in the previous 6 months  9. does not have daily access to an iOS/Android smartphone and/or tablet with internet  access  10. is currently on PrEP or has plans to start/restart PrEP in the following 7 days; and  11) is currently enrolled in another HIV prevention study.

this study will compare the efficacy and safety of use either Ranibizumab and Aflibercept in  treatment of macular edema resulting from non ischemic central retinal vein occlusion in  patients younger than 5o years old This is a prospective randomized interventional study, Forty eyes of forty patients younger  than 50 years with macular edema due to non-ischemic CRVO were enrolled in the study.  Patients will be randomized into 2 groups. First group will receive intravitreal injection of  Ranibizumab 0.5 mg\0.1ml. the second group will receive intravitreal injection of 2.0 mg\0.1  ml Aflibercept. All patients will be followed up for 12 months. Inclusion Criteria:  -  patients younger than 50 years with macular edema due to non-ischemic CRVO Exclusion Criteria:  1. diabetic retinopathy, intraocular inflammation, age related macular degeneration,  patients with solar or radiation retinopathy,  2. patients with ischemic type CRVO and patients who had recent intraocular surgery.  3. patients who had previous intravitreal injections, ophthalmic laser surgeries.  4. patients with dense cataracts whom fundus was difficult to scan.  5. Patients who were lost to follow up visits were also excluded

To investigate the effect of trazodone on sleep, hippocampal-dependent memory and hippocampal  excitability. The investigators hypothesize that trazodone will improve total sleep time and  proportion of time in Slow Wave Sleep (SWS). The REST trial is a randomized, placebo-controlled, double-blind crossover study of trazodone  (50 mg at bedtime) in participants with Amnestic Mild Cognitive impairment (aMCI) and sleep  complaints. The investigators will randomize 100 subjects and administer trazodone and  placebo for 4 weeks each with a 4-week washout period in between. A 4-week washout period is  more than sufficient due to trazodone's elimination half-life of 10-12 hours. The crossover  design will facilitate recruitment and enable the use of the subjects as a control without  requiring a parallel placebo arm. Inclusion Criteria:  1. Mild Cognitive Impairment (MCI) as defined by Albert et al.2 including subjective  memory complaint and/or objective evidence of memory problems;  2. Clinical Dementia Rating (CDR) of 0.5 with a Memory Box score of >=0.5;  3. Evidence of sleep complaints with Pittsburgh Sleep Quality Index score of >5 (a  well-validated cutoff observed in >40% of older persons);  4. Memory performance > 1.5 Standard Deviation (SD) below age-and education-matched  control subjects on the Repeatable Battery for the Assessment of Neuropsychological  Status (RBANS) List Recall;  5. Visual and auditory acuity adequate for neuropsychological testing;  6. Good general health with no disease expected to interfere with the study;  7. Able to have Magnetic Resonance Imaging (MRI) scan;  8. Availability of knowledgeable informant (KI) Exclusion Criteria:  1. Less than 55 years of age to reduce likelihood of including individuals with  frontotemporal dementia or non-dementia MCI;  2. Too frail or medically unstable to undergo study procedures;  3. Prior diagnosis of Obstructive Sleep Apnea (OSA) or evidence of moderate-to-severe OSA  on baseline Home Sleep Test (HST) as evidenced by an apnea/hypopnea index of >15;  4. Dementia;  5. Cognitive complaints and deficits better explained by other medical/neurologic  conditions;  6. Delirium;  7. Allergic to trazodone;  8. Taking sleep medications including trazodone;  9. Current substance abuse;  10. Current major depressive, manic, or acute psychotic episode;  11. Prior diagnosis of significant systemic illness or unstable medical condition which  could lead to difficulty complying with the study protocol or represent alternate  primary cause of memory problems beyond Alzheimer's Disease (AD) pathology:  12. Lack of available KI;  13. Prior diagnosis of Q wave T wave Corrected for heart rate (QTc) > 470 msec (females)  or > 450 msec (males);  14. Inability to provide informed consent

This study aims to predict and minimize post-discharge adverse events (AEs) during care  transitions through early identification and escalation of patient-reported symptoms to  inpatient and ambulatory clinicians by way of predictive algorithms and clinically integrated  digital health apps. We will (1) develop and prospectively validate a predictive model of  post-discharge AEs for patients with multiple chronic conditions (MCC); (2) combine, adapt,  extend, and iteratively refine our EHR-integrated digital health infrastructure in a series  of design sessions with patient and clinician participants; (3) conduct a RCT to evaluate the  impact of ePRO monitoring on post-discharge AEs for MCC patients discharged from the general  medicine service across Brigham Health; and (4) use mixed methods to evaluate barriers and  facilitators of implementation and use as we develop a plan for sustainability, scale, and  dissemination. Adverse events (AE) during care transitions range from 19-28% and may lead to readmissions,  representing an ongoing threat to patient safety. Early identification and escalation of  patient-reported symptoms to inpatient and ambulatory clinicians is critical, especially for  patients with multiple chronic conditions (MCC). Clinically integrated digital health apps  have the potential to more accurately predict post-discharge AEs and improve communication  for patients, their caregivers, and the care team. Such tools can provide individualized risk  assessments of AEs by systematically collecting relevant patient-reported outcomes (PROs) and  leveraging standardized application programming interfaces (API) to combine them with  electronic health record (EHR) data. While patient-reported outcomes (PROs) are increasingly  used in ambulatory settings, their use for real-time symptom monitoring and escalation during  transitions from the hospital is novel and potentially transformative-by both empowering  patients to better understand their individualized risks of post-discharge AEs, and improving  monitoring while transitioning out of the hospital. Our proposed intervention is grounded in  evidence-based frameworks for care transitions, and scaling and spread of digital health  tools. To inform our intervention, we propose developing and validating a predictive model of  post-discharge AEs for 450 MCC patients using relevant PRO questionnaires and electronic  health record (EHR) derived variables during our baseline pre-implementation period.  Simultaneously, we will combine, adapt, extend, and refine our previously developed  EHR-integrated hospital and ambulatory-focused digital health infrastructure to support MCC  patients in real-time symptom monitoring using PROs when transitioning out of the hospital.  Our intervention uses interoperable, data exchange standards and APIs to seamlessly integrate  with existing vendor patient portal offerings, thereby addressing critical gaps and  supporting the complete continuum of care. Our multidisciplinary team uses principles of  user-centered design and agile software development to rapidly identify, design, develop,  refine, and implement requirements from patients and clinicians. Our team will rigorously  evaluate this intervention in a large-scale randomized controlled trial of 850 in which we  compare our real-time symptom monitoring intervention (425) to usual care (425) for patients  with MCCs transitioning out of the hospital. Finally, we will conduct a robust mixed methods  evaluation to generate new knowledge and best practices for disseminating, implementing, and  using this interoperable intervention at similar institutions with different EHR vendors Inclusion Criteria:  -  Adult (18 years or older)  -  Hospitalized on the general medicine services at Brigham and Women's Hospital or  Brigham and Women's Faulkner Hospital for at least 24 hours  -  Have a discharge status of home, home with services, or facility  -  English-speaking patients or their English-speaking legally designated healthcare  proxy or next of kin (i.e., a family caregiver)  -  Non-English-speaking patients who have an English-speaking legally designated  healthcare proxy or next of kin (i.e., a family caregiver)  -  Two or more chronic conditions: Anxiety, Asthma*, Arthritis (Osteoarthritis,  Rheumatoid), Atrial Fibrillation, Cancer*, Cerebral vascular accident, Chronic kidney  disease*, Chronic obstructive pulmonary disease (COPD)*, Cirrhosis, Coronary artery  disease/Ischemic heart disease, Dementia, Depression, Diabetes mellitus*, End-stage  renal disease*, Heart failure*, Hepatitis B, C*, HIV/AIDs, Hyperlipidemia,  Hypertension, Inflammatory bowel disease, Osteoporosis, Sickle cell disease, Substance  abuse (Alcohol/Opioid) Exclusion Criteria:  -  Less than 18 years of age  -  Less than two chronic conditions  -  Hospitalized less than 24 hours  -  No identifiable healthcare proxy or next of kin (i.e., a family caregiver)

Neural stimulation with photons has been proposed for a next generation of cochlear implants  (CIs). The potential benefit of photonic over electrical stimulation is its spatially  selective activation of small populations of spiral ganglion neurons (SGNs). Stimulating  smaller neuron populations along the cochlea provides a larger number of independent channels  to encode acoustic information. Hearing could therefore be restored at a higher fidelity and  performance in noisy listening environments as well as music appreciation are likely to  improve .  While it has been demonstrated that optical radiation evokes auditory responses in animal  models, it is not clear whether the radiant exposures used in the animal experiments are  sufficient to stimulate the auditory system of humans. The proposed tests are:  1. to demonstrate that light delivery systems (LDSs) can be inserted and oriented optimally  in the human cochlea.  2. to show that the LDSs are able to deliver sufficient amount of energy to evoke a  compound action potential of the auditory nerve.  3. to validate that the fluence rate (energy / target area) required for stimulation is  below the maximal fluence rate, which damaged the cochlea in animal experiments.  4. to show that combined optical and electrical stimulation is able to significantly lower  the threshold required for optical stimulation in humans.  The endpoints for the study are either the completion of the experiments proposed or the  demonstration that not sufficient energy can be delivered safely in the human cochlea to  develop an action potential. The patient is admitted to one of the participating clinical centers because of a brain  tumor, which requires surgery to be removed. As discussed in detail with the treating  surgeon, the tumor is large, and an approach will be used that accesses the tumor from the  side through the temporal bone. This approach passes by the balance and hearing organ, and  the partial or complete removal of the organ responsible for balance and hearing on this side  is necessary. Participation in the study will extend the time of surgery by 30 minutes. There  is no special preparation and no follow-up required for the study.  In this study, a cochlear implant system that uses light to stimulate the cochlea will be  tested. It is a small light delivery system consisting of optical fibers and light sources  the size of a human hair. This light delivery system will be inserted into the hearing organ,  the cochlea before it is damaged or removed during the tumor surgery. After insertion into  the cochlea, pulses of infrared light will be delivered to the cochlea, and auditory  responses will be measured with a small electrode placed at the cochlea.  If possible, after completion of the measurements and during the continuation of the tumor  surgery, the tissue of the hearing organ, which is typically destroyed through the drilling,  will be harvested for histological evaluation. Inclusion Criteria:  Criterion for inclusion of a patient is the requirement of the translabyrinthine approach  for tumor removal. The surgical approach is determined by the tumor size, the tumor  location and the remaining hearing of the patient. Criteria for a translabyrinthine  approach are:  1. the tumor grows in the pontine angle and the facial nerve is at risk for damage during  the surgery because the tumor is already large and in close proximity of the facial  nerve AND  2. the tumor is larger than 2.5 cm AND  3. Pure tone hearing thresholds are elevated by at least 50 dB AND  4. Speech discrimination scores are 50% or less Exclusion Criteria:  -  adults unable to consent.  -  individuals who are not yet adults (infants, children, teenagers).  -  pregnant women.  -  prisoners.  -  vulnerable populations

Surgical interventions are not only a physiological trauma, but also a psychological and  social trauma because they cause deterioration of the individual's comfort. Comfort is among  the most basic human needs and provides a better care output. One of the conditions that  cause deterioration of comfort and anxiety in patients is hunger and thirst before surgery.  Since 1994, several guides published by professional groups in many countries on  pre-operative fasting periods have published that clear liquids can be taken up to 2 hours  before the surgery in elective surgeries, and solid foods can be taken up to 6 hours before  the surgery. One of the basic principles of ERAS protocols, which include evidence-based care  interventions applied at all stages of the surgical process, for the preoperative period is  to ensure that the patient takes a carbohydrate drink up to two hours before anesthesia and  to shorten the long fasting period. In many countries, the problems experienced by patients  as a result of long-term hunger have been identified. When the comfort status of the patients  who were given carbohydrate-rich drinks before the surgery was examined, it was observed that  the symptoms such as thirst, hunger, insufficiency, fatigue, nausea, pain, anxiety and  depression were reduced and oral carbohydrate solutions were recommended. In the literature,  it is stated that the prolongation of the fasting period causes an increase in the anxiety of  the person and negatively affects his comfort, and it is recommended to drink 800 ml of  carbohydrate liquid food until midnight the day before the surgery and 400 ml of liquid  carbohydrate food 2-3 hours before the surgery in order to provide metabolic satiety. The  nurse, who is one of the health workers responsible for the care of the patient, has to  manage the restriction of oral food and liquid intake and the comfort of the patient in the  best way before the operation. Accordingly, in our study, the answers were sought whether the  oral carbohydrate solution given before hip arthroplasty had an effect on anxiety and patient  comfort. Hip arthroplasty (HA) is a very common treatment method in orthopedic surgery worldwide. HA  is considered a successful, safe and cost-effective medical intervention to regain pain-free  mobility and functionality of the hip joint in patients with severe joint disease or trauma.  It is stated that the annual number of patients undergoing HA in the United States is  193,000, and this number is approximately one million worldwide. In the next 15 years, it is  estimated that the number of patients undergoing HA will continue to increase in the world  and in Turkey.  It is stated that health care services should start in the preoperative period and continue  in the postoperative period, especially in HA surgeries performed due to limitation of  mobility. Because HA application is seen as a major surgical intervention and as with many  surgical interventions, it can affect the individual as a whole.  Surgical intervention is a combination of anesthesia, drug therapy, tissue trauma, blood loss  and body temperature changes. These developing events stimulate metabolic changes and cause  postoperative anxiety and stress response at the same time. Exposure of the human body to  surgery or other trauma elicits a neurohumoral response and activates a catabolic process.  Surgical stress causes an increase in the release of regulatory hormones such as  catecholamine, glucagon and cortisol in the body and a decrease in insulin sensitivity. The  increase in cortisol level leads to the development of insulin resistance and hyperglycemia,  which have an important effect on the healing process. Changes in this process increase the  risk of postoperative complications and mortality.  On the other hand, fasting the patient overnight as a standard practice in the preoperative  period in order to reduce the risk of lung aspiration in elective surgery patients may cause  a change in the insulin glucagon ratio. This increases the stress response to surgical trauma  and may have a major impact on glycemic control and insulin resistance. Prolongation of the  preoperative fasting period may cause negative effects such as feeling of hunger, anxiety,  restlessness, headache, dehydration, hypovolemia and hypoglycemia. However, the increase in  the preoperative fasting period causes a decrease in patient satisfaction, and causes  undesirable conditions such as nausea and vomiting in the postoperative period, delaying the  healing process and prolonging the hospital stay of the patients.  In the guidelines published in countries such as America, Canada and Europe, it is reported  that the longer the fasting period, the negative effects on patient safety and comfort. In  elective surgeries, it is recommended that clear liquids can be consumed up to the last two  hours and solid foods up to six hours before the surgical procedure in order to reduce  anxiety, reduce the negative effects of the stress response on the patient, and ensure  patient comfort. In the guideline published by the Turkish Society of Anesthesiology and  Reanimation (TARD) in 2005, it is recommended to comply with these criteria in patients who  will undergo elective surgery. Therefore, modern perioperative care aims at maximizing the  shortening of the fasting period before an elective surgery.  According to Enhanced Recovery After Surgery (ERAS) protocols, one of the elements of modern  perioperative care is the administration of preoperative oral carbohydrate loading (OCS). In  the literature; oral carbohydrate solution administration before elective surgery; It is  stated that it is absorbed from the stomach of the patient in an average of 90 minutes,  reduces protein catabolism in the muscles, increases glycogen storage in the liver and  reduces insulin resistance. In addition, in other studies conducted in abdominal, orthopedic  and cardiac surgery; It has been determined that OCS reduces postoperative metabolic stress,  preserves lean body mass and muscle strength, and increases patient comfort by reducing the  length of hospital stay.  The concept of patient comfort is defined as the comfort that facilitates daily life. In  providing the health care needs, which are extremely stressful for the patient, nurses apply  nursing interventions for comfort, which is a concept unique to the individual, allowing the  patient to experience less anxiety, be more peaceful and overcome their problems.  Discomforts experienced by the patient during the operation or procedures (pain, nausea,  vomiting, hypothermia, anxiety, etc.) may increase the patient's anxiety and may be the main  reason for the decrease in comfort. The nurse should provide all necessary nursing  interventions to reduce or eliminate the situations that will cause anxiety in the patient  before and after each procedure to be applied to the patient. With all these practices,  patients can receive a quality nursing care, contribute to their faster recovery and increase  their quality of life.  Quality patient care in surgical nursing; should be shaped within the framework of ethical  principles such as not harming and providing benefit. In the literature; Evidence for the  duration of fasting in the preoperative period is reflected in clinical practice, emphasizing  the need to prevent patients from being harmed without putting them at risk. Thus, by  managing the hunger period within the scope of evidence-based practices; It is stated that  many therapeutic benefits can be obtained, such as reducing anxiety, discomfort, headache,  thirst and hunger in the preoperative period, and providing patient comfort by reducing  nausea, vomiting and dehydration in the postoperative period.  Managing food and fluid restriction in line with the guidelines in the preoperative period is  one of the important responsibilities of the surgical nurse. Thus, the comfort of the  patients will be increased, their anxiety will be reduced, and they will be able to return to  their normal lives as soon as possible. Working from here; It was aimed to determine the  effect of preoperative OCS on anxiety and patient comfort in patients undergoing HA. Inclusion Criteria:  -  Who volunteered to participate in the research,  -  Total hip replacement surgery planned,  -  Who are over 18 years old,  -  ASA I and II group,  -  First time hip replacement surgery Exclusion Criteria:  -  Diabetes mellitus,  -  In the emergency patient group,  -  with gastroesophageal reflux,  -  Those with esophageal disease (Hiatus hernia, esophagitis, achalasia…)  -  Having endocrine problem,  -  Diagnosed with ileus,  -  With pyloric stenosis,  -  ASA III and IV group,  -  Intravenous fluid administered before surgery,  -  Using drugs that affect blood glucose levels,  -  Previous hip replacement surgery  -  Body mass index over 35kg/m2 (The value obtained by dividing the weight in kilograms  by the square of the height in meters),  -  Having a psychiatric and neurological diagnosis, poor general condition,  -  Needing all kinds of fluid and blood support in the pre-operative period,  -  Patients who use alcohol or cigarettes

The purpose of this study is to evaluate the objective response rate, safety and identify potential biomarkers in platinum-resistant ovarian cancer patients treated with voreloxin injection given on a 28-day cycle. Other objectives of this study are to evaluate Progression-free survival and measure CA-125 response rate. Inclusion Criteria:   -  Histologically or cytologically documented epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer   -  Completed at least one Platinum Based Therapy (PBT) regimen (carboplatin, cisplatin, or another organoplatinum compound).   -  Evidence of platinum-resistant disease, relapse/progression within 6 months of the completion of PBT, or intolerant to PBT (inability to receive PBT due to hypersensitivity reactions to platinum)   -  Patients with primary platinum-resistant disease are allowed to receive no more than one nonplatinum cytotoxic regimen and no more than one noncytotoxic regimen for the management of recurrent or persistent disease after the development of primary platinum-resistance.   -  Measurable disease per GOG-RECIST criteria   -  GOG Performance Status of 0 or 1 Exclusion Criteria:   -  Radiotherapy, chemotherapy, and hormonal, cytokine, or targeted therapy, within 3 weeks (nitrosurea or mitomycin C within 6 weeks) prior to the anticipated first day of treatment.   -  Monoclonal antibody therapy within 4 weeks prior to clinical study entry   -  Unresolved or impending bowel obstruction   -  Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia   -  Prior radiotherapy to more than 25% of the marrow space   -  Requiring hemodialysis or peritoneal dialysis   -  Myocardial infarction or cerebrovascular accident/transient ischemic attack within the 6 months prior to the anticipated first day of treatment   -  Thromboembolic event (deep vein thrombosis [DVT] or pulmonary embolus [PE]) within 28 days prior to the anticipated first day of treatment   -  History of active CNS metastases   -  Any other medical, psychological, or social condition that would contraindicate the patient's participation in the clinical study due to safety or compliance with clinical study procedures. Please note: There are additional inclusion/exclusion criteria for this study. Please contact the study center for additional information and to determine if you meet all study criteria.

The purpose of the Stanford Center for Back Pain is to investigate and characterize the  mechanisms of four treatments for chronic low back pain. These interventions (research  treatment) include real-time fMRI neurofeedback, mindfulness based stress reduction,  cognitive behavioral therapy, and acupuncture treatment. The investigators plan to  characterize both mechanisms of treatment effects and efficacy. The Stanford Center for Back Pain establishes a collaborative, multidisciplinary research  program to investigate CAM interventions for the treatment of chronic low back pain (CLBP).  The investigators' overall goal is to characterize the shared and distinct mechanisms of four  CAM interventions and translate the investigators' findings to tailored and effective  treatments for CLBP. CLBP is a highly prevalent and difficult-to-treat condition for which  many patients seek CAM therapies. Basic science has revealed that abnormalities in central  pain modulatory and emotion regulatory systems play a crucial role in CLBP. What is not clear  is how CAM therapies alter the functioning of the brain systems involved in chronic pain. The  Stanford Center for Back Pain aims to fill this gap by conducting 3 projects, each aiming at  elucidating mechanisms underlying different CAM therapies for CLBP.  Project 1 will focus on a promising novel alternative therapy for CLBP real-time fMRI  neurofeedback which trains patients to control specific neural processes that lead to  improvements in pain. Project 2 will characterize the pain modulatory and emotion regulatory  effects of mindfulness based stress reduction and cognitive behavioral therapy for CLBP.  Project 3 will characterize psychophysical and neuroimaging based neural mechanisms  underlying verum and placebo acupuncture.  The Stanford Center for Back Pain will provide optimal collaboration and synergy within a  multidisciplinary framework to identify mechanisms of CAM therapies for CLBP so that they can  eventually translate them into enhance clinical care of CLBP. Inclusion Criteria:  -  English Fluency  -  Chronic Low Back Pain as defined by NIH task-force or Healthy Controls Exclusion Criteria:  -  MRI contraindications  -  Pregnant or planning to become pregnant  -  Medical conditions that would interfere with study procedures, at the discretion of  the study team  -  Neurologic disorder, history of seizures, stroke, or brain abnormalities, which would  interfere with brain integrity, at the discretion of the study team.  -  Mental health conditions or treatment for mental health problems that would interfere  with study procedures, at the discretion of the study team.  -  Other project specific criteria may apply.

Cardiac amyloidosis is a major cause of early treatment-related death and poor overall  survival in individuals with systemic light chain amyloidosis. This project will develop a  novel approach to visualize cardiac amyloid deposits using advanced imaging methods. The  long-term goal of this work is to identify the mechanisms of cardiac dysfunction, in order to  guide the development of novel life-saving treatments. Primary light chain amyloidosis (AL) is the most common systemic amyloidosis, resulting from  a plasma cell dyscrasia, a hematological malignancy. It causes a restrictive cardiomyopathy  (AL-CMP) in over 70% of individuals. AL-CMP is as lethal as stage 4 lung cancer and more  lethal than any other form of restrictive heart disease; if untreated, the mortality rate is  50% within 18 months. Moreover, myocardial dysfunction, the hallmark of AL-CMP, significantly  increases early treatment related mortality, predominantly cardiovascular death, and is a  powerful predictor of poor long-term survival. Two potentially treatable mechanisms underlie  myocardial dysfunction-mechanical effects of amyloid and toxic effects from circulating light  chain/ amyloid interactions-and predispose to heart failure, arrhythmias, and sudden death in  individuals with AL-CMP. Until now, efforts to determine the mechanisms of AL-CMP have been  hampered by a lack of animal models and the limitations of noninvasive techniques to directly  image myocardial amyloid. A recent breakthrough, 18F-florbetapir PET/CT, has provided for the  first time specific and quantitative imaging of myocardial amyloid including toxic amyloid  protofibrils. Furthermore, we propose to investigate three pre-clinically proven pathways of  light chain toxicity in humans-myocardial oxidative metabolism, oxidative stress, and  coronary microvascular function. Our central hypotheses are that myocardial 18F-florbetapir  retention is a biomarker for aggressiveness of AL-CMP and that effective chemotherapy will,  by reducing circulating light chains, decrease aggressiveness of AL-CMP and improve oxidative  stress, myocardial oxidative metabolism, microvascular function and contractile function,  prior to an improvement in myocardial amyloid content. In Aim 1, we will quantify myocardial  18F-florbetapir retention as a marker of aggressive myocardial disease in individuals with  AL-CMP and active plasma cell dyscrasia compared to control individuals with AL-CMP and  long-term hematological remission. In Aim 2, we propose, using advanced imaging, to assess  the effects of light chain reduction due to chemotherapy on myocardial structure, function,  and metabolism and define the time course of these changes. Serial ECV and strain imaging by  CMR, serum F2-isoprostanes and peroxynitrite levels, myocardial oxidative metabolism (Kmono)  and coronary flow reserve by 11C-acetate PET, and 18F-florbetapir imaging will not only  intricately characterize the myocardial substrate in AL-CMP, but also identify changes in  response to therapy. The proposed studies offer the potential to transform our current  understanding of AL-CMP as a restrictive heart disease caused by passive amyloid-related  architectural damage to that of a more complex disorder resulting from both passive and  aggressive factors. The results of these studies may form the foundation for drug discovery  programs to prevent and cure AL-CMP.  Interactions of environmental factors, immunity, and host-related factors likely trigger  AL-amyloidosis, but have not yet been explored. Changes in metal ions and gut microbiota may  be causal, representing the integrated effects of all these factors, or may be the downstream  effect of systemic amyloid deposition in the organ systems. A plethora of recent literature  strongly support the role of microbiota in the pathogenesis of several diseases, suggesting  that gut microbiota changes with age, influences heart failure (HF) outcomes, and plays a  role in the formation of β-amyloid deposits in Alzheimer's disease. Importantly, alterations  in lifestyle, diet, prebiotics, probiotics, or phenols and gut microbiota may represent  therapeutic and preventative strategies in amyloid disease, but it has not been explored in  AL-amyloidosis. We propose to study the role of salivary and gut microbiome in AL  amyloidosis. Inclusion Criteria:  -  Age > 18 years  -  Diagnosis of light chain amyloidosis by standard criteria (immunofixation of serum and  urine, IgG free light chain (FLC) assay, a biopsy of fat pad/ bone marrow, or organ  biopsy, followed by typing of the light chain using immunohistochemistry or immunogold  assay with confirmation by Mass spectroscopy as needed)  -  For subjects traveling from out of town referred for systemic AL therapy based on  clinical evaluation and laboratory testing, but, pending biopsy results, study  enrollment and procedures may begin before official confirmation of biopsy  results. If biopsy is negative for AL amyloidosis, subject will be considered a  screen failure. There will be no more than 10 subjects who fall under this screen  failure for the duration of the study.  -  Subjects with localized amyloid deposition and non-systemic AL disease will be  eligible for enrollment in group D.  -  Willing and able to provide consent  -  Additional inclusion criteria for the Remission AL-CMP: Hematological response defined  as complete hematological remission or very good partial response-differential free  light chain (dFLC)<40 mg/dL for > 1 year prior to enrollment  -  Additional inclusion criteria for the Active AL-CMP - exercise: Ability to perform  supine bicycle exercise. Enrollment to this arm will stop after 36 subjects complete  baseline and 6 months studies.  -  Additional inclusion criteria for the Active AL Pre-CMP - Normal left ventricular wall  thickness (≤ 12 mm) and normal LVEF (≥55%) on echocardiography within 3 months or  increased wall thickness with normal cardiac biomarker levels: not meeting above  definition.  -  Additional inclusion criteria for Control Multiple Myeloma subjects: diagnosis of  multiple myeloma without concomitant amyloidosis by standard criteria  -  Additional inclusion criteria for Control Heart Failure subjects: diagnosis of heart  failure without amyloidosis by standard criteria  -  Additional inclusion criteria for the active AL-CMP: Abnormal TnT 5th generation  levels (>9 ng/L: Female, >14 ng/L: Male) or abnormal age appropriate N terminal  pro-brain natriuretic peptide, NT-proBNP (abnormal values: <50 years: >450 pg/ml;  50-75 years:>900 pg/ml; >75 years: >1800 pg/ml) Exclusion Criteria:  -  Hemodynamic instability  -  Decompensated heart failure (unable to lie flat for 1 hour)  -  Concomitant non-ischemic non-amyloid heart disease (valvular heart disease or dilated  cardiomyopathy)  -  Known obstructive epicardial coronary artery disease with stenosis > 50% in any single  territory  -  Severe claustrophobia despite use of sedatives  -  Presence of MRI contraindications such as metallic implants (pacemaker or ICD) at the  time of study enrollment except for Control Heart Failure subjects. Control HF  subjects with no devices, or, with strictly MR compatible devices will be eligible to  undergo MRI.  -  Significant renal dysfunction with estimated glomerular filtration rate < 30 ml/min/m2  within 14 days of each cardiac MRI study. Subjects who develop renal dysfunction over  the course of the study, meeting criteria listed above, will be excluded from the  cardiac MRI scan except for control HF subjects. These subjects with eGFR < 30  ml/min/1.73 m2 will undergo MRI without gadolinium contrast.  -  Subjects on dialysis will be excluded  -  Pregnant state. For women in child bearing age, a urine pregnancy test will be  performed prior to the PET and the cardiac MRI studies  -  Documented allergy to F-18 florbetapir, C-11 acetate or gadolinium.  -  Additional exclusion criteria for the active AL-CMP subjects: Subjects unable to  return to BWH for 6 and 12 month clinical evaluation  -  Additional exclusion criteria for active AL-CMP-exercise subjects: Inability to  exercise or return to BWH for C-11 acetate PET/CT at baseline and 6 month clinical  evaluations.  -  Additional exclusion criteria for active AL Pre-CMP- Inability to return to BWH 12  month clinical evaluation.  Additional exclusion criteria for microbiota study: Documented hypertrophic cardiomyopathy,  HIV or chronic viral hepatitis, documented inflammatory bowel disease, systemic  antibiotics, antivirals, antifungals or antiparasitic agents within 6 months, unable to  mail the stool sample in a timely manner, bowel surgery, colon cancer, received  chemotherapy, and pregnancy.

