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The investigators would like to conduct a double blind placebo-controlled prospective study  to show the impact of a treatment combining a specific cognitive rehabilitation program and  acetylcholinesterase inhibitors on executive function of young patients 3 months after a  first symptomatic stroke. The secondary objectives will be to assess cognitive changes  performance (executive but also non trained functions such as memory) before and after  treatments and treatment effect on activity of daily living and on quality of life.  The main objective of this study is to show the impact of this combined treatment on brain  activation maps in VCI-ND patients in the post-acute phase (3 months) after a stroke.  Treatment effect will be assessed by functional MRI (fMRI) while patients will be performing  a specific executive task.  The investigators hypothesize that the specific rehabilitation associated with  acetylcholinestrase inhibitors treatment will focalize cerebral activation observed in fMRI,  improve executive functions specifically, improve non trained cognitive functions  (generalization effect). Recent studies, including the investigators', have shown that neuropsychological alteration  is frequent and underestimated after stroke (Vascular Cognitive Impairment (VCI). VCI-No  Dementia (VCI-ND) is characterized by a mild cognitive alteration in relation to a  cerebrovascular lesion, diagnosed by a neuropsychological assessment, and without major  alteration in the activities of daily living, but that can represent an issue in return to  work for young patients. Some studies demonstrated that cognitive rehabilitation or  pharmacological intervention may to improve patients' cognition and social functioning.  The investigators hypothesize that a combination of pharmacological and cognitive  rehabilitation treatments is beneficial on executive but also other cognitive function in  VCI-ND patients  Therefore the investigators would like to conduct a double blind placebo-controlled  prospective study to show the impact of a treatment combining a specific cognitive  rehabilitation program and acetylcholinesterase inhibitors on executive function of young  patients 3 months after a first symptomatic stroke. The secondary objectives will be to  assess cognitive changes performance (executive but also non trained functions such as  memory) before and after treatments and treatment effect on activity of daily living and on  quality of life.  The main objective of this study is to show the impact of this combined treatment on brain  activation maps in VCI-ND patients in the post-acute phase (3 months) after a stroke.  Treatment effect will be assessed by functional MRI (fMRI) while patients will be performing  a specific executive task.  The investigators hypothesize that the specific rehabilitation associated with  acetylcholinestrase inhibitors treatment will focalize cerebral activation observed in fMRI,  improve executive functions specifically, improve non trained cognitive functions  (generalization effect). Inclusion Criteria:  -  Written consent form signed by the patient,  -  Patient must be affiliated with a social security system,  -  Age: 35-70,  -  First symptomatic stroke,  -  Brain ischemic lesion on MRI DWI consistent with a recent ischemic stroke,  -  Absence of cognitive decline before the stroke,  -  Detailed cognitive complaint of patient or the environment,  -  Patients with a cognitive impairment (VCI-ND criteria: impairment in at least one  cognitive domain with a score below 2 standard deviation according to clinical norms  in at least two cognitive functions exploring this domain. VCI-ND was diagnosed in the  absence of dementia according to the DSM IV,  -  Absence of hospitalization for cardiovascular disease from the acute phase of the  qualifying event,  -  NIHSS < 6,  -  mRs < 4,  -  Absence of aphasia, apraxia and neglect severe,  -  Patients not previously treated with cholinesterase inhibitors or memantine centrally  acting regardless of the duration of treatment and date of prescription,  -  Visual skills, auditory and oral or written expression sufficient to achieve adequate  neuropsychological tests,  -  Women of childbearing potential must be using contraception and a pregnancy test will  be conducted at the screening visit. Exclusion Criteria:  -  Subjects with contraindication to MRI (a pacemaker or a defibrillator, an implanted  material activated by an electrical, magnetic or mechanical carriers of hemostatic  clips of intracerebral aneurysms or carotid arteries, bearing orthopedic implants,  claustrophobia),  -  Preexisting cognitive decline,  -  VCI-ND criteria not fulfilled,  -  Patients previously treated with cholinesterase inhibitors or memantine centrally  acting regardless of the duration of treatment and date of prescription,  -  Known allergy or intolerance to cholinesterase inhibitors or their excipients,  -  Depression,  -  General Health scalable,  -  Progressive neurological disease causing cognitive impairment,  -  Clinically significant endocrine disease,  -  Patients with urinary retention or who have recently had surgery at the bladder,  -  Patients with rare hereditary problems of fructose intolerance, malabsorption of  glucose and galactose or sucrase-isomaltase insufficiency should not take this  medicine,  -  Patient with severe hepatic impairment,  -  Patient with severe renal impairment,  -  Patients with both hepatic and renal significant,  -  Patients with sick sinus disorder or other supraventricular cardiac conduction or in  those receiving concomitant drugs significantly slowing heart rate, such as digoxin  and beta blockers or in patients with uncorrected electrolyte disorders,  -  Period immediately post-myocardial infarction, recent-onset atrial fibrillation,  bundle branch block second degree or higher degree, unstable angina or congestive  heart failure, especially NYHA group III-IV,  -  Patients with gastrointestinal obstruction or recent surgery in gastrointestinal,  -  Patients receiving other cholinomimetic agents (such as ambenonium, donepezil,  neostigmine, pyridostigmine, rivastigmine and pilocarpine) administered systemically,  -  Breast feeding women,  -  Alcohol abuse,  -  Substance abuse,  -  Psychiatric condition scalable,  -  Patients who will have surgery during the study participation,  -  Known or suspected pregnancy, confirmed by a urine pregnancy test. This test will be  done prior to randomization if a woman of childbearing age without oral contraception  is included in the study, if a pregnancy is declared during the participation in the  study, the blind will be removed and the patient will be directed towards a  specialist,  -  Patient can not stop all treatment prohibited for this project at least 2 months  before inclusion,  -  French language level insufficient to properly participate in neuropsychological  assessment,  -  Transient ischemic stroke,  -  Subarachnoid hemorrhage or intraparenchymal,  -  Patient under protection of law or under another protection.

This is a single site, non-randomized, open-label, long-term safety and efficacy follow-up  Phase 1 study for subjects who have been treated with CARv3-TEAM-E T cells in clinical Study  DF/HCC IRB #20-532 (the main study), that evaluated the safety and efficacy of CARv3-TEAM-E T  cells in subjects with newly diagnosed or recurrent glioblastoma This is a single site, non-randomized, open-label, long-term safety and efficacy follow-up  Phase 1 study for subjects who have been treated with CARv3-TEAM-E T cells in clinical Study  DF/HCC IRB #20-532 (the main study), that evaluated the safety and efficacy of CARv3-TEAM-E T  cells in subjects with newly diagnosed or recurrent glioblastoma.  CARv3-TEAM-E drug product is defined as autologous T lymphocytes transduced with a CAR  lentiviral vector encoding a chimeric antigen receptor targeting human EGFRvIII antigen and a  T cell engaging antibody molecule (TEAM) targeting wildtype EGFR. CARv3-TEAM-E T cells are  administered in subjects up to six times in main Study #20-532.  No investigational treatment will be administered in this study.  The United States Food and Drug Administration (FDA, 2018) recommend long-term follow-up for  subjects treated with gene therapy drug products to monitor for selected adverse events (AEs)  and the durability of clinical response.  After the subjects in the parent study has been completed (24 months after CARv3-TEAM-E T  cells infusion, or <24 months after CARv3-TEAM-E infusion if subject discontinues due to  disease progression or any other reason), subjects will be asked to participate in a  long-term follow-up study. Inclusion Criteria:  - Subjects will be asked to participate leading up to the last Study #20-532 visit.  Subjects meeting the following criteria are eligible for study participation:  -  Provision of voluntary written informed consent by subject  -  CARv3-TEAM-E T cells were administered in DF/HCC IRB Study #20-532  -  Able to comply with study requirements Exclusion Criteria:  -  Subjects meeting the following criteria are to be excluded from study participation:  -  Subject has disease progression AND has 2 consecutive VCN measurements at least 1  month apart, at least 6 months after drug product infusion where testing demonstrates  undetectable VCN (<0.0003 vector copies per diploid genome) in peripheral blood cells.  -  Withdrew consent to Study #20-532.

