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This is a neoadjuvant study to determine the feasibility and tolerability of 2 weeks of a  very low carbohydrate ketogenic diet in combination with letrozole for patients with early  stage operable ER+disease. Primary Objective:  • To evaluate the feasibility and tolerability of a 2 week ketogenic diet in combination with  endocrine therapy prior to surgery for early stage ER+ breast cancer.  Secondary Objectives  -  To determine whether endocrine therapy in combination with a dietary intervention to  reduce insulin pathway signaling results in enhanced inhibition of cancer cell  proliferation (measured byKi67)  -  To determine the effectiveness of 2 weeks of a ketogenic diet to reduce measures of  insulin/PI3Kpathway activation in breast tumors  -  To measure changes in weight and body composition after 2 weeks of a ketogenic diet  -  To measure changes in insulin resistance after 2 weeks of a ketogenic diet  -  To measure the effectiveness of a ketogenic diet in combination with endocrine therapy  to induce and maintain a ketogenic state.  Outline:  Participants will have baseline metabolic parameters measured and will begin a 2-week diet  consisting of meal replacement shakes to induce a ketogenic state. Patients will also receive  letrozole 2.5 mg daily. At the end of 2 weeks, metabolic parameters will again be measured  and patients will proceed with surgical treatment of their breast cancer. A tumor biopsy from  the surgical specimen will be obtained to measure cell proliferation compared with the  pre-treatment diagnostic biopsy. Inclusion Criteria:  -  All participants must provide written informed consent.  -  Patients must have histologically confirmed primary invasive mammary carcinoma  -  The tumor must be estrogen receptor positive  -  The tumor must be HER2 negative (negative IHC or FISH)  -  The primary tumor size must be at least 2 mm in size.  -  Patients must be post-menopausal defined by any of the following:  -  Subjects at least 55 years of age.  -  Subjects younger than 55 years of age and amenorrheic for at least 12 months or  serum follicle-stimulating hormone (FSH) levels and estradiol levels in the  post-menopausal range by local lab criteria  -  Subjects with history of bilateral oophorectomy or prior radiation castration  with amenorrhea for at least 6 months.  -  Patients must have clinical stage I, II, or III invasive mammary carcinoma planning to  undergo surgical treatment with either segmental resection or total mastectomy.  -  Patients must have BMI >= 30.  -  A core biopsy from the time of diagnosis must be available.  -  Mammogram or ultrasound required prior to screening  -  Patients must have adequate organ function based on the following laboratory  parameters:  -  Serum creatinine <= 1.5x ULN  -  SGOT, SGPT <= 4x ULN (unless known steatohepatitis)  -  Serum albumin >= 2.0 g/dL  -  Total serum bilirubin <= 1.5x ULN (or <= 3x ULN if known Gilbert's syndrome) Exclusion Criteria:  Patients with locally advanced disease who are candidates for other preoperative  (chemo)therapy at the time of initial evaluation. This includes patients with inflammatory  breast cancer.  -  Evidence of distant metastatic disease (stage IV).  -  Serious medical illness that in the judgment of the treating physician places the  patient at high risk of operative mortality.  -  Serious medical illness that in the judgment of the treating physician would preclude  the use of a ketogenic diet.  -  Severe uncontrolled malabsorption condition or disease (e.g. grade II/III diarrhea,  severe malnutrition, short gut syndrome).  -  Diabetes mellitus requiring insulin therapy.  -  Dementia, altered mental status, or any psychiatric condition that would prohibit the  understanding or rendering of informed consent.  -  Participation in any other neoadjuvant therapeutic clinical trial.  -  Concurrent anti-cancer therapy other than endocrine therapy (e.g. chemotherapy,  radiotherapy, immunotherapy, or any other biologic therapy).  -  Concurrent treatment with an investigational agent.  -  Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,  preceding the first day of dietary intervention.

Left atrial appendage occlusion is being widely recommended as a treatment strategy for  patients with nonvalvular AF to prevent stroke, especially those who cannot tolerate  long-term oral anticoagulation or have other reasons for nonpharmacologic therapy. Currently,  there are a number of guidance for left atrial appendage occlusion, such as transesophageal  echocardiography, intracardiac echocardiogram, fluoroscopy, computed tomographic/computed  tomographic angiography and so on. Procedures such as atrial septal puncture, device size  selection and operational view are guided by different methods in various centers. Our center  has developed a new approach to guidance: Cone-beam CT and cardiac computed tomographic  angiography were combined by three-dimensional - three-dimensional image fusion in guiding  left atrial appendage occlusion. Eligible NVAF patients were recruited consecutively and received our LAAO workflow of local  anesthesia, intracardiac echocardiography-guided transseptal puncture, and 3DCTA-3DCBCTF  fusion-guided occluder implantation. The primary outcome was optimal occluder implantation  (successful implantation with no occluder recapture and replacement). Other outcomes were  procedure/fluoroscopic time, contrast agent consumption, radiation dose, and peri-procedure  complications. We compared our results with existing publications of LAAO guided by 3DCTA and  two-dimensional fluoroscopy (3DCTA-2DF) fusion images. Inclusion Criteria:  1. An age of >18 years;  2. A CHA2DS2-VASc score of ≥2;  3. Clinical conditions allowing TEE and sedation;  4. Left ventricular ejection fraction >30%;  5. And at least one of the following indications: (a) HAS-BLED score of ≥3; (b)  intolerance to long-term OAC, and (c) stroke, transient ischemic attack, or  thromboembolism even under oral anticoagulation treatment; Exclusion Criteria:  1. A glomerular filtration rate of <50 mL/min/1.73 m2;  2. The presence of a thrombus in the LA and LAA;  3. Acute myocardial infarction or unstable angina, decompensated heart failure (New York  Heart Association functional class III-IV), or heart transplantation;  4. Stroke or transient ischemic attack within 30 days;  5. Very poor peripheral vessel access not allowing device delivery;  6. Moderate or massive pericardial effusion.

The purpose of this project is to obtain important information about the tumour and  surrounding organs during preoperative chemo-radiotherapy for patients with adenocarcinoma of  the rectum. The knowledge generated in this project has the potential to make future  radiotherapy treatments (RT) of rectal cancer patients more precise, with less side effects.  This could lead the way to make chemo-radiotherapy the main treatment modality and spare a  large group of patients from the risk of severe complications after surgery. Specifically, we  aim to obtain:  -  A characterization of systematic and random changes in position and shape of tumours and  surrounding organs during RT.  -  A patient-specific pre-treatment characterization of random uncertainties in position  and shape of the tumour during radiotherapy. This will be used to create and assess an  individual, patient-specific treatment strategy, with the possibility to implement an  adaptive RT strategy using the information obtained from the MRI-scans during treatment.  -  Information about treatment response and local toxicity from morphological and  functional data before, during and after CRT. Patients diagnosed with locally advanced adenocarcinoma of the rectum are treated with  concomitant chemo-radiotherapy (CRT), with the aim of reducing local recurrences. Depending  on tumor location, this is a pre-operative procedure prior to total mesorectal excision or  partial mesorectal excision. The surgery is associated with a high risk of postoperative  morbidity, however, especially when combined with CRT. Consequently, recent years have seen  an increasing focus on other therapeutic approaches, such as "watch and wait", where the aim  is to treat some patients with definitive CRT alone. The success of these new approaches  directly relies on the effectiveness of the radiotherapy (RT) treatment and thereby on the  level as well as the accuracy of the delivered dose to the tumor.  Standard treatment today is based on a single set of CT- and MRI-scans, which are  insufficient to estimate the organ motion during RT. Precise knowledge about the variation in  position and shape of the tumor using multiple MRI scans before and during RT will have the  potential to make future radiotherapy treatments more precise with less side effects.  The investigators will conduct a prospective study of sequential MRI scans before and during  CRT. Patients will be MRI scanned six times in addition to the standard MRI-scan appointments  and follow-up. This will provide a total of 9 MRI-scans of each patient; 3 before RT, 3  during RT and 3 during follow up. The information gained from these additional scans will  provide a much better understanding of the tumor and organs during RT.  This project's overall focus is to make future RT treatments of rectal cancer patients as  precise and efficient as possible. This could contribute to and aid the paradigm shift of  making chemo-radiotherapy the main treatment strategy for some rectal cancer patients. This  has the potential to spare patients of the severe morbidities associated with surgery, as  well as the need for stomas. Inclusion Criteria: All patients referred to standard chemoradiotherapy for locally advanced rectal cancer. Exclusion Criteria:  -  Prior surgery in pelvic minor region  -  Pacemaker  -  Neurostimulator  -  Other non MR-compatible implants  -  Pregnancy  -  Incapable of undergoing MRI  -  Incapable of understanding the patient information  -  Allergic to contrast agent  -  Contraindication for Buscopan  -  Reduced renal function (GFR < 50 ml/min) Patients who cannot tolerate the contrast  used for DCE-MRI (due to allergies, contraindications for Buscopan or reduced renal  function (GFR < 50 ml/min)) will still be offered inclusion in the study, but without  the contrast-based MRI scans.

The underlying hypothesis is that vedolizumab will modify immune cell trafficking in type 1  diabetes, and that this will be enhanced by pre-treatment with etanercept. This study will  determine whether there is mechanistic evidence in support of this hypothesis and provide  preliminary information about safety, efficacy, and tolerability of vedolizumab with and  without pretreatment with etanercept in adults with type 1 diabetes (T1D) Vedolizumab directly blocks integrin α4ß7 on circulating immune cells preventing their egress  from the blood, while etanercept blocks the TNFα signaling necessary for the α4ß7 cognate  addressin MAdCAM-1 to be expressed in pancreatic endothelial cells. For these reasons, the  investigators hypothesize that the two agents may synergistically prevent diabetogenic immune  cells from trafficking from the periphery to their target tissue to cause islet cell  destruction. Cells from both the myeloid (e.g., myeloid DC1 cells and non-classical  monocytes) and lymphoid compartments (e.g., diabetes antigen-specific T cells) would be  impacted by this therapeutic combination. Inclusion Criteria:  1. Males and females 18-45 years of age, inclusive  2. Diagnosis of T1D between 21 days and 3 years from screening  3. Positive for at least one diabetes-related autoantibody any time since diagnosis,  including but not limited to:  -  Glutamate decarboxylase (GAD-65)  -  mIAA, if obtained within 10 days of the onset of exogenous insulin therapy  -  IA-2  -  ZnT8 (Zinc transporter 8)  4. Random (non-fasting) C-peptide or peak MMTT stimulated C-peptide ≥ 0.2 pmol/mL.  5. Females of child-bearing potential must be willing to use effective birth control from  the screening visit through 12 weeks post last dose of study medication.  6. Up to date for clinically recommended immunizations including COVID-19 and seasonal  influenza vaccine at least 3 weeks prior to baseline treatment.  7. Willing to forgo live vaccines 6 weeks prior to baseline treatment visit until 6 weeks  following last treatment visit.  8. HbA1c ≤ 8.5% at screening  9. Willing and able to give informed consent for participation Exclusion Criteria:  1. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal  antibodies  2. History of malignancy or serious uncontrolled cardiovascular, nervous system,  pulmonary, renal, or gastrointestinal disease  3. History of immunodeficiency  4. Recent (within 3 months) serious bacterial, viral, fungal, or other infections  5. Pending or positive SARS-CoV-2 test or symptoms of possible COVID-19 illness at  baseline treatment visit.  6. Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.  7. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.  8. Active infection with EBV as defined by real-time polymerase chain reaction (PCR).  9. Active infection with CMV as defined by real-time PCR.  10. Clinically significant liver function abnormalities as defined by ALT or AST> 1.5 x  the upper limit of age-determined normal (ULN).  11. Any of the following hematologic abnormalities:  -  White blood count <3,000/μL or >14,000/μL  -  Lymphocyte count <800/μL  -  Platelet count <75,000 /μL  -  Hemoglobin <10.0 g/dL  -  Neutrophil count <1500 cells/μL  12. Females who are pregnant or lactating.  13. Receipt of live vaccine (e.g., varicella, MMR (measles, mumps and rubella), intranasal  influenza vaccine) within 6 weeks of randomization.  14. Receipt of other vaccines within 3 weeks of baseline treatment.  15. Receipt of an immune modulating biologic or investigational drug within 3 months or 5  half-lives before screening visit.  16. Use of non-insulin therapies aimed to control hyperglycemia within 30 days of  screening visit.  17. History of other clinically significant autoimmune disease needing chronic therapy  with biologics or steroids with the exception of celiac disease and stable thyroid  disease.  18. Use of medications known to influence glucose tolerance. Topical, nasal, inhaled  corticosteroids acceptable per investigator discretion.  19. Any medical or psychological condition that in the opinion of the principal  investigator would interfere with the safe completion of the trial.

The aim of this study is to evaluate the effect of administration of folic acid and /or  pentoxifylline on patients with chronic kidney disease (CKD). Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of  kidney failure, cardiovascular disease (CVD), and premature death. Chronic kidney disease  (CKD) affects between 8% and 16% of the population worldwide.Defined by a glomerular  filtration rate (GFR) of less than 60 mL/min/1.73 m2, albuminuria of at least 30 mg per 24  hours, or markers of kidney damage (eg, hematuria or structural abnormalities such as  polycystic or dysplastic kidneys) persisting for more than 3 months.That nutrient loss  because of diet restriction and chronic inflammation contributed by CKD itself may stimulate  progression in advanced chronic kidney disease. Folic acid was then selected as a nutrient  intervention. In the mean time, pentoxifylline was well studied in this field for its  anti-inflammatory effects.Pentoxifylline (PTF) appears to improve circulation through its  ability to alter erythrocyte deformability and enhances capillary microcirculation. This  hemorheological property and the potential capacity in decreasing intraglomerular pressure  has led to recent interest in PTF as a therapeutic agent in patients with kidney disease. In  addition to these properties, PTF has an effect on inflammation, oxidative stress and  endothelial function. Inclusion Criteria:  1. Patients who have chronic kidney disease(CKD) stages 3-5  2. Aged between18 - 60 years old.  3. Both sexes.  4. Stable clinical condition defined as no hospitalizations or cardiovascular events  within the 3 months before screening  5. Stable renal function (baseline serum creatinine had to have not increased by 50% in  the 3 months before screening)  6. No changes in concomitant medication during the study.  7. Patients who accept to participate in the study. Exclusion Criteria:  1. Pregnant women  2. Current use of PTF  3. Contraindication to use of PTF drug: history of PTF or theophylline allergy, history  of severe retinal hemorrhage or recent cerebral hemorrhage  4. Those with active infections or inflammatory diseases or HIV infection  5. Those with chronic liver disease .  6. Patients who had received immunosuppressive therapy  7. Non-compliant patients

Randomized. double blind, placebo controlled, parallel arms dose finding study with a 4 weeks treatment period The study consists of a screening period of approximately 1 week, a wash out period of up to 3 weeks, where existing phosphate lowering medication is withheld, a 4-week treatment period and a follow-up period of up to 2 weeks, during which patients are put back on their pre washout phosphate lowering medication. The wash out period will be either 1 week, 2 weeks or 3 weeks depending on the increase in s-phosphate levels. There are 7 parallel treatment arms in the study with bid and od treatment regimens. Laboratory efficacy endpoints and safety assessments will be evaluated at various times throughout the study. The target population of the study is: male or female patients, above18 years of age with End Stage Renal Disease (ESRD) on chronic maintenance hemodialysis (HD) 3 times a week for a minimum of 3 months. Inclusion Criteria:   1. Females and males aged ≥18 years   2. Chronic maintenance hemodialysis 3 x/week for a at least 3 months   3. Prescribed and taking at least 3 doses of phosphate binder per day   4. Serum phosphate levels should be between 3.5 and 8.0 mg/dL ; 1.13 mmol/L and 2.58 mmol/L (inclusive) at screening   5. Total serum calcium levels 2.0 - 2.6 mmol/L inclusive at screening   6. For randomization in the study, after up to 3 weeks wash out of phosphate binders, patients must have serum phosphate levels of at least 6. 0 mg/dL (1.94 mmol/L) but below 10 mg/dL (3.23 mmol/L) and have had an increase of at least 1.5 mg/dL (0.48 mmol/L) vs pre wash out Exclusion Criteria:   1. Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at all time points during clinical routine monitoring for the 3 preceding months before screening visit.   2. Serum parathyroid hormone >1200 pg/mL   3. Significant metabolic acidosis   4. Clinical signs of hypovolemia at randomization      -

Single Center, Randomized, Double Blind, Placebo Controlled, Single ascending dose trial at 3 levels. Ten subjects will be enrolled at each dose. This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose trial with single oral doses of HTI-2088 tablets to subjects at 3 levels (2.5, 3.75, 5 mg). Ten subjects will be enrolled at each dose level, randomized within groups at an active: placebo ratio of 4:1. Inclusion Criteria:   1. Healthy male or female between 18 and 55 years of age (inclusive), without diabetes FPG <126 mg/dL.   2. Body mass index (BMI) of 19 to 30 kg/m2 (inclusive); and a total body weight ≥50 kg.   3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.   4. An informed consent document signed and dated by the subject.   5. Male subjects must agree to utilize a highly effective method of contraception (condom with or without spermicide) during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 90 days following IP dosing, and must agree to refrain from sperm donation from Day 0 until at least 90 days after the IP dose.   6. Females must meet at least one of the following criteria:        -  sexually inactive (abstinent) for at least 14 days prior to the first dose, throughout the study and for 90 days after IP dose        -  postmenopausal, defined by at least 12 consecutive months of amenorrhea without an alternative medical cause        -  using one of the following acceptable birth control methods: surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) at least 6 months prior to the first dose; intra-uterine device in place for at least 3 months prior to the first dose; barrier method (condom, diaphragm) with spermicide for at least 14 days prior to the first dose, throughout the study and for 90 days after IP dose; surgical sterilization of the partner (vasectomy for at least 6 months prior to the first dose); hormonal contraception for at least 3 months prior to the first dose, throughout the study and for 90 days after IP dose. Exclusion Criteria:   1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or drug allergies. In particular, any history or evidence at Screening of chronic GI disorders (e.g., celiac sprue, ulcerative colitis, Crohn's disease, etc.), thyroid disease, or pancreatitis, any condition possibly affecting drug absorption (e.g., gastrectomy).   2. History of gastrointestinal surgery within one year of the screening visit.   3. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that could have increased the risk associated with study participation or investigational product administration or could have interfered with the interpretation of study results and, in the judgment of the investigator, made the subject inappropriate for entry into the study.   4. Positive results of alcohol or substances of abuse at screening or upon admission to the clinical research unit.   5. A positive pregnancy test at screening and upon admission to the clinical research unit, or subject is lactating, if the subject is female.   6. History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounce (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening; Consumption of alcohol within 24 hours of receiving IP.   7. Treatment with any investigational drug within 30 days or 5 half-lives preceding the first dose of IP.   8. Have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study.   9. Blood donation of approximately 1 pint (approximately 473 mL) or more within 56 days, or plasma donation within 7 days of receiving IP.  10. Use of prescription, nonprescription drugs, illicit drug use, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of IP. Herbal supplements and hormone replacement therapy should be discontinued 28 days prior to the first dose of IP.  11. Evidence of human immunodeficiency virus (HIV)/ hepatitis C/ hepatitis B infection and/or positive human HIV/hepatitis C/hepatitis B antibodies (a negative test result within the 3 months prior to screening may be used instead of obtaining a screening laboratory sample for these laboratory tests)  12. History of using GLP-1 analogs.  13. Known sensitivity to any of the components of the investigational product formulation or SNAC  14. Current smoker or user of any tobacco products.  15. Consumption of any grapefruit or grapefruit-containing juices within 14 days of receiving the IP.  16. Consumption of any caffeine- or xanthine-containing foods or beverages within 24 hours of receiving IP.  17. Have poor venous access and are unable to donate blood.  18. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study.  19. Subjects who are investigational site staff members or subjects who are Sponsor employees directly involved in the conduct of the study.

This is an open label Phase 1, first-in-human (FIH) study of TST005, a bi-specific antibody  consisting of a PD-L1 monoclonal antibody (mAb) and a transforming growth factor beta (TGF-β)  trap in subjects with locally advanced or metastatic cancers The study has 2 parts. Part A is a dose escalation portion where the patients will be doses  every three weeks following an accelerated 3+3 design. This portion will enroll approximately  25 patients with locally advanced or metastatic cancers.  Part B is an expansion portion where approximately 30 additional patients will be dosed at  the recommended dose level every 3 weeks. This part will include patients with locally  advanced or metastatic HPV related malignancies.  The trial will last approximately 2 years, with assessments including safety labs, ECGs, PKs  and PDs and CT/MRI tumor assessments, based on the Q3W dosing schedule. Inclusion Criteria:  1. Willing and able to provide signed and dated informed consent  2. Patients with histologically or cytologically confirmed, locally advanced or  metastatic solid tumors, evaluable by RECIST v1.1. (Part B includes metastatic HPV+  malignancies)  3. Subject who has tumor progression during or after prior therapy and for whom no  standard therapy exists that would confer clinical benefit.  4. At least one measurable lesion per RECIST 1.1 (Part B only).  5. Eastern Cooperative Oncology Group Performance Status (ECOG PS)0~1.  6. Provide archived tumor tissue samples  7. Adequate organ function Exclusion Criteria:  1. Concurrent malignancy within 3 years prior to entry other than adequately treated  cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell  carcinoma, prostate cancer not requiring treatment (with or without resection), ductal  carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma.  2. Untreated or symptomatic central nervous system (CNS) metastases.  3. Any unresolved Grade 2 or greater toxicity from previous anticancer therapy except  alopecia.  4. Active leptomeningeal disease.  5. Active autoimmune diseases or history of autoimmune diseases that may relapse, with  the following exceptions:  -  Controlled type 1 diabetes  -  Hypothyroidism (provided it is managed with hormone-replacement therapy only)  -  Controlled celiac disease  -  Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or  alopecia)  -  Any other disease that is not expected to recur in the absence of external  triggering factors  6. Any condition that required systemic treatment with either corticosteroids (> 10 mg  daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days  before the first dose of investigational product, with the following exceptions:  -  Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)  -  Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with  minimal systemic absorption  -  Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for  contrast dye allergy) or for the treatment of a non-autoimmune condition (eg,  delayed-type hypersensitivity reaction caused by contact allergen)  7. History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung  diseases, including but not limited to pulmonary fibrosis, active pneumonitis.  8. Severe cardiovascular disease, including cerebrovascular accident, transient ischemic  attack, myocardial infarction, or unstable angina, New York Heart Association class  III or IV heart failure or uncontrolled arrhythmia within 6 months of first dose.  9. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic  therapy within 2 weeks of screening.  10. Clinically significant bleeding within three months of the first dose.  11. Uncontrolled hypertension, defined as systolic ≥150 mm Hg or diastolic ≥90 mm Hg  maintained over time and despite antihypertensive treatment.  12. Patients with QTcF > 480 ms on screening ECG or with a history of additional risk  factors for TdP (e.g., heart failure, hypokalemia，family history of Long QT Syndrome)  13. Pregnant or nursing.  14. Known human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.  15. A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled  intercurrent illness, etc.) that could compromise protocol objectives in the opinion  of the Investigator and/or the Sponsor.  16. Any other condition that, in the opinion of the Investigator, would prohibit the  subject from participating in the study.  17. Active autoimmune disease requiring systemic therapy in the last 2 years prior to the  first dose (i.e., with use of disease modifying agents, systemic corticosteroids or  immunosuppressive drug).  • Subjects with Type 1 diabetes mellitus (TD1M), hypothyroidism requiring only hormone  replacement, or skin disorders not requiring systemic treatment are permitted to  enroll.  18. A history of (non-infectious) pneumonitis that required steroids or has current  pneumonitis.  19. < 4 weeks after any major procedures/surgery; clinically significant unhealed wound;  any unhealed ulceration in GI prior to first dose of TST005.  20. History of severe immune-related adverse effects from checkpoint inhibitor (CPI)  therapy (NCI CTCAE Grade 3 or 4) with the exception of endocrinopathy managed with  replacement therapy or subjects who discontinued CPI therapy for CPI-associated  toxicity or intolerability.

Study aiming at determining the efficacy of eccentric versus concentric exercises for  improving tendon biological characteristics, pain, and shoulder overall function for rotator  cuff tendinopathy in patients with Rheumatoid arthritis (RA).  Moreover, investigation the relationship between RA activity and the severity of rotator cuff  tendinopathy.  Patients will be randomly assigned into either concentric or eccentric exercise group.  Randomizations will be done using computer random generated numbers. Study aiming at determining the efficacy of eccentric versus concentric exercises for  improving tendon biological characteristics, pain, and shoulder overall function for rotator  cuff tendinopathy in patients with RA. Moreover, investigation the relationship between RA  activity and the severity of rotator cuff tendinopathy.  Patients will be randomizations using computer random generated numbers. patients will  receive either eccentric or concentric exercises for internal, external rotators and  abductors muscles All patient will do stretching for posterior capsule and pectoralis minor  Tendon biological changes and subacromial space will be assessed using musculoskeletal  ultrasonography Shoulder function will be assessed using SPADI (shoulder pain and disability  index Pain will be assessed using Visual Analogue Scale (VAS) Rheumatoid arthritis disease  activity will be assessed using Disease Activity Score-28 for Rheumatoid Arthritis with  erythrocyte sedimentation rate (DAS 28 ESR) patient will be assessed at base-line and after  finishing of the study Inclusion Criteria:  1. Adult patients diagnosed with RA according to 2010 (American College of  Rheumatology)(ACR)/European League Against Rheumatism (EULAR) Classification Criteria  for RA  2. Patients diagnosed with rotator cuff tendinopathy based on clinical and  musculoskeletal Ultrasonography (MSUS) finding.  3. Patient complaining of shoulder pain for at least 3 months  4. Positive jobs test or hornblower sign or left off test  5. Age ranged from 18 to 50 years. Exclusion Criteria:  1. Patient indicated for surgical repair of rotator cuff  2. Patient with previous shoulder surgery.  3. Patient with history of intra-articular shoulder fracture.  4. Patient with history of shoulder dislocation  5. Diabetes mellitus

Brief Summary: The study compares four models of pertussis vaccination dispensation to  pregnant women on the vaccine coverage obtained. In addition, the cost of the different  models of vaccination will be evaluated. This is a quasi-experimental study with a non-equivalent control group in pregnant women,  taking place in 4 regions of Québec (Montréal, Montérégie, Capitale-Nationale, Mauricie).  Four models of vaccine dispensation will be evaluated: one university hospital around  gestational diabetes screening, local health and social services centres (CSLC) and a high  volume clinic. 250 participants will be recruited in each of the four types of centres.  In addition, the study will also evaluate the costs incurred by all those involved in the  pertussis vaccination program for pregnant women as well as the cost per woman vaccinated.  Health Professionals:  15 to 20 health professionals involved in providing immunization services to pregnant women:  obsterician-gynaecologists, family doctors and nurses in participating clinics will be  interviewed to evaluate their knowledge, attitudes and professional practises regarding  pertussis vaccination during pregnancy.  Evaluating the Cost:  A detailed costing approach (micro-costing) will be used. Time and movement will be studied  by direct observation using a grid on an electronic file in each of the 5 environments  studied in order to identify the services and activities carried out as well as to determine  the resources involved in the implementation of these services and activities. Three typical  vaccination days will be chosen to make these observations, in each of the four study  environments.  The main activities observed will be related to preparations for vaccination up to the  vaccination itself (informed consent, injection, etc.), the capture of vaccination data the  management of vaccines and equipment, clinical manifestations, etc. If necessary, the people  observed can be interviewed directly to better understand the activities or services  provided. Otherwise, some questions may be included in the interviews described above.  The major cost categories that will be evaluated for each of the delivery modalities are  human resources and supplies. The cost components listed are: nursing time (immunization /  training), coordination time, support staff time, office supplies, vaccine storage equipment,  vaccine transportation equipment, vaccine transportation, health and safety equipment,  emergency, single-use vaccination equipment and others.  With regard to the costs borne by women, the main categories of variables evaluated will be:  the time spent making appointments and attending vaccination appointments, working time lost,  if any, transportation, childcare and other expenses Inclusion Criteria:  -  Pregnant women at least 18 years old who speak English or French  -  Signed Informed Consent Exclusion Criteria: -

The person-centered, motivational, recovery-, and activity-based intervention model 'Everyday  Life Rehabilitation´ (ELR), integrated in sheltered and supported housing facilities for  people with severe psychiatric disabilities, has shown significant outcomes in feasibility  studies, and thus a RCT is required, for the purpose of establishing the effectiveness and  cost-effectiveness of ELR.  All municipalities within 270 kilometers from Umeå will be invited. Residents who meet the  inclusion criteria, will be invited to participate. Housing-units, with associated residents  giving consent, will be randomized to either receive intervention with ELR plus treatment as  usual (TAU), or TAU alone for control group. Hence, the present study is a cluster RCT. The  control group will, after control-period, be offered ELR. Professionals involved in the ELR  intervention group; that is occupational therapists, housing staff and housing managers, will  receive an educational package. It is hypothesized that the intervention-group will improve  in personal and social recovery as well as quality of life.  The primary outcome is recovering quality of life assessed by ReCoL, and secondary outcomes  are self-perceived recovery, everyday functioning, and goal-attainment at 6 months, assessed  using RAS-DS, and GAS, respectively. ReQoL will be transformed into QALY´s for calculation of  cost-effectiveness.  The study has an adaptive design, including an internal pilot year one, in order to determine  required sample sizes before continuing with the full scale RCT year two. The investigators intend to study the extent to which the intervention under study; the  Everyday Life Rehabilitation (ELR), is an effective, and cost-effective model for co-planned  rehabilitative services in sheltered and supported housing facilities, aiming at supporting  residents´ personalized recovery pathway. The project is of high relevance with its  permeating perspectives of severe psychiatric disability (SPD), equity, and quality  improvement, in the intersection of health and social care in accommodations.  The ELR project is both user- and practice-oriented. The main focus is to study whether the  ELR-model is effective, cost-effective, and relevant for users, based on  pre-/post-intervention variables from a resident perspective, such as self-perceived  recovery, quality of life, everyday functioning, and goal fulfilment of residents. The  project is also practice-oriented with a web-based training, methods and tools for staff. The  project is pragmatic in the sense of implementing and studying the ELR model in as natural  context as possible. Throughout the investigators will collaborate with user- and relative  associations, municipalities, and R&D units, in order to develop an intervention that is  relevant and useful.  It has been shown that people with SPD and impaired autonomy have significantly poorer health  than the general population, while at the same time they do not have access to equal health  care, despite that they belong to the highest priority group according to the Swedish  Parliament's principles for prioritization of healthcare. The high priority is based on the  fact that the target group has low autonomy and does not speak out loudly for themselves, or  can argue for their right to health care, further that they do not actively seek and demand  health care, along with the magnitude of suffering, and the impact on life quality. There is  a gap in knowledge, regulations, and lack of interventions suiting this context. Both  rehabilitative healthcare interventions in practice, and RCT´s, are sparse regarding  interventions for this target group living in sheltered or supported housing facilities.  Thus, it is important to develop and test new potentially useful and effective interventions.  Therefore, a manualized but individually flexible model for integrated  healthcare-rehabilitation in collaboration with housing staff in supported or sheltered  housing facilities; the Everyday Life Rehabilitation (ELR), has been developed by the project  manager (Lindström, 2007), and tested in feasibility studies (Lindström et al, 2011; 2011b;  2012; 2013; 2017), aiming at personal recovery and meaningful everyday activities for persons  with SPD. The ELR development is thus based on five years of previous research with  feasibility studies, and has shown significant impact on residents' everyday functioning and  health, as well as the practices of professionals. Based on these feasibility studies, the  original ELR has been slightly revised, adding a monthly follow-up by housing managers, and  clarified tools for co-planning, in order to promote early involvement in enhancing  strategies. The Medical Research Council (MRC) guidelines for complex interventions have been  thoroughly applied in the development process, and next, evidence is needed for  implementation, requiring randomized controlled trial (RCT)-studies. Therefore, the  investigators want to expand the design, and go further with a cluster RCT built on a  slightly revised manual of the ELR intervention, adding clarified focus on management, the  tools for collaboration, and a cost-effectiveness perspective.  Overall aim and research questions:  The overall aim of the project is to investigate the effectiveness, and cost-effectiveness of  a co-planning, person-centered, motivational, recovery-, and activity-based intervention  package for people with SPD living in sheltered or supported housing facilities.  The specific research questions (RQs) are as follows 1-2:  RQ 1. What is the effectiveness of ELR intervention on recovery, quality of life, everyday  functioning, and goal attainment, compared to Treatment as usual (TAU)? RQ 2. What is the  estimated cost-effectiveness based on participant outcomes following ELR plus TAU, and TAU  alone, according to baseline differences of recovering quality of life (ReQoL) transformed  into QALY´s? For RQ 1 and 2, data will be collected pre- and post intervention. Allocation  will be concealed for the independent blinded testers, and partly concealed for the people  with SPD giving consent to participate in the study, being informed that a waiting list of up  to six months may become relevant. The treating occupational therapists, housing staff, and  housing managers, will due to practical reasons not be masked to the intervention. Data will  also be blinded to researchers until analysis have been conducted. A person at Umeå  university, who is not involved in neither the interventions nor analysis, will administrate,  collect and store coded data in a safety-box.  An initial power-analysis has been conducted. The investigators consider a difference of 5  points on the ReQoL-scale as the minimum difference of interest in the present study.  Assuming a standard deviation of 10 (Keetharuth et al, 2018), an average cluster size of 2  participants per hosting facility and an intraclass correlation of 0.1, a total of 35 housing  facilities in each group is required to reach a power of 80% when using a significance level  of 5%.  Oral explanation of the study and a leaflet describing the methods will be given prior to the  participant consent. Considering the target population of the intervention is a vulnerable  group, there are particular ethical reasons to minimize the number of exposed participants,  and thus an internal pilot from year one will form the basis for the determination of the  sample size for the full scale RCT year two. This is in line with the recommendation of MRC  guidelines for complex intervention. An internal pilot offers a chance to recalibrate the  target sample size of the study, using the pilot's information on expected effect size and  the size of the design effect due to the cluster design of the study. Further, it offers an  opportunity to interrupt the study if problems with feasibility is observed, e.g. if  recruitment of housing facilities will not be sufficient to detect a clinical meaningful  difference.  Statistical analyses:  Regarding analysis for RQ 1, mixed effects models will be used to analyse the primary  outcome, including a random intercept for the clustering factor housing facility. The  post-intervention measurements will be used as outcome variables, while adjusting for  corresponding baseline measurements. The adjustment for baseline variables will performed on  both individual level and on aggregated cluster level using the average of the baseline  measurement within the housing facility (Hooper et al, 2018). Details about the model, and  the adjustment for baseline covariates will be prespecified in thein the statistical analysis  plan.  The primary analysis will use an intention-to-treat (ITT) approach and include all allocated  participants with valid data, whether they did or did not receive the complete intervention.  Multiple imputation will be used for variables where missing-at-random can be assumed. A  complementary per protocol analysis will also be made.  For the intervention group only, goal attainment scaling (GAS) will be calculated according  to the specific statistical formula of GAS. The secondary outcomes (RAS-DS and GAS) will be  analysed using mixed effects models or semi-parametric ordinal cumulative link models,  including housing facility as a random effect. This is pre-specified in detail in the  statistical analysis plan.  Subgroup analysis will also be conducted, stratifying on gender in all outcomes.  Specifically, for RQ2 on cost-effectiveness, the following analyses will be conducted: For  univariate testing of significance of cost and ReQoL, Student´s test will initially be used.  For cost-effectiveness analysis, the costs and effects of the ELR and the TAU alternative,  will be calculated and presented in a ratio of incremental cost to incremental effect.  Effects are health outcomes, such as quality-adjusted-life-years (QALY). For this matter,  ReQoL will be transformed into QALY, accounting for baseline differences.  The Swedish Board for Health and Welfare has developed a model for priorities in health care,  which consists of the following criteria: severity of the condition, effectiveness in  treatment, cost-effectiveness in treatment, and evidence base. The model assumes a specific  condition linked to a specific treatment.  In this study the conditions are X and Y, and the treatments are X and Y. This study is  designed to provide this model with proper data. A high degree of severity in these  conditions have repeatedly been reported.  Thus, the trial is designed to measure effectiveness, and cost-effectiveness. The latter is  defined as the cost per QALY gained. The resources needed for the interventions will be  measured in physical units (mainly time) and transformed to monetary values.  When all sub-studies have been finalized, the investigators plan to suggest a priority rank  for the interventions under study. The Board for Health and Welfare use a scale in 10 steps;  1 is the highest possible rank and 10 is the lowest. This ranking is based on the four  criteria described above.  Protocol amendments:  After the first year, the internal pilot will be analyzed. A non-comparative interim analysis  will be performed to assess variability in outcome variables. This will form the basis of an  updated sample size calculation.  The internal pilot will also be used as a basis for possible minor adjustments of the study  protocol. In addition, feasibility of the full scale study will be evaluated. Should it be  concluded that ethical problems arise due to unexpected problems in the study process and it  is unlikely that further knowledge will be gained from continuing the full study with  recruitment of more housing facilities and participants, the study will be interrupted.  Results and gained insights about feasibility from the interval pilot alone will be  published.  Results and conclusions from the internal pilot will be presented at the trial's site at  clinicaltrials.gov. Any adjustments of the protocol and the statistical analysis plan  following from the evaluation of the internal pilot will be published as amendments. Inclusion Criteria:  -  adults with severe psychiatric disability (SPD)  -  living in sheltered or supported housing facility for people with SPD in  municipalities within the geografic area and with access to occupational therapy Exclusion Criteria:  -  comorbidity of dementia or severe developmental disability  -  not being able to communicate in Swedish  -  currently being in acute psychosis, or acute suicidal risk

The purpose of this study is to evaluate the efficacy and safety of Senaparib in metastatic  castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair  (HRR) gene alterations after docetaxel treatment This is a randomized, double-blinded, placebo-controlled, multicenter, Phase II study in  mCRPC patients with HRR gene alterations after docetaxel therapy to evaluate the anti-tumor  activity and safety of Senaparib. Inclusion Criteria:  1. Patients must voluntarily participate in this clinical study. Be willing written  informed consent form (ICF) prior to any study activity.  2. Male ≥18 years of age on the day of signing the ICF.  3. Patients must have histologically or cytologically confirmed prostate adenocarcinoma.  4. Surgically or medically castrated, with serum testosterone levels of ≤50 ng/dL (≤1.73  nmol/L). If the patient is being treated with LHRH agonists/antagonists (patient who  have not undergone orchiectomy), this therapy must be continued throughout the study.  5. Patients have adequate organ functions, as indicated by the following laboratory  values (had not received blood transfusion, apheresis infusion, erythropoietin,  granulocyte colony-stimulating factor (G-CSF), and other relevant medical support  within 14 days before the administration of study drug).  6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to  2.  7. Male patients must use a condom during treatment and for 3 months after the last dose  of study drug when having sexual intercourse with a woman of childbearing potential.  Female partners of male patients should also use an acceptable method of contraception  if they are of childbearing potential. Exclusion Criteria:  1. Previous allogenic bone marrow transplant or double umbilical cord blood  transplantation (dUCBT).  2. Prior treatment with a polyadenosine 5'diphosphoribose polymerisation (PARP)  inhibitor, including Senaparib.  3. Patients with a known hypersensitivity to Senaparib or any of the component of  Senaparib.  4. Initiating bisphosphonate/denosumab therapy or adjusting bisphosphonate/denosumab  dose/regimen within 28 days prior to the first dose of study drug. Patients on a  stable bisphosphonate/denosumab regimen are eligible and may continue.  5. Patients who have received strong inhibitors/inducers of CYP3A4 which cannot be  discontinued 21 days prior to the first dose of study drug and withheld throughout the  study drug treatment. Patients received phenobarbital/enzalutamide will require a  5-week washout prior to the first dose of study drug.  6. Patients with MDS or AML, or with clinical features suggestive of MDS or AML.  7. Patients with serious acute or chronic infections.  8. Patients who have received a live virus or bacterial or RNA vaccination within 28 days  prior to the first dose of study drug.  9. Patients are unable or unwilling to abide by the study protocol or cooperate fully  with the investigator or designee.