Blockchain technology has gained attention for its decentralized feature and data integrity.  The study aims to apply blockchain technology to implement dynamic consent model and evaluate  the real-world experience as a form of virtual clinical trial. The study will simulate a clinical trial that implements dynamic consent module. In this  study, two major and three minor protocol amendments will be conducted on the scheduled date.  Each subjects will give consent using the dynamic consent platform, METORY, and will be  informed when the protocol is amended. The communication only be conducted under the METORY  and the real-world experience of METORY would be evaluated. Inclusion Criteria:  -  Subjects who can use METORY (application platform)  -  Subjects who completely understand the study and voluntarily decide to participate in  the study Exclusion Criteria:  -  Subjects who are not able to use the web or application due to cognitive dysfunction  or other reasons  -  Subjects who are not able to measure body temperature by themselves  -  Subjects who investigators decide not be appropriate for the study for other reasons

The purpose of the study is to identify the most promising sequence of modalities in total  neoadjuvant treatment of localy advanced rectal cancer with high risk of recurrence International recommendations for the treatment of LARC with a high risk of disease  recurrence are inconsistent, regarding TNT. In Germain randomised study more pCR were  achieved with consolidation chemotherapy. We will compare our standard approach (induction  plus consolidation CT) with consolidation CT. Inclusion Criteria:  -  no distant metastases on CT scan (M0 disease)  -  at least one high risk factor for disease recurrence identified on MR imaging:  -  T4 tumor (cT4)  -  N2 disease (cN2)  -  extramural venous invasion (cEMVI+)  -  positive lateral lymph nodes  -  distance of tumor to mesorectal fascia or positive lymph nodes is 1 mm or less  (cMRF+)  -  capacity for informed consent  -  willingness to attend regular check-ups during and after treatment Exclusion Criteria:  -  absolute contraindications for MR imaging  -  distant metastases cannot be reliably excluded  -  synchronous cancer  -  chronic inflammatory bowel disease

A secondary analysis of the Turkish National Perioperative Transfusion Study (TULIP TS)  database will be performed. The Turkish National Perioperative Transfusion Study (TULIP TS) was conducted by The Turkish  Society of Anesthesiologists' Multicentre Clinical Trials Network.  TULIP TS included 6481 patients undergoing major elective surgery, from 61 study sites across  the country.  Transfusion practices of clinicians working at diverse surgical fields; differences between  current transfusion practices and patient blood management strategies; the areas for  improvement and the obstacles that could prevent change were evaluated and identified.  Data relevant to perioperative transfusion rates of red blood cells, fresh frozen plasma and  platelets, the indications for transfusion and postoperative adverse outcomes including 1  month all cause mortality was obtained.  The TULIP TS group aims to collect further data concerning 1 year all cause mortality of the  same patient population and to evaluate adverse outcomes in transfused and non transfused  patients. Inclusion Criteria: • Patients undergoing major elective surgery Exclusion Criteria: • Trauma patients, emergency surgery

The purpose of this study is to evaluate and compare the clinical and radiographic  performance of zirconia and stainless steel crowns on permanent molar Zirconia and stainless steel crowns will be placed on at least two permanent molars, in a  split mouth design. 100 patients will be included in the study. The teeth will be randomized  into two groups according to the crown type.  Group 1: Zirconia crown 2: Stainless steel crown. Plaque index, gingival index, crown  retention, presence of restoration failure, gingival margin extension and pulpal health of  the teeth will be clinically evaluated at baseline and 1., 6., 12., 18., 24. months. The  restorations will be evaluated radiographically at 6., 12. and 18. months. Intra-oral photos  will be taken directly after treatment and at control appointments.  The data will be analysed statistically using Fisher's Exact Test and pearson's chi-square  test; and Log-rank and the Kaplan-Meier will be used to estimate survival percentages. Inclusion Criteria:  -  Patients and parent of the patients who accept to participate and sign the informed  consent  -  Patients who have at least two permanent molars with caries that require crown  restoration  -  Patients that have good cooperation to the procedure Exclusion Criteria:  -  Patients and parent of the patients who don't accept to participate and sign the  informed consent  -  Teeth that doesn't have opposing permanent molars  -  Patients who have bruxism or deep-bite  -  Patient who are allergic to nickel

This trial phase I studies how well fingolimod works in preventing chemotherapy-induced nerve  pain (neuropathy) in patients with breast cancer who are taking paclitaxel. Fingolimod acts  by suppressing immune reactions in the brain. This study is being done to see if fingolimod  can reduce neuropathy caused by paclitaxel. PRIMARY OBJECTIVES:  I. To obtain preliminary data to support whether fingolimod hydrochloride (fingolimod) will  prevent chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving weekly  adjuvant/neoadjuvant paclitaxel therapy.  SECONDARY OBJECTIVES:  I. To obtain pilot data regarding the possible relative toxicities related to fingolimod  therapy in this study situation.  OUTLINE:  Patients receive fingolimod hydrochloride orally (PO) once daily (QD) starting the day before  chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks.  After the completion of study, patients are followed up at 6, 12, and 18 months. Inclusion Criteria:  -  Ability to complete questionnaires by themselves or with assistance.  -  Paclitaxel at a dose of 80 mg/m^2 given every week for a scheduled course of 12 weeks  for treating breast cancer.  -  Life expectancy >= 6 months.  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1.  -  Negative pregnancy test (serum or urine) done =< 14 days prior to registration, for  persons of childbearing potential only.  -  Provide written informed consent. Exclusion Criteria:  -  Previous exposure to paclitaxel (please note that it is acceptable for patients to  receive non-neurotoxic chemotherapy, like doxorubicin hydrochloride (Adriamycin) and  cyclophosphamide (AC), before or after the weekly paclitaxel and/or to receive  concurrent anti-her 2 therapy).  -  Any of the following because this study involves an agent that has known genotoxic,  mutagenic and teratogenic effects:  -  Pregnant persons  -  Nursing persons  -  Persons of childbearing potential who are unwilling to employ adequate  contraception.  -  Previous diagnosis of diabetic or other peripheral neuropathy.  -  Current or previous use of fingolimod.  -  History of the following preexisting conditions: ischemic heart disease, cardiac  arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia,  macular edema, recurrent syncope, severe untreated sleep apnea, herpes simplex virus  (HSV), varicella zoster virus (VZV), chronic hepatitis, tuberculosis, fungal  infections, skin cancer, or diabetes.  -  Myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA),  decompensated heart failure requiring hospitalization or class III/IV heart failure <  6 months prior to registration.  -  History or presence of Mobitz type II second-degree or third-degree atrioventricular  (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker.  -  History of a hypersensitivity reaction to fingolimod or any of the excipients  including rash, urticarial, and angioedema upon treatment initiation.  -  Baseline corrected QT (QTC) interval >= 450 ms (on electrocardiography [EKG]).  -  Concurrent use of a class Ia or III antiarrhythmic.  -  Drugs with a known risk of torsades de pointes.  -  Concurrent use of beta blockers, calcium channel blockers or digoxin.  -  Use of immunosuppressive, or immune-modulating therapies that may have  immunosuppressive effects.  -  Immunocompromised patients including patients known to be human immunodeficiency virus  (HIV) positive.  -  Uncontrolled intercurrent illness including, but not limited to:  -  Ongoing or active infection  -  Unstable angina pectoris  -  Cardiac arrhythmia  -  Or psychiatric illness/social situations that would limit compliance with study  requirements.  -  Receiving any other investigational agent.  -  Family history of a genetic/familial neuropathy.  -  Received a vaccine (inactivated) =< 14 days prior to registration.

This phase II trial studies the side effects of and how well neratinib works in treating  older patients with stage IV HER2-positive breast cancer. Neratinib may stop the growth of  tumor cells by blocking some of the enzymes needed for cell growth. PRIMARY OBJECTIVES:  I. To estimate the safety and tolerability of neratinib in adults age 60 or older with  locally advanced or metastatic HER2 over-expressing breast cancer.  SECONDARY OBJECTIVES:  I. To describe the full toxicity profile including all grade toxicities measured by National  Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.  II. To estimate the rate of all grades of gastrointestinal (GI) toxicities such as diarrhea,  nausea, and vomiting.  III. To estimate the rate of dose reduction, delays and discontinuation related to study  drug.  IV. To describe pharmacokinetic parameters of neratinib in adults 60 and older. V. To  estimate overall response rate (ORR) and clinical benefit rate (CBR) defined by Response  Evaluation Criteria in Solid Tumors (RECIST) 1.1.  VI. To estimate event free survival (EFS), progression-free survival (PFS) and overall  survival (OS).  VII. To evaluate the role of cancer-specific geriatric assessment tool in predicting  treatment toxicities.  VIII. To estimate adherence rate to neratinib in older adults (percentage of doses of  neratinib taken).  IX. To explore the association of pharmacokinetic (PK) parameters and geriatric assessment  findings.  X. To explore if serum biomarkers of aging (interleukin [IL]-6, C-reactive protein [CRP], and  D-dimer) are associated with treatment toxicities.  OUTLINE:  Patients receive neratinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28  days in the absence of disease progression or unacceptable toxicity.  After completion of study treatment, patients are followed up for 30 days and then  periodically thereafter. Inclusion Criteria:  -  Eastern Cooperative Oncology Group (ECOG) performance 0-2  -  Life expectancy of greater than 12 weeks  -  Histologically or cytologically proven metastatic breast cancer (metastases can be  proven with imaging results in certain circumstances provided that the initial tumor  was demonstrated histologically)  -  Stage IV HER2/Neu positive breast cancer patients who failed previous anti-HER2  targeted therapies  -  HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of  American Pathologists (CAP) guidelines  -  If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization  (FISH), but activating somatic mutations of HER2 gene identified through genomic  sequencing including but not limited to the following (Clinical Laboratory Improvement  Act [CLIA] certified lab test): missense substitutions (G309A, G309E, S310F, S310Y,  S653C, V659E, R678Q, V697L, T733I, L755S, L755P, E757A, D769H, D769Y, D769N, G776V,  G776C, V777L, L841V, V842I, R849W, L869R, R896C); insertions/deletions  (A775_G776insYVMA aka Y772_A755dup, G776VinsC, G776AinsVGC, G776 insertions,  G778_S779insCPG, P780_781insGSP aka G778_P780dup, L755_T759del) and/or HER3 activating  mutations; there is no limitation on the number of prior lines of systemic therapy or  HER2-targeted therapies (prior neratinib not allowed)  -  Both measurable as well as non-measurable disease will be allowed  -  Hemoglobin >= 9 g/dL (after transfusion, if necessary) within 4 weeks of  pre-registration  -  Total bilirubin within normal institutional limits within 4 weeks of pre-registration  -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase  [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])  =< 2.5 x institutional upper limit of normal within 4 weeks of pre-registration  -  Creatinine clearance >= 30 mL/min as calculated by Cockcroft-Gault formula within 4  weeks of pre-registration  -  Baseline left ventricular ejection fraction LVEF >= 50% as evaluated by echocardiogram  (ECHO) or multiple-gated acquisition scan (MUGA)  -  All grade >= 2 toxicities other than alopecia from prior therapy have resolved by the  time of study commencement  -  Patient must have completed radiation therapy with adequate recovery of bone marrow  and organ functions, before starting neratinib  -  Patient with stable or treated brain metastases are eligible; asymptomatic patients  with metastatic brain disease who have been on a stable dose of corticosteroids for  treatment of brain metastases for at least 14 days are eligible to participate in the  study  -  Provide written, informed consent to participate in the study and follow the study  procedures Exclusion Criteria:  -  Prior treatment with neratinib  -  Concurrent usage of other investigational agents, chemotherapy, or hormone therapy;  prior chemotherapy, hormonal therapy, targeted therapy, and investigational agents are  allowed but all toxicities grade >= 2 must have resolved by the time of study  commencement (except alopecia)  -  Any major surgery =< 28 days prior to the initiation of investigational products  -  Received chemotherapy or biologic therapy =< 3 weeks prior to the start of neratinib  -  Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart  failure (New York Heart Association functional classification of >= 2, including  individuals who currently use digitalis specifically for congestive heart failure),  unstable angina, myocardial infarction within 12 month of enrollment or ventricular  arrhythmia  -  Concurrent use of digoxin due to cardiac disease; corrected QT (QTc) interval >= 450  milliseconds in men and >= 470 milliseconds in women within 2 weeks of registration or  known history of QTc prolongation or Torsades de Pointes  -  Inability to take oral medication  -  Other malignancy within the past 3 years with the exception of: a) adequately treated  basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) cervix or vulva  carcinoma in situ; c) cancer considered cured by surgical resection or unlikely to  impact survival during the duration of the study, such as localized transitional cell  carcinoma of the bladder, or benign tumors of the adrenal or pancreas  -  Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g.,  Crohn?s disease, malabsorption, or grade >= 2 National Cancer Institute [NCI] Common  Terminology Criteria for Adverse Events [CTCAE] v.4.0 diarrhea of any etiology at  baseline)  -  Known clinically active infection with hepatitis B or hepatitis C virus  -  Evidence of significant medical illness, abnormal laboratory finding or psychiatric  illness/social situations that would, in the investigator?s judgment, makes the  patient inappropriate for this study

Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by motor and  phonic tics. The studies proposed in this application will explore the endocrine mechanisms  underlying two of the least well-understood biological characteristics of TS, namely its  marked male predominance and stress susceptibility. In particular, our exploratory studies  will characterize the steroid profile in TS-affected boys and girls to identify novel  potential biomarkers and therapeutic targets for this disorder. Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by motor and  phonic tics. Available treatment strategies remain unsatisfactory, due to limited knowledge  of the biological foundations of this disorder. The studies proposed in this application will  explore the mechanisms underlying two of the least well-understood biological characteristics  of TS, namely its marked male predominance and stress susceptibility. Studies from the  investigators suggest that these features of TS are contributed by neuroactive steroids, a  family of mediators implicated in sex and stress regulation.  The typical age of onset of TS is 6-7 years, coinciding with adrenarche, a phase of adrenal  maturation characterized by an upsurge in adrenal neuroactive steroids, such as  dehydroepiandrosterone (DHEA) and its sulfate (DHEAS). In preliminary studies, the  investigators found that DHEA exacerbated tic-like responses in animal models of TS.  Interestingly, the dose of DHEA needed to elicit TS-like responses in females is higher than  those needed in males, possibly pointing to a mechanism of sex differences in TS.  Stress reduces the ability of TS patients to suppress tics, but the underlying mechanisms  remain unknown. Studies in animal models indicate that this process may be due to the  elevation of the neuroactive steroid allopregnanolone (AP) in the prefrontal cortex. By  inhibiting the ability of the prefrontal cortex to suppress tics, AP promotes tic execution.  In a pilot study, the investigators found that tic suppression, a well-known stressful task  in TS patients, increases AP salivary levels. Furthermore, in another proof-of-concept study,  the investigators found that inhibiting AP synthesis led to a reduction in tic severity and  facilitated voluntary control of tics in stressful situations.  These findings lead to the hypothesis that TS patients exhibit alterations of the composition  of their neuroactive steroid profiles, including: 1) an increase in baseline DHEA(S) levels  in male TS patients, in correlation with life-time severity; and 2) an exaggerated elevation  in AP in response to acute stress.  The two Aims of this proposal will test this hypothesis by: 1) comparing the baseline urinary  steroidomic profile of TS-affected boys and girls with non-affected sex- and age-matched  controls; and 2) charting the dynamic alterations in steroidomic salivary profiles in  response to tic suppression. These studies will advance understanding of the endocrine  mechanisms in TS and lead to the identification of potential biomarkers for the severity of  tics and comorbid symptoms. In the long run, the results of these studies may open the way  for the development of new therapies for TS that may reduce tic severity and increase  patients' responsiveness to behavioral interventions. Inclusion Criteria:  -  Diagnostic criteria of TS for cases (and lack of any tic disorders for controls)  -  Age between 8 and 12 years old (this age range is to ensure that TS participants can  perform the tic suppression task)  -  confirmation of sexual development by parent and/or self-reported Tanner stage of  pubic hair development. Exclusion Criteria:  -  major psychiatric disorders such as a psychotic disorder, autism spectrum disorder,  conduct disorder, and substance use disorder;  -  other neurological disorders;  -  clinically significant endocrinological disorders;  -  use of therapies that can modify hormonal profile;  -  pharmacotherapies that may change stress sensitivity, such as antidepressants and  anxiolytics.

The purpose of this study is to determine if sublingual allergen immunotherapy tablets work  by inducing a state of desensitization in mast cells and basophils. To induce clinical tolerance, a failure to respond to an allergen to which one was previously  responsive, is an important objective for physicians, one that plays a significant role in  the primary prevention of allergic reactions in the clinical practice of Allergy &  Immunology. The tolerance resulting after standard subcutaneous immunotherapy to aeroallergen  and insect venom allergens is long lasting and allergen-specific, and may involve  antigen-specific T regulatory cells. In contrast, tolerance resulting from drug  desensitization protocols is short-lived, and postulated to target mast cells and basophils.  Research into the cellular and biochemical processes by which desensitization occurs has  revealed that mast cells desensitized to one antigen in vitro, under certain conditions, lose  the ability to degranulate to unrelated antigens or to direct FcεRI cross-linking.  Preliminary data suggests that this cross-desensitization can happen in patients undergoing  incremental desensitization, depending in part on the percentage of IgE targeted to the  allergen used for desensitization. This proposal therefore aims to explore desensitization  and cross-desensitization in human volunteers undergoing standard sublingual (SL)  immunotherapy to grass or ragweed pollen.  Subjects will undergo SL immunotherapy with either Timothy or Short Ragweed tablets, taking  one tablet per day, or will take a placebo tablet. Titration skin testing to Timothy or Short  Ragweed, to one or preferably two additional allergens to which the subject is sensitive, and  to codeine as a control for mast cell activation capability through a non-IgE-dependent  pathway will be performed to determine the PC3 value (see below). Skin testing, including  histamine and diluent controls, will be performed prior to and at one and four weeks after  initiation of immunotherapy. At each time point, blood will be obtained to measure total and  antigen-specific IgE levels, tryptase and cytokine levels, and basophil activation with the  relevant allergens and C5a as a non-IgE-mediated control for basophil activation. Inclusion Criteria:  -  Verified allergic sensitivity to either Timothy Grass or Short Ragweed pollen (primary  allergen)  -  Verified allergic sensitivity to at least one allergen in addition to the primary  allergen Exclusion Criteria:  -  Negative skin testing to Timothy Grass or Short Ragweed pollen and at least one other  environmental allergen  -  Dermatographism  -  Severe dermatologic condition that may interfere with skin testing  -  Pregnancy  -  H1 receptor antihistamine taken within 7 days of testing  -  Systemic steroids  -  Omalizumab taken at any time in the past  -  Receiving or received allergen immunotherapy  -  Desensitized to any drug within 6 months  -  Current uncontrolled or severe asthma  -  Eosinophilic esophagitis  -  Significant pulmonary, cardiovascular, renal, hepatobiliary, or neurological diseases,  or another disease process felt to put a subject at increased risk for adverse events  -  Hypersensitivity to any of the inactive ingredients in the allergen extract tablets  -  History of mental illness or drug or alcohol abuse that could interfere with the  ability to comply with study requirements  -  Inability or unwillingness to give written informed consent

The investigators hypothesize gold is inert and thereby there is no pure-gold allergy. The  primary aim of this study is to measure the prevalence of allergy to metallic pure gold  microparticles and allergy to GSTS. TRUE test panel which includes gold sodium thiosulphate (GSTS), 1 % w/v in petrolatum, and  gold microparticles, 20-micron diameter, 1 % w/v in petrolatum, will be added added to the  baseline series. It will be applied to the upper back of healthy adults in aluminum Finn  Chamber for 48 hours. Clinical evaluation will be performed 24 hours after removal the test  according to standard procedures for evaluation of epi-cutaneous challenging (Johansen 2015). Inclusion Criteria:  -  Patients with chronic dermatitis Exclusion Criteria:  -  age < 18

This study will evaluate the overall remission rate of treatment with vosaroxin (formerly voreloxin) Injection in patients at least 60 years of age with previously untreated AML Other objectives of this study include:   1. Assess the safety of treatment with vosaroxin, including the 30 and 60 day all-cause mortality   2. Assess leukemia free survival (LFS), event-free survival (EFS), overall survival (OS), and duration of remission (DR).   3. Characterize the pharmacokinetic (PK) profile of vosaroxin in this patient population.   4. Evaluate potential stratification biomarkers by evaluating DNA-damage and apoptotic pathways in bone marrow samples before and after treatment with vosaroxin Inclusion Criteria: None Exclusion Criteria: None

The purpose of this study is to determine whether recombinant Alkaline Phosphatase (recAP) is effective and save, and to determine the most effective dose, in the treatment of patients with acute kidney injury caused by sepsis. Design: Adaptive trial with two stages and interim analysis   -  Stage 1: four arms; three dose groups and placebo. n=30/arm. (n=120)   -  Interim analysis based on 120 subjects, with continued recruitment, adding 11 subjects to Stage 1 safety population (n=131): to evaluate safety and select dose for stage 2   -  Stage 2: one dose group and placebo. N=85/arm. (n=170) Total n in the study: 301. Primary objectives   -  To investigate the effect of recAP on renal function (measured creatinine clearance D1-D7 period, incidence and duration of renal replacement therapy (RRT) over 28 days, eGFR at D60 and D90) and related clinical parameters (ICU stay, Hospital stay, Mechanical ventilation over 28 days, SOFA and SAPS2 scores 28 days) in patients with SA-AKI.   -  To determine effective therapeutic dose(s) of recAP. Secondary objectives   -  To investigate the safety and tolerability of recAP in patients with SA AKI. (assessed by independent Data Monitoring Board, adverse events over 90 days study period, laboratory values, ECG, physical examniations, vital signs, Anti Drug Antibodies)   -  To investigate the pharmacokinetic profile (PK) of recAP in a subset of patients (part 1, n=120) with SA AKI. (Population PK; AUC D1-7, Cmax, Cmin, Tmax, terminal T1/2)   -  To investigate the immunogenic potential of recAP in patients with SA AKI. (anti-drug antibodies at D14, D28, D60 and D90)   -  To investigate the effect on quality of life (using the EuroQol, EQ-5D) following study inclusion, at ICU discharge, and Day 90. Other objectives • To evaluate whether specific patient groups can be identified that benefit most from recAP treatment or patient groups that are non-responders Inclusion Criteria:   1. Signed Informed Consent Form (patient, legal representative or independent investigator)   2. Age 18 to 85 years, inclusive   3. Is admitted to the ICU or Intermediate Care Unit   4. Has diagnosis of sepsis (< 96 hrs prior to first study drug), according to criteria defined by the American College of Chest Physicians/Society of Critical Care Medicine:        1. Has a proven or strongly suspected bacterial infection.        2. Has at least 2 of 4 SIRS criteria 72 hrs < screening and 96 hrs < first study drug   5. First diagnosis of AKI: AKI Stage 1 or greater, according to the AKIN criteria (time-window adjusted):        1. Increase in serum creatinine > 26.2 µmol/L (0.30 mg/dL) in 48 hrs prior to screening, or        2. Increase in serum creatinine to > 150% (> 1.5-fold) from reference creatinine value in 48 hrs prior to screening        3. Urinary output < 0.5 mL/kg/h for > 6 hours following adequate fluid resuscitation   6. Continuing AKI needs to be confirmed by a confirmative fluid corrected serum creatinine measure, or   7. When the AKI diagnosis was made according to the AKIN urine output criteria (urinary output < 0.5 mL/kg/h for > 6 hours), the oliguria or anuria should still meet the AKIN urine output criteria prior to randomization. Exclusion Criteria:   1. Woman of childbearing potential with a positive pregnancy test, pregnant, or breastfeeding.   2. Weighs more than 115 kg (253 lb).   3. Has life support limitations.   4. Is known to be human immunodeficiency virus positive.   5. Has urosepsis.   6. Is already on dialysis (RRT) or anticipated to receive RRT within 24 hours after study drug dosing due to the underlying disease.   7. Is receiving immunosuppressant treatment or is on chronic high doses of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with hydrocortisone (e.g., 3 × 100 mg) can be included.   8. Is expected to have rapidly fatal outcome (within 24 hours).   9. Has known, confirmed fungal sepsis.  10. Has advanced chronic liver disease, confirmed by a Child-Pugh score of 10 to 15.  11. Has acute pancreatitis with no established source of infection.  12. Has participated in another investigational study within 30 days prior to enrollment.  13. Is not expected to survive for 28 days due to medical conditions other than SA AKI, including cancer, end-stage cardiac disease, cardiac arrest requiring cardiopulmonary resuscitation or with pulseless electrical activity or asystole within the past 30 days, end stage lung disease, and end stage liver disease.  14. Has known prior history of Chronic Kidney Disease with a documented estimated Glomerular Filtration Rate (eGFR) < 60 mL/min by Modification of Diet in Renal Disease MDRD or CKD-EPI formula, known GFR < 60 mL/min, or a known history of persistent creatinine level > 150 µmol/L (1.70 mg/dL) for reasons other than the current sepsis condition.  15. Has diagnosis of malaria or other parasite infections.  16. Has burns on > 20% of body surface.  17. Has had AKI diagnosis according to inclusion criteria > 24 hours prior to study drug administration.  18. Is anticipated to be treated with non-continuous RRT from Day 1 to Day 7.  19. During Day 1 to Day 7 continuous RRT is anticipated to be started or stopped not according to per protocol criteria.  20. The AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs and renal perfusion-related.  21. Improvement in serum creatinine of at least 0.30 mg/dL or (26.2 µmol/L) prior to administration of the study drug.  22. Patients who use nephrotoxic medication and who fulfill the SA-AKI inclusion criteria at screening are not eligible if the use of this nephrotoxic medication is to continue when alternative, medically appropriate, non-nephrotoxic medication is available.  23. Has a history of known IV drug abuse.  24. Is an employee or family member of the investigator or study site personnel.  25. Has active hematological malignancy.

The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens: CD24Fc  vs placebo with the standard GVHD prophylaxis of tacrolimus / methotrexate.  The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens:  CD24Fc/tacrolimus / methotrexate (CD24Fc/Tac/MTX) versus placebo/tacrolimus / methotrexate  (placebo/Tac/MTX) in the setting of myeloablative conditioning (MAC), matched unrelated donor  (MUD) allogeneic hematopoietic stem cell transplantation in participants with acute leukemia  (AML/ALL) or myelodysplastic syndrome (MDS). The study agent, CD24Fc, will be administered  through IV infusion on days -1, 14, and 28 at the dose of 480mg, 240 mg and 240mg,  respectively. The placebo will be 100 ml normal saline intravenous (IV) solution. The Sponsor decided to discontinue screening and enrollment in this study on 18 May 2021 for  business reasons. This decision was not related to any new or unexpected safety or efficacy  findings. Inclusion Criteria:  1. A prospective participant for allogeneic HCT for a malignant hematologic disorder.  2. The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at  the HLA-A, -B, -C, and - DRB1 loci. High-resolution typing is required for all alleles  for unmatched donors. Only matched unrelated donors are acceptable for this trial.  3. The following diagnoses are to be included:  1. Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or  second remission. Remission is defined as the absence of blasts in the peripheral  circulation at the time of enrollment, < 5% blasts in the bone marrow and absence  of extramedullary disease including CNS involvement.  2. Myelodysplastic syndrome (MDS) with intermediate or high-risk International  Prognostic Scoring System (IPSS) or equivalent Revised International Prognostic  Scoring System (IPSS-R) score with < 10% blasts in the bone marrow.  4. Males or non-pregnant, non-lactating females, ≥ 18 years of age. Note there is no  defined upper age limited, so long as deemed appropriate candidate for myeloablative  conditioning.  5. Karnofsky Performance Status >70%.  6. Participants must have normal or near normal organ function as defined by their  treating institutions bone marrow transplant (BMT) program clinical practice  guidelines. In addition, for purposes of this protocol minimum organ function criteria  within 30 days of beginning conditioning include: Eligibility According to Pre HCT  Organ Function:  1. Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related);  2. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase  (SGOT))/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase  (SGPT)) <5.0 X institutional upper limit of normal;  3. Estimated or actual glomerular filtration rate (GFR)>50 mL/min/1.73 m2 for  participants with creatinine levels above institutional normal (GFR should be  corrected for BSA);  4. Pulmonary Function Tests include diffusing capacity of the lungs for carbon  monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital  capacity (FVC)> 50% DLCO should be corrected for hemoglobin;  5. Ejection Fraction >50%;  6. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5.  Item d and e may be assessed up to 10 weeks prior to the start of conditioning  therapy.  7. Ability to understand and the willingness to sign a written informed consent document.  8. Women of child bearing potential and men must agree to use contraception prior to  study entry and through day 100 post HCT (hormonal or barrier method of birth control;  abstinence). Should a woman become pregnant or suspect she is pregnant while she or  her partner is on treatment in this study, she should inform her study physician  immediately. Men treated or enrolled on this protocol must also agree to use adequate  contraception prior to the study until day 100 post HCT. Exclusion Criteria:  1. Subjects may not have presence of active central nervous system (CNS) disease or  extramedullary disease.  2. Prior cytotoxic chemotherapy within 21 days from the initiation of HCT conditioning  (i.e. intensive induction / consolidation for AML). Note, certain low intensity  treatments not intended to induce remission but rather stabilize disease are  acceptable up to 24 hrs prior to initiation of HCT conditioning (i.e. Tyrosine Kinase  Inhibitor, sorafenib).  3. Cord blood and haploidentical donors are not eligible.  4. HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are  permissible.  5. Pregnant and nursing mothers are excluded from this study. This is because the risk to  the fetus is unknown.  6. Any physical or psychological condition that, in the opinion of the investigator,  would pose unacceptable risk to the participant or raise concern that the participant  would not comply with protocol procedures.  7. Uncontrolled infections. Participants still under therapy for presumed or proven  infection are eligible provided there is clear evidence (radiologic, clinical and/or  culture) that the infection is well controlled.  8. Participants seropositive or polymerase chain reaction (PCR) positive for the human  immunodeficiency virus (HIV). Participants with evidence of Hepatitis B or Hepatitis C  PCR positivity.  9. Prior HCT (allograft or prior autograft).  10. Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin (ATG),  alemtuzumab) is prohibited.  11. Current or prior diagnosis of antecedent Myelofibrosis is excluded.

The purpose of this study is to examine whether weight reduction decreases intramyocellular  (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue  in people who are insulin resistant and have a family history of type 2 diabetes. In this study, we will examine whether a small weight loss in lean, insulin-resistant  offspring of type 2 diabetic patients will improve insulin resistance. The control group will  consist of subjects matched for gender, age and body weight with no family history of  diabetes. Before and after weight loss, rates of basal and insulin stimulated whole body  glucose metabolism will be measured using [6,6-2H] glucose during a 3 hour basal period and a  4 hour euglycemic hyperinsulinemic (20 mU/m2-min) clamp. Rates of whole body lipolysis will  be determined using [2H5] glycerol, localized rates of lipolysis will be measured using the  microdialysis technique and muscle PI 3-kinase activity will be assessed in muscle biopsies.  FFA metabolites (fatty acyl CoA, ceramides, diacylglycerol) will be measured in fat tissue  collected from the abdominal subcutaneous fat cell depot. Body composition will be determined  with bioelectrical impedance and whole body MRI; IMCL will be measured with MRS. Before and  after weight loss, insulin secretion will be measured with the hyperglycemic clamp (as  described under Day 2 Hyperglycemic Clamp). Inclusion Criteria:  -  Healthy, sedentary, non-smoking and not taking any medications other than birth  control pills.  -  Hematocrit >35%  -  Subjects will have no systemic or organ disease including diabetes.  -  Subjects will have no history eating disorders.  -  Women must be using a form of birth control (sexual abstinence, birth control pills,  Norplant, IUD or condoms) and will be studied between day 0 and 7 of their menstrual  cycle.  -  Those who are taking birth control pills or have had a hysterectomy may be studied at  any time.  -  Physical activity will be assessed using a standard questionnaire with an activity  index cut off at 2.3. Exclusion Criteria:  -  Any subject, who does not fit the inclusion criteria. Including history of eating  disorders, any systemic and organ disease including diabetes.  Lactose intolerance Any blood count, clotting abnormalities HYpertriglyceridemeia (TG over  100 mg/dL)  -  Hematocrit <35%.  -  Women of childbearing potential, who are not using contraception (as mentioned above)  or who are not abstinent.  -  Subjects who have a regular exercise regimen will not be enrolled.  -  Metal implants and/or body piercing, which cannot be removed before the MR studies.

This study will conduct an evaluation of a program that is being implemented SickKids /  Toronto Public Health that provides take-home saliva testing kits in schools. Operationally,  there is a planned randomization so that all schools have an equitable chance to receive the  intervention at various time periods during the planned operational roll-out, which will  require a staggered implementation consistent with the stepped-wedge study design. This study  will leverage this chance implementation to do a robust evaluation of the public health  intervention. Schools that are not being rolled out to week one, will begin in the "control  phase" (testing at an assessment center, primary care or acute care center) and transition to  the program "intervention phase" (take home saliva kits available at schools) at a randomly  assigned time (wedge) over a 6-week period with all schools receiving the program by the end  of the study. The investigators will evaluate the impact of the program on SARS-CoV-2 case  identification in schools. This is a prospective evaluation of a program that is being implemented using a  stepped-wedge, cluster randomized design.  Eligible elementary public schools high SARS-CoV-2 incidence regions (quintiles 4 and 5) in  Toronto will be randomized. The study will occur over a 7-week period with a minimum of  one-week of baseline data (control phase - testing at an assessment center, primary care or  acute care center) and then schools will start the program in a stepwise manner (20  crossovers per week) with take-home saliva being available to all 120 schools by the end of  the study period. The primary objective of the study is to assess whether the availability of  take home saliva kits at schools for symptomatic testing leads to increased diagnosis of  SARS-CoV-2 cases in the school. Inclusion Criteria: None Exclusion Criteria:  Schools that are middle schools only, that are not open for in-person learning, have fewer  than 200 students or are not a complete elementary school (i.e. schools offering  independent courses, prep schools with 1-2 grades, elementary schools with < 4 grades) will  be excluded.