Transcutaneous electrical nerve stimulation (TENS) is a non-invasive electro-physical  modality used for several pain conditions including labor pain control. Despite several years  of research, there is still no agreement within the literature regarding the selection of  TENS parameters. It is aimed to investigate TENS1 alternating between 4 to 100 Hz compared to  sham-TENS.  The present study aims to evaluate TENS in combination with cardiotocography (CTG).  The combination of TENS with CTG in a feedback-loop has not been reported in any studies  before. Midwives and the study investigator will ask parturients, who are admitted to the labor ward  at Region Hospital Herning satisfying the inclusion and exclusion criteria, whether they are  interested in attending the experimental session.  The study will be conducted as soon as the subject is admitted at the labor ward. The study  will only be conducted during early and active labor and not during the birth of the baby.  The subject in this study includes the package of a parturient and her neonate (after birth)  as we also obtain data about the neonate. Hereby, two consent forms will be obtained. As this  study is a non-invasive study, it is decided to have at least the consent of one parent.  The investigator will fill out a screening questionnaire about the laboring parturient in  cooperation with the subject and the midwife, including screening questions related to  inclusion and exclusion criteria before the experimental session starts.  The study will last approximately one hour and will be conducted during laboring  circumstances. KT (Kenoja Thuvarakan) will carry out the experiment, and she will be present  in the delivery room during the whole session.  The study includes several outcomes, including subjective and semi-objective pain measures.  The primary outcome is VAS (0-10 cm scale), while secondary outcomes include PPT and  satisfaction questionnaire (only at the end of the study). The subjects will be asked before,  and immediately after the experimental exposure about the outcomes (VAS and PPT). The  subjects will be exposed to one of the two combinations of TENS stimulation (low-to-high and  high alternating frequency), which will be compared to sham-TENS. Inclusion Criteria:  -  Singleton pregnancy  -  Vertex presentation  -  Speak, read and understand Danish Exclusion Criteria:  -  Gestational age < 37+0 weeks  -  Gestational age > to 41+6 weeks  -  High-risk pregnancies (including risk factors: eclampsia, pre-eclampsia, diabetes,  gestational diabetes, hypertension (above 140/90), and hypotension (below 90/60),  Intrauterine growth restriction (IUGR), polyhydramnious, and oligohydramnious).  -  Pre-gestational body mass index (BMI) above 40 kg/m2  -  Use of fetal scalp-electrode during the experiment  -  Use of pacemakers and other electronic implants  -  Severe arrhythmia  -  Present musculoskeletal illnesses (including myopathy and arthritis).  -  Chronic pain within last 6 months (Pelvic girdle pain (PGP) to a mild degree (VAS 0-6  cm) is accepted in the experiment. Severe degree (VAS 6-10 cm) (e.g. bedridden or  difficulty walking) especially within 24 hours before birth is excluded).  -  Present/previous neurologic illnesses (including epilepsy, migraine, and sclerosis).  -  Present medicated mental disorders (including dementia, personality disorders,  bipolar, ADHD, and anxiety).  -  Dermatological disorders (including skin allergy, tattoos or scars on the locations of  electrodes)  -  Use of other long-acting pain relief before the experiment (including Epidural,  Morphine less than 16 hours before experiment), Acupuncture, Paracetamol (less than 8  hours before experiment), Cocktail (less than 8 hours before experiment), nitrous  oxide (less than one hour before experiment), sterile water injection (less than two  hours before experiment).  -  Use of TENS 48 hours before the trial  -  Drug addiction defined as the use of cannabis, opioids or other drugs.  -  Smokers  -  Lack of ability to cooperate

-  cooperation of an International team with many years of experience in surgical  management of lymphedema  -  description of an effective surgical strategy to treat cancer-related lymphedema, a high  incidence pathology  -  the combination of LVA and liposuction guarantees long lasting results Cancer-related lymphedema represents one of the major complications of cancer treatment,  especially for breast and gynecologic cancers. Moreover, it has high impact on cancer  survivors and healthcare systems. Lymphedema management still remains challenging. The better  understanding of lymphedema physiopathology as well as the development of sophisticated  surgical and diagnostic techniques have led to effective strategies to address lymphedema  patients but, despite the considerable interest in international literature, no consensus  exist. The combination of LVA and liposuction may represent an effective strategy in treating  patients with cancer-related lymphedema, in order to reach a significant decrease in volume  and reduction of lymphangitis rate as well as stable results in time. In addition, it has the  aim of being minimally invasive and well tolerated by patients Inclusion Criteria:  -  free from cancer disease Exclusion Criteria:  - persistence of the neoplastic pathology  - patients affected by primary lymphedema

Fluid status and congestion can be determined by the CPM wearable device and correlates with  invasive measures, non-invasive measures and biochemical markers of congestion and changes in  congestion. HF is associated with frequent and lengthy hospitalisations. These hospitalisations are  usually as a result of congestion. The signs of congestion that can be recognised by  physicians or health care professionals such as lung crackles or worsening of peripheral  oedema are often seen at a late stage before an intervention can be made to prevent overt  decompensation and admission to hospital. Recognising changes in excess fluid status either  before a patient becomes unwell or during decongestion treatment is highly desirable so that  timely treatment can be started or so that treatment can be adjusted based on an individual's  response to therapy. The ability to assess patients by applying a single, non-invasive device  would potentially provide a useful tool for assessing a patient's congestion levels and allow  patients with progressive deterioration to be identified earlier. Inclusion Criteria:  Written informed consent  -  Male or female over18 years of age Cohort A  -  Meet European Society of Cardiology 1 (ESC) criteria for diagnosis of HF  -  Undergoing clinically-indicated RHC Cohort B  -  Established on haemodialysis for >90 days  -  Undergoing haemodialysis with target volume removal ≥1.5 litres fluid Cohort C  -  Meet ESC criteria for diagnosis of HF including heart failure  -  Requiring treatment with intravenous (IV) diuretics Training Cohort  -  Meet ESC criteria for diagnosis of HF including heart failure  -  Requiring treatment with intravenous (IV) diuretics Exclusion Criteria:  -  Unable to consent to inclusion in study due to cognitive impairment  -  Allergies or skin sensitivities to silicone-based adhesive  -  Skin breakdown or dermatological condition on the left chest or breast areas or chest  wall deformity where the device is placed  -  Pregnancy or breast-feeding  -  Conditions that may confound congestion assessments  -  COVID-19 infection.

This is a prospective, multi-center observational survey study to uncover how antibiotic  differences can influence utilization decisions. The purpose is to assess the trade-offs  between drug side effects and infection prevention that patients are willing to make when  taking prophylactic antibiotics. Misuse of antibiotics or non-adherence to prescribed  regimens is a public health issue that may be due to a variety of reasons including unclear  instructions, symptom improvement and adverse events Subjects will be healthcare providers  (physician or nurse) and individuals 18+ years of age in the dermatologic surgery waiting  area (including patients and accompanying individuals). Participants will complete a  conjoint.ly survey and choose between treatment (antibiotic vs no antibiotic) scenarios. This is a prospective, multi-center observational survey study to uncover how antibiotic  differences can influence utilization decisions. The purpose is to assess the trade-offs  between drug side effects and infection prevention that patients are willing to make when  taking prophylactic antibiotics. Misuse of antibiotics or non-adherence to prescribed  regimens is a public health issue that may be due to a variety of reasons including unclear  instructions, symptom improvement and adverse events Subjects will be healthcare providers  (physician or nurse) and individuals 18+ years of age in the dermatologic surgery waiting  area (including patients and accompanying individuals). Participants will complete a  conjoint.ly survey and choose between treatment (antibiotic vs no antibiotic) scenarios.  Adults in the dermatologic surgery department waiting room with age greater than or equal to  18 years (this includes both patients and accompanying individuals (family members, friends,  caregivers)) and healthcare providers in dermatologic surgery. A member of the study team  will approach patients in the Perelman Dermatology Clinic to determine if they meet inclusion  criteria and educate them about the study using the verbal script. If interested, patients  will receive a link to the online survey, which will contain an informed consent page.  Dermatology healthcare providers will be identified in clinic or from academic center staff  directories. Individuals meeting inclusion criteria will also be recruited from the  dermatologic surgery waiting rooms of other collaborating institutions (Penn State Health,  University of Missouri Health Care, Indiana University Health, University of Minnesota,  Oregon Health & Science University, Washington University in St. Louis, UT Southwestern, UC  Davis and Ohio State University) once approved by their IRB.  All data will be collected and stored in a secured password-protected conjoint.ly account  managed by the Penn Dermatologic Surgery Clinical Research Team. Collaborating institutions  will not have access to the survey responses. Data analysis: Multivariate random parameters  logit will be used to estimate preference weights for each attribute level. These preference  weights will be used to estimate the maximum acceptable risk of various side effects that  subjects would be willing to accept in exchange for infection prevention. Collaborating  researchers from other institutions will not be involved in data analysis. Inclusion Criteria:  -  Age ≥ 18 years  -  Individual in the dermatologic surgery waiting room: patient, caregiver, family member  or accompanying individual to patient receiving dermatologic surgery service, or  dermatology healthcare provider Exclusion Criteria:   -  Age less than 18 years.