Roller Hockey is a sport played on a 40*20 metres rink characterized by combined periods of  high intensity and short breaks, there´s a lack of epidemiological studies in this field. In  line with the well-established model of sports injury prevention research proffered by van  Mechelen, the first stage in this process is establishing the extent of the problem i.e.  injury incidence, severity and burden. Through an online survey filled by semiprofessional  athletes, it is posible to obtain all this important information. This way, it will be  possible to fulfill a gap in the literature and take action in the near future in order to  reduce the prevalence of injuries in this sport. A retrospective study was performed in male Roller Hockey players. 275 players will be  recruited. Data of all injury along a whole season will be collected. Patients' information,  including age, number of years playing, skill level and injured body part, will be analysed. Inclusion Criteria:  participated in the 2020-2021 season third division league (Ok Liga Bronce). Play in at  least one match in the season.  - Exclusion Criteria:  participating in the study.  -

The aim of this study is to provide robust data on the head-to-head comparison of the two  ligands of the prostate specific membrane antigen (PSMA) available in Switzerland for  positron emission tomography (PET)-imaging, i.e. 68Ga-PSMA-11 und 18F-PSMA-1007. Prostate Cancer (PC) is the most common malignancy in men and the second leading cause of  cancer-related death in men. Despite initial therapy at early stage disease, biochemical  recurrence remains a commonly encountered entity and presents a challenge for conventional  imaging modalities given their limited abilities to detect disease at early stages of  recurrence.  PET/CT with ligands of the prostate specific membrane antigen has been shown to have a  significant impact on treatment and is now the sine qua non for staging of recurrent PC. For  example, accurate identification of PC lesions allows for more accurate radiotherapy  planning, allowing for an individualised treatment strategy. There is therefore a substantial  clinical requirement for the accurate identification and stratification of individuals in  whom prostate cancer is diagnosed and at earlier stages of recurrent disease when the chance  of a curative treatment is at its highest.  It is in this context that PSMA has become the focus of much attention owing to its high  levels of expression on PC cells and has rapidly established itself as the investigation of  choice in recurrent PC. Furthermore, PSMA-directed radioligand therapy is a rapidly evolving  treatment modality for metastatic disease, creating an additional therapeutic role for  PSMA-ligand molecular imaging, for which the term "theragnostics" has been coined. The  challenge for nuclear medicine is therefore to develop tracers and examination protocols that  provide optimal detection and characterisation of disease, thus improving upon this promising  technique.  There are currently no published prospective head-to-head studies comparing these two tracers  in recurrent PC. Because of this lack of data, there are no clear recommendations about which  tracer to use and in which situation.  This study aims to fill this gap and provide comprehensive data with the potential to improve  the diagnosis of PC. By providing robust data comparing the two tracers, such data will also  provide guidance to clinicians faced with the scenario of an initially negative 68Ga-PSMA-11  PET as to the diagnostic utility of an additional 18F-PSMA-1007 PET, or vice-versa, and in  which scenarios repeated scanning may be justified.  Finally, the application of the radiotracer into the same patient allows for a comparison of  tracer kinetics. Although radiotracer kinetics are well known from the original pioneering  dosimetric publications, they have never been compared in a head to head fashion and not in  biochemical recurrence. Obtaining dynamic scans over the first hour post injection will allow  intra-individual dosimetry and a head-to-head comparison of parametric imaging parameters,  allowing a direct comparison of the radiotracer's affinity using standard parametric imaging  techniques. Inclusion Criteria:  -  Patients with known biochemical recurrence of a histologically confirmed prostate  cancer post radical prostatectomy, defined as two consecutive prostate specific  antigen (PSA) values > 0.2 ng/ml:  -  Post prostatectomy: Patients > 18 y/o  -  PSA measured within ± 4 weeks of the first PSMA-PET/CT  -  Patients providing written informed consent  -  No change in PC treatment in the period between the first and second scans Exclusion Criteria:  -  Patients receiving androgen deprivation therapy (ADT) within 6 months prior to the  PSMA-PET/CT  -  Patients with contraindication to diuresis with 20mg Furosemide  -  Patients with renal dialysis or relevant renal impairment (eGFR < 35 ml/min)  -  Inability to provide written informed consent  -  Inability to schedule and attend two consecutive PET examinations  -  Patients undergoing active treatment for a second non-prostatic malignancy at the time  of the first scan.  -  Known sensitivity or allergy to PSMA-ligands or one of the components of the  radiotracer solutions used.

Veterans at high-risk for hospitalization, including those with complex care needs, represent  a large population of VHA patients who often do not receive evidence-based primary care  practices that would help them avoid the hospital and improve their health. The high-RIsk  VETerans (RIVET) Program will implement evidence-based practices that can support VHA Primary  Care teams to deliver more comprehensive and patient-centered care, better strategies to  manage medications, and avoid unnecessary hospitalizations. The RIVET Program is designed to  find the most effective approaches to increasing use of evidence-based practices for  high-risk Veterans in primary care, provide rapid data feedback to VHA on high-risk patient  care, build capacity for the implementation of evidence-based practices, and train future  leaders in high-risk Veteran care. The top 5% of Veterans at the highest risk for hospitalizations account for almost 50% of VHA  healthcare costs, have significant multimorbidity, and are also at high risk for poor health  outcomes. In the VHA, most (88%) high-risk patients are managed by general primary care teams  (i.e., Patient-Aligned Care Teams; PACTs). Few PACTs, however, have implemented  evidence-based practices (EBPs) known to address the most common issues among high-risk  Veterans. Some evidence indicates that usual implementation strategies, such as dissemination  of toolkits and training are not effective for improving uptake of EBPs. The most effective  implementation strategies to achieve evidence-based care for high-risk patients, however, are  unknown.  The overall impact goal of the high-RIsk VETerans (RIVET) QUERI Program is to improve VHA  primary care capacity to provide comprehensive, evidence-based care for complex, high-risk  Veterans. The investigators will test 2 implementation strategies to evaluate their impact on  the uptake of two separate EBPs. These EPBs are 1) Comprehensive Assessment and Care Planning  (CACP), and 2) Phone-Based Health Coaching for Medication Adherence (HCMA). CACP is based on  the Comprehensive Geriatric Assessment and guides teams in systematically addressing  patients' cognitive, functional, and social needs through a comprehensive care plan. HCMA  addresses common challenges to medication adherence using a patient-centered approach through  virtual encounters. Both comprehensive assessments and health coaching have demonstrated  efficacy in randomized, controlled trials and have been implemented by two of the national  partners in geriatrics and Whole Health teams. However, both EBPs have had low uptake in  primary care. Implementing these practices in primary care has the potential to improve  quality of care for the large majority of high-risk Veterans. The investigators will conduct  a mixed methods type 3 hybrid effectiveness-implementation design to test the effectiveness  of EBQI-IC and EBQI-LC versus usual care (national tool dissemination and training efforts)  in at least 14 sites in 2 VISNs using a Concurrent Stepped Wedge design (Aim 2). The primary  outcome is proportion of eligible high-risk patients that receive each EBP. The investigators  will use the Practical, Robust Implementation and Sustainability Model (PRISM) framework to  compare and evaluate Reach, Effectiveness, Adoption, Implementation, and costs. The  investigators will then assess the Maintenance/sustainment and spread of both EBPs in primary  care across 3 VISNs after the active 18-month implementation period (Aim 3). Inclusion Criteria:  -  VA site in VISN 9,10 and 12 Exclusion Criteria:  -  Not a VA site in VISN 9, 10 and 12

This study evaluates the safety, feasibility, and acceptability of a novel medical abortion  via telemedicine service in the Republic of Moldova. Women and girls in Moldova, especially those in rural areas, must travel to regional medical  centers to obtain an abortion from a certified gynecologist. This creates barriers to  accessing safe abortion that disproportionately affect poor women and girls, through wage  loss due to missed work and accrued costs due to transportation. This innovation is a novel  service delivery model that allows self-management of medical abortion (MA) with remote  guidance from a provider. After confirming their pregnancy, women seeking MA will receive  counseling from a gynecologist via videoconference and will subsequently obtain the necessary  medication via mail or at at participating pharmacy with prescription. Follow-up will occur 1  weeks later via phone/videoconference (with referral to a doctor if necessary) to confirm MA  success and assess the patient's and provider's satisfaction with the service. We hope to  demonstrate the feasibility, effectiveness and acceptability of telemedicine MA services in  Moldova so that it can thus be integrated into the national public healthcare system. As a  result, this project will serve as a model that could be adapted and implemented in nearby  countries within the Eastern Europe and Central Asia region. Inclusion Criteria:  -  16 years or older  -  Has an unwanted pregnancy  -  Confirmed the pregnancy using a test or via ultrasound  -  Gestational age of 9 weeks or less  -  Has personally decided to end the pregnancy  -  Has a device (phone, tablet, or computer) with internet connection, a webcam, and a  microphone.  -  Has immediate access to emergency services  -  Reports no contraindication to medical abortion Exclusion Criteria:  -  Under 16 years of age  -  Does not have an unwanted pregnancy  -  Did not confirm pregnancy  -  Gestational age greater than 9 weeks  -  Does not have a device (phone, tablet, or computer) with internet connection, a  webcam, and a microphone  -  Does not have immediate access to emergency services  -  Has an intrauterine device  -  Is allergic to abortion medications (mifepristone or misoprostol)  -  Has severe anemia or acute porphyria  -  Has a condition that affects the ability of blood to clot normally  -  Has hepatic failure or chronic renal disease  -  Has an ectopic pregnancy  -  Has heart disease or other cardiovascular problem  -  Has a condition that requires hormone treatment

A Registry Study to Evaluate the Survival and Long-Term Safety of Subjects Who Previously  Received Talimogene Laherparepvec in Amgen or BioVEX-Sponsored Clinical Trials A registry study is to evaluate the overall survival, use of subsequent anti-cancer therapy,  and the long-term safety of subjects who have received at least one dose of talimogene  laherparepvec on an Amgen or BioVEX-sponsored clinical trial for any tumor type. Follow-Up  will occur every 3 months. Inclusion Criteria:  All subjects must provide informed consent prior to initiation of any study activities.  All subjects must have received at least one dose of talimogene laherparepvec on an Amgen  or BioVEX-sponsored clinical trial for any tumor type and must have discontinued treatment  and participation, including long-term follow-up (if applicable) in that trial. Exclusion Criteria:  Subjects currently receiving talimogene laherparepvec in Amgen or BioVEX-sponsored clinical  trial.  Subject currently participating, including for long-term follow-up (if applicable), in  other Amgen-sponsored talimogene laherparepvec clinical trial.

This study is being conducted to explore the efficacy and safety of camrelizumab combined  with SHR1020 in the treatment of advanced melanoma. This trial is a prospective, single-center, single-arm clinical research. Based on current  experience, single agent immunotherapy has limited efficacy in advanced melanoma. SHR1020 is  a multi-target tyrosine kinase inhibitor. This study is aiming to evaluate the efficacy and  safety of camrelizumab combined with SHR1020 in patients with advanced melanoma. The safety  and efficacy of this study will be assessed through ORR, DCR, PFS, OS and adverse effects as  graded by CTCAE 5.0. Inclusion Criteria:  -  Has unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer  (AJCC) staging system version 8. At least one measurable lesion conforming to RECIST  1.1 criteria.  -  The toxicity of prior treatment has recovered to ≤1 grade according to CTCAE 5.0  (excepted alopecia).  -  ECOG score 0-1.  -  The expected survival time is ≥ 12 weeks.  -  Had normal swallowing function, without dysfunction of gastrointestinal absorption.  -  Adequate organ and bone marrow function.  -  Female patients of childbearing age must undergo a serum pregnancy test within 7 days  before the commencement of the study and the results are negative, and are willing to  use a medically approved high potency contraceptive method during the study period and  within 12 months after the last administration of the study drug; For male patients  whose partner is a female of childbearing age, they should be surgically sterilized or  agree to use an effective method of contraception during the study period and for 12  months after administration of the last study.  -  Willing to consent and signed the informed consent, and able comply with the planned  visit, research treatment, laboratory examination and other test procedures. Exclusion Criteria:  -  Other malignant tumors occurred in the past 5 years, except for cured skin basal cell  carcinoma, squamous cell carcinoma of skin, early stage prostate cancer and cervical  carcinoma in situ.  -  Has uveal melanoma.  -  The patient has previously received anti-angiogenic drugs.  -  The first study drug treatment was less than 4 weeks from the last chemotherapy or 5  half-lives from the last targeted therapy; less than 4 weeks from major surgery; less  than7 days from immunosuppressive drug; less than 3 weeks from immunomodulatory; less  than 4 weeks from live attenuated vaccine.  -  Systemic antibiotic use for 7 days within 4 weeks prior to initial administration, or  unexplained fever during screening/prior to initial administration.  -  Received hematopoietic stimulating factors (eg: G-CSF, EPO) within 1 week prior to  initial administration.  -  Patients with central nervous system disease or brain metastases; patients who have  received treatment, such as imaging confirmed stable has been maintained for at least  4 weeks, and have stopped systemic hormone therapy for more than 2 weeks, no clinical  symptoms can be included.  -  With active autoimmune disease or a history of autoimmune disease.  -  With history of allogeneic organ transplantation or allogeneic hematopoietic stem cell  transplantation.  -  With immunodeficiency, eg HIV, HBV, HCV.  -  Known to be allergic to the active ingredients or excipients in this study.  -  Have a clear history of serious and uncontrolled other disease or mental disorders.  -  Has a bleeding tendency or abnormal clotting function (INR>2.0, PT>16s).  -  Other situations that the researcher considers inappropriate to participate in the  research.

The purpose of this study is to determine the rate of insulin pump discontinuation 18 months  after initiation in patients with diabetes, and to determine factors associated with this  discontinuation. Insulin pump discontinuation has been mostly studied in children and young adults living with  diabetes, and rarely with a time-to-event analysis. We aim to evaluate the rate of insulin  pump discontinuation after 18 months from initiation and factors associated with it in adults  with diabetes.  Knowing these factors would allow better support for patients in difficulty. Inclusion Criteria:  All patients (adults and adolescents) with diabetes and an insulin pump initiation from 1  January 2015 to 30 June 2018 in the diabetes department of the Centre hospitalier sud  francilien. Exclusion Criteria:  -  Pregnant women (or women planning pregnancy in the short term) with an insulin pump  initiation from 1 January 2015 to 30 June 2018  -  Patients hospitalized for an insulin pump replacement or change between 1 January 2015  and 30 June 2018.  -  Patients with a history of insulin pump initiation within a period of less than 6  months before a new pump start between 1 January 2015 and 30 June 2018.

It is the aim of the study to prove, if intravenous supplementation with ferric  carboxymaltose in iron-deficient patients with heart failure with reduced ejection fraction  (HFrEF) leads to better exercise training effects compared to exercise training without  previous iron supplementation. In patients with heart failure with reduced ejection fraction (HFrEF) exercise training (ET)  is recommended. In iron-deficient HFrEF patients iron supplementation by ferric  carboxymaltose (FCM) is recommended. Both treatment options (ET and iron supplementation)  affect oxidative metabolism.  In this study iron-deficient HFrEF patients are included and randomly assigned to two study  arms:  Study arm A: Intravenous iron supplementation with FCM, subsequent (after 2 months) ET  program.  Study arm B: ET program, subsequent (after 2 months) intravenous iron supplementation with  FCM.  Primary study endpoint is exercise capacity (Peak VO2). Secondary endpoints are 6-minute  walking distance, NYHA class, echocardiographic parameters and the combined endpoint  cardiovascular hospitalizations and death. Inclusion Criteria:  -  Heart failure with reduced ejection fraction ≤ 40%  -  New York Heart Failure Asssociation class II-III  -  Iron deficiency (ferritin < 100 ng/ml or 100-299 ng/ml, if transferrin saturation <  20%) Exclusion Criteria:  -  Planned cardiovascular interventions (such as bypass surgery or valve interventions)  -  Acute coronary Syndrome  -  Malignant rhythm disturbances  -  Acute or chronic infection  -  Reduced prognosis or exercise capacity by non-cardiac comorbidities  -  Missing informed consent

The goal of this study is to evaluate the effectiveness of financial incentives delivered in  real-time at point of purchase, on low-income consumers' purchase of fruits and vegetables,  fruits and vegetables consumption, diet quality, and weight/BMI. The study will test  real-time incentives compared to a no-incentive control condition. To address diet quality disparities in low-income families, policy makers and health experts  recommend strategies such as financial incentives to promote consumption of fruits and  vegetables. Real-time incentives for purchasing fruits and vegetables are promising  strategies to improve families' diets and health.  The aims of the study are:  1. To test the effects of financial incentives, delivered in real-time at the point of  purchase, on low-income consumer purchases of fruits and vegetables  2. To evaluate the impact of real-time financial incentives compared to a control condition  on FV consumption among adults and their children ,shopping habits, home food  environments, diet quality, and weight/BMI  3. To adapt mobile platform technology to provide regular feedback to participants to  motivate use of the incentive program to increase purchases and consumption of fruits  and vegetables  4. To evaluate participant satisfaction with real-time healthy food choice incentives  technology in both SNAP participants and income-eligible non-SNAP participants  5. To assess the acceptability and ease of use of real-time healthy food choice incentives  technology among retails supermarket managers and staff in low-income neighborhoods. Inclusion Criteria:  -  18 years of age or older  -  Speak English  -  Do most of their food shopping at a participating supermarket  -  Receive or are eligible to receive SNAP benefits  -  Have a child in the household between the ages of 2-17  -  Have a working smartphone  -  Be the main household shopper Exclusion Criteria:  -  Participants will be excluded if the primary shopper and/or any children in the family  have major medical or dental conditions that would prevent them from eating fruits and  vegetables, or if they have a serious neurological disorder, dementia, or psychiatric  condition that interferes with understanding study procedures

The aim of this study is to determine the SPF of two test materials ChapStick Moisturizer,  Classic Flavor and ChapStick Moisturizer, Strawberry Flavor using the methodology described  in the International Standard Test Method. This static methodology also meets the  requirements of the Australia/New Zealand standard. A single-center, randomized, evaluator blind, intra-individual comparison, no treatment and  positive controlled clinical study to determine the SPF of two ChapStick sunscreen-containing  lip balms as per ISO 24444:2010. For each participant, 4 test sites will have a random  assignment number for up to two test materials, control standard, and minimal erythemal dose  of unprotected skin (MEDu), with at least 3 of the test sites being utilized for application.  All three test sites will be exposed to UV radiation at the expected MED and subsequently  evaluated for erythema 16-24 hours after UV exposure. Inclusion Criteria:  -  Participant must read and execute an informed consent document (that includes a HIPAA  statement) indicating that the participant has been informed of all pertinent aspects  of the trial before any assessment is performed;  -  Participant must complete a Medical History Form (MHF) prior to their trial  initiation;  -  Participant must be willing and able to comply with scheduled visits, treatment plan,  laboratory tests, and other trial procedures;  -  Participant must agree not to expose their back to additional sunlight or tanning  beds, as either can alter the test results;  -  Participant must agree not to apply any topical skin-care product to the test sites  during this trial;  -  Male or female participants of childbearing potential must agree to use a highly  effective method of contraception throughout the trial and for 14 days after the last  application of assigned treatment. A participant is of childbearing potential if, in  the opinion of the investigator, he/she is biologically capable of having children and  is sexually active;  -  Female participants of childbearing potential must be willing to comply with urine  pregnancy testing requirements prior to initiation of trial testing procedures and as  may be required for the duration of the trial;  -  Participant must be considered dependable and capable of understanding and following  directions;  -  Participant must have self-perceived Fitzpatrick skin phototype I, II, or III:  Skin Phototype Sunburn and Tanning History I Always burn easily; never tans II Always burns  easily; tans minimally III Burns moderately; tans gradually; and  -  Participant must have an Individual Typology Angle value >28 degrees, determined by  the Testing Facility by colorimetric methods, within 1 week of trial participation. Exclusion Criteria:  -  Participant is in ill health as determined by the Principal Investigator;  -  Participant is an employee of the Clinical Division of the investigational site or a  member of their immediate family;  -  Participant is a GSK CH employee directly involved in the conduct of the trial or a  member of their immediate family;  -  Female participant is pregnant or intending to become pregnant over the duration of  the trial or any female participant of childbearing potential who fails to produce a  negative urine pregnancy test;  -  Female participant who is lactating (self-reported);  -  Participant using medication with photo-sensitizing potential;  -  Participant has a history of adverse reactions or hypersensitivity to azo dyes,  cosmetics, OTC drugs, or other topical personal care products;  -  Participant taking medications other than birth control that could influence the  purpose, integrity or outcome of the trial;  -  Participant has used topical or systemic steroids, antihistamines, or antibiotics  within 7 days of trial initiation or during the trial;  -  Participant has used anti-inflammatory medications within 7 days of trial initiation  or during the trial, that in the opinion of the PI, could interfere with the trial;  -  Participant has used medication suspected of causing photobiological reactions (e.g.,  tetracyclines, thiazides, etc.), that has not been taken by the participant through a  summer season;  -  Participant has a dermatological condition;  -  Participant has a history of abnormal response to the sun, or a condition such as  lupus erythematosus or skin cancer;  -  Participant uses tanning beds frequently;  -  Participant whose test site was exposed to sunlight within the previous 4 weeks;  -  Participant has a sunburn, suntan, uneven skin color, visible skin disease, scarring,  or tattoo that would interfere with evaluation of test results; Note: The presence of  non-dysplastic nevi, blemishes, or moles will be acceptable if, in the PI's judgment,  they will neither compromise the clinical trial, nor jeopardize a participant's  safety. A participant with dysplastic nevi should be disqualified.  -  Participant has existing sun damage in the test site;  -  Participant has excessive hair in the test area and are unwilling to have it clipped;  or  -  Participant whose test sites have been used for clinical testing in which they were  exposed to ultraviolet radiation within the past 2 months.

Despite its popularity, there has been limited research on futsal, possibly due to the lack  of financial interest in the game, and most of these research articles have addressed game  analysis and/or physiological demands on players during match playing and training. For this  reason, our aim is to evaluate the effectiveness of an 8-week neuromuscular training program  on performance, physical fitness and injury risk in university futsal players. Futsal, known as five-on-five indoor soccer, is a team sport officially authorized by FIFA  and is becoming more and more popular all over the world. Futsal is among the 10 risky sports  with the highest traumatic injuries. Futsal-induced traumas cause undesirable consequences  such as accelerated osteoarthritis, different types of injuries in the muscle-tendon region,  ligament injuries, cartilage injuries, loss of physical activity and higher repetitive  injuries. Activities that result in a higher level of fitness can significantly reduce the  likelihood of injury and serve as a useful tool for athletes' professional careers and  post-career periods.  Neuromuscular control, which is considered a critical component of motor skills, is defined  as the ability to keep the body's center of gravity within the base of support (17, 18). It  can be categorized as static or dynamic balance and may be the most modifiable risk factor  for the prevention of knee injuries (19). Interventions targeting neuromuscular control  include dynamic lower extremity alignment during landing from a jump, shock absorption,  muscle recruitment patterns; and gains improvement in balance through plyometric,  strengthening, balancing, endurance and stability exercises (20-22). Neuromuscular training  program can improve neuromuscular control, which can lead to improvement in balance and joint  stability (23-24).  In our study, it was aimed to evaluate the effectiveness of an 8-week neuromuscular training  program on performance, physical fitness and injury risk in university futsal players. Inclusion Criteria:  -  Playing in Istanbul Medipol University futsal team  -  2 days a week, 2 hours training for futsal or 1 game a week and 2 hours a week, 2 days  a week Exclusion Criteria:  -  History of lower extremity injury or surgery within 6 months prior to the test  -  Injury three months before the study,  -  Failure to heal or complete rehabilitation of previous injury,  -  Physical or mental conditions that prevent them from participating in technical and  tactical futsal training and/or experimental training programs  -  Two or more missed training sessions

This study is an analytical observational retrospective cohort study. It is a single-center  study conducted in the Nancy University Hospital.  End stage renal disease is the ultimate stage of the chronic kidney disease. Patients need  extra-renal replacement techniques. Kidney transplantation is the most effective option for  survival, quality of life and costs.  Then long-term immunosuppressive agents are required to prevent allograft rejection and  improve graft survival.  The number of patients who return in dialysis after graft loss is increasing and accounts for  10% of incident dialysis patients and 14% of patients on the kidney transplant waiting list  registered in 2019. This population may develop complications induced by end-stage renal  disease and adverse events related to prolonged exposure to immunosuppressive agents.  There are currently no formal guidelines on the management of immunosuppressive agents when  patients return to dialysis. Reduction or discontinuation of therapy appears to decrease  cardiovascular, infectious, and neoplastic complications. However, continuing these  treatments may limit anti-HLA sensitization which may access to retransplantation.  Only a few low-powered cohort studies have evaluated the impact of the management of  immunosuppressive therapy on the HLA-sensitization.  The hypothesis of our study is that the continuation of immunosuppressive agents when  patients return in dialysis may limit anti-HLA sensitization. Therefore, access to  retransplantation could be facilitated.  The main objective is to compare the evolution of anti-HLA sensitization according to the  management of immunosuppressive treatment after the return in dialysis (maintenance,  reduction, cessation).  Secondary objectives are time to re-transplantation for patients on the transplant waiting  list, survival of the new graft, patient survival, and dialysis complications  (cardiovascular, infectious and neoplastic complications). Cohort constitution :  The cohort of patients returning to dialysis after graft loss is extracted from the REIN  (Réseau Epidémiologique et Information en Néphrologie) Lorraine registry, which follow all  patients in end-stage renal failure under replacement therapy in the Lorraine region since  2001.  Patients returning to dialysis after graft loss between 1st January 2007 and 31st December  2019 are extracted from the register and included.  From this cohort, 3 groups were created according to the management of their  immunosuppressive therapy : maintenance, reduction, and discontinuation. The immunological  data of the patients are recovered from the HLA laboratory of the Nancy University Hospital. Inclusion Criteria:  -  Patients included in the Lorraine regional REIN registry over the period 2007-2019,  -  Returning in dialysis after a kidney transplantation, with a living or deceased donor.  -  On haemodialysis or peritoneal dialysis.  -  Registered or not on the waiting-list for retransplantation Exclusion Criteria:  -  Patients with graft dysfunction receiving a pre-emptive retransplantation  -  Absence of serum tested for anti-HLA (human leukocyte antigen) antibodies after the  return to dialysis.  -  No information on immunosuppressive agents

The investigators will conduct a proof-of-concept randomized controlled trial study to  provide preliminary evidence of efficacy of a resistance exercise training program for  maintaining white matter health and improving cognitive function in older adults with  vascular cognitive impairment, defined as the presence of cognitive impairment combined with  cerebral small vessel disease, compared with a stretch and relaxation program. A total of 88 adults with vascular cognitive impairment will be randomized to either a  12-month twice-weekly resistance training program or stretch and relaxation program. There  will be three measurement sessions: baseline, 6 months (midpoint of intervention period), and  12 months (end of intervention period). Inclusion Criteria:  The study will specifically recruit individuals who fulfill the diagnostic criteria for  SIVCI -- the presence of both cognitive impairment and small vessel ischaemic disease.  Specifically, individuals must meet the following inclusion criteria:  1. Montreal Cognitive Assessment (MoCA) score less than 26 at screening;  2. MMSE score of = or > 20 at screening;  3. Community-dwelling;  4. Lives in Metro Vancouver;  5. Able to comply with scheduled visits, treatment plan, and other trial procedures;  6. Must be able to read, write, and speak English in which psychometric tests are  provided with acceptable visual and auditory acuity;  7. Stable on a fixed dose of cognitive medications (e.g., donepezil, galantamine,  rivastigmine, memantine, etc.) that is not expected to change during the 12-month  study period, or, if they are not on any of these medications, they are not expected  to start them during the 12-month study period;  8. Provide a personally signed and dated informed consent document indicating that the  individual (or a legally acceptable representative) has been informed of all pertinent  aspects of the trial. In addition, an assent form will be provided at baseline and  again at regular intervals;  9. Able to walk independently; and  10. Must be in sufficient health to participate in study's aerobic-based exercise training  program. This will be based on medical history, vital signs, physical examination by  study physicians, and written recommendation by family physician indicating  individual's appropriateness to participate in an aerobic-based exercise training  program. Exclusion Criteria:  1. Absence of relevant small vessel ischaemic lesions on an existing brain computed  tomography (CT) or MRI;  2. Diagnosed with another type of dementia (e.g., AD) or other neurological conditions  (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and  mobility;  3. Diagnosed previously with a genetic cause of SIVCI (e.g., CADASIL);  4. At high risk for cardiac complications during exercise and/or unable to self-regulate  activity or to understand recommended activity level (i.e., Class C of the American  Heart Risk Stratification Criteria);  5. Participating in regular RT in the last six months;  6. Have clinically significant peripheral neuropathy or severe musculoskeletal or joint  disease that impairs mobility;  7. Taking medications that may negatively affect cognitive function, such as  anticholinergics, including agents with pronounced anticholinergic properties (e.g.,  amitriptyline), major tranquilizers (typical and atypical antipsychotics), and  anticonvulsants (e.g., gabapentin, valproic acid, etc.); or  8. Individual who plans to participate or is enrolled in a clinical drug trial concurrent  to this study.  9. Unable to meet the specific scanning requirements of the UBC 3T MRI Research Centre.  Specifically, we will exclude anyone with: pacemaker, brain aneurysm clip, cochlear  implant, recent surgery or tattoos within the past 6 weeks, electrical stimulator for  nerves or bones, implanted infusion pump, history of any eye injury involving metal  fragments, artificial heart valve, orthopedic hardware, other metallic prostheses,  coil, catheter or filter in any blood vessel, ear or eye implant, bullets, or other  metallic fragments.

To compare efficacy safety & side effects of multiload 375 IUD versus copper T 380 IUD when  inserted during elective CS Insertion of an intrauterine device (IUD) immediately after delivery is appealing for several  reasons. The woman is known not to be pregnant, her motivation for contraception may be high,  and the setting may be convenient for both the woman and her provider The World Health  Organization (WHO) recommends that a woman should wait at least 24 months after delivery  before the next pregnancy to decrease the adverse maternal, perinatal ,and infant outcomes.  Compared with other contraceptive methods, early post-partum IUD insertion has several  advantages. It provides immediate contraception without interfering with breast feeding, and  it may avoid discomfort related to insertion. Inserting an IUD immediately after placental  removal has not been associated with increased infection, uterine perforation, postpartum  bleeding, or uterine subinvolution . The expulsion rate is higher (approximately 12% in the  first postpartum year) after immediate postpartum insertion compared to insertion 4 to 8  weeks later. Continuation rates are relatively high (87.6% and 76.3%, at 6 and 12 months,  respectively Studies have shown that with effective provider training, the immediate  postpartum IUD insertion (IPPIUD) complications such as expulsion, pelvic infection,  bleeding, pain, missing threads ,and failure rates are not significantly different from those  of interval PPIUD insertion (4:6 weeks) after delivery Inclusion Criteria:  women delivered by elective CS ≥ 36 wks Exclusion Criteria:  Patients with PROM Patients on corticosteroids therapy Patients on anticoagulant patients  who refuse participate in the study with written consent

There are very few treatments that are effective in reducing severe behavioral problems  associated with autism. These behaviors include aggressive and self-harm behaviors, frequent  repetitive behaviors and severe hyperactivity. This study is being conducted to determine  whether cannabidiol can reduce any or all of these problem behaviors. Children with autism spectrum disorders (ASD) may have severe behavior problems, including  aggression, self-injurious behaviors, severe and persistent stereotypic behaviors, and  extreme hyperactivity, which limit their ability to function socially and academically and  are often disruptive to family life as well. Cannabidiol (CBD), a compound originally derived  from the cannabis plant but without the psychoactive effects found in cannabis, has been  shown to be safe and effective in the treatment of children with severe epilepsy. Two  non-controlled studies using CBD from local sources have demonstrated improvements in  behavior in children with autism. Parents of autistic children have been using CBD products  in an unregulated fashion with unknown dosing with anecdotal reports of improved behavior.  This study will use EPIDIOLEX (EPX), a purified CBD oral solution that was FDA approved in  June 2018 to treat severe forms of pediatric epilepsy. Study subjects will be 30 boys between  7 and 14 years of age with autism who have severe behavior problems. Every child will undergo  baseline clinical evaluation, neuropsychological, behavioral, cognitive, and language  testing, will have a test of brain wave activity (EEG) and a brain MRI scan. parents will  complete questionnaires on various aspects of their child's behavior. Fifteen children will  receive CBD for 8 weeks and 15 will receive a placebo that looks and tastes similar to the  CBD (Period 1). All of the baseline tests and questionnaires will then be repeated. After a 4  week washout period, behavioral and cognitive tests and questionnaires will be repeated and  then the treatments will be reversed (Period 2). At the end of 8 weeks, all of the baseline  tests and questionnaires will be repeated. Study personnel and parents will be blinded to the  treatment status of each child. Statistical analyses will be used to determine whether there  are significant differences between baseline testing and results after placebo or CBD  treatment. Types and severities of adverse events will be tracked to provide information  about the safety and tolerability of CBD in this population. If CBD is found to be safe and  effective in treating the behavioral problems associated with autism, this would be a major  new tool in the treatment of those children that could lead to improved functioning and  quality of life for the affected individuals and their families. Inclusion Criteria:  -  Boys ages 7-14 years  -  Confirmed diagnosis of autism based on ADOS testing  -  Autism severity assessed as severe with substantial behavioral problems  Severity of symptoms will be based on a number of criteria:  1. Aggressive and/or self-injurious (SIBs) behaviors occur almost daily (more than 6  times per week) in any situation (home, school, clinic, etc.).  2. Frequent (daily), persistent (lasting at least 5-10 minutes and repeated through the  day) stereotypies (repetitive behaviors such as hand flapping, running in circles,  jumping repeatedly, waving fingers in front of eyes)  3. Pervasive hyperactivity (child is so physically active that he cannot sit for meals or  school work, is moving all the time, jumping off furniture, climbing onto furniture,  etc.)  4. One of more of the above activities is deemed to contribute significantly to child's  inability to function by parental report and with clinician agreement based on history  and/or direct observation Exclusion Criteria:  -  the presence of epilepsy  -  a known genetic condition such as tuberous sclerosis  -  other significant health issues such as cardiac disease, presence of known congenital  brain malformation, or a history of central nervous system infection.  -  children who are on anticonvulsant medications such as clobazam or valproic acid will  also be excluded because of potential drug-drug interactions. At the time of  screening, each child's medication list will be checked for drugs that are known to  cause interactions with cannabidiol.  -  children with an allergy to any components of the study drug  -  children who are taking CBD from another source, unless parents are willing to stop  the treatment for at least 4 weeks prior to entering the study. CBD and other  cannabinoid blood levels will be performed at baseline and if CBD is detected in the  blood, the child will be not be included in the study.  -  children who might travel out of the area for a significant time during the study  -  children who recently participated in another investigational drug trial may be  excluded

Helicobacter Pylori (H Pylori) is a bug found in the digestive system. It can cause soreness  and redness in the stomach (gastritis). It can also cause ulcers in the stomach and other  parts of the digestive system. Vonoprazan is a medicine to treat people with H Pylori. It is  taken together with other medicines to fight infections caused by H Pylori.  The main aim of this study is to learn if vonoprazan changes how the other medicines are  processed by the body. It will be compared with another medicine called esomeprazole. Other  aims are to check for side effects from the study medicines.  At the first visit, the study doctor will check who can take part. Participants who take part  will be picked for 1 of 2 treatments by chance.  -  Vonoprazan taken with bismuth, clarithromycin, and amoxicillin  -  Esomeprazole taken with bismuth, clarithromycin, and amoxicillin  Both treatments will last for 14 days. Participants will stay in the clinic throughout their  treatment.  After treatment, the clinic staff will telephone the participants 2 days later for a  check-up. The participants will visit the clinic 4 weeks later for a final check-up. This is a study in healthy participants with Helicobacter pylori (HP positive) to evaluate  the safety, tolerability and PK of a quadruple therapy with bismuth, clarithromycin,  amoxicillin, and vonoprazan versus quadruple therapy with bismuth, clarithromycin,  amoxicillin, and esomeprazole.  The treatment phase consists of quadruple therapy twice daily (BID) with bismuth potassium  citrate (600 mg), clarithromycin (500 mg), amoxicillin (1000 mg), and vonoprazan (20 mg)  (Group B) or quadruple therapy BID with bismuth potassium citrate (600 mg), clarithromycin  (500 mg), amoxicillin (1000 mg), and esomeprazole (20 mg) (Group A) from Days 1 to 14.  Participants will be discharged on Day 15 after all procedures have been performed.  This single-center will be conducted in China. Participants will remain confined to the study  site from check-in (Day -1) through Day 15 and will followed up through call on Day 17 and  return on Day 42 for a follow-up assessment. Inclusion Criteria:  1. HP positive participants.  2. Weighs at least 50 kilogram (kg) and has a body mass index between greater than (>) 18  and less than equal to (<=) 30 kilogram per square meter (kg/m^2), inclusive, at  screening and Day -1 (check-in).  3. Is willing to abstain from strenuous exercise from 72 hours before first dose (Day 1)  until the Follow-up call on Day 17. Exclusion Criteria:  1. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).  2. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol  abuse (defined as regular consumption of 21 units or more units per week) at any time  prior to the Screening Visit or is unwilling to agree to abstain from alcohol and  drugs throughout the study (up to Day 17).  3. Has history of gastroesophageal reflux disease (GERD), symptomatic GERD, erosive  esophagitis, duodenal ulcer, gastric ulcer, Barrett's esophagus, or Zollinger-Ellison  syndrome, or has current or recent (within 6 months) gastrointestinal disease that  would be expected to influence the absorption of drugs.  4. Has undergone therapeutic upper gastrointestinal endoscopic therapy (example,  endoscopic hemostasis or excision including biopsy) within 30 days prior to Screening.  5. Has undergone major surgical procedures within the past 1 month or are scheduled to  undergo surgical procedures that may affect gastric acid secretion (example, abdominal  surgery, vagotomy, or craniotomy).  6. Has a history of cancer, except basal cell carcinoma or Stage 1 squamous cell  carcinoma of the skin that has been in remission for at least 5 years prior to Day 1.  7. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus  (HCV) antibody, human immunodeficiency virus (HIV) antibody/antigen at Screening.  8. Has used nicotine-containing products (including but not limited to cigarettes, pipes,  cigars, chewing tobacco, nicotine patch or nicotine gum) within 6 weeks prior to  Check-in. Cotinine test is positive at Screening or Check-in.  9. Has poor peripheral venous access.  10. Has donated or lost 450 milliliter (mL) or more of his blood volume (including  plasmapheresis), or had a transfusion of any blood product within 90 days prior to Day  1.  11. Has abnormal Screening or Check-in laboratory values that suggest a clinically  significant underlying disease or subject with the following laboratory abnormalities:  alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin >  the upper limit of normal (ULN).  12. Has reduced renal function assessed by having an estimated glomerular filtration rate  <90 milliliter per min per 1.73 square meter (mL/min/1.73 m^2) (as estimated by  Chronic Kidney Disease-Epidemology Collaboration) at Screening or Check-in.