Patients with chronic kidney disease (CKD) with criteria for renal replacement therapy (RRT)  including uremic syndrome, have a stable state of hyperosmolarity due to urea despite not  being an osmotically inactive ion. Also, these patients have alterations in urea transporters  in the central nervous system (CNS) conferring a risk of neurological involvement due to an  abrupt decrease in serum urea causing manifestations of the post-dialytic syndrome.  Hemodialysis results in rapid removal of urea from the blood, much faster than the  equilibrium rate between the brain and the bloodstream through the blood-brain barrier,  resulting in an osmotic gradient that favors movement from water to the brain, causing  cerebral edema, intracranial hypertension and dialysis-associated imbalance syndrome.  Conventional hemodialysis (HD) uses diffusion and primarily decreases small solutes, while  hemofiltration (HF) is based on convection that provides clearance mainly of medium-size  molecules and small solutes with a slower rate of reduction. Currently, there is little information about which is the safest modality in the first  session of intermittent hemodialysis. Other than dialysis-associated imbalance syndrome,  there is no evidence exploring the neurocognitive effects of the first hemodialysis session.  Cognitive impairment is defined as a new deficit in two or more areas of cognitive function  and its progression is associated with impaired kidney function. Most of the dysfunctions  reported are in the domains of orientation, attention and executive functions. Therefore, the  recognition of cognitive impairment can be done with tools such as the Minimental State  Examination (MMSE) and the Montreal Cognitive Assessment (MOCA) test. Brain magnetic  resonance imaging (MRI) can identify brain lesions such as 'silent' infarcts, microbleeds and  white matter abnormalities in patients with CKD with and without RRT. Diffusion-weighted MRI  before and after HD has shown brain edema in rats with dialysis-associated imbalance  syndrome. In fact, there is evidence from brain MRI that before first HD session patients  have interstitial cerebral edema, which worsens after the first HD treatment.  Because there is no clear evidence to support the choice of the modality in the first session  and the prescription is still based on personal experiences and shared views. Therefore, we  conducted a pilot study to determine the safest hemodialysis modality with the lowest risks  and neurocognitive effects for patients with CKD and first HD treatment. Inclusion Criteria:  -  Age > 17 years  -  Both gender  -  CKD stage 5 with clinical or biochemical criteria to kidney replacement therapy  initiation that includes:  -  Urea nitrogen > 80 mg/dl  -  Hyperkalemia  -  Fluid overload  -  Metabolic acidosis (ph < 7.2 and/or bicarbonate <12) Exclusion Criteria:  -  Visual disturbances  -  Altered mental status at enrollment  -  Hypothyroidism without optimal supplementation  -  Advanced neoplasia  -  Acute kidney injury

The purpose of this phase I/Ib study is to determine the safety profile of Epidiolex (CBD  oil) in biochemically recurrent prostate cancer patients. The study consists of a dose  escalation part and dose expansion part. The dose expansion part of the study will use the  maximum tolerated dose (MTD) determined in the dose escalation part to assess the activity,  safety and tolerability of the investigational product in patients with biochemically  recurrent prostate cancer after localized therapy with either surgery or radiation. Cannabinoids (CBD) have been widely used in medicines for centuries to control pain, nausea  or vomiting, and to stimulate appetite, especially in cancer patients. Both cannabinoids  receptor 1(CB1) and cannabinoids receptor 2 (CB2) were highly expressed in cultured prostate  cancer cells compared to normal prostate cell lines. CBD inhibits tumor growth in xenograft  model.  Clinicians have been challenged to improve the treatment of biochemically recurrent (BCR)  prostate cancer in which prostatic specific antigen (PSA) rises without radiological or  clinical progression years after localized treatment (radical prostatectomy or radiation  therapy) with or without hormonal treatment. Approximately 50-90% of men with high-risk  prostate cancer will experience a BCR. Based on the abovementioned preclinical observations  of CBD's effect on prostate cancer and its safety data in two non-cancer populations, a phase  I study of CBD in men with biochemically recurrent prostate cancer will be conducted. Inclusion Criteria:  -  Completion of localized therapy (prostatectomy or radiotherapy) for prostate  adenocarcinoma (either histologically or cytologically confirmed)  -  Biochemical (PSA) recurrence, defined as: * PSA of >= 0.2 ng/ml that has increased  above nadir following radical prostatectomy OR * PSA increase of 2.0 ng/ml above  post-therapy nadir after radiotherapy NOTE: PSA measured at two consecutive time  points (separated by 4 or more weeks) is required in order to demonstrate the  requisite increase in PSA  -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2  -  Absolute neutrophil count >= 1,500/microliters (at baseline [pre-study])  -  Platelets >= 80,000/microliters (at baseline [pre-study])  -  Total bilirubin =< institutional upper limit of normal (at baseline [pre-study])  -  Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase/alanine  aminotransferase (ALT)(serum glutamate pyruvate transaminase) =< institutional upper  limit of normal (at baseline [pre-study])  -  Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 using the Cockcroft-Gault  formula (at baseline [pre-study])  -  Patients with a prior or concurrent malignancy (non-prostate) whose natural history or  treatment does not have the potential to interfere with the safety or efficacy  assessment of the investigational regimen as determined by the treating physician are  eligible  -  Given that worsening of an underlying state of mental depression or suicidal ideation  has been reported with Epidiolex, patients should be carefully screened for depression  at baseline and if there are indications or a history of depression it is strongly  recommended that these patients be closely followed together with behavioral health or  psychiatric medical support. Patients with an established diagnosis of depression  that, in the assessment of the investigator may make the administration of Epidiolex  hazardous, should not be enrolled on this protocol  -  Concurrent use of over-the-counter CBD oil, Marinol or marijuana is not permitted.  Patients with a history of current over-the-counter CBD oil, Marinol or marijuana use  for any reason are eligible only if they do the following: * Complete a one-week  washout period prior to study initiation * Refrain from non-study related CBD oil,  Marinol or marijuana use while on-study  -  Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria:  -  History of hypersensitivity to Epidiolex (cannabidiol) or sesame seeds (one of the  inactive ingredients in Epidiolex)  -  Any radiological evidence of metastatic disease (determined by standard of care  computed tomography [CT] scans of abdomen. pelvis, chest, whole body bone scan or  Axium positron emission tomography scan). Questionable lesions on bone scan will be  confirmed by standard of care methods such as plain X-rays or Axium positron emission  tomography scan, if not previously performed  -  Receipt of prior cytotoxic chemotherapy for recurrent prostate cancer  -  Use of androgen deprivation therapy (for example, bicalutamide, flutamide, nilutamide,  or leuprolide acetate) concurrently or within the previous 3 months.  -  Uncontrolled intercurrent illness such as active infections. Other illnesses will be  evaluated and eligibility status determined at the discretion of the treating  physician and the investigator  -  Psychiatric illness/social situations that would limit compliance with study  requirements  -  Concomitant use of valproate or clobazam  -  Concurrent use of over-the-counter CBD oil, Marinol or marijuana  -  Epidiolex is a moderate inhibitor of CYP2C19 and a moderate/strong inhibitor of  CYP3A4, therefore concurrent use of CYP2C19 substrates is not allowed

The management of pain in the emergency department is a major issue, especially for sickle  cell patients who regularly consult for vaso-occlusive seizure (VOS). The place of virtual  reality remains to be defined in a busy environment, in which the permanence of care  generates a significant turn over of medical and paramedical personnel.  With Its immersive nature, allowing the patient to detach from his immediate environment,  wich is often stressful for patients, we can hope that in multimodal management, Virtual  Reality (VR) can contribute to a faster reduction in pain with lower doses of morphine, but  so far we have no data.  Our pilot study aims to assess the effectiveness, feasibility and tolerance of adding virtual  reality to the management of VOS in sickle cell patients in the ER. It will be a Before-after study: this study will be conducted in 2 phases in the emergency  department  -  a period of usual management of sickle cell patients with VOS  -  then a phase during which the device will be used. Each phase will last 3 months; the  duration of the periods may be shorter if recruitment targets are met. Patients will be  included consecutively.  The main objective of the study is to measure the impact of virtual reality on the total dose  of morphine administered to the emergency room in the treatment of vaso-occlusive seizures  after initial morphine titration.  The primary endpoint is the total dose of morphine (in milligrams), used in the emergency  room after initial titration, meaning the dose administered by PCA (patient-controlled  analgesia) and secondary titrations in the event of a recurrence of painful spikes with  analog verbal scale (AVS) >7. Inclusion Criteria:  -  Age ≥ 18 years  -  sickle cell patient consulting in the emergency room for VOS  -  Signature free and informed consent Exclusion Criteria:  -  Consultation in the ER for the same reason in the 14 days prior to inclusion (same  episode)  -  Emergency room consultation more than 12 times in the previous year  -  Nausea and vomiting at the time of inclusion  -  History of epilepsy  -  A visually impaired or hard of hearing patient  -  Pregnant patient  -  Previous inclusion in the study

Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses.  In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas  when conventional methods are impractical, such as with multiple lesions or difficult  treatment sites. There is evidence that the metabolism of Fluorouracil in the anabolic pathway blocks the  methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, Fluorouracil  interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits  the formation of ribonucleic acid (RNA). As DNA and RNA are essential for cell division and  growth, the effect of Fluorouracil may be to create a thymine deficiency, which, provokes  unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most  marked on those cells that grow more rapidly and take up Fluorouracil at a more rapid rate.  The catabolic metabolism of Fluorouracil results in degradation products (e.g., CO2, urea,  α-fluoro-β-alanine), which are inactive.  Systemic absorption studies of topically applied Fluorouracil have been performed on patients  with actinic keratoses using tracer amounts of 14C-labeled Fluorouracil added to a 5%  preparation. All patients had been receiving nonlabeled Fluorouracil until the peak of the  inflammatory reaction occurred (2 to 3 weeks), ensuring that the time of maximum absorption  was used for measurement. One gram of labeled preparation was applied to the entire face and  neck and left in place for 12 hours. Urine samples were collected. At the end of 3 days, the  total recovery ranged between 0.48% and 0.94%, with an average of 0.76%, indicating that  approximately 5.98% of the topical dose was absorbed systemically. If applied twice daily,  this would indicate systemic absorption of topical Fluorouracil to be in the range of 5 to 6  mg per daily dose of 100 mg. In an additional study, negligible amounts of labeled material  were found in plasma, urine, and expired CO2 after 3 days of treatment with topically applied  14C-labeled Fluorouracil. Inclusion Criteria:  -  Willing and able to provide voluntary informed consent and follow the protocol  requirements  -  Males or females at least 18 years of age  -  Subjects with at least five (5) and no more than ten (10) clinically typical, visible,  discrete, AK lesions, each at least 4 mm in diameter on the face or bald scalp. In  this interpretation, if the total number of lesions on the face and bald scalp exceeds  10 and there are either 5-10 lesions on the face or 5-10 lesions on the bald scalp  then select the designated treatment area that has 5-10 lesions (i.e., face or bald  scalp)  -  Skin pigmentation (Fitzpatrick skin type I, II, and III) that will allow  differentiation of erythema assessment  -  Females of childbearing potential must not be pregnant or lactating at Visit 1 (as  confirmed by a negative urine pregnancy test with a sensitivity of less than 50 mIU/mL  or equivalent units of human chorionic gonadotropin)  -  Women of childbearing potential must agree to the use of a reliable method of  contraception (e.g., total abstinence, intrauterine device, a double barrier method,  oral, transdermal, injected, or implanted nonhormonal or hormonal contraceptive)  throughout the study. Female patients using hormonal contraceptives should have been  on the same product/dosing regimen for at least 28 days before Visit 1 and should not  change this regimen during the study. A sterile sexual partner is not considered an  adequate form of birth control. Exclusion Criteria:  -  Known hypersensitivity or allergy to Fluorouracil or any of the excipients in the  Test, Reference or Placebo products  -  Presence of atopic dermatitis, basal cell carcinoma, eczema, psoriasis, rosacea,  squamous cell carcinoma, or other possible confounding skin conditions on the face or  bald scalp  -  Use within 6 months before Visit 1 on the face or bald scalp of 1) chemical peel, 2)  dermabrasion, 3) laser abrasion, 4) PUVA (psoralen plus ultraviolet A) therapy, or 5)  ultraviolet B therapy  -  Use within 1 month before Visit 1 on the face or scalp of 1) cryo destruction or chemo  destruction, 2) curettage, 3) photodynamic therapy, 4) surgical excision, 5) topical  5-fluorouracil, 6) topical corticosteroids 7) topical diclofenac, 8) topical  imiquimod, 9) topical retinoids, or 10) other treatments for AK including glycolic  acid or over-the-counter products containing retinol, alpha or beta hydroxy acids  -  Use within 1 month before Visit 1 of 1) immunomodulators or immunosuppressive  therapies, 2) interferon, 3) oral or injectable corticosteroids, or 4) cytotoxic drugs  -  Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency  -  Inability to understand the requirements of the study and the relative information or  are unable or not willing to comply with the study protocol  -  Employees of the Investigator or research center or their immediate family members  -  Patients who have participated in this study previously  -  Patient lived in the same household as currently enrolled subject

To inform the effective management of adolescent suicide risk by evaluating promising  treatments and developing the evidence-base for interventions that are well suited for  widespread adoption, sustained quality, and impact. The current study aims to evaluate Safety Planning Intervention with follow-up (SPI+),  Collaborative Assessment and Management of Suicidality (CAMS) and usual care. Adolescents,  parents, and clinicians will participate in the project to advance to following Research  Aims: 1) Assess the comparative effectiveness of CAMS and SPI+ compared to usual care, 2)  Evaluate the mechanism of change accounting for the therapeutic effects of the interventions  3) Identify moderators of treatment effects. Participants and their parents will receive  study assessments at baseline, 2-week, 1-month, 2-month, 6-month, and 12-month timepoints.  Study assessments will ask about participant demographics (sample characterization), suicide  attempts, suicidal ideation, non-suicidal self-injury, service utilization, self-assessed  risk, treatment integrity, sleep, family cohesion, and social experiences. Youth participants  and their legal guardian both consent to participate in the research procedures. Inclusion Criteria:  1. Provision of signed and dated informed consent form  2. Youth, aged 11-17  3. Endorse suicidal ideation and/or behavior  4. Admitted to acute care (emergency, inpatient medical or inpatient psychiatric) due to  suicidality Exclusion Criteria:  1. Presence of psychosis, intellectual disability, autism spectrum disorder, eating  disorder with unstable vitals  2. Limited English proficiency that would interfere with the ability to complete study  assessments

Modified Bakay technique offers a novel colpotomy and cuff closure technique for total  laparoscopic hysterectomy (TLH), and consists of placing a single continuous running  purse-string suture facilitating the cuff closure before colpotomy. The modified Bakay  technique adds a standard apical compartment support and has the potential to facilitate the  primary healing of the vaginal cuff. This study aimed to compare the surgical and clinical  outcomes of the Modified Bakay technique to conventional standard technique in patients  undergoing TLH. The basis for minimizing the rate of severe haemorrhage and ureteral injuries, the most  serious events related to these steps, is meticulous dissection providing a clear operative  field and the skill and experience of the surgeon. In total laparoscopic hysterectomy (TLH),  the altered anatomy after the removal of the uterus may cause the retraction of vagina and  shifting of neighbouring structures such as bladder and/or bowel to this pouch, thereby,  leading to obstruction of the operative field for vaginal cuff closure.  Bakay published his novel colpotomy and cuff closure technique for TLH. It was the first to  describe placing a single continuous running purse-string suture facilitating the cuff  closure before colpotomy. The main advantage of the technique involved retrieving the safe  suture margins required for vaginal cuff closure before the pelvic anatomy was altered by the  removal of the uterus.  In addition to this advantage, we modified the technique to achieve a better cuff healing and  standardized apical support and the modified Bakay technique (MT) proposes:  i) placing a single continuous running purse-string suture for vaginal cuff closure before  the pelvic anatomy is altered by the colpotomy and removal of the uterus;  ii) suspension/plication of USLs (as a well-defined, efficient, concomitant apical support  procedure to prevent future vaginal vault prolapse) routinely in each case before colpotomy  while the margins of these ligaments and adjacent structures such as ureters are still  prominent and pelvic anatomy is not altered; and  iii) using cold-knife colpotomy instead of electrosurgical colpotomy to support the primary  healing of the vaginal cuff. In the present study, we aimed to compare the surgical and  clinical outcomes of the MT to standard technique (ST) in patients undergoing TLH. Inclusion Criteria:  -  Patients who needed laparoscopic hysterectomy Exclusion Criteria:  -  Patients with anaesthetic contraindications to laparoscopy  -  premalignant or malignant genital disease  -  prior pelvic and/or abdominal radiotherapy  -  large adnexal masses; large fibroids obscuring the visualization of the cervicovaginal  junction  -  Suspicion of malignancy  -  Pelvic organ prolapse Stage >2

Blood volume measurements are a critical step in the emergency care of trauma patients. The  typical approach to this is to rely on historical information, physical examination and  metrics such as heart rate. There is currently no good real-time measure to track blood  volume. This study investigates the use of phonocardiography (listening to the sounds made by  the heart) to track changes in central blood volume. Blood draw subjects:  Participation in this study group may last up to 60 minutes. Participants will begin with a  brief medical exam to determine eligibility. This will include a review of any history of  cardiovascular disease and of medications. Prior to a scheduled blood draw, eligible  participates will have physiological measurements taken, which may include phonocardiographic  measurements, cardiac output, plethysmography (volume changes), multifrequency bioimpedance,  thoracic impedance, heart rate, blood pressure, pulse oximetry, continuous non-invasive  hematocrit measurement, and respiration. The phonocardiographic measurements may be taken  with both a commercial and a custom-built device. These are all non-invasive measurements.  After 15 minutes of baseline measurements, a blood draw will proceed normally while the  physiological measurements continue. After the participant is finished donating blood, the  participant will be asked to stay in place for an additional 15 minutes to continue to  collect physiological data. Participants are asked not to eat or drink during the 15 minutes  as this will provide better data collection. The information collected as data for this study  includes: information about medical history, body measurements, and physiological  measurements. Inclusion Criteria:  -  In generally good health  -  Free of systemic diseases  -  No contraindications to LBNP exposure.  -  No prior history of cardiovascular disease  -  Normal resting systolic blood pressure (SBP, 100-140 mm Hg) and diastolic blood  pressure (DBP, 60-90 mm Hg).  -  In generally good health  -  Free of systemic diseases  -  No current or prior history of cardiovascular disease or cardiovascular reactive drugs  -  Blood donors through the DHMC blood donation center  -  Healthy volunteers  -  People who are taking part in another study where about 500 ml of blood is being drawn  -  Therapeutic phlebotomy patients (hemochromatosis or polycythemia vera patients) Exclusion Criteria:  -  Individuals who, after lying supine for five minutes, show a greater than 10 mm Hg  drop in systolic pressure or a greater than 20 beats/minute increase in heart rate  with standing during pre-enrollment evaluation  Blood draw participants:  -  Pregnancy

Characterizing the impact and treatment of reproductive tract bleeding on women and  post-menarchal girls with bleeding disorders.  Objectives: This is a cross-sectional observational study of women and girls (WG) with  bleeding disorders enrolled in the American Thrombosis and Hemostasis Network (ATHN) dataset.  Based on the investigators' study of currently available data of WG with bleeding disorders  in the ATHNdataset, the investigators hypothesize that the information currently captured in  the core data elements of the ATHNdatasest does not adequately capture data specific to WG  with bleeding disorders. Further, the investigators hypothesize that it is feasible for  Hemophilia Treatment Centers (HTCs) to include data points specific to WG with bleeding  disorder when enrolling participants in the ATHNdataset. This hypothesis will be evaluated  through the following specific aims:  Specific Aim 1: Characterize reproductive tract bleeding in a cohort of WG with bleeding  disorders cared for at US HTCs.  Specific Aim 2: Characterize the treatment strategies for and the impact of heavy menstrual  bleeding in a cohort of females with bleeding disorders cared for at HTCs.  Specific Aim 3: Evaluate the feasibility of adding female specific core data points to the  ATHNdataset. This is a multi-center, cross-sectional study of women and girls with bleeding disorders  receiving care at Hemophilia Treatment Centers (HTCs). To further characterize this  population, WG who receive care at federally funded US HTCs will be approached regarding  participation. Following assent and/or consent, participants will be asked to complete a  series of forms. In order to assess their bleeding symptoms, they will complete the self-BAT  (Bleeding Assessment Tool) as well as the Menstrual Bleeding Questionnaire (MBQ). In order to  assess their quality of life, they will complete the PROMIS-29 quality of life inventories.  Patients may be contacted if they miss a question on any of these forms. Phone call should  take no more than 15 minutes. Study staff will complete an intake form which includes data  regarding bleeding disorder diagnosis as well as treatment, using information obtained from  the patient, chart review, and the ATHNdataset. Inclusion Criteria:  -  Women and girls with an active diagnosis of a congenital bleeding disorder (as  designated by the institution inputting data);  1. Deficiencies of factors VIII, IX, II, V, VII, VII, IX, X, XI, FV+VIII, XIII,  Plasminogen Activator Inhibitor 1(PAI-1), hypo-, a-, or dys-fibrinogenemia  2. von Willebrand Disease (Type 1, Type 1c, Type 2A, Type 2B, Type 2M, Type 2N, Type  3, Low VWF)  3. Any platelet function disorder (i.e. Glanzmann Thrombasthenia, Bernard Soulier  Syndrome, Platelet Storage Pool disorder, MYH9 disorders, Gray Platelet syndrome,  Dense granule deficiency)  4. Ehlers Danlos Syndrome  -  Post-menarchal: has had at least 1 period at the time of study entry  -  Participating in the ATHNdataset Exclusion Criteria:  -  Male gender  -  Acquired bleeding disorder  -  Thrombotic disorder  -  Non-English speaking

This study will investigate the clinical efficacy of micro water jet technology in the  debridement and healing of chronic lower extremity ulcers. This is a prospective cohort, single-center, open-label study in subjects with chronic lower  extremity wounds. The study will enroll up to 20 subjects. Subjects will undergo screening  evaluations to determine eligibility to enroll in the study. All study subjects will receive  micro water jet technology debridement as opposed to other debridement methods as part of  their wound care treatment. The other aspects of subjects wound care protocol will remain  unchanged. In the case of bilateral limb ulcers, or multiple ulcers, subjects will have the  option to receive micro water jet debridement on one or all of the ulcers. Inclusion Criteria:  -  Male or female age 18 or older  -  The ability and willingness to provide Informed consent  -  Presence of a chronic lower extremity ulcer  -  Chronic ulcer is defined as that greater than 4 weeks in duration.  -  Subject's informed consent for participation prior to proceeding with micro water jet  technology debridement  -  Patient's ulcer cannot exhibit any gross clinical signs of infection.  -  Patient is willing to participate in all procedures and follow up evaluations  necessary to complete the study.  -  Patient willing and able to comply with having micro water jet technology debridement  potentially weekly or biweekly as part of their wound care treatment plan for up to 20  weeks. Exclusion Criteria:  -  Patients with active wound infection, or untreated osteomyelitis  -  Patients with dementia, or impaired cognitive function  -  Patients who are unable or unwilling to participate in all procedures and follow up  evaluations  -  Patient has Active Charcot foot  -  Patient with malignant wounds

The aim of this randomized controlled trial is to test the effect of 12 weeks Adaptive  Servo-Ventilation (ASV) therapy (additionally to optimal medical management of myocardial  infarction) on myocardial salvage (MSI=myocardial salvage/area at risk, primary endpoint). Primary Outcome Measure: myocardial salvage index, MSI  - To test the effect of 12 weeks of ASV (additionally to percutaneous coronary intervention,  PCI, and optimal medical management of AMI) on myocardial salvage (myocardial salvage index,  MSI, assessed by cardiovascular magnetic resonance imaging, CMR).  Secondary Outcome Measures:  - To test whether ASV therapy in patients with SA early after AMI decreases infarct size and  improves left ventricular remodelling (myocardial salvage, microvascular obstruction change  of infarct size, infarct size at 12 weeks, change of left ventricular ejection fraction  (LVEF), left ventricular systolic volume (LVSV), left ventricular diastolic volume (LVDV) and  LVEF at 12 weeks; assessed with CMR).  B-type natriuretic peptide (NT-proBNP)  -  To test whether ASV therapy in patients with SA early after AMIimproves disease specific  symptom burden (Seattle Angina Questionnaire)  -  To test whether ASV therapy in patients with sleep apnea early after AMI suppresses  sleep apnea (apneas and hypopneas/hour of sleep, mean oxygen saturation).  -  To test whether ASV therapy in patients with sleep apnea early after AMI increases renal  function (Glomerular Filtration Rate, calculated using the 4vMDRD formula). Inclusion Criteria:  1. age 18-80 years  2. first AMI (ST-elevation in ECG or acute occlusion of coronary artery)  3. Primary successful PCI achieved <24 h after symptom onset  4. SA with an AHI >=15 per hour recording time  5. written informed consent Exclusion Criteria:  1. previous myocardial infarction  2. previous myocardial revascularization (PCI or surgical)  3. LVEF <45% and central sleep apnea  4. indication for a surgical revascularisation  5. cardiogenic shock, mean supine blood pressure <60mmHg or NYHA class IV  6. implanted cardiac device or other contraindications for CMR  7. known allergies or other contraindication to contrast medium (e.g.  GFR<30ml/min/1.73m²)  8. history of stroke  9. contraindications for positive airway pressure support (hypotension with mean supine  BP <60mmHg, dehydration, inability to clear secretions, patients at risk for  aspiration of gastric contents, severe bullous lung disease, history of pneumothorax  and/or pneumomediastinum, a history of epistaxis, causing pulmonary aspiration of  blood, cerebrospinal fluid leak or recent skull operations or injury) patients on or  with indication for oxygen therapy, mechanical/non-invasive ventilation  10. patients on nocturnal positive airway pressure support  11. severe obstructive or restrictive airway disease  12. heart failure due to primary valve disease  13. patients awaiting heart transplantation  14. diurnal symptoms of OSA requiring immediate treatment  15. pregnancy

Prospective observational study on patients undergoing decompressive craniotomy A prospective study of 20 neurosurgical patients evaluating the dynamic decompressive  craniotomy technique using NeuroVention, LLC craniotomy bone flap fixation plates. The plates  allow for rigid and semi-rigid bone flap fixation dependent on the implantation technique. A  dynamic craniotomy involves bone flap fixation wherein a limited transient outward bone flap  movement is allowed by the plates to compensate for an increase in intracranial pressure from  brain swelling. The plates also prevent the craniotomy bone flap from sinking inside the  skull and compressing on the brain. Cerebral decompression surgery is undertaken for patients  with cerebral swelling from malignant strokes, medically intractable intracranial pressure  elevation in traumatic brain injuries and brain tumors. The dynamic craniotomy technique  eliminates or reduces the need for a cranioplasty surgery with a potentially significant  improvement in outcome. Inclusion Criteria:  -  Patients undergoing craniotomy who are at an increased risk for developing post-  operative brain swelling or increased intracranial pressure from a malignant stroke  -  Patients undergoing craniotomy who are at an increased risk for developing post-  operative brain swelling or increased intracranial pressure from traumatic brain  injury  -  Patients undergoing craniotomy who are at an increased risk for developing post-  operative brain swelling or increased intracranial pressure from brain tumors. Exclusion Criteria:  -  Patients with blown pupil (cerebral herniation),  -  Massive brain swelling  -  Dismal outcome not expected to survive more than 1-2 weeks.