This trial is a single-arm, multicenter phase Ib/II clinical study to evaluate the efficacy  and safety of Docetaxel for Injection (Albumin-bound) combined with Nivolumab and the  pharmacokinetic characteristics of Docetaxel in patients with recurrent or metastatic SCCHN  who are positive for PD-L1 expression and have progressed on or after platinum-based therapy. This study will be conducted in two stages (phase Ib and phase II). Phase Ib: To explore the  safety and tolerability of Docetaxel for Injection (Albumin-bound) (75 mg/m^2 and 100 mg/m^2)  combined with Nivolumab 360 mg. Dose exploration will be started at low dose and proceed in  turn.  Phase II: According to the recommended phase II dose (RP2D) determined in the phase Ib study,  a phase II study of Docetaxel for Injection (Albumin-bound) combined with Nivolumab will be  conducted to observe the efficacy of the combination regimen, with ORR as the primary study  endpoint. Simon's optimal 2-stage design will be adopted for phase II study.  All patients in Phase Ib and Phase II will be treated with Docetaxel for Injection  (Albumin-bound) combined with Nivolumab until participants meet the criteria for termination  or withdrawal criteria, for a maximum of 2 years Inclusion Criteria:  1. Age ≥ 18 years old and voluntarily signed the informed consent form.  2. Patients with histologically or cytologically confirmed SCCHN (primary tumor located  in the oral cavity, oropharynx, larynx or hypopharynx), with positive PD-L1  expression, and who are not suitable for local radical therapy.  3. Patients with platinum-based regimen failure, defined as:  1. . Recurrent or metastatic SCCHN with disease progression during or after  platinum-based therapy;  2. . Locally advanced head and neck carcinoma with recurrence or metastasis within 6  months after platinum-based therapy in previous multimodal therapy.  4. Previous or qualified tumor tissue samples are available for testing PD-L1.  5. Patients with oropharyngeal carcinoma should provide previous HPVp16  immunohistochemical test results, or eligible tumor tissue samples for testing HPV  status.  6. At least one measurable lesion confirmed by CT or MRI according to RECISTv1.1  (previously irradiated, progressive disease or tumor persistence ≥ 3 months after  radiotherapy can be considered as measurable lesions).  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.  8. Life expectancy ≥ 3 months.  9. Main organ function meets the following criteria within 7 days before treatment (no  medical supportive treatments such as blood component transfusion, human granulocyte  colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11, and  erythropoietin (EPO) within 2 weeks before administration of the investigational  product).  Absolute neutrophil count ≥1.5×10^9/L Platelets ≥90×10^9/L Hb≥90 g/L or ≥5.6 mmol/L  Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 40 mL/min Total bilirubin  ≤1.0×ULN (≤ 1.5 × ULN for patients with liver metastasis or liver cancer); Alanine  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN ( ≤ 2.5 × ULN  for patients with liver metastasis or liver cancer); Activated Partial Thromboplastin  Time (APTT) ≤ 1.5×ULN, International Normalized Ratio (INR) ≤ 1.5×ULN.  10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test  within 7 days prior to the first dose of the investigational drug. The patient and  his/her spouse must agree to take adequate contraception from signing of ICF through 6  months after last dose, during which time women should be nonlactating and men should  refrain from donating sperm. Exclusion Criteria:  1. Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal  carcinoma, SCCHN with unknown primary lesion, salivary gland carcinoma, or  non-squamous tissue carcinoma (e.g., mucosal melanoma).  2. Patients with active brain metastasis and leptomeningeal metastasis. Patients with  brain metastasis for whom there is no evidence of PD by MRI at least 8 weeks after  treatment and within 28 days before the first dose of the investigational drug can be  included; Those who do not require systemic cortisol therapy (prednisone > 10 mg/day  or equivalent) at least 2 weeks before the first dose of the investigational drug can  be included; Patients with skull base lesions without definite evidence of dural or  parenchymal brain involvement can be considered to be included only after discussion  with the sponsor's medical monitor.  3. History of other malignancies within 5 years prior to the first dose of the  investigational drug, except for the following: a. Any other invasive malignancy (for  which the patient has received adequate treatment) with disease free status lasting >  3 years, which will not affect the assessment of tumor efficacy as assessed by the  investigator; b. Cured basal cell or squamous cell skin carcinoma, superficial bladder  cancer, prostate cancer, cervical cancer, or breast cancer in situ, and other locally  curable cancers.  4. Patients with known or suspected autoimmune disease within 2 years before the first  dose of the investigational drug, except for the following: a. well-controlled type I  diabetes; b. well-controlled hypothyroidism requiring only hormone replacement  therapy; c. skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring  systemic treatment; d. patients who are not expected to relapse in the absence of  external triggers.  5. Patients with an uncontrollable third space effusion (e.g. pleural effusion, ascites,  or pericardial effusion), who, in the judgment of the investigator, are not suitable  for the study.  6. Patients with a history of severe cardiovascular disease within 6 months before the  first dose of the investigational drug, including but not limited to:  1. . Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia  requiring clinical intervention and third-degree atrioventricular block;  2. . History of myocardial infarction, angina pectoris, angioplasty and coronary  artery bypass surgery;  3. . Heart failure with New York Heart Association (NYHA) Classification of Class  III and above;  4. . Poorly controlled hypertension.  7. Patients with prolonged QT/QTc interval (QTcF > 480 ms, Fridericia's formula: QTcF =  QT/RR^0.33, RR = 60/heart rate) by ECG during the screening period and/or with left  ventricular ejection fraction (LVEF) ≤ 50% by echocardiography (ECHO) or multi-gated  acquisition (MUGA) during the screening period;  8. Patients with positive HCV antibody (+) (patients with negative HCV RNA can be  included, and anti-HCV treatment other than interferon is allowed), active hepatitis B  (patients with HBV DNA ≤ 500 IU/mL can be included, and anti-HBV treatment other than  interferon is allowed), known HIV positive or known acquired immunodeficiency syndrome  (AIDS) during the screening period.  9. Patients who have undergone major organ surgery within 4 weeks before the first dose  of the investigational drug, or who need to undergo elective surgery during the study.  10. Patients who fail to recover from the toxic responses caused by previous anti-tumor  treatment to Grade 1 and below (CTCAE 5.0), except for the following: Grade 2  neuropathy, alopecia, hypothyroidism caused by previous anti-tumor treatment  (including hormone replacement therapy) and toxicity without safety risks as judged by  the investigator.  11. Patients who have previously received T cell costimulating drugs or drugs acting on  immune checkpoint pathways (including PD-1, PD-L1/2, CTLA-4 inhibitors, etc.).  12. Patients who have previously received other immunotherapies and experienced ≥ Grade 3  irAE (immune-related adverse event).  13. Patients who have previously received taxanes (patients who previously received  taxane-containing induction chemotherapy and progressed after 6 months can be  included).  14. Patients who have received anti-tumor treatments such as chemotherapy, radiotherapy,  targeted therapy, immunotherapy and other clinical study drugs within 4 weeks before  the first dose of the investigational drug, and other conditions are as follows:  Local palliative radiotherapy within 2 weeks before the first dose of the  investigational drug; oral fluoropyrimidines, small molecule targeted drugs, etc.  within 2 weeks before the first dose of the investigational drug or within known 5  half-lives of the drug (whichever is longer); Traditional Chinese medicines with  anti-tumor indications within 2 weeks before the first dose of the investigational  drug.  15. Patients who have received corticosteroid (prednisone > 10 mg/day or equivalent) or  other immunosuppressive therapies within 2 weeks before the first dose of the  investigational drug, except for the following: a. use of topical, ocular,  intra-articular, intranasal and inhaled glucocorticoids; b. short-term use of  glucocorticoids for prophylaxis (such as prevention of contrast agent allergy).  16. Patients who have received live attenuated vaccine within 2 weeks before the first  dose of the investigational drug or planned to receive live attenuated vaccine during  the study period.  17. Patients who have used potent inhibitors or inducers of CYP3A4 within 2 weeks before  the first dose of the investigational drug.  18. Patients with known ≥ Grade 3 hypersensitivity and/or contraindication to albumin or  monoclonal antibodies.  19. Other situations that the investigator considers not suitable for participating in the  clinical study, including but not limited to: the patient is complicated by severe or  uncontrolled medical conditions, which interfere with the interpretation of study  results and affect the study compliance.

Temporomandibular joint (TMJ) arthroscopy has been used successfully for intra-articular  disorders. Until now, limited studies are available regarding the clinical evidence of  bilateral TMJ arthroscopy for Dimitroulis 2-3. This prospective study investigated the  efficacy of TMJ arthroscopy in patients with bilateral disorders, and also the need for a  posterior surgery. Temporomandibular joint (TMJ) arthroscopy has been used successfully for intra-articular  disorders. It was first introduced by Onishi at 1975, as a pioneering technique to treat  painful joints and has been associated with a reduction in the number of open joints  surgeries. This minimally invasive technique allows observation of the TMJ upper compartment  tissues, and sometimes the lower compartment. Moreover, this intervention allows joint lysis  and lavage (level 1 arthroscopy) and intra-articular surgical procedures (level 2-3  arthroscopy).  Recent studies updated that TMJ arthroscopy promotes a reduction in pain and inflammatory  process and restoring the mandibular function with low morbidity. Moreover, TMJ arthroscopy  seems to be also long-term effective for relieving TMJ symptoms. Until now, limited studies  are available regarding the clinical evidence of bilateral TMJ arthroscopy for Dimitroulis  2-3. This prospective study investigated the efficacy of TMJ arthroscopy in patients with  bilateral disorders, and also the need for a posterior surgery. Inclusion Criteria:  -  age >16 years;  -  clinical diagnosis of bilateral intra-articular disorder;  -  clinical criteria for bilateral TMJ arthroscopy;  -  magnetic resonance imaging (MRI) assessing the intra-articular derangement Exclusion Criteria:  -  The exclusion criteria included any history of previous TMJ surgical intervention or  any facial trauma within the last 4 weeks prior the study.  -  Severe medical problems or mental illness, and pregnancy were also exclusion criteria

The purpose of this clinical study is to evaluate the surgical, refractive, and visual  outcomes with implantation of an investigational intraocular lens (IOL). Eligible subjects will be enrolled into one of two groups: BAL-FAIOL IOL or Monofocal IOL.  Both eyes will receive cataract surgery with IOL implantation. IOL implantation in the second  eye is intended to occur between 7 and 15 days after IOL implantation in the first eye.  Subjects will be followed for 1 year after implantation. Inclusion Criteria: None Exclusion Criteria: None

Managing patients with renal failure requires an understanding of the molecular mechanisms  that lead to its occurrence (i.e. upstream of the disease), its worsening and its persistence  (i.e. downstream), while also specifying the risk of worsening renal failure (risk  stratification, intolerance to the treatment or complications (infectious, metabolic,  cardiovascular, cancer…). Nephrogene 2.0 aims to study these different components of kidney,  immune and solid organ transplantation (SOT)-related diseases. Acute renal failure (ARF) and chronic kidney disease (CKD) are frequent pathologies (850  million people are affected worldwide). Renal failure is associated with an increased  morbidity and mortality, including an increased risk of infections, drug toxicity and  cardiovascular death. The causes of renal failure are numerous: metabolic (diabetes,  hypertension), immunological (autoimmune diseases, monoclonal gammopathies), toxic  (environment, drugs), genetic, infectious, ischemic, paraneoplastic... Any episode of ARF is  also accompanied by a risk of secondary CKD (relative risk multiplied by 9).  The mechanisms leading to renal failure are multiple and combine predisposing genetic  factors, inadequate intra-renal or systemic immune response, endothelial and epithelial  dysfunctions, and potentially inappropriate regenerative capacity. In addition, renal failure  or its treatment itself may be accompanied by additional renal lesions (e.g. nephrotoxicity  of calcineurin inhibitors used as anti-rejection treatment in transplantation, hemodynamic  intolerance with secondary ARF during hemodialysis sessions, iatrogenic ARF when using  diuretics or inhibitors of the renin angiotensin system) or extra-renal complications (e.g.  immunosuppression and infections induced by immunomodulatory therapies during autoimmune  diseases or for prevention of transplant rejection; vascular diseases secondary to  phosphocalcic disorders).  Patients included in the NEPHROGENE 2.0 cohort will be followed during 10 years and clinical  data and biological samples will be collected at the inclusion in the cohort, at each  monitoring programmed in their usual care and and at each event (infection, acute kidney  injury, cancer…). Samples will be collected according to the symptoms of the patients. Inclusion Criteria:  -  Patients (> 18 year of age) with kidney disease or at risk to develop a kidney  disease,  -  Patients followed by a practitioner of the Department of Nephrology and Organ  Transplantations of the University Hospital of Toulouse (France) Exclusion Criteria:  -  consent deny  -  inability of the patient or its family to give consent.