This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482)  compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as  assessed by the rate of sustained recovery through Day 29. This study was intended to include two parts: Part 1 was a dose-ranging phase 2 study, and  Part 2 was a phase 3 study to evaluate the dose selected in Part 1. However, this study was  terminated due to business reasons prior to conducting Part 2. Participants in Part 1 were  followed until Month 7. Inclusion Criteria:  -  Has documentation of polymerase chain reaction (PCR)-confirmed severe acute  respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with sample collection ≤ 10  days prior to the day of randomization. PCR is the preferred method; however other  diagnostic methods are allowed if authorized by use in the country  -  Had initial onset of signs/symptoms attributable to COVID-19 for ≤10 days prior to the  day of randomization and ≥1 sign/symptom attributable to COVID-19 present at  randomization  -  Requires medical care in the hospital for ongoing clinical manifestations of COVID-19  (not just for public health or quarantine purposes)  -  Has mild, moderate, or severe COVID-19  -  Is willing and able to take oral medication  -  Males agree to the following during the intervention period and for at least 90 days  after the last dose of study intervention: Refrain from donating sperm; and either  abstain from heterosexual intercourse as their preferred and usual lifestyle  (abstinent on a long term and persistent basis) and agree to remain abstinent; or must  agree to use contraception  -  Females are not pregnant or breastfeeding, and at least one of the following  conditions applies: Is not a woman of child bearing potential (WOCBP); or is a WOCBP  and using a contraceptive method that is highly effective (a low user dependency  method OR a user dependent method in combination with barrier method), or be abstinent  from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a  long-term and persistent basis) for 28 days from the start of study intervention; a  WOCBP must have a negative highly sensitive pregnancy test (serum test is required)  within 24 hours before the first dose of study intervention Exclusion Criteria:  -  Has critical COVID-19 with any of the following: respiratory failure (including  endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow  nasal cannula (flow rates >20L/min with fraction of delivered oxygen ≥ 0.5),  noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation  (ECMO))  -  Is on dialysis or has reduced estimated glomerular filtration rate (eGFR) <30  mL/min/1.73m^2 by the Modification of Diet in Renal Disease (MDRD) equation  -  Has any of the following conditions: human immunodeficiency virus (HIV) with a recent  viral load >50 copies/mL or cluster of differentiation 4 (CD4) <200 cell/mm^3;  chemotherapy required within 6 weeks before randomization; a neutrophilic granulocyte  absolute count <500/mm^3; autologous or allogeneic hematopoietic stem cell transplant  recipient  -  Has history of Hepatitis B or Hepatitis C infection with any of the following: 1)  cirrhosis 2) end-stage liver disease 3) hepatocellular carcinoma 4) aspartate  aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit  of normal at screening  -  Has a history of acute pancreatitis within 3 months prior to randomization or a  history of chronic pancreatitis  -  Is taking or is anticipated to require any prohibited therapies  -  Is unwilling to abstain from participating in another interventional clinical trial  through Day 29 with an investigational compound or device, including those for  COVID-19 therapeutics  -  Is anticipated to require transfer to a non-study hospital within 72 hours  -  Has a baseline heart rate of < 50 beats per minute at rest  -  Has a platelet count <100,000/μL or received a platelet transfusion in the 5 days  prior to randomization  -  Has hypersensitivity or other contraindication to any of the components of the study  interventions as determined by the investigator  -  Has any condition for which, in the opinion of the investigator, participation would  not be in the best interest of the participant or that could prevent, limit, or  confound the protocol-specified assessments including but not limited to: participants  who are not expected to survive longer than 48 hours after randomization or  participants who are expected to require mechanical ventilation within 48 hours after  randomization or participants with a recent history of mechanical ventilation or  participants with conditions that could limit gastrointestinal absorption of capsule  contents

To investigate dynamic change of gut microbiomes and metabolites, and their effects on immune  modulation. To evaluate the efficacy and safety of TNT with GEN-001 (Lactococcus lactis) and  identify predictive biomarkers for pathologic response in patients with locally advanced  rectal cancer (LARC). The multimodality strategy, neoadjuvant chemoradiotherapy (CRT) or total neoadjuvant therapy  (TNT) followed by surgery, has been widely used to improve local control and overall survival  in locally advanced rectal cancer (LARC). TNT is a recently promising strategy incorporating  systemic chemotherapy following short-course radiotherapy before surgery in LARC, and showed  superior rates of pathologic complete response (pCR) compared with the concurrent CRT  followed by surgery and adjuvant chemotherapy (CRT-A). However, issues regarding neoadjuvant  therapy-related toxicity as well as disease progression during TNT have been raised, which  need to identify biomarkers for prediction of treatment responses and safety in patients with  LARC.  Growing evidence suggests that gut microbiomes interact with tumor microenvironment and are  related with inflammation and immunomodulation. The association between gut microbiomes and  responses of chemotherapy or immunotherapy has been previously reported. The administration  of certain beneficial microbiome can be one of the strategies to treat gut dysbiosis in  cancer patients, restoring microbial diversity and changing the composition of microbiome.  GEN-001, Lactobacillus lactis is a live, purified facultative anaerobic gram-positive  probiotic lactic acid bacterial strain. The preclinical studies showed the potential  therapeutic effects of GEN-001 as an anti-cancer treatment through the activation of immune  cells, including CD4 or CD8 T-cells and natural killer cells, and synergistic effects with  oxaliplatin chemotherapy. Therefore, the investigators plan to investigate dynamics of gut  microbiomes and metabolites, and their effects on immune modulation. Additionally  investigators plan to evaluate the efficacy and safety of TNT with GEN-001 and identify  predictive biomarkers for pathologic response in patients with LARC. Inclusion Criteria:  1. Age > 19 years  2. Locally advanced rectal cancer, histologically confirmed; clinically T3/4, clinically  N+, enlarged lateral lymph nodes, extramural vascular invasion (+), or mesorectal  fascia (+)  3. Patients who schedule to receive total neoadjuvant therapy, including short-course  radiotherapy (25 Gy in 5 fractions), followed by FOLFOX chemotherapy (5-fluorouracil,  leucovorin, and oxaliplatin)  4. Patients with ability to swallow and retain oral medication and no clinically  significant gastrointestinal abnormalities that may alter absorprtion  5. Patients with ability to collect their blood and stool samples Exclusion Criteria:  1. Rectal cancer, other histologic type than adenocarcinoma (such as squamous cell  carcinoma)  2. Patients who schedule to receive concurrent chemoradiotherapy or short-course  radiotherapy alone followed by surgery and adjuvant chemotherapy  3. Patients who need emergent surgery or colostomy due to obstruction or bleeding  4. Prior use of proton pump inhibitors or H2 blockers, probiotics, immunosuppressive  agents, and antibiotics within 4 weeks  5. Patients have concurrent medication that may interact with fluoropyrimidine or  oxaliplatin (i.e. flucytosine, phenytoin, or warfarin)  6. Known prior history of severe adverse events during fluoropyrimidine or deficiency of  dihydropyrimidine dehydrogenase (DPD)  7. Known prior severe hypersensitivity to platinum  8. Patients who have an active infection requiring antibiotics, antifungal, or antiviral  agents  9. Prior solid organ or allogenic stem cell transplantation  11. Patients who have clinically significant medical disease  -  Cardiovascular disease <6 months prior to enrollment (myocardial infarction, unstable  angina, coronary artery bypass surgery or percutaneous coronary intervention)  -  Cerebral vascular accident/stroke (<6 months prior to enrollment)  -  Congestive heart failure (≥New York Heart Association (NYHA) Classification Class II)  -  Uncontrolled hypertension by standard therapy: systolic blood pressure >160 mmHg or  diastolic blood pressure > 100 mmHg  -  Serious cardiac arrhythmia requiring medication 12. Pregnant women 13. Patients who  have psychiatric condition that would prohibit the understanding or rendering of  informed consent or that would limit compliance with study requirements

Rationale: The observational data of University Children's Hospitals of Nice, suggest that  about a quarter of children and adolescents with ADHD may present with an abnormal thyroid  profile.  Main objective: To confirm that a subsample of children and adolescents with ADHD present  with an abnormal thyroid profile using the gold standard for free fraction of hormones :  chromatography with mass spectrometry.  Secondary objective: To examine to what extent this categorization holds using classic  immuno-analytic assays. To characterize clinically and from a neuropsychological point of  view this subsample and compare it to the other participants.  Study duration and design: 30 months (24 months for inclusion and 6 months for data analyses)  open-label, (category 2 : interventional research with minimal risks or constraints),  multicentre, without treatment or placebo administration.  Expected outcomes: Ancillary studies will investigate genetic physiopathological mechanisms  (polymorphisms of deiodase or transmembrane carriers of thyroid hormones) and link this  profile to other biological markers proposed in the literature (low ferritinemia, higher  oxidative stress, atopic comorbid disease). The clinical trajectory of this subgroup and the  persistence of this abnormal thyroid profile in adulthood will be a relevant issue in the  future. Rationale: The internal observational data on 514 children and adolescents with ADHD suggest  that 16-28% of them have an abnormal thyroid profile in immuno-analysis: normal free  thyroid-stimulating hormone TSH and T4 but abnormally high free T3. Several  pathophysiological hypotheses can be formulated, some of which relate to possible  polymorphisms of the deiodase or transmembrane carriers of thyroid hormones, and also with  other suspected biological markers of ADHD reported in the literature (low ferritin, atopic  disease and oxidative stress). This abnormal thyroid profile may be an endophenotype of a  subgroup of children and adolescents with ADHD. However, the reference technique for the  determination of free fractions of hormones is chromatography with mass spectrometry and not  immuno-analysis.  Main objective : To confirm by chromatography with mass spectrometry the existence of a  subgroup of children and adolescents with ADHD with this abnormal thyroid profile.  Secondary objectives:  -  Describe this subgroup by sex (male/female) and age (before 12 and after 12 years)  clinically and neuropsychologically (Attention Network Task and Tower of London coupled  with eye-tracking) and compare it with the rest of the sample.  -  Dose thyroid hormones and TSH levels with 4 different techniques of immuno-analysis  -  Calculate the classification concordance (abnormal profile / normal profile) between all  pairs of dosage methods (chromatography and 4 immuno-analysis based techniques)  -  Calculate 95% reference intervals for all assays and techniques throughout the sample.  Main evaluation criterion: free T3 greater than the 97.5 percentile of the reference interval  in chromatography, free T4 between the 2.5 percentile and the 97.5 percentile with this same  technique, and free TSH between the 2.5 percentile and the 97.5 percentile of the  immuno-analytical reference interval.  Secondary evaluation criteria:  -  Describe the subgroup and compare it to the rest of the sample:  -  Number of criteria for inattention, hyperactivity-impulsivity and therefore  clinical presentation of ADHD (Predominant Inattentive, Predominant  Hyperactive-Impulsive, Combined)  -  Scores for inattention, hyperactivity-impulsivity and their sum on the ADHD-Rating  Scale and score on the Clinical Global Impression - Severity  -  Pattern of comorbidities diagnosed with Kiddie-SADDS-PL, manual, ocular and  pedestrian preference, presence of atopic disease  -  Performance at the Attention Network Task and Test of the Tower of London coupled  with eye-tracking  -  Calculate the classification concordance all pairs of dosage methods (chromatography and  4 immuno-analysis based techniques): correlation, concordance indices 2x2 (for example,  Cohen's kappa)  -  Calculate 95% reference intervals with age as co-variable and separately for boys and  girls.  Study duration: 30 months (24 months for inclusion and 6 months for data analyses) Study  design: Open-label, cross-sectional (category 2 : interventional research with minimal risks  or constraints), multicentre, no treatment or placebo administration.  Selection criteria:  -  Inclusion criteria: Boys or girls aged 7 to 17 with ADHD (as per Diagnostic and  Statistical Manual DSM-5 criteria).  -  Criteria for Non-Inclusion:  -  Known or concurrent diagnosis of Autism Spectrum Disorder, Schizophrenia or  Psychotic Disorder (as determined by DSM-5), thyroid disease of any origin, genetic  disease known to affect thyroid function.  -  Any psychotropic treatment (for ADHD or others) in the month before inclusion or  any treatment that may affect thyroid function  -  Exclusion criteria: Withdrawal of informed consent by at least one of the child's  parents or their legal representative.  Course of the study: The criteria for non-inclusion are checked, the diagnosis is confirmed  using the Kiddie-SADS-PL before the child can be included. The patient's participation stops  after the venous blood collection and the administration of two neuropsychological tests  (Attention Network Task and Tower of London). The tubes are transported to the biochemistry  laboratory of the CHU of Nice which prepares five aliquots (4 for assays in immuno-analysis  including 2 on site, and one for assay in chromatography with mass spectrometry at the CHU of  Toulouse).  Expected outcomes: The identification and clinical characterization of a subgroup of children  and adolescents with ADHD with an abnormal thyroid profile will support the clinical  diagnosis for these at least. Ancillary studies will investigate genetic physiopathological  mechanisms (polymorphisms of deiodases or transmembrane carriers of thyroid hormones) and  link this profile to other biological markers proposed in the literature (low ferritinemia,  higher oxidative stress, atopic comorbid disease). The clinical trajectory of this subgroup  and the persistence of this abnormal thyroid profile in adulthood will be relevant in the  future Inclusion Criteria:  -  Boys or girls aged by 7 and 17 years old included  -  Diagnosed with ADHD according to DSM-5 criteria with either Inattentive predominant,  Hyperactive-impulsive predominant or Combined presentations.  -  Scoring at least 28 (maximum value 54) on the ADHD-RS total score that is the sum of  18 items each rated on a 0-3 scale.  -  Scoring at least 4 (= Moderate) on the Clinical Global Impression - Severity scale  -  Without any clinical symptom of either hypothyroidism or hyperthyroidism  -  Who signed an informed consent form  -  Whose at least of parents (or default a legal representative) signed an informed  consent form Exclusion Criteria:  Known or concomitant diagnosis of Autism Spectrum Disorder according to DSM-5 criteria  Known or concomitant diagnosis of Schizophrenia or Psychotic Disorder according to DSM-5  criteria Known or concomitant diagnosis of any thyroid disorder (hypothyroidism or  hyperthyroidism) whatever the cause might be Known or concomitant diagnosis of any genetic  condition affecting the thyroid function (e.g. Down syndrome)  Intake in the last month of a psychotropic drug for:  ADHD: methylphenidate, atomoxetine, dexamphetamine, lisdexamphetamine, guanfacine or  clonidine.  Any psychiatric disorder (antipsychotic, anxiolytics, antidepressant, etc.)  Intake in the last month of a molecule affecting the thyroid function:  -  Any compound containing thyroid hormones  -  Anti-thyroid drugs: carbimazole, thiamazole, propylthiouracil and perchlorate  -  Any compound containing iodine  -  Significant application on the skin of iodized products in the last six months  -  Injection of water-soluble iodine contrast agents in the last 2 months or fat-soluble  in the last 6 months

The proposed research will characterize of the time course of neurological and locomotor  recovery as well as development of compensatory strategies throughout sub-acute and chronic  phases post stroke. In addition, we will also investigate the extent to which measures of  recovery and compensation are malleable and can be altered with specific interventions in  both the early and late stages post-stroke. Delineation of the time course of development and  magnitude of patterns of recovery and compensation should result in alternative predictive  "rules' regarding how patients early post-stroke could recovery functional and neurological  function. Recovery of locomotion is a primary goal of rehabilitation post-stroke and a major  determinant of future morbidity and mortality. While substantial recovery is observed early  post-stroke, recent evidence suggests the magnitude and time course of recovery is  deterministic and based primarily on initial motor deficits. The "proportional recovery" rule  suggests ~70% of neurological recovery (measured by the lower limb Fugl-Meyer Assessment -  LL-FMA) is typically achieved and is not influenced by the dosage of therapy. These findings  suggest the physical interventions applied to patients are of minimal importance to long-term  recovery. That hypothesis conflicts directly with our recent efforts suggesting that  maximizing the amount and intensity of task-specific (stepping) practice (high-intensity  training; HIT) directly influences gains in locomotor function. Providing HIT at heart rates  (HRs) greater than traditional aerobic paradigms (mean 110% baseline HRmax) is associated  with gains in locomotor speed, which challenges the notion of "proportional recovery".  These conflicting hypotheses likely arise from differences in terminology and methodology  used to characterize recovery post-stroke. First, the traditional measure of neurological  recovery (LL-FMA) does not adequately characterize other impairments (strength, postural  stability) that are more closely associated to locomotor function and are responsive to  physical interventions. Second, despite gains in selected impairments, patients often utilize  alternative (compensatory) movement patterns to accomplish locomotor tasks. More directly,  locomotor recovery (i.e., speed/distance) is often accomplished using strategies employed  prior to stroke and compensatory strategies, particularly in those with substantial  impairments.  Our central hypothesis is that if changes in neurological recovery are deterministic, other  measures of locomotor recovery or compensations may also be predictable. Our published data  detail how HIT or conventional interventions can alter impairments and locomotor recovery, as  well as changes in locomotor compensations. More directly, our data provide evidence that  specific subgroups of patients demonstrate substantial compensations with improved recovery,  whereas others reveal limited changes despite similar interventions. Data that detail the  progression of neurological recovery, locomotor recovery, and locomotor compensations  throughout the subacute to chronic phase post-stroke and their responsiveness to HIT is  uncertain. Similar to upper limb recovery algorithms, predictions of mobility outcomes could  provide valuable information to clinicians who make decisions regarding patient's prognosis,  including whether patients will be able to walk with or without assistance or at certain  speeds, and what compensatory strategies they may require to ambulate independently (braces,  devices or altered movement patterns). The overarching goal of this project is to examine the  time course of neurological and locomotor recovery, and associated compensatory strategies,  over the subacute to chronic stages post-stroke and their responsiveness to HIT. Inclusion Criteria:  -  individuals early post-stroke (<15-30 days)  -  first ever stroke  -  unilateral hemiparesis  -  currently receiving inpatient rehabilitation  -  ability to follow 1-step commands  -  provision of informed consent  -  medical clearance from the rehabilitation physician to participate. \ Exclusion Criteria:  -  uncontrolled cardiovascular, metabolic or respiratory disease that limits exercise  participation (e.g., congestive heart failure, resting blood pressure > 200/110 mmHg,  uncontrolled diabetes, end-stage renal disease)  -  absolute criteria for termination of exercise testing during initial and repeated ECG  testing during graded exercise testing using ACSM guidelines .  -  other orthopedic or neurological disorder that limited walking prior to stroke

This phase II trial studies the effects of isatuximab given as a rapid-infusion in treating  multiple myeloma that has come back (recurrent) or has not responded to treatment  (refractory). Isatuximab, also known as Sarclisa, is an antibody (proteins that can protect  the body from foreign organisms, such as bacteria and viruses) directed against cluster of  differentiation 38 (CD38), a receptor antigen (a receptor or protein on the outside of blood  cells that can be used as a target). Isatuximab may stop the growth of some blood cancers.  Normally, the fastest that intravenous isatuximab can be given - for patients who have not  had any reactions to their first two doses - is over 1 hour and 15 minutes. This study is  designed to test whether intravenous isatuximab can be given over 30 minutes ("rapid  infusion") among patients who have not developed any reactions to at least 2 prior doses of  intravenous isatuximab at normal speeds. If shown to be safe, "rapid infusion" isatuximab may  ultimately improve the patient experience while reducing the overall cost of the infusion. PRIMARY OBJECTIVE:  I. To evaluate the incidence of grade 2 or higher (Gr2+) infusion-related reactions (IRRs)  with rapid-infusion (RI) isatuximab across 6 doses.  SECONDARY OBJECTIVE:  I. To estimate time savings with RI isatuximab (versus estimated standard of care [SOC]  isatuximab duration lengths) across 6 doses of isatuximab.  OUTLINE:  Patients must have received standard of care isatuximab IV over for at least 2 doses without  any Gr2+ IRRs reported. Patients will then receive a rapid infusion of isatuximab IV over 30  minutes. If a >=Grade 2 iRR occurs, then participants will revert to a SOC infusion time and  be taken off the study. If a Grade 1 or no IRR occurs, then participants will receive another  rapid infusion of 30 minutes and assessed again for IRRs. Rapid infusions and IRR assessment  after each RI will continue for up to at least 6 doses or until the patient experiences an  Grade 2 or higher IRR. Inclusion Criteria:  -  Histologically confirmed diagnosis of multiple myeloma (International Classification  of Disease (ICD-10) code: C90.0)  -  Previous exposure to at least one proteasome inhibitors (PI) and lenalidomide (or  candidacy for isatuximab as per updated Food and Drug Administration (FDA) package  insert information in the future)  -  Planned or current isatuximab-containing therapy. Patients receiving isatuximab as  part of a clinical trial are eligible for this study if allowed by the trial sponsor.  -  For ease of registration, patients will be allowed to enroll at any point after  the decision is made to initiate isatuximab (with the understanding that their  initial doses will be standard of care (SOC), including the first 2 doses for all  patients). However, rapid infusion (RI) isatuximab will only be administered to  participants who have not had infusion-related reactions (iRRs) during >= 2  consecutive prior doses of SOC isatuximab  -  Ability to understand a written informed consent form (ICF) document, and the  willingness to sign the ICF document Exclusion Criteria:  -  Age < 18  -  Body weight > 70 kilograms (kg) at the time of any RI isatuximab dose  -  Current pregnancy or (if of reproductive age) unwillingness to follow contraception  requirements as per the FDA package insert  -  New York Heart Association Stage IV heart disease, i.e. unable to carry on any  physical activity without discomfort or symptoms of heart failure (as per study  investigator)  -  Any medical condition, including mental illness or substance abuse, deemed by the  principal investigator to interfere with the ability to provide consent or cooperate  with study procedures

Objective: To determine whether ultrasound-guided Intra-Articular Hypertonic Dextrose and  hydrodilatation improves pain and function in patients with frozen shoulder(FS) Setting: a medical center hospital. Participants: Subjects with primary FS with shoulder pain  more than 3 months. Interventions: Participants randomly be assigned into A and B group:  group A received ultrasound-guided hydrodilatation with hypertonic Dextrose with a mixture of  2mL of 50%, 1mL of 2% lidocaine, and 6ml normative saline ; group B : ultrasound-guided  hydrodilatation with 9 mL of normative saline and 1 mL of 2% lidocaine.  Main Outcome Measures: The primary outcome measure was the Shoulder Pain and Disability Index  score. Secondary outcomes were the VAS of shoulder pain level, muscle power and angles of  shoulder passive range of motion, including flexion, abduction, extension, external rotation,  and internal rotation at pretreatment and weeks 2, 4, 8, 12 and 24 of post-treatment. Inclusion Criteria: None Exclusion Criteria: None

This study's specific aims were to: develop a digital intervention as a prevention  intervention through focus groups with 40 youth; pilot-test the developed digital  intervention with 30 adolescents, using methods from the investigator's prior research;  develop implementation strategies and partners through focus groups with 50 School Based  Health Alliance affiliates and 30 adolescents from an Advisory Council. Most opioid misuse begins during adolescence and young adulthood. Adolescence is the time to  intervene with prevention interventions (i.e., interventions focused on adolescents who have  not yet misused opioids) in settings like school-based health centers (HCs), yet few  interventions exist that prevent initiation of opioid misuse. "Serious videogame"  interventions can improve health behaviors. They meet adolescents "where they are," and  compared to standard interventions, they can reach large populations, with consistent  fidelity, place limited demands on personnel/resources, and facilitate rapid sustainable  distribution, all at a potentially lower cost.  This study harnessed the power of videogame interventions and incorporated components of  effective substance use prevention programs to develop an evidence-informed intervention to  prevent the initiation of opioid misuse in adolescents. Building on our experience developing  videogame interventions and in partnership with the national School-Based Health Alliance  (SBHA), we developed and tested a new videogame intervention, PlaySmart.  PlaySmart was built upon our PlayForward videogame intervention platform that has  demonstrated efficacy in improving attitudes and knowledge related to risk behaviors. Through  rigorous formative work and with input from adolescents, and our SBHA and game development  partners, we created the PlaySmart videogame intervention.  PlaySmart is designed to provide players with behavioral skills and knowledge through  repetitive and engaging videogame play to target adolescent perception of risk of harm from  initiating opioid misuse.  The gap in the research on preventing initiation of opioid misuse in youth and in  implementing prevention programs with good fidelity needs to be urgently addressed given the  high prevalence of adolescent opioid misuse and overdose. This research has the potential to  create a videogame intervention to prevent initiation of opioid misuse with far-reaching and  sustained impact on adolescents. Inclusion Criteria:  -  Adolescent participants must attend high school that has a school-based health center,  to participate in pilot testing Exclusion Criteria:   -  Failure to meet Inclusion Criteria

Pre-operative anxiety is a major problem in children because it produces undesired results on  induction and postoperative outcome. Dexmedetomidine is a highly specific alpha 2 adrenergic  receptor agonist. Studies suggest that Dexmetomidine administration is safe as it is less  invasive and have a short half-life.  Paracetamol is a potent physical pain killer. It also reduces psychological reactivity and  blunts physical and social pain.  Adenotonsillectomy is one of the most common surgeries performed in pediatric age groups, so  it is important to reduce pre-operative anxiety in those children. Pre-operative anxiety is a major problem in children because it produces undesired results on  induction and postoperative outcome. Dexmedetomidine is a highly specific alpha 2 adrenergic  receptor agonist. Studies suggest that Dexmetomidine administration is safe as it is less  invasive and have a short half-life.  Paracetamol is a potent physical pain killer. It also reduces psychological reactivity and  blunts physical and social pain.  Adenotonsillectomy is one of the most common surgeries performed in pediatric age groups, so  it is important to reduce pre-operative anxiety in those children.  The objective of this descriptive study is to compare the efficacy of dexmedetomidine and  paracetamol premedication, measuring the degree of anxiety in the children prepared for  adenotonsillectomy when they are separated from their parents. Inclusion Criteria:  -  The patients who are clinically free or with controlled medical condition [ASA I or  ASA II].  -  Age between 2 to 8 years. Exclusion Criteria:  -  ASA III or ASA IV.  -  Age greater than 8 years.  -  Parents' refusal to participate in the study.  -  Patients with obstructive sleep apnea.  -  Patients with known allergy or hypersensitivity reaction to any of the drugs used in  the study.  -  Patients with nasal infection or nasal pathology.

Dietary fibres are complex carbohydrates present in fruit, vegetables, grains, and beans  which are broken down into smaller molecules (short-chain fatty acids) in the colon by the  gut microbiota. Increased intake of dietary fibres is associated with a lower risk of type 2  diabetes, obesity, or heart disease. Despite their health benefits, most people consume half  of the daily recommended intake (30 grams) of dietary fibres. This trend has become more  apparent in the past few decades with the advent of ultra-processed foods which are poor in  dietary fibres. Since this change in dietary habits is more recent, the research team  hypothesizes that older generations have a more diverse and better adapted gut microbiota at  breaking down dietary fibres compared to younger generations.  The aims of this study are to examine the effects of the daily intake over four weeks of a  dietary fibres supplement on the gut microbiota, metabolic profiles, and general health in a  transgenerational cohort (grandmother, mother and daughter OR mother and daughter) compared  to placebo. Eligible participants will need to take daily for 14 days a dietary fibre supplement or  placebo (depending on the randomisation) followed by wash-out period of 14 days and then  followed by taking daily for 14 days the opposite arm of intervention (placebo or dietary  fibre supplement). During the study period, participants will come to the research facility  to assess the impact of these supplements on their gut microbiota, metabolic profiles and  blood glucose, insulin and gut hormone levels. Inclusion Criteria:  -  Any of the following groups of people (in direct descent and from the same family)  Grandmother, mother and daughter Mother and daughter Grandmother and granddaughter  -  Age 18-85 (inclusive)  -  BMI: 18.5-30 kg/m2 (inclusive)  -  Considering themselves healthy Exclusion Criteria:  -  Intake of antibiotics in the past 3 months and during the study  -  Intake of probiotic supplements in the past month and during the study  -  Regular intake of laxatives in the past month and during the study  -  Subjects with the following conditions Inflammatory Bowel Disease (IBD) Irritable  Bowel Syndrome (IBS) Coeliac Disease Type 2 Diabetes Any type of cancer Autoimmune  conditions Conditions that affect the liver Conditions that affect the pancreas  -  Subjects who require medical intervention in the coming 3 months  -  Smokers  -  Shift workers  -  Gluten and/or lactose intolerance  -  Pregnant and lactating women  -  Subjects living in care homes  -  had weight changes >5% in the preceding 3 months  -  Subjects who are unable to give informed consent by themselves  -  Subjects who are currently participating in other clinical trials

This study aimed to examine the effects of using probiotic yogurt on body components (body  weight, height, etc.) and digestive system (distention, gas, etc.) in obesity (obese women),  which is an important public health problem all over the world. Obesity is an important public health problem worldwide and is associated with  non-communicable diseases such as Type 2 Diabetes, hypertension, coronary heart disease,  hyperlipidemia, non-alcoholic fatty liver, some neoplasms, and infertility disease.However,  it is supported by the literature that nutrition and obesity cause microbial dysbiosis.  In this study, it was aimed to use probiotics and yogurt with the thought that nutrition can  manipulate the microbiota.  It was aimed to investigate the effects of probiotic yogurt consumption on anthropometric  measurements, metabolic parameters, and gastrointestinal symptoms in obese women (25-45 years  old) with the prospective method.  The study was carried out in patients who were diagnosed with obesity by the doctor,  consulted the Dietitian, and accepted + signed the voluntary consent form.  Total data and measurements were followed and recorded by the same Dietitian. Compliance with  medical nutrition therapy, recording of scales were followed weekly.Patients diagnosed with  COVID-19 during the study were excluded from the study. Inclusion Criteria:  -  Female patients aged 25-45 years, with a BMI of 27-35 kg/m2 diagnosed as obese by the  doctor  -  Female patients without a chronic disease  -  Female patients between the ages of 25-45 with regular menstrual cycles,  -  Female patients between the ages of 25-45 who are not pregnant or lactating  -  Female patients who do not use drugs, herbal products, etc. nutritional supplements. Exclusion Criteria:  -  Patients with BMI≥ 36 kg/m2  -  Patients with diabetes, gastrointestinal diseases, CRF, etc.  -  Women in pregnancy and lactation period,  -  Male patients  -  Weight loss medicine etc. patients with drug use  -  Patients who use antibiotics  -  Patients using probiotics, propolis, herbal products, etc.  -  Patients with menstrual irregularity  -  Female patients who have entered the menopause

Comparing the amount of papules, macules, pustules, and irritation caused by  pseudofolluculitis barbae in subjects using depilatory cream versus traditional shaving  methods. Comparing an experimental group that will remove facial hair with magic shave powder gold,  and a control group that will continue using traditional shaving methods. Both the subject  and a physician will make observations to determine the efficacy of depilatory creams in  reducing pseudofolliculits barbae. Inclusion Criteria:  -  Male  -  PFB patient Exclusion Criteria:   -  Failed sensitivity testing

In the United State, there are millions of US teens who are not vaccinated against the human  papillomavirus (HPV) putting them at risk of getting HPV-related cancers. Although there are  clinical guidelines recommending the HPV vaccine and interventions encouraging parents to  vaccinate their children to prevent HPV-related cancers, the vaccination rate for teens  remains low according to a 2018 national survey. Survey data shows that HPV vaccine complete  series coverage for teens aged 13-15 years was 50%, far below the 80% target of Healthy  People 2020. Receiving a strong provider recommendation is the most powerful strategy for  improving HPV vaccine rates. Yet, little is known about how to include provider  recommendations and other important factors into an intervention to improve the HPV  vaccination rates. Studies show there are provider, patient and system-level barriers in the  initiation and completion of HPV vaccine series among 9-12 years old children. Barriers to  the HPV vaccine also differ across demographic subgroups, communities, and clinics.  Interventions that address only one component are not responsive to site barriers and as  effective as one that addresses multiple components and site-specific barriers. This study  uses a 3-arm cluster randomized controlled trial (RCT) to compare three implementation  strategies to improve provider recommendations on the HPV vaccine. Two of the implementation  strategies (local-tailored and prescribed strategy) utilize a multilevel approach. The three  implementation strategies of interest are (1) a "local-tailored" implementation strategy,  co-designed with local care teams to address local barriers and contexts (2) A "prescribed"  strategy, most commonly used by health systems, that involves pre-specified interventions  addressing pre-selected vaccination barriers and (3) usual standard of care where there are  no research-led activities. We will use surveys, interviews, and electronic health records to  evaluate the three implementation strategies and their impact on improving HPV vaccination  rates. The study surveys and interviews will include pediatric providers, nurses,  administrators, staff members, and parents of HPV vaccine-eligible children (9-12 years old).  Successful implementation will be defined as improvement in HPV vaccination rates (primary  outcome), strengthening provider recommendation (secondary outcome), and the  cost-effectiveness of the implementation strategy. US teens remain at risk of developing human papillomavirus (HPV)-related cancers due to  inadequate HPV vaccine uptake, despite strong endorsement in clinical guidelines and  substantial intervention efforts by healthcare providers and public health entities. A strong  recommendation from a clinician has been identified as the most powerful facilitator of HPV  vaccine uptake, yet less than half of parents of pre-teens for whom routine HPV vaccination  is recommended by the CDC's Advisory Committee on Immunization Practices receive an HPV  vaccine recommendation from their providers. Unfortunately, training clinicians in effective  HPV vaccine communication alone produces only a small improvement in vaccination rates. In  order to develop effective interventions for improving HPV vaccine uptake, there is a  critical need to understand the full range of multilevel factors influencing providers'  likelihood and effectiveness in a strong recommendation (secondary outcome). Previous studies  have demonstrated the complexity of barriers to HPV vaccination, including their multilevel,  multi-factorial nature and heterogeneity across communities and practice settings; as  reflected in our and others' data. However, most intervention studies display two  limitations: 1) many are single level and single component (e.g., parent education only),  leaving many barriers unaddressed; and 2) most address pre-selected barriers using  pre-specified interventions that are fixed for all sites. This "prescribed" approach ignores  differences in barriers across sites (due to varying context, culture, etc.), and likely  leaves key local barriers unaddressed. These interventions have mostly shown modest and  inconsistent success. Current thinking in implementation science suggests that significant  improvement in HPV vaccination rates will require synergistic, multi-level, multi-component  interventions tailored to the local context and barriers.  The study goal is to evaluate the effectiveness of three implementation strategies  (local-tailored, prescribed strategy, and usual care) to improve HPV vaccination rates among  children 9-12 years old. Study Aims A1) Examine baseline associations between patient-,  provider-, and clinic-level factors and variations in (a) HPV vaccination rates; (b) the  quality of the provider recommendation; and (c) the impact of provider recommendation on  vaccine uptake. A2) Conduct a cluster RCT comparing the effectiveness of a "tailored"  multilevel implementation strategy to a "prescribed" multilevel implementation strategy and  to usual care in improving HPV vaccination rates (primary outcome) and strengthening the  provider recommendation (secondary outcome). Sub-aim: Conduct cost-effectiveness analyses of  the implementation strategies based on the RCT results. A3) Study mechanisms of the effect of  the implementation strategies to understand the interaction between the intervention, local  context, and participant experience combined with quantitative measures. Study Descriptions:  In this study, we are using a 3-arm cluster randomized controlled trial (RCT) to compare: (1)  An innovative "local-tailored" implementation strategy, engaging local care teams, using  local barrier assessment and barrier-driven local tailoring of interventions versus (2) A  "prescribed" strategy, that involves pre-specified interventions addressing pre-selected  vaccination barriers, guided by the 4 Pillars for Practice Transformation Program versus (3)  Usual care - there are no research-led activities. This study will examine two theses: (a)  interventions need to be multilevel and multi-component, and (b) local barrier assessment and  intervention tailoring with the engagement of local teams (who are familiar with the local  context) are needed to increase the uptake of the HPV vaccine.  Clinics will be randomized into one of the three groups. Prior to randomization, clinics will  be matched in triads on key attributes that may be associated with implementation success  (e.g. geographic location, Consolidated Framework for Implementation Research (CFIR)  constructs, membership, race/ethnicity, and baseline HPV vaccine coverage) using a SAS  algorithm. The three clinics matched in a triad will be most like each other in these  attributes. Within each triad, the three clinics will then be randomized to determine which  receives the local-tailored strategy ( 20 clinics) vs prescribed ( 20 clinics) vs usual care  (20 clinics). The study subjects will include pediatric physicians, nurses, and other  clinical staff. We will also include other non-clinical individuals, such as department  administrators. The outcome of interest is: improving HPV vaccination rates (primary outcome)  and strengthening provider recommendations (secondary outcome). We will also examine assess  other outcome measures such as HPV vaccine series completion rate in children 9-12 years,  time taken to recommend the HPV vaccine (provider-centered outcome); perceived  comfort/distress in discussing HPV vaccination with parents (provider-centered outcome),  parent satisfaction with HPV vaccine communication (parent-centered outcome) and sustainment  of interventions (system-centered outcomes). Study data will be obtained through collection  electronic medical record extraction, patient surveys, and semi-structured interviews. The  analysis will follow an intent-to-treat (ITT) strategy using a log-binomial or Robust Poisson  model. Content analysis will be used to evaluate the qualitative data collected. We will use  the Consolidated Framework for Implementation Research (CFIR) and the Multilevel Influences  on the Cancer Care Continuum (MICC) to inform our overall study approach and provide rigor  and structure to our analyses. Inclusion Criteria:  -  All KPSC pediatric clinics.  -  All providers (physicians, nurses, and medical assistants) and department  administrators from the pediatric department.  -  Parents of HPV vaccine-eligible children (9-12 years old). Exclusion Criteria:  -  Providers and administrators who do not work for the pediatric department  -  Parents of children older than 12 years and/or who did not have a clinic visit in the  study period.