The standard treatment approach for patients with high-grade primary brain tumors includes  maximum feasible surgical resection, followed by 6 weeks of concurrent cranial irradiation  and daily low-dose temozolomide chemotherapy, followed by 12 cycles of high-dose temozolomide  administered for 5 consecutive days every 4 weeks [Stupp 2005]. Contrast-enhanced MRI is the  current standard for evaluating the success of therapy and monitoring for tumor recurrence.  MRI is typically obtained prior to initial surgery, within 24 hours after surgery, at the  conclusions of cranial irradiation, and then every 8 weeks during temozolomide chemotherapy  until evidence of recurrence. Despite this careful clinical and radiographic surveillance,  and despite decades of research into the histologic and molecular classification of primary  brain tumors, our ability to predict tumor behavior remains very limited. Some gliomas will  result in overall survival times of only months, whereas other histologically-identical  gliomas may yield survivals of years to decades [Carson 2007, Curran 1993, Lamborn 2004].  Current assessment of tumor response to therapy is also poor. Patients with complete  radiographic response after cranial irradiation often progress rapidly post-irradiation. In  contrast, some patients with enhancing masses at the end of chemoradiotherapy may respond  dramatically to further chemotherapy alone, or the masses may even disappear in the absence  of further therapy (so called "tumor pseudoprogression") [Chamberlain 2007]. This confounding  situation demonstrates a need for better assessment of tumor response. Positron emission tomography (PET) is a molecular imaging modality that can probe various  aspects of tumor function using a variety of radio-labeled imaging agents ("tracers").  Oncologic PET imaging has seen a dramatic rise in clinical utilization over the past decade  for cancer detection, staging, and evaluating residual or recurrent disease following  therapy. These clinical scans use the tracer [18F]fluoro-2-deoxy-D-glucose (FDG), which  accumulates in cells in proportion to glucose (GLUT) transporter and hexokinase activity. FDG  thus provides a measure of tissue glucose metabolism. Concurrent with this clinical growth, a  number of other PET tracers have received significant attention in research for a variety of  imaging targets. Of special interest are the tracers 3'-deoxy-3'-[18F]fluorothymidine (FLT),  1-[11C]-acetate (ACE), and [15O]water (H2O). The uptake, retention/washout, and ultimate  biodistribution of these tracers are each related to different functional or molecular  processes. As such, each can be used to probe a different aspect of tumor function: FLT  directly assesses tumor proliferation, ACE provides a measure of tumor growth related to  fatty acid and membrane synthesis, and H2O quantifies tumor perfusion.  OBJECTIVES:  This study has two primary objectives: a translational objective in which a new PET imaging  technology will be translated from experimental development (with simulations and in animals)  to the first use in human subjects; and an exploratory objective in which the complementary  value of multiple PET tracers will be investigated. Each of these objective is described  below, where the study design has been carefully setup to fulfill both objectives in the same  study population.  The translational objective of this study is to implement and evaluate a new imaging  technology for rapid, single-scan multi-tracer PET imaging of these tracers. Current PET  technology prohibits imaging of more than one tracer in a single scan since the imaging  signals from each tracer cannot be distinguished by normal techniques; as such, separate  scans with each tracer currently need to be acquired hours or days apart. Our group has  developed techniques and algorithms for recovering individual-tracer images from  rapidly-acquired multi-tracer PET data using dynamic imaging techniques. These methods have  been tested through extensive simulations and verified experimentally in a canine model with  spontaneously-occurring tumors. Refinement of the methods with more advanced algorithms is  ongoing. The patient imaging studies of this protocol will be implemented in two phases. In  Phase A, separate single-tracer imaging of each tracer will be performed. The data from these  scans will be co-registered and combined to "emulate" multi-tracer scans, which will then be  processed by the multi-tracer signal-separation algorithms. This will permit a direct  comparison of imaging biomarkers from multi-tracer vs. single-tracer scans for each tracer.  Such comparison techniques have been established by the investigators and have been accepted  by peer review for testing multi-tracer signal-separation algorithms. Once  statistically-significant evidence is obtained that multi-tracer scans can accurately provide  the same imaging biomarkers as separate single-tracer scans, the imaging will transition to  Phase B-in which actual multi-tracer scans will be performed.  The objectives of this exploratory study is to preliminarily evaluate the complementary value  of FDG, FLT, ACE, and H2O PET in patients with primary glial neoplasms. Multi-tracer PET  profiles with these four tracers will be obtained in 20 patients with primary glial neoplasms  at up to three timepoints: (1) at "baseline" prior to surgery or immediately after surgery  providing a complete surgical resection was not possible and confirmed by a post-operative  contrast MRI scan where residual tumor greater than 1.0 cm in diameter was present and prior  to any tumor-directed therapy; (2) at the conclusions of the initial (~6-8 weeks)  chemoradiotherapy; and (3) at the time of MRI-documented recurrence within 2 years. In  addition, patients with a known primary brain tumor who have previously undergone treatment  and have recurred based on standard clinical and imaging criteria will be eligible for the  study. A number of quantitative and pseudo-quantitative imaging biomarkers for each tracer  will be computed at each imaging timepoint, and the change in each biomarker between  timepoints will also be computed. These data will be compared with clinical endpoints  (survival, time to progression), and with tumor biologic information (histology, WHO grade,  vascularity, Ki-67, vascular endothelial growth factor (VEGF), epidermal growth factor  receptor (EGFR), p53) in cases when tumor tissue becomes available from standard care. These  data will provide pilot information into the potential value of concurrent multiple PET  biomarkers for predicting tumor behavior prior to the start of therapy, for improved  prognostication, for more efficient and effective tumor surveillance, and/or for more  appropriate assignment of patients to conventional, aggressive, or investigational therapies  early in their clinical courses.  The driving hypothesis for the overall line of research is that multiple PET imaging  biomarkers obtained in conjunction can provide improved image-guided personalized care of  patients with primary glial neoplasms. The term "personalized care" is used here to broadly  include the prediction of tumor behavior prior to the start of therapy, tumor surveillance,  prognostication, and individualized assignment of patients to conventional, aggressive, or  investigational therapies early in their clinical courses. This pilot project will obtain  initial data on the value of these PET biomarkers for such image-guided personalized care.  Specific hypotheses to be tested include:  -  HYPOTHESIS I a: Rapid, single-scan multi-tracer PET imaging can recover PET imaging  biomarker information of each tracer that are not significantly different from those  obtained from conventional, single-tracer scans of each tracer.  -  HYPOTHESIS II b: Multi-tracer PET biomarkers, obtained in conjunction, are better able  to predict tumor aggressiveness than individual-tracer biomarkers or conventional  radiographic imaging.  -  HYPOTHESIS III b: Multi-tracer PET biomarkers, obtained in conjunction, are better able  to detect functional changes in tumor state that occur in response to therapy than  individual-tracer biomarkers or conventional radiographic imaging.  -  HYPOTHESIS IV b: Characterization of multiple aspects of tumor function (glucose  metabolism, proliferation, membrane growth, and perfusion) provides new insight into  tumor status that can guide selection of the most appropriate therapy.  a Sufficient statistical power is expected to be obtained under this protocol to validate the  extensive simulations and experimental evaluations performed previously and concurrently with  these patient imaging studies.  b Pilot data regarding these three hypotheses will be obtained in this work by studying the  correlation of PET imaging biomarkers with clinical outcomes and tumor biologic information.  Though high statistical power cannot be expected from the limited number of patients in this  pilot study, underlying trends in the data will be identified, permitting the formulation of  formal hypotheses to be tested in future rigorous trials. Inclusion Criteria:  Three different adult patient groups will be eligible for inclusion in this study:  -  Group 1: Adult patients with compelling evidence of primary brain tumor based on  clinical and MRI or CT imaging characteristics that have not yet received surgery,  histological diagnosis, or any tumor-directed therapy. Such evidence will include: MRI  or CT scan-documented mass lesion within the brain, accompanied by anatomically  appropriate neurological signs and symptoms, in the absence of a probable competing  diagnosis such as brain abscess or primary intracranial hematoma.  -  Group 2: Newly diagnosed primary malignant brain tumors (WHO Grade II - IV glial-based  tumors) who have not had a complete surgical resection and by contrast MRI or CT have  residual tumor greater than 1.0 cm in diameter and will be receiving radiotherapy  and/or chemotherapy.  -  Group 3: Patients with probable or possible recurrent primary brain tumor as  determined by standard clinical criteria or MRI or CT imaging. The abnormality must be  greater than or equal to 1.0 cm in diameter by contrast MRI or CT or show changes on  non-enhancing MRI sequences (T2 or FLAIR).  -  Patients must be 18 years or older for inclusion in this study. There is little  experience with the safety of [18F]FLT in children, and the risks associated with  radiation exposure may be increased for children under 18 years old as well.  -  Karnofsky performance status ≥ 60%.  -  Patients must document their willingness to be followed for at least 24 months  after recruitment by signing informed consent documenting their agreement to have  clinical endpoints and the results of histopathologic tissue analysis (when  tissue becomes available from routine care) entered into a research database.  -  All patients, or their legal guardians, must sign a written informed consent and  HIPAA authorization in accordance with institutional guidelines.  -  Determination of pregnancy status: Female patients that are not postmenopausal or  surgically sterile will undergo a serum pregnancy test prior to each set of  multi-tracer PET scans. A negative test will be necessary for such patients to  undergo research PET imaging.  -  Pre-treatment laboratory tests for patients receiving [18F]FLT must be performed  within 21 days prior to study entry. These must be less than 2.5 times below or  above the upper or lower limit range for the respective laboratory test for entry  into the study. In those instances where a baseline laboratory value is outside  of this range, then such a patient will be ineligible for enrollment. For the  follow-up scanning sessions after therapy has been instituted, laboratory testing  will also be required due to the use of FLT. The patients have brain tumors and  will receive various forms of therapy; therefore many routine laboratory tests  may not be within the typical normal range. As such, a factor of 4.0 times above  or below the upper or lower value for the normal range for any laboratory test  will be used to determine the acceptable range for the 2nd and possible 3rd  imaging timepoints. The baseline laboratory testing will include liver enzymes  (ALT, aspartate aminotransferase (AST), alkaline phosphatase (ALK), LDH),  bilirubin (total), serum electrolytes, complete blood count (CBC) with platelets  and absolute neutrophil counts, prothrombin time, partial thromboplastin time,  blood urea nitrogen (BUN), creatinine. Previous urinalysis abnormalities will not  preclude the patient from being studied. For those patients receiving coumadin or  another anticoagulant the upper limit for prothrombin time or partial  thromboplastin time must not exceed 6 times the upper limit of the normal range. Exclusion Criteria:  -  Patients with clinically significant signs of uncal herniation, such as acute  pupillary enlargement, rapidly developing motor changes (over hours), or rapidly  decreasing level of consciousness, are not eligible.  -  Patients with known allergic or hypersensitivity reactions to previously administered  radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune  diseases may be enrolled at the Investigator's discretion.  -  Patients who are pregnant or lactating or who suspect they might be pregnant. Serum  pregnancy tests will be obtained prior to each set of multi-tracer PET scans in female  patients that are not postmenopausal or surgically sterile.  -  Adult patients who require monitored anesthesia for PET scanning.  -  HIV positive patients due to the previous toxicity noted with FLT in this patient  group.  -  Patients who have undergone surgery or receive any previous tumor-directed therapy for  their brain tumor.

Every year thousands of persons suffer from brain damage resulting in anomia, that is, word  finding difficulties affecting their ability to talk to other people. Anomia may be a result  of stroke or of progressive neurological diseases such as Parkinson's disease or multiple  sclerosis (MS). Word retrieval is dependent on a complex system of different neural networks  and to name objects and activities can be affected to different degrees. The present project  explores different aspects of naming ability in altogether 90 persons that has anomia related  to stroke or to Parkinson's disease or MS. Furthermore, the communicative strategies and  resources used by conversation partners in everyday conversational interaction and in care  situations, affected by anomia are studied. Finally, the project includes a study of the  effectiveness of a word finding training program based on stimulation of semantic and  phonological networks in the brain, involved in the production of words. There is a lack of  research on effects on communication from anomia in Parkinson's disease and MS and there is  no research on anomia that investigates both object and action naming using a material  adapted to the Swedish language. In the project quantitative and qualitative methods are used  to explore and describe how persons with different neurogenic communication disorders can use  different resources and communicative strategies to express themselves. Project out line  The main project consists of:  1. A descriptive study of the occurrence and type of naming difficulties in people with  stroke, Parkinson's disease or Multiple sclerosis (MS) where quantitative data is  compared at group level, (study 1).  2. A descriptive study in which word search strategies are investigated with both  quantitative and qualitative methods (study 2).  3. A series of three intervention studies examining the effect of treatment of anomia  (studies 3-5).  Study 1: The relation between type of injury and ability to name objects and actions and  complex semantic-pragmatic word fluency  Participants The project includes a total of 90 people with anomia: 50 subjects with anomia  after stroke, 20 individuals with Parkinson's disease and 20 individuals with MS are  recruited are recruited through patient associations and health care facilities in Västra  Götaland and included consecutively.  In the study confrontation naming ability, and word fluency is explored. In addition, the  type of naming difficulties and consequences of anomia in everyday communication are examined  with a questionnaire and communication analysis.  1) Confrontation naming ability is examined with a material consisting of 42 images  representing 21 nouns and 21 verbs. The selection of images comes from The Object & Action  Naming Battery and is adapted to Swedish linguistic and cultural conditions. The images  consist of simple black and white drawings. There is a 20-second time limit for response for  each image. In addition to scoring, an analysis and categorization of the response according  to the coding scheme is performed; 2) Word fluency is examined with semantic (animals and  activities) and phonological (F, A and S) word fluency tests where the participant will  produce as many words as possible for each category during one minute. The results are  compared with reference data for healthy participants and the use of strategies is analyzed  by calculating cluster size and number of switches between different categories; a more  complex semantic-pragmatic word fluency task is also administrated.  Participants' experience of their communication skills in everyday life and quality of life  is gathered in a questionnaire with image support: The Communication Outcome After Stroke  (COAST) scale. COAST consists of 20 questions where participants estimate themselves on a  5-degree likert scale. Stroke and Aphasia Quality of Life Scale (SAQOL-39) and Communicative  Participation Item Bank (CPIB) are also administrated as well as a formalized interview.  Study 2: Word search strategies in naming difficulties in people with different types of  neurogenic communication disorders  Participants In this descriptive study fifteen participants with Parkinson's disease and  fifteen participants with MS are included.  Material and methods Word search strategies in ten-twenty minutes of naturally occurring  conversations are assessed through communication analysis. Sequences where participants are  involved in repair due to difficulties to express themselves are analyzed with the  qualitative method Conversation Analysis in combination med Aktivity based communication  analysis.  Studies 3-4: Training with semantic feature analysis to improve naming  Participants Six participants with MS and six participants with Parkinson's disease and 40  participants with anomia due to stroke will be included.  Intervention Participants receive training in semantic feature analysis (SFA) for naming of  objects and activities. The training is administered by presenting an image representing  either an object or an activity are presented to the participant. The participant is  encouraged to try to produce the target word as well as a number of words semantically  related to the target word. The related words are listed in a certain order and describe  different semantic aspects of the target word. The participants get to choose a number of  words which they want to practice.  The participants receive training at 20 occasions, three times a week. The training is  delivered during one hour each session in individual training for the participants with MS  and in a group setting for two hours, including 30 minutes pause for participants with stroke  Study 3-4 - training anomia due to Parkinson's disease and MS Since semantic feature analysis  has not previously been used as treatment for people with Parkinson's disease or MS, the  effect is evaluated in using time series design with multiple baselines. Three-five baseline  measures of the dependent variable is collected before start of training and then every  fourth training session.  Study 5 - training anomia due to stroke In study 5 the effect of intervention for  participants with anomia due to stroke is assessed in a randomized group study with a control  group. The control group receives training in comprehension. The groups are matched in terms  of age, severity of anomia time since onset and level of education. Before and after the  intervention, as well as at a twelve week follow up, the effects are assessed in both groups. Inclusion Criteria:  -  Subjective experience of word finding difficulties  -  Diagnosed left hemisphere stroke or Parkinson's disease or MS  -  With correction, sufficient hearing and vision to be able to participate in the  assessment  -  Participants with stroke at least six months post-onset and documented location of  injury. Exclusion Criteria:  -  Mother tongue other than Swedish  -  Moderately or severely impaired comprehension  -  Other neurological injury or disease  -  Moderate-severe apraxia of speech or dysarthria  -  Fatigue or impaired attention deficit which prevents participating in intensive  training

Study comparing the same drugs as a dual combination product (budesonide and formoterol)  given via two different inhalers. To see which one results in the best effect on breathing. This is a Randomized, Open-Label, Two Period Crossover, Chronic Dosing, 1-Week, Pilot Study  to Assess the Efficacy and Safety of Budesonide and Formoterol Fumarate Inhalation Aerosol  Administered with a Spacer Compared with Symbicort® Turbuhaler® in Subjects with Severe to  Very Severe Chronic Obstructive Pulmonary Disease and Low Peak Inspiratory Flow to assess  lung function Inclusion Criteria: None Exclusion Criteria: None

The objective of this protocol is to obtain on Parkinson's disease more accessible  therapeutic targets than deep brain stimulation (HFS-STN), the neurosurgical treatment for  this pathology. This study will pave the way for new forms of adaptive processing for the  HFS-STN. It could become functionally coupled to a minimalist EEG centred on the motor cortex  and to software for decoding, live or slightly delayed, classes of movements performed. On  the one hand, this device could be used as a sensor of the quality of the information  transmitted by the cortical network, thus allowing the selection of the optimal parameters of  the HFS-STN on the basis of the movement decoding score. On the other hand, this device could  lead to adapting the HFS-STN treatment over time by regularly calculating the recognition  scores of the different movements performed and comparing them to the initial scores. One of the therapies for Parkinson's disease, a condition affecting nearly 150,000 patients  in France, is the invasive neurosurgical implantation of high-frequency deep brain  stimulation of the subthalamic nuclei (HFS-STN). Although HFS-STN is very effective, the  underlying mechanisms are still relatively poorly understood, particularly at the cortical  level, a region that could become an alternative therapeutic target because it is easier to  access. This study aims to measure the changes induced by the antiparkinsonian drug treatment  and the HFS-STN on the encoding and transmission of motor information at the level of the  motor cortex, thanks to the recording of the electroencephalogram of patients. These  recordings, made during the performance of certain movements, will be subjected to an  analysis using "machine learning" methods that will make it possible to decode the identity  of the movement performed more or less efficiently. Inclusion Criteria:  Patients :  1. Patient over 18 years of age  2. Patient meeting the clinical diagnostic criteria for Parkinson's disease (Postuma et  al, Mov Dis, 2015)  3. Signed consent to participate in the study  4. Absence of cognitive impairment (MoCA>24)  5. Affiliation to a French social security scheme  Healthy volunteer :  1. Healthy volunteer over 18 years of age  2. Signed consent to participate in the study  3. Absence of cognitive disorders (MoCA>24)  4. Affiliation to a French social security system Exclusion Criteria:  Patients :  1. Patient refusal to participate  2. Pregnancy or breastfeeding in progress  3. Participation in another therapeutic interventional study  4. Patient under guardianship or curatorship  5. Person subject to a legal protection measure  Healthy volunteers :  1. Refusal of the healthy volunteer to participate  2. Pregnancy or breastfeeding in progress  3. Participation in another therapeutic interventional study.  4. Patient under guardianship or curatorship  5. Person subject to a legal protection measure

This phase I trial studies the side effects and best dose of stereotactic body radiation  therapy in treating patients with prostate cancer after undergoing surgery. Stereotactic body  radiation therapy may be able to send x-rays directly to the tumor and cause less damage to  normal tissue. PRIMARY OBJECTIVES:  I. To determine the maximum tolerated dose (MTD) with an upper limit of 45 Gray (Gy) in 5  fractions, in the delivery of stereotactic body radiation therapy (SBRT) to the prostate  fossa.  SECONDARY OBJECTIVES:  I. To assess acute and late toxicities from treatment.  II. To assess biochemical progression-free survival.  III. To collect prospective quality-of-life data related to bowel, urinary, and sexual  health.  OUTLINE: This is a dose-escalation study.  Patients receive 5 fractions of SBRT over 1.5 weeks.  After completion of study treatment, patients are followed up at 90 days and then  periodically for 3 years. Inclusion Criteria:  -  History of diagnosis of prostate cancer after undergoing prostatectomy  -  No evidence of regional nodal or distant metastases based on computed tomography (CT)  abdomen and pelvis and whole body bone scan within 120 days prior to study entry;  nodes less than 1.5 cm will be considered reactive and biopsy is not required; nodes  1.5 cm or larger are required to undergo biopsy and be negative prior to study  registration; bone scan findings in the absence of blastic or lytic lesion correlates  on CT imaging will also be deemed non-neoplastic  -  Eastern Cooperative Oncology Group (ECOG) performance scale 0-2  -  Child bearing potential: In this patient population, this pertains to the ability to  conceive a child; eligible patients already have received prostatectomy, and therefore  this risk is not applicable  -  Prostate specific antigen (PSA) value can be undetectable up to a value of 2.0 within  30 days prior to study entry  -  PSA value that is undetectable can be enrolled if pathology from prostatectomy  demonstrates one or more of the following: positive margin, extracapsular extension,  or seminal vesicle invasion  -  All subjects must have the ability to understand and the willingness to sign a written  informed consent Exclusion Criteria:  -  Patients should not have any uncontrolled illness including ongoing or active  infection  -  Patients may not be receiving any other investigational agents, or concurrent  biological chemotherapy  -  Patients with history of prior malignancies (with exception to non-melanoma skin  cancer) are ineligible for this study, unless they are documented to be disease-free  for at least 5 years  -  Study-specific exclusions:  -  History of prior radiation to the pelvis  -  History of uncontrolled inflammatory bowel disease  -  Unable to comply with radiation therapy procedures  -  Subjects, who in the opinion of the investigator, may not be able to comply with the  safety monitoring requirements of the study

The overarching aim of the study is to determine the role of insulin signaling on the  neurobiological substrates subserving anhedonia within individuals with mood disorders (i.e.,  Bipolar Disorder (BD) and Major Depressive Disorder (MDD)).  Specific aims include:  1. Molecular: Assessment of components of the insulin cascade, as well as of anhedonia and  reward-related processes, using a proteomics and gene expression approach;  2. Physiology: Measurement of peripheral sensitivity to insulin and metabolic correlates,  including body mass index and dyslipidemia;  3. Neural Circuits: Evaluation of the insulin sensitivity of prefrontal (e.g. prefrontal  cortex) and striatal (e.g. nucleus accumbens, ventral tegmental area) networks in the  resting-state and during an effort-based decision making test, using acutely  administered intranasal insulin and functional magnetic resonance imaging (fMRI);  4. Behavioral: Measurement of willingness to make effort for rewards, as well as of other  components of reward response and anhedonia, using validated behavioral tasks and  clinical scales (e.g. Snaith-Hamilton Pleasure Scale - SHPS).  This initiative represents a proof-of-concept study that insulin is important to anhedonia,  neurocognitive functioning, and behavioural deficits in MDD, representing a novel and safe  therapeutic avenue. Seventy-five adults between the ages of 18 to 50 years with DSM-5 defined MDD or BDI/II, in a  depressive episode will be enrolled, in addition to seventy-five age- and sex-matched healthy  controls. Enrollment into the study is voluntary. Eligible participants will provide written  informed consent. Participants will be enrolled from the outpatient Mood Disorders  Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto.  The MDPU case report form will gather information on the participant's course of illness  variables. Conventional pharmacological treatments for MDD and BD will be permitted.  Participants will be excluded if they are receiving insulin and/or oral hypoglycemiants; have  been diagnosed with possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or  any other dementia; have a history of neurological disorder, or evidence of neurologic or  other physical illness that could produce cognitive deterioration; have substance use  disorder within 3 months before screening or a positive baseline toxicology screen; have a  clinically unstable general medical illness; are pregnant or breastfeeding; have MRI  contraindications.  The ongoing provision of care is not contingent on enrollment and/or completion of the study  protocol. Furthermore, there will be ongoing communication with the participant's primary  care provider in regards to their participation in this study.  This is a randomized double-blind, placebo-controlled, cross-over study. The initial visit  entails the provision of detailed study information to the patient and obtainment of written  informed consent from the participant. The participant will then meet a research team member  at a later date for a screening visit. This study requires a total of 3 visits: one screening  visit and two fMRI scan visits.  Screening and Baseline Assessment: Subjects will first meet with a staff psychiatrist for a  clinical consultation. After obtaining consent and if inclusion criteria are met, a medical  comorbidity questionnaire will be administered to screen for concurrent and lifetime medical  conditions. Participant's demographic characteristics and current medications, as well as  lifetime psychotropic medications received will be recorded. The investigators will also  assess dietary intake with the short food frequency questionnaire (SFFQ); smoking, by  questioning number of cigarettes smoked per day, age when smoking stated, and quit date, if  applicable, to calculate a smoking pack-year history; physical activity using the  International Physical Activity Questionnaire (IPAQ); and alcohol and/or substance abuse with  the Addiction Severity Index (ASI). In addition, the investigators will assess demographics,  socioeconomic status, medical history, and family psychiatric history; childhood trauma  history with the Childhood Trauma Questionnaire (CTQ) will also be assessed. Participants  will also be asked to complete an MRI screening questionnaire to ensure that they have no  contraindications. The following self-reported measures will be carried out: Perceived  Deficits Questionnaire-Depression (PDQ-D), Sheehan Disability Scale (SDS), UCLA life Stress  (Episodic), DeJong Gierveld Loneliness Scale, Pittsburg Sleep Quality Index (PSQI), Social  and Occupational Functioning Assessment Scale (SOFAS). Participants will be required to  complete a urine drug screen. Female participants will be asked to do blood work to confirm  they are not pregnant.  Physiological Assessment: Anthropometric (i.e. BMI, waist-hip ratio) and metabolic  measurements (i.e. fasting glucose, fasting insulin, glycated hemoglobin, lipids and HOMA-IR)  will be completed at each study visit.  Behavioral assessment: These tasks are simple, user-friendly tools that provide an  opportunity, when used in conjunction with the most widely used questionnaires, to gain novel  insights on reward behaviors in mood disorders.  1. The primary behavioral measurement will be effort-based decision-making, assessed using  the Effort-Expenditure for Rewards Task (EEfRT), which will be done in a fMRI paradigm.  2. Assessments will include the validated anhedonia scale Snaith-Hamilton Pleasure Scale  (SHPS), and the mood questionnaires Montgomery-Åsberg Depression Rating Scale (MADRS),  and Young Mania Rating Scale (YMRS) during each study visit.  Neural Circuits Assessment: A promising tool to study the effect of insulin on CNS is  intranasal insulin, which is delivered directly into the brain, without relevant effects on  peripheral glucose. A single dose of intranasal insulin has been shown to influence brain  activation, increasing regional perfusion and functional connectivity between the hippocampus  and the PFC. Acute administration of intranasal in randomized, placebo-controlled, cross-over  designs has been previously used to determine regional responses to insulin in the  resting-state or during tasks.  After screening and baseline assessment, participants will receive a crossover treatment  assignment of either insulin or diluent followed by an MRI scan, with a washout period of 1  week. Therefore, participants will receive a total of 2 MRI scans throughout the course of  the study- one following the first treatment, and one following the second treatment. The  subsample will be enriched for the presence of self-reported anhedonia, using a score of  greater than 2 on the SHPS as a cut-off, which provides the best discrimination between  "normal" and "abnormal" level of hedonic tone. This subsample will also have equal  representation of normal weight and obese participants. Imaging procedures will be done in  collaboration with the Centre for Addiction and Mental Health (CAMH). CAMH is Canada's  largest mental health teaching hospital and one of the world's leading research centres in  its field. CAMH is fully affiliated with the University of Toronto and is a Pan American  Health Organization/World Health Organization Collaborating Centre.  To proxy insulin activity within pre-selected brain regions, the investigators will use a  provocation paradigm, involving the administration of exogenous intranasal insulin, based on  the published work of other research groups. Activation of brain regions will be assessed  during the resting state and task-based reward paradigm (i.e. EEfRT), following an intranasal  administration of either 160 units of intranasal insulin or diluent (insulin and placebo will  be prepared as nasal sprays), in a randomized, double-blinded, cross-over design. A  hypothesis-driven region of interest approach will be used to investigate initially the  striatum and the medial PFC (mPFC). Willingness to make effort for rewards will be measured  with the EEfRT.  Imaging procedures will be started with a safety monitoring for glucose and cardiovascular  vital signs. An insulin/placebo spray will be administered intranasally and, within 30 min,  fMRI measurement will be performed. Venous blood samples, for determination of plasma glucose  and insulin concentrations, will be obtained at the time of the insulin/placebo spray  administration and immediately after the scan. The 2 scans for each individuals will be  acquired on the same scanner. Subjects will be scanned using a 3.0-Tesla Signa HDx scanner  with an 8-channel phased-array receiver coil (GE Healthcare, Milwaukee, Wisconsin) consisting  of a structural and functional neuroimaging, comprising:  1. Whole-brain 3-D T1-weighted Inversion-Recovery prepared Fast Spoiled Gradient-Echo  (IR-FSPGR) anatomical scan with the following parameters: (TI/TR/TE = 450/8/3 ms, matrix  size 256 × 256, field of view 22 × 22 cm, slice thickness = 1 mm, and flip angle = 15°)  2. Whole-brain, T2*-weighted BOLD echo planar imaging (EPI) during awake resting state with  the following parameters: (TR/TE = 2000/30 ms, 3.5 x 3.5 x 3.5 mm voxel size, field of  view 24x24 cm, 39 slices, slice thickness 3.5 mm, matrix size 64x64, number of frames =  405, flip angle = 70°)),  3. Three runs of whole-brain, T2*-weighted BOLD EPI series during task-based reward  paradigm with the same parameters as in ii. Inclusion Criteria:  1. Age 18-50  2. DSM-5 defined MDD/BD and a total score ≥20 on the Montgomery-Åsberg Depression Rating  Scale (MADRS) and no history of dementia or intellectual disability  3. A written, voluntary informed consent prior to study enrollment  1. Age 18-50  2. A written, voluntary informed consent prior to study enrollment Exclusion Criteria:  1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects  2. Diagnosis of possible or probable AD, MCI, or any other dementia  3. History of neurological disorder, or evidence of neurologic or other physical illness  that could produce cognitive deterioration  4. Substance use disorder within 3 months before screening or a positive baseline  toxicology screen  5. Presence of clinically unstable general medical illness  6. Pregnancy or breastfeeding  7. MRI contraindications  1. Use of insulin and/or oral hypoglycemiants, due to its confounding effects  2. Presence of any current or lifetime psychiatric or neurological conditions  3. Substance use disorder within 3 months before screening or a positive baseline  toxicology screen  4. Presence of clinically unstable general medical illness  5. Pregnancy or breastfeeding  6. MRI contraindications

The purpose of this study is to determine the effects of a brain stimulation technique known  as transcranial direct current stimulation, or tDCS, on the benefits of Prolonged Exposure  therapy, or PE, which is an effective treatment for posttraumatic stress disorder, or PTSD.  tDCS has been demonstrated to be safe and effective for influencing brain activity by passing  a weak electrical current through the scalp. In this study, tDCS is provided in addition to  PE treatment, through the National Crime Victim's Research and Treatment Center at MUSC, or  the PTSD Clinical Team Clinic within the Ralph H. Johnson VA Medical Center. This project implements a multiple baseline within-subject clinical trial design aiming to  test whether tDCS targeting excitation of the medial prefrontal cortex (mPFC) can enhance a  standard course of PE in a sample of adult civilians and Veterans (ages 18-65) who meet full  DSM-5 criteria for chronic PTSD (i.e., > 3 months post-trauma; N = 20). All participants will  receive a total of ten 60-min. sessions of manualized PE, preceded by 20 min. of either  active or sham HD-tDCS. The stepped-wedge multiple baseline design features tDCS as a 2-level  within-subject factor (Sham tDCS+PE vs. Active tDCS+PE), and between-subject comparisons  based on stratified random assignment to cross-over from sham to active tDCS just prior to  sessions 4 through 8. Strata will be defined by dichotomous classifications of possible  confounds, including baseline severity (moderate vs. severe), psychotropic medication status  (no vs. yes), and sex (female vs. male). The sample will consist of treatment-seeking  civilian and Veteran participants referred by either of two of our consortium sites,  including the National Crime Victim's Research and Treatment Center (NCVC) at MUSC, or the  PTSD Clinical Team (PCT) at the Ralph H. Johnson VAMC, as well as community participants who  respond to study advertisements. Inclusion Criteria:  -  Age 18-65.  -  Fluent in English.  -  Diagnosis of chronic PTSD based on MINI for DSM-5 (> 3 mo. post-trauma)  -  For Veterans recruited at the Ralph H. Johnson VA only: eligible to receive PE in the  PCT clinic. Exclusion Criteria:  -  Currently receiving psychotherapy for another anxiety- or stress-related condition.  -  Unstable dose of psychotropic medications within 6 weeks prior to baseline assessment  -  Medical condition that would contraindicate participation in treatment or assessment  activities (e.g., severe cardiovascular problems).  -  Pregnancy  -  Current severe major depressive disorder  -  Current, or history of bipolar disorder  -  Current, or history of psychotic symptoms  -  Serious suicidal risk  -  Active neurological conditions, e.g., seizures, stroke, loss of consciousness or  concussion  -  Contraindications for tDCS:  -  Metal in the head.  -  Implanted brain medical devices.