Background:  Bladder and bowel dysfunction (BBD) is characterized by lower urinary tract symptoms  accompanied by bowel complaints. BBD is a common condition in childhood. The present  treatment strategy for BBD is a step-wise approach starting with management of bowel symptoms  before initiation of standard urotherapy and further medical treatment of LUTS symptoms. This  is, however, based on clinical experience and few retrospective, non-randomized studies and  high-level evidence of the succession of the elements in treatment of BBD children is  missing.  Our microbiome, and its role in health and disease, has gained increased focus during the  past years. Studies suggest the urine and gut microbiome to be critical for maintenance of a  well-functioning bladder- and bowel system. The microbiome in children is only sparsely  investigated and its role in BBD is to the investigator's knowledge still unexplored.  Study 1:  Aim: To investigate if combination therapy is more effective in treating urinary incontinence  in BBD children.  Materials and methods: A prospective randomized multicentre study on children with BBD  (n=100) between 5-14 years and 9 months old. They are randomized to: 1) Medical treatment of  bowel symptoms (n=50) or 2) Medical treatment of bowel symptoms combined with standard  urotherapy.  The effect of treatment will be evaluated after 3 months. Primary endpoint: Resolution of  incontinence after treatment. Secondary endpoint: Improved quality of life after successful  treatment of urinary incontinence.  Study 2:  Aim: To investigate the urofecal microbiome in children with BBD  Materials and methods:  1. A cohort study to investigate, whether the urofecal microbiome can predict response to  treatment and whether it changes during treatment period  2. A case control study to investigate whether the urofecal microbiome is different in  children with BBD and recurrent UTI 's and children with BBD without recurrent UTI 's.  The study population consists of children with BBD included in study 1. A urine-, stool  sample and a perineum swab will be collected from all participants before and after  treatment. Bacterial DNA will be extracted and the microbiome will be determined.  Perspectives:  BBD is a common condition in childhood. It is associated with a considerable psychological  burden and a risk of more severe physical complications.  The studies will provide basic knowledge about characteristics of the BBD patients and  contribute new information about the optimal treatment of BBD children. Background Bladder and bowel dysfunction (BBD) is characterised by lower urinary tract  symptoms (LUTS) accompanied by bowel complaints, primarily functional constipation and/or  faecal incontinence. To standardise the terminology used for BBD, LUTS symptoms related to  the disease have been defined by International Children's Continence Society (ICCS).  The prevalence of BBD is probably underestimated but studies suggest BBD to be present in up  to 20 % of school children and to represent up to 40% of paediatric urology consults.  Embryological, anatomical and functional interactions between the rectum and urinary bladder  are well known. Bladder and bowel are anatomically closely related and share innervation from  the parasympathetic S2-S4 and sympathetic L1-L3 nerve roots.  Research on successful treatment of BBD is sparse, with only few retrospective,  non-randomized studies, documenting that treatment of defecation problems in children with  BBD enhances successful management of lower urinary tract disturbances such as daytime  urinary incontinence (DUI), enuresis and urinary tract infections (UTI's). Based on this  knowledge and clinical experience, the present treatment strategy for children with BBD is a  step-wise approach starting with management of bowel symptoms before initiation of standard  urotherapy and further medical treatment of LUTS symptoms. Standard urotherapy encompasses  information and demystification of the disorder along with behavioural modification such as  timed voiding, proper voiding posture, avoidance of holding manoeuvers and balanced fluid  intake. Standard urotherapy is well-established as first-line treatment for children with  LUTS. However, high-level evidence of the succession of the elements in treatment of BBD  children is missing.  BBD is commonly associated with vesicoureteral reflux (VUR) and recurrent UTI's, which may  lead to renal scarring , kidney failure and hypertension. It is a potential cause of  significant physical and psychosocial burden for children and families. Therefore,  optimization of treatment is critical to avoid secondary comorbidities.  Our microbiome, and its role in health and disease, has gained increased focus during the  past few years.  Studies suggest the urine and gut microbiome to be critical for maintenance of a  well-functioning bladder- and bowel system.  Dysbiosis is defined by the presence of unbalanced and disease-promoting composition of the  microbiome. It is well-established that dysbiosis is associated with constipation in children  and the condition is suspected to be involved in urological disorders such as overactive  bladder, urge, incontinence and recurrent UTI's in adults. However, the composition of the  urine microbiome in children is only sparsely investigated and its role in BBD and childhood  UTI's is to the investigator's knowledge still unexplored.  Study 1: Does successful treatment of bowel symptoms resolve urinary incontinence in children  with BBD? Aim and hypothesis Aim: To investigate if effective treatment of bowel problems  resolves urinary incontinence in BBD children.  The hypothesis of the investigators is:  1. Treatment of bowel symptoms resolves urinary incontinence in BBD children.  2. It is more effective to initiate urotherapy from the beginning in combination with  treatment of bowel symptoms instead of the present regime where bowel symptoms are  managed before urotherapy is started.  3. Succesful treatment of urinary incontinence in children with BBD improves their quality  of life.  1.2 Materials and methods A prospective multicentre randomised study on children with BBD  referred to the Pediatric Incontinence and Gastroenterology outpatient clinics at the  Department of Pediatrics, Aarhus University Hospital, Aalborg University Hospital and  Regional Hospital Goedstrup.  Children (n=100) between 5-14 years and 9 months diagnosed with BBD at their first visit to  the outpatient clinic will be included if they meet in- and exclusion criteria.  The included children will be randomised to one of the following treatments:  1. Medical treatment of bowel symptoms in accordance with the guidelines of The European  Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=50)  2. Medical treatment of bowel symptoms in accordance with the ESPGHAN guidelines combined  with standard urotherapy (n=50)  At first visit to the outpatient clinic, enrolled children will undergo physical examination  including neurological examination. Data on medical history will be collected including  number of and time for UTI's. Participants will be asked to fill in a 48-hour flow-volume  chart and in case of enuresis nocturna the chart will also include registration for 7 nights.  Participants will also fill in "Toerfisk" which is a validated tool to monitor severity of  urinary incontinence. Routine uroflowmetry will be performed for further evaluation of lower  urinary symptoms. A urine sample will be collected for diagnosing on-going UTI and for  microbiome analysis in study 3. The children will be screened for constipation in accordance  with the ROME IV criteria. Rectal examination will be performed or transrectal diameter will  be evaluated with point-of-care ultrasound. Stool sample and perineum swab will be collected  for microbiome analysis.  The psychological burden from the children´s BBD condition will be evaluated by PinQ, a  validated questionnaire used for assessment of quality of life according to the incontinence  issue of the patients.  All participants will be informed about bladder and bowel function in order to demystify the  disorder. Daily defecation will be induced by reconditioning to normal bowel habits through  timed toilet sitting and daily administration of laxatives (e.g. PEG3350) in relevant dosage  according to the ESPGHAN guidelines.  Participants randomized to combined medical treatment for bowel symptoms and urotherapy will  be instructed in urotherapy in accordance with earlier description.  After 1 month of treatment the participants will be contacted by telephone to ensure  compliance and for adjustment of laxative dose depending on the bowel symptoms.  The second visit in the outpatient clinic will be after 3 months of treatment. Before the  consultation, the participants will be asked to fill in a second flow-volume chart as well as  "Toerfisk" and PinQ questionnaires. Uroflowmetry will be repeated and a second urine sample  will be collected for stix, culturing and microbiome analysis. Bowel symptoms will be  evaluated using ROME IV, rectal examination and transrectal diameter and a second stool  sample and perineum swab will be collected for microbiome analysis for study 3.  Data storage Data will be entered into RedCap, which is a secure web platform for building  and managing online databases.  Power estimation The sample size (n=100) was calculated for each group to achieve a power of  80% for detecting a difference in proportions of 0.30 between the two groups (test -  reference group) at a two sided p-value of 0.05.  Study 2: Urine, perineal and gut microbiome in children with BBD before and after treatment  Aim and hypothesis To investigate the urine, perineal and gut microbiome in children with BBD  before and after treatment.  The hypothesis of the investigators is that  1. Response to treatment can be predicted by the composition of the urine, perineal and gut  microbiome in children with BBD.  2. The composition of the urine, perineal and gut microbiome is different in BBD children  with recurrent UTI's compared to BBD children without recurrent UTI's.  3. The urine, perineal and gut microbiome in children with BBD will change when bladder and  bowel symptoms successfully treated.  Materials and methods  The study is a multicentre study consisting of two elements:  1. a cohort study to investigate, whether the urine, perineal and gut microbiome can  predict response to treatment and whether it changes during treatment period  2. a case control study to investigate whether the urine, perineal and gut microbiome is  different in children with BBD and recurrent UTI 's and children with BBD without  recurrent UTI 's.  The study population consists of children with BBD included in study 1.  Collection and analysis of samples A urine-, stool sample and a perineum swab will be  collected from all participants before initiation of treatment and after 3 months of  treatment as described in study 1. Bacterial DNA will be extracted and the microbiome will be  determined.  Data storage Biological material will be pseudonymised and stored in a -80 degree fridge  until analysis is performed.  Statistical analysis for all 3 studies Distribution and variance will be analysed by QQ plot,  Shapiro-Wilks test and Bartletts test. Microbiota alpha-diversity will be addressed by ASV  richness, Faith's phylogenetic diversity, Shannon diversity index, and Pielou's evenness  index. Beta-diversity analysis will include principal coordinate analysis (PCoA) using  Bray-Curtis dissimilarity, weighted and unweighted UniFrac. Parametric data will be compared  using Student's t-test or one-way ANOVA and Tukey´s post hoc test, while non-parametric data  will be compared with Kruskal-Wallis test or Mann-Whitney U-test. Chi Squared test will be  used for proportions. Level of significance will be as following *: p <0.05, **: p<0.01 and  ***: p<0.001.  Ethics The studies will be conducted in accordance with the Declaration of Helsinki. All side  effects will be handled in accordance with the actual legislation. No risk or unknown side  effects are expected to urotherapy or medical treatment of bowel symptoms. No risk, side  effects or discomfort is expected from collection of urine, stool and perineum samples or  from uroflowmetry or transabdominal ultrasound.  Perspectives BBD is a common condition in childhood. It is associated with a considerable  psychological burden and a risk of more severe physical complications.  The term BBD is recently defined and therefore only sparsely investigated. The studies will  provide basic knowledge about characteristics of the BBD patients and contribute new  information about the optimal treatment of BBD children. Inclusion Criteria:  -  Age 5-14 years and 9 months at time of inclusion  -  Diagnosed with urinary incontinence and/or enuresis nocturna defined by the ICCS  criteria  -  Diagnosed with constipation and/or faecal incontinence defined by the ROME IV criteria  -  Normal clinical examination  -  Parents/guardian can understand the written and spoken information  -  Informed assent to participation from both parents/guardian Exclusion Criteria:  -  Neuropathic or anatomical abnormalities in the urinary tract or gastrointestinal canal  -  Earlier surgical intervention of the urinary tract (except circumcision)  -  Neurological illness or earlier cerebral surgical intervention  -  On-going urinary tract infection  -  On-going treatment with anticholinergics and/or β3-adenoceptoragonist  -  On-going treatment with laxatives in correct dosage (PEG3350 1-2 g/kg/day)  -  Inflammatory bowel disease  -  Other disorder affection bladder or bowel function  -  For Study 2 (microbiome): Systemic antibiotics within the past 3 months