The aim of this study was to evaluate whether C4d is a better biomarker and examine whether  C4d plasma levels correlate with treatment response and C4d kidney deposition in systemic  lupus erythematosus (SLE) with lupus nephritis (LN). Evaluation of C4d in lupus nephritis in children C4d level difference in children with  systemic lupus with and without renal affection C4d level in lupus nephritis at activity and  after remission Detection of C4d deposition in renal tissue relation to disease activity Inclusion Criteria:  -  This will include children and adolescents who fulfill the 2012 Systemic Lupus  International Collaborating Clinics (SLICC)(10) classification criteria of SLE.  -  Age younger than 18 years.  -  Active SLE with and without renal affection  -  Patients with biopsy proven LN according to ISN/RPS classification criteria  of Lupus nephritis. Exclusion Criteria:  -  -Patients in remission.

The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in  certain subgroups of patients. To date, no treatment has been shown to be effective in  patients with early-onset disease and mild symptoms. Experimental studies have demonstrated a  potential anti-inflammatory role of Fluvoxamine, Fluoxetine, Budesonide and Pegilatrd  Interferon Lambda in SARS-CoV-2 infections and observational studies have suggested a reduced  complications in patients with COVID-19 disease. In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China  and a new subtype of coronavirus has been identified as the causative agent of this  condition. On February 11, 2000 the disease has been characterized as COVID-19 and on March  11 the World Health Organization (WHO) declared a state of worldwide pandemic. On January 25,  2021 there are 98,794,942 cases and 2,124,193 documented deaths (global case-fatality ratio  of 2.15%).  To date, no early treatment has been identified as effective in combating this disease which  has been identified as with high morbidity and mortality. Epidemiological data suggest that  despite development of vaccines we will have hundreds od thousands of cases in the next two  years.  Thus, we propose the prospective, double-blinded, randomized evaluation of potential  therapies against SARS-CoV2 and some clinical evidence derived from observational studies on  reducing complications if used early on the disease, before inflammatory cascade is fully  activated.  Important considerations on TOGETHER Trial:  1. Vaccinated patients were proposed to be an exclusion criteria on amendment 3 which was  received final National Ethics Committee (CONEP) decision letter number 4.747.755_E3  dated June 01, 2021. We evaluated vaccination data and outcomes on two large cities  involving 150.000 individuals and based on these results we submitted to the IRB a  notification request to withdraw the exclusion criteria 4 (vaccination > 14 days) on  July 14, 2021, which was granted.  2. The amendment 5 proposed a collaborative partnership with ANTICOV Consortia and  incorporating the fluoxetine + budesonide and its active comparator (paracetamol) arms,  as per ANTICOV protocol WHO ERC approval version 13.0. These generated data will be  analyzed along with ANTICOV fluoxetine + budesonide and paracetamol arms. Inclusion Criteria: None Exclusion Criteria:  1. Diagnostic test for negative SARS-CoV2 associated with acute flu symptoms (patient  with a negative test collected early and becomes positive a few days later is  eligible, as long as it is < 07 days since the onset of flu symptoms).  2. Patients with an acute respiratory condition compatible with COVID-19 treated in the  primary care network and with a decision to be hospitalized.  3. Patients with acute respiratory symptoms due to other causes.  4. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg,  decompensated COPD, Acute bronchitis, Pneumonia other than viral, Primary pulmonary  arterial hypertension).  5. Patients requiring hospitalization due to COVID-19 or SpO2 ≤ 93%. NOTE: Patients  allocated to the fluvoxamine arm alone may be included if SpO2 is below 94%, with no  evidence of acute respiratory failure, provided that the attending physician decides  to discharge the unit and continue treatment on an outpatient basis.  a. Patients on chronic use of prednisone, prednisolone or other corticosteroids with  doses > 10 mg/day equivalent to prednisone.  1. Abnormal findings on physical examination: Respiratory rate ≥ 25 sisters; blood  pressure < 90/60 mmHg or > 160/100 mmHg; Weight < 45 kg; recent episodes of  vomiting within the last 24 hours or recurrent diarrhea or serum potassium below  3.5 mEq/L.  2. Severe organ damage that requires resuscitation and ongoing treatment.  3. Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day  4. Immunosuppressive treatment in progress  5. History of known pulmonary arterial hypertension or pulmonary fibrosis  6. Patients who have received a previous dose of SARS-CoV-2 vaccine  7. Use of serotonin reuptake inhibitors (all).  1. Chronic use of serotonin reuptake inhibitors other than sertraline  2. Chronic corticosteroid use with equivalent prednisone doses of > 40 mg/day;  9. Continued use of monoamine oxidative inhibitors (MAOI): Phenelzine, Tranylcypromine,  Selegiline, Isocarboxazid, moclobemide.  10. Patients with severe psychiatric disorders - schizophrenia, uncontrolled bipolar  disorders, major depression with suicidal ideation.  11. Pregnant or breastfeeding patients.  12. History of severe ventricular cardiac arrhythmia (Ventricular tachycardia, recovered  ventricular fibrillation patients) or Long QT Syndrome.  13. Known history of decompensated heart failure (NYHA III or IV), recent myocardial  infarction (event < 90 days of screening), unstable angina, recent coronary bypass  surgery (procedure < 90 days of screening), recent stroke ( event < 90 days from  screening), symptomatic carotid disease, or moderate to severe mitral or aortic  stenosis.  14. Surgical procedure or hospitalization planned (for other indications) to occur during  treatment or up to 5 days after the last dose of study medication.  15. Current daily and/or uncontrolled alcohol consumption, which, in the investigator's  view, could compromise participation in the study.  16. History of seizures in the last month or uncontrolled seizures.  17. Clinical history of moderate to severe hepatic impairment or hepatic cirrhosis with  Child-Pugh C classification.  18. Patients with known serious degenerative neurological diseases and/or serious mental  illnesses as assessed by the investigator.  19. Inability of the patient or representative to give consent or adhere to the procedures  proposed in the protocol.  20. Any clinical conditions, including psychiatric conditions, which, in the  investigator's view, could prevent the use of research drugs.  21. Known hypersensitivity and/or intolerance to Fluvoxamine, Budesonide, Pegylated  Interferon Lambda and Fluoxetine.  22. Use of drugs which have a known interaction with Fluvoxamine, Budesonide, Pegylated  Interferon Lambda and Fluoxetine.  23. Inability to use the drugs and formulations provided for in this research.

This study aims to examine the effects and potential mechanisms of theta-burst stimulation  (TBS) on cognitive function in individuals with mild cognitive impairment (MCI). The investigators apply the NIA-AA criteria to subtype different endophenotypes of  biomarker-defined MCI individuals. This is a prospective, open-label clinical trial, and  combined functional neuroimaging study of 18F-FDG-PET to further explore the potential  mechanisms. A total of 80 MCI patients will be consecutively recruited and be subjected to  iTBS for 5 daily interventions per week for two consecutive weeks. Cognitive evaluation will  be performed before and immediately after TBS intervention, and 8 weeks after TBS. Data on  functional neuroimaging will be also collected before and after TBS protocol. Inclusion Criteria:  1. Subjects aged 50-90 year  2. Subjects meet Petersen's criteria for mild cognitive impairment (Petersen, Smith et  al. 1999)  3. The CDR of MCI patients can be 0-0.5  4. Amyloid PET should ever be performed Exclusion Criteria:  1. Any subject has a definite diagnosis of epilepsy or history of seizure attack.  2. Current or past history of clinically significant neurological insults affecting brain  structure or function like completed stroke, head injury or brain tumor.  3. Any subject has clinically significant or unstable medical diseases including  metabolic, renal,liver, lung or cardiovascular disorders including metabolic, renal,  liver, lung or cardiovascular disorders.  4. Any subject has current alcohol or other substances abuse and/ or dependence within  the recent one year, or prolonged history of major psychiatric disorder like  schizophrenia,bipolar disorder, and previously prolonged substances abuse.  5. Any females who is pregnant or lactating.  6. General MRI, TMS and/or PET exclusion criteria including subjects who had received  brain aneurysm surgery, or implanted pacemaker, mechanical valves, cochlear implant or  other metal devices/ objects that are not MR compatible in the body.  Withdrawal criteria  1. Complications onset after intervention that affect efficacy and safety judgments.  2. New onset or progression of disease that may affect outcomes.  3. Use of other therapies or drugs during the intervention period to change cognitive  functions.  4. Any subjects who are recognized as high risk of adverse effects by principle  investigator.

This study compares two methods of dosing methadone for complex spine cases Patients with spine surgery experience a significant amount of pain that can interfere with  healing, rehabilitation and contribute to morbidity in the post-operative period. This study  will compare post-operative opioid requirement at 24 and 48 hours to determine if methadone  given in small aliquots until respiratory depression can act as a self-control to determine  the correct dose required. Inclusion Criteria:  -  Patients must consent to participate and sign the Institutional Review Board (IRB)  approved informed consent prior to beginning any study specific procedures.  -  Undergoing multiple thoracolumbar spine surgery with instrumentation and fusion Exclusion Criteria:  -  History of methadone use  -  Morbid obesity with BMI>40 Kg/m2.  -  Chronic renal failure with creatinine>2.0 mg/dL  -  Liver failure as determined by cirrhosis or history of fulminant hepatic failure  -  History of alcohol abuse  -  History of drug abuse  -  History of myocardial infarction or heart failure.  -  Patients with American Society of Anesthesiologists (ASA) status IV or V

This study is designed to collect real world evidence (RWE) safety and efficacy data on  patients who plan to undergo a single-level Transforaminal lumbar interbody fusion (TLIF) or  Posterior lumbar interbody fusion (PLIF) instrumented with pedicle screws, using the  framework of a prospective clinical study (with defined enrollment criteria and pre-specified  research follow-up timepoints). A prospective, multi-center (up to 20), non-blinded study of patients who plan to undergo a  single-level Transforaminal lumbar interbody fusion (TLIF) or Posterior lumbar interbody  fusion (PLIF) stabilized with pedicle screws. Investigators will only select those patients  who are planned for treatment with on-label use of FDA cleared TLIF/PLIF devices (cage and  screw system).  At least 200 subjects with a potential sample size re-estimation at completion. The subjects  will return for follow-up at 6-weeks, 3-months, 6-months, and then annually for 5-years post  surgery. Inclusion Criteria:  1. Male or female, age 21-80 (inclusive) with at least 3 years of life expectancy;  2. Subject plans to undergo a one-level Open or Mini-Open TLIF or PLIF procedure  (stabilized with pedicle screws) independent of this research protocol;  3. Subject is to be treated with on-label use of an FDA-cleared TLIF or PLIF cage(s) and  pedicle screw system independent of this research protocol;  4. The subject has a primary diagnosis of symptomatic lumbar degeneration with or without  foraminal or recess stenosis of the lumbar spine at a single level from L1/L2 to L5/S1  confirmed by subject history and radiographic imaging (CT, MRI, X-rays) with no more  than a Grade 1 (<25% translation) spondylolisthesis. Symptomatic lumbar degeneration  that may be associated with a co-morbid condition such as:  1. Herniated nucleus pulposus;  2. Scarring/thickening of the ligamentum flavum, annulus fibrosus, or facet joint  capsule;  3. Facet joint degeneration/osteophyte formation;  4. Spondylosis (defined by the presence of osteophytes);  5. Disc degeneration and/or annular degeneration; and/or  6. Lumbar stenosis defined by spinal cord or nerve root compression;  5. Exhausted conservative treatment (e.g. bed rest, physical therapy, medications,  transcutaneous electrical nerve stimulation (TENS), manipulation, and/or spinal  injections) for at least 3 months or has a neurologic emergency;  6. Preoperative Oswestry Disability Index score > 40/100 at baseline;  7. Psychosocially, mentally and physically able and willing to fully comply with this  protocol including adhering to follow-up schedule and requirements and filling out  forms; and  8. Signed informed consent. Exclusion Criteria:  1. More than one vertebral level requiring treatment;  2. Previous instrumented surgery (i.e.: anterior disc replacement, spinal fusion,  interspinous device, etc.) at the index lumbar level or an adjacent level;  3. Degenerative or lytic spondylolisthesis greater than Grade 1 (<25% translation);  4. Rotatory scoliosis at the level to be treated;  5. Congenital bony and/or spinal cord abnormalities at the level to be treated;  6. Subcaudal defect, disrupting the integrity of the pedicle;  7. Clinically compromised vertebral bodies at the involved level due to current or past  trauma, e.g., by the radiographic appearance of the fracture callus, malunion or  nonunion;  8. Disrupted anterior longitudinal ligament at the index level;  9. Overlying thoracolumbar kyphosis (greater than or equal to 15 degrees) within one  level (includes target and adjacent level) of the level to be treated;  10. Back pain of unknown etiology without leg pain;  11. Severe spondylosis at the level to be treated as characterized by any of the  following:  1. Autofusion (solid arthrodesis) determined radiographically (CT);  2. Totally collapsed disc, or;  3. Vertebral body that cannot be mobilized;  12. Known allergy to cobalt, chromium, molybdenum, nickel, polyethylene, titanium, or  vitamin E;  13. Unable to undergo a CT scan or other radiograph assessments;  14. Osteopenia: The SCORE/MORES will be utilized to screen if a DEXA scan is indicated. If  SCORE/MORES value ≥ 6, then a DEXA scan is required. If DEXA is required, exclusion  will be defined as a DEXA bone density measured T score ≤ -1. An existing DEXA is  allowed if completed within 6 months of subject screening;  15. Has history of any endocrine or metabolic disorder known to affect osteogenesis (e.g.:  Paget's disease, renal osteodystrophy, Ehler-Danlos syndrome, or osteogenesis  imperfecta);  16. Insulin-dependent diabetes mellitus;  17. Lactating, pregnant or interested in becoming pregnant in the next 3 years;  18. Active infection - systemic or local;  19. Any medical condition requiring treatment with any drug known to potentially interfere  with bone/soft tissue healing or receiving radiation therapy that is expected to  continue for the duration of the study;  20. Body Mass Index > 40;  21. Recurrent history of deep vein thrombosis, symptoms of arterial insufficiency, or  thromboembolic disease;  22. Systemic disease including Lupus disease, Reiter's disease, Rheumatoid disease, AIDS,  HIV, hepatitis or autoimmune disease that requires immunosuppressive therapy,  including biologics, for systemic inflammation;  23. Spinal tumor;  24. Active malignancy: A patient with a history of any invasive malignancy (except  non-melanoma skin cancer), unless he/she has been treated with curative intent and  there have been no clinical signs or symptoms of the malignancy for at least 5 years;  25. Any degenerative muscular or neurological condition that would interfere with  evaluation of outcomes, including but not limited to Parkinson's disease, amyotrophic  lateral sclerosis (ALS), or multiple sclerosis;  26. Has chronic or acute renal and/or hepatic impairment and/or failure or prior history  of renal and/or hepatic parenchymal disease;  27. Has a Waddell Signs of Inorganic Behavior score of 3 or greater;  28. In the opinion of the investigator, the subject has a behavioral, cognitive, social or  medical problem that may interfere with the assessment of the safety or effectiveness  of the device;  29. Current or recent history of chemical/alcohol abuse or dependency using standard  medical definition of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5)  code;  30. Currently smoking or using tobacco products, including e-cigarette products (e.g.,  vaping); (Use within 30 days of screening date is considered 'current');  31. Currently pursuing or in active spinal litigation for medical negligence, or trauma,  or workers compensation;  32. Is a prisoner, incarcerated, or has been coerced to participate in the study that  could impact the validity of results;  33. Is currently participating in an investigational therapy (device and/or  pharmaceutical) within 30 days prior to entering the study or such treatment is  planned during the 24 months following enrollment into the study.

To assess safety and tolerability at increasing dose levels of IO-202 as monotherapy and in  combination with Azacitidine in successive cohorts of participants with relapsed or  refractory AML with monocytic differentiation and CMML in order to estimate the maximum  tolerated dose (MTD) or maximum administered dose (MAD) and select the recommended Phase 2  dose (RP2D) and dose schedule as monotherapy and combination therapy. This is a Phase 1, Multicenter, Open-Label, Dose-Escalation and Dose Expansion Study to  Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity  Study of IO-202 as Monotherapy and in combination with Azacitidine in Relapsed/Refractory  Acute Myeloid Leukemia (AML) Patients with Monocytic Differentiation and in  Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML) Patients. Inclusion Criteria:  1. Patients must be ≥18.  2. For the Part 1 Dose-Escalation Phase, patients must be diagnosed with the following:  1. Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic  differentiation according to the World Health Organization 2016 criteria and has  failed treatment with available therapies known to be active for AML.  2. Relapsed or refractory CMML and has failed treatment with available therapies  known to be active for CMML  3. Part 2 Expansion Phase:  1. Relapsed or refractory AML with myelomonocytic or monoblastic/monocytic  differentiation and has failed treatment with available therapies known to be  active for AML.  2. Relapsed or refractory CMML and has failed treatment with available therapies  known to be active for CMML.  4. Patients must be amenable to serial BM aspirates/biopsies and peripheral blood  sampling during the study.  5. Patients must be able to understand and willing to sign an informed consent. A legally  authorized representative may consent on behalf of a patient who is otherwise unable  to provide informed consent, if acceptable to and approved by the site and/or site's  Institutional Review Board (IRB) or Ethics Committee.  6. Patients must have an ECOG performance status of 0 to 2  7. Patients must have adequate hepatic function  8. Patients must have adequate renal function  9. Patients must be recovered from any clinically relevant toxic effects of any prior  surgery, radiotherapy, or other therapy intended for the treatment of cancer (patients  with residual Grade 1 toxicity, or any grade of alopecia, are allowed; patients with  peripheral neuropathy that is not more than Grade 2 and stable are allowed).  10. Patients must be off systemic calcineurin inhibitors (e.g., cyclosporine, tacrolimus)  for at least 4 weeks prior to study drug treatment.  11. Female patients with reproductive potential must have a negative serum pregnancy test  within 7 days prior to the start of therapy. Exclusion Criteria:  1. Patients who have previously who received a monoclonal antibody therapy targeting  LILRB4 (including IO-202). Prior azacitidine treatment is allowed.  2. Patients who have undergone HSCT within 60 days of the first dose of IO-202, or  patients on immunosuppressive therapy post human stem cell transplantation (HSCT) at  the time of screening, or with clinically significant graft-versus-host disease (GVHD)  (the use of a stable dose of oral steroids post-HSCT of <10 mg prednisone/day or dose  equivalent of other corticosteroid and/or topical steroids for ongoing skin GVHD is  permitted with Medical Monitor approval).  3. Patients who received systemic anti-cancer therapy or radiotherapy <7 days prior to  their first day of study drug administration (Hydroxyurea or leukapheresis is allowed  up to 24 hours prior to the first dose. However, hydroxyurea must be ceased 24 hours  prior to the first dose of IO-202 treatment in Cycle 1); it may be initiated again if  necessary 24 hours after the first dose of IO-202 treatment in Cycle 1).  4. Patients who received an investigational agent <7 days prior to their first day of  study drug administration. In addition, the first dose of IO-202 should not occur  before a period ≥5 half-lives of the investigational agent has elapsed.  5. Patients for whom potentially curative anti-cancer therapy is available.  6. Patients who are pregnant or breast feeding.  7. Patients with uncontrolled, active infection.  8. Patients with known pulmonary lesions and/or history of pneumonitis or interstitial  lung disease.  9. Patients with known hypersensitivity to any of the components of the IO-202  formulation.  10. Active known malignancy with the exception of any of the following:  1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or  in situ cervical cancer;  2. Low-risk prostate cancer for which observation or hormonal therapy only is  indicated;  3. Any other malignancy treated with curative intent with the last treatment  completed ≥6 months before study initiation (with the exception of hormonal  therapies when indicated).  11. Patients with New York Heart Association (NYHA) Class III or IV congestive heart  failure (CHF) or left ventricular ejection fraction (LVEF) <40% by echocardiogram  (ECHO) or multi-gated acquisition (MUGA) scan ≤28 days prior to Cycle 1, Day 1.  12. Any of the following in the previous 6 months: myocardial infarction, congenital long  QT syndrome, Torsades de pointes, clinically significant arrhythmias (including  sustained ventricular tachyarrhythmia and ventricular fibrillation), and left anterior  hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass  graft, symptomatic CHF (NYHA class III or IV), cerebrovascular accident, transient  ischemic attack, or pulmonary embolism. Patients with asymptomatic right bundle branch  block or controlled atrial fibrillation are allowed.  13. Ongoing cardiac dysrhythmias Grade 2 or higher per of NCI CTCAE, Version 5.0, Grade  ≥2.  14. Known or suspected hypersensitivity to recombinant human proteins.  15. Known active bacterial, viral, and/or fungal infection including hepatitis B (HBV),  hepatitis C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome  (AIDS)-related illness, or active Covid-19 infection. . Hepatitis B and C and HIV  testing are not required for asymptomatic patients; however, for patients who have  previously tested positive or have a known history of hepatitis B and C, HIV, and/or  tuberculosis, clinical laboratory assessments at screening will include repeat testing  for the previous infection. A sample for SARS-CoV-2 should be obtained during the  screening period, and results must be available prior to C1D1.  16. Patients with any psychological, familial, sociological, or geographical condition  potentially hampering compliance with the study protocol and follow-up schedule; those  conditions should be discussed with the patient before trial entry.  17. Patients with clinical signs and/or symptoms suggesting active, uncontrolled central  nervous system (CNS) leukemia or known active, uncontrolled CNS leukemia (a lumbar  puncture is not required in patients without signs or symptoms that are suggestive of  CNS leukemia). Note: Patients with controlled CNS leukemia (documented by 2  consecutive assessments of zero blast count in cerebrospinal fluid), and who are still  receiving intrathecal (IT) therapy at study entry are considered eligible and will  continue to receive IT therapy.  18. Patients with immediately life-threatening, severe complications of leukemia such as  uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular  coagulation.  19. Donor Lymphocyte Infusion within 30 days prior to first IO-202 administration.  20. Current active treatment in another interventional therapeutic clinical study.  21. Chronic systemic corticosteroid treatment with a dose of ≥10 mg prednisone/day or dose  equivalent of another corticosteroid. Topical applications, inhaled sprays, eye drops,  local injections of corticosteroids, and systemic steroids required for acute medical  interventions are allowed.  22. Other severe acute or chronic medical or psychiatric condition 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 patient  inappropriate for entry into this study.  23. Acute Promyelocytic Leukemia patients or patients with known Philadelphia chromosome  (Ph+) positive AML or chronic myelogenous leukemia (CML) blast crisis.  24. Hyperleukocytosis (leukocytes ≥25 x 10e9/L) at first dose of IO-202. These patients  may be treated with hydroxyurea or receive leukapheresis treatment according to  routine practice, and enrolled in the study when the leukocyte count falls below 25 x  10e9/L.

To investigate the effect of ultrasound-guided thoracic paravertebral nerve block on  postoperative acute and chronic pain and cognitive function in elderly patients with  thoracoscopic partial lung resection. A total of 100 patients who were admitted to Qinhuangdao First Hospital for and divided into  control group (group C ), thoracic paravertebral nerve block combined with general anesthesia  group (group T).  Group C received general anesthesia, and group T received 0.375% ropivacaine 20 ml of  thoracic paravertebral nerve block combined with general anesthesia after induction of  anesthesia. SBP（Systolic Blood Pressure）/DP （Diastolic Pressure）and HR（Heart Rate） of the two  groups were recorded before anesthesia induction (T1), at the time of intubation (T2), at the  beginning of surgery (T5), immediately after surgery (T6), and five minutes after extubation  (T7) . rScO2（Regional cerebral oxygen saturation） was recorded in both groups at (T1), five  minutes after induction(T3), five minutes after single lung ventilation on lateral  recumbent(T4), (T6), (T7). The incidence of acute and chronic pain after surgery was compared  between the two groups by VAS（Visual analogue scale）after extubation , one day after surgery,  and three months after surgery.  The cognitive function of the two groups was assessed with the Mini Mental State Scale (MMSE)  and the Montreal Cognitive Assessment Scale (MoCA-Beijing) on the day before , one day after  and three months after surgery, comparing the incidence of POD (postoperative cognitive  dysfunction) between the two groups.Analyze whether paravertebral block can reduce the  incidence of POD by improving brain oxygen saturation. Inclusion Criteria:  -  BMI less than 30 kg/m2  -  American Society of Anesthesiologists (ASA) grades I-III  -  The score of Mini Mental state examination≥24  -  The score of Montreal Cognitive Assessment-Beijing Scale≥26 Exclusion Criteria:  -  Patients with heart, lung, brain and other vital organ disorders  -  The score of Mini Mental state examination≤23  -  The score of Montreal Cognitive Assessment-Beijing Scale≤25  -  Preoperative psychiatric disorders or long-term use of drugs affecting the psychiatric  system  -  Have severe visual, hearing, speech impairment or other inability to communicate with  the visitor  -  Have contraindications to thoracic parathymic block  -  Refuse to sign informed consent

This is a single-center, interventional, single arm clinical study of the MyoVista wavECG for  the detection of LV relaxation abnormalities. The study will be conducted at a single  investigational site within the United States. Study subjects will predominately be screened  from among those who have been enrolled in prior registry studies by the institution. The study has a planned enrollment of at least 50 subjects to obtain approximately 40  subjects with a "normal" septal and lateral e' value on echocardiogram. The criteria defined  as septal e'< 7 cm/s or lateral e'< 10 cm/s for relaxation abnormality based on ASE/AECVI  guidelines will be used for the evaluation of LV diastolic function which is associated with  abnormal relaxation in echocardiography. An independent Core Lab will verify all septal and  lateral e' values on the site-acquired echocardiograms and these Core Lab measurements will  serve as the ground truth standard with regard to the presence of LV relaxation  abnormalities.  Analysis of data from a prior multi-center study has revealed good correlation between the  MyoVista wavECG results and echocardiography for the presence of LV relaxation abnormalities.  This current study (HS-CLINVAL-002) is intended to supplement data collected in prior and  ongoing studies, namely HS-CLINVAL-001, by recruiting individuals who are >60 years old and  who are anticipated to have normal echocardiogram results based on a screening of selected  clinical characteristics. Subjects in this study will be invited to participate and receive  non-standard-of-care echocardiograms and a study driven MyoVista test.  The study will continue to focus on LV relaxation abnormalities by gathering additional  device validation data for the purposes of regulatory approval peer-reviewed publications.  Echocardiograms of study subjects will be used to compare/validate the study findings. Inclusion Criteria:  -  Subject is >=60 years of age  -  Subjects will predominately be recruited among those who are already enrolled in  existing registry studies within the institution.  -  The subject provides written informed consent using an Informed Consent Form that is  reviewed and approved by the site's Institutional Review Board (IRB).  -  Conventional ECG results show a sinus rhythm and no other contraindicated rhythm  abnormalities (see exclusions below). Exclusion Criteria:  -  The subject has current acute coronary syndrome, decompensated heart failure or stroke  -  The subject has received any prior cardiac interventions or surgical therapeutic  procedures relating to cardiac abnormalities: valve replacement, pacemaker  implantation, coronary artery bypass grafting (CABG), heart transplant, ablation,  coronary stent placement, etc.  -  Conventional ECG results indicating a lack of sinus rhythm and/or any other  contraindicated rhythm abnormalities, including: active atrial fibrillation or atrial  flutter, left anterior fascicular block, left and/or right bundle branch block  -  The subject is pregnant at the time of the study testing  -  The subject has chest deformities that interfere with accurate measurement of ECG  (either conventional or wavECG)  -  Subjects with central nervous system or musculoskeletal abnormalities that may  interfere with accurate acquisition of ECG and/or echocardiogram measurements.  -  The subject is enrolled in another clinical study that may interfere with MyoVista or  echocardiogram measurements. Exceptions to this may be approved by HeartSciences.

The objective of this study is to investigate the hemodynamic effects of two strategies of  alveolar recruitment maneuver in patients undergoing major abdominal surgery in the operating  room In practice, after induction of general anesthesia and intubation, patients will be  conditioned with the recommended monitoring (arterial catheter, central venous catheter, and  transpulmonary thermodilution).  Once conditioning is complete, optimization of blood volume will be performed with volumetric  expansions (250 mL of Ringer lactate) to achieve a change in stroke volume of less than 10%,  as recommended (RFE SFAR 2013 - Perioperative Vascular Filling Strategy). The patient will  then be randomized to one of the following groups: [ extended sigh then CPAP ] or [ CPAP then  extended sigh ] (random order of ARMs - each patient becoming their own control). In order to  homogenize the settings, the mechanical ventilation will be standardized with in particular  the use of a PEEP of 6 cmH2O before inclusion and between the ARMs (for a duration of at  least 10 minutes in each case).  Hemodynamic values will be recorded during the last 10 seconds of each procedure. Once the  two ARMs have been performed, the rest of the management will then be left to the discretion  of the practitioner in charge of the patient.  The included patient will be managed according to the recommendations at the time of the  study. Inclusion Criteria:  -  patient over 18 years old  -  patient under general anesthesia  -  patient intubated under controlled invasive mechanical ventilation  -  patient with invasive hemodynamic monitoring (transpulmonary thermodilution)  -  patient sedated (BIS between 40 and 60) and/or curarized with TOF monitoring to avoid  inspiratory effort  -  patient optimized on the hemodynamic level, in particular with regard to blood volume,  following the hemodynamic monitoring data and the recommendations of the French  Society of Anesthesia and Resuscitation (RFE SFAR 2013 - Perioperative vascular  filling strategy)  -  patient covered by a Social Security plan  -  patient consent to participate in the study Exclusion Criteria:  -  contraindication to the use of cardiac output measurement  -  cardiac arrhythmia  -  pace-maker/implantable defibrillator  -  severe valvulopathy  -  contraindication to the use of the tomographic electroimpedancemetry technique  -  thoracic lesions, thoracic dressing  -  left ventricular ejection fraction (LVEF) < 45% and/or right ventricular failure.  -  history of pulmonary lobectomy and/or pneumonectomy and/or known emphysema  -  patient with restrictive or obstructive lung disease  -  body mass index (BMI) < 16.5 or > 30 kg.m-2  -  pregnancy  -  intracranial hypertension or suspected intracranial hypertension  -  patient under limitation of care  -  patient under legal protection (guardianship, curatorship, safeguard of justice)

The Chinese American Family Caregiver Writing Study is a Randomized Controlled Trial (RCT)  testing the efficacy of the Expressive Helping (EH) intervention among Chinese Americans who  are providing care for family members undergoing cancer treatment. Because the psychosocial health of Chinese cancer patients and their caregivers are linked,  there is a need to improve health outcomes for not just the patients, but also for the  caregivers. While many caregiving interventions have focused on the caregiver-patient dyad as  the "the unit of care", interventions that solely target caregivers are crucial given the  emotional, social, financial, and physical toll of caregiving. To address this need,  investigators are testing a writing intervention, Expressive Helping (EH), with Chinese  family members who are providing care for their family members diagnosed with cancer. Over  four brief structured writing sessions, participants write about their cancer caregiving  experiences, disclosing their emotions and providing encouragement and guidance, with the  knowledge that their narratives will be shared with and used as a resource for other Chinese  cancer caregivers. Participants will be adult cancer caregivers of Chinese descent. After  screening and consent, eligible participants will be enrolled in a 1:1 randomized controlled  trial. Assessments of psychological symptoms will occur at baseline (prior to randomization),  1-month post-intervention, and 3-month post-intervention. Investigators will also assess  potential mediators and moderators of the potential intervention effects. Investigators  interacting with the participants will be blind to condition assignment. Inclusion Criteria:  -  Over 18 years old  -  Of Chinese descent  -  Informal (i.e., uncompensated) caregiver of individual diagnosed with cancer Exclusion Criteria:  -  Inability to read or write English or Traditional/Simplified Chinese

Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody  cocktail is a medical device innovated to provide the dual-action physical barrier on nasal  mucosa that aids the natural defence in which the mucus layer is fortified by a steric  barrier-forming agent HPMC and invading viral particles of all major SARS-CoV-2 VOCs,  including Delta and Omicron, are locally trapped and blocked from entering the cells by the  highly-specific human IgG1 anti-SARS-CoV-2 monoclonal antibody cocktail. The transmission of SARS-CoV-2 through inhalation results in the nasal cavity and nasopharynx  being the primary entry point of the virus and containing the highest viral load in the body  during the virus incubation period. Recently, the administration of vaccines and agents via a  nasal route has gained a lot of momentum because it takes advantage of the direct delivery of  an agent to the site of primary infection. The local defence system, especially  antibody-mediated immunity at the nasal epithelium, is crucial for COVID-19 prevention.  However, people who responded to the vaccination against COVID-19 typically maintain  sufficient local antibody levels in the nasal cavity for only a short period; hence a  repeated boosting strategy is required to control the rate of SARS-CoV-2 breakthrough  infection. In addition, the new VOCs such as Omicron are known to escape vaccine immunity;  therefore, an innovative approach is needed in this unprecedented situation  Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody  cocktail is a medical device innovated to provide the dual-action physical barrier on nasal  mucosa that aids the natural defence in which the mucus layer is fortified by a steric  barrier-forming agent HPMC and invading viral particles of all major SARS-CoV-2 VOCs,  including Delta and Omicron, are locally trapped and blocked from entering the cells by the  highly-specific human IgG1 anti-SARS-CoV-2 monoclonal antibody cocktail. Inclusion Criteria:  1. Male or female, ≥ 18 and ≤ 50 years of age with BMI ≥ 18 and ≤ 30 kg/m2  2. Healthy as defined by:  1. No previous clinically significant disease and surgery within 4 weeks prior to  dosing.  2. No previous sinus and nasal septum surgery or radiotherapy  3. No evidence of clinically significant history of neurological, endocrine,  cardiovascular, pulmonary, hematological, immunologic, psychiatric,  gastrointestinal, renal, hepatic, and metabolic disease which the Investigator  believes may be detrimental to the study or its aims.  4. No evidence of febrile or infectious disease within 1 week prior to dosing.  3. Have received at least 2 doses of COVID-19 vaccine.  4. Have no history of close contact with COVID-19 patients within 2 weeks before  enrolment  5. Have negative result of COVID-19 test using RT-PCR method using sample collected from  nasopharyngeal or nasal or oropharyngeal swab within 72 hours before sinusoscopy  6. Provide signed written informed consent prior to the initiation of any study-specific  procedures.  7. Willing and able to comply with the requirements of the protocol and be available for  the planned duration of the trial. Exclusion Criteria:  1. Any clinically significant abnormality at physical examination at screening or  enrolment  2. Vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg,  diastolic blood pressure lower than 40 or over 90 mmHg, heart rate less than 40 or  over 100 bpm, respiratory rate less than 10 or over 22 bpm, oral temperature less than  35.5°C or over 37.5°C) at screening.  3. Positive urine pregnancy test for women or women who are breast feeding  4. History of COVID-19 infection within 3 months before enrollment  5. History of allergic reactions or hypersensitivity to any excipients of the study  products.  6. Use any nasal product use within 14 days prior to the first dosing  7. History of pulmonary infiltrate or pneumonia within 6 months before the screening  visit.  8. Signs or symptoms of respiratory tract abnormalities such as allergies or chronic  obstructive pulmonary disease.  9. History or signs of chronic allergic rhinitis that may interfere with study procedures  and/or interpretation of local adverse events.