Exaggerated inflammation in the body and brain is thought to play a role in the vulnerability  to and aggravation and perpetuation of adverse consequences among those with posttraumatic  stress disorder (PTSD). The proposed study begins the process of investigating the use of a  natural immunoregulatory/anti-inflammatory probiotic, Lactobacillus rhamnosus GG (LGG;  ATCC53103), to treat chronic symptoms associated with PTSD among Veterans. By looking at the  impact of probiotic supplementation on biological signatures of increased inflammation, as  reflected by biomarkers of inflammation, gut microbiota composition, intestinal permeability,  stress response, decision making, and PTSD symptoms, this study may identify a novel  intervention for the treatment of symptoms associated with this frequently occurring  condition. United States military Veterans from recent conflicts are coping with symptoms related to  posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and  mental health interventions (e.g., medication, psychotherapy), and often symptoms are not  significantly improved by traditional treatments. Alternative treatment methods are needed.  An underlying feature of PTSD is exaggerated inflammation, both peripherally and in the  central nervous system, which is thought to play an important role in the vulnerability to,  aggravation of, and perpetuation of adverse consequences of this condition. Therefore, an  innovative intervention strategy would be the use of immunoregulatory/anti-inflammatory  probiotics to reduce inflammation. In this study, the investigators will investigate the  effects of an 8-week oral administration of an immunoregulatory probiotic, Lactobacillus  rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and  immunoregulatory effects (i.e., decreases in C-reactive protein [CRP]). Project aims will be  assessed using a longitudinal, double blind, randomized placebo-controlled design. After  initial evaluation procedures to confirm PTSD diagnosis, 59 participants will be randomized  to probiotic supplementation and 59 will be randomized to placebo supplementation.  Primary Aim. Demonstrate the effects of LGG in a cohort of OEF/OIF Veterans with PTSD and  Functional Bowel Disorders (FBD), including IBS, on plasma CRP concentrations (mechanistic,  primary outcome), and PTSD symptom severity (clinical, exploratory). Additional biological  signatures associated with this condition will be considered exploratory, including gut  microbial community and intestinal permeability [IP]), other biological signatures of  inflammation, as well as stress responsivity and decision making. Hypothesis 1.1. Those who  receive LGG supplementation will respond with lower plasma levels of CRP as compared to those  allocated to placebo. Exploratory Hypothesis 1.2. Those who receive LGG supplementation will  respond with decreased PTSD symptoms (PCL-5), as compared to those allocated to placebo.  Exploratory Hypothesis 1.3. Those who receive LGG supplementation will respond with increased  abundance of LGG and community-level shifts (e.g.,increased alpha diversity) in the gut  microbiota (measured using qRT-PCR and DNA sequencing of the 16S rRNA gene, respectively),  decreases in IP (decreased fatty acid binding protein 215 and D-amino acid oxidase16),  increases in plasma concentrations of anti-inflammatory biomarkers (IL-10, IL-4), decreases  in additional plasma biomarkers of inflammation (IL-6, IL-8, IFNγ, IL- 1α, IL-1β, and  IL-12p70), reduced stress response (biological and psychological) during and after Cyberball,  and improved decision-making (measured by performance on the modified Iowa Gambling Test  [mIGT]) as compared to those allocated to placebo. Exploratory Hypothesis 1.4. The effect of  LGG supplementation on stress response, decision-making, and PTSD symptom severity is  mediated by effects of LGG supplementation on the gut microbiota, intestinal permeability,  and plasma biomarkers of inflammation. Inclusion Criteria:  -  History of at least one deployment in support of OEF/OIF  -  Current diagnosis of PTSD per the Clinician Administered PTSD Scale-5 (CAPS-5)  -  Current diagnosis of Functional Bowel Disorder by ROME IV  -  CRP level of 1.0 mg/L or above at baseline  -  Medical clearance to participate by study providers  -  Age between 18 and 60  -  Ability to provide informed consent  -  Willingness to abstain from probiotic supplements (pills, tablets, oils, foods, etc.)  other than the investigational product provided until all study procedures are  completed  -  Willingness to provide blood and stool samples Exclusion Criteria:  -  Inability to adequately respond to questions regarding the informed consent procedure  -  Currently involved in the criminal justice system as a prisoner or ward of the state  -  Non-English speaking  -  Current (past month) alcohol or substance abuse or dependence  -  Lifetime history of bipolar disorder or psychosis or anxiety disorders (excluding  PTSD).  -  Consistent (e.g., 5x/week or greater) probiotic supplementation within the last month,  including probiotic food products such as yogurt, as determined by phone screen  interview and Probiotic Food Check List  -  Receiving intravenous, intramuscular, or oral antibiotics within the last month  -  Presence of central venous catheters (CVCs)  -  Gastrointestinal (GI) barriers as identified by the 2-week run-in period as determined  by the study team  -  Participation in conflicting interventional research protocol  -  Vital signs outside of acceptable range, i.e., blood pressure >160/100, pulse >100  -  Use of any of the following drugs within the last 6 months: antifungals, antivirals or  antiparasitics (intravenous, intramuscular, or oral); oral, intravenous,  intramuscular, or inhaled corticosteroids; cytokines or cytokine inhibitors;  methotrexate or immunosuppressive cytotoxic agents  -  Acute disease at the time of enrollment (defer sampling until the participant  recovers). Acute disease is defined as the presence of a moderate or severe illness  with or without fever (e.g., oral temperature >100° F)  -  Any medical condition deemed exclusionary by the Principal Investigators  -  History of cancer  -  Unstable dietary history as determined by the PIs (e.g., major changes in diet during  the previous month, where the subject has eliminated or significantly increased a  major food group in the diet)  -  Positive test for human immunodeficiency virus (HIV), Hepatitis B virus, or Hepatitis  C virus  -  Any confirmed or suspected condition/state of immunosuppression or immunodeficiency  (primary or acquired) including HIV infection, or those receiving immunosuppressive  drugs or treatment including antineoplastic therapy, post-transplantation  immunosuppressive therapy, and/or radiation therapy  -  Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy,  in the past five years. Any major bowel resection at any time  -  Female who is pregnant or lactating  -  Treatment for or suspicion of ever having had toxic shock syndrome  -  History of moderate and/or severe traumatic brain injury

To determine the associations among biometric data, arrhythmias, subject-reported symptoms  and subject wellness. The Arrhythmia Management System records rhythm, heart rate, subject-reported symptoms and  multiple parameters that include respiration rate, activity and body posture. These biometric  data could provide clinicians better insight into the context of the detected arrhythmias,  subject-reported symptoms and wellness status. Hence, the purpose of the study to determine  the associations among biometric data, arrhythmias, symptoms and subject wellness. Inclusion Criteria:  -  Subjects who require monitoring for non-lethal cardiac arrhythmias  -  Subjects who have an indication for mobile cardiac telemetry (MCT) monitoring  -  Subjects 21 years of age or older Exclusion Criteria:  -  Subjects with an implantable cardiac device such as left ventricular assistive device,  pacemaker, implanted cardioverter defibrillator (ICD), cardiac resynchronization  therapy device, subcutaneous ICD's, pressure monitors and loop monitors  -  Subjects with wearable cardioverter defibrillator, Holter monitors, wearable event  recorders, and other mobile cardiac telemetry devices at the same time  -  Subjects currently hospitalized  -  Subjects with a skin condition preventing them from wearing the AMS device  -  Subjects who are non-ambulatory  -  Subjects who are self-reporting to be pregnant  -  Subjects participating in another study

This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose  cancer has a genetic change called PTEN mutation or deletion. GSK2636771 may block a protein  called PI3K-beta, which may be needed for growth of cancer cells that express PTEN mutations.  Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth. PRIMARY OBJECTIVE:  I. To evaluate the proportion of patients with objective response (OR) to targeted study  agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.  SECONDARY OBJECTIVES:  I. To evaluate the proportion of patients alive and progression free at 6 months of treatment  with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple  myeloma.  II. To evaluate time until death or disease progression. III. To identify potential  predictive biomarkers beyond the genomic alteration by which treatment is assigned or  resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and  imaging-based assessment platforms.  IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes  from pre- through post-therapy imaging can predict objective response and progression free  survival and to evaluate the association between pre-treatment radiomic phenotypes and  targeted gene mutation patterns of tumor biopsy specimens.  OUTLINE:  Patients receive PI3K-beta inhibitor GSK2636771 (GSK2636771) orally (PO) once daily (QD) on  days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable  toxicity.  After completion of study treatment, patients are followed up every 3 months if less than 2  years from study entry, and then every 6 months for year 3 from study entry. Inclusion Criteria:  -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol  prior to registration to treatment subprotocol  -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment  assignment and must have no clinically important abnormalities in rhythm, conduction  or morphology of resting ECG (e.g. complete left bundle branch block, third degree  heart block)  -  Patients must have PTEN gene mutation/deletion  -  There must be evidence of PTEN expression by immunohistochemistry (IHC) (any  amount of staining will be considered positive for expression)  -  Patients with complete loss of PTEN by IHC, regardless of PTEN mutations/deletion  status, will be enrolled into MATCH subprotocol EAY131-P, not this subprotocol  (EAY131-N)  -  Patients must have hemoglobin >= 9 g/dL  -  Patients must have a serum creatinine that =< 1.5 x upper limit of normal (ULN) or  have a 24-hour creatinine clearance of >= 50 mL/min Exclusion Criteria:  -  Patients must not have known hypersensitivity to GSK2636771 or compounds of similar  chemical or biologic composition.  -  Patients must not have tumors harboring co-existing aberrations activating the  PI3K/MTOR and MAPK pathways, such as PIK3CA, PIK3R1, BRAF, KRAS and AKT1, TSC1/2,  mTOR, NF2, NRAS, HRAS, NF1  -  Patients must not have received prior treatment with agents targeting the PI3K beta,  AKT, or mTOR pathways:  -  This includes (but is not limited to):  -  mTOR inhibitors: temsirolimus, everolimus, ridaforolimus, sirolimus,  salirasib, CC-223, INK128, DS-3078, CC-115, AZD-2014  -  Dual PI3K/mTOR inhibitors: BEZ235, XL-765, GDC 0980, PF-04691502, GSK  2126458, Quinacrine, PKI-587, P-P7170, LY3023414, GDC 0084, DS 7423,  CBLC-137  -  Pan-PI3K inhibitors: BKM-120 (buparlisib), PX-866, XL-147, GDC-0941  (pictilisib), BAY-806946, ZSTK-474, WX 037, SRX5000, SRX2523, AMG511,  PQR308, BAY 94-9343  -  PI3K inhibitors with beta isoform activity: prior GSK2636771 is not allowed,  nor is GS-9820, PQR3XX, KAR4139  -  The following treatments are allowed:  -  BYL719 (PI3Kalpha inhibitor)  -  GDC-0032 (PI3Kalpha inhibitor)  -  INK1117 (PI3Kalpha inhibitor)  -  Idelalisib (PI3Kdelta inhibitor)  -  IPI-125 (PI3K gamma delta inhibitor)  -  TGR1202 (PI3Kdelta inhibitor)  -  SRX2558 (PI3Kdelta inhibitor)  -  RP6530 (PI3K gamma delta inhibitor)  -  PWT143 (PI3Kdelta inhibitor)  -  IPI443 (PI3K gamma delta inhibitor)  -  GNE293 (PI3Kdelta inhibitor)  -  Patients with a history of interstitial lung disease or pneumonitis are excluded  -  Patients must not have any congenital platelet function defects and cannot be on any  of the following anti-platelet drugs: clopidogrel, ticlopidine, prasugrel, that act at  platelet purinergic receptors  -  Any need for starting anti-platelet therapy in a patient enrolled to this arm  will have to be evaluated by the subprotocol chair

This project is a pilot study exploring the effects of dietary choices and quantitative  digestion of gluten ingested by individuals with IBD compared to a control population. The  aim of the study is to evaluate for the first time in an Italian population of subjects with  IBD the presence of a diet based on GFD (gluten free diet). Subjects with IBD will be recruited among the patients referred to the IBD clinic of the  Policlinico of Milan. These patients are subject to annual check-ups during which, where  possible, they will be asked to sign an informed consent. These patients are subjected during  the visits of normal clinical follow-up to:  -  Questionnaire on eating habits for the patient with IBD versus control patients;  -  Modified Food Habits Frequency Questionnaire (FFQ), validated for the celiac population.  The questionnaire assesses the extent, frequencies of consumption and quantity of  gluten-containing foods in a year; this, in order to estimate the average introduction  of gluten through the diet versus control patients;  -  Anthropometric and plicometric analysis;  -  Validated clinical activity questionnaires for RCU (ulcerative rectocolitis) and CD  (Chron disease) (Mayo Score and Harvey-Bradshaw Index). Inclusion Criteria:  -  Age: 18 years  -  Gender: women and men  -  Patients who have been diagnosed with IBD for at least 12 months  -  patients who have signed an informed consent Exclusion Criteria:  -  Pregnancy status  -  Patients not suffering from the two main forms of IBD, i.e. CD or RCU (unclassified  IBD colitis, collagenous colitis, lymphocytic colitis will be excluded).

Fibroblasts have demonstrated potent immune modulatory and therapeutic activity in the  experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, as well as in  other models of autoimmune and inflammatory diseases.  This study will assess primary safety and secondary efficacy endpoints of intravenous  administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting  MS resistant to interferon. While the safety of fibroblasts administered clinically is  established, it is unknown whether these cells are effective in the treatment of multiple  sclerosis (MS).  Our hypothesis is that the tolerogenic fibroblasts will be well-tolerated and meet our  primary objective. In addition, The investigators are optimistic that they will see signs of  efficacy based on the following: Neurological assessment of the MS functional composite  assessment which comprises of EDSS, the expanded EDSS (Rating Neurologic Impairment in  Multiple Sclerosis, the Scripps neurological rating scale (NRS), paced auditory serial  addition test (PASAT), the nine-hole peg test, and 25-foot walking time, short-form 36  (SF-36) quality of life questionnaire and gadolinium-enhanced MRI scans of the brain and  cervical spinal cord. Fibroblasts have demonstrated potent immune modulatory and therapeutic activity in the  experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, as well as in  other models of autoimmune and inflammatory diseases. Mechanistically, tolerogenic  fibroblasts produce anti-inflammatory and immune modulatory factors, which appear to be  therapeutic in the context of autoimmunity, including IL-10 and TGF-beta. Additionally,  tolerogenic fibroblasts produce neurotrophic mediators that enhance myelin production and/or  prevent neuronal apoptosis.  This study will assess primary safety and secondary efficacy endpoints of intravenous  administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting  MS resistant to interferon. While the safety of fibroblasts administered clinically is  established, it is unknown whether these cells are effective in the treatment of multiple  sclerosis (MS).  Research Hypothesis: Intravenous administration of 100 million tolerogenic fibroblasts will  be well tolerated and induce a therapeutic effect in relapse remitting MS patients.  Rationale: The family of Mesenchymal Stem Cells (MSCs) is immune-modulatory, and bone marrow  MSCs (BM-MSCs) have induced therapeutic responses in patients with MS [1]. Tolerogenic  fibroblasts possess superior immune modulatory activity compared to BM-MSCs and adipose MSCs.  The investigators, therefore, seek to perform a five-patient trial to assess the safety and  signs of efficacy of this cell population in MS patients resistant to interferon.  The trial's primary objective is freedom from treatment-associated adverse events at 1, 2, 4,  8, and 16 weeks post-treatment. The study's secondary objective will be efficacy as assessed  at baseline, weeks 2, 4, 8, and 16. The results will be quantified based on the following:  Neurological assessment of the MS functional composite assessment, which comprises of EDSS,  the expanded EDSS (Rating Neurologic Impairment in Multiple Sclerosis, the Scripps  neurological rating scale (NRS), paced auditory serial addition test (PASAT), the nine-hole  peg test, and 25-foot walking time, short-form 36 (SF-36) quality of life questionnaire and  gadolinium-enhanced MRI scans of the brain and cervical spinal cord. Inclusion Criteria:  1. Patients willing to sign an informed consent and capable of understanding the features  of this clinical trial.  2. Willing to keep a weekly diary and undergo observation for four months  3. Non-pregnant patients 18-55 years of age with MS according to the revised McDonald  criteria and meeting the Possner criteria for clinically defined MS.  4. EDSS scores of 2·0 to 5·5 points assessed at least three months after the last acute  attack of MS. Exclusion Criteria:  1. Patients with evidence of active proliferative retinopathy.  2. Patients with poorly controlled diabetes mellitus (HbA1C > 8.5%).  3. Patients with renal insufficiency (Creatinine > 2.5) or failure.  4. Infection as evidenced by WBC count of >15,000 k/cumm and/or temperature >38C.  5. History of organ transplant.  6. History of previous or active malignancy, except for localized cutaneous basal or  squamous cell carcinoma or carcinoma in situ of the cervix  7. History of sickle cell anemia  8. Cardiovascular conditions:  1. Exercise limiting angina ( Canadian Cardiovascular Society Class greater or equal  to 3  2. Congestive heart failure (New York Heart Association class greater or equal to 3  3. Unstable angina  4. Acute ST elevation myocardial infarction (MI) within one month  5. Transient ischemic attack or stroke within one month  6. Severe valvular disease

This study will enroll heart failure (HF) patients who are under active management with an  implanted pulmonary artery pressure sensor (CardioMEMS). Subjects will be provided an  electronic stethoscope (the Eko DUO) to take at-home heart sound, lung sound, and ECG  recordings in conjunction with regimented CardioMEMS measurements. These two datasets will be  used to confirm whether an AI/ML model to track HF status can be developed. Heart failure (HF) affects an estimated 6.2 million Americans over the age of 20 and carries  a very high healthcare system burden worldwide. Annual costs for HF management in the United  States were estimated at $30.7 billion in 2012 and are projected to increase to $68.7 billion  by 2030. The primary cost driver for HF management is a high rate of acute decompensation and  subsequent hospitalization. The mean per-patient cost of an HF-related hospitalization is  estimated to be $14,631.  Among the conditions that the Centers of Medicare and Medicaid Services (CMS) monitors for  their Hospital Readmission Reduction Program, HF has the highest median readmission rate at  days 1-29 (23%) and days 1-60 (11.4%) postdischarge. The cost burden of HF readmission is  $2.7 billion in 2013. A meta-analysis from 2012 estimated that 23.1% of HF readmissions are  avoidable, although individual studies ranged from 5% to 79%. Many health plans, including  CMS, have focused on interventions that monitor patients for early detection of HF  decompensation. Earlier interventions can help care teams prevent avoidable hospitalizations.  Invasive hemodynamic sensor devices have enabled HF care teams to better predict and prevent  HF decompensation events, and thus prevent rehospitalizations. One such device is the  CardioMEMS pulmonary artery (PA) sensor (Abbott Inc., Atlanta, GA, USA). The CardioMEMS is  implanted in a branch of the left PA, allowing for daily measurements of PA pressures. PA  pressures are used as a surrogate marker of filling pressure, and rising filling pressures,  in turn, are a marker that precedes the exacerbation of HF. The CHAMPIONS trial demonstrated  that remote diuretic management using CardioMEMS reduced HF all-cause hospitalizations by 43%  and mortality by 57%. Unfortunately, CardioMEMS as an HF solution is invasive, costly  (average sales price of $17,750), indicated for a restricted patient population (NYHA class  III HF who have been hospitalized within the last year), and has limited reimbursement  coverage due to equivocal cost-effectiveness projections.  This has stimulated a search for less expensive, non-invasive sensors that may correlate with  fluid status in HF patients. A study in Taiwan demonstrated that outpatient therapy guided by  an inpatient device with ECG and sound sensors reduced post-discharge HF utilization by 31%  when compared to a control group using symptoms to guide therapy. The LINK-HF study  demonstrated that a wearable patch with ECG and sound sensors could predict HF readmissions  with a sensitivity of 76% to 88%, a specificity of 85%, and a median lead time of 6.5 days.  Despite these initially promising results, however, these devices have significant  disadvantages. The inpatient device used in the Taiwanese study could not be adapted into a  portable form factor for outpatient use. Wearable devices can be rigid, uncomfortable, and  highly visible, all of which can interfere with patient function and decrease monitoring  compliance.  Therefore, there remains an unmet clinical need for a widely available, non-invasive,  affordable medical device that can estimate an HF patient's hemodynamic fluid status and  inform the HF care management team. The ultimate goal remains to decrease an HF patient's  risk for hospital readmission, all from the comfort of the patient's home.  To meet this need, Eko has developed the DUO, an FDA-cleared, portable, hand-held, wirelessly  connected medical device with ECG and sound sensors. Data from the DUO can be wirelessly  streamed to a mobile phone or tablet, which can then be transmitted to a HIPAA-compliant  internet cloud infrastructure for storage and analysis. In 2020, Eko introduced into the US  market a package of AI/ML algorithms that follows this workflow to identify heart murmurs,  atrial fibrillation, and other cardiac conditions, and intends after this proof of concept  study to build upon this platform to estimate and trend PA pressures.  But beyond measuring and trending PA pressures, the DUO can be used to capture additional  important HF features that will further improve any HF algorithm's performance. For example,  because patients with decompensated HF often have an audible third heart sound,  characteristic ECG findings, and altered time interval durations between their heart sounds  and ECG signals, the Eko DUO device may be uniquely positioned to detect these types of  changing signals.  In addition, because heart failure and fluid overload are reflected in the lungs as crackles  (and occasionally effusions), the lung examination is and has always been a cornerstone of  the overall physical examination of HF patients. By using the DUO to capture lung sounds in  patients with HF, and comparing not only the presence or absence of crackles, but also how  these adventitious sounds change over time, we will be able to explore the utility of the Eko  DUO in helping to predict exacerbated HF.  This proof-of-concept study evaluates the feasibility of the Eko DUO in capturing and  measuring signals relevant to HF exacerbation (e.g., time intervals, adventitious lungs  sounds, pathologic heart sounds), as well as the feasibility of developing an AI/ML algorithm  to model PA pressures in HF patients with the implantable CardioMEMS device. Inclusion Criteria:  -  Aged 18 years and older  -  Patient or healthcare proxy willing to give written informed consent to participate  -  Presence of an implanted CardioMEMS device or imminent implantation of a CardioMEMS  device  -  Expressed willingness to take DUO recordings immediately before or after taking their  CardioMEMS measurements, on the same schedule prescribed by their physician  -  Functioning iOS or Android smartphone or tablet that can download and run the  companion Eko application  -  Access to WiFi or cellular data connection at home Exclusion Criteria:  -  Patient or healthcare proxy is unwilling or unable to give written informed consent  -  Patient is enrolled in another study that may interfere with the observations from  this study  -  Acute pericarditis  -  Healing chest wall wounds (e.g., sternotomy or thoracotomy)

Brief summary:  Background: Rib fractures are one of the most common causes of trauma disabilities and have  become an important health issue. Patients usually suffer from severe pain. A rapid and  adequate pain control is considered as a priority to improve respiratory mechanics and reduce  the risk of pulmonary and systemic complications. So far, there was no gold standard  regarding pain control for rib fractures.  Objective: To assess the effect of the newly-designed Prosthorax Thoraxbelt in addition to  oral analgesics on pain control of rib fractures  Method: There will be two groups of patients in this study. One group will be the patients  with rib fractures who are necessary for in-hospital intense pain control. The other will  consist of follow-up patients with rib fractures at an outpatient clinic. The investigators  will aim to recruit 30 and 82 patients respectively. The study has been approved by the hospital research ethics committee.  Arm1: The management and assessment of pain control in rib fracture with non-invasive  stabilization: a randomized controlled trial (inpatients)  Arm2: The management and assessment of pain control in rib fracture with non-invasive  stabilization: a randomized controlled trial (outpatients)  Primary outcome:  1. inpatient: Visual analog scale (VAS) for 6 hours, 12 hours and 24 hours after the  surgery  2. outpatient: Visual analog scale (VAS) for the times at emergency room; 3 days, 3 weeks  and 3 months after rib fracture at an outpatient clinic.  Secondary outcome:  -  inpatients  1. The accumulated dose of the inter-venous patient-controlled analgesic drug within 6  hours, 24 hours and 48 hours after the surgery  2. Complication during the hospital stay  3. Hospital stay  4. VAS before discharge  5. Unanticipated events (ICU admission, a second surgery, death)  6. VAS during the 1-week, 1-month and 3-month outpatient clinic visit after the  surgery  7. An X-ray examination at an outpatient clinic  8. Compliance on ThoraxBelt after discharge  -  outpatients  1. Complication during the follow-up period  2. Unanticipated events (ward admission, ICU admission, a surgery, OHCA)  3. Compliance on ThoraxBelt after discharge  4. An X-ray examination at an outpatient clinic Inclusion Criteria:  -  The adult patients with rib fractures (inpatients/outpatients)  -  The patients will be assessed to the further admission (inpatients)  -  The patients will be assessed to be at follow-up clinic visit (outpatients) Exclusion Criteria:  -  The accident of rib fractures has been occurred over 24 hours.  (inpatients/outpatients)  -  Refuse to be arranged to the admission (inpatients)  -  Refuse to receive the CT scan (inpatients/outpatients)  -  Chest wall infection or other diseases (inpatients/outpatients)  -  Chest wall infected by rumors (inpatients/outpatients)  -  Pregnancy (inpatients/outpatients)  -  Further complications arise (inpatients/outpatients)  -  Known allergy to ThoraxBelt (inpatients/outpatients)

The purpose of this trial is to investigate the effects of delgocitinib, taken as a capsule,  on the heart rhythms of healthy people, compared to a placebo. The trial will be performed in two parts.  -  Part 1: Group 1 (dose 1 or placebo) and Group 2 (dose 2 or placebo)  -  Part 2: Group 3 (dose 3 or placebo) and Group 4 (dose 4 or placebo)  The doses in Part 2 may be adjusted depending on the results of Part 1.  Participants will be screened within 28 days of their dose. Participants will stay in the  clinic from Day -1 to Day 2 (1 day postdose) and will be dosed on Day 1. A follow up phone  call will take place 2 week (±2 days) after dosing. Inclusion Criteria:  -  Body mass index of ≥18.0 and <30.0 kg/m2.  -  In good health, as judged by the investigator based on: medical history, physical  examination, vital sign assessment, clinical laboratory evaluations .  -  ECG without any clinically relevant abnormal findings at both screening and baseline  -  No history of additional risk factors for torsades de pointes (for example, heart  failure, hypokalaemia, family history of long QT syndrome).  -  Female subjects of childbearing potential and male subjects with a female partner of  childbearing potential must be willing to use highlly effective methods of  contraception. Exclusion Criteria:  -  Any disorder which is not stable and could:  -  Affect the safety of the subject throughout the trial.  -  Influence the findings of the trial.  -  Impede the subject's ability to complete the trial.  -  Use of any medication known to prolong the QT/QTc interval within 3 months or 5  half-lives of the drug, whichever is longer, prior to randomisation.  -  Any medications, including St. John's wort, known to chronically alter drug absorption  or elimination processes within 30 days prior to dosing.  -  Current use of combined hormone contraceptives or combined hormonal replacement  therapy.  -  Subjects who have smoked (use of any type of tobacco and nicotine containing products)  within the last 3 months prior to screening.  -  History of chronic alcohol or drug abuse within 12 months prior to screening.  -  Receipt of any vaccine approved for SARS-CoV-2 within 4 weeks prior to baseline and/or  2 weeks after dose.  -  Receipt of live, attenuated vaccines within 4 weeks prior to baseline.

The aim of this prospective observational study is to identify the specific reasons that  prolong a hospital stay after elective tumor craniotomy. Optimal postoperative in-hospital  stay is considered to be two days from surgery to discharge from the neurosurgical ward.  However, a variable length of stay at a neurological department for follow-up of late  recognized deficits of neurological consequences of the surgical procedure are common. The concept of fast-track surgery and later enhanced recovery after surgery (ERAS) was first  imputed in 1990s. Since then, ERAS protocols have been successfully adopted in many surgical  fields, often with dramatic benefits for the patients. Length of hospital stay is one of the  main questions addressed in many ERAS studies, as it by a simple approach address many of the  complications encountered by the patients or the case flow in the perioperative period. Why  patients have prolonged hospital stay after surgery has been investigated by Husted et al. in  2011 after hip and knee arthroplasty and P. Munk-Madsen et al. in 2019 after laparoscopic  colorectal surgery. Both studies could isolate dominating factors prolonging hospital stay,  some of them preventable. Existing length of stay studies on tumor craniotomy patients have  focused on specific variables affecting hospital duration, but never explored the true cause  of prolonged hospitalization. Inclusion Criteria:  -  Patients scheduled for elective brain tumor craniotomy Exclusion Criteria:  -  Stereotactic biopsy, pituitary surgery and laser interstitial thermal therapy (LITT)

The aim of this study is to evaluate the difference of breast milk microbiota between mothers  with and without vaginal infections during pregnancy. The maternal microbiota is one of the relevant factors in the development of the infant's  immune system, whereby the colonization of microbes in human begins at birth, when the  newborn baby is exposed to maternal vaginal, gastrointestinal microbiota and as well as the  microbes from the external environment. The neonatal intestine is colonized by symbiotic  bacteria can be divided into four main steps; (i) acquisition of maternal vaginal, colonic,  and skin flora at birth; (ii) introduction of oral feedings (breastfeeding or formula  feeding); (iii) weaning; and (iv) acquisition of complete adult colonization.  Breastfeeding is associated with the protection of the infants from either infections or  infection-related conditions, such as gastroenteritis, upper and lower respiratory tract  infection, acute otitis media, urinary tract infection, neonatal septicaemia and necrotizing  enterocoltis. The protection is through the combination of action of the breast milk  components, such as maternal immunoglobulins, immunocompetent cells, or variety of  anti-microbial compounds. Besides that, breast milk also contains prebiotic substances which  may selectively stimulate the growth of limited number of beneficial bacteria in the gut.  A total number of 100 lactating mothers are needed for this study. Subjects will be recruited  from HUSM Kubang Kerian, USM Main Campus Penang, and Institut Perubatan & Pergigian Termaju  USM Penang. The subjects will be explained on all related information in the consent form  prior to signing. The procedure of collecting sample is hands must be washed before milk  expression, and nipples are cleaned with sterile water and alcohol swab. 15mL of fresh breast  milk will be collected into a tube and stored at -20℃ until further analyses. Inclusion Criteria:  -  Lactating women  -  Willing to commit throughout the experiment Exclusion Criteria:  -  Long term medication due to certain illnesses for over 3 months during pregnancy  -  Gestational diabetes during pregnancy  -  History of diabetes, coronary heart disease, and hypertension in life  -  BMI before pregnancy above 24.9  -  Consuming probiotic product during pregnancy  -  Consuming probiotic product during lactation period

The aim of the current study is to explore the effect of virtual reality on pain in children  who undergo an intrathecal pump refill compared to usual care and distraction. Virtual reality (VR) is a technological rehabilitation tool that allows the user to  experience the interaction with a computer-generated environment. It may provide some  advantages over conventional care: it allows the simulation of realistic environments and  patients feel more motivated by this kind of virtual environment. VR constitutes an enriched  environment with augmented multiple sensory feedbacks (auditory, visual, tactile VR enriched  environment) that has already shown some efficiency in reducing chronic pain. There is  mounting evidence from acute pain conditions, such as wound care, that VR could play a role  as an additional treatment method to relieve pain A possible explanation for its mechanism of  action is provided by "the gate-theory of attention". VR reduces the perception of pain by  diverting attention away from the pain. Most children experience pain and fear when receiving  a medical treatment; two feelings which are closely related and affecting one another.  Moreover, children often describe procedures involving needles as the most stressful portion  of the hospital experience. Children who have been implanted with an intrathecal baclofen  (ITB) pump, need to come to the hospital for a refill approximately every 3 months, depending  on the exact dose. During the refill, the physician places a needle directly into the  reservoir to refill the pump. To alleviate the pain and fear with these refill procedures, it  is hypothesized that VR could alleviate pain and make these refills more feasible. Therefore,  the aim of this study is to evaluate whether VR is reducing pain during a refill procedure,  in children receiving intrathecal drug delivery compared to usual care. Inclusion Criteria:  -  Children with cerebral palsy between 8 and 16 years who have an implanted pump for  intrathecal drug delivery  -  Child and parents have been informed of the study procedures and have given written  informed consent  -  Child and parents willing to comply with study protocol  -  Child and parents are able to speak Dutch/French (questionnaires)  -  Cognitive and language functioning enabling communication between the  physician/researcher and the child Exclusion Criteria:  -  Children with susceptibility to motion sickness or cyber-sickness  -  Children with susceptibility to claustrophobia  -  History of seizures/epilepsia

Caudal block (CB), a regional anesthesia technique, is the most commonly used neuraxial block  method for postoperative pain control in sub-umbilical surgeries in children. However,  peripheral nerve blocks have been reported to be preferred in recent years in the literature  since they provide longer and safer analgesia. One of these blocks, the erector spina plane  (ESP) block, has been shown to provide effective postoperative analgesia when administered  from the lumbar level for sacral and lower abdominal surgeries and urogenital surgeries in  pediatric patients. Circumcision and any lower abdominal surgery in the pediatric population result in a very  painful postoperative period, even when each procedure is evaluated separately. Caudal block  (CB), a regional anesthesia technique, is the most commonly used neuraxial block method for  postoperative pain control in sub-umbilical surgeries in children. However, peripheral nerve  blocks have been reported to be preferred in recent years in the literature since they  provide longer and safer analgesia. One of these blocks, the erector spina plane (ESP) block,  has been shown to provide effective postoperative analgesia when administered from the lumbar  level for sacral and lower abdominal surgeries and urogenital surgeries in pediatric  patients. As far as we know, there is no previous study in the literature comparing CB and  ESP block in pediatric patients. Inclusion Criteria:  -  1-7 years of age  -  ASA (American Society of Anesthesiologists) I-II group  -  Scheduled for circumcision and unilateral lower abdominal surgery at the same session  -  Able to communicate in Turkish  -  Willing to participate to the study (parents and children) Exclusion Criteria:  -  Less than 1 or more than 7 years of age  -  A neurological deficit, bleeding diathesis, or a history of local anesthetic allergy;  an infection or redness in the injection area, congenital lumbar anomaly, liver and/or  kidney disorder, a psychiatric disorder, mental retardation, or communication problems  detected during examination  -  Unwilling to to participate to the study ((parents or children)

The purpose of this study is to estimate phosphodiesterase 10A (PDE10A) occupancy in brain following a single dose of TAK-063. The drug being tested in this study is called TAK-063. TAK-063 is was tested to estimate phosphodiesterase10A (PDE10A) occupancy in the brain following a single dose of TAK-063. This study used positron emission tomography (PET) scans to look at changes in the volume of tissue distribution before and after TAK-063 administration to calculate PDE10A occupancy in the brain. The study enrolled 13 participants. Participants were assigned to a treatment group based on an enrollment schedule. The first 4 participants were assigned to the Pilot Cohort and received one dose of TAK-063 30 mg or 1000 mg tablets. The remaining participants were enrolled into the Main Cohort and  received one dose of TAK-063 at 3, 10, 30 or 100 mg. Participants in both cohorts also received 3 separate intravenous infusions of [^11C]T-773 <8 μg; 400MBq ± 10% followed by a PET scan. This single-centre trial was conducted in Sweden. The overall time to participate in this study was 46 days. Participants made 3 visits to the clinic, including one 3-day period of confinement to the clinic. Participants were contacted by phone on Day 16 for follow-up safety assessments. Inclusion Criteria:   1. Has never previously participated in a positron emission tomography (PET) study (lifetime).   2. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.   3. The participant, informed consent form and any required privacy authorization prior to the initiation of any study procedures.   4. Is a healthy adult male, as determined by a physician based upon medical history and physical examination findings at Screening.   5. Is aged 20 to 45 years, inclusive, at the time of informed consent.   6. Weighs at least 50 kg and less than 100 kg and has a body mass index (BMI) between 18 and 32 kg/m^2 inclusive at Screening.   7. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.   8. Has clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not to be clinically significant (CS) by the investigator or sponsor at screening. Participants must have normal hemoglobin levels.   9. Has a normal magnetic resonance imaging (MRI) scan or findings that are deemed not clinically significant at screening (the MRI scan may be performed on a day after other screening activities have been performed but before dosing). Exclusion Criteria:   1. Has received any investigational compound within 90 days prior to Screening.   2. Has received TAK-063 in a previous clinical study or as a therapeutic agent.   3. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.   4. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.   5. Has a known hypersensitivity to any component of the formulation of TAK-063 or [^11C]T-773.   6. Has a positive urine drug result for drugs of abuse or a positive breathalyzer test for alcohol at Screening or Day -1.   7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the screening visit or is unwilling to agree to abstain from alcohol until discharge from the Phase 1 unit and drugs throughout the study.   8. Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.   9. Intends to donate sperm during the course of the study or within 12 weeks after last dose.  10. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking TAK-063 or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias.  11. The participant, in the opinion of the investigator, has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis frequent [more than once per week] occurrence of heartburn, or any surgical intervention [eg, cholecystectomy]).  12. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1.  13. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen, at Screening.  14. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-In Day -1.  15. Has poor peripheral arterial/venous access or recent arm or wrist trauma.  16. Has donated or lost 450 mL or more of his blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1.  17. Has a Screening or Check-in (Day -1) abnormal (clinically significant) electrocardiogram (ECG).  18. Has a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic and 50 to 90 mm Hg for diastolic, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1).  19. Has a resting heart rate outside the range 45 to 90 beats per minute (bpm), if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1).  20. Has an increase in pulse of ≥30 beats per minute or an increase in pulse ≥120 beats per minute within 3 minutes of standing at Screening.  21. Has a decrease of ≥20 mm Hg in systolic blood pressure or a decrease of ≥10 mm Hg in diastolic blood pressure within 3 minutes of standing at Screening.  22. Has a QT interval with Fridericia correction method (QTcF) >430 ms or PQ interval outside the range 120 to 220 ms, if out of range may be repeated once for eligibility determination within a maximum of 5 minutes, at the Screening Visit or Check-in (Day -1) Visit.  23. Has abnormal Screening laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 the upper limits of normal.  24. Has had administration of radioactive substances or exposure to significant radiation (eg, serial x-ray or computed tomography [CT] scans, barium meal) within the past 12 months prior to Day 1 predose.  25. Has any condition that would prevent an MRI from accurately or safely being performed (eg, claustrophobia, cardiac pacemaker, metallic implants or clips)  26. Has any condition that would prevent the performance of a safe or accurate PET scan.  27. Has any clinically significant MRI finding that in the opinion of the investigator would exclude the participant.  28. Is unwilling to refrain from strenuous exercise from 120 hours before Check-in (Day -1) until discharge from the Phase 1 unit.  29. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale (C-SSRS) or has made a suicide attempt in the previous 6 months.  30. Has abnormal international normalized ratio (INR) or activated prothrombin time (aPTT) or other risk of bleeding disorder.