This project adopts a prospective clinical trial study to compare and evaluate the efficacy  of local transplantation of human umbilical cord mesenchymal stem cells combined with silver  ion dressing and simple silver ion dressing in the treatment of venous lower extremity ulcer  wounds. To improve the healing rate and quality of life of patients. Chronic wounds refer to the pathological changes such as cell senescence, imbalance of  synthesis and degradation of extracellular matrix, and decreased activity of growth factors  caused by different reasons when the wound is prolonged and does not heal after conventional  treatment for more than 1 month without healing tendency. Chronic wound can be caused by a  variety of diseases, including arterial disease, diabetes, vasculitis, venous disease and  skin malignant tumor, chronic venous insufficiency (CVI) is a disease leading to chronic  wound, Venous ulcer (VLU) of lower limbs is the advanced manifestation of CVI, and the  incidence of this disease ranges from 0.4% to 1.3% in China. 60% of VLU patients' ulcer  wounds heal in 3-6 months, 33% in 12 months, and 7% May be permanently unhealed. The  probability of recurrence is as high as 70% in patients 3-5 months after wound healing, which  not only seriously affects the health and quality of life of patients, but also causes a very  heavy social medical burden. At present, the conventional treatment for VLU mainly includes  drug therapy, stress therapy, wound treatment and surgical treatment, but the therapeutic  effect is not ideal. Inclusion Criteria:  1. Age from 18 to 70, no gender limitation;  2. It met the diagnostic criteria of venous ulcer of lower limbs in Clinical Vascular  Surgery (5th edition), and the following conditions were met: the ulcer lasted for  more than 1 month; The wound area was between 10cm2 and 40cm2. Wound depth: All wounds  were deep tissue ulcers below the epidermis.  3. Participate in the clinical study voluntarily, observe the study procedure, and  observe the curative effect cooperatively. Exclusion Criteria:  1. Pregnant or lactation women; Women who have planned to have children recently (within  6 months);  2. Patients with peripheral artery disease with ankle-brachial index (ABI) < 0.8;  3. Patients with active clinical systemic infection;  4. Serious skin wound infection is not under control;  5. low immune function and systemic failure; Severe heart, liver, lung, kidney and other  important organ lesions (ALT, AST, Cr & GT; Normal 1.5 times, congestive heart failure  ejection fraction &lt; Normal 30%) and severely impaired hematopoietic function;  6. Abnormal coagulation function or current anticoagulant treatment;  7. Systemic autoimmune diseases in the active stage;  8. With systemic organ or hematological malignancy;  9. PERSONS infected with HIV or addicted to drugs, tobacco and alcohol;  10. Have a clear history of mental illness;  11. Participation in clinical studies of any drug within 1 month prior to treatment (or  the 5 half-life of the investigational drug, whichever is longer).

Transfusion practice for surgical patients has changed from replacing surgically lost blood  with allogeneic blood transfusions to implementing strategies that reduce transfusion  requirements. Patient Blood Management (PBM), which is "the timely application of  evidence-based medical and surgical concepts designed to maintain haemoglobin concentration,  optimize hemostasis and minimize blood loss in an effort to improve patient outcome. There is  mounting evidence that multimodal patient blood management (PBM) programmes can be effective  at improving postoperative outcomes and reducing perioperative blood transfusions and costs  The Turkish Society of Anaesthesiologists PBM Task Force has been working on this subject and  studied transfusion practice throughout all through the peri-operative periods. Unfortunately  we documented a high transfusion rate in major surgical patients in Turkey. One of the  surgeries, that has high transfusion rate, was orthopaedic surgery. According to our recent  data we planned to implement PBM in major orthopaedic surgical patients and evaluate the  effects PBM in transfusion rate and patient outcomes. While some elements of PBM have a  strong evidence base in hip or knee replacement, such as the use of tranexamic acid (TXA) the  evidence for preoperative anaemia optimisation with iron is less robust. Implementing PBM all  through the operative period gains more importance. Active PBM Implementation: Patients undergoing hip or knee arthroplasty will be treated as  follows: PBM will be performed as shown in the graph below "PBM Implementation Group".  Active PBM group will be treated for preoperative anemia at least 3 weeks prior to the  surgical intervention as per the "Anemia Algorithm" below Other pillars of PBM will be also  performed to the treatment group as per the visual graph below. The parameters included in  the PBM pillars will be recorded including preoperative anemia parameters. Postoperative  variables and parameters related to complications will be recorded.  For the control group (Non-PBM group), the data of the patients, will be prospectively  included.  The 1:1 ratio of the control and active groups will be done. Inclusion Criteria:  In order to be eligible to participate in this trial, an individual must meet all of the  following criteria:  -  Signed patient informed consent  -  Male or female patient at least 18 years old  -  Patients scheduled for an elective major orthopaedic surgery (hip arthroplasty, knee  arthroplasty, primary and revision operations)  -  Patients with confirmed iron deficiency anemia (IDA), defined as Hb 100-130 g/L, and  serum ferritin < 100 ng/ml or TSAT < 20%.  Patients with iron deficiency anemia will be taken into surgery at least 3 weeks after the  treatment. Exclusion Criteria:  -  Patients that undergo emergency surgical procedure and trauma cases are excluded from  the study.  -  Patients with non-iron deficiency anaemia (thalassemia, sickle cell anaemia and etc.)  -  Patients with renal anaemia (Hb < 130 g/L and CCL < 50 mL/min, irrespective of iron  parameters) or any diagnosis that require EPO will be excluded  -  Patients with known anaphylactic/hypersensitivity reactions to parenteral iron  products.  -  Patients with iron overload or disturbances in utilization of iron (e.g.  haemochromatosis, hemosiderosis)  -  Patients with ≥3 times increase in aspartate aminotransferase or alanine  aminotransferase as per reference range.  -  Patients with excessive blood loss requiring massive transfusion (≥ 10 more red blood  cell units)  -  Patients with known myelodysplastic syndromes.  -  Patients with chronic kidney disease with an estimated GFR < 30 ml/min or with  end-stage renal disease requiring scheduled dialysis.  -  Patients with known urinary tract infections with urea-splitting bacteria  -  Any patient judged to lack the ability to give informed consent or perform the trial  assessments (e.g. due to dementia)  -  Women who are pregnant or breast feeding  -  Intention to become pregnant during the course of the study,  -  Lack of safe contraception, defined as: Female participants of childbearing potential,  not using and not willing to continue using a medically reliable method of  contraception for the entire study duration, such as oral, injectable, or implantable  contraceptives, or intrauterine contraceptive devices, or who are not using any other  method considered sufficiently reliable by the investigator in individual cases  (Female participants who are surgically sterilized / hysterectomized or  post-menopausal for longer than 2 years are not considered as being of child bearing  potential),  -  Known or suspected non-compliance, drug or alcohol abuse,  -  Participation in another study with investigational drug within the 30 days preceding  and during the present study