Surgery and radiotherapy in breast cancer patients can cause treatment changes and may affect  the final breast appearance. In this study, we are trying to evaluate the post treatment  breast photographs of the patients and subject these to Artificial Intelligence based program  so as to classify into appropriate categories based upon changes from baseline. This  automated solution will help in decreasing the time required to achieve this task by  physicians in the clinic. A new algorithm was introduced which is based on deep neural network (DNN) which receives an  image as input and returns the coordinates of the breast key points as output. These key  points are then given to a shortest-path algorithm that models images as graphs to refine  breast key point localization. The algorithm learns, directly from the image, to compute  features and to use those features in the analysis of the aesthetic result. This comprises of  two main modules: regression and refinement of heatmaps, and regression of key points. To  perform the heatmap regression, the U-Net model is used.  The goal of the first module is to generate an intermediate representation consisting on a  fuzzy localization for the key points that are to be detected.  The second module receives and refines this fuzzy localization, and through complex  calculations, outputting the x and y coordinates of the keypoints, and the data generated  from which can be used for disease / image classification. Inclusion Criteria:  -  Confirmed diagnosis of primary breast cancer (invasive or in situ)  -  Patient undergone breast conservation / Whole breast reconstruction  -  Patient received breast RT  -  Already provided written informed consent on earlier projects  -  Patient provided photographs of both breasts  -  Non-metastatic disease or oligometastatic  -  Age > 18 years  -  Reconsent given Exclusion Criteria:  -  Mastectomy without whole breast reconstruction  -  Bilateral breast cancer  -  Partial breast irradiation  -  Male patient  -  Limited life expectancy due to co-morbidity  -  Patients undergoing brachy boost

Acute rehabilitation in critically ill patients can improve post-intensive care unit  (post-ICU) physical function. Scientific evidence has considered neuromuscular electrical  stimulation (NMES) as a promising approach for the early rehabilitation of patients during  and/or after ICU.  Neuromuscular electrostimulation can be an alternative form of muscle exercise that helps to  gain strength in critically ill patients with COVID -19, due to the severe weakness that  patients experience due to longer MV, analgesia and NMB duration. Thus, the general objective  of evaluating the effects of an early rehabilitation protocol on the strength and  functionality of patients affected by SARS-CoV-2 variants and specifically compare the  effectiveness of NMES associated with the functional rehabilitation protocol(FR). Also,  describe demographics, clinical status, ICU therapies, mortality estimates and Hospital  outcomes, of every patients admitted in ICU during the observation periods. Patients in both groups received the functional rehabilitation protocol adapted from the  precoce mobilization protocol of Morris et al, 2008. The protocol was defined in 5 stages,  with a period between the application of the stages according to the clinical conditions of  the patient, in an interval maximum of 24 hours from the beginning of the application of the  first stage. The steps included active assisted mobilization exercises, active with  Proprioceptive Neuromuscular Facilitation (PNF) method diagonals for upper limbs and bridge  exercises, bedside sitting, balance reactions, weight bearing, transfer to an armchair,  passive and active orthostatism, static gait and ambulation. The experimental group also  received a protocol of neuromuscular electrical stimulation (NMES), applied bilaterally for  30 minutes, using an electrical stimulator with rectangular pulse waves, symmetrical  biphasic, applied to the quadriceps femoris and tibialis anterior muscle at the best motor  point, activating fast fibers with a pulse time of less than 300 ms and slow pulses with a  pulse time of more than 300 ms, with intensity adjusted to obtain visible muscle contraction  and/or according to the patient's tolerance. Inclusion Criteria:  Subjects admitted in ICU for >72hs, undergoing orotracheal intubation and on mechanical  ventilation for >48hs, with a diagnosis of Acute Respiratory Distress Syndrome (ARDS)  according to Berlin definition secondary to COVID-19, with shock or organ failure,  according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (7th  Interim Edition) Guideline, and clinical stability:  -  mean arterial pressure < 60 mmHg;  -  heart rate >60 and <120 beats/minute;  -  respiratory rate <30 breaths/minute;  -  oxygen saturation ≥ 92%;  -  fraction of inspired oxygen (FiO2) ≤0.6;  -  absence of vasopressor dose increase  -  absence of dysrhythmia (except for chronic atrial fibrillation);  -  controlled sepsis;  -  hemoglobin (Hb) > 8g m/d, plaquettes >20.000, Glucemia >70 e <180;  -  without NMBs Exclusion Criteria:  -  Patients with movement resistance  -  Walking without assistance before the ICU (except using a cane)  -  Cognitive impairment before acute illness  -  Signs of intracranial hypertension, neuromuscular disease (myasthenia gravis,  amyotrophic lateral sclerosis, Guillain-Barré) and stroke; hip fracture, unstable  cervical spine, or pathological fracture  -  Prior hospitalization (30 days before ICU)  -  Readmission to the ICU, within the current hospitalization  -  Presence of an implanted cardiac pacemaker or defibrillator, pregnancy, acute  myocardial infarction and, for the experimental group (EG), against indications for  NMES (deep vein thrombosis, skin lesions, rhabdomyolysis).

The study consists of two Phases with the first phase (Pilot Phase) divided into two sub  phases.  In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to  the first drug administration on Day -1 until approximately 12 hours following the last study  drug administration. Screening of alcohol and drugs of abuse will be performed before the  first study drug administration. For female subjects, a pregnancy test will be performed  before the first drug administration. Clinical nasal irritation rating and the Brief Smell  Identification Test will be performed at screening. The study consists of two Phases with the first phase (Pilot Phase) divided into two sub  phases.  In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to  the first drug administration on Day -1 until approximately 12 hours following the last study  drug administration. Screening of alcohol and drugs of abuse will be performed before the  first study drug administration. For female subjects, a pregnancy test will be performed  before the first drug administration. Clinical nasal irritation rating and the Brief Smell  Identification Test will be performed at screening.  Phases 1A and , 1B, and 1C (Pilot Phase) The first sub-phase, Phase 1A, will be an inpatient,  5-period, 5-treatment, crossover study involving 10 healthy subjects.  In Phase 1A of the study, qualified subjects will receive one of the following treatment in  the morning, after a 10 hour overnight fast:  -  Treatment-1: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL  injection, into the gluteus maximus muscle using a 23-gauge needle).  -  Treatment-2: Single 4 mg intranasal naloxone spray will be administered in one nostril  (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved  Instructions for Use).  -  Treatment-3: Single 8 mg naloxone nasal swab administered as one swab in one nostril,  swirled 3 times around the inside of the nasal mucosa.  -  Treatment-4: Single 4 mg naloxone nasal swab administered as one swab in one nostril,  swirled 3 times around the inside of the nasal mucosa.  -  Treatment-5: Single 12 mg naloxone nasal swab administered as one swab in one nostril,  swirled 3 times around the inside of the nasal mucosa.  Based on preliminary results from Phase 1A, additional administration technique and higher  dose will be tested. The second sub-phase, Phase 1B, will be a separate inpatient crossover  study involving 10 healthy subjects which will start after completion of Phase 1A. Every  attempt will be made to include the same subjects from Phase 1A in Phase 1B.  In Phase 1B of the study, qualified subjects will receive one of the following treatments in  the morning, after a 10 hour overnight fast:  -  Treatment-1: Single 12 mg naloxone nasal swab administered into the nasal cavity -  administered in one nostril and using two fingers to squeeze outside of both nostrils.  -  Treatment-2: Two 12 mg naloxone nasal swabs in both nostrils- administered one per  nostril and using two fingers to squeeze outside of both nostrils (two doses given  sequentially)  -  Treatment-3: Two 8 mg naloxone nasal swab in both nostrils - administered one per  nostril and using two fingers to squeeze outside of both nostrils (two doses given  sequentially) For all intranasal treatments (nasal spray and nasal swab), participants  will be instructed to not breathe through the nose during treatment administration. The  same nostril will be used throughout the study for all nasal treatments requiring one  nostril only administration. If a Coronavirus Disease 2019 (COVID-19) test is performed  prior to administration, the opposite nostril will be used for administration for  treatments requiring one nostril administration.  The order in which subjects receive their treatment will not be randomized. During Phase 1A,  subjects will receive Treatment-1 in period 1, Treatment-2 in period 2, Treatment-3 in period  3, Treatment-4 in period 4, and Treatment-5 in period 5. In Phase 1B, subjects will receive  Treatment-1 in period 1, Treatment-2 in period 2, and Treatment-3 in period 3. There will be  a 4 day wash out window between treatment periods. At the end of Phase 1A and Phase 1B, a  dose will be selected as the proposed target dose for the Phase 2 to confirm the PK profiles.  Phase 2 (Confirmatory Phase)  Phase 2 of the study will be an inpatient, randomized, laboratory-blinded, balanced, 4-way (4  treatments) crossover study with 4 sequences (Williams design). Below are the 4 treatments to  be utilized:  -  Treatment-1: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg)  administered as one swab in one nostril, using the insert into nostril and squeeze  method of administration.  -  Treatment-2: Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg)  using the insert into each nostril and squeeze method of administration (two doses given  in total).  -  Treatment-3: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL  injection, into the gluteus maximus muscle using a 23-gauge needle).  -  Treatment-4: Single 4 mg intranasal naloxone spray will be administered in one nostril  (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved  Instructions for Use) For all intranasal treatments (nasal spray and nasal swab),  participants will be instructed to not breathe through the nose during treatment  administration. The same nostril will be used throughout the study for all nasal  treatments except Treatment-2 where the swab administered in both nostrils. If a  COVID-19 test is performed prior to administration, the opposite nostril will be used  for administration of all single swab or spray doses. Inclusion Criteria:  1. Provision of signed and dated informed consent form (ICF)  2. Stated willingness to comply with all study procedures and availability for the  duration of the study  3. Healthy adult male or female  4. If female, meets 1 of the following criteria:  1. Is of childbearing potential and agrees to use an acceptable contraceptive  method. Acceptable contraceptive methods include:  -  Abstinence from heterosexual intercourse from the first study drug  administration through to at least 30 days after the last dose of the study  drug  -  1 of the following highly-effective contraceptive methods, used from at  least 28 days prior to the first study drug administration through to at  least 30 days after the last dose of the study drug: Systemic contraceptives  (combined birth control pills, injectable/implant/insertable hormonal birth  control products, transdermal patch) Intrauterine device (with or without  hormones) Male partner vasectomized at least 6 months prior to the first  study drug administration  -  The following effective contraceptive method, used from the first study drug  administration through to at least 30 days after the last dose of the study  drug:  Male condom with diaphragm/cervical cap plus spermicide Or  2. Male partner has had a vasectomy less than 6 months prior to dosing, and the  female subject agrees to use an additional acceptable contraceptive method from  the first study drug administration through to at least 30 days after the last  dose of the study drug Or  3. Is of non-childbearing potential, defined as surgically sterile (i.e. has  undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is  in a postmenopausal state (i.e. at least 1 year without menses without an  alternative medical condition prior to the first study drug administration)  5. Aged at least 18 years but not older than 55 years  6. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively  7. Non- or ex-smoker (An ex smoker is defined as someone who completely stopped using  nicotine products for at least 180 days prior to the first study drug administration)  8. Have no clinically significant diseases captured in the medical history or evidence of  clinically significant findings on the physical examination (including vital signs),  ECG, and/or nasal cavity examination, as determined by an investigator Exclusion Criteria:  1. Female who is lactating at screening  2. Female who is pregnant according to the pregnancy test at screening or prior to the  first study drug administration  3. Seated blood pressure higher than 140/90 mmHg at screening or prior to the first study  drug administration  4. History of significant hypersensitivity to naloxone or any related products (including  excipients of the formulations) as well as severe hypersensitivity reactions (like  angioedema) to any drugs  5. Presence or history of significant gastrointestinal, liver or kidney disease, or any  other condition that is known to interfere with drug absorption, distribution,  metabolism or excretion, or known to potentiate or predispose to undesired effects  6. History of significant cardiovascular, pulmonary, hematologic, neurological,  psychiatric, endocrine, immunologic or dermatologic disease  7. Presence of clinically significant ECG abnormalities at the screening visit, as  defined by medical judgment  8. Any intranasal conditions including nostril piercing, abnormal nasal anatomy, nasal  symptoms (i.e., blocked and/or runny nose, nasal polyps, etc.), or having a product  sprayed into the nasal cavity prior to drug administration  9. Current or recent upper respiratory tract infection (within 28 days before the first  study drug administration)  10. Maintenance therapy with any drug or significant history of drug dependency or alcohol  abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)  11. Any clinically significant illness in the 28 days prior to the first study drug  administration  12. Use of any prescription drugs (with the exception of hormonal contraceptives or  hormone replacement therapy) in the 28 days prior to the first study drug  administration, that in the opinion of an investigator would put into question the  status of the participant as healthy  13. Any history of tuberculosis  14. Positive test result for alcohol and/or drugs of abuse at screening or prior to the  first drug administration  15. Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or  hepatitis C virus antibody tests  16. Any other clinically significant abnormalities at screening that would, in the opinion  of an investigator, increase the subject's risk of participation, jeopardize complete  participation in the study, or compromise interpretation of study data  17. Inclusion in a previous group for this clinical study (for Phase 2 only)  18. Intake of naloxone in the 28 days prior to the first study drug administration  19. Intake of an Investigational Product (IP) in the 28 days prior to the first study drug  administration  20. Donation of 50 mL or more of blood in the 28 days prior to the first study drug  administration  21. Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical  studies, etc.) in the 56 days prior to the first study drug administration

The purpose of this research study is to test the safety and effectiveness of Seleno-L  Methionine (SLM) when combined with the standard dose and schedule of Axitinib and  Pembrolizumab in patients who have locally advanced or metastatic clear cell renal cell  carcinoma (ccRCC). The proposed study is a single arm, open-label Phase I/II trial of Seleno-L Methionine (SLM)  in sequential combination with the standard dose and schedule of Axitinib and Pembrolizumab  in previously untreated patients with advanced ccRCC. The hypothesis is that adding SLM to  the Pembrolizumab and Axitinib combination will improve efficacy without added toxicity.  This is a two-part study:  -  Escalation Part 1: The study will begin with a dose-escalation study to find the maximum  tolerated dose (MTD) of study drug, SLM.  -  Expansion Part 2: Once the appropriate dose of SLM is determined, the second part of the  study will begin. Inclusion Criteria:  To be eligible to participate in this study, an individual must meet all the following  criteria:  -  Written and voluntary informed consent.  -  Histologically and radiologically confirmed locally advanced or metastatic ccRCC.  Locally advanced is defined as non resectable in the opinion of the treating  providers. Participants must be treatment naïve in metastatic setting. Prior  immunotherapy treatment in adjuvant setting is allowed.  -  > 18 years of age  -  At least one Response Evaluation Criteria in Solid Tumors (RECIST 1.1)-defined target  lesion that has not been irradiated  -  Eastern Cooperative Oncology Group performance status of 0 (fully active, able to  carry on all pre-disease performance without restriction) or 1 (restricted in  physically strenuous activity but ambulatory and able to carry out work of a light or  sedentary nature, such as light housework or office work).  -  Renal function (creatinine level within normal institutional limit, or creatinine  clearance >15 mL/min/1.73 m2 for patients with creatinine levels above institutional  normal, calculated using the Cockcroft-Gault formula).  -  Liver function (AST/ALT <3.0 X institutional upper limit of normal OR < 5 x  institutional upper limit of normal in cases of liver metastases; Total bilirubin ≤  1.5 times ULN.)  -  Adequate hematological lab values including  -  Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L  -  Platelets ≥ 100 x 109/L  -  Hemoglobin ≥ 7.0 g/dL  -  Has adequately controlled BP with or without antihypertensive medications, defined as  BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week before  randomization/allocation.  -  Female subjects of childbearing potential and non-sterilized male subjects who intend  to be sexually active during the study must agree to use a highly effective method of  contraception from the time of screening, throughout the total duration of the drug  treatment, and during the 6 month post-drug washout period. See section 5.6 for full  details. Exclusion Criteria:  An individual who meets any of the following criteria will be excluded from participation  in this study:  -  Patients with a prior or concurrent malignancy whose natural history or treatment may  have the potential to interfere with the safety or efficacy assessment of the  investigational regimen.  -  Untreated metastases in the central nervous system.  -  Pregnant or breastfeeding.  -  Present use or anticipated need for cytochrome P450 (CYP) 3A4-inhibiting,  CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir,  indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and  voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine,  phenobarbital, and St. John's wort, bosentan, efavirenz, etravirine, modafinil, and  nafcillin).  -  Myocardial infarction, uncontrolled angina, congestive heart failure, or  cerebrovascular accident within previous 6 months. Participants with history of deep  vein thrombosis or pulmonary embolism, at provider discretion.  -  Major surgery within 4 weeks of starting study treatment.  -  Patients with HIV infection with CD4+ T-cell (CD4+) counts < 350 cells/uL  -  Patients with HIV infection and a history of AIDS-defining opportunistic infections  No exclusions will be made based on sex, race, or ethnic background.

Repetitive transcranial magnetic stimulation (rTMS) is a modality for probing and altering  brain function in humans non-invasively. The technology relies on the principles of  electromagnetic induction, whereby magnetic fields have an associated electrical field. By  intersecting two magnetic fields safely generated outside the head, one can induce a focal  electrical current where the magnetic fields intersect in the brain, and this can depolarize  cell membranes and impact brain activity.  A well investigated phenomenon in neuroscience is the principle of long term potentiation  (LTP), and its converse long term depression (LTD), referring to the ability of neurons to  increase or decrease their connection strength in an activity dependent manner. They do this  through modifications to their electrochemical junctions, the synapses. We have previously  used the motor system as a model system to study the impact D-Cycloserine, an NMDA receptor  partial agonist, on synaptic plasticity after TMS.  Conventional therapeutic TMS is delivered once daily, however it is increasingly being  delivered multiple times per day in an effort to speed treatment effects. It is unclear how  adjunctive agents would impact these repeated stimulation designs.  Research Question:  Does the N-methyl-D-aspartate receptor partial agonist D-Cycloserine stabilize motor  plasticity across multiple daily sessions of TMS? Objectives:  1. To recruit 20 participants into a cross-over trial. These participants will complete two  study phases (active and placebo), and will not know whether they are taking a low-dose  d-cycloserine capsule (100mg) or a placebo capsule at each of these phases.  2. To measure motor evoked potentials (MEP) in the hand in relation to magnetic stimulation  of the motor cortex responsible for this muscle. These will be measured at baseline, and  after receiving rTMS over the motor cortex.  3. To deliver intermittent theta-burst rTMS stimulation (TBS) to the FDI region of the  motor cortex.  4. To measure the magnitude (and associated change from baseline) of the MEPs after rTMS at  a fixed stimulus intensity, and using a range of stimuli to generate a stimulus response  curve.  5. To repeat iTBS one hour later and measure the impact on MEPs.  6. To measure changes in performance on computerized cognitive tasks following ingestion of  the blinded capsule.  Methods:  D-Cycloserine will be purchased from Parsolex and repackaged into 100mg placebo-controlled  capsules by Script Pharmacy in Calgary.  1. We will recruit 20 participants aged 18-65 through community advertisement, carefully  screened for exclusion factors related to rTMS and DCS.  2. Participants will be randomly assigned by random number sequence with allocation  concealment to one of two first arms of the crossover study: a) placebo-DCS 100mg and b)  DCS 100mg-placebo.  3. Participants will complete the QIDS-SR (Quick Inventory of Depressive Symptoms-Self  Report), the BAI (Beck Anxiety Inventory), and the STAI (State Trait Anxiety Inventory).  4. Participants will take their blinded capsule at least 1 hour prior to TBS. (we  anticipate that it will take approximately 30 minutes to do steps 5-7)  5. Electromyographic (EMG) electrodes will be positioned over the first dorsal interosseous  (FDI) bilaterally. These are non-invasive electrodes that use an adhesive to stick to  the skin.  6. Using neuronavigation in conjunction with an atlas brain, the M1 hand strip will be  localized using single pulse TMS (MagPro X100).  7. Motor evoked potentials are measurements of muscle activation, in this case in response  to TMS stimulation of the brain. We will use single pulse TMS to record the magnitude of  responses. As a baseline, we will collect twenty single-pulse (120% resting motor  threshold (RMT), 0.25Hz) MEPs every 5 minutes for the 15 minutes preceding TBS rTMS. We  will also characterize the stimulus response curve at baseline by delivering single  pulse TMS at stimulus intensities ranging from 100-150% resting motor threshold  presented in random order.  8. TBS rTMS will be applied to the FDI 'hotspot'. TBS consists of 2s trains every 10s.  Trains are composed of 3 pulses at 50Hz, 200ms intervals, 80% RMT. Total time 190s and  600 pulses.  9. After TBS, twenty MEPs will be acquired (single pulse, 120% RMT, 0.25Hz) every 5 minutes  for the first 15 minutes after iTBS. A stimulus response curve will be acquired at 30  minutes and 60 minutes post iTBS.  10. One hour following TBS, a second train of TBS rTMS will be applied to the FDI 'hotspot'.  TBS consists of 2s trains every 10s. Trains are composed of 3 pulses at 50Hz, 200ms  intervals, 80% RMT. Total time 190s and 600 pulses.  11. After TBS, twenty MEPs will be acquired (single pulse, 120% RMT, 0.25Hz) every 5 minutes  for the first 15 minutes after iTBS. A stimulus response curve will be acquired at 30  minutes and 60 minutes post iTBS.  12. During one of the breaks in the stimulation procedure, a brief, computerized  neurocognitive assessment will take place after ingestion of the blinded capsule.  13. Participants will be asked if they believe they received the study medication or placebo  in this first phase of the crossover trial.  This is study involves a crossover design, therefore after a minimum of 7 days the experiment  will be repeated with the second blinded capsule. Inclusion Criteria:  1. Healthy (absence of chronic medical conditions) individuals  2. Aged 18-65. The lower limit is justified by the absence of safety studies involving  DCS in pediatric studies, and the upper limit is justified by the increasing  prevalence of chronic illness. Exclusion Criteria:  1. Allergy to cycloserine  2. Are currently pregnant, breast feeding or plan to become pregnant  3. Have an alcohol or substance use disorder within the last 3 months  4. Current psychiatric concerns  5. are at a significant risk of harm to themselves or others  6. Have any significant neurological disorder or insult including, but not limited to:  any condition likely to be associated with increased intracranial pressure, space  occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's  disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of  consciousness for greater than or equal to 5 minutes  7. Have concomitant major unstable medical illness, cardiac pacemaker or implanted  medication pump  8. Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear  implants, or electrodes) or any other metal object within or near the head, excluding  the mouth, that cannot be safely removed  9. Conditions that may impair the ability to metabolize cycloserine including, but not  limited to current Renal or Liver Disease.  10. Inability to refrain from alcohol use for 24 hours prior to each session and following  each session.  11. Use of isoniazid or ethionamide  12. Are currently (or in the last 4 weeks) using any benzodiazepine, cyclopyrrolone,  gabapentin/pregabalin or anticonvulsant due to the potential to limit rTMS efficacy

1-to identify the prognostic value of serum bicarbonate and serum electrolytes at time of  admission and their association with development of complications ,length of hospital stay  ,prognosis and mortality in hospitalized cirrhotic patient the purpose of this study will be explore the impact of data obtained for the arterial blood  gas parameters and serum bicarbonate and electrolytes at the time of hospital admission on  adverse clinical outcomes ,duration of length of hospital stay and mortality in patients with  cirrhosis .Furthermore incorporation these parameters into model of end stage liver disease  could help to improve the prognostic value of MELDscore in comparison to the prognostic value  of traditional equation of original MELD and child score Inclusion Criteria:  patients with confirmed diagnosis of cirrhosis (age >18 years ) who will be admitted to  internal medicine department or will be admitted to intermediate care unit  -  willing and agree to be included in the study Exclusion Criteria:  -  patients without evidence of cirrhosis  -  cirrhotic patients whom -younger than 18 years old  -  have diabetic ketoacidosis  -  with acute coronary syndrome  -  with fulminant liver failure  -  with heart failure  -  with organ transplantation  -  when arterial blood gases not be available  -  patient refusal  -  patient with HCC

This study investigates the feasibility and preliminary efficacy of a self-guided,  exposure-based intervention for individuals who suffer from severe health anxiety. The study  is a prospective single-group study based at Karolinska Institutet, Stockholm, Sweden, where  20-25 adults with DSM-5 Illness anxiety disorder or Somatic symptom disorder are enrolled in  8 weeks of unguided exposure-based treatment via the Internet. Outcomes include self-reported  health anxiety symptoms, credibility and expectancy, adherence to the treatment protocol,  client satisfaction, and negative events. Background  Severe health anxiety (Corresponding to a DSM-5-diagnosis of Illness anxiety disorder or  somatic symptom disorder) is a condition associated with high distress, disability and  increased health service utilization. Therapist guided Internet delivered cognitive  behavioural therapy (ICBT) is efficacious in the treatment of severe health anxiety and has  the advantage of requiring less treatment support per patient compared to traditional CBT,  thus making the treatment more cost effective. Despite this, the access to ICBT is limited as  it requires the active participation of a therapist. Given the relatively high prevalence of  individuals experiencing excessive health anxiety, there is need for research on more  accessible treatment options.  Unguided self-care interventions have the potential to improve access to treatment and  increase cost-effectiveness and have a more immediate scalability. Also, unguided  interventions have the advantage of being more easily disseminated outside the traditional  mental health care systems and thus, have the potential to reach patients with subclinical,  yet distressful, health anxiety.  Aim  The overall aim of this study is to develop a new internet-delivered CBT program based on  exposure and response prevention - without therapist support - for patients with severe  health anxiety and to examine its feasibility and potential clinical efficacy.  Design  This is a prospective single-group feasibility study with a pre-post design where a total of  25 participants with Illness anxiety disorder or Somatic symptom disorder (suffering from  health anxiety) according to the Diagnostic and statistical manual of mental disorders 5  (DSM-5) are enrolled in an 8 weeks unguided internet based treatment targeting exposure and  response prevention. The study will evaluate patient-reported satisfaction, engagement and  adherence to treatment protocol, credibility, safety and pre-post changes in health anxiety. Inclusion Criteria:  -  Age ≥ 18 years  -  A principal diagnosis Illness anxiety disorder or somatic symptom disorder (DSM-V)  -  Access to a computer and the internet  -  No serious medical illness  -  Participants on psychotropic medication must have been on a stable dose for the last 4  weeks prior to baseline assessment Exclusion Criteria:  -  Difficulties to read or write that makes it hard to understand the content of the  intervention  -  Currently receiving similar psychological treatment for anxiety  -  High risk of suicide  -  Diagnosed with psychosis disorder or bipolar disorder  -  Ongoing substance dependence  -  Have an urgent need for more intensive psychiatric care

The investigators intend to compare Epstein-Barr virus antibody and Epstein-Barr virus DNA  screening efficacy in first-degree relatives of nasopharyngeal carcinoma patients. The investigators intend to test Epstein-Barr virus antibodies (Viral Capsid  Antigen-immunoglobulin A， Epstein-Barr nuclear antigen 1-immunoglobulin A， early  antigen-immunoglobulin A， Zta-immunoglobulin A， Rta-immunoglobulin G, Bnlf 2b) by ELISA and  Epstein-Barr virus DNA by quantitative polymerase chain reaction, target sequencing and  CRISPR-associated protein 12a in nasopharyngeal brushing and plasma of the same population at  high-risk of nasopharyngeal carcinoma so as to determine the best method in nasopharyngeal  carcinoma screening. Inclusion Criteria:  -  residents in Southern China  -  30-62 years old  -  male  -  a first-degree relative of at least one nasopharyngeal carcinoma patient  -  no medical record of nasopharyngeal carcinoma  -  Eastern Cooperative Oncology Group score of 0-2  -  be able to comprehend, sign, and date the written informed consent document to  participate in the study Exclusion Criteria:  -  history of nasopharyngeal carcinoma  -  heavy cardiovascular, liver or kidney disease  -  on systemic steroid or immunosuppressant treatment or active autoimmune disease

The CLIP program will train Community Health Workers (CHWs) to screen and identify Black men  with elevated blood pressure (BP) or stage 1 hypertension (HTN), initiate lifestyle  counseling; and link them to primary care and social services. The study will consist of:  1. An implementation phase that will use a cluster randomized cluster trial of 20  barbershops among Black men with elevated BP or Stage 1 HTN, to compare the effect of  the Barbershop-based Facilitation (BF) strategy (n=10 barbershops; n=210 participants)  vs. self-directed control (i.e. receipt of information for implementation of CLIP  without the BF strategy; n=10 barbershops; n=210 participants), on BP reduction, HTN  prevention, linkage to care, and adoption of CLIP at 12 months  2. A post-implementation phase that will use Reach Effectiveness Adoption Implementation  and Maintenance (RE-AIM) to evaluate the effect of the BF strategy versus self-directed  control on sustainability of CLIP 6 months after completion of the trial; and  cost-effectiveness over a 10-year time horizon. Inclusion Criteria:  1. 18 years of age as of date of data extraction  2. Repeat customer within the last 3 months  3. Self-identify as Black  4. Self-identify as male  5. Have elevated blood pressure (PB) (120-129/<80 millimeters of mercury (mm Hg)) or  untreated stage 1 hypertension (HTN) (130-139/80-89 mm Hg) (defined by American Heart  Association's 2017 HTN clinical guidelines) Exclusion Criteria:  1. Age <18 years  2. Prescribed antihypertensive medication  3. Diagnosis of end-stage renal disease (ESRD)  4. Condition which interferes with outcome measurement (e.g., dialysis)  5. Serious medical condition which either limits life expectancy or requires active  management (e.g., cancer)  6. Cognitive impairment or other condition preventing participation in the intervention  7. Upper arm circumference >50 cm (maximum limit of the extra-large BP cuff)  8. Active alcohol or substance use disorder (i.e., not sober/abstinent for ≥ 30 days)  9. Pregnant or planning pregnancy in the next 24 months  10. Currently nursing a child  11. Current participation in another research study focused on reducing BP  12. Unwillingness to provide informed consent

The aim of this study is to evaluate the clinical and radiographic success of Lesion  Sterilization And Tissue Repair [ LSTR] antibiotic paste versus Zinc Oxide and Eugenol  pulpectomy in the treatment of non-vital primary molars. Primary teeth with infected root canals are a common problem, particularly in patients where  the infection has reached the peri radicular tissues .  Among the pastes used in the pulp therapy of primary teeth with pulp necrosis, zinc oxide and  eugenol paste has been a reference in dentistry since 1930. Endodontic treatment using zinc  oxide and eugenol paste has shown satisfactory clinical and radiographic results, requires  mechanical chemical preparation before filling root canals.  The main difficulties of endodontic treatment of primary molars are related to the anatomical  complexity of the root canals and the long time needed to carry out the treatment. The  additional difficulty involved in diagnosing root resorption is a limiting condition for  determining the actual working length and instrumentation.  Other pastes have been studied, such as those containing antibiotics in their composition,  thus dispensing with root canal instrumentation (such as lesion sterilization and tissue  repair using triple antibiotic paste in treatment of non-vital primary molars.  Lesion sterilization and tissue repair using triple antibiotic paste has relevant clinical  and radiographic success rates in treatment of non-vital primary molars. Inclusion Criteria:  -  Children:  1. Aged between 5 years and 7 years.  2. With deep caries involving pulp in primary molars.  -  Teeth:  1. Necrotic teeth with or without periapical or furcal lesions.  2. Primary molars with minimal root resorption not more than 1/3 of root. Exclusion Criteria:  -  Children:  1. Children with systemic disease  2. Previous history of allergy to antibiotics used in the study.  3. Children that will not attend follow up.  -  Teeth:  1. Caries in primary teeth exhibiting pre-shedding mobility.  2. Non restorable teeth.

The continued access study of the VIG (hereafter referred to as the 'Venous InterGraft  Continued Access Study, or 'VIG-CAS') allows for continued enrollment of subjects while the  marketing application is being prepared and subsequently reviewed by FDA. The VIG-CAS will  include the same patient population, follow-up schedule, and study endpoints as the VIG-only  study. The VIG-CAS is a multicenter, prospective, single-arm (non-randomized) study that will  include up to 15 subjects contributed from up to five (5) study sites/investigators who  previously participated in the VIG-only study. No new investigators will be included. All  subjects will be assigned to treatment with the VIG and a standard sutured arterial  anastomosis for implantation of an AVG for hemodialysis. The selection criteria (patient  population), follow-up schedule, and study endpoints are the same as those used in the  VIG-only study.  Study data will be collected up to the point at which each subject has completed the final  6-month follow up or experienced a terminal study event Inclusion Criteria:  1. Subject is ≥ 18 years of age.  2. Subject requires the creation of a vascular access graft for hemodialysis, secondary  to a diagnosis of End Stage Renal Disease.  3. Subject has the vascular access graft placed in an upper extremity.  4. Baseline imaging shows suitable vascular anatomy/ vessel size for the InterGraft™  Venous Connector and an artery at least 3.5 mm in diameter that is suitable for  creating the arterial anastomosis.  5. Subject has a reasonable expectation of remaining on hemodialysis for at least 6  months.  6. Subject or his/her legal guardian understands the study and is willing and able to  comply with the dialysis schedule and follow-up requirements.  7. Subject or his/her legal guardian provides written informed consent. NOTE: In  accordance with the requirements of some Institutional Review Boards (IRBs), where  applicable, only those subjects with capacity to consent for themselves will be  included. Thus, where required by the IRB, adult individuals who lack capacity to  consent for themselves will be excluded from the study.  8. Physician's examination at time of surgery shows no significant vessel lesions,  calcification(s), anatomic structures, or abnormalities that may limit ability to  safely deploy the InterGraft™ Venous Connector or create a sutured arterial  anastomosis. Exclusion Criteria:  1. Subject has a documented and unsuccessfully treated ipsilateral central venous  stenosis as determined by imaging.  2. Subject currently has a known or suspected bacterial, fungal, or HIV infection. NOTE:  Subjects with hepatitis B or C may be included in the study.  3. Subject has a known hypercoagulable or bleeding disorder or requires treatment with  warfarin or heparin. NOTE: The intent of this criterion is to exclude patients with  high risk for bleeding or clotting complications. Patients who are taking the oral  anticoagulant Eliquis® (apixaban) may be included in the study if Eliquis is  temporarily discontinued prior to the study procedure, in accordance with the approved  prescribing instructions. Patients may receive anticoagulation therapy any time after  the study AV graft implant procedure, at their physician's discretion. This should be  driven by an indication unrelated to the vascular access.  4. Subject has had a previous instance of Heparin Induced Thrombocytopenia type 2 (HIT-2)  or has known sensitivity to heparin.  5. Subject has co-morbid conditions that may limit their ability to comply with study and  follow-up requirements.  6. Subject has had >2 previous arteriovenous accesses in treatment arm.  7. Subject is currently taking Aggrenox®.  8. Subject needs or is scheduled for any major surgery within 30 days of the study  procedure.  9. Subject is currently taking maintenance immunosuppressant medication such as  rapamycin, mycophenolate or mycophenolic acid, prednisone (>10 mg), cyclosporine,  tacrolimus, or cyclophosphamide.  10. Life expectancy is less than 12 months.  11. Subject is pregnant. NOTE: A negative urine pregnancy test within 24 hours of the  study procedure is required in all female subjects with reproductive capacity.  12. Subject is a poor compliance risk (i.e.. history of IV or oral drug abuse).  13. Subject is enrolled in another dialysis or vascular investigational study.