This phase III trials studies whether maintenance immunotherapy (nivolumab) following  definitive treatment with radiation and chemotherapy (cisplatin) result in significant  improvement in overall survival (time being alive) and progression-free survival (time being  alive without cancer) for patients with intermediate risk human papillomavirus (HPV) positive  oropharynx cancer (throat cancer) that has spread to nearby tissue or lymph nodes. Drugs used  in chemotherapy such as cisplatin work in different ways to stop the growth of tumor cells,  either by killing the cells, by stopping them from dividing, or by stopping them from  spreading. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors.  Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune  system attack the cancer, and may interfere with the ability of tumor cells to grow and  spread. It is not yet known whether chemotherapy and radiation therapy followed by  maintenance nivolumab therapy works better than chemotherapy and radiation therapy alone in  treating patients with HPV positive oropharyngeal cancer. PRIMARY OBJECTIVE:  I. To assess the efficacy of concurrent definitive therapy followed by nivolumab compared  with concurrent definitive therapy followed by observation in terms of overall survival (OS).  SECONDARY OBJECTIVES:  I. To further assess the efficacy of nivolumab compared with observation in terms of:  Ia. To evaluate treatment effect within the subset of patients tested as PD-L1+ .  Ib. To evaluate the prognostic effect of baseline saliva and/or plasma HPV status .  Ic. To evaluate the prognostic effect of mutation burden among patients on the nivolumab arm.  Id. To evaluate the association of 12-week post therapy fludeoxyglucose F-18 (FDG) positron  emission tomography(PET)/computed tomography (CT) OS and progression free survival (PFS).  Ie. To establish the prognostic value of standardized uptake value (SUV) max of primary tumor  or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).  If. To correlate SUV max of primary tumor or nodal metastasis of baseline FDG PET/CT with  PD-L1 expression (positive versus [vs.] negative).  Ig. To compare the PET based therapy response assessment (Hopkins criteria) to the Response  Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessment at 12 week post chemoradiation  therapy, for patients who have a PET/CT scan at 12 weeks.  II. To assess the efficacy of concurrent definitive therapy followed by nivolumab in terms of  progression free survival (PFS).  OUTLINE: Patients are randomized to Arm A or Arm B. Patients in Arm B may cross-over to Arm C  with clearly documented disease progression.  ARM A: Patients receive cisplatin intravenously (IV) over 60 minutes weekly and intensity  modulated radiation therapy (IMRT) 5 days a week for 7 weeks for a total of 35 fractions.  Within 4 weeks after completion of concurrent therapy, patients receive nivolumab IV once  weekly over 30 minutes every 4 weeks for 12 months in the absence of disease progression or  unacceptable toxicity.  ARM B: Patients receive cisplatin IV over 60 minutes weekly and IMRT 5 days a week for 7  weeks for a total of 35 fractions, and then go on observation. Patients will be offered the  option to cross-over to Arm C if they have clearly documented progression within 12 months  from the end of cisplatin/radiation therapy.  ARM C: Patients receive nivolumab IV over 30 minutes every 4 weeks for 12 months in the  absence of disease progression or unacceptable toxicity.  After completion of study treatment, patients are followed up every 3-6 months for 3 years  and then annually for a total of 10 years. Inclusion Criteria:  -  STEP 1: Age >= 18 years  -  STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.  -  STEP 1: Patients must have oropharynx cancer (American Joint Committee on Cancer  [AJCC] 8) that is p16-positive by immunohistochemistry OR p16 equivocal by IHC and HPV  positive by in situ hybridization with the following criteria: >= 10 pack-years, stage  T1-2N2-N3 or T3-4N0-3 (less than 10 pack-years is considered a non-smoker) OR < 10  pack-years, stage T4N0-N3 or T1-3N2-3  -  STEP 1: Patients must not have known hypersensitivity to nivolumab or compounds of  similar chemical or biologic composition.  -  STEP 1: Patients with a history of allergic reactions attributed to platinum-based  chemotherapy agents are excluded.  -  STEP 1: Patients must not have had prior systemic therapy, radiation treatment or  surgery for p16 positive oropharyngeal squamous cell carcinoma (OPSCC).  -  NOTE: Patients who had resection of T1 or T2 carcinoma with no radiation or  chemotherapy are eligible if surgery was done 5 years prior to enrollment  -  STEP 1: Patients must not have received previous irradiation for head and neck tumor,  skull base, or brain tumors.  -  STEP 1: Patients must not receive investigational agents within 4 weeks of enrollment  or at any time while on study.  -  STEP 1: Patients with evidence of distant metastases or leptomeningeal disease (LMD)  are excluded.  -  STEP 1: Patients with uncontrolled inter-current illnesses which in the opinion of the  investigator will interfere with the ability to undergo therapy including chemotherapy  are excluded.  -  STEP 1: Patients with a history of prior or second malignancy are excluded, with the  exception of curatively treated non-melanoma skin cancer, or curatively treated  cervical cancer; additionally, patients curatively treated for malignancy who remain  disease-free at > 2 years of follow up, are not excluded.  -  STEP 1: Absolute neutrophil count (ANC) >= 1500/mm^3 (must be obtained =< 2 weeks  prior to randomization).  -  STEP 1: Hemoglobin (Hgb) >= 8.0 g/dL (must be obtained =< 2 weeks prior to  randomization).  -  STEP 1: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to  randomization).  -  STEP 1: Creatinine clearance of >= 60 ml/min (must be obtained =< 2 weeks prior to  randomization). Creatinine clearance may be measured or calculated. If calculating,  creatinine clearance, use the Cockcroft-Gault formula.  -  STEP 1: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2  weeks prior to randomization).  -  STEP 1: Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase  [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase  [ALT]) within 2.0 times the normal limits (must be obtained =< 2 weeks prior to  randomization).  -  STEP 1: Alkaline phosphatase within 2.0 times the normal limits (must be obtained =< 2  weeks prior to randomization).  -  STEP 1: Patients must not be pregnant or breast-feeding as chemotherapy, radiation,  and immunotherapy may have possible teratogenicity effects; in addition, complications  from pregnancy may interfere with the ability of patients to have an uninterrupted  therapy. All patients of childbearing potential must have a blood test or urine study  within 2 weeks prior to randomization to rule out pregnancy. A patient of childbearing  potential is any female, regardless of sexual orientation or whether they have  undergone tubal ligation, who meets the following criteria: 1) has achieved menarche  at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has  not been naturally postmenopausal (amenorrhea following cancer therapy does not rule  out childbearing potential) for at least 24 consecutive months (i.e., has had menses  at any time in the preceding 24 consecutive months).  -  STEP 1: Patients of childbearing potential must use an accepted and effective method  of contraception or abstain from sexual intercourse for at least one week prior to the  start of treatment, and continue for 5 months after the last dose of protocol  treatment. Patients must also not donate ova during this same time period.  -  STEP 1: Patients must have measurable disease  -  STEP 1: Patients must have tumor measurements with CT of neck and CT of chest (or CT  of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 1  randomization.  -  STEP 1: Patients with active autoimmune disease or history of autoimmune disease that  might recur, which may affect vital organ function or require immune suppressive  treatment including systemic corticosteroids, should be excluded. These include but  are not limited to patients with a history of immune related neurologic disease,  multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome,  myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus  (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD),  Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal  necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be  excluded because of the risk of recurrence or exacerbation of disease. Patients with  vitiligo, endocrine deficiencies including thyroiditis managed with replacement  hormones including physiologic corticosteroids are eligible. Patients with rheumatoid  arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with  topical medication and patients with positive serology, such as antinuclear antibodies  (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ  involvement and potential need for systemic treatment but should otherwise be  eligible.  -  STEP 1: Patients are permitted to enroll if they have vitiligo, type I diabetes  mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone  replacement, psoriasis not requiring systemic treatment, or conditions not expected to  recur in the absence of an external trigger (precipitating event).  -  STEP 1: Patients must not have a condition requiring systemic treatment with either  corticosteroids (> 10 mg/day prednisone equivalents) or other immunosuppressive  medications which are expected to continue during nivolumab administration. Inhaled or  topical steroids and adrenal replacement doses > 10 mg/day prednisone equivalents are  permitted in the absence of active autoimmune disease  -  STEP 1: Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV  viral load must be undetectable on suppressive therapy, if indicated  -  STEP 1: Patients with a history of hepatitis C virus (HCV) infection must have been  treated and cured. For patients with HCV infection who are currently on treatment,  they are eligible if they have an undetectable HCV viral load  -  STEP 1: Patients with a known history of testing positive for human immunodeficiency  virus (HIV) or known acquired immunodeficiency syndrome (AIDS) must have no detectable  viral load on a stable antiviral regimen  -  STEP 1: Patients must not be receiving any other investigational agents.  -  STEP 1: Patient must not have a baseline clinically significant hearing loss, which in  the opinion of the investigator would preclude the use of cisplatin  -  STEP 2: Patients must have progression per RECIST criteria AND tissue-proven  progression on Arm B treatment within 12 months after completion of radiation therapy.  -  STEP 2: ECOG performance status of 0 or 1.  -  STEP 2: Patients must not have known hypersensitivity to nivolumab or compounds of  similar chemical or biologic composition.  -  STEP 2: Patients must not have received non-protocol anti-cancer therapy after  completion of radiation and chemotherapy.  -  STEP 2: ANC >= 1500/mm^3 (must be obtained =< 2 weeks prior to registration).  -  STEP 2: Hgb >= 8.0 g/dL (must be obtained =< 2 weeks prior to registration).  -  STEP 2: Platelet count >= 100,000/mm^3 (must be obtained =< 2 weeks prior to  registration).  -  STEP 2: Creatinine within institutional limits of normal (must be obtained =< 2 weeks  prior to registration)  -  STEP 2: Total bilirubin within 1.5 times the normal limits (must be obtained =< 2  weeks prior to registration).  -  STEP 2: SGOT (AST) or SGPT (ALT) within 2.0 times the normal limits (must be obtained  =< 2 weeks prior to registration).  -  STEP 2: Alkaline phosphatase within 1.5 times the normal limits (must be obtained =< 2  weeks prior to registration).  -  STEP 2: Patients must not be pregnant or breast-feeding as chemotherapy, radiation,  and immunotherapy may have possible teratogenicity effects; in addition, complications  from pregnancy may interfere with the ability of patients to have an uninterrupted  therapy. All women of childbearing potential must have a blood test or urine study  within 2 weeks prior to registration to rule out pregnancy. A women of childbearing  potential is any female, regardless of sexual orientation or whether they have  undergone tubal ligation, who meets the following criteria: 1) has achieved menarche  at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has  not been naturally postmenopausal (amenorrhea following cancer therapy does not rule  out childbearing potential) for at least 24 consecutive months (i.e., has had menses  at any time in the preceding 24 consecutive months).  -  STEP 2: Patients of childbearing potential must use an accepted and effective method  of contraception or abstain from sexual intercourse for at least one week prior to the  start of treatment, and continue for 5 months after the last dose of protocol  treatment. Patients must also not donate ova during this same time period.  -  STEP 2: Patients must have measurable disease at the time of documented progression  -  NOTE: For patients that have undergone salvage surgery for disease recurrence,  measurable disease is not required at the time of registration to Step 2  -  STEP 2: Patients must have tumor measurements with CT of neck and CT of chest (or CT  of neck and FDG PET/CT if standard of care) within 4 weeks prior to Step 2  registration  -  NOTE: Patients that have undergone salvage surgery for disease recurrence prior  to Step 2 are not required to have measurable disease post-resection, but must  have CT of neck and CT of chest (or CT of neck and FDG PET/CT if standard of  care) after salvage surgery and within 4 weeks prior to step 2 registration to  establish a baseline prior to nivolumab Exclusion Criteria: None

This is a multi-center, Phase 2, open-label, single dose level study of PRL3-zumab  monotherapy in patients with unresectable or metastatic solid tumor. The study consists of a Screening Period (Day - 14 to Day -1), a Treatment Period during  which visits will occur every 2 weeks, an End of Treatment visit within 14 days of the  decision to discontinue treatment for any reason, and a Safety Follow-up visit at 14 ± 4 days  after the last dose of study treatment. PRL3-zumab will be administered by intravenous (IV)  infusion till patient meets any of the discontinuation criteria (progressive disease,  clinically or per RECIST v1.1 and iRECIST, intolerable toxicity or withdrawal of consent).  One cycle of treatment will be 4 weeks (2 infusions, 12 days ±2 days apart). Inclusion Criteria:  -  Patients with unresectable or metastatic solid tumors willing to provide signed  informed consent.  -  Histopathological diagnosis and metastatic status cancer at study entry.  -  Must have received at least 1 prior line of systemic therapy for metastatic disease  but no more than 3 prior lines of treatment for metastatic disease.  -  Life expectancy of more than 6 months.  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) score or less than  2.  -  Adequate organ and hematological function.  -  Measurable disease by RECIST v1.1 and iRECIST. Exclusion Criteria:  -  Patient has known untreated or symptomatic central nervous system metastasis.  -  Patient is receiving systemic glucocorticoids or other immunosuppressive treatments  for autoimmune disease or any other medical condition.  -  Patient has experienced a severe hypersensitivity reaction to another monoclonal  antibody.  -  Patient has received treatment with any systemic anti-cancer therapies within 3 weeks  prior to starting study treatment.  -  Patient has undergone radiotherapy ≤ 4 weeks prior to starting study treatment.  -  Patient has received > 3 lines of prior systemic chemotherapy for metastatic disease

The aim of this study is to investigate whether minimally invasive thymectomy achieves  comparable efficacy and safety results compared to open thymectomy in patients with  myasthenia gravis. The planned investigation is a multicenter observational study based on  retrospective (present patient data) and prospective data (questionable outcome data).  Primary hypothesis: Minimally invasive thymectomy is not inferior to open thymectomy in terms  of efficacy and safety (non-inferiority study). Based on large cohort studies of the last decades, the thymectomy has become a central  component of the immunomodulating therapy in MG patients without thymoma detection. Because  randomized studies were missing, remained a residual uncertainty on the importance of  Thymectomy. In the study "Randomized Trial of Thymectomy in Myasthenia Gravis" (MGTX-study)  published 2016 the effectiveness of thymectomy by patients without thymoma detection has been  indisputable confirmed. A significant improvement of the patient's complaints and the  reduction of the immunosuppressive drugs were particularly evident by early onset MG (EOMG)  two to three years after performing a complete resection of the thymic tissue.  While the MGTX study (with an open operative procedure) was being done, the  minimally-invasive thymectomy has gained more and more acceptance. From a surgical point of  view, the minimally invasive thoracoscopic procedure represents a gentler alternative.  According to the momentaneous clinical-scientific point of view, further studies are  necessary to compare both procedures. Furthermore, the MGTX study included only patients with  generalized MG and positive anti-Acetylcholine Receptor (AChR)-antibodies, who were younger  than 65 years, so that the relevance of thymectomy in other important subgroups, such as late  onset MG (LOMG), the ocular MG (OMG), as well as the patients without detected antibodies  (seronegative MG patients), who represent about 10 % of whole population of MG patients, is  still not clear. Inclusion Criteria:  -  Patients with Myasthenia Gravis  -  Age ≥18 years Exclusion Criteria:  -  a proper communication with the patient is not possible  -  an informed consent could not be signed  -  a patient reject a participation or requires breaking up

To evaluate if the use of Hemopatch in axillary lymph node dissection shows potential in  reducing clinically significant seroma and seroma related complications, which might serve as  a basis for a randomized controlled trial. Rationale:  Sentinel lymph node biopsy has reduced the number of patients needing to undergo axillary  lymph node dissection (ALND). However, axillary lymph node dissection is part of curative  therapy for a large group of patients with advanced invasive breast cancers and melanoma.  Seroma may cause symptomatic discomfort requiring needle aspiration and is often associated  with infection, wound dehiscence, skin necrosis, persistent fibrotic encapsulated seromas and  may even delay adjuvant therapies [1]. Therefore, extensive research in finding the best  technique in reducing seroma is needed.  Substances intended to seal small blood vessels by triggering collagen and fibrinogen  synthesis supporting surgical hemostasis, are assumed to be able to contribute to sealing of  these lymphatic vessels. Contradicting results were found in the effect of several  fibrin-glue coated collagen patches [2-5] and fibrin glue [6,7]. Furthermore, the use of  electrothermal bipolar vessel sealing system (LigaSure) in axillary dissection showed no  significant reduction in rate of aspiration of seroma [8].  This pilot study is intended to assess the value of a haemostatic sealant (Hemopatch), a pad  of collagen derived from bovine dermis, coated with NHS-PEG (pentaerythritol polyethylene  glycol ether tetra-succinimidyl glutarate), in reducing seroma related complications after  ALND with the advantage that this sealant is pliable and flexible.  Objective:  To evaluate if the use of Hemopatch in axillary lymph node dissection shows potential in  reducing clinically significant seroma and seroma related complications, which might serve as  a basis for a randomized controlled trial.  Study design:  A prospective cohort will be compared to a historical control group. Eighteen consecutive  patients will undergo axillary lymph node dissection and after completion of lymphadenectomy,  Hemopatch will be applied to the axillary surgical field. These results will be compared to  the results of a historical control group consisting of 46 patients who have undergone ALND  without the Hemopatch between January 2014 and December 2018.  Follow-up will be conducted for three months postoperatively.  Study population:  Patients of 18 years or older, diagnosed with stage III melanoma or breast cancer and  indication for wide local excision (WLE) and/or axillary lymphadenectomy (ALND).  Intervention (if applicable):  Application of Hemopatch after standard axillary lymph node dissection.  Main study parameters/endpoints:  Proportion of patients treated with Hemopatch who develop clinically significant seroma.  Nature and extent of the burden and risks associated with participation, benefit and group  relatedness:  Patients will be informed about the study before inclusion in the outpatient clinic. Informed  consent will be obtained in the outpatient clinic a week after patients were initially  informed. Postoperative check-ups will be done more frequently. Standard postoperative  check-ups are planned at one week and three months. Additional study postoperative check-up  will be performed at six weeks. Therefore, patients will be required to undergo one  additional check-up. During out patients' visits, the wound will be evaluated and patients  will be asked to fill in a questionnaire. Application of the Hemopatch is expected to reduce  clinically significant seroma after ALND. The only potential risk for the patient is that the  Hemopatch is ineffective. Inclusion Criteria:  -  Male and female patients of 18 years or older.  -  Patients with melanoma and indication for axillary lymph node dissection.  -  Patients with breast cancer and indication for breast conserving therapy and axillary  lymph node dissection  -  Patients with an indication for secondary axillary lymph node dissection. Exclusion Criteria:  -  Patients with breast cancer who have an indication for modified radical mastectomy.  -  Unable to comprehend implications and extent of study and sign for informed consent  -  Pregnant women  -  Patients included in another breast related clinical trial

Aging is associated with significant declines in muscle mass, strength, and physical  performance, all of which lead to disability, loss of independence, and adverse clinical  outcomes. Obesity exacerbates these age-related declines in function and is associated with  poorer clinical outcomes and quality of life. Weight loss can also worsen age-related loss of  muscle mass and decrease bone mineral density. The overall goals of this study are to  determine if the short-term functional benefits of intentional weight loss are sustained  long-term, and to examine the long-term benefits and risks of weight loss. Obesity exacerbates age-related declines in function and is associated with poorer clinical  outcomes and quality of life. Although clinical trials conducted study teams show that  diet-induced weight loss interventions in obese older adults, when combined with exercise,  improve body composition and physical and metabolic function in the short-term, the overall  safety and long-term benefits of intentional weight loss in older adults remain  controversial. Weight loss can also worsen age-related loss of muscle mass and decrease bone  mineral density. Because of these concerns, health care providers are reluctant to recommend  weight loss in obese older adults. The goal is to determine whether weight loss-induced  improvements in body composition and physical and metabolic function observed in short-term  clinical trials persist over time is critical to inform geriatric obesity treatment. Inclusion Criteria:  -  All former participants from the five intervention trials who respond to our  recruitment strategies will be scheduled for clinic/home visits or a phone interview. Exclusion Criteria:  -  None - all former participants from the five intervention trials are eligible

The purpose of this prospective, non-randomized, single-center pilot exploratory study is to  investigate whether established circulating tumor cell (CTC) cultures have a similar response  to targeted therapy treatment as the in vivo (patients') disease. This study will isolate circulating tumor cells (CTCs) from blood samples taken from patients  with liver and/or lung metastases who will receive systemic treatments. The CTCs will be  cultured and given the same treatment as the patient received. The main goals of this project  are 1) to assess CTC cultures' treatment response and compare the in vitro response to the  clinical response, and 2) determine the sensitivity, specificity, positive predictive value  (PPV) and negative predictive value (NPV) of CTC cultures' response in predicting clinical  response including complete response (CR), partial response (PR), stable disease (SD) and  progressive disease (PD). Inclusion Criteria:  -  Patients with a metastatic solid tumor malignancy with either liver and/or lung  metastasis. Patients with newly diagnosed metastatic disease who have not had systemic  therapy or are progressing on systemic therapy fitting one of the following cohorts:  -  Patients had a tumor or liquid biopsy with molecular analysis (genomic analysis  or other type of molecular characterization) resulting in a therapeutic target  with planned targeted therapy by the patient's treating physician.  -  Gastric cancer patients who have failed the first and second line chemotherapy.  -  Bladder cancer patients (with liver and/or lung metastasis) who will receive  systemic treatment.  -  Scheduled to initiate systemic treatment for management of their disease. The systemic  treatment will be either cytotoxic chemotherapy or targeted therapy but not checkpoint  inhibitor immunotherapy.  -  ≥18 years of age  -  Written informed consent obtained and signed  -  Able to have blood collection without excessive difficulty Exclusion Criteria:  -  Patient unwilling or unable to complete informed consent  -  Currently pregnant or lactating women  -  Physical or psychological inability to complete sample collection for any reason  including but not limited to: inability to tolerate any study procedures, any physical  limitation that would undermine the safety of the subject in the study, or any  psychiatric or neurological condition that inhibits full comprehension of study  requirements and inability to complete informed consent, as determined by treating  physician

Postmenopausal women with differentiated thyroid cancer (DTC) taking suppressive doses of  levothyroxine (L-T4) are thought to have accelerated bone loss and increased risk of  osteoporosis. Therefore, the investigators try to investigate the effects of  99Tc-MDP,alendronate sodium in postmenopausal women with DTC under TSH suppression and  osteoporosis. Differentiated thyroid cancer (DTC) has become one of the most common endocrine malignancies.  According to American Thyroid Association (ATA) and Chinese Thyroid Association (CTA), most  of DTC patients undergo total or near total thyroidectomy, radioiodine ablation and TSH  (thyroid stimulating hormone) suppression. Osteoporosis (OS) and fractures are important  comorbidities in patients with DTC, with potential negative impact on quality of life (QOL)  and survival. The main determinant of skeletal fragility in DTC is the TSH suppression.  Postmenopausal women with DTC under TSH suppression therapy are more vulnerable to OS.  Technetium-99 methylene diphosphonate (99Tc-MDP) is a decay product of 99mTc-MDP (used for  bone scintigraphy) and a novel bisphosphonates, which has been used in China for diseases  like rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteochondral lesions of the  talus, etc. However, as a member of bisphosphates, little attention has been paid to its  anti-OS effect for DTC under TSH suppression. Inclusion Criteria:  (1) They were pathologically diagnosed with DTC including papillary or follicular  carcinoma. (2) They received a near total thyroidectomy and radioiodine treatment. (3) TSH  suppression should be at least one year before the study. (4) Bone mineral density (BMD) in  lumbar spine and/or hip was tested by Dual-energy X-ray absorptiometry (DXA) at baseline, 6  month (m) and/or 12m follow up. 5) The diagnosis of osteoporosis was T-score ≤-2.5 SD at  the lumbar spine, or hip. Exclusion Criteria:  1. patients having medications for osteoporosis before TSH suppression treatment;  2. secondary osteoporosis ;  3. severe liver or kidney disease;  4. myelosuppression;  5. digestive disease;  6. long term use of immunosuppressive agent, estrogen or estrogen receptor modulators.  This study was approved by the Institutional Review Board of Hospital Research Ethics.  All the patients were fully acquainted with their treatment and consented to  participate in the clinical trial.

This phase 2b study will evaluate safety, tolerability, and immunogenicity of an RSV vaccine  when given together with Tdap in approximately 710 healthy nonpregnant women 18 through 49  years of age. This study will evaluate non-inferiority of RSV vaccine when given with Tdap  and vice-versa. This Phase 2b study will evaluate safety, tolerability, and immunogenicity of an RSV vaccine  when given together with Tdap in approximately 710 healthy nonpregnant women 18 through 49  years of age.  The participants will be equally split into 5 treatment groups: One of a possible two dose  levels of RSV vaccine (the higher dose level will be formulated with an aluminum hydroxide  adjuvant) with either the Tdap or Placebo, or a Tdap and placebo combination.  This study will evaluate non-inferiority of the Tdap when co-administered with RSV vaccine  candidate and vice-versa by measuring participants' immune response through appropriate  antibody and component levels 1 month after vaccination. Inclusion Criteria:  -  Healthy women ≥18 and ≤49 years of age who are of childbearing potential or not of  childbearing potential. (Healthy participants with preexisting stable disease, defined  as disease not requiring significant change in therapy or hospitalization for  worsening disease during the 6 weeks before enrollment, can be included.)  -  Willing and able to comply with all scheduled visits, treatment plan, lifestyle  considerations, and other study procedures.  -  Expected to be available for the duration of the study and can be contacted by  telephone during study participation.  -  Body mass index (BMI) of <40 kg/m2 at the time of the consent.  -  Capable of giving signed informed consent as which includes compliance with the  requirements and restrictions listed within. Exclusion Criteria:  -  Other acute or chronic medical or psychiatric condition including recent (within the  past year) or active suicidal ideation or behavior or laboratory abnormality that may  increase the risk associated with study participation or investigational product  administration or may interfere with the interpretation of study results and, in the  judgment of the investigator, would make the participant inappropriate for entry into  this study.  -  Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or  hepatitis B virus (HBV).  -  History of severe adverse reaction associated with a vaccine and/or severe allergic  reaction (eg, anaphylaxis) to any component of the vaccines being administered in the  study.  -  History of latex allergy.  -  Immunocompromised participants with known or suspected immunodeficiency, as determined  by history, laboratory tests, and/or physical examination.  -  Any contraindication to Tdap (including encephalopathies).  -  History of autoimmune disease or an active autoimmune disease requiring therapeutic  intervention, including but not limited to systemic or cutaneous lupus erythematosus,  autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple  sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura,  glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis),  psoriasis, and insulin dependent diabetes mellitus (type 1).  -  Bleeding diathesis or condition associated with prolonged bleeding that would, in the  opinion of the investigator, contraindicate intramuscular injection.  -  Women who are pregnant or breastfeeding.  -  Previous vaccination with any licensed or investigational RSV vaccine, or planned  receipt of nonstudy RSV vaccine throughout the study.  -  Treatment with immunosuppressive therapy, including cytotoxic agents or systemic  corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt  throughout the study. If systemic corticosteroids have been administered short term  (<14 days) for treatment of an acute illness, participants should not be enrolled into  the study until corticosteroid therapy has been discontinued for at least 28 days  before investigational product administration. Inhaled/nebulized, intra-articular,  intrabursal, or topical (skin or eyes) corticosteroids are permitted.  -  Receipt of blood/plasma products or immunoglobulin within 60 days before  investigational product administration or planned receipt throughout the study.  -  Current alcohol abuse, marijuana abuse, or illicit drug use.  -  Vaccination within 5 years with DTaP or tetanus and diphtheria toxoids adsorbed (Td)  vaccine before investigational product administration.  -  Investigator site staff members directly involved in the conduct of the study and  their family members, site staff members otherwise supervised by the investigator, or  Pfizer employees, including their family members, directly involved in the conduct of  the study.  -  Current febrile illness (oral temperature ≥38.0C [≥100.4F]) or other acute illness  within 48 hours before investigational product administration.  -  Receipt of any inactivated vaccine within 14 days and any live vaccine within 28 days  before or anticipated receipt of any vaccine within the 14 days after investigational  product administration.  -  Receipt of short-term (<14 days) systemic corticosteroids. Investigational product  administration should be delayed until systemic corticosteroid use has been  discontinued for at least 28 days. Inhaled/nebulized, intra-articular, intrabursal, or  topical (skin or eyes) corticosteroids do not require temporary delay of  investigational product administration.