This will be a randomized, double-blind, double-dummy, placebo- and active-controlled, 6  treatment, 6-period crossover single-dose, Williams square design study in healthy male  and/or female adult, non-drug-dependent recreational opioid users. The study includes Screening, a Qualification Phase consisting of a Naloxone Challenge and  Drug Discrimination crossover study, a Treatment Phase and Follow-up. Following successful  completion of the Qualification Phase the participants will be enrolled in the Treatment  phase. The Treatment Phase is a randomized, double-blind, double dummy, placebo- and active  controlled, 6 treatment, 10-sequence, 6 period crossover, single-dose, Williams square design  study in healthy male and/or female adult, non drug-dependent recreational users. On Day 1 of  each of the Treatment Phase 6 periods, which will be separated by a washout of at least 14  days, participants will receive an oral dose of either gabapentin 600 mg or 1200 mg alone, or  concomitantly with a 20 mg dose of oxycodone HCl or 20 mg monotherapy of oxycodone HCl or a  placebo. Study treatments will be administered under fasted conditions (overnight fast and no  food until 4 hours after dosing). Water will be allowed without restriction until 1 hour  prior to dosing and 1 hour after dosing. Inclusion Criteria:  1. Male and female participants must be 18 to 55 years of age, inclusive, at the time of  screening. Participants must meet reproductive criteria as outlined in the protocol.  2. Male and female participants who are overtly healthy. Healthy is defined as no  clinically relevant abnormalities identified by a detailed medical history, complete  physical examination, vital signs, 12-lead ECG, and/or clinical laboratory tests.  3. Participants must have drug abuse experience with opioids; ie, must have used opioids  for non-therapeutic purposes (ie, for psychoactive effects) on at least 10 occasions  within the last year and at least once in the 8 weeks before the Screening Visit  (Visit 1).  4. Participants must satisfactorily complete both the Naloxone Challenge and the Drug  Discrimination.  5. Participants who are willing and able to comply with all scheduled visits, treatment  plan, laboratory tests, lifestyle considerations, and other study procedures.  6. Body mass index (BMI) of 17.5 to 34 kg/m2, inclusive; and a total body weight ≥50 kg  (110 lb).  7. Capable of giving signed informed consent as described in the protocol, which includes  compliance with the requirements and restrictions listed in the informed consent  document (ICD) and in this protocol. Exclusion Criteria:  1. Current or past diagnosis of any type of drug dependence within the past year.  Diagnosis of substance and/or alcohol dependence (excluding caffeine and nicotine)  will be assessed by the Investigator using the Diagnostic and Statistical Manual of  Mental Disorders-IV (DSM-IV) criteria performed at Screening. Current drug use will be  allowed if the candidate can produce a negative urine sample and are free of any  signs/symptoms of withdrawal. The candidate will be informed if they have a positive  breathalyzer test.  2. Evidence or history of clinically significant hematological, renal, endocrine,  pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or  allergic disease (including drug allergies, but excluding untreated, asymptomatic,  seasonal allergies at the time of dosing).  3. Any condition possibly affecting drug absorption (eg, gastrectomy) excluding  cholecystectomy within 1 year prior to study.  4. Abnormal baseline EtCO2 <35mm Hg or >45 mm Hg.  5. Clinical or laboratory evidence of active hepatitis A infection or a history of human  immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C, and/or positive  testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody  (HBcAb), or hepatitis C antibody (HCVAb).  6. Participants with active suicidal ideation or suicidal behavior within 5 years prior  to Screening as determined through the use of the Columbia Suicide Severity Rating  Scale (C-SSRS) or active ideation identified at Screening or on Day 0.  7. Participants with any history of sleep apnea, myasthenia gravis or glaucoma.  8. Other acute or chronic medical or psychiatric condition including recent (within the  past year) or active suicidal ideation or behavior or laboratory abnormality that may  increase the risk associated with study participation or investigational product  administration or may interfere with the interpretation of study results and, in the  judgment of the investigator, would make the participant inappropriate for entry into  this study.  9. Use of prescription or nonprescription drugs and dietary supplements within 7 days or  5 half lives (whichever is longer) prior to the first dose of investigational product.  (Refer to Section 6.5 for additional details).  10. Herbal supplements, herbal medications and hormone replacement therapy must be  discontinued at least 28 days prior to the first dose of study medication.  11. Previous administration with an investigational drug within 30 days (or as determined  by the local requirement) or 5 half lives (whichever is longer) preceding the first  dose of investigational product used in this study.  12. Positive urine drug screen (UDS) for substances of abuse at each admission in  Qualification and Treatment Phase, excluding tetrahydrocannabinol (THC). If a  participant presents with a positive UDS excluding THC at any admission or any visit,  the investigator, at his/her discretion, may reschedule a repeat of UDS until the UDS  is negative, excluding THC, before the participate is permitted to participate in any  phase of the study.  13. Unable to abstain from using THC during the Qualification and Treatment Phase of the  study.  14. Has participated in, is currently participating in, or is seeking treatment for  substance and/or alcohol related disorders (excluding nicotine and caffeine).  15. Has a positive alcohol breathalyzer or urine test at each admission to the study  center during Qualification and Treatment Phases. Positive results may be repeated  and/or participants re scheduled at the Investigator's discretions.  16. Participants are heavy smokers or users of other types of nicotine products (>20  cigarettes equivalents per day).  17. Participants are unable to abstain from smoking for at least 2 hours before and at  least 8 hours after study drug administration.  18. Screening sitting blood pressure (BP) >=140 mm Hg (systolic) or >=90 mm Hg  (diastolic), following at least 5 minutes rest. If BP is >=140 mm Hg (systolic) or  >=90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the  3 BP values should be used to determine the participant's eligibility. Repeated BP  tests should be spaced at least 5 minutes apart.  19. Baseline (screening) 12 lead electrocardiogram (ECG) that demonstrates clinically  relevant abnormalities that may affect participant safety or interpretation of study  results (eg, baseline corrected QT (QTc) interval as determined by the Fridericia  method (QTcF) >450 msec, complete left bundle branch block [LBBB], signs of an acute  or indeterminate age myocardial infarction, ST T interval changes suggestive of  myocardial ischemia, second or third degree atrioventricular [AV] block, or serious  bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is >450  msec, this interval should be rate corrected using the Fridericia method and the  resulting QTcF should be used for decision making and reporting. If QTcF exceeds 450  msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average  of the 3 QTcF or QRS values should be used to determine the participant's eligibility.  Computer interpreted ECGs should be overread by a physician experienced in reading  ECGs before excluding participants.  20. Participants with ANY of the following abnormalities in clinical laboratory tests at  screening, as assessed by the study specific laboratory and confirmed by a single  repeat test, if deemed necessary:  -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >=1.5 ×  upper limit of normal (ULN);  -  Total bilirubin level >=1.5 × ULN; participants with a history of Gilbert's  syndrome may have direct bilirubin measured and would be eligible for this study  provided the direct bilirubin level is <= ULN.  21. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more  within 60 days prior to dosing.  22. History of sensitivity to heparin or heparin induced thrombocytopenia.  23. Unwilling or unable to comply with the criteria in the Lifestyle Considerations  section of this protocol.  24. History of hypersensitivity to gabapentin or oxycodone or any of the components in the  formulation of the study products.  25. Investigator site staff members directly involved in the conduct of the study and  their family members, site staff members otherwise supervised by the investigator, or  Sponsor employees, including their family members, directly involved in the conduct of  the study.