In this project, the investigators will perform a multicenter randomised controlled trial to  determine whether advice to consume a moderate, whole food-based low-carbohydrate high-fat  (LCHF) ad libitum diet (CarbCount program) can produce and maintain equal remission rates of  type 2 diabetes (T2D) as a nutritionally complete very-low-calorie formula diet followed by a  energy-restrictive (i.e., calorie counting) diet (DiRECT principles). Within the principles  of each approach, the dietary goals and change will be adjusted according to individual  needs/capabilities conducive to long-term adherence. Furthermore, the investigators aim to  determine whether the rate of diet-induced remission is reflected in/can be predicted by  baseline or diet-induced changes in glucose variability (e.g., time-in-range measured by  continuous glucose monitoring) and other factors such as anthropometric changes and genetic  susceptibility. Each center will also conduct locally-lead standalone mechanistic research,  including analyses of intra-abdominal/hepatic fat accumulation, adipose tissue biopsies  and/or measurements of energy metabolism. Additionally, changes in medication use,  nutritional status, cardiovascular disease risk, as well as adverse events, will be  monitored. At least 588 patients with T2D will be recruited, approximately 120-150 men and women at each  research center. The participants will be randomised to 1) a nutritional complete formula  diet for 3 months followed by an energy restricted diet for 12 months or 2) a very  low-carbohydrate high-fat (VLCHF) diet for 3 months, followed by a low-carbohydrate high-fat  diet (LCHF) for 12 months. Each of the diets will cover all basic requirements for essential  nutrients including amino acids, fatty acids, vitamins and minerals. Participants will be  encouraged to consume at least 200 g of vegetables per day. Furthermore, we will emphasize  high-quality, minimally processed foods. In arm 2 they will receive advice to eat specific  fat sources such as extra virgin olive oil, butter and high-fat cheeses.  The DiRECT trial showed remission in 46% of participants after 12 months. Assuming that both  the DiRECT program and LCHF dietary strategies yield a 45% chance of T2D remission after 15  months, it is calculated (using nQuery v8) that each group needs 235 participants to complete  the trial. This sample size yields 90% statistical power to conclude, with respect to the  primary outcome, whether the CarbCount Program is no more than 15% more or less effective  than the DiRECT principles (equivalence study, one-sided p-value at 0.025). To allow for  expected loss to follow-up (estimated at 20%), each of the arms needs at least 294  participants for a total of 588.  Participants will have access to electronic platforms that include an online database of  recipes (breakfast, easy-to-cook lunches, snacks, dinners, and food for special occasions).  The platforms will facilitate planning of week menus, and include an e-learning course  covering topics such as how to cook and prepare foods, meal planning, dining out, sleep and  individual aspects that challenge habit change. If the participants are failing in their  efforts to establish or maintain lifestyle change, they will be encouraged to seek possible  solutions in the e-learning courses or to contact one of the study's health educators and/or  dietitians. Specific rescue plans involving direct contact with study staff will be  implemented if a participant regains more than 2 kg or experiences T2D relapse.  After individual assessment by a doctor, the participants will be taken off diabetes  medication upon starting the diet, and be asked to self-monitor blood sugar changes during  the first 2 weeks on the diet, followed by a consultation that includes evaluation of these  changes. The need of reintroduction of medication will be done in consultation with the study  doctor at least every 3 months.  Between visits, the participants will complete dietary assessments and an e-learning course,  and at least once a month have follow-ups with dietitians/health educators and/or online  group workshops.  The study will enroll eligible participants to the study continuously, until the total number  of participants needed for the study is reached. Each participant will follow their own  timeline, and attend visits at the study center at baseline, 3, 9 and 15 months.  During 2 weeks before each visit, participants will wear a continuous glucose monitor (CGM)  and record food intake for at least 3 consecutive days during this period.  Measurements during visits will include anthropometric variables/body composition and energy  expenditure, blood, saliva, urine and stool samples will be collected, and participants will  be asked to fill out questionnaires on physical activity, sleep pattern, meal frequency,  quality of life, problem areas in diabetes, eating efficacy and eating behaviors. They will  also have a consultation with a registered dietitian and meet with the study medical doctor  when needed.  A blinded statistician will perform the statistical analyses for the primary outcome of the  study. Inclusion Criteria:  -  HbA1c ≥48 mmol/mol (with or without medical treatment)  -  Less than 10 years since the diagnosis of T2D  -  BMI ≥27 kg/m2 (≥25 kg/m2 for Asians) Exclusion Criteria:  -  Treatment with insulin >25 IU  -  HbA1c concentration of 12% or more (≥108 mmol/mol)  -  Insulin to C-peptide ratio <0.8 (indicative of insulin deficiency)  -  Myocardial infarction within the previous 6 months, and severe or unstable heart  failure or other severe diseases including cancer, psychiatric/eating disorders,  severe depression and substance abuse

Antimicrobial resistance is one of today''s most urgent public health problems. An important  strategy to slow the spread of antimicrobial resistance is the promotion of judicious  antimicrobial use. There are many opportunities to reduce unnecessary  antimicrobial-prescribing, including in patients undergoing surgical procedures. The  following study will specifically study opportunities to improve antimicrobial use in  patients undergoing common urologic procedures at hospitals in the Veterans Health  Administration (VHA).  Guidelines recommend giving antibiotics for no more than 24-hours after most urologic  procedures, but the investigators have shown that the unnecessary use of post-procedural  antimicrobials is common in this setting. In a national cohort of nearly 30,000 VHA patients,  excessive post-procedural antimicrobials were prescribed after 37.2% of urologic procedures  for a median duration of 3.0 excess days.  In this study, the investigators will evaluate whether giving regular feedback to providers  at 3 VHA hospitals can reduce unnecessary antimicrobial use after urologic procedures. Trial design: The investigators propose a before/after quasi-experimental design, which will  be analyzed with an interrupted time-series analysis.  Participants: There will be 3 intervention VHA hospitals. To be eligible, a VHA hospital must  perform the following 3 urologic procedures: transurethral resection of the prostate (TURP),  transurethral resection of a bladder tumor (TUBRT), and ureteroscopy (URS).  Interventions: The study team will conduct an audit-and-feedback intervention focused on the  unnecessary use of prolonged antimicrobial therapy after common urologic procedures.  The audit-and-feedback intervention will target the urology providers at the 3 intervention  sites.  Outcomes: The primary outcome for this study will be the frequency of excessive  post-procedural antimicrobial-prescribing in the 3 urologic procedures of interest. Secondary  outcomes include several safety outcomes, such as late antimicrobial prescriptions, return  visits, mortality, C. difficile testing and C. difficile infection.  For each site, the pretest period will be the 2-years prior to the intervention. The  intervention itself will last 1-year.  Selection of sites: Intervention sites will be randomly selected from the top quartile of all  sites, as ranked on the frequency of excessive post-procedural antimicrobial-prescribing. If  sites refuse to participate, additional sites will be invited until 3 sites agree to be  enrolled.  Statistical methods: At the conclusion of the pilot trial, a quasi-experimental interrupted  time-series (ITS) analysis will be performed to assess the change in monthly antimicrobial  use for the 3 intervention sites combined. The time frame for this ITS analysis will be the  two-years prior to the pilot trial's initiation through the trial's 1-year intervention  period for a total of 36 months. Inclusion Criteria:  -  A practicing urologist at an intervention site, OR  -  A member of the antimicrobial stewardship team at an intervention site Exclusion Criteria: None

The purpose of this study is to learn more about the metabolic properties of lung cancer  cells. It has long been known that cancer cells absorb and break down substances in the body  differently than healthy, non-cancer cells. This process of absorbing and breaking down  substances is known as metabolism and is increased in cancer cells. Recent research suggests  that this increased metabolic activity makes it easier for cancer cells to multiply. The  objective of the study is to characterize the metabolism of glucose by lung tumors by serum  metabolite analysis, using a variant of glucose (sugar) which makes up 1% of glucose in  nature. Inclusion Criteria:  -  patients with suspected, clinically diagnosed, or histologically diagnosed lung  cancer. Occasionally, other cancers (including metastatic cancers to the lung) may be  resected for the study as negative controls for NSCLC, as warranted by the particulars  of the case.  -  patients must have general medical conditions to allow them to undergo surgical  resection of their primary tumor  -  at least 30 years of age  -  preferably be fasting for 12 hours (minimum 8 hours) prior to enrollment Exclusion Criteria:  -  history of diabetes for the experimental group (surgery + glucose); patients with a  history of diabetes are allowed in the control group (surgery/no glucose)  -  known hepatitis C or HIV (AIDS)  Healthy Subjects (Group 3)  -  prior history of diagnosed lung cancer  -  known hepatitis C or HIV (AIDS)

The purpose of this study is to evaluate whether therapy with MORAb-004 is effective and safe  in the treatment of metastatic, colorectal cancer. Tumor endothelial marker-1 also referred to as TEM-1 is expressed in the supportive tissue,  as well as, on the cells within the tumor. TEM-1, which is a cell surface glycoprotein, and  is expressed in the stromal compartment (cells) of nearly all human tumors. In preclinical  studies, it has been shown that TEM-1 plays a key role in tumor growth and the  vascularization of tumors. There is evidence suggesting an association between the level of  TEM-1, 7, 7R, 8 in relation to lymph node involvement and disease progression. MORAb-004 is a  humanized immunoglobulin G (IgG1/κ) antibody directed against endosialin/TEM-1. Nonclinical  pharmacological studies showed that MORAb-004 has the ability to block specific TEM-1  receptor-ligand interactions. Immunohistochemistry studies of human tumor biopsy samples  demonstrate TEM-1 expression and MORAb-004 binding to tumor stromal cells, in particular  mural cell compartment of neovessels and cancer-associated fibroblasts. All of which suggests  a potential effective treatment. Researchers hypothesize that an antibody therapy that binds  to TEM-1 may be efficacious in the treatment of metastatic, colorectal cancer. This clinical  study is a proof of concept study to see if an anti-TEM-1 agent is safe and effective in the  treatment of metastatic, colorectal cancer. Inclusion Criteria:  -  Males and females >18 years old  -  Diagnosis of metastatic, colorectal cancer  -  Significant medical conditions must be well-controlled and stable for at least 30 days  prior to the first treatment infusion  -  Be willing and able to provide written informed consent Exclusion Criteria:  -  No prior treatment for metastatic colorectal cancer  -  Other serious systemic diseases (bacterial or fungal)  -  Clinically significant heart disease or an arrhythmia on an ECG within the past 6  months  -  Known allergic reaction to monoclonal antibody therapy

This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single  ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety,  tolerability, PK and PD of DD01 administered by subcutaneous (SC) injection in  overweight/obese subjects with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease  (NAFLD).  The study will be conducted in 2 Parts (Part A and B), with up to 8 cohorts included in each  part (Part A; Cohorts A1 to A8 and Part B; Cohorts B2 to B8). Part A (SAD):  In Part A, subjects will receive a single dose of study drug, and the safety and efficacy of  DD01 will be evaluated in overweight/obese subjects with T2DM.  Part B (MAD):  In Part B, subjects will receive once-weekly doses of the study drug for 4 weeks, and the  safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM and  NAFLD. Inclusion Criteria: None Exclusion Criteria: None

Development and validation of first clinical diagnostic interview for assessing Prolonged  Grief Disorder (PGD) with the ICD 11 and DSM 5 Tr criteria. Development and validation of first clinical diagnostic interview for assessing Prolonged  Grief Disorder (PGD) with the ICD 11 and DSM 5 Tr criteria.  Background: With WHO's introduction of PGD in the ICD 11, which will be implemented in Health  Services worldwide from January 2022, there is a need to accurately diagnose people with  ICD-11PGD (PGD caseness) with a valid structured clinical interview.  With ICD-11 a slightly different set of symptoms for PGD is defined as the gold standard for  PGD. This standard will be used for diagnosing and understanding PGD in future research and  health service. ICD-11 aims to be descriptive, e.g. provides a support for the clinicians to  identify PGD by describing common reactions and symptoms of this disorder, but there is still  a need to evaluate the validity of these criteria. Strict diagnostic criteria with defined  numbers, combinations, and intensity of symptoms (e.g. for the use in research) are not yet  defined in ICD-11 and no structured clinical interview that measure ICD-11 or the upcoming  DSM 5 tr PGD has yet been developed and validated for this purpose. This means that the field  currently stand without reliable ways to classify accurately who has PGD diagnosis and who  has not. Without such constructs, PGD is not possible to identify, and ultimately to treat,  in a validated and reliable way.  There is therefore a need to develop accurate tests that measure ICD 11 PGD, both in a  structured clinical interview for use in direct meetings between patients and health service  professionals and in relation to a self-report scale. The investigators already developed the  Aarhus PGD scale but still need a structured clinical interview.  Aim: In this project we will  1. Develop and validate the first structured, clinical interview for ICD-11 PGD and DSM-5  Tr PGD  2. Identify a valid clinical cut-off for diagnostic PGD on The Aarhus PGD Scale.  Method:  Based on the ICD-11 and DSM 5 Tr PGD criteria and our work with the self-report scale above  the investigators will develop a structured, clinical interview, The Aarhus PGD Interview, in  line with the strategy used in SCID-I interviews [6]. This study will examine the content  validity, the concurrent validity, the test-retest reliability and the inter-rater  reliability of this interview.  After the Aarhus PGD Interview is validated, this study will compare the participant's scores  on the Aarhus PGD Scale for ICD 11 and DSM 5 Tr PGD with the clinical interview as the gold  standard. This will allow investigating the diagnostic test accuracy of the ICD-11 PGD scale,  and to identify a valid clinical cut-off on this scale.  Perspectives: The main aim of this study is to develop and validate the first structured,  clinical interview for ICD 11 and DSM 5 Tr PGD. It will provide reliable constructs to  separate PGD from other, trans-diagnostic forms of complicated grief reactions such as PTSD,  depression and anxiety following a loss. The ability to identify who actually has a diagnosis  of PGD and are in need of treatment is crucial to be able to allocate health benefits as  efficient and helpful as possible. It is also crucial in identifying the vast majority of  bereaved people with normal grief reactions, and to reduce the risk of pathologizing healthy  grief, which is a concern brought on by the introduction of PGD as a diagnostic entity Inclusion Criteria:  -  Bereaved by the loss a loved one to death minimum 6 month ago  -  18 years or above  -  The grief is still (more or less) affecting function/everyday life Exclusion Criteria:  -  Bereaved by other losses than a loved person (e.g., pet, divorce)  -  17 years or younger  -  Less than 6 month ago since the loss.

Invasive mechanical ventilation is a life-saving treatment in critically ill newborns with  respiratory failure. However, continuing this treatment for a long time may have negative  consequences, especially bronchopulmonary dysplasia (BPD) secondary to mechanotrauma. For  this reason, it is essential to terminate the mechanical ventilation treatment at the most  appropriate time.  About half of the extremely preterm babies may fail extubation even if the clinical criteria  traditionally used for extubation are met. Unsuccessful extubation is associated with  increased intraventricular bleeding, death, BPD, death or BPD, longer duration of ventilator  support.  When respiratory failure and lung pathologies of extremely preterm babies begin to improve,  the target for mechanical ventilation should be early and successful extubation. Currently,  the decision to extubate a preterm baby is primarily based on clinical judgment. Only a few  studies that showed the low predictive value and limited utility using different measures  have evaluated readiness for extubation. Lung ultrasonography (USG) is a noninvasive bedside  technique that has been found useful for predicting the success of weaning from the  ventilator in adults; however, very little data are available in neonates. In a recently  published study, it was proposed an extubation readiness estimation tool based on clinical  and demographic data of preterm babies who were attempted elective extubation.  The researchers' hypothesis is that the use of a model based on extubation success scoring  and lung USG scoring before extubation reduces the failure of the first extubation attempt in  very low birth weight infants. The aim of the study is to evaluate the value of using an  integrated model based on pre-extubation "extubation readiness predictor" and lung USG  scoring to predict extubation success in preterm babies undergoing invasive mechanical  ventilation. Long-term invasive mechanical ventilation may have detrimental effects in preterm infants,  although it is a life-saving treatment in critically ill newborns with respiratory failure.  (e.g. bronchopulmonary dysplasia (BPD), superimposed bacterial infections and colonization,  air leak, etc.). For this reason, it is essential to terminate the mechanical ventilation  treatment at the most appropriate time.  A significant portion of the extremely preterm babies may fail extubation even if the  clinical criteria traditionally used for extubation are met. Unsuccessful extubation is  associated with increased intraventricular bleeding, death, BPD, death or BPD, longer  duration of ventilator support.  When respiratory failure and lung pathologies of extremely preterm babies begin to improve,  the target for mechanical ventilation should be early and successful extubation. Currently,  the decision to extubate a preterm baby is primarily based on clinical judgment. Only a few  studies that showed the low predictive value and limited utility using different measures  have evaluated readiness for extubation. Lung ultrasonography (USG) is a noninvasive bedside  technique that has been found useful for predicting the success of weaning from the  ventilator in adults; however, very little data are available in neonates. In a recently  published study, it was proposed an extubation readiness estimation tool based on clinical  and demographic data of preterm babies who were attempted elective extubation.  The researchers' hypothesis is that the use of a model based on extubation success scoring  and lung USG scoring before extubation; reduces the failure of the first extubation attempt  in very low birth weight infants. The aim of the study is to evaluate the value of using a  model based on pre-extubation "extubation readiness predictor" and lung USG scoring to  predict extubation success in preterm babies undergoing invasive mechanical ventilation.  This study is a prospective observational study. The study is planned to be conducted in  infants with a birth weight <1250 g, who were intubated within the first 7 days of life,  remained intubated invasive conventional mechanical ventilation for at least 48 hours, did  not complete the postnatal 60 days, and met the traditional extubation criteria of the  institution and were considered for elective extubation for the first time.  An "informed consent form" will be obtained from the parents of the babies included in the  study. The birth dates, protocol numbers, birth types, maternal histories, genders, weeks of  gestation and birth weights of the babies will be recorded.  The usual institutional routine approaches will be applied after the baby is born. Inclusion Criteria:  -  Birth weight <1250 gr  -  Being intubated within the first 7 days of life and then followed on mechanical  ventilation  -  Being intubated for at least 48 hours  -  Not completing the postnatal 60 days  -  Meeting conventional clinical extubation criteria  -  Having planned extubation for the first time  -  Having no air leakage occurred  -  Having no structural heart and lung disease  -  Having no congenital and chromosomal anomalies  -  Having an intact diaphragm  -  Having no PVL, IVH (Grade 2 and above), HIE, meningitis or known CNS anomaly during  extubation Exclusion Criteria:  -  Infants with a gestational age of 34 weeks or more  -  Infants with unplanned and spontaneous extubation  -  Infants who have tried extubation before  -  Infants with hydrops fetalis  -  Infants with chest deformities  -  Infants with central respiratory failure (insufficient respiratory effort/control or  continuous apneic)  -  Infants who are neurologically depressed and do not have spontaneous breathing  (hypocarbia due to hyperventilation, presence of severe sedation, use of neuromuscular  drugs)  -  In the presence of genetic or congenital anomalies (esophageal atresia, severe  diaphragmatic hernia, diaphragm paralysis)  -  Having phrenic nerve damage  -  Presence of congenital myopathy  -  Having any air leakage  -  Having structural heart and lung disease  -  Having no intact diaphragm  -  Having PVL, IVH (Grade 2 and above), HIE, meningitis or known CNS anomaly during  extubation

The purpose of this study is to determine whether infliximab can favourably and safely be  discontinued in patients with Crohn's disease in sustained complete clinical, biochemical,  and endoscopic remission on infliximab.  Further to examine the clinical utility of measuring levels/activity of infliximab and  activity of anti-infliximab Ab in patients in sustained complete remission, in order to  investigate whether pharmacoimmunological data can predict the clinical outcome and  rationalize therapeutic management of these patients with respect to continuation or  discontinuation of infliximab therapy. Additional, to investigate the optimal time-point, out  of three, to measure this activity. Recent guidelines for the management of Crohn's disease conclude that currently available  data are insufficient to make firm recommendations on when and in whom to stop TNF-α antibody  (TNF-α Ab) treatment after having obtained clinical remission. Further, the term "remission"  is not well uniformly defined and may incorporate one or more features such as clinical  remission, as assessed by CDAI, biochemical remission, endoscopical remission etc. The  recently published prospective STORI study of 115 patients with luminal Crohn's disease  reported that 56% of patients with Crohn's disease who had discontinued infliximab (IFX)  while in clinical remission, maintained remission one year after discontinuation of therapy.  Predictors of relapse included certain clinical features as well as objective biochemical and  endoscopical markers of disease activity. Consistent with these data, we have recently  reported that 61% of our own patients with Crohn's disease, who discontinued IFX while in  complete clinical, steroid free IFX induced remission, maintained remission after one year;  and half the patients were still in remission after nearly two years (median 680 days  [412-948]).  A prospective randomized study of patients with Crohn's disease is necessary to confirm and  extend the limited findings above, and assess whether IFX can be safely discontinued in a  selected subgroup of patients with complete clinical, biochemical, and endoscopical  remission.  Methods:  Study design: Prospective, double-blinded, randomized, placebo-controlled, Danish  multi-center study with estimated seven Danish participating centers. Patients and treating  physicians are blinded for the type of intervention.  Study population: Patients with luminal Crohn's disease in sustained complete remission on  IFX.  Study treatment: Patients are randomized to either continue IFX treatment at an unchanged  dosage and frequency, or alternatively to receive matching placebo. All patients will be  graded for disease activity (Crohn's Disease Activity Index (CDAI), biochemical parameters,  endoscopy, and/or MRI). Following screening and inclusion patients are seen after four weeks,  and then every eight weeks. Endpoints are assessed at 48 weeks.  Investigators will, as explorative analyses, examine the clinical utility of measuring IFX  levels and antibodies against IFX in patients with complete remission, in order to  investigate whether pharmacoimmunological data can predict the clinical outcome and  rationalize therapeutic management of these patients with respect to continuation or  discontinuation of IFX therapy. Additional, investigators will investigate the optimal  time-point out of three to measure this activity. Patients will on the day of infusion have  three blood samples drawn: one just before infusion (trough), one right after the infusion  (obtained from the other arm)(peak) and one an hour after infusion (C1). Samples will be  measured by common solid - and fluid phase assays for this purpose, e.g. Reporter Gene Assay  (RGA). Inclusion Criteria:  -  Luminal Crohn's disease defined according to standardized diagnostic criteria.  -  Age ≥ 18 years.  -  IFX induction treatment week 0, 2, 6 followed by maintenance therapy.  -  IFX treatment length minimum 12 months. Episodic therapy with IFX pause > 12 weeks is  not accepted within the last year. The treatment interval in the last three months has  to be of 6-10 weeks.  -  Complete remission defined as:  -  CDAI score < 150 and  -  Biochemical remission, and  -  No other signs of disease activity as evaluated by endoscopic examination or by  magnetic resonance imaging (MRI).  -  Stable remission, judged by the treating physician, at two consecutive treatments  visits corresponding 2 scheduled IFX infusions. Thus, the first visit is during IFX  maintaining therapy (screening visit). The second visit is at time of inclusion  corresponding time of next scheduled IFX infusion (i.e. after ≈ 8 weeks).  -  No use of oral steroids within 3 months prior to inclusion.  -  Concomitant therapy with other immune suppressants, except steroids, is allowed. The  dosage and frequency must have been stable three months prior to inclusion and must  remain stable throughout the study period. Exclusion Criteria:  -  Initial indication for IFX being predominantly fistulizing perianal disease.  -  Any contraindications for continuing IFX treatment, including prior acute or delayed  infusion reaction to a TNF- inhibiting agent, any active infection requiring  parenteral or oral antibiotic treatment, known infection with tuberculosis, human  immunodeficiency virus (HIV) or hepatitis virus.  -  Any condition including physician finds incompatible with participation in the study  or the patient being unwilling or unable to follow protocol requirements.

To establish the infrastructure for a national neuropathic pain database.  To determine the longterm outcome of the management of chronic neuropathic pain including  pain relief, disability, and quality of life. The database will provide standard information on demographics, diagnosis, treatment  interventions and outcome modeled on guidelines from the expert panel on initiatives on  Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT)(Turk et al.,Pain  2003;106:337-345) The IMMPACT panel determined that patients should be evaluated according to  six core domains as follows: Pain, physical functioning, emotional functioning, subject  rating of global satisfaction with treatment, symptoms and adverse events and subject  disposition.  The database will allow us to examine outcomes based on single (eg. pregabalin) and multiple  (e.g tricyclic antidepressants and gabalin) therapeutic interventions. Standard guidelines  for management of neuropathic pain acknowledge that polypharmacy is appropriate when  individual first line treatments fail to provide adequate pain relief (Gilron I et al., CMAJ  2006; 175: 265-275; Attal N et al., European Journal of Neurology 2006; 13: 1153-1169) Inclusion Criteria:  -  Primarily Neuropathic Pain  -  Able to give informed consent  -  Estimated Life Expectancy of 2 years Exclusion Criteria:  -  Not primarily neuropathic pain  -  Declined participation- too much traveling  -  Declined participation- Unknown  -  Declined participation- Other, specify  -  Considered unreliable- personality disorder  -  Considered unreliable- cognitive impairment  -  Considered unreliable- substance abuse  -  Considered unreliable- Other  -  Language barrier  -  Exceeded quarterly quota  -  Presentation with progressive or recurrent cancer, fibromyalgia, perineal pain of  unknown etiology  -  Other, specify

One in ten adults experience widespread pain. Neck pain, for example, is a prevalent  condition with a high rate of recurrence that affects between 10.4% and 21.3% of the  population annually.  Massage is a common manual therapy intervention for individuals with musculoskeletal pain.  However, the mechanisms of massage are not well established. Also, the conditioned pain  modulation (CPM) paradigm is a dynamic quantitative sensory testing measure of a pain  inhibitory process in which pain sensitivity is lessened in response to a remotely applied  painful stimulus.  This study will evaluate the association between pain inducing massage and the conditioned  pain modulation paradigm in participants with a history of neck pain. Conditioned pain modulation (CPM) is the physical manifestation of the diffuse noxious  inhibitory control (DNIC), an endogenous pain inhibitory pathway in which pain inhibits pain.  Conditioned pain modulation is less efficient in individuals with chronic pain conditions and  it is a predictor for the development of chronic pain.  Massage is a common manual therapy intervention for individuals with musculoskeletal pain.  Greater changes in pain sensitivity occur following pain inducing massage suggesting a  mechanism dependent upon the efficiency of the conditioned pain modulation response. Previous  research has indicated pain inducing massage is more effective than pain free massage  suggesting a mechanism dependent upon conditioned pain modulation.  The study team will evaluate the association between pain inducing massage and the  conditioned pain modulation paradigm. Participants with neck pain will be randomly assigned  to receive a pain inducing massage, pain free massage, or a coldpressor task. Pre-and post  intervention pain will be assessed. The study team will determine if analgesia induced by  pain inducing massage is similar to the conditioned pain modulation paradigm and if baseline  conditioned pain modulation predicts responders to pain inducing massage and short term  clinical outcomes in patients with a history of neck pain. Inclusion Criteria:  -  currently experiencing neck pain with or without arm pain  -  neck pain symptom intensity rated as 4/10 or higher during the last 24 hours  -  neck pain for greater than or equal to 3 months Exclusion Criteria:  -  non-English speaking  -  systemic medical conditions known to affect sensation (e.g. diabetes, hypertension)  -  history of neck surgery or fracture within the past 6 months  -  current history of chronic pain condition other than neck pain  -  diagnosis of cervical radiculopathy or cervical myelopathy  -  history of whiplash; g) currently using blood thinning medication  -  any blood clotting disorder such as hemophilia  -  any contraindication to application of ice, such as: uncontrolled hypertension, cold  urticaria, cryoglobulinemia, paroxysmal cold hemoglobinuria, and circulatory  compromise.

This study will be conducted to evaluate the safety and efficacy of sumatriptan nasal powder  (AVP-825) compared to placebo in the acute treatment of migraine in adolescent participants,  12 through 17 years of age. This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating  AVP-825 for the acute treatment of migraine with or without aura in adolescent subjects (12  to 17 years old). Inclusion Criteria:  -  Male and female participants 12 to 17 years (inclusive) of age at the time of informed  consent  -  Have a diagnosis of episodic migraine with or without aura according to International  Classification of Headache Disorders-Third edition, beta version (ICHD-IIIB, 1.2.1 or  1.1) criteria, for at least 1 year prior to the screening/enrollment visit  -  Experienced migraine attacks of moderate-to-severe intensity and typically lasting ≥ 3  hours untreated, occurring at a frequency of ≥ 2 to ≤ 14 attacks per month for the  past 6 months prior to the screening/enrollment visit  -  Participant's parent or legal guardian must be willing to sign a copy of the informed  consent form as well as documentation for Written Authorization for Use and Release of  Health and Research Study Information, after the nature and risks of study  participation have been fully explained. Participants must be willing to provide  informed assent. Exclusion Criteria:  -  Participants with ≥ 15 headache days per month in total (migraine, probable migraine,  or tension-type)  -  Participants with the following headache types: retinal (ICHD-IIIB, 1.2.4), with  brainstem aura (ICHD-IIIB, 1.2.2), hemiplegic (ICHD-IIIB, 1.2.3), status migrainosus  (ICHD-IIIB, 1.4.1), other forms of complicated migraine, or secondary headaches  -  Participants who have not responded to an adequate dose and appropriate duration of  treatment with 2 or more triptans  -  Participants with known nasal obstruction, current uncontrolled nasopharyngeal  illness, or known velum insufficiency (i.e., a cleft palate and/or structural  abnormalities in the soft palate and nasopharynx) that may interfere with the proper  use of study medication  -  Participants whose conditions in the investigator's opinion may put the participant at  significant safety risk or confound the study results. This includes participants who  in the investigator's opinion should not be enrolled in the study due to the risks  described in the Warnings and Precautions or Contraindications sections of the ONZETRA  Xsail Prescribing Information.

The aim of the study is to describe the feasibility, cultural appropriateness, and  acceptability of Trauma-informed Cognitive Behaviour Therapy (TiCBT) to promote community  healing and encourage the reintegration of repentant terrorists and their families to avoid  reoffending. The study will adopt a mixed-method single-arm experimental design. Approximately 24  participants will be recruited for the intervention. The Trauma-informed Cognitive Behaviour  Therapy (TiCBT) is an 8-session intervention lasting approximately 1 hour each and designed  to address trauma, dispel negative attitudes and encourage positive behaviour towards  repentant terrorists. Measurement will be collected at baseline pre-intervention, end of  intervention and three months post-intervention to determine its feasibility and  effectiveness. Interviews will also be conducted post-intervention. Repeated-measures  univariate analyses of variance (ANOVA) will be performed to examine differences between the  pre- and post-intervention stages. Interviews will be analysed using thematic analysis. Inclusion Criteria:  -  community members who are victims of Boko Haram terrorism and had previous experiences  of trauma/depression,  -  score five and above for the culturally-adapted Trauma Screening Questionnaire  (Brewinn et al., 2002)  -  aged 18+ years,  -  able to give informed consent,  -  speak English  -  are residents or from areas within Nigeria including Maiduguri, Adamawa, and Plateau  environs. Exclusion Criteria:  -  less than 18 or above 85 years  -  unable to give consent  -  clinically diagnosed with severe PTSD/suicidal ideations or undergoing treatment  -  temporary or non-residents who are unlikely to be available for follow up

The aim of this study is to evaluate schizophrenic patients who benefit from community mental  health center services in terms of physical activity, physical fitness, and quality of life. Mental health is defined (according to the World Health Organization) as a state of  well-being in which a person can realize his/her abilities, coping with the normal stresses  of life, and supporting society by working efficiently and productively. In other words,  mental health is a dynamic internal balance that enables individuals to use their diversity  of skills in harmony with the universal values of the society. For example, it is the  flexibility and ability to cope with negative life experiences and social functioning and the  harmonious connection between body and mind. To be more concrete, mental health includes  different components of life, for example in terms of relationships, good relationships with  friends and family, the ability to talk about feelings. Examples of leisure activities  include taking up a hobby, exercising regularly, and routinely taking vacations. It is also  important to maintain a lifestyle that consists of having a nutritious and regular diet, not  smoking and using over-the-counter drugs, and achieving at least some goals in life.  Mental disorders involve a wide variety of problems. Mental disorders are often characterized  by a combination of abnormal thoughts, behaviors, emotions, and relationships with other  people. Mental disorders include: depression, drug use disorders, mental disabilities,  bipolar disorder and schizophrenia.  Schizophrenia is a chronic mental disorder characterized by the appearance of both positive  symptoms such as hallucinations and delusions and negative symptoms such as apathy and  withdrawal, repetition of cognitive skills and disorganization. The number of schizophrenic  patients in the world is approximately 20 million and this number will continue to increase  every year. According to a systematic review of general population studies, the lifetime  median prevalence of schizophrenia in Turkey was found to be 8.9 per 1000 people. In  addition, schizophrenia patients have irregular self-esteem, inability to maintain social  relationships, deterioration in cognitive skills, and sedentary behaviors in their daily  lives. Sedentary behavior in patients with schizophrenia will increase the risks of  cardiovascular and obstructive pulmonary disease, diabetes mellitus (especially type 2),  cancer that can contribute greatly to death and disability. Therefore, it was found that  patients with schizophrenia have a shorter life expectancy of 10-20 years compared to the  general population.  It has been found that people with schizophrenia are less physically active and less  physically fit than the general population. Physical activity means any bodily movement  produced by skeletal muscles that results in energy expenditure. Exercise is a subset of  physical activity, which is planned, structured and repetitive bodily movements performed to  increase and maintain one or more aspects of physical fitness. Physical fitness can be  defined as a set of independent qualities associated with the ability to perform physical  activities. Components such as cardiorespiratory fitness, muscle strength, muscular endurance  and flexibility are more related to health, while components such as coordination and  whole-body balance are more related to the performance of physical activities.  There is an inverse relationship between sedentary behavior (related to time spent lying or  sitting) and physical activity level in patients with schizophrenia. In addition, physical  activity has a direct relationship with physical fitness and physical health in patients with  schizophrenia. In addition, one study showed that poor physical activity level and poor  physical fitness had a negative effect on the ability of schizophrenia participants to  perform activities of daily living performance causes a decrease in the quality of life in  these patients. According to the World Health Organization, quality of life is defined as  individuals' perceptions of their position in life in the context of the value systems and  culture in which they live and in relation to their goals, expectations, standards and  concerns. Quality of life is a subjective, multidimensional term defined as a standard level  for physical, emotional, material and social well-being.  Community Mental Health Centers are State institutions that provide treatment and  rehabilitation services to patients with certain mental health diseases outside the hospital  and within the scope of State Hospitals. Community Mental Health Centers (CMHC) were opened  in 2011 by the Ministry of Health in Turkey. Patients diagnosed with serious chronic mental  disorders such as depression, drug use-related disorders, mental disabilities, bipolar  disorder and especially schizophrenia are treated. The aim of these centers is to improve  functional recovery, physical activity level and quality of life and integrate it into daily  life, society and business life. It consists of a very comprehensive team of different  professionals, such as physicians, psychologists, social workers, and nurses.  Schizophrenic patients are treated in a community mental health center with a comprehensive  treatment program. The content of the comprehensive rehabilitation program in community  mental health centers includes: Psychosocial skills training / occupational treatments such  as painting, music, and also these are done according to the patient's condition /  psycho-education for patients and their families (information about the disease and  treatment, methods of coping with symptoms are explained) training is provided on issues such  as illness, crisis management of patients and their relatives), social skills training  (patients who cannot participate in social life due to their illness are given training to  gain the ability to reorganize human relations) and group treatment is provided for suitable  patients.  Evaluation of physical activity levels, physical fitness, and quality of life of patients  with schizophrenia is essential to confirm the effectiveness of treatments and care  activities at CMHCs and to plan new therapeutic and rehabilitative activities. In one study,  they found that the level of physical activity - physical fitness has a positive effect on  psychiatric services and can improve the physical health outcomes of people with  schizophrenia. They also reveal improvement in psychological and social outcomes in these  patients. Therefore, physical activity level and physical fitness are critical parameters of  the biopsychosocial approach in recovery-oriented mental health services. In conclusion, our  study aims to decide on physical activity, physical fitness and quality of life levels among  a group of patients with schizophrenia treated at CMHC and to evaluate the relationship  between these three important treatment parameters.  The aim of this study is to evaluate schizophrenic patients who benefit from community mental  health center services in terms of physical activity, physical fitness and quality of life.  Therefore, given the importance of our study, our findings may contribute to the literature  and improvement for mental health systems for people with psychotic disorders, especially  schizophrenia. As a result of this study, an evaluation can be made in terms of physical  activity, physical fitness and quality of life in schizophrenic patients who receive service  from a community mental health center. According to this study, it will be possible to  contribute to the effectiveness of treatments and care activities in CMHCs for patients with  schizophrenia. Inclusion Criteria:  -  Individuals diagnosed with schizophrenia by a physician according to DSM-5 criteria  -  Patients treated at CMHC  -  Individuals with schizophrenia who are 18 years or older  -  Patients without other comorbid psychiatric disorders  -  Patients who can communicate and collaborate  -  Patients who agreed to participate in this study and gave informed consent Exclusion Criteria:  -  Those who did not give consent to participate in the study  -  Patients with a diagnosis other than schizophrenia  -  Pregnancy  -  Patients with chronic metabolic diseases such as diabetes, heart problems and cancer

Fractures of the shaft, distal to zone three, of the fifth metatarsal often occur after foot  distortion. There is very little evidence available regarding the optimal treatment.  Currently the most common treatment is prolonged cast immobilization. Operative treatment has  been reported as an alternative and could promote early recovery. No comparative study has  been published regarding optimal treatment Objective: The main objective is to determine experienced pain, as measured by NRS-11 score,  3 months after intervention and compare this between the intervention and control group.  Secondary objectives are functional outcome as measured by AOFAS Lesser Toe Scale, FAAM  score, progress of NRS-11 score through time and PROMIS Mobility/pain interference.  Furthermore, quality and duration of fracture healing will be compared between groups. The  impact on daily life will be compared as measured by duration of return to work and normal  footwear.  Study design: Randomised controlled clinical intervention trial  Study population: Humans with an acute shaft fracture of the fifth metatarsal bone, 18 years  or older. Inclusion Criteria:  -  18 years or older at the time of study entry  -  Informed consent  -  Competent to participate in follow up and fill out questionnaires  -  Dislocated (1mm or more on plain radiography) fracture of the shaft, distal from zone  3, of the fifth metatarsal according to the Orthopedic Trauma Association (OTA)  classification 87.5.3 A-C Exclusion Criteria:  -  Open fracture  -  Proximal fifth metatarsal fracture, Jones fracture  -  Clinically significant or symptomatic vascular or neurologic pathology on the  ipsilateral leg  -  Former surgery or history of development disorder of the contralateral fifth  metatarsal  -  Multiple fractured metatarsals in the affected foot  -  Medical history of Rheumatoid Arthritis  -  Unable to undergo surgical procedure

Lennox-Gastaut syndrome is a severe epileptic encephalopathy of childhood. In that syndrome,  various type of seizure occur, mainly tonic seizures, atonic seizures and atypical absences.  The tonic seizure occur mostly at night.  The hypothesis is that the melatonin could have a positive effect in that syndrome, by  reducing the epileptic activity (assessed in the polysomnographic record by counting the  number of interictal and ictal discharges) and stabilizing the structure of sleep.  The study is double blind, randomised, cross-over designed. The aim of the trial is to study the efficacity of melatonin in the Lennox-Gastaut syndrome,  by assessing the reduction of the seizure/interictal discharges in polysomnography and  assessing the sleep structure.  After initial recruitment, the baseline visit includes a polysomnography. The patients will  then be randomised in two groups: melatonin (1 cp containing melatonin 2 mg 1x/d 1h before  sleep) vs placebo (1 cp 1x/d 1h before sleep). The treatment (melatonin or placebo) will be  given for 1 month.  After 1 month, the treatment will be stopped and another polysomnography will be recorded.  The patients will take no treatment (wash-out period) for 15 days. The second treatment phase  is cross-over: the group that had melatonin in the first phase will take placebo for one  month, and the group that had placebo in the first treatment phase will take melatonin for  one month. A last polysomnography will be recorded after the second treatment phase.  The other medications (antiepileptic drugs) taken by the patients before the trial will not  be modified. Inclusion Criteria:  -  Lennox-Gastaut syndrome (based on ILAE classification, 1989)  -  light mental retardation (QI 50-69)  -  french mother tongue  -  having someone helping the patient (parent and/or referent educator)  -  informed consent have been given by the patient / guardian  -  absence of concomitant evolutive affection or associated sleep pathologies  -  collaboration of the patient, ability to complete all aspects of the trial. Exclusion Criteria:  -  epileptic syndrome other than Lennox-Gastaut, other neurologic and/or psychiatric  disease  -  moderate to severe mental retardation (QI < 50)  -  psychiatric disease that could interfere with the diagnostic procedure  -  specific sleep disorder (anamnestic and diagnosed on the polygraphic record), for  example: sleep apnea syndrome, narcolepsy, restless legs syndrome, periodic legs  movements, etc...