Based on the changing understanding of carious biofilm development and caries progression,  Sealing carious dentine beneath a restoration deprives the caries biofilm of nutrients and  alters the environment sufficiently to slow or arrest lesion progression. This has the added  benefit of avoiding pulp exposure and subsequent treatment .The evidence base supporting the  biological approaches which include Hall technique has been steadily increasing in the last  few years. This has given rise to a growing trend towards a biological approach by Paediatric  dentists and has led to an increasing concern about the merits of conventional approach in  treatment of carious primary molars . In orofacial development of the child, preservation of the primary dentition for as long as  possible is of great importance. As primary teeth maintain arch length and preserve  masticatory function. Unfortunately, the occurrence of cavitated caries lesions is still a  problem in developed and developing countries, with an increasing prevalence, particulary in  developing communities, conflicting with a general descending trend in prevalence worldwide.  The management of carious primary molars in children is problematic, additionally, primary  teeth commonly remain unrestored, especially in the younger children,The high levels of  dental disease in primary teeth, and its inadequate management, remains a major public health  issue for children, and one with a significant impact on their lives. In addition many  children are having to accept toothache as a part of their childhood. Set against this  background, there would seem to be some scope for the investigation of alternative approaches  to the management of carious primary teeth. If an alternative technique was found to be  simpler and more acceptable to children, their parents and general dental practitioners than  the conventional restorative approach, yet just as effective, then it might be more readily  applied in the general practice setting.  A novel, simplified method of using stainless steel crwons, the Hall Technique, has been  investigated. According to American Academy of Pediatric Dentistry, Hall technique calls for  cementation of a Stainless steel crown over a caries-affected primary molar without local  anesthetic, caries removal or tooth preparation, This technique was developed for use when  delivery of ideal treatment wasn't feasible.  As the crown is fitted with no occlusal reduction in the Hall technique, it was observed in  several studies that the occlusion would has been temporarily opened and returned to the  pretreatment situation within 2 weeks and no child reported Tempromandibular joint pain. This  goes in accordance with the study of Innes et al., as they stated that after placement of  stainless steel crowns using the Hall technique, the occlusion returns to the pretreatment  situation within 15-30 days. Also, Dr. Hall stated that the occlusion tended to equilibrate  by the next recall appointment and none of her patients reported Tempromandibular joint pain.  A published data from Dr Hall's practice records has indicated that Hall technique might have  similar survival rates to other, more conventional, restorative options currently being used  in Primary Care. In addition, avoiding the use of Local anesthesia and rotary instruments for  tooth preparation and caries removal might mean that the technique is less demanding of both  children and their dental team. The technique is therefore minimally invasive and can be  expected to cause less discomfort than conventional treatment approaches. This aspect could  be a considerable advantage as the Hall technique is a child centered approach and it is not  surprising that the first data published on patient perceptions of the hall technique are  promising. It was reported a clear difference in levels of discomfort, subjectively assessed  by the operators, between the Hall technique and a conventional treatment approach. The Hall  stainless steel crowns caused 'no discomfort' to 'mild discomfort' in comparison to the  conventional restorations. Several conducted studies showed that the majority of the  children, their caretakers and dentists expressed a preference for the Hall technique to the  conventional restorations.  The Hall Technique embraces changing concepts of managing dental caries, moving from the  dogma requiring its complete surgical excision, even at the expense of cavity size and pulpal  health, to the understanding that caries in dentine can be slowed, arrested, and possibly  even reversed, within a meticulously sealed environment. It is known that the microflora in  sealed carious dentine changes, with the predominating organisms no longer being cariogenic  having been sealed from the oral environment. This may be important in the apparent arrest of  caries progression.  Owing to its non invasive design, acceptance by patients and rate of restoration longevity,  the Hall technique maybe an improved treatment option to increase access to care, decrease  rates of untreated caries and provide a restoration that will allow for natural tooth  exfoliation.  In the last few years, conventional restorations including complete removal of carious tissue  with or without pulp therapy for the treatment of carious lesions in primary teeth have been  challenged and a more biological approach has been suggested. This has given rise to a  growing trend towards a biological approach by paediatric dentists and has led to an  increasing concern about the merits of the conventional approach and whether to retain this  treatment modality as the standard technique in restoring primary teeth or to adopt the  biological approach as the treatment norm. Inclusion Criteria:  -  Children:Aged 5 to 7 years, in good general health and medically free.The parents  provided a written informed consent.  -  Primary molar with deep dentin caries involving occlusal and or occluso proximal  surfaces.  -  Vital pulp with absence of clinical signs and symptoms of irreversible pulpitis such  as spontaneous pain. Only presence of pain provoked with stimulation, such as  complaints of food impaction when eating is allowed.  -  Absence of clinical swelling or pus exaudate or fistula of soft or periodontal  tissues.  -  Absence of abnormal tooth mobility  -  Absence of pain on percussion Exclusion Criteria:  -  Patients experience any signs or symptoms of pulpal or periapical pathology.  -  Patients with systemic diseases requiring special dental consideration.  -  Unmotivated uncooperative patients.  -  Patients unable to attend follow up visits.

TB-Speed HIV is a prospective multicentre management study evaluating the safety and  feasibility of the recently proposed PAANTHER TB treatment decision algorithm for  HIV-infected children with presumptive TB. It will be conducted in four countries with high  and very high TB (Tuberculosis) incidence (Côte d'Ivoire, Uganda, Mozambique, and Zambia)  which have not participated in the study that developed the PAATHER algorithm. The ANRS 12229 PAANTHER 01 (Pediatric Asian African Network for Tuberculosis and HIV  Research) study, which enrolled 438 HIV-infected children of median age 7.3 (IQR: 3.3 - 9.7)  years with presumptive TB in four countries (Burkina Faso, Cameroon, Cambodia, Vietnam) from  2011 to 2014, aimed at developing a diagnostic prediction score and algorithm for TB  treatment decision in HIV-infected children. This was the first study developing a TB  diagnostic score exclusively in HIV-infected children, using methods recommended for  diagnostic prediction models. Based on microbiological, clinical and radiological features,  the best scoring system obtained had a sensitivity of 88.6% and specificity of 61.2% when  Xpert MTB/RIF was included in the algorithm. The investigators showed previously that  mortality is high in children with both confirmed and unconfirmed TB and that initiation of  anti-TB treatment, that occurred at a median time of 7 (IQR: 5 - 11) days in the study, led  to delayed ART initiation, which is associated to significantly increased mortality. The  score, based on easily collected clinical features, chest radiographic features, Xpert  MTB/RIF results, and abdominal ultrasonography, could enable same-day TB treatment decision.  Abdominal ultrasonography has shown promise for the diagnosis of TB in both HIV-infected  adults and children. In the PAANTHER study, it detected abdominal lymphadenopathy in 50% of  culture confirmed TB cases and 35% of all confirmed and unconfirmed cases, with a specificity  of 85%.  Developed in tertiary research-experienced health facilities, the PAANTHER score could enable  standardized treatment decision in HIV-infected children with presumptive TB, and could be  recommended for extensive use in secondary and primary healthcare settings where most of  these children are seeking care. However, external validation studies are now needed to  assess the predictive performance of the PAANTHER diagnostic score on independent datasets.  The PAANTHER TB treatment decision algorithm will be used for a TB treatment decision by site  clinicians in all children enrolled in the study. Validation of the algorithm will be  performed by evaluating the safety of withholding TB treatment in children not initiated on  treatment as per the PAANTHER TB treatment decision algorithm. The safety of this strategy  will be carefully assessed through review of safety reports every 4 to 6 months during study  conduct by the safety sub-committee of the SAB.  Occurrence of algorithm failures in terms of missed TB cases (TB cases subsequently detected  among untreated cases, i.e. false negatives) and cases with unlikely TB among those initiated  on TB treatment as per the algorithm (cases not secondarily validated as confirmed or  unconfirmed TB cases by the expert committee, i.e. false positives) will enable to estimate  the negative and positive predictive values of the algorithm.  A centralized international Expert Committee will clinically review and validate TB diagnosis  in children. This will enable assessment of the added value of new markers (MLR and CRP) and,  if need be, to propose a new version of the score based on an optimised predicted  probability.  The TB-Speed HIV study will be implemented in 7 tertiary healthcare level hospitals in  capital cities of Côte d'Ivoire, Uganda, Mozambique, and Zambia. A total of 550 HIV-infected  children (aged < 15 years) with clinically suspected TB (presumptive TB) will be enrolled,  using standard entry criteria. The inclusion period will last until all sites have reached  the expected number of children enrolled. Inclusion Criteria:  1. Children aged 1 month to 14 years  2. Documented HIV-infection (i.e., confirmed before entry into the study)  3. Presumptive TB based on at least one criteria among the following:  1. Persistent cough for more than 2 weeks  2. Persistent fever for more than 2 weeks  3. Recent failure to thrive (documented clear deviation from a previous growth  trajectory in the last 3 months or Z score weight/age < 2)  4. Failure of broad spectrum antibiotics for treatment of pneumonia  5. Suggestive CXR features  OR  History of contact with a TB case and any of the symptoms listed under point 3 with a  shorter duration (< 2 weeks)  4. Informed consent signed by parent/guardian Exclusion Criteria:  Ongoing TB treatment or history of intake of anti-TB drugs in the last 3 months (isoniazid  alone or rifampin/isoniazid for preventive therapy is not an exclusion criteria)

This trial examines the impact of a topical formulation of rapamycin on dermal thickness and  senescence. Aging of the skin is the most prominent feature of the aging process, being caused by  multiple factors such as intrinsic aging process and UV light exposure.  Dermal atrophy, also called skin atrophy or atrophy, is a disorder manifesting thinning or  depression of skin due to reduction of underlying tissue. Dermal atrophy is a major clinical  problem in the elderly population. Loss of dermal integrity leads to increased fragility of  the skin and precludes the use of intravenous lines in many cases. Skin tears are a  significant concern in elderly individuals directly related to dermal atrophy. Impairment in  wound healing is an important clinical sequelae of reduced dermal integrity leading to an  increase in the number of the infections and complications following injury. Seborrheic  keratosis, which comprise focal areas of epidermal thickening, can occur, possibly  representing a response to damage. It has been estimated that 100% of individuals over 50  years of age harbor at least one of these lesion. There is not treatment for dermal atrophy  and seborrheic keritoses require excision if they become large enough to cause discomfort or  distress.  Therefore, there is a need to develop novel compositions and methods for treating or  preventing certain age-related dermal conditions.  Rapamycin is an FDA approved drug that has been in clinical use for over 15 years. Systemic  application of rapamycin has been a central part of immuno suppressive therapy for transplant  patients in combination with other immuno suppressants. The safety record for systemic use of  rapamycin is excellent and few side effects are associated with extended use. Inclusion Criteria:   -  Healthy adults Exclusion Criteria:  -  Individuals with any chronic disease will be excluded from the study including those  with the following conditions:  -  Diabetes  -  Any type of Malignancy  -  Severe coronary artery disease  -  HIV infection  -  Hepatitis C or B  -  Any sign of skin disorder or disease aside from normal aging, dermal atrophy, or  seborrheic keratoses.  -  Premenopausal women will be excluded  -  Patients taking the following medications will be excluded:  -  Cyclosporin  -  Calcium channel blockers: diltiazem, verapamil  -  Antifungal agents e.g. clotrimazole, fluconazole, itraconazole  -  Antibiotics: clarithromycin, erythromycin, rifampicin  -  Anticonvulsants: carbamazepine, phenobarbitone, phenytoin  -  Antinausea drugs e.g. metoclopramide  -  Other drugs e.g. danazol, protease inhibitors (e.g. for HIV and hepatitis C  including ritonavir, indinavir, boceprevir, and telaprevir)  -  Grapefruit juice  -  St John's wort (Hypericum perforatum, hypericin)

The main objective of this study is to examine the transfusion rate and appropriateness in  patients undergoing elective knee and hip replacement surgery at Siriraj Hospital The main objective of this study is to examine the transfusion rate and appropriateness in  patients undergoing elective knee and hip replacement surgery at Siriraj Hospita by reviewing  data from previous medical records (retrospective chart review). Inclusion Criteria:   -  Patients Having elective Hip or Knee Arthroplasty in Siriraj Hospital Exclusion Criteria:   -  none

Patient's pain level and narcotic requirements will be evaluated after routine outpatient  Otolaryngology procedures. This will be done by having study participants record their pain  level and medication usage from home. It is routine practice to give narcotic medication after surgery for pain control however the  abuse of prescription medications has become the fastest growing drug problem in the United  States. Research has shown that post operative pain for some common Ear, Nose, and Throat  (ENT) procedures are not severe but there is limited data looking at patient narcotic needs  and their usage pattern to help inform physicians on how much to prescribe.  The objective of this study is to evaluate patient pain level in the immediate post-operative  period and quantify pain medication usage in patients who undergo outpatient ENT surgeries.  Patients who undergo the following procedures will be invited to participate: thyroidectomy,  parathyroidectomy, parotidectomy, tympanoplasty, mastoidectomy, endoscopic sinus surgery, and  septoplasty. All patients will receive Hydrocodone/acetaminophen and Ibuprofen in standard  dosage and assigned to one of two groups before surgery. Group 1 will use the narcotic  medication for pain control and ibuprofen for breakthrough pain. Group 2 will use ibuprofen  for pain control and the narcotic medication for breakthrough. Patients will fill out a data  sheet for 7 days recording their pain level three times per day as well as pain medication  usage for each day. This will be collected on their first clinic visit after surgery at which  point the patient's involvement is completed. Inclusion Criteria:  Patients undergoing one of the following outpatient procedure:  -  Septoplasty  -  Unilateral or Bilateral Functional endoscopic sinus surgery  -  Tympanomastoidectomy  -  Tympanoplasty  -  Total or Partial Thyroidectomy  -  Parathyroidectomy  -  Parotidectomy.  -  Age >18 years and < 89 years Exclusion Criteria:  -  Age < 18 years or > 89 years  -  Post operative hospital admission  -  Allergy to Hydrocodone  -  Allergy or contraindication to Ibuprofen or NSAIDs  -  Pregnancy  -  Hepatic disease  -  Chronic kidney disease  -  Sickle cell anemia

Cataract (cloudiness of the lens) is the major cause of avoidable child blindness in the  world and affects 1 in 3000 UK infants. Screening may fail to detect a cataract in an  affected child (false-negative) or mistakenly suggest there is a cataract (false positive)  triggering urgent unnecessary referral.  Screening is currently undertaken using an ophthalmoscope into the eye to assess the reddish  reflected light (red-reflex). This study aims to test if screening using a new hand-held  digital imaging device (Neocam) is more accurate than the ophthalmoscope for newborn eye  screening. Cataract (cloudiness of the lens) is the major cause of avoidable child blindness in the  world and affects 1 in 3000 UK infants. Cataracts are present in both eyes in more than half  of the babies affected. Surgery is required by 8 weeks of age to prevent permanent visual  impairment at this critical time of vision and brain development. All UK babies are examined  (screened) for cataract twice within the first 8 weeks of life but late diagnosis continues  to be a problem, causing avoidable visual impairment in some affected children.  Screening may fail to detect a cataract in an affected child (false-negative) or mistakenly  suggest there is a cataract (false positive) triggering urgent unnecessary referral, parental  anxiety and wasted NHS resources. Screening is currently performed by midwives and doctors  shining a bright white light torch (an ophthalmoscope) into the eye to assess the reddish  reflected light (red-reflex), similar to "red eye" seen in flash photos. Cataract causes a  dark shadow on the red-reflex but the test can be difficult because bright light causes the  pupils to constrict and the babies to forcefully shut their eyes. Assessment is particularly  difficult in ethnic minority infants since eye pigmentation affects the hue and brightness of  the red-reflex.  This study aims to test if screening using a new hand-held digital imaging device (Neocam) is  more accurate than the ophthalmoscope for newborn eye screening. Neocam painlessly images the  eye's reflection firstly to infrared light and then to a brief green light flash. Its  infrared light causes no pupil constriction or avoidance response and the reflection is  bright and consistent regardless of the baby's ethnicity. Its brief green flash and immediate  imaging allows a photo of the red-reflex to be captured before the pupil has time to  constrict.  To compare the accuracy of both tests, the investigators seek to enrol 140,000 newborn babies  in a two year study period. All babies will have both the current ophthalmoscope screening  test and additional Neocam imaging. If either test is potentially abnormal, the baby will be  referred for specialist examination.  A more accurate screening test could prevent life-long disability and reduce costs to the NHS  and society. This study will allow a future estimation of what these savings might be and  whether changing to a digital imaging screening service might be justified. The result may  have an impact on eye screening world-wide to prevent childhood blindness from cataract. Inclusion Criteria:  All newborn babies having the newborn physical examination Exclusion Criteria:  None

BACKGROUND  An essential part of neonatal care is providing nutrition to ensure that babies grow and  develop. Providing this can be difficult in premature babies because their intestines are  underdeveloped. They often have difficulty digesting milk so feeds are introduced gradually.  To help babies grow and develop during this period, additional nutrition may be provided as a  fluid into a vein; this is called "parenteral nutrition" (PN). Unfortunately, PN increases  the risk of serious complications like bloodstream infection (also known as "sepsis"). For  babies who are moderately premature there is little evidence to guide decision making about  which babies will benefit from PN. This group of babies have more reserves of fat and are  less dependent on PN, but are still at risk of sepsis. As a consequence, some doctors use PN  and others do not.  AIMS  Firstly, to describe which babies are given PN during the first postnatal week in neonatal  units in England, Scotland and Wales.  Secondly, to determine whether in babies born 7-10 weeks preterm (moderately premature),  providing PN in the first week after birth, compared to not to providing PN, improves  survival to discharge from the neonatal unit.  Finally, to evaluate if the early use of PN in moderately preterm babies affects other  important outcomes in the neonatal core outcomes set.  IMPORTANCE  This work will describe the extent of PN use in England, Scotland and Wales. This is  currently unknown. This project will improve understanding of the balance of benefits and  harms of PN use in premature babies and will help doctors and parents make informed treatment  choices.  METHODS  The investigators will use the National Neonatal Research Database (NNRD) to study all babies  born in England, Scotland and Wales; they will identify which babies were given PN during the  first week, and which were not. The investigators will use the NNRD to identify babies born  7-10 weeks prematurely and compare outcomes in babies that were given and not given PN in the  first week after birth. The investigators will use statistical techniques to identify two  sets of babies in the NNRD who are very similar (in terms of how prematurely they were born,  their birth weight, and so on), the only difference being whether they were given PN or not.  As the two groups will be similar any difference in their outcomes (such as survival) is  likely to be due to whether or not they received PN. Premature birth abruptly ends the transplacental transmission of nutrients that allows normal  foetal growth and development. Providing adequate nutrition is essential to allow premature  babies to continue to grow and mature. Very preterm infants often have difficulty tolerating  adequate volumes of milk feeds shortly after birth and so are given supplemental parenteral  nutrition (PN). Preterm babies are among the highest PN users of all NHS patients. It has  been estimated that PN is received by around 70% of neonatal unit admissions but it is not  known exactly which babies receive PN. In addition, how PN affects outcomes has never been  tested in a large scale, randomized, placebo controlled neonatal trial.  It is known that PN carries well established risks, of which the most serious and the most  common is sepsis with estimates of risk ratios varying from 2.2 to 14.6. In addition there is  a growing body of evidence that use of PN within the first seven days of admission to an  intensive care unit is associated with worse outcomes in critically unwell adults and  children. A subgroup analysis of the paediatric intensive care unit population focusing on  neonates showed an increase in infections with early PN use. This suggests that uncertainty  exists over the benefit of giving neonates PN in the early postnatal period. It is generally  accepted that PN is beneficial to extremely preterm neonates, but in moderately preterm  neonates the effect that PN use has on neonatal survival has never been conclusively  demonstrated.  The uncertainty over how PN use affects neonatal outcomes is reflected by the wide variety in  how PN is used in different units with large variation in use, timing and composition of PN.  This is, in part, due to the lack of clear evidence of how PN affects neonatal outcomes like  growth and survival. Neonates are also vulnerable to unanticipated treatment effects which  can occur in different organ systems and so it is important to show that PN is not  detrimental to important neonatal outcomes.  The postmenstrual age at which the nutritional benefits of PN outweigh the risks in  moderately preterm babies (30-33 weeks postmenstrual age) is unknown. It is therefore  unsurprising that their nutritional management is very variable. In moderately preterm  neonates in 2012 and 2013 across England, Scotland and Wales PN was given to 45% of neonates,  suggesting clinician equipoise around the balance of benefit to risk. Identifying whether  moderately preterm neonates benefit from PN would have important implications for practice in  the UK. This work will provide information to guide practice and inform future research.  In summary, PN is widely used in neonates but it is not known exactly how it is used in the  UK. It is known to have risks and benefits but there is insufficient evidence to guide  practice in moderately preterm neonates.  Study objectives:  -  To describe the use of PN in neonatal units across England, Scotland and Wales.  -  To identify if use of PN in the first seven postnatal days affects survival in neonates  born between 30 and 33 weeks postmenstrual age.  -  To explore how PN use in the first seven postnatal days affects other important neonatal  outcomes in neonates born between 30 and 33 weeks postmenstrual age.  Study design:  Project A: an epidemiological survey of practice using the National Neonatal Research  Database (NNRD).  Project B: a retrospective cohort study of matched groups of babies using data held in the  NNRD. Inclusion Criteria:  Project A:  -  Must be born between 1st January 2012 and 31st December 2017  -  Must be admitted to a National Health Service (NHS) neonatal unit in England, Scotland  or Wales  Project B:  -  Must be born between 30 and 33 weeks postmenstrual age  -  Must be born between 1st January 2012 and 31st December 2017  -  Must be admitted to an NHS neonatal unit in England, Scotland or Wales Exclusion Criteria:  Project A:  No exclusion criteria.  Project B:  -  Major congenital gastrointestinal malformations  -  Life limiting conditions  -  Congenital conditions requiring surgery in the neonatal period  -  Missing key background data (birthweight, sex or gestational age)  -  Missing data for the primary outcome

This study is an exploratory study aimed at gaining a greater understanding of the cause of  abdominal bloating in response to two distinct fibre types. This is a single-center,  interventional double blinded randomized cross-over study. Each participant will consume each  of the study products (placebo, fibre 1 and fibre 2) for a 7-day period with a 3-week washout  period in between. Outcomes will be measured before and after each intervention period. The investigators have 4 hypotheses linked to 4 research questions that will be answered by  this research:  Hypothesis 1: participants with self-reported functional bloating in response to either  fibre-1 or fibre-2, but not both, will respond symptomatically to fibre-1 or fibre-2, defined  as 'fibre-1 responders' and 'fibre-2 responders'.  Hypothesis 2: participants with functional bloating who are 'fibre-1 responders' will be  distinguishable from 'fibre-1 non-responders', and 'fibre-2 responders' will be  distinguishable from 'fibre-2 non-responders', based upon faecal microbial profiles  identified using faecal metagenomics, transcriptomics and metabolites at baseline and  following the fibre-1 and fibre-2 interventions.  Hypothesis 3: the microbiota, clinical and nutritional profiles of participants with  functional bloating will be interrelated and these relationships will be distinguishable  between 'fibre-1 responders', 'fibre-1 non-responders', and 'fibre-2 responders' and 'fibre-2  non-responders'.  Hypothesis 4: participants with visceral hypersensitivity will have different faecal  microbiota and will be more likely to be a 'fibre-1 responders' or 'fibre-2 responders' than  'non-responders'.  Participants in the trial will take three different dietary substances, each at a dose of 8  grams per day (split into two serves of 4 gram doses) for 7-days in a double-blinded  randomised order with a 3-week washout period in between each intervention. The products are  provided in powdered format and will be mixed with water before drinking. The products being  provided are glucose, and fibre-1 or fibre-2 (all extracts of commonly consumed food  products). Inclusion Criteria:  1. Healthy adults (18-60 years of age inclusive, and BMI 19-29 kg/m2 inclusive) who  fulfil criteria for functional bloating as per Rome IV Criteria (to be assessed at  screening phone call).  2. Individuals willing to provide consent and follow the protocol  3. Individuals who report that due to perceived trigger food avoidance, symptoms are well  controlled i.e. report that over the past 3 days they have had absent or mild bloating  on ≥2 days.  4. Individuals that do not fulfil Rome IV criteria for irritable bowel syndrome,  functional constipation or functional diarrhoea  5. Individuals that report heightened bloating in response to foods predominantly high in  just one type of study fibre i.e not those that report bloating in response to foods  high in both. The goal will be to recruit equal proportion of each.  6. Individuals that are not diagnosed with any other chronic gastrointestinal disease or  condition including inflammatory bowel disease, coeliac disease. Exclusion Criteria:  -  1. Excessive habitual intake of fructans, galacto-oligosaccharides, polyols or  fructose, as defined by clinician as the sole cause of symptoms.  2. Individuals with specific diets (eg: strict low-FODMAP). 3. Participation in  another clinical trial within the past 4 weeks 4. Subject with known or suspected  allergy to any component of the study product(s).  5. Individuals receiving treatment for anorexia, weight loss, or any form of treatment  likely to interfere with metabolism or dietary habits.  6. Vulnerable subjects defined as individuals whose willingness to volunteer in the  clinical trial may be unduly influenced by the expectation, whether justified or not,  of benefits associated with participation, or of a retaliatory response from senior  members of a hierarchy in case of refusal to participate. (Examples are members of a  group with a hierarchical structure linked to the Investigator or to the Sponsor, such  as students, subordinate hospital and laboratory personnel, employees of the  Investigator or of the Sponsor).  7. Individuals with antibiotics or proton pump inhibitor (e.g. omeprazole,  lansoprazole and esomeprazole, pantoprazole, Rabeprazole) use within the previous 2  months 8. Individuals with current use of medication with potential central nervous  system effects as judged by the investigator.  9. Individuals with previous digestive surgery (except for appendectomy and  cholecystectomy performed more than 2 years ago).  10. Athletes as defined as performing daily strenuous daily exercise for more than 1.5  hours at a time.  11. Oral disease that may impact on breath sampling e.g. gingivitis, halitosis, oral  thrush, candidiasis.  12. Individuals starting or routinely taking drugs (occasional use is acceptable) that  might modify gastrointestinal function such as:  -  Prokinetic agents e.g. metoclopramide (Reglan), tegaserod (Zelnorm), domperidone  (Motilium),  -  Anti-emetics agents  -  Corticosteroids  -  Narcotic analgesic agents e.g. methadone, fentanyl  -  Anticholinergic agents for irritable bowel syndrome  -  Medications for constipation e.g. enemas, cathartics, polyethylene glycol solutions,  and lactulose.  -  5HT3 antagonists e.g. alosetron and ondansetron.  -  Anti-diarrheal agents e.g. Imodium (loperamide)  -  Opiate agents used to treat diarrhoea.  -  NSAIDs e.g. ibuprofen  -  Histamine2 blockers e.g. cimetidine (Tagamet), famotidine (Pepcid), and ranitidine  hydrochloride (Zantac), nizatidine (Axid)  -  Antacids e.g. Gaviscon, Maalox, Tums, or any that contain magnesium or aluminium  -  Supplements used to treat bloating: activated charcoal, alpha galactosidase 13. Women  who report they are pregnant/lactating/planning pregnancy 14. Recent/ongoing  consumption of probiotics/prebiotic supplements (past 4 weeks) 15. Anticipated changes  to consumption of naturally probiotic/prebiotic containing foods e.g. yogurt with live  cultures or cereals with chicory etc, in the next 2 months 16. Anticipated changes to  smoking habits in the next 2 months 17. Ongoing abuse of alcohol (>40 units per  week)/non-prescription drugs/other medication

determine the early toxicity and loco-regional control comparing outcome of radiothrapy  rither by using INRT or IFRT in treatment of early stage hodgkin lymphoma  determine progression-free survival and late toxisty Hodgkin lymphoma (HL) is one of the most frequent lymphomas in the Western world, with an  annual incidence of about 3 cases per 100,000 persons. This lymphoid malignancy involves  peripheral lymph nodes and can also affect organs such as liver, lung, and bone marrow. About  40% of patients suffer from constitutional symptoms ("B-symptoms"). Based on differences in  the histological picture and the phenotype of the tumor cells, HL is subclassified into  nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-depleted, and nodular  lymphocyte-predominant HL (NLPHL) (1) Hodgkin lymphoma is estimated to account for about 10%  of cases of newly diagnosed lymphoma in the United States (8,260 of 80,500), the remainder  being Non-Hodgkin lymphoma. Of 21,210 estimated deaths yearly due to lymphoma, about 1,070  (or 5%) are from Hodgkin lymphoma. It accounts for about 0.5% of newly diagnosed cases of  cancer in the United States and about 0.2% of all cancer deaths. However lymphoma is the most  common cancer diagnosed in adolescents (aged 15 to 19 years) accounting for 21% of new  diagnoses, almost two-thirds of which is Hodgkin lymphoma (2) In patients with Hodgkin  lymphoma, a definitive diagnosis is critical and requires that the treating physician provide  the pathologist with an adequate pathologic specimen. Fine-needle aspiration or core-needle  biopsy specimens are commonly inadequate because they do not represent the architecture of  the lymph node and therefore preclude an accurate diagnosis. Hodgkin lymphoma has the unique  characteristic of malignant cells constituting only a minority of the intratumoral cell  population, and therefore, a small biopsy specimen may not include sufficient malignant  cells.(3)  To establish a definitive diagnosis, it is necessary to identify Reed-Sternberg cells within  the biopsy specimen. These cells are commonly seen within a rich cellular environment  composed of reactive lymphocytes, eosinophils, and histiocytes. Two distinct disease entities  have been defined in Hodgkin lymphoma, the commonly diagnosed classical Hodgkin lymphoma and  the uncommon nodular lymphocyte-predominant Hodgkin lymphoma.(4)  The past few decades have seen significant progress in the management of pt with HL, it is  curable in at least 80% of patient. Early stage Hodgkin's lymphoma (HL) patients treated with  a combination of chemotherapy and radiotherapy have an excellent clinical outcome, with  overall survival of approximately 90% [5].  With modern techniques, including better CT scan imaging, FDG-PET/CT scans and more accurate  radiation technology ,It is now possible to customize radiotherapy for each patient with  accurate delivery of radiation to the initially involved volume while minimizing the  radiation dose to normal tissues(6).  The advent of combined modality treatment had previously led to a Shift in practice from  extended field radiotherapy techniques to involved Field radiotherapy (IFRT)(7-8).  Some recent studies have shown the safety of further reductions in field sites. With the  concept of involved node radiotherapy (INRT) in order to reduce the risk of  radiotherapy-induced toxicity. INRT is based on treating only initially involved lymph nodes  and excluding adjacent uninvolved nodal areas(9-11) Inclusion Criteria:  -  Histologically proven Hodgkin's Lymphoma, with exclusion of the nodular lymphocyte  predominant subtybe  -  Clinical stage I or II, only supra-diaphragmatic nodes, both favorable and unfavorable  prognostic subsets  -  Previously untreated.  -  Age: between 18 and 75 years.  -  Good general condition(WHO performance status 0-2).  -  Free of concurrent disease. Exclusion Criteria:  -  Patients with impaired heart, lung, liver, or kidney function.  -  Previous malignant diseases or HIV-positive status  -  Patient with advanced or infra-diaghragmatic Hodgkin's disease  -  Pregnant or lactating women  -  Patient with prior irradiation to the neck and thorathic region

This is a subject single blinded, randomized, placebo-controlled, single dose, first-time-in-human study with three or more ascending cohorts. Each subject will undergo Screening (Day -28 to Day -2). Subjects will return to the clinical site on Day -1, be admitted to the unit, and eligibility will be reconfirmed. Eligible subjects will receive a single dose of investigational medicinal product (IMP, NSI-189 Phosphate or Placebo) on Day 1 and will be followed for safety and PK until discharge on Day 3. Subjects who are experiencing any significant AEs that are considered possibly related to study drug will be kept at the unit for an additional day (or longer) until the event resolves or it is considered medically safe for the subject to be discharged. Subjects will have a telephone Follow-up on Day 4 and return to the unit on Day 7 (± 1) for End-of-study. Participation of an individual subject may last up to 36 days from the time of Screening until the End-of-study. Inclusion Criteria:   -  A subject must meet all of the following criteria:        1. Subject has the ability to understand the purpose and risks of the study and to provide signed and dated informed consent.        2. Males and females between 18 to 55 years of age, inclusive, at the time of informed consent.        3. The following applies to female subjects:           • Non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal = 1 year with follicle stimulating hormone >40 U/L).        4. The following applies to male subjects:           • Male subjects with a female partner of childbearing potential will be required to use an effective method of birth control or practice abstinence during this study and for 3 months following discontinuation of IMP.        5. Non-smokers (or other nicotine use) as determined by history (no nicotine use over the past year) and by negative urine cotinine test at screening and Day -1.        6. BMI = 19.5 and =30.0 kg/m2, at screening. Bodyweight must be >50 kg.        7. Healthy, determined by pre-study medical evaluation and investigator discretion (medical history, physical examination, vital signs, ECG, and clinical laboratory evaluations). Exclusion Criteria:   1. Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, dermatological or psychiatric disorder(s), or other major disease as determined by the Investigator or designee.   2. History of seizures including febrile seizures, loss of consciousness, or any clinically significant finding on the neurologic examination.   3. Clinically significant abnormal clinical chemistry values, as determined by the Investigator.   4. Clinically significant (as determined by the Investigator) 12-lead ECG abnormalities, including corrected QT interval using Bazett's correction method of >450 msec for males and >470 msec for females.   5. History of severe allergic or anaphylactic reactions.   6. Subjects who have plans to undergo elective procedures/surgeries at any time during the study through the follow-up visits.   7. A positive screening test for human immunodeficiency virus (HIV), hepatitis C virus antibody (HCVAb), hepatitis B core antibody (HBcAb), or hepatitis B surface antigen (HBsAg).   8. Serious infection (e.g. pneumonia, septicemia) as determined by the Investigator within 3 months prior to Day -1.   9. Fever or bacterial, or viral infection (including upper respiratory tract infection) within 2 weeks prior to Day -1.  10. Treatment with any prescribed medication within 28 days prior to Day -1.  11. Treatment with any over-the-counter products (OTC), including herbal and/or alternative health preparations and procedures within the 14 days prior to Day -1. Note: Intermittent treatment with acetaminophen [=1000 mg/day] and/or ibuprofen [=400 mg/day] is permitted.  12. Current enrollment in any other drug, biologic, device, or clinical study, or treatment with an investigational product or approved therapy for investigational use within 30 days (or 5 half-lives, whichever is longer) prior to Day -1.  13. Any live or attenuated immunization/vaccination within 1 month prior to the study drug administration or planned to occur during the study period.  14. Donation of blood (>500 mL) or blood products within 1 month prior to screening.  15. History of alcohol or substance abuse (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, etc.) (as determined by the Investigator).  16. Vigorous exercise (as determined by the Investigator) within 48 hours prior to the study drug administration.  17. Inability to comply with study requirements.  18. Any disorder that would interfere with the absorption, distribution, metabolism, or excretion of drugs.  19. Any concurrent disease or condition that, in the opinion of the Investigator, would make the subject unsuitable for participation in the clinical study.  20. Subject unwilling to avoid consumption of coffee and caffeine containing beverages within 48 hours prior to Day -1 until discharge from the clinical site.  21. Use of an investigational product within 30 days prior to Day -1.  22. Subject is unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope and possible consequences of the clinical study.  23. Subject is unlikely to comply with the protocol requirements, instructions and study-related restrictions.  24. Subject has previously been enrolled in this clinical study.