This phase Ib/II trial studies the side effects and best dose of ribociclib, tucatinib, and  trastuzumab for the treatment of HER2 positive breast cancer that has spread to other parts  of the body (metastatic), and then compares the effect of ribociclib, tucatinib, trastuzumab  with or without fulvestrant to docetaxel, carboplatin, trastuzumab, and pertuzumab (standard  of care) for the treatment of early stage breast cancer before surgery (neoadjuvant therapy).  Ribociclib and tucatinib may stop the growth of tumor cells by blocking some of the enzymes  needed for cell growth. Trastuzumab is a form of targeted therapy because it attaches itself  to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors.  When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are  blocked and the tumor cell may be marked for destruction by the body's immune system.  Pertuzumab is a monoclonal antibody that may interfere with the ability of tumor cells to  grow and spread. Estrogen can cause the growth of breast tumor cells. Fulvestrant blocks the  use of estrogen by the tumor cells. Chemotherapy drugs, such as docetaxel and carboplatin,  work in different ways to stop the growth of tumor cells, either by killing the cells, by  stopping them from dividing, or by stopping them from spreading. Giving ribociclib,  tucatinib, and trastuzumab with or without fulvestrant before surgery may make the tumor  smaller and may reduce the amount of normal tissue that needs to be removed. PRIMARY OBJECTIVES:  I. To assess the safety of the combination of ribociclib, tucatinib, and trastuzumab in  patients with metastatic, HER2+ breast cancer. (Phase 1 Dose Escalation Trial) II. To  determine the recommended phase 2 dose of ribociclib when combined with tucatinib and  trastuzumab. (Phase 1 Dose Escalation Trial) III. To assess the pathologic complete response  (pCR). (Phase 2 Neoadjuvant Study)  SECONDARY OBJECTIVES:  I. To evaluate the pharmacokinetics of ribociclib and tucatinib when given in combination.  (Phase 1 Dose Escalation Trial) II. To assess the clinical objective response rate after 3  cycles via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase 1 Dose  Escalation Trial) III. To assess the clinical objective response rate in the experimental  arms. (Phase 2 Neoadjuvant Study) IV. To assess quality of life by evaluating toxicity burden  using a quality of life (QOL)/patient-reported outcomes (PRO) questionnaire- the European  Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30  (EORTC QLQ-C30) instrument. (Phase 2 Neoadjuvant Study) V. To assess the molecular changes in  tumor biomarkers after 1 cycle of targeted therapy (anti-HER2, anti-estrogen, and CDK 4/6  directed therapy). (Phase 2 Neoadjuvant Study) VI. Pathological Assessment According to  Residual Cancer Burden (RCB) Index at surgery. (Phase 2 Neoadjuvant Study)  EXPLORATORY OBJECTIVE:  I. To investigate potential serum and tumor predictive biomarkers to predict response to  experimental therapy. (Phase 2 Neoadjuvant Study)  OUTLINE: This is a phase Ib, dose-escalation study of ribociclib followed by a phase II  study.  PHASE Ib: Patients receive ribociclib orally (PO) once daily (QD) on days 1-21, tucatinib PO  twice daily (BID) on days 1-28, and trastuzumab intravenously (IV) over 30-90 minutes every 7  days. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or  unacceptable toxicity.  PHASE II: Patients with hormone receptor (HR) positive status are randomized to Arm A or Arm  B. Patients with HR negative status are randomized to Arm B or Arm C.  ARM A: Patients receive ribociclib PO QD on days 1-21, tucatinib BID on days 1-28,  trastuzumab IV over 30-90 minutes every 7 days and fulvestrant subcutaneously (SC) on days 1  and 15 of cycle 1 and day 1 of every subsequent cycle. Cycles repeat every 28 days for up to  6 cycles in the absence of disease progression or unacceptable toxicity.  ARM B: Patients receive docetaxel IV over 1 hour on day 1, carboplatin IV on day 1,  trastuzumab IV over 30-90 minutes on day 1, and pertuzumab IV over 1 hour on day 1. Cycles  repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable  toxicity.  ARM C: Patients receive ribociclib PO QD on days 1-21, tucatinib BID on days 1-28, and  trastuzumab IV over 30-90 minutes every 7 days. Cycles repeat every 28 days for up to 6  cycles in the absence of disease progression or unacceptable toxicity.  After completion of study treatment, patients are followed-up within 7 and 30 days. Inclusion Criteria:  -  PHASE IB AND II: Patients over age of 18  -  PHASE IB AND II: Available archival tissue for confirmatory central HER2 testing.  Results not required prior to enrollment.  -  PHASE IB AND II: Left ventricular ejection fraction (LVEF) >= 50% based on  echocardiogram or multigated acquisition (MUGA).  -  PHASE IB AND II: Platelet count >= 100,000/mm^3 (within 7 days before enrollment)  -  For Phase Ib only: Phase Ib allows for red blood cell transfusion, filgrastim  (G-CSF), and hydration to meet eligibility requirements at the discretion of the  investigator  -  PHASE IB AND II: Hemoglobin >= 9.0 g/dL (within 7 days before enrollment)  -  For Phase Ib only: Phase Ib allows for red blood cell transfusion, G-CSF, and  hydration to meet eligibility requirements at the discretion of the investigator  -  PHASE IB AND II: Absolute neutrophil count (ANC) >= 1500/mm^3 (within 7 days before  enrollment)  -  For Phase Ib only: Phase Ib allows for red blood cell transfusion, G-CSF, and  hydration to meet eligibility requirements at the discretion of the investigator  -  PHASE IB AND II: Creatinine clearance >= 30 mL/min as calculated using the  Cockcroft-Gault equation or Serum creatinine =< 1.5 × upper limit of normal (ULN)  (within 7 days before enrollment)  -  For Phase Ib only: Phase Ib allows for red blood cell transfusion, G-CSF, and  hydration to meet eligibility requirements at the discretion of the investigator  -  PHASE IB AND II: Alanine aminotransferase (ALT) < 2.5 × ULN, except for patients with  liver metastasis, who are only included if the ALT is < 5 × ULN (within 7 days before  enrollment)  -  PHASE IB AND II: Aspartate aminotransferase (AST) < 2.5 × ULN, except for patients  with liver metastasis, who are only included if the AST is < 5 × ULN (within 7 days  before enrollment)  -  PHASE IB AND II: Total bilirubin =< 1.5 x ULN. Participants with Gilbert's syndrome  with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are  permitted (within 7 days before enrollment)  -  PHASE IB AND II: Serum Albumin >= 2.5 g/dL (within 7 days before enrollment)  -  PHASE IB AND II: International normalized ratio (INR)/prothrombin time (PT) and  activated partial thromboplastin time (aPTT) =< 1.5 × ULN (within 7 days before  enrollment)  -  PHASE IB AND II: Potassium within normal limits or corrected to within normal limits  prior to first dose  -  PHASE IB AND II: Magnesium within normal limits or corrected to within normal limits  prior to first dose  -  PHASE IB AND II: Total calcium (corrected for serum albumin) within normal limits or  corrected to within normal limits prior to first dose  -  PHASE IB AND II: Willingness and ability to comply with scheduled visits, treatment  plans, laboratory tests, and other study procedures  -  PHASE IB AND II: Patient can be premenopausal, perimenopausal, or post-menopausal at  the time of study entry.  -  Premenopausal status is defined as either:  -  Patient had last menstrual period within the last 12 months, OR  -  If on tamoxifen or toremifene, plasma estradiol and follicle stimulating  hormone (FSH) are in the premenopausal ranges according to central/local  laboratory definition, OR  -  In case of therapy-induced amenorrhea, plasma estradiol and/or FSH are in  the premenopausal ranges according to central/local laboratory definition  -  Perimenopausal status is defined as neither premenopausal nor  postmenopausal  -  Postmenopausal is defined as not meeting premenopausal status  -  For pre-menopausal patients: Confirmed negative serum pregnancy test  (beta-hCG) before starting study treatment or patient has had a  hysterectomy. Male and female participants of reproductive/childbearing  potential must agree to use a highly effective form of contraception or  avoid intercourse during and upon completion of the study and for at  least 7 months for females and 4 months for males after the last dose  of study drug  -  PHASE IB AND II: Male and female participants of reproductive/childbearing potential  must agree to use a highly effective form of contraception or avoid intercourse during  and upon completion of the study and for at least 7 months for females and 4 months  for males after the last dose of study drug. Highly effective contraception methods  include:  -  Total abstinence (when this is in line with the preferred and usual lifestyle of  the patient). Periodic abstinence (e.g. calendar, ovulation, symptothermal,  post-ovulation methods) and withdrawal are not acceptable methods of  contraception  -  Double barrier method of contraception. The following are considered adequate  barrier methods of contraception, must use 2: diaphragm, condom (by the partner),  sponge, or spermicide/spermicidal jelly.  -  Female sterilization (have had surgical bilateral oophorectomy with or without  hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before  taking trial treatment. In case of oophorectomy alone, only when the reproductive  status of the woman has been confirmed by follow up hormone level assessment.  -  Male partner sterilization (at least 6 months prior to randomization). For female  patients on the trial the vasectomized male partner should be the sole partner  for that patient. If vasectomy of the male partner is the highly effective method  of contraception chosen, the success of the vasectomy should be medically  confirmed according to local practice  -  Placement of an intrauterine device (IUD)  -  PHASE IB: Locally advanced/non-operable or metastatic HER2/neu amplified breast  cancer, defined as 3+ by immunohistochemistry (IHC), or IHC 2+ and fluorescence in  situ hybridization (FISH) + breast cancer  -  PHASE IB: Received 1 or more prior lines of HER2 directed therapy in the metastatic  setting  -  PHASE IB: Recommended by the patient's treating oncologist to receive a tucatinib  containing regimen as part of the next standard of care (SOC) line of therapy  -  PHASE IB: Eastern Cooperative Oncology Group (ECOG) performance status 0-2  -  PHASE IB: Measurable or non-measurable disease per RECIST 1.1  -  PHASE IB: Based on screening contrast brain magnetic resonance imaging (MRI), patients  must have one of the following:  -  No evidence of brain metastases  -  Untreated brain metastases not needing immediate local therapy. For patients with  untreated central nervous system (CNS) lesions > 2.0 cm on screening contrast  brain MRI, discussion with and approval from the medical monitor is required  prior to enrollment  -  Previously treated brain metastases  -  Brain metastases previously treated with local therapy may either be stable  since treatment or may have progressed since prior local CNS therapy,  provided that there is no clinical indication for immediate re-treatment  with local therapy in the opinion of the investigator  -  Patients treated with CNS local therapy for newly identified lesions found  on contrast brain MRI performed during screening for this study may be  eligible to enroll if all of the following criteria are met:  -  Time since whole-brain radiotherapy (WBRT) is >= 21 days prior to first  dose of treatment, time since stereotactic radiosurgery (SRS) is >= 7  days prior to first dose of treatment, or time since surgical resection  is >= 28 days  -  Other sites of disease assessable by RECIST 1.1 are present  -  Relevant records of any CNS treatment must be available to allow for  classification of target and non-target lesions  -  PHASE II: Operable HER2/neu amplified invasive breast cancer, defined as 3+ by IHC, or  IHC 2+ and FISH +  -  PHASE II: Known Ki67 status  -  PHASE II: Previously untreated operable invasive carcinoma of the breast greater than  2.0 cm (cT2) in size based on imaging or physical exam or imaging. Patients with  clinical node negative disease or clinical node (cN1/cN2) positive are allowed  provided they are deemed to have operable disease at study entry  -  PHASE II: Patients with clinically involved lymph nodes should not have evidence of  distant disease based on standard of care staging imaging prior to informed consent  form (ICF) signature  -  PHASE II: Breast cancer suitable for mandatory baseline core biopsy  -  PHASE II: No prior systemic therapy or radiotherapy for currently-diagnosed invasive  or non-invasive breast cancer  -  PHASE II: Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria:  -  PHASE IB AND II: Concurrent therapy with any other non-protocol anti-cancer therapy  -  PHASE IB AND II: History of any other malignancy within the past 5 years, with the  exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix  -  PHASE IB AND II: Proteinuria estimated by urine protein: creatinine ratio > 3.5 on a  random urine sample  -  PHASE IB AND II: Uncontrolled arterial hypertension despite optimal medical management  -  PHASE IB AND II: Patient has known active hepatitis B virus (HBV) or hepatitis C virus  (HCV), or Human immunodeficiency virus (HIV) infection (testing is not mandatory,  unless required by local regulation)  -  PHASE IB AND II: Uncontrolled infection; active, clinically serious infections (>  Common Terminology Criteria for Adverse Events [CTCAE] grade 2)  -  PHASE IB AND II: Clinically significant, uncontrolled heart disease and/or cardiac  repolarization abnormality, including any of the following:  -  History of documented myocardial infarction (MI), angina pectoris, symptomatic  pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to  study entry  -  Documented cardiomyopathy  -  Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated  acquisition (MUGA) scan or echocardiogram (ECHO)  -  Long QT syndrome or family history of idiopathic sudden death or congenital long  QT syndrome, or any of the following:  -  Risk factors for Torsades de Pointe (TdP) including uncorrected  hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or  history of clinically significant/symptomatic bradycardia  -  Concomitant medication(s) with a known risk to prolong the QT interval  and/or known to cause Torsades de Pointe that cannot be discontinued or  replaced by safe alternative medication (e.g., within 5 half-lives or 7 days  prior to starting study drug)  -  Inability to determine the corrected QT using Fridericia's formula (QTcF)  interval  -  Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia),  complete left bundle branch block, high-grade atrioventricular (AV) block  (e.g., bifascicular block, Mobitz type II and third degree AV block)  -  Systolic blood pressure (SBP) > 160 or < 90 mmHg  -  PHASE IB AND II: Congestive heart failure > New York Heart Association (NYHA) class 2  -  PHASE IB AND II: History of baseline QT prolongation > 450 msec  -  PHASE IB AND II: Unstable angina (angina symptoms at rest), new-onset angina (begun  within the last 3 months)  -  PHASE IB AND II: Myocardial infarction less than 6 months before start of test drug  -  PHASE IB AND II: Anti-arrhythmic therapy (beta blockers or digoxin are permitted)  -  PHASE IB AND II: Arterial or venous thrombotic or embolic events such as  cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis  or pulmonary embolism within 3 months before the start of study medication.  -  PHASE IB AND II: Participants receiving anticoagulation therapy are not allowed  -  PHASE IB AND II: Patients with evidence or history of bleeding diathesis. Any  hemorrhage or bleeding event >= CTCAE Grade 3 within 4 weeks of start of study  medication  -  PHASE IB AND II: Non-healing wound or ulcer  -  PHASE IB AND II: History of, or current autoimmune disease (other than Hashimoto's  thyroiditis with normal thyroid stimulating hormone [TSH])  -  PHASE IB AND II: Major surgical procedure or significant traumatic injury (as judged  by the investigator) within 28 days before start of study medication, open biopsy  within 7 days before start of study medication  -  PHASE IB AND II: Unable to swallow pills or has significant gastrointestinal disease  which would preclude the adequate oral absorption of medications  -  PHASE IB AND II: Patients with seizure disorder requiring medication  -  PHASE IB AND II: Known hypersensitivity to any of the study drugs, study drug classes,  or excipients in the formulation  -  PHASE IB AND II: Systemic continuous corticosteroid therapy at a daily dose higher  than 15 mg prednisone or equivalent is not allowed. Patients may be using topical or  inhaled corticosteroids. Previous corticosteroid therapy must be stopped or reduced to  the allowed dose at least 7 days prior to the first study drug administration. If a  patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated  to the maximum allowed dose after the patient has signed the consent document  -  PHASE IB AND II: History of having received an allogeneic bone marrow or organ  transplant  -  PHASE IB AND II: Chronic oxygen therapy  -  PHASE IB AND II: Use of a strong cytochrome P450 (CYP)2C8 inhibitor within 5  half-lives of the inhibitor or use of a strong CYP3A4 or CYP2C8 inducer within 5 days  prior to the first dose of study treatment  -  PHASE IB: Early stage (curable) breast cancer  -  PHASE IB: Based on screening brain MRI, patients must not have any of the following:  -  Any untreated brain lesions > 2.0 cm in size, unless discussed with medical  monitor and approval for enrollment is given  -  Ongoing use of systemic corticosteroids for control of symptoms of brain  metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent).  However, patients on a chronic stable dose of =< 2 mg total daily of  dexamethasone (or equivalent) may be eligible with discussion and approval by the  medical monitor  -  Any brain lesion thought to require immediate local therapy, including (but not  limited to) a lesion in an anatomic site where increase in size or possible  treatment-related edema may pose risk to patient (e.g. brain stem lesions).  Patients who undergo local treatment for such lesions identified by screening  contrast brain MRI may still be eligible for the study based on criteria  described under CNS inclusion criteria  -  PHASE IB: Known or suspected leptomeningeal disease (LMD) as documented by the  investigator  -  PHASE IN: Have poorly controlled (> 1/week) generalized or complex partial seizures,  or manifest neurologic progression due to brain metastases notwithstanding  CNS-directed therapy  -  PHASE II: Metastatic breast cancer (local spread to axillary or internal mammary lymph  nodes is permitted)  -  PHASE II: Current therapy with raloxifene, tamoxifen, aromatase inhibitor, or other  selective estrogen receptor modulator (SERM), gonadotrophin-releasing hormone (GNRH)  agonist/antagonist, either for osteoporosis or prevention of breast cancer. Subjects  must have discontinued therapies for at least 28 days prior to first baseline biopsy