Recurrent pregnancy loss (RPL) is a multifactorial disorder defined by the American Society  for Reproductive Medicine (ASRM) as two or more clinical miscarriages (CMs). However, US  guidelines differ with European guidelines which defined recurrent miscarriage as three  consecutive prior pregnancy losses (The Royal College of Obstetricians and Gynaecologists  Green-Top Guideline, 2011). Thus, there is currently no uniformly agreed upon definition of  RPL, the ASRM recommends that a clinical evaluation for RPL commence following two early  pregnancy losses, and that a threshold of three prior pregnancy losses be utilized for  epidemiologic studies (The Practice Committee of the American Society for Reproductive  Medicine, 2012).  Although the overall incidence of RPL is low and estimated at 5% of women (The Practice  Committee of the American Society for Reproductive Medicine, 2012), it presents a significant  diagnostic and treatment challenge for both patients and clinicians. Guidelines for the  evaluation of patients with RPL include evaluation of the uterine cavity and blood work to  determine parental karyotypes and the presence of anti-phospholipid antibodies (APLA). In at  least 50% of patients, however, an etiology for RPL is not identified (Stirrat, 1990;  Stephenson, 1996; Stephenson and Kutteh, 2007; The Practice Committee of the American Society  for Reproductive Medicine, 2012). The ASRM recommends expectant management as the current  standard of care for patients with unexplained RPL (The Practice Committee of the American  Society for Reproductive Medicine, 2012). Counseling patients with unexplained RPL to pursue  expectant management presents several challenges. Patients often feel an urgency to conceive  and expectant management can feel like a passive and time-consuming approach to conception.  In addition, patients often carry a significant amount of guilt and grief in association with  miscarriage. Attempting spontaneous conception can feel emotionally vulnerable; Despite  reassurance of good prognosis, patients doubt that a subsequent pregnancy will be successful  (Lachmi-Epstein et al., 2012). For all of these reasons, IVF and preimplantation genetic  testing (PGT) have been investigated as a treatment strategy in RPL patients with the goals  of shortening time to pregnancy, decreasing CM rates and increasing live birth (LB) rates. The role of aneuploidy in CM is well known, with over 50% of pregnancy losses attributed to  fetal chromosomal abnormalities (Viaggi et al., 2013). Furthermore, for patients greater than  35 years of age with RPL, fetal aneuploidy is responsible for up to 80% of first trimester  losses (Marquard et al., 2010). Due to the prevalence of aneuploidy in first trimester losses  and in the RPL population, PGT has been proposed as a method for reducing miscarriage by  selecting only euploid embryos for transfer (Shahine and Lathi, 2014). The ultimate effect of  PGT on increasing LB rates in the RPL population and the time interval to conception are  areas of investigation. Current studies are largely retrospective in design with several  limitations. For example: Inconsistent definitions of CM and RPL are employed. In addition,  the treatment group (IVF and PGT) has been compared with a variety of control groups  including IVF without PGT, a control infertile population, or to predicted LB and CM rates  based on age and clinical history, but has not been compared with expectant management  (Shahine and Lathi, 2014). Finally, the majority of studies report clinical outcomes only of  patients who reach PGT biopsy and/or embryo transfer, so all possible cycle outcomes are not  captured (Hodes-Wertz et al., 2012).  For the absence of well-designed prospective studies with high level of evidence comparing  IVF and PGT to the current standard of care, expectant management, have been performed to  date for the treatment of RPL patients. The objective of this study is to perform an intent  to treat analysis comparing live birth rate of IVF and PGT to expectant management in fertile  RPL patients in one year followed- up period. Inclusion Criteria:  -  Age of women <45 years  -  Two or more clinical miscarriages with identified foetal chromosomal abnormalities, or  three consecutive prior pregnancy losses between 6 and 20 weeks gestational age,  excluding biochemical pregnancies. Exclusion Criteria:  -  Presence of APLA including anti-cardiolipin antibody, lupus anticoagulant and  b-2-glycoprotein  -  Diagnosis for hypothyroidism and hyperprolactinemia with uncontrolled serum  thyroid-stimulating hormone and prolactin  -  Having a anomaly uterine cavity  -  Abormal parental karyotypes (translocation carriers and monogenetic defect)

The research work proposes an exposure treatment through a virtual therapeutic assistant  called Thera, that interacts verbally with the patient, to guide and control exposure  therapies for phobias to small animals delivered through several channels at the same time  that it analyzes the Physiological records of the patient in real-time to determine their  emotional state during the intervention.  In this study it is proposed to evaluate the efficacy of a self-applied treatment where the  virtual assistant allows to gradually guide an exposure treatment for rat phobias, taking  advantage of intelligent devices for patient monitoring and being considered to determine the  progress of the treatment. Specific phobias are a common disorder that deteriorates the lives of people who suffer from  them. Exposure therapies have been shown to reduce the symptoms produced. However, low- and  middle-income countries have the lowest rate of treatment for specific phobia due to multiple  barriers that prevent approaching mental health problems, such as the disparity between the  number of people who need care and the availability of professionals who can provide  psychological services. To reduce the gap in the treatment of mental health problems in low  and middle-income countries, the use of internet-based interventions has been proposed since  they reduce the cost, the availability of the service, the waiting time, and they can be  guided by a minimum amount of therapeutic care, which allows a greater number of people to  receive treatment. Among the most effective proposals that have emerged to carry out  psychological interventions for Specific Phobia are self-applied treatments. However, one of  the main challenges posed by self-administered interventions in reducing the dropout rate of  participants, since it is difficult to engage participants, which leads to attrition and  non-completion of treatment. Therefore, it is necessary to consider elements that are  attractive and motivate the participants to engage with the treatment. One option to increase  patient's adherence could be a virtual therapist assistant that is an application focused on  the area of health therapies that uses interaction with the user based on voice commands, it  requires a reduced cognitive learning load and are accessible to most of the people. The  content of the intervention will be self-applied through a web application including the  guidance of a virtual therapist assistant. In order to integrate the benefits that  Internet-based interventions provides and the assistance of a virtual therapist to guide and  personalize the progress of the treatment according to the user.  The study will have two groups : 1) experimental, where the participants carry out the  self-applied treatment for rat phobia supported by the virtual therapist assistant; and 2)  control, where participants are on a waiting list and afterwards receive the treatment.  The group assignment of participants will be randomized.  Participants in both groups will be measured pre and post the intervention. The measurements  to be obtained are the following:  Fear scale. Anxiety scale. Sense of presence and judgment of reality. User's satisfaction.  Perception of utility and ease of use. Patient improvement scale. Inclusion Criteria:  1. Meet the diagnostic criteria for specific phobia towards rats (with a mild to moderate  symptomatology).  2. Have basic digital knowledge and skills (computer and internet use).  3. Have the necessary technological devices: email, computer / laptop, Smartphone,  microphone, internet connection, and Bluetooth.  4. Sign the informed consent. Exclusion Criteria:  1. Receiving another type of psychological or psychopharmacological treatment.  2. Being diagnosed with another type of anxiety disorder or some psychopathology.  3. Present any medical condition that puts the life of the person at risk (eg. heart  disease, respiratory disease, pregnancy, among others).

Chemokine receptor-4 (CXCR4) is overexpressed in multiple myeloma (MM) cells. 68Ga-pentixafor  is a radio-labled tracer for CXCR4 . 68Ga-pentixafor PET/CT has shown good diagnostic  performance in MM. But an exchange of Ga3+ by Lu3+ or Y3+ will lead to a significant loss of  CXCR4 affinity. Investigators conduct this prospective study to evaluate the diagnostic  performance of 68Ga-pentixather compared with 68Ga-pentixafor, in order to parallel  68Ga-pentixather and 177Lu/90Y-pentixather in theranostics of MM. Multiple myeloma (MM) is a malignant plasma cell disorder which is characterized by clonal  proliferation of plasma cell in bone marrow microenvironment. Chemokine receptor-4 (CXCR4) is  overexpressed in MM cells, and has been identified as a potential therapy target.  68Ga-pentixafor is a radiolabeled ligand with high affinity for CXCR4. 68Ga-pentixafor PET/CT  has been reported with better diagnostic performance than 18F-FDG PET/CT. However,  considering both diagnostic and therapeutic applications, an exchange of Ga3+ by other M3+  ions (Lu or Y) will lead to a significant loss of CXCR4 affinity. Thus, pentixather was  developed as the precursor of 177Lu-pentixather or 90Y-pentixather, which can be used in  CXCR4-targeted peptide receptor radionuclide therapy (PRRT). Investigators conduct this  prospective study to evaluate the diagnostic performance of 68Ga-pentixather compared with  68Ga-pentixafor, in order to parallel 68Ga-pentixather and 177Lu/90Y-pentixather in  theranostics of MM. Inclusion Criteria:  1. Suspected or confirmed untreated multiple myeloma (MM), relapsed MM, MM in remission  2. Signed written consent Exclusion Criteria:  1. pregnancy  2. breastfeeding  3. known allergy against pentixather or pentixafor  4. any medical condition that in the opinion of the investigator, may significantly  interfere with study compliance.

The aim of this study is to investigate if a new irrigation system for transanal irrigation  (TAI) is effective and more tolerable than the currently used system at the Pediatric Ward at  Aarhus University Hospital. This is a randomized, controlled study.  This study will be performed at Aarhus University Hospital (Denmark) and Aalborg University  Hospital (Denmark) following the same protocol.  According to the initial randomization, children will be allocated to treatment with the new  system (group A) or with the currently used system (group B). After a period of 6 weeks the  child will crossover to use the contrary system.  The hypothesis is that A TAI system specifically developed for children will enhance the  child's toleration of irrigation due to fewer reports on pain at insertion which will lead to  better compliance. This outcome will induce a comparable or better effect on their fecal  incontinence and reduce the needed follow-up period due to fewer incontinence relapse. Inclusion Criteria:  -  Fecal incontinence on neurogenic or non-neurogenic basis, where transanal irrigation  is indicated. Exclusion Criteria:  -  Morbus Hirschsprungs disease.  -  Anorectal malformations.  -  Use of medication that are known to cause constipation (e.g. anticholinergics)

The aim of this pilot study is to assess the feasibility of a RCT whose topic would be the  effect of a motor imagery program on the postural control in persons who have undergone ACL  plasty. Primary and secondary outcomes will be measured twice at the hospital, a first time six weeks  after the beginning of the intervention and a second time eight weeks after the four weeks of  the intervention.  Twelves home-based motor imagery sessions will occur in four weeks, three times a week, to  activate. The training sessions will last between 15 and 20 minutes. During each training  session, the participant will note on his/her own "Tracking sheet" how long they listened to  the audio and their comments. The "Tracking sheet" will document whether or not the patient  has participated in each of the twelve sessions.  In parallel, a control group will follow a placebo programme according to the same  formalities.  Twenty-three participants (min.) will take part in this study. Inclusion Criteria:  -  men and women of legal age  -  to be capable of discernment  -  to have a telephone number or email address to communicate with the investigators, to  have a device with internet access to access the mental imagery programs.  -  to have had an ACL surgery performed by the Doctor Siegrist within the last three days  using the Hamstrings Tendon Graft or the Kenneth Jones method. Exclusion Criteria:  -  not having a good spoken knowledge of the French language  -  recurrence of ACL injury in the same knee  -  meniscal sutures  -  associated fractures  -  pre-existing balance problems (tested at recruitment)  -  pre-existing neurological problems diagnosed by a doctor.

This is a randomized, double-blind, placebo-controlled Multiple Ascending Dose (MAD) study to  evaluate the safety, tolerability and pharmacokinetics of oral nafamostat solution  administered t.i.d.. for up to 5 days in healthy volunteer adult subjects Subjects will undergo a medical screening (Days -1 to -10) and, if eligible, informed consent  will be obtained prior to 6 days of confinement at the clinic site. Up to 20 subjects will be  randomized. Subjects will be stratified to include an equal number of male and female  subjects who will receive active drug within each dose cohort, and an equal number of male  and female subjects in the combined placebo group. Separate groups of volunteers will be used  for each dose cohort. There will be 4 dose cohorts in this study with active drug doses of  10, 50, 100, and 200 mg nafamostat in succeeding cohorts. Each cohort of 5 subjects will  enroll 2 male and 2 female to receive active drug and 1 subject (male or female) to receive  placebo for a total of 20 subjects. The placebo subject from each cohort will be combined  into a placebo cohort that will have 4 subjects to compare to 4 subjects in each of the  active dose groups. Inclusion Criteria:  1. Males or females, age 18 to 70 years old, able and willing to provide written informed  consent to participate in the study;  2. Subjects must be in generally good health as determined by pre-study medical history,  physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG);  3. Subjects must be willing to remain in confinement at the clinical study unit for 6.5  consecutive days and to return to the unit at Day 14±2 for followup safety  assessments;  4. Body mass index (BMI) 19-32 kg/m2;  5. Normal blood pressure (BP) [systolic BP 90-140 mmHg, diastolic BP 50-90 mmHg] and  heart rate (HR) [resting HR 45-90 beats per minute (bpm)] without medication;  6. Clinical chemistry profile including electrolytes, alkaline phosphatase (ALK), lactate  dehydrogenase (LDH), creatine phosphokinase (CPK), creatinine, and urea must be within  the normal range without medication; screening liver enzymes may be up to 1.5x normal  range; screening CPK must be within 2x normal range;  7. Urinalysis including urinary creatinine must be within normal limits (trace findings  and minor deviations are acceptable per the clinical decision of the Principal  Investigator);  8. Subjects must be non-smokers or willing to abstain from smoking for the duration of  study;  9. Subjects must be able to read, understand and follow the study instructions;  10. Male subjects and their female sexual partners must agree to use double barrier  contraception during the study period and for 2 months afterward, or provide proof of  post-menopausal state (minimum 1 year) or surgical sterility.  11. Female subjects will be non-pregnant, non-lactating, and either postmenopausal for at  least 1 year, or surgically sterile for at least 3 months, or will agree to use  double-barrier contraception from 28 days and/or their last confirmed menstrual period  prior to study enrollment (whichever is longer) until 2 months after Clinic Discharge.  Double barrier contraception may include, but is not limited to, non-hormonal  intrauterine device with spermicide, female condom with spermicide, diaphragm with  spermicide, cervical cap with spermicide; having a male sexual partner who agrees to  use a male condom with spermicide; or having a sterile sexual partner. Females will  refrain from using hormonal contraceptives for at least 28 days prior to study entry  until the end of the study period (Day 14). For all females, the pregnancy test result  must be negative at Screening and Pre-Study Baseline (Days -1 to -10). Exclusion Criteria:  1. Use of any non-study medication(s) including low dose aspirin for cardiovascular  prophylaxis within one week prior and two weeks after receipt of study drug;  2. Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer  that has been completely excised, within five years prior to the screening visit;  3. History of bacterial or viral infection requiring treatment with antibiotics or  antivirals within 1 month of study;  4. History of congestive heart failure;  5. Use of drugs which are P450 inducers or inhibitors within the past 30 days (e.g.  cimetidine, paroxetine, fluoxetine, haloperidol, ketoconazole, itraconazole,  fluconazole, erythromycin, clarithromycin);  6. Use of any dietary aids or foods that are known to modulate drug metabolizing enzymes  (e.g. St. John's Wort, grapefruit juice) within 14 days of dose administration;  7. History of seizure disorder;  8. Serious psychosocial co-morbidities;  9. Cognitive or psychiatric disorders, or any other condition that could interfere with  compliance with study procedures and/or confinement in a clinical study unit for 6.5  days;  10. History of drug or alcohol abuse within one year prior to screening;  11. Use of any other investigational drug within 1 month prior to enrollment;  12. Use of prescription drugs within 1 month prior to enrollment;  13. Use of over the counter medication excluding routine vitamins, but including mega-dose  vitamin therapy, within one week of enrollment;  14. Donation and/or receipt of any blood or blood products within 3 months prior to  enrollment;  15. Family history of significant cardiac disease (i.e. sudden death in first degree  relative; myocardial infarction prior to 50 years old).

Our current focus is to reduce the spread of COVID through distribution of Rapid Antigen Test  Kits (ATKs) to low-income, high-risk communities across Bangkok.  Hospitals across Thailand have been operating over capacity for many months, both in  receiving the high number of cases as well as in testing for COVID. RT PCR, although highly  sensitive, requires potentially infectious people to travel to testing sites, wait in line,  and takes 1-2 days to return results, leading to further spread of COVID through increased  contact with other high-risk individuals.  On the contrary, testing via an Antigen Test Kit (ATK) can be done by everyone at home with  the potential to test more frequently than the PCR test due to much cheaper cost. This means  that ATK testing can be mixed into people's daily lifestyle, but another underlying reason is  that ATKs only show test results as positive only when an infected person is contagious.  Another key advantage is the rapid results, which helps people identify risks quickly,  limiting spread even faster.  Our trial therefore aims to achieve the following primary objective:  To monitor the results of freely distribute ATKs in real environments to measure its  effectiveness in reducing COVID spread in communities by comparing the incidence of COVID-19  between communities with rapid antigen tests and without rapid antigen tests.  Secondary objectives are:  1. To compare the incidence of severe COVID-19 between communities with rapid antigen tests  and without rapid antigen tests.  2. To study the decrease in incidence of community-acquired COVID-19 in communities with  rapid antigen tests.  3. To study factors affecting community-acquired COVID-19 in these communities.  4. To campaign for the government to recognize the importance and effectiveness of weekly  testing, and propose suitable strategies to fight COVID. The cluster randomized controlled trial will be conducted in Bangkok communities supported by  Thaicare. A total number of 70,000 participants will be enrolled from 70 clusters. (1,000  from each cluster). Participants from each area will be divided into three groups according  to the accommodation type. The rational between intervention group 1 to intervention group 2  and control group will be 1:1:1. The characteristics of population in each stratum will be  reproduced as closely as possible. Cluster randomization by software will be used to blind  the order of randomization. Demographic data (i.e., age, gender, weight, height, body mass  index), concomitant diseases, income, type of accommodation, vaccination profile) of the  control and intervention groups will be collected. The collection of data and the obtaining  of the consent will be conducted by Socialgiver volunteers. There will be 2 intervention  groups. Group 1 will receive 4 rapid antigen kits at the beginning of the study and will be  asked to conduct a weekly self-test for 3 weeks. Group 2 will receive 7 rapid antigen kits at  the beginning of the study and will be asked to conduct a twice-weekly self-test for 3 weeks  (total of 6 tests) Inclusion Criteria:  criteria (community level): any Bangkok community in which the community coordinator cannot  participate in the study.  (individual level): anyone who are not consent or unable to give consents. Those who are  known to be COVID-19 positive or currently treated with favipiravir Exclusion Criteria: None

The Prostate Active Surveillance Study (PASS) is a research study for men who have chosen  active surveillance as a management plan for their prostate cancer. Active surveillance is  defined as close monitoring of prostate cancer with the offer of treatment if there are  changes in test results. This study seeks to discover markers that will identify cancers that  are more aggressive from those tumors that grow slowly. This is a multi-center, prospective active surveillance study with selective intervention in  patients with previously untreated, clinically localized prostate cancer at diagnosis.  Candidates are assessed based on an extended core biopsy, serum PSA (including PSA kinetics,  if available), digital rectal examination (DRE), and assessment of cancer grade and extent.  Active surveillance is defined as serial PSA measurements and prostate examination with  routine prostate biopsy and therapeutic intervention considered at the time one or more of  the following:  -  Grade or volume progression  -  Clinical progression  The objectives of the study are as follows:  Primary Objective  • To discover and confirm biomarkers that predict aggressive disease as defined by  pre-specified histological, PSA, clinical criteria, or outcomes based on these variables.  Secondary Objectives  -  To determine the proportion of patients on active surveillance who progress based on the  above criteria.  -  To determine the clinical predictors of disease progression. Inclusion Criteria:  -  Histologically confirmed adenocarcinoma of the prostate.  -  Clinically localized prostate cancer: T1-2, NX or N0, MX or M0.  -  No previous treatment for prostate cancer (including hormonal therapy, radiation  therapy, surgery, or chemotherapy).  -  ECOG Performance Status 0 or 1.  -  Patient has elected Active Surveillance as preferred management plan for prostate  cancer.  -  Patient consent has been obtained according to local Institutional Review Board for  acquisition of research specimens.  -  Patient is accessible and compliant for follow-up.  -  Prostate biopsy requirements:  1. If diagnosis was within one year of baseline visit, participant must have at  least one biopsy with at least 10 cores.  2. If diagnosis was more than 1 year prior to baseline visit, participant must have  a minimum of 2 biopsies, one of which must be within 2 years prior to baseline  visit. Exclusion Criteria:  -  Unwillingness or inability to undergo serial prostate biopsy.  -  History of other malignancies, except: adequately treated non-melanoma skin cancer or  adequately treated superficial bladder cancer (Ta) or other solid tumors curatively  treated with no evidence of disease for > 5 years.

Aim of the study: To compare radiographically the morphometric changes in the nasal airway  after using three types of rapid maxillary expansion (RME) conventional hyrax (CH), hybrid  hyrax (HH) and maxillary skeletal expander (MSE) using cone beam computed tomography (CBCT). Abstract Aim of the study: To compare radiographically the morphometric changes in the nasal  airway after using three types of rapid maxillary expansion (RME) conventional hyrax (CH),  hybrid hyrax (HH) and maxillary skeletal expander (MSE) using cone beam computed tomography  (CBCT).  Material and Methods: A total sample of thirty CBCT of patients presented with constricted  maxilla with mean age of 14±3Y was randomized in to three groups. Group 1 CH, group 2 HH and  group 3 MSE.  CBCT records were taken before(T1) and after six months (T2) of RME; the Airway was segmented  and quantified using software (version 5.3.4.39USA). Inclusion Criteria:  -  Patients suffering maxillary collapse with a skeletal background  -  Patients with unilateral or bilateral posterior crossbite.  -  Patients with reduced or average anterior face height.  -  Patients with no periodontal disease.  -  Patients with good oral hygiene and general health.  -  No systemic diseases that may affect bone quality or interfere with orthodontic  treatment.  -  Patients with erupted maxillary permanent first molars and premolars.  -  Patients with no previous orthodontic treatment. Exclusion Criteria:  -  previous treatment  -  syndromes  -  cleft lip and palate

BrainTale has developed a standardization approach based on averaging measurements in  predefined brain regions of interest and use of reference data acquired from healthy  volunteers under conditions (MRI machine, acquisition protocol) identical to those used for  the examination of the patient. The present study is intended to support the normalization  step on healthy volunteers in clinical centres that will be equipped with the BrainTale  medical device software dedicated to clinical routine practice and to assess, through a  multicentre study, the impact of this normalization step on the variability of the MRI  diffusion parameters. The data collected will support characterization and modelisation of  the variability to explore further biais corrections methods. The study will be conducted by  neuroradiologists of the neuroradiology departments of five clinical centres in France. Advances in medical imaging have made it possible, from the 1990s, to be able to visualize  structural microlesions of the brain thanks to post-processing of the Magnetic Resonance  Imaging (MRI) data acquired by the sequence using the diffusion tensor. Mathematical models  such as the diffusion tensor have made it possible to quantify in each of the volumetric  units of the brain (voxels) measurements correlated to the microstructure of neuronal axons  such as the Fractional Anisotropy (FA), the Mean Diffusivity (MD), the Radial Diffusivity  (RD) or the Axial Diffusivity (AD). These measurements thus make it possible to quantify the  microstructural alterations.  However, the use of Diffusion Tensor Imaging (DTI) technology has limitations and currently,  there is no "gold-standard" to validate diffusion measurements, which are currently dependent  on acquisition protocols, post-processing software and observers.  To make these diffusion parameters usable in a clinical context, BrainTale has developed a  standardization approach based on averaging measurements in predefined brain regions of  interest and use of reference data acquired from healthy volunteers under conditions (MRI  machine, acquisition protocol) identical to those used for the examination of the patient.  This process requires the acquisition of 10 healthy volunteers to calibrate a new MRI  protocol, which greatly limits access to the technology in clinical routine and limits the  potential technological evolutions of the acquisition.  The study aims to assess the impact of a patented normalization process on the  interindividual variability of Fractional Anisotropy (FA) measurements derived from cerebral  Diffusion Tensor Imaging (DTI) acquisitions.  A total of 60 healthy volunteers will be included. One or two acquisition will be performed  during a single on-site visit in order to collect diffusion parameters outcome data for  further analyses (with or without normalization process).  After each acquisition and before inclusion of the following healthy volunteer, anonymised  subject's data will be transferred to BrainTale on a secured web platform. BrainTale will be  in charge of the Quality Control (QC) of the acquired data and will attribute a QC-passed or  QC-failed. Inclusion Criteria:  1. Male or female aged 18 up to 80 years old  2. Covered by a healthcare insurance  3. Agreeing to be informed about any incidental finding discovered on brain MRI  4. Written informed consent form signed Exclusion Criteria:  1. History of brain pathology, cognitive or psychiatric disorder  2. Any contraindication * for undergoing brain MRI  3. Subject refusing to participate or having expressed refusal to data  collection/processing or unable to give his/her agreement to participate  4. Vulnerable subject (i.e. pregnant or breast-feeding woman, child, subject under  curatorship or deprived of liberty)  -  contraindications to MRI include: pacemaker, neural stimulator, intraocular or  intracerebral device, cochlear implant, MR-incompatible prosthetic heart valves,  any implant with metallic, ferromagnetic or electrically conductive parts, any  metal in the body which cannot be removed, claustrophobia.

In recent years, vitrectomy has moved toward a minimally invasive vitrectomy surgery (MIV)  system, which could effectively reduce the occurrence of operation complications, while  reducing the time of post-operation recovery.  With an improved design of bevel tip and a high cutting rate capacity of 10000cpm, Advanced  ULTRAVIT® probes potentially provide an strong technical support for the application of MIV.  The new probe facilitates great control during delicate surgical maneuvers, such as  separating the hyaloid from the retinal surface, dissecting fibrovascular tissue off the  surface of retina.  However, there was no sufficient clinical evidence to support the benefits of Advanced  ULTRAVIT ® probes in the complicated vitreoretinal surgery, such as proliferative diabetic  retinopathy. More importantly, there is an urgent need of clinical evidence to support  10000cpm launch and conversion which is major objective of 2021 VR growth strategies. This exploratory study, aiming to demonstrate the beneficial of 27 Gauge probe, which can be  flexibly applied as a multifunctional tool for membrane removal by reducing frequencies of  switching device, reducing the traction to eyeball during device entering and leaving the  eye. Moreover, the outcomes from this study would be an strong evidence to support further  comparative study to comprehensively demonstrate the superior function compare to current  heavily used 5K 25 gauge probe. Inclusion Criteria:  1. Patients with vitreous hemorrhage and tractional retinal detachment (TRD) confirmed by  fundus image and B ultrasound examination, consistent with the diagnosis of severe  proliferated diabetic retinopathy (PDR).  2. Patient that could follow up postoperatively at the clinic for 6 months more.  3. All the surgeries were performed by one well-experienced retinal surgeon. Exclusion Criteria:  1. Corneal lesions affecting operative field, such as corneal opacity or scar; History of  vitreoretinal surgery;  2. External eye infections;  3. History of systemic thromboembolism;  4. Uncontrolled hypertension or hyperglycemia;  5. Coagulation abnormalities or currently using anticoagulant drugs other than aspirin;  6. Unable to meet postoperative position requirements;  7. Unable to be followed up regularly.

Aim of the study is to translate and culturally adapt the modified Barthel index into Urdu  language and to investigate the reliability and validity of this scale in Urdu speaking  Stroke population for performance evaluation. Also check its correlation with Functional  independence measure and Katz index of Activities of Daily Living. The English version of the Barthel index will be translated and traditionally adapted as  prior endorsement. In Activities of Daily Livings disabled stroke population, Urdu Version of  Modified Barthel Index will distributed among sixty participants choose by convenience  sampling technique based on pre-distinct inclusion and exclusion standards. To test inter and  intra-observer reliability of the final Urdu Version of Modified Barthel Index will be  completed on the same day, by two observers, and for the inter-observers evaluation, with an  interval of 30 minute between the first and the second submission. Third evaluation will be  carried out after 7 days by Observer-1, for intra-observer assessment. Data will be entered  and analyzed using Statistical Package of Social Sciences Version 24. Core steadiness will be  analyzed with Cronbach alpha value. Test-retest reliability will be evaluated using an  intra-class correlation coefficient.The Urdu Version of Modified Barthel Index will be  evaluated for content validity, construct validity, criterion validity and responsiveness. Inclusion Criteria:  -  Male and female both genders  -  Adults between the ages of 18 and above  -  Patient suffering from Stroke  -  Ability to provide informed consent Exclusion Criteria:  -  Suffering from any cardiovascular pathologies  -  Any disorder of contagious infections  -  Any history of neurological disorders  -  Having any spinal deformity

This research study is looking at biomarkers in DNA samples from patients with acute  lymphoblastic leukemia or acute myeloid leukemia. Studying samples of DNA from patients with  cancer in the laboratory may help doctors identify and learn more about biomarkers related to  cancer. PRIMARY OBJECTIVES:  I. Collect DNA samples from patients with cytogenetically, well characterized, and uniformly  treated acute lymphoblastic leukemia or acute myeloid leukemia for use in analysis of a wide  range of host factors influencing etiology and outcome of the disease.  II. Identify host factors that can be determined at onset of treatment to predict outcome of  chemotherapy, and thus modify the therapy administered.  OUTLINE:  Previously collected DNA samples are analyzed for polymorphisms at a variety of loci. Gene  expression and expression profiles are correlated with genotype and therapy outcomes. Inclusion Criteria:  -  DNA samples available from patients meeting the following criteria:  -  Infants with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML)  -  Patients with pre-B ALL, including responders vs non-responders in selected  genotypes [hyperdiploid, hypodiploid, t(12;21), t(9;22), t(1;19), and t(4;11)]  and responders and non-responders regardless of genotype  -  Pediatric patients with AML registered on POG-9421  -  Adult patients with ALL, including t(8.21), inv(16), t(15;17), complex  cytogenetics, and secondary AML  -  Pediatric patients with relapsed ALL enrolled on COG-AALL01P2  -  Pediatric patients enrolled on COG-9900 and other CCG or POG trials Exclusion Criteria: None

This study is designed to identify Dermatophagoides farinae, or Der f, sensitive asthmatics  who demonstrate a late phase asthmatic response after Der f inhalation. These subjects may be  invited to participate in a planned future study investigating novel asthma treatments. Asthma is an increasingly common chronic illness among children and adults, and allergen  exposure is among the most common common triggers for asthma exacerbations. Exacerbations of  allergic asthma are characterized by an early phase response (EPR), mediated by release of  preformed mediators like histamine from mast cells, and a late phase response (LPR) 3-7 hours  later mediated by chemokines and cytokines that attract leukocytes such as neutrophils and  eosinophils to the airways, increase mucus production, trigger airway smooth muscle  contraction, and result in airway constriction and airway hyperreactivity (AHR). The LPR does  not occur in the absence of an EPR. The LPR is thought to be predominantly responsible for  the symptoms associated with acute exacerbations of allergic asthma and is often used as the  measure of efficacy in trials of asthma therapeutics.  This group has taken a particular interest in targeting an inflammatory cytokine,  Interleukin-1β, involved in both the early and late phase asthmatic responses to inhaled  allergen in allergic asthmatics. In the lung, interleukin 1 beta (IL-1β) is produced by  numerous cell types (including epithelial cells, macrophages, neutrophils, eosinophils, and  mast cells), where it signals through its receptor to induce transcription of  pro-inflammatory genes (17-19). IL-1β is increased in bronchoalveolar lavage fluid from  persons with symptomatic asthma vs. those with asymptomatic asthma; likewise,  immunohistochemistry of bronchial biopsies of allergic asthmatics reveal increased expression  of IL-1β in both bronchial epithelial cells and macrophages. Previous studies in animal and  in vitro models demonstrate that IL-1β can directly impact three aspects of an airway  inflammatory response: 1). granulocyte (neutrophil/eosinophil) recruitment; 2). non-specific  (23, 24) and allergen-specific airway reactivity; and 3). production and clearance of airway  mucous. Supporting literature and preliminary studies in human subjects further promote the  study of IL-1 blockade for mitigating features of acute allergen-induced asthma exacerbation.  The role of IL-1 in allergen challenge models has not been fully defined. In a study  examining 12 asthmatics allergic to D. farinae at this research center, we found that 9/12  asthmatics had a greater than 10% reduction in forced expiratory volume in 1 second (FEV1)  after inhaled dust mite challenge. These individuals were considered responders. It was  notable that when comparing post-allergen levels of cytokines between responders and  non-responders there was a much greater concentration of IL-1β in post-challenge sputum from  responders vs. nonresponders, Furthermore, within the responders, post challenge IL-1β also  significantly correlated with sputum eosinophil concentrations (r=0.83, P<0.05) and  neutrophil concentrations (r=0.89, P<0.05) 24 hours after allergen challenge. These data  suggest that IL-1β may play a role in both immediate airway hyperresponsiveness and the late  phase recruitment of inflammatory cells (neutrophils and eosinophils) after inhaled allergen  challenge.  In order to better understand the role of IL-1β in allergen-induced airway inflammation,  induced sputum will be obtained to determine if higher baseline sputum IL-1β concentrations  or larger increases in IL-1β following allergen challenge impact non-specific airway  hyperresponsiveness (via methacholine challenge), sputum granulocyte recruitment (neutrophil  and eosinophil counts and exhaled nitric oxide (eNO), a marker of airway eosinophilia), or  changes in expression of inflammatory or allergy-related genes. To this last point, little is  known about the mechanisms contributing to response patterns in allergic asthmatics  undergoing allergen challenge. Changes in gene expression occurring during the window of time  between the EPR and LPR, as these expression changes may dictate whether or not a LPR occurs  or to what extent it occurs.  The goal of this screening protocol is to identify subjects who exhibit both an EPR and LPR  and who will be eligible for enrollment in the yet to be developed Il-1β protocols. Subjects  will undergo a baseline methacholine challenge to establish reactivity, then allergen  exposure, followed 24 hours later by methacholine challenge. Inclusion Criteria:  1. Age range 18-45 years, inclusive  2. FEV1 of at least 80% of predicted and forced expiratory volume in 1 second/forced  vital capacity (FEV1/FVC) ratio of at least 0.7 (without use of bronchodilator  medications for 8 hours or long acting beta agonists for 24 hours), consistent with  lung function of persons with no more than mild intermittent or mild persistent  asthma.  3. Physician diagnosis of asthma  4. Positive methacholine inhalation challenge as performed in the separate screening  protocol within the prior 12 months (defined as provocative concentration of  methacholine of 10 mg/ml or less producing a 20% fall in FEV1 (PC20 methacholine)  5. Allergic sensitization to house dust mite (D. farinae) as confirmed by positive  immediate skin prick test response  6. Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy or  who have been amenorrheic for 12 months or more.  7. Oxygen saturation of >94% and blood pressure within the following limits: (Systolic  between 150-90 mmHg, Diastolic between 90-60 mmHg). Exclusion Criteria:  1. Clinical contraindications:  1. Any chronic medical condition considered by the PI as a contraindication to  participation in the study including significant cardiovascular disease,  diabetes, chronic renal disease, chronic thyroid disease, history of chronic  infections or immunodeficiency.  2. Physician directed emergency treatment for an asthma exacerbation within the  preceding 12 months.  3. Exacerbation of asthma more than 2x/week which could be characteristic of a  person of moderate or severe persistent asthma as outlined in the current NHLBI  guidelines for diagnosis and management of asthma.  4. Daily requirements for albuterol due to asthma symptoms (cough, wheeze, chest  tightness) which would be characteristic of a person of moderate or severe  persistent asthma as outlined in the current NHLBI guidelines for diagnosis and  management of asthma (not to include prophylactic use of albuterol prior to  exercise).  5. Viral upper respiratory tract infection within 4 weeks of challenge.  6. Any acute infection requiring antibiotics within 6 weeks of exposure or fever of  unknown origin within 6 weeks of challenge.  7. Severe asthma  8. Mental illness or history of drug or alcohol abuse that, in the opinion of the  investigator, would interfere with the participant's ability to comply with study  requirements.  9. Cigarette smoking >1 pack per month  10. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not  during a clearly recognized viral induced asthma exacerbation) which would be  characteristic of a person of moderate or severe persistent asthma as outlined in  the current NHLBI guidelines for diagnosis and management of asthma.  11. Allergy/sensitivity to study drugs or their formulations  12. Known hypersensitivity to methacholine or to other parasympathomimetic agents  13. History of intubation for asthma  14. Unwillingness to avoid coffee, tea, cola drinks, chocolate, or other foods  containing caffeine after midnight on the days that methacholine challenge  testing is to be performed.  15. Unwillingness to use reliable contraception if sexually active (IUD, birth  control pills/patch, condoms).  2. Pregnancy or nursing a baby. Female volunteers will be asked to use effective birth  control (stable regimen of hormonal contraceptive use for at least 3 months,  intrauterine device placement, tubal ligation or endometrial ablation for at least 3  months through at least one week after study completion) and will provide a urine  sample to test for pregnancy on study days. If the test is positive or the subject has  reason to believe she may be pregnant, she will be dismissed from the study. Women who  have been amenorrheic for 12 months may participate. Male volunteers will be asked to  use condoms for the duration of the study through at least one week after study  completion.  3. Usage of the following medications:  1. Use of systemic steroid therapy within the preceding 12 months for an asthma  exacerbation. All use of systemic steroids in the last year will be reviewed by a  study physician.  2. Subjects who are prescribed daily inhaled corticosteroids, cromolyn, or  leukotriene inhibitors (Montelukast or Zafirlukast) will be required to  discontinue these medications at least 2 weeks prior to their screening visit.  3. Use of daily theophylline within the past month.  4. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest  tightness) which would be characteristic of a person of moderate or severe  persistent asthma as outlined in the current NHLBI guidelines for diagnosis and  management of asthma. (Not to include prophylactic use of albuterol prior to  exercise).  5. Use of any immunosuppressant therapy within the preceding 12 months will be  reviewed by the study physician.  6. Receipt of Live Attenuated Influenza Vaccine (LAIV), also known as FluMist®, or  any other live viral vaccine within the prior 30 days, or any vaccine for at  least 5 days  7. Use of beta blocking medications  8. Antihistamines in the 5 days prior to allergen challenge  9. Routine use of NSAIDs, including aspirin.  4. Physical/laboratory indications:  1. Abnormalities on lung auscultation  2. Temperature >37.8 C  3. Oxygen saturation of <94%  4. Systolic BP>150 mmHg or <90 mmHg or diastolic BP>90 mmHg or <60 mmHg  5. Inability or unwillingness of a participant to give written informed consent.