A phase 1, dose escalation study of evorpacept (ALX148) in patients with advanced solid  tumors and lymphoma This phase 1 clinical study (AT148001) is an open-label, multi-center, multiple-dose,  dose-escalation, safety, PK, and PD study of evorpacept (ALX148). The phase 1 protocol will  have 2 parts: a single agent dose escalation phase (Part 1) and a combination therapy phase  (Part 2). Part 2 will include an initial dose escalation portion followed by a dose expansion  portion. Approximately 184 adult patients are expected to be enrolled in the study. Inclusion Criteria:  -  Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy;  or relapsed or refractory Non-Hodgkin lymphoma for whom no standard therapy is  available..  -  Adequate Bone Marrow Function.  -  Adequate Renal & Liver Function.  -  Adequate Performance Status Exclusion Criteria:  -  Patients with known symptomatic CNS metastases or lepotomeningeal disease requiring  steroids.  -  Previous high-dose chemotherapy requiring allogenic stem cell rescue.  -  Prior treatment with a CD47 or signal regulatory protein (SIRP) alpha targeting agent.

The focus of this study will be to conduct a prospective, multi-center randomized controlled  trial (RCT) at Cape Regional Medical Center (CRMC), Oroville Hospital (OH), and UCSF Medical  Center (UCSF) in which a machine-learning algorithm will be applied to EHR data for the  detection of sepsis. For patients determined to have a high risk of sepsis, the algorithm  will generate automated voice, telephone notification to nursing staff at CRMC, OH, and UCSF.  The algorithm's performance will be measured by analysis of the primary endpoint, in-hospital  SIRS-based mortality. From January 2020 to February 2021, inclusive, investigators will perform a multi-center  randomized controlled trial (RCT) at CRMC, OH, and UCSF. All aims of this study have been  have been submitted for approval by the Pearl Institutional Review Board with a waiver of  informed consent.  During the study period, all patients over the age of 18 presenting to the emergency  department or admitted to an inpatient unit at the participating facilities will  automatically be enrolled in the trial, until the target enrollment for the study is met.  Enrollment will entail randomization to either the control or the experimental arms. Patients  will be assigned to the experimental group or control group based on a random allocation  sequence, generated by a computer program before the start of the trial, using simple  randomization, with a 1:1 allocation ratio. This allocation sequence will be concealed to  patients, healthcare providers and study investigators. However the trial will have an  open-label design, as full blinding is not possible as some group assignments will become  naturally revealed upon receipt of telephonic alerts.  There will be two arms in the study. The control arm will involve patients with the usual  standard of care, and the experimental arm will involve patients monitored by InSight. If the  applicable algorithm determines a patient to be at a high risk for sepsis, a telephonic alert  will be sent to the charge nurse on duty in the patient's current location. Response to  alerts will follow the protocol from our previous sepsis clinical trial. The procedure  consists of a nurse conducting a patient bedside evaluation to rule out suspected infection.  This includes assessment of patient vital signs, EHR notes, and recent laboratory results. If  the nurse suspects sepsis, a physician subsequently assesses the patient and, if appropriate,  places an order for administration of the standard sepsis treatment bundle.  In the administration of clinical trials, some open-label studies are cluster-randomized  while others are randomized at an individual patient level. Cluster randomization is  frequently used to minimize "contamination" between treatment and control groups, because  exposure of providers to patients from both arms in an open-label study often invites  unintentional behavioral biases. These biases may cause providers to adjust their  interventions in the control group to mimic their actions in the experimental group, thereby  masking the intervention's effect and skewing the study results towards the null. Although  open-label, cluster-randomized trials are effective in minimizing contamination among groups,  they have several significant disadvantages, including greater complexity in design and  analysis as well as larger patient enrollment requirements to achieve the same statistical  power. Because larger sample sizes often necessitate increases in cost, length, or complexity  of a trial, current research has indicated that trialists should use individual randomization  if possible due to the drawbacks of cluster allocation. Given these considerations,  investigators concluded that individual randomization was the best strategy for the trial, as  it affords a significant amount of increase in statistical power and allows each patient  outcome to be assessed independently of every other patient. To minimize possible bias,  investigators also decided to make the automated phone call text identical in both arms. The  successful use of patient-level randomization in a previous sepsis clinical trial conducted  by investigators gives confidence in this trial design.  After the discharge of the last enrolled patient, investigators will evaluate whether the  primary endpoint of in-hospital SIRS-based mortality is met. Additional outcome measures of  interest for each SIRS-based group will include: time to completion of each element of the  Surviving Sepsis Campaign (SSC) bundle; ventilator-free days; ICU days; and 30-day hospital  readmission rate. The 1-hour SSC bundle consists of obtaining blood cultures, measuring  lactate level, administering broad-spectrum antibiotics, administering 30 mL/kg of  crystalloid fluid for hypertension or lactate >4 mmol/L, and applying vasopressors if patient  is hypotensive during or after fluid resuscitation.  Investigators plan to draw from EHR-based clinical data for primary endpoint analysis, as  opposed to claims-based data, due to its ability to provide more objective measurements on  patient outcomes.  At the conclusion of the study, significant findings will be published as scientific papers. Inclusion Criteria:  -  During the study period, all patients over the age of 18 presenting to the emergency  department or admitted to an inpatient unit at the participating facilities will  automatically be enrolled in the trial, until the enrollment target for the study is  met Exclusion Criteria:   -  Patients under the age of 18

This study is an open-label, phase 1/1b study of the pressure-enabled hepatic artery infusion  of SD-101, a TLR 9 agonist, alone or in combination with intravenous checkpoint blockade in  adults with metastatic uveal melanoma. In the Sentinel Cohort, patients will receive 2 SD-101 infusions (2 weeks apart) with  assessments for toxicity prior to escalating from the first dose level (0.5 mg) to the second  dose level (2 mg). In the absence of dose-limiting toxicities (DLTs), each patient will be  eligible to transition into Cohort A.  In Cohorts A-C and Phase 1b, patients will receive 2 cycles of SD-101. Each cycle consists of  3 consecutive weekly infusions. Escalating doses of SD-101 will be administered alone (Cohort  A), together with nivolumab (Cohort B), and together with combined ipilimumab and nivolumab  (Cohort C). Cohort B will begin dosing at the minimum anticipated biological effect level  (MABEL(2mg SD-101)). Cohort C will begin one dose level below the MTD or optimal dose from  Cohort B to optimize safety when adding CPI to SD-101.  Following determination of the recommended MTD or optimal dose of SD-101 for PEDD/HAI and  which checkpoint inhibitor (CPI) regimen(s) are tolerated, the study will progress to Phase  1b. Patients in Phase 1b will receive the SD-101 dose selected from Phase 1 in the presence  of systemic single- or double-agent checkpoint blockade. The choice of single- or  double-agent CPI therapy together with SD-101 for Phase 1b will consider safety data in  addition to response rates from Cohorts B and C in Phase 1. Inclusion Criteria:  1. Male or female, age ≥18 years of age at screening  2. Able to understand the study and provide written informed consent prior to any study  procedures  3. Has histologically or cytologically confirmed metastatic UM with liver-only or liver  dominant disease. Liver-dominant disease will be defined as intrahepatic metastases  representing the largest fraction of disease relative to other organs.  4. Has not received prior cytotoxic chemotherapy, targeted therapy, or external radiation  therapy within 14 days prior to screening  5. Has not received therapy with prior immunological checkpoint blockade within 21 days  before the first dose of study intervention and has no ongoing immune-mediated AEs  Grade 2 or higher  6. Has not ever received prior embolic HAI therapy with permanent embolic material Note:  Previous embolic HAI therapy with permanent embolic material will not be exclusionary  if following this therapy, the target vessels are not occluded and the liver segments  containing target tumors are perfused based on the patient's screening CT/MRI.  7. Prior surgical resection or radiofrequency ablation of oligometastatic liver disease  is allowed on both the Phase 1 and Phase 1b portions of this study. Liver lesions that  received ablative therapies should not be considered target lesions unless they have  clearly progressed since the therapy.  8. Has no prior history of or other concurrent malignancy unless the malignancy is  clinically insignificant, no ongoing treatment is required, and the patient is  clinically stable  9. Has measurable disease in the liver according to RECIST v.1.1 criteria  10. Has an ECOG PS of 0-1 at screening  11. Has a life expectancy of >3 months at screening as estimated by the investigator  12. Has a QTc interval ≤480 msec  13. All associated clinically significant (in the judgment of the investigator)  drug-related toxicity from previous cancer therapy must be resolved (to Grade ≤1 or  the patient's pretreatment level) prior to study treatment administration (Grade 2  alopecia and endocrinopathies controlled on replacement therapy are allowed)  14. Has adequate organ function at screening as evidenced by:  -  Platelet count >100,000/μL  -  Hemoglobin ≥8.0 g/dL  -  White blood cell count (WBC) >2,000/μL  -  Serum creatinine ≤2.0 mg/dL unless the measured creatinine clearance is ≥30  mL/min calculated by Cockcroft-Gault formula.  -  Total and direct bilirubin ≤2.0 × the upper limit of normal (ULN) and alkaline  phosphatase ≤5 × ULN. For patients with documented Gilbert's disease, total  bilirubin up to 3.0 mg/dL is allowed.  -  ALT and AST ≤5 × ULN  -  Prothrombin time/International Normalized Ratio (INR) or activated partial  thromboplastin time (aPTT) test results at screening ≤1.5 × ULN (this applies  only to patients who do not receive therapeutic anticoagulation; patients  receiving therapeutic anticoagulation should be on a stable dose for at least 4  weeks prior to the first dose of study intervention) Note: Laboratory tests with  exclusionary results judged by the investigator as not compatible with the  patient's clinical status may be repeated once for eligibility purposes.  15. Females of childbearing potential must be nonpregnant and nonlactating, or  post-menopausal, and have a negative serum human chorionic gonadotropin (hCG)  pregnancy test result at screening and a negative urine or serum pregnancy test prior  to the first dose of study intervention.  -  Females of childbearing potential must agree to abstain from sexual activity with  nonsterilized male partners, or if sexually active with a nonsterilized male  partner must agree to use highly effective methods of contraception from  screening, throughout the study and agree to continue using such precautions for  100 days after the final dose of study intervention.  -  Nonsterilized males who are sexually active with a female of childbearing  potential must agree to use effective methods of contraception and avoid sperm  donation from Day 1, throughout the study, and for 30 days after the final dose  of study intervention. Exclusion Criteria:  1. Has received chemotherapy or an investigational agent within 14 days (or 5 half-lives,  whichever is shorter) before screening  2. Has active, untreated brain metastasis  3. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.  4. Has portal vein thrombosis, or severe portal hypertension as defined by a history of  variceal hemorrhage or active ascites accumulation  5. Has more than 2/3 parenchymal replacement by tumor of both liver lobes  6. Phase 1 and Phase 1b:  1. Has Child-Pugh Class B or C cirrhosis, or  2. Has experienced a Grade 3 or higher immune-related AE from prior CPI therapy that  has not recovered to Grade 1 for a minimum of 14 days prior to administration of  SD-101 or CPI, or  3. Is unable to be temporarily removed from chronic anticoagulation therapy, or  4. Has a history of bleeding disorders  7. Has active coronavirus disease 2019 (COVID-19), other severe infection, including a  liver infection, within 2 weeks before the first dose of study drug, or uncontrolled  human immunodeficiency virus (HIV) infection at screening  8. Has had bacterial pneumonia within 8 weeks of first dose of study drug  9. Has active, known, or suspected autoimmune disease or immune-mediated disease. Type I  diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders  (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment or  conditions not expected to recur in the absences of an external trigger are not  exclusionary.  10. Is receiving systemic steroid therapy >10 mg of prednisone daily or equivalent or any  other immunosuppressive medication at any dose level. Local steroid therapies (e.g.,  otic, ophthalmic, intra-articular or inhaled medications) are acceptable.  11. Has significant concurrent or intercurrent illness, psychiatric disorder, or alcohol  or chemical dependence that would, in the opinion of the Investigator and/or Medical  Monitor, compromise their safety or compliance or interfere with interpretation of the  study  12. Lactating women are excluded from study participation  13. Has previously received SD-101  14. Medical history of significant hypersensitivity, severe and unresolved immune-mediated  reactions, severe infusion-related reactions, or allergic reaction to TLR9 agonists or  CPI agents in the judgment of the investigator  15. Patients who were enrolled in the Phase 1 portion of the study will not be eligible  for enrollment in Phase 1b

The purpose of this study is to learn if taking a drug called direct oral anticoagulant after  an ablation procedure keeps blood clots from forming and lowers the chance of having a stroke  in patients with ventricular tachycardia or arrhythmia (VT). Ventricular tachycardia (VT) or fast heart rhythm is a condition where the lower chambers  (ventricles) of the heart beat too fast. This condition can be life threatening because these  ventricles are the main pumping chambers of the heart. The fast heartbeat is caused by  electrical impulses that travel incorrectly in your heart.  One way to treat VT is to have a catheter ablation procedure. A catheter ablation is a  procedure that creates scar tissue in the heart to interrupt the electrical impulses that  create irregular heart rhythms.  It is possible that the ablation procedure might cause a blood clot to form. The blood clot  can stop blood flow to the brain and cause a stroke. When blood flow is interrupted to a  certain part of the brain, that part does not receive enough oxygen. As a result of the  stroke the affected areas of the brain are unable to function normally.  Direct oral anticoagulant (DOAC) is a blood thinning drug, also called an anticoagulant. It  interferes with the body's natural blood clotting ability by inactivating a specific enzyme  that the body needs to form blood clots.  Participation in this study will last about 30 days. Inclusion Criteria:  -  Patients undergoing radiofrequency catheter ablation for scar VT which includes VT  secondary to ischemic cardiomyopathy and non-ischemic cardiomyopathy  -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy  test within 24 hours prior to the start of study drug  -  Women must not be breastfeeding  -  WOCBP must agree to follow instructions for method(s) of contraception for the  duration of treatment with Apixaban plus 33 days post-treatment completion  -  Males who are sexually active with WOCBP must agree to follow instructions for  method(s) of contraception for the duration of treatment and for a total of 93 days  post-treatment completion  -  Participants must agree to the use of one approved method of contraception Exclusion Criteria:  -  History of cerebral vascular accident/transient ischemic attack (CVA/TIA) in last 3  months  -  Cardiac surgery or neurosurgery within 3 months of the intended procedure date  -  Any active bleeding  -  Severe hypersensitivity reaction to ELIQUIS (including drug hypersensitivity, such as  skin rash and allergic reactions)  -  Participants cannot have prosthetic heart valves  -  History or bleeding and clotting disorders  -  Contraindications to Aspirin therapy  -  Contraindication to oral anticoagulation  -  Patient on an anticoagulant prior to the ablation for other primary indications like  atrial fibrillation (AF), deep vein thrombosis (DVT) or a mechanical valve  -  Evidence of intracardiac thrombus  -  Patient with Creatinine Clearance of < 30 cc/min  -  Participation in another investigational study related to oral anticoagulation, drug  and/or device intervention  -  Claustrophobic patients  -  Implantable Cardioverter Defibrillator (ICD) generator placement before the year 2000  -  Has an ICD and is pacing dependent without underlying rhythm upon interrogation at  baseline  -  Patient has abandoned leads  -  Patients who are on p-glycoprotein inducers or inhibitors where the dose of Apixaban  cannot be effectively altered

Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There  is still no cure for the disease which only control the development of the disease in various  ways.Chimeric Antigen Receptor-transduced T cell (CAR-T) therapy is one of revolutionary  targeted immunotherapy.The efficacy of CAR-T cells for the treatment of acute B lymphocytic  leukemia has been widely recognized, and several clinical trials have been reported in the  treatment of multiple myeloma with CAR-T cells. Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There  is still no cure for the disease which only control the development of the disease in various  ways.  In recent years, the understanding of pathogenic molecular mechanism in MM , many new types  of drugs can be used in the treatment of this disease, one of the most widely used is  proteasome inhibitors and immune regulator.Hematopoietic stem cell transplantation has also  been shown to improve complete remission rates and prolong patient survival.Combined with the  advantages of multiple therapies, chimeric antigen receptor T cells (CAR-T) have gradually  become one of the strongest and most powerful weapons against multiple myeloma.  CAR - T cells was taken in the form of genetic modification, and specific identified target  antigen monoclonal antibody of single variable region (scFv) expression in T cell surface,  and coupled with the activation of intracellular proliferation signal domain.  When scFv recognizes antigens expressed in malignant cells, it stimulates the activation  signal of downstream T cells and produces specific killing effects. CAR-T therapy is one of  revolutionary targeted immunotherapy.The efficacy of CAR-T cells for the treatment of acute B  lymphocytic leukemia has been widely recognized, and several clinical trials have been  reported in the treatment of multiple myeloma with CAR-T cells.Throughout registration of  clinical trials and published research results, B-cell maturation antigen (BCMA) as one of  targets , its effect is more significant than other molecules.As with BCMA antigens, cluster  of differentiation 138(CD138), cluster of differentiation 56 (CD56) or cluster of  differentiation 38(CD38) antigens are also highly expressed in multiple myeloma cells.With  CD138 as the target for the treatment of CAR-T cells, several clinical studies have been  registered, and the results show that some of them are effective.  In order to lay a foundation for the application of relapsed/refractory multiple myeloma  patients with CAR-T therapy，objects are refractory/ relapsed patients with multiple  myeloma,and plans to into the group of the number of cases in 50 cases.The main content is  safety, efficacy and feasibility analysis of the CAR-T cells （single CAR-T or double CAR-T  cells with BCMA、CD138、CD56 or CD38 ) in the treatment of refractory/relapsed multiple  myeloma. Inclusion Criteria:  1. Relapsed/Refractory MM patients  2. Cell phenotype is BCMA/CD138/CD38/CD56 positive (single or combined) ,and minimal  residual disease (MRD) was positive(cytology, genetic testing)  3. Estimated survival time is more than 3 months in multiple myeloma,and Karnofsky  performance status(KPS) score is more than 60.  4. No cytapheresis and cell separation contraindication.  5. Hemoglobin is more than 80 gram per litre.  6. The function of important organ was satisfied:(1)cardiac ultrasound indicated that  cardiac ejection fractions is more than 50%（EF≥50%）, and the electrocardiogram showed  no obvious abnormality;(2)Blood oxygen saturation is more than  90%（SpO2≥90%）;(3)Creatinine（Cr） is less than 2.5 times normal range;(4)Alanine  transaminase（ALT） and glutamic-oxalacetic transaminase（AST）is less than 3 times normal  range,and total bilirubin is less than 2 milligram per deciliter(TBil≤2.0mg/dL).  7. After discussion by the expert group, the patient's condition was analyzed and  combined with the general physical condition of the patient, the benefit of  participating in the clinical trial was greater than the risk.  8. Volunteered for this clinical trail and signed a consent form . Exclusion Criteria:  1. Patients with high tumor burden or progression of disease need to control the  progression of disease in order to decrease the tumor burden.  2. Patients with active infection and fever.  3. Patients' neutrophilic granulocyte has decreased more than 10 days,and is difficult to  control after treatment.  4. Patients are infected with fungus,bacteria or virus,and are difficult to control after  treatment.  5. Patients with infection of HIV or with actively infection of Hepatitis B Virus(HBV) or  Hepatitis C Virus(HCV).  6. Pregnant or lactating women.  7. Patients with severe insufficient cardiac, pulmonary and hepatorenal functions.  8. Patients had been treated with cell therapy but was invalid.After analyzing the  patient's condition , the expert group think that the patient doesn't fit to attend  the therapy of CART.  9. The monoclonal antibodies of BCMA or CD38 are invalid for the patients who have used  the drug.  10. Any situation may do harm to the subjects or interfere the results.  11. After allogeneic transplantation, patients are more than 3 degrees of acute  Graft-Versus-Host disease(GVHD).

The purpose of the study is to see how practical it is to inject a radiotracer called  99m-Technetium Sulfur Colloid around the tumors for the imaging of patients with  oropharyngeal cancer. This study will evaluate a technique called lymphatic drainage mapping. This is a technique  where a radiotracer (a radioactive material that can be seen with a special computed  tomography [CT] scanner to create 3D images) is injected into a vein around the tumour,  either with local anesthesia or under general anesthesia. The radiotracer that will be used  for the lymphatic drainage mapping is called 99m-Technetium Sulfur Colloid. Images will be  taken of neck to detect the movement of the radiotracer. This will allow the doctors to see  the drainage pattern of the lymph nodes in the neck.  The information from this study will be used to better understand the tendency for  oropharyngeal cancers to spread to lymph nodes. In addition, the information from this  clinical trial will be used in future clinical studies to help specialists identify  strategies to help plan treatment based on this type of imaging study. Inclusion Criteria:  -  Patient has lateralized oropharyngeal carcinoma (tonsil or tongue base) not involving  midline  -  Has squamous cell carcinoma, T1-3 tumours, with no contralateral nodes on clinical  exam or axial imaging  -  Human papillomavirus (HPV) positive or negative  -  Patient should have normal organ function as per Investigator judgement  -  Patient is planned for definitive or adjuvant radiotherapy (RT) or chemo radiotherapy  (CRT) with bilateral neck RT, or surgery  -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria:  -  T4 tumours  -  Contralateral/bilateral nodal disease or node(s) > 6cm on clinical exam or axial  imaging or positron emission tomography (PET)  -  Primary tumour involving or crossing midline  -  Soft palate or posterior pharyngeal wall tumour subsites  -  Previous head and neck cancer  -  Previous radiotherapy (RT) to the head and neck  -  Previous neck dissection  -  Distant metastases  -  Prior invasive malignancy (except non-melanoma skin cancer) unless disease free for 3  years  -  Prior radiotracer allergy  -  Multiple primary head and neck cancers  -  Pregnancy

A Comprehensive Geriatric Assessment (CGA) is a set of tests used to evaluate a patient's  medical, social, and functional status, and can identify impairments in these domains that  may not be noticed otherwise. Prior studies have shown that a CGA can accurately predict  which patients are more likely to have serious side effects from cancer treatment. However,  it is unknown whether interventions can be done to address the impairments found during a CGA  in order to reduce the risk of these side effects. This pilot study will test the feasibility  of targeted interventions for deficits identified during a CGA in patients 65 years or older  with bladder cancer that have not yet started treatment. This study will enroll patients with muscle-invasive bladder cancer that have not yet started  systemic cancer treatment. The participants will complete a CGA and patient-reported outcome  (PRO) measures at baseline. Based on any impairments found during the CGA, participants will  be referred to specialists to help address these difficulties. Participants will complete the  CGA and PRO measures again at 3 months and 1 year after the initial assessment. The goal of  this study is to see if patients with advanced bladder cancer are interested in referrals to  specialists to address their impairments, and whether participants attend those appointments. Inclusion Criteria:  -  Age 65 years or older  -  Confirmed diagnosis of muscle-invasive bladder cancer  -  Plan to undergo systemic treatment but have not yet started therapy Exclusion Criteria:   -  Must be able to read English

iSpecimen aims to create a clinical partner network of hospitals, laboratories, academic  institutions, and other healthcare organizations ("institutions") capable of providing  researchers and educators ("researchers") with annotated biospecimens for use in biomarker  discovery and validation; diagnostic test and instrumentation development and validation;  therapeutics development; other medical research including the impact that various specimen  collection and handling methods and conditions have on research results; and in education  such as researcher or physician training (collectively "research"). The level of involvement for each network institution will vary based on the type of specimen  to which they have access (e.g. biofluids, tissues and/or cells) and the category of  collection (remnant specimens that were originally collected for clinical testing and/or  specimens specifically collected for research) in accordance with the institution's elected  preferences.  In most cases, potential participants will be identified and approached upon presenting for  clinical care or recruited specifically for the study using outreach programs. If additional  screening activities are required to determine eligibility criteria, the potential  participant may be presented with the opportunity to participate in these activities as part  of the study. These screening activities will be minimal risk in nature and are described  further below. Should potential participants meet screening criteria, they may then be asked  to provide biospecimens according to current research needs. Individual participants or  groups of participants may be sought according to specific clinical, lifestyle, and/or  demographic characteristics. The providers of these samples may be healthy participants or  participants with a medical condition of interest to the research community but regardless,  all specimens collected under this protocol (whether for screening purposes and for  distribution to researchers) will qualify as minimal risk activities.  Biospecimens may be distributed to researchers at academic institutions, hospitals, clinical  and government laboratories, and corporations including diagnostic, medical device,  biopharmaceutical and biotechnology companies. The types of research studies and testing that  may be performed using the biospecimens will be varied, and it is not possible to provide a  description of all potential studies. Some researchers may perform genetic testing on the  specimens, some may use the specimens to develop cell lines, and some may cryopreserve the  specimens for many years, awaiting a research use. The specimens may also be used for  educational purposes, such as training lab techs on the proper testing of samples or  physicians on the proper reading of stained slides. The iSpecimen consent forms will indicate  a broad scope of possible research and educational uses and activities. Inclusion Criteria:  -  Individual is developmentally aged 7 years old and above for RUO collections (only)  -  Individual meets requirements of a current request for research materials from  iSpecimen  -  If a blood collection will be performed as part of the screening process or RUO  collection, the individual's health will be assessed by medical staff through medical  record review, clinical exam, and/or the review of an updated medical history as  provided by the participant  -  Individual has reviewed and signed a consent form for an RUO specimen collection if  required as part of the research or if a minor or a person with diminished  decision-making capacity, their parent/guardian or Legally Authorized - Representative  has reviewed and signed the consent form on their behalf.  -  Individual has reviewed and signed a consent form for remnant specimen usage in  research if required as part of the research or if a minor or a person with diminished  decision-making capacity, their parent/guardian or Legally Authorized Representative  has reviewed and signed the consent form on their behalf Exclusion Criteria:  - Subjects that do not meet the inclusion criteria outlined above.

This study was a prospective, multi-center, single-arm, Phase II clinical study. Compared  with the literature data, objective response rate (ORR) and complete response rate (CR) were  the primary endpoint, and 1-year and 2-year progression-free survival (PFS) and 2-year  overall survival (OS) were the secondary endpoint. To evaluate the efficacy and safety of  TR2-ICE sequential Tirelarizin, lenalidomide alone, or both maintenance therapy in the rescue  of patients with relapsed and refractory diffuse large B or high-grade B-cell lymphoma. All patients eligible for inclusion were treated with TR2-ICE, and the first efficacy  evaluation was conducted after the second course of treatment. If the patient can achieve  complete response (CR), partial response (PR), and disease stability (SD), the clinical  benefit is considered, and the TR2-ICE treatment regimen is continued. The second efficacy  assessment was performed after the 4th course of treatment. If patients achieved complete  response (CR) or partial response (PR) compared to baseline, the clinical treatment was  considered effective and the TR2-ICE treatment regimen was continued. After the completion of  six courses of induction chemotherapy, an end-of-course assessment was performed. Patients  with CR and PR can choose to undergo autologous hematopoietic stem cell transplantation  consolidation therapy, or lenalidomide or Tirelarizin monotherapy or both combination  maintenance therapy. If patients still had SD after four courses of treatment or PD at any  time during the study, they were dropped out of the study and given salvage therapy. Inclusion Criteria:  1. Age range ≥16 years old, no gender limitation;  2. Diffuse large B-cell lymphoma or high-grade B-cell lymphoma (HGBL) was confirmed by  histopathology.  3. Have received prior first-line chemotherapy for DLBCL or HGBL, failed to reach CR in  four cycles, or relapsed.  4. At least one positive lesion under 18F-deoxyglucose (18FDG) positron emission computed  tomography (PET-CT) according to the 2014 Lugano criteria for Hodgkin's and  non-Hodgkin's lymphoma;  5. ECOG physical status score is 0-3;  6. At the time of screening, laboratory tests met the following criteria, unless the  investigator could determine that lymphoma was the cause (no corrective and supportive  treatment for the parameters described below was performed within 2 weeks prior to  evaluation) : (1) Routine blood test: Hemoglobin (Hb) ≥90g/L, absolute neutrophil  (ANC) ≥1.5×109/L, platelet count (PLT) ≥90×109/L; (2) biochemical examination: serum  creatinine (Cr) ≤1.5× upper limit of normal value (ULN), creatinine clearance rate >  50ml/min (Cockcroft formula); Total bilirubin (TBIL) ≤1.5×ULN; Alanine  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (liver  metastasis: ≤5ULN).  7. Life expectancy was at least three months, the researchers judged;  8. Understand and voluntarily sign written informed consent. Exclusion Criteria:  1. With central nervous system metastasis or piameningeal metastasis;  2. Prior organ transplant;  3. Previous or current combination of other malignant tumors, except adequately treated  basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the  cervix;  4. Patients who have been treated with PD-1 inhibtor before;  5. History of severe allergy to antibody drugs;  6. Those with active immune diseases, such as systemic lupus erythematosus;  7. Uncontrolled or significant cardiovascular disease, including: (1) New York Heart  Association (NYHA) class II or higher congestive heart failure, unstable angina,  myocardial infarction, or arrhythmia requiring treatment, or left ventricular ejection  fraction (LVEF) <50% at the time of screening within 6 months prior to initial  administration of the study drug; (2) primary cardiomyopathy (such as dilated  cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular  cardiomyopathy, restricted cardiomyopathy, unshaped cardiomyopathy); (3) clinically  significant prolonged history of QTc interval, or screening QTc interval >470ms for  women and >450ms for men; (4) symptomatic coronary heart disease requiring drug  treatment during screening period; (5) Other cardiovascular diseases deemed unsuitable  for inclusion by the investigator.  8. A history of severe interstitial lung disease (ILD), such as pulmonary fibrosis, or  baseline chest CT or MRI showing evidence of ILD;  9. Clinically significant gastrointestinal abnormalities that may affect drug intake,  transport or absorption (such as inability to swallow, chronic diarrhea, intestinal  obstruction, etc.), or total gastrectomy;  10. High-risk surgery for vital organs or poor healing of other surgical wounds as  determined by the investigator 6 weeks prior to screening;  11. Active infection or active or uncontrolled HBV, HCV infection, HIV/AIDS (Acquired  Immune Deficiency Syndrome) or other serious infectious diseases (including: active  infection requiring systemic treatment; HBV/HCV/HIV qualitative detection is  preferred, quantitative detection is required; HBV DNA can be included after treatment  to turn negative);  12. Any mental or cognitive impairment that may limit their understanding of informed  consent, performance of informed consent, and compliance with the study;  13. Drug and alcohol abuse;  14. Women of reproductive age who are unwilling or unable to use an effective method of  contraception during the entire treatment period of the trial and within 12 weeks of  the last Tirelizu administration or within 12 months of the last rituximab  administration, whichever is the latest [women of reproductive age include: Any woman  who has menstruated and has not undergone successful artificial sterilization  (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or has not been  menopausal], is pregnant or breastfeeding;  15. Other conditions that the investigator considers inappropriate for participation in  the study.