This trial attempts to evaluate the treatment efficacy of magnetic seizure therapy (MST) and  its safety among schizophrenia patients. Half of the participants will be randomized to MST  group, while the other half will be randomized to receive electroconvulsive therapy (ECT). Magnetic seizure therapy (MST) is likely to be an alternative options to electroconvulsive  therapy (ECT).  Widespread stimulation of cortical and subcortical regions is inevitable for ECT since the  substantial impedance of the scalp and skull shuts most of the electrical stimulus away from  the brain. Nevertheless, magnetic pulses are capable to focus the stimulus to a specific area  of the brain because they can pass the scalp and skull without resistance. In Addition,  electric current will penetrate into deeper structures, while magnetic stimulus are only  capable to reach a depth of a few centimeters. As a consequence, MST are able to generate  focus stimuli on superficial regions of the cortex while ECT can't, which may give MST the  capability to produce comparable therapeutic benefits with the absence of apparent cognitive  side effects. Inclusion Criteria:  1. DSM-5 diagnosis of schizophrenia;  2. convulsive therapy clinically indicated, such as severe psychomotor excitement or  retardation, attempts of suicide, being highly aggressive, pharmacotherapy  intolerance, and ineffectiveness of antipsychotics;  3. the positive and negative syndrome scale (PANSS)[20] score ≥ 60;  4. informed consent in written form. Exclusion Criteria:  1. diagnosis of other mental disorders;  2. severe physical diseases, such as stroke, heart failure, liver failure, neoplasm, and  immune deficiency;  3. present with a laboratory abnormality that could impact on efficacy of treatments or  safety of participants;  4. failure to respond to an adequate trial of ECT lifetime;  5. are pregnant or intend to get pregnant during the study;  6. other conditions that investigators consider to be inappropriate to participate in  this trial.

The aim of this study was to compare the functional and radiological outcomes of fixation by  using double plating technique versus replacement using distal femur tumor prothesis as a  primary management for the distal femoral fractures in geriatric patients. The hypothesis was  that the distal femoral replacement will yield better functional outcome and earlier  rehabilitation and return to pre-injury level of activity. Geriatric distal femoral fractures represent a major challenge for the orthopedic surgeons,  to the present days still there is no definite algorithm or specific guidelines that can be  used accurately in the management of these fractures. Unlike hip fractures however, there is  no widely accepted treatment algorithm or standard of care.  The surgical treatment of distal femoral fractures depends on both patient and fracture  characteristics. Options include conservative treatment, open reduction internal fixation,  intramedullary nails, or recently distal femoral replacement.  There is currently a move towards distal femoral replacement (DFR) for these complex  fractures which has the potential benefit of allowing early weight bearing, and therefore  aiming to prevent complications associated with immobility and non-union.  Using distal femoral replacement had yield good results in small case series, as it allows  immediate full weightbearing, eliminate the risk of nonunion and may provide greater  satisfaction scores. However, DFR has its own risks, most notably deep infection, and  loosening. While a DFR is more costly compared with fixation plates and nails, the initial  increased cost may be outweighed by faster rehabilitation and return to the patient's usual  place of residence.  In the study, the investigators are aiming to compare the functional and radiological  outcomes of fixation by using double plating technique versus replacement as a primary  management for the geriatric distal femoral fractures. Inclusion Criteria:  -  AO 33 A3 and 33 C fractures  -  Age group ≥ 60 years  -  Closed fractures  -  Neurovascular intact Exclusion Criteria:  -  Open fractures  -  Non ambulant patients  -  Patients with peripheral neurovascular diseases  -  Peri-prosthetic fractures  -  Associated other orthopedic injuries  -  Poly-traumatized patients  -  Pathological fractures

Aims: to evaluate the success rate of radial artery cannulation in patients undergoing  cardiac catheterization, using different methods such as palpation, hyperemia or  ultrasound-guided puncture, together or each method separately. Specifically, the success  rate at the first attempt, the number of attempts with each technique and the time spent will  be assessed.  The hypothesis is that there are different success rates for each puncture technique when  cannulating radial artery for cardiac catheterization.  Methods: randomized clinical trial with four parallel groups, with operator blinding. Those  patients who will have the radial artery cannulated for an interventional cardiology  procedure will be selected.  Once the participant agrees to be included in the study and signs the informed consent, they  are randomized to one of four groups: ultrasound and hyperemia puncture, only ultrasound  puncture, only hyperemia puncture, palpation puncture (control group). Subsequently, an  ultrasound assessment of the participant's radial artery (diameter, depth and systolic peak  velocity) will be performed. Once in the intervention room, the puncture will be performed  according to the corresponding method. The puncturing operator in charge will not perform the  randomization or the ultrasound assessment to avoid bias.  Variables will be collected in an ad hoc questionnaire designed to respond all study aims.  Regarding the sample size, accepting an alpha risk of 0.05 and a beta risk of 0.2 in a  bilateral contrast, 92 subjects per group are required to detect significant differences.  Therefore, the total sample size would be made up of 368 participants, estimating losses of  5%.  For variables description and hypotheses contrast, the statistical program SPSS version 22.0  for Windows will be used, working with a significance level of 5%. Background: ultrasound-guided puncture seems to facilitate cannulation of the radial artery  in patients who undergoing cardiac catheterization. The efficacy of reactive hyperemia has  also been seen, however, the combination of different methods in radial artery puncture has  not been evaluated.  Aims: to evaluate the success rate of radial artery cannulation in patients undergoing  cardiac catheterization, using different methods such as palpation, hyperemia or  ultrasound-guided puncture, together or each method separately. Specifically, success rate at  the first attempt, attempts numbers with each technique and time spent will be assessed.  Possible complications and perceived pain by the participant in each technique will be  evaluated.  The hypothesis is that there are different success rates for each puncture technique when  cannulating radial artery for cardiac catheterization.  Methods: randomized clinical trial with four parallel groups, with operator blinding.  Participation in the clinical trial does not imply an increased risk for the patient since  both ultrasound and hyperemia are harmless and non-invasive methods.  Once the participant agrees to be included in the study and signs the informed consent, they  are randomized to one of four groups: ultrasound and hyperemia puncture (for hyperemia, a  blood pressure cuff is inflated 50mmHg above systolic until a maximum of 200mmHg for 5  minutes before puncture, it is known that maximum hyperemia is achieved 60 to 180 seconds  after deflation), ultrasound puncture only, hyperemia puncture only, palpation puncture  (control group).  Similarly, before the puncture, an ultrasound assessment of the participant's radial artery  (diameter, depth and systolic peak velocity) will be performed. Once in the intervention  room, the puncture will be performed according to the corresponding method. The puncturing  operator will not perform the randomization or the ultrasound assessment to avoid bias.  Participation in the study ends once the radial artery has been cannulated with the guide  according to the Seldinger technique.  The randomization sequence was generated by the center's Biostatistics and Epidemiology Unit.  The four possible puncture methods were stratified by operator.  All operators have performed hundreds of radial punctures by palpation and more than 20  ultrasound-guided punctures, as established by the study of the learning curve carried out by  Jayanti S et al, before starting participants recruitment.  All the variables will be collected in an ad hoc questionnaire designed to respond all study  objectives.  Regarding the sample size, accepting an alpha risk of 0.05 and a beta risk of 0.2 in a  bilateral contrast, 92 subjects per group are required to detect a statistically significant  difference, which for the control group (traditional puncture) is expected to be 0.44 the  percentage of success at the first puncture attempt, and for the rest is at least 0.65.  Therefore, the total sample size would be made up of 368 participants, estimating a follow-up  loss of 5%.  Regarding the statistical analysis, the quantitative variables will be described with the  mean and the standard deviation if they follow a normal distribution, or with the median and  the interquartile range if they do not follow a normal distribution. The normality will be  contrasted using the Kolmogorov-Smirnov test. The qualitative variables will be described  through the distribution of frequencies and percentages.  For the comparisons of the quantitative variables following a normal distribution, the one  factor analysis of variance (ANOVA) will be used for the global comparison, and the Student's  t-test in the comparisons by pairs. For variables do not following a normal distribution, the  Kruskal Wallis test will be used in the global comparison, and Dunn's test in pairwise  comparisons. For comparisons of qualitative variables, the Chi-square test will be used, or  Fisher's exact test in those situations in which the criteria for using the Chi-square are  not met. In pairwise comparisons, the Bonferroni correction will be applied for multiple  comparisons.  In all hypothesis contrasts, a significance level of 5% will be used. The statistical program  SPSS version 22.0 for Windows will be used. Inclusion Criteria:  -  over 18 years of age  -  understand, accept and sign the informed consent  -  participants undergoing radial artery cannulation for a diagnostic, therapeutic, or  structural interventional cardiology procedure  -  patent radial artery in the previous ultrasound evaluation Exclusion Criteria:  -  systolic blood pressure greater than 150mmHg  -  diagnosis of acute myocardial infarction (with or without ST-segment elevation)  -  previous surgeries that have affected the arterial system of the upper limbs  (arteriovenous fistula, radial artery for bypass surgery, etc.)  -  language barrier that hinders a clear study understanding for potential participant

MEIGES is a prospective, multicenter, randomized controlled clinical trial with the primary  hypothesis that, STN-DBS is non-inferior to GPi-DBS for motor symptoms improvements at 365  days postoperatively in patients with idiopathic craniofacial dystonia. Evaluating therapeutic effects of GPi-DBS vs. STN-DBS on patients with idiopathic  craniofacial dystonia: Clinical data of patients at different treatment time points will be  collected, using different clinical assessments. The main purpose is to assess whether  STN-DBS is non-inferior to GPi-DBS for motor symptoms improvements at 365 days  postoperatively in patients with idiopathic craniofacial dystonia.  Primary endpoints: Differences between the two groups in BFMDRS-M change scores in the  stimulation state from before to 365 days (±14 days) after STN-DBS and GPi-DBS.  Secondary endpoints: Differences between the two groups in BFMDRS-M change scores in the  stimulation state from before to 90, 180 days (±14 days) after STN-DBS and GPi-DBS.  Differences between the two groups in BFMDRS-D, BDSI, JRS, MMSE, MoCA, HRSD, HAMA, SF-36 and  programming parameters change scores in the stimulation state from before to 365 days (±14  days) after STN-DBS and GPi-DBS. Inclusion Criteria:  1. Adult subject (male or female, 18-75 years);  2. Diagnosed with idiopathic craniofacial dystonia for more than 1 year, including at  least one of the eye and oromandibular region. Cervical dystonia may be present;  3. Treated with oral drugs or botulinum toxin injections, but with no satisfactory  curative effect;  4. Normal cognitive function with MMSE score ≥ 24;  5. Informed consent signed. Exclusion Criteria:  1. Only cervical dystonia, or combined with dystonia in other parts of the body other  than the cervical region;  2. Diagnosed with other neuropsychiatric diseases(Alzheimer's disease, amyotrophic  lateral sclerosis, Parkinson's disease, etc.);  3. History of brain surgery;  4. Severe depression with HRSD score ≥ 35;  5. Contraindications to neurosurgery(cerebral infarction, hydrocephalus, cerebral  atrophy, sequelae of cerebrovascular disease, etc);  6. Contraindications to CT or MRI scanning(claustrophobia, etc);  7. pregnant or breastfeeding female, or has positive pregnancy test prior to  randomization;  8. Contraindications to general anesthesia (severe arrhythmia, severe anemia, abnormal  liver and kidney function, etc.);  9. Expected lifetime < 12 months;  10. Currently receiving an investigational drug or device;  11. Other circumstances that the investigator considers unsuitable to participate in this  study or that may pose a significant risk to the patient (inability to understand or  comply with research procedures and follow-up, etc.).

Despite widespread awareness of significant negative health consequences, cigarette smoking  remains the leading cause of preventable morbidity and mortality in the US (Creamer et al.,  2019; Jamal, 2018). Moreover, the highest rate of smoking and heaviest burden of  smoking-related illness occurs among low-socioeconomic status (SES) individuals relative to  higher SES groups (Businelle et al., 2010; Clegg et al., 2009). Low SES individuals are also  40% less likely to succeed in quitting smoking when they attempt to do so (National Center  for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health, 2014).  One potential explanation for the disparity in rate of smoking and successful quit attempts  may be differences in individual rates of delay discounting (DD), i.e., the degree to which  rewards loses their value as the delays to their receipt increase (Odum, 2011). A proposed  way to reduce steep DD and, potentially, substance use has been computer training for working  memory, which has shown favorable results in a sample of individuals with stimulant  dependence (Bickel et al., 2011) and substance use broadly (Felton et al., 2019), with the  latter even showing decreases in cigarette smoking in a subset of the sample. The highest rate of smoking and heaviest burden of smoking-related illness occurs among  low-SES individuals (Businelle et al., 2010; Clegg et al., 2009). One explanation for this  disparity may be differences in individual rates of DD, which have been showed to be reduced  with working memory training. (Bickel et al., 2011; Felton et al., 2019). Given the low cost  of administering working memory training, such an intervention may be favorable for low-SES  populations to improve smoking cessation outcomes.  DD has significant associations with:  Cigarette smoking (smokers tend to have higher rates of DD compared to non-smokers; Bickel et  al., 1999);  Smoking treatment outcome (individuals who remained smoke free after a smoking cessation  intervention had lower DD compared to those who didn't; González-Roz et al., 2019;  Krishnan-Sarin et al., 2007; MacKillop & Kahler, 2009; Yoon et al., 2007); SES (individuals  with lower education and income have higher DD rates compared to those who are more educated  and affluent; de Wit et al., 2007; Reimers et al., 2009).  An innovative way to reduce DD that has been proposed is via working memory (WM) training. WM  refers to one's capacity to hold information while engaging in complex mental tasks,  including reasoning, comprehension, and learning (Baddeley, 2010). Previous research has  shown that DD and WM correlate negatively (Shamosh et al., 2008), that individuals with  higher DD rates show neural deficits in WM (Herting et al., 2010), and that acute nicotine  abstinence is associated with WM deficits (Mendrek et al., 2006; Patterson et al., 2010).  Furthermore, previous studies targeting WM to reduce DD have shown favorable results in a  sample of individuals with stimulant dependence (Bickel et al., 2011) and substance use  broadly (Felton et al., 2019), with the latter even showing decreases in cigarette smoking in  a subset of the sample.  Although previous research has shown WM training to reduce DD (which would support H3), and  cigarette use in a small subsample, the hypotheses of this study are largely exploratory.  However, given the theoretical connections between DD, SES, and WM, it is expected that the  hypotheses of this project will be supported.  The performance of this project may advance our knowledge of the relevant clinical targets  for smoking cessation in low-SES individuals. In particular, this project is expected to shed  light on DD as the putative mechanism in smoking for low-SES individuals and the durability  of reductions in smoking as a result of reductions in DD through WM training.  Despite the evidence for some successful techniques for reducing DD, little of this work has  been translated into intervention approaches to target clinical outcomes. This application  seeks to capitalize on the emerging literatures indicating (1) WM training may be an  effective and efficient way to reduce DD, and (2) DD is associated with SES, cigarette  smoking, and treatment outcomes. Though WM training has been successfully implemented in  laboratory-controlled experiments to reduce DD, we are not aware of any interventions for  clinical disorders that specifically seek to do so and potentially enhance treatment  outcomes.  The development of effective, theoretically coherent interventions addressing cigarette  smoking is imperative, particularly interventions that would be feasible, efficacious, and  acceptable in low-SES individuals. The proposed research is an innovative approach that  capitalizes on previous findings showing reductions in delay discounting and even cigarette  smoking. If working memory training is found to improve smoking cessation outcomes as a  function of reductions in delay discounting, the project results could be helpful in future  development of low-cost interventions for cigarette smoking. Inclusion Criteria:  older, who have smoked at least four cigarettes per day for at least 6 months, are  interested in quitting cigarette smoking, are at or below the federal poverty line based on  persons in family/household and annual household income:  -  1 -- $12,880  -  2 -- $17,420  -  3 -- $21,960  -  4 - $26,500  -  5 -- $31,040  -  6 -- $35,580  -  7 -- $40,120  -  8 -- $44,660  -  9 - add $4,540 for each additional person,  OR they or their child(ren) utilize a federal program for low-income individuals, and are  willing to participate in a 5-week working memory training program as a pretreatment  adjunct to behavioral group + nicotine replacement therapy (NRT; via nicotine patches). Exclusion Criteria:  according to the DSM-V with any substance other than tobacco or have any significant  medical or psychiatric condition. Such conditions could include traumatic brain injury,  dementia, significant learning disability, or psychotic symptoms. Participants must be at  least at a 5th-grade reading level. In case that participants are excluded, they will be  provided with resources in the community and provided with contact information for the  Kansas Tobacco Quitline.

Patients primary malignant peritoneal mesothelioma (MPM), without extra-abdominal disease,  that are not eligible (or willing) to undergo cytoreductive surgery (CRS) with hyperthermic  intraperitoneal chemotherapy (HIPEC) can be included in this study. Patients will be treated  with intraperitoneal (IP) chemotherapy (paclitaxel) in weekly cycles. The primary aim of this  study is to determine the maximum tolerable dose (MTD) of IP monotherapy with paclitaxel for  patients with MPM. The secondary aims are to assess safety and feasibility of this strategy,  and to study the pharmacokinetics of paclitaxel in this setting. Malignant Peritoneal Mesothelioma (MPM) is a rare, but unfortunately very aggressive cancer  with a poor prognosis. Currently, the only possibly curative treatment is cytoreductive  surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority  of patients are not eligible to undergo this treatment, mainly due to extensive local  disease. Currently, a palliative treatment with low morbidity is not available. Overall  response rates to systemic chemotherapy are low, though morbidity rates are high.  Immunotherapy presents similar shortcomings, as the morbidity rate is comparable to that of  systemic chemotherapy, while its benefit for MPM patients is not proven. Especially given the  high morbidity rate, and the limited effectiveness of systemic treatment with either  immunotherapy or chemotherapy, there is lack of treatments suitable as palliative treatment  for patients with MPM. Thereby, the majority of MPM patients currently receive no anti-tumor  treatment.  As MPM very rarely disseminates outside the abdominal-cavity, the use of intraperitoneal (IP)  chemotherapy seems a logical and promising step. This therapy can be delivered through an IP  port-a-cath (PAC), and potentially has major advantages over systemic treatment. A higher,  more effective dose of chemotherapy can directly be delivered at the site of disease, while  systemic uptake is limited likely resulting in fewer toxicity. In rare cases where metastases  do develop, a switch can be made to systemic treatment. By first applying local treatment,  most patients will be spared a toxic and often ineffective systemic therapy. Another major  advantage of the suggested approach is that ascites, a common MPM-symptom that causes major  morbidity, can be drained through the same PAC-system. Paclitaxel is a well-known  chemotherapeutic agent and is considered extremely favorable for IP use.  The aim of this study is to determine the maximum tolerable dose (MTD) of IP monotherapy with  paclitaxel for patients with MPM, and to assess safety and feasibility of this strategy. The  investigators will conduct a classic three-plus-three dose escalation study with three dose  Three patients are initially enrolled into a given dose cohort. If there is no dose limiting  toxicity (DLT) observed in any of these patients, the trial proceeds to enroll additional  patients to the next higher dose cohort. If one patient develops a DLT at a specific dose  level, three additional subjects are enrolled into that same dose cohort. Development of a  DLT in more than 1 patient in a specific dose cohort (≥33%) suggests that the MTD has been  exceeded, and further dose escalation is not pursued. The previous dose is considered the  MTD. When the MTD is found, an expansion of 3-6 more patients in that dose cohort will be  performed, to achieve a total number of 9 patients treated at the MTD-level.  Patients undergo a diagnostic laparoscopy (DLS) according to standard work-up for CRS-HIPEC.  If the disease is considered not resectable, a peritoneal PAC will be placed during DLS.  Through this PAC intraperitoneal paclitaxel will be administered weekly (dosage according to  dose-escalation schedule). The number of cycles depends on toxicity and response to the  treatment. The first response evaluation is scheduled after 8 cycles. There is no limit to  the number of cycles, in case of continuing response to treatment. During the first and the  fourth cycle, additional blood samples and IP-fluid samples will be collected for  pharmacokinetic analysis. Inclusion Criteria:  -  Histological confirmed diagnosis of malignant peritoneal mesothelioma  -  Patients that are not eligible (or willing) to undergo cytoreductive surgery (CRS)  with hyperthermic intraperitoneal chemotherapy (HIPEC)  -  Age ≥ 18 years old  -  Written informed consent according to the International Conference on  Harmonisation-Good Clinical Practice (ICH-GCP) and national/local regulations  -  Patients must be ambulatory, i.e. World Health Organization-Eastern Cooperative  Oncology Group (WHO-ECOG) performance status 0 or 1  -  Ability to return to the Erasmus Medical Center for adequate follow-up as required by  this protocol  -  Patients must have normal organ function and adequate bone marrow reserve as assessed  by the following laboratory requirements; absolute neutrophil count >1.5 * 10^9/l,  platelet count >100*10^9/l and Hemoglobin >6.0mmol /l. Patients must have a Bilirubin  <1½ x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and alanine  aminotransferase (ALT) <2.5 x ULN Exclusion Criteria:  -  Extra-abdominal disease/metastatic disease established by preoperative CT-scan of  thorax-abdomen and/or PET-scan. Imaging not older than two months at time of surgery  -  Medical or psychological impediment to probable compliance with the protocol  -  Serious concomitant disease or active infections  -  History of auto-immune disease or organ allografts, or with active or chronic  infection, including HIV and viral hepatitis  -  Serious intercurrent chronic or acute illness such as pulmonary (COPD or asthma) or  cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the  study coordinator to constitute an unwarranted high risk for participation in this  study  -  Pregnant or lactating women; for all women of child-bearing potential a negative urine  pregnancy test will be required as well as the willingness to use adequate  contraception during the study until 4 weeks after finishing treatment  -  Absence of assurance of compliance with the protocol  -  An organic brain syndrome or other significant psychiatric abnormality which would  comprise the ability to give informed consent, and preclude participation in the full  protocol and follow-up

The primary objective of this study is to determine whether intranasal application of  aminoglycoside (Neosporin) increases local nasal innate immune responses compared to placebo  control in healthy participants. The primary objective of this study is to determine whether intranasal application of  aminoglycoside (Neosporin) increases local nasal innate immune responses compared to placebo  control in healthy participants.  This study will evaluate the role of nasally applied neomycin at inducing local antiviral  interferon responses that have been associated with protection against SARS-CoV2 ( severe  acute respiratory syndrome coronavirus 2). Local interferon immune responses including the  nasal compartment are important in driving early protective responses against the virus.  Given the current challenges with vaccine access in lower- and middle-income countries (LMIC)  as well as varying vaccine acceptance and hesitancy, additional strategies are needed to help  curb the spread of SARS-CoV2. There is a need for easily available agents that are low cost  and effective at decreasing the effects of SARS-CoV2 exposure. The investigators will  evaluate the effectiveness of intranasal Neosporin (which contains neomycin) at inducing  interferon responses in human subjects.  This will be a proof of concept that such approach will provide local immune response that  could be beneficial against the SARS-CoV2 infection. The potential impact of this study is  the utilization of existing and available topical medications for the purpose of providing  local prophylaxis against SARS-CoV2.  The overall hypothesis is that neomycin containing agents such as Neosporin when applied  topically in the nose can induce local antiviral interferon responses in adult human  subjects. Neosporin will be compared to placebo, control Vaseline (Unilever) or equivalent. A  run-in cohort of 6 participants to test optimal sampling and storage conditions will be used.  The focus of this study is the randomized double-blinded placebo-controlled trial.  The study will enroll an estimated 40 healthy subjects at one study site, Yale University.  Local nasal immune responses will be measured using RT-PCR and multiplex ELISA for interferon  response. Participants will apply a small amount of the cream (less than a pea size) to the  inside of both nostrils, then pinch the nose to spread the cream. Participants will use  Neosporin or placebo twice a day for 7 days. Inclusion Criteria:  -  Completion of written informed consent  -  Covid-negative within 48 hours of enrollment based on PCR or Antigen test. If subjects  are found to be positive, the PI will recommend appropriate follow-ups.  -  In good general health as evidenced by medical history  -  Ability to take Nasal medication and be willing to adhere to the nasal agent regimen Exclusion Criteria:  -  Participant with active nasal or respiratory symptoms.  -  Participant with active or chronic respiratory nasal or respiratory infections and or  is currently on antibiotics  -  Participant who has been treated with oral or topical antibiotics with the past 14  days  -  Participant who is on intranasal or oral corticosteroids or systemic immunosuppression  medication  -  Participant who has immunocompromised conditions such as rheumatological diseases,  HIV, cancer on chemotherapy or biologic therapies.  -  Participant who is on any intranasally applied medications (prescription or over the  counter) including nonmedical nasal products and the use of Netipot or other nasal  flush products.  -  Participant with known allergic history to Neosporin (allergic history to neomycin or  bacitracin or polymyxcin or pramoxine or the inactive ingredients that include cocoa  butter, cottonseed oil, olive oil, sodium pyruvate, tocopheryl acetate and white  petrolatum)  -  Participant with known allergies to aminoglycoside antibiotics (neomycin, tobramycin,  gentamycin, others)  -  Participant with history of COVID-19 infection in the past 8 weeks.  -  Participant who is pregnant

It is an interventional study in which 60 obese elderly patients (30 male & 30 female)  estimated to enroll according to random allocation and divided into two groups. The study  group will receive active acupuncture low level laser in addition to nasal laser irradiation  and aerobic exercises while the control group will aerobic exercises. The laser consists of a  semiconductor and operates at a wavelength of 650 nanometre. The laser installed in the watch  comprises 10 individual laser beams for the wrist and an additional adapter for nasal  stimulation. The output power is 5 megawatt, but it can also be adjusted. The device operates  at an ambient temperature of -20 to +40 ° C and a relative humidity of ≤ 85%. The laser watch  can be used for a variable irradiation period of 10-60 min. the device will be applied on  specific acupuncture points ( acupuncture point, Radial artery acupuncture points, and ulnar  artery acupuncture points) combined with nasal laser irradiation at the same time, once per  day, 3 times per week for three months PURPOSE:  To determine whether low level laser light therapy is effective as an adjunctive therapy on  countering hypercoagulable state parameters (fibrinogen, bleeding time, Prothrombin time) and  total cholesterol (, d-dimer and c-reactive protein) as preventive strategy of venous  thromboembolism incidence in obese elderly patients  BACKGROUND:  In the general population the annual incidence of venous thrombosis (VT) approximates 1 in  1000 persons and appears to be increasing over time. Notably, incidence rates rise  exponentially with age with an approximate 7- to 10-fold increase from less than 55 years to  greater than 75 years. Aging is associated with increased levels of coagulation factors and  decrease in natural anticoagulant factors. This strongly supports that age-related  hypercoagulable state occurs in elderly.  Blood coagulation plays a critical role not only in homeostasis but also in many  physiological and pathological conditions. Blood coagulation potential in humans reaches a  young adult level around the time of weaning, followed by a gradual increase during young  adulthood and an almost 2-fold increase by old age.  Fibrinogen may contribute to the cardiovascular risk due to their influence on blood  viscosity, platelet aggregation, low-density lipoprotein deposition, blood vessel diameter  and cell proliferation. Most of the factors that cause venous thromboembolism are related to  changes in blood flow and changes in the composition of the blood.  In recent years, an innovative technology using low-level laser light has garnered an  exceptional level of interest across myriad medical disciplines because of its unique ability  to modulate cellular metabolism, therefore inducing beneficial clinical effects  Low level laser radiation has particular effect on blood viscosity by changing the sizes of  erythrocyte aggregates which lead to an increase in the blood flow velocity in the human  body. There are several reasons for the increase in the blood microcirculation under  irradiation. One of the major reasons is the activation of the respiratory chains of cells  leading to a cascade of biochemical reactions that resulting in an increase in the  permeability of erythrocyte membranes and an increase in the concentration of oxygen in the  bio tissues.  HYPOTHESES:  countering hypercoagulable state parameters (fibrinogen, bleeding time, Prothrombin time) and  total cholesterol (, d-dimer and c-reactive protein) as a preventive strategy of venous  thromboembolism incidence in obese elderly patients  RESEARCH QUESTION:  Does low level laser therapy with aerobic exercises influence on obese elderly patients'  hemostatic state parameters as coagulation profile ((fibrinogen, bleeding time, Prothrombin  time) and total cholesterol (, d-dimer and c-reactive protein) as prevention of venous  thromboembolism in the obese elderly patient Inclusion Criteria:  -  • aged from 60 to 75 y  -  • sedentary individuals  -  Body mass index 30-39.9 kg/m2 Exclusion Criteria:  -  • The exclusion criteria were as follows: smokers, diabetes, drinking alcohol,  presence of uncontrolled hypertension or cardiovascular diseases, weight loss program  participation for at least 6 months prior to the current study, medications affecting  blood coagulation or body weight, recent or chronic active disease, cognitive  impairment, presence of malignant disease, blood donation, or participation in any  other research during the previous 90 days of the current study Individuals suffering  from hepatic, renal, cardiac, chest, and endocrine diseases, as well as  musculoskeletal disease

This study will be a randomized control trial conducted on 44 patients diagnosed as adhesive  capsulitis in headquarter hospital Gujar khan. Subjects will be divided equally into 4 groups  (n=11 in each group) that are Group A, B, C and D by sealed envelope method. Pre-intervention  assessment will be done by using data collection tools and then intervention will be applied.  Group A will receive mobilization with movement (MWM) technique along with Spencer's muscle  energy technique (MET) with conventional therapy. Group B will receive MWM along with  conventional therapy. Group C will receive Spencer's MET along with conventional therapy.  Group D will receive conventional therapy alone. All subjects will be given a home exercise  plan. Assessment will be done after 1st session, 1st week, 2nd week, 3rd week and finally  after 2 weeks on follow up using data collection tool. Data collection tools are  semi-structured questionnaire (informed consent, demographic details, goniometric  measurements), Visual analogue scale (VAS), shoulder pain and disability index (SPADI) and  universal goniometer. One of the numerous disorders that causes pain and increase resistance to the active and  passive movements of shoulder is the adhesive capsulitis. The pathology of the shoulder can  be the extrinsic or intrinsic that induces pain and stiffness that is why the treatment  should be according to the actual cause of pathology. Another term which is used for these  pathology is 'Frozen Shoulder' which is used by the Codman for the first time in history.  Adhesive capsulitis does not represent a single pathology rather it is applicable to most of  the conditions that causes myospasm most specifically adhesion that forms in the bursa or  joint capsule and rotators of the shoulder. Most specifically the term adhesive capsulitis is  actually a pathology that includes the capsule's inflammation which results in thickness and  fibrosis and consequently adherence to the shoulder as well as the neck of humerus.  About 2%-5% of the global population is affected by the adhesive Capsulitis that's why it is  considered as a common condition. Frozen shoulder the alternative term for adhesive  capsulitis affect the 2% of the total world population because of the absent of most accurate  criteria for diagnosis and sometime due to the over diagnosis. It is uncommon in people under  the age of 40, peak prevalence is in people elder than 40 and younger than 60 and is uncommon  in people above 70years except for secondary cause and in the manual workers as according to  a cumulative incidence of 2.4 persons per 1000 in a year. Economically the impact of adhesive  Capsulitis is underscored i-e 8.2% for men and 10.1% for women for adults in working age. It  is more prevalent in women as compared to the men. It cannot develop in the same shoulder  after the first time but in 20% of people it is seen to develop in the opposite Shoulder.14%  of patients have seen to develop in both shoulders at one time, and 80% are those who develop  this condition on opposite side within the next five years.  Frozen shoulder is mostly common in patients suffering from diabetes mellitus. 71.5% of the  people are estimated to have the diabetes and frozen shoulder at the same time half of them  are previously diagnosed with type I or type II diabetes mellitus and remaining have high  glucose tolerance test or increased fasting glucose level.The suspected risk of having frozen  shoulder have increased a 10% to 20% in people who are diabetic, having 4% point prevalence,  and 2-4 times on greater risk as compared to normal population. Inclusion Criteria:  -  Both male and female  -  Age bracket is 30-70 years  -  Pain in the shoulder for at least three months  -  All active and passive shoulder movements restricted, with a reduction in external  rotation of at least 50%. Exclusion Criteria:  -  Patients with  -  Recent history of surgery on particular shoulder  -  Post-traumatic and rotator cuff rupture  -  Neurological deficits affecting shoulder function  -  Pain or disorders of cervical spine, elbow, wrist or hand  -  Tendon calcification  -  Rheumatoid arthritis  -  Osteoporosis  -  Malignancies  -  Pregnancy  -  Open wounds or skin infections  -  Recent steroid injection  -  Previous manipulation under anesthesia of affected shoulder.