Rationale: Nutrition and lifestyle interventions are currently not implemented in usual  clinical care of PAH-patients. Mainly because there is little known on the relation between  pathology, nutrition and lifestyle. Patients who suffer from Pulmonary Arterial Hypertension  feel insecure about their nutrition and lifestyle. The investigators hypothesize that an  intervention on nutrition and lifestyle can improve the patients' quality of life.  Objective: To explore the effect of a nutrition and lifestyle intervention on quality of life  for patients suffering from PAH.  Study design: Investigator initiated intervention study with control group. Study population:  investigators aim to include 70 patients (18 - 80 years) with idiopathic, hereditable or drug  related PAH, who have been stable for at least three months and are self-sufficient and/or  have a family who's willing to participate in the lifestyle changes.  Intervention (if applicable): Nutritional status, - education, - intervention and -  compliance.  Main study parameters/endpoints: This is an intervention study in which the investigators  will asses the effect of a nutrition and lifestyle intervention on quality of life measured  by SF-36 overall outcome with a significant difference of 6.35.  Nature and extent of the burden and risks associated with participation, benefit and group  relatedness: The burden for the patient exists of 12 extra visits to the hospital and contact  moments, over a period of 11 months, as well compliance to the diet and lifestyle. There is  minimal risk in participation. Baseline nutritional assessment  Nutritional education:  8 online lessons containing information about nutrition, lifestyle and general health with  complementary tips regarding PH. All participants recieve workbook with assignments.  Nutritional intervention:  Group A: MedDASH diet (55% carbohydrates, 25% amino acids, 20% fatty acids) Group B:  MedDASHfat diet (10% carbohydrates, 25% amino acids, 65% fatty acids) Control group: no diet.  Follow-up:  Patients in intervention arm followed for a period of 6 months to assess compliance. Inclusion Criteria:  -  Diagnosis of idiopathic PAH, hereditable PAH or drug related PAH  -  Age between 18 and 80  -  NYHA II or III and stable for at least 3 months, determined by a stable 6minute walk  test with a difference of <10%.  -  Self-sufficient and/or compliance from partner and/or family  -  Creatinine > 30 ml/min  -  Able to understand and willing to sign the Informed Consent Form Exclusion Criteria:  -  - Pregnant subjects  -  Fat percentage < 10% > 50 %  -  One or more of the following comorbidities: diabetes mellitus type one or two,  clinically relevant thyroid disease  -  Known history of noncompliance considering therapies

Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often  leading to kidney failure and markedly magnifying risks of cardiovascular disease and  premature death. Landmark T1D kidney biopsy studies identified the classic pathological  lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in  continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved  glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and  insulin resistance (IR) have accompanied intensive glycemic therapy and may promote  mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in  modern-day T1D and identifying modifiable risk factors could lead to more effective and  targeted therapies to prevent DKD. The overall goal of this project is to characterize the molecular, morphometric, and  metabolic features of DKD over the modern clinical course of T1D. The investigators  hypothesize that perturbed kidney energetics and hypoxia are central metabolic pathways in  the development of DKD. Kidney hypoxia stems from a mismatch between increased renal energy  demand (e.g., increased glomerular filtration rate [GFR] and tubular reabsorption of sodium)  and impaired substrate metabolism (e.g., IR and mitochondrial dysfunction) and results in  activation of the hypoxia-inducible factor (HIF) system. Although upregulation of HIF1α  confers favorable short-term effects, sustained activation promotes cellular injury.  Supporting these hypotheses, data from our group and others have shown that obesity, IR, and  The investigators also found that youth with T1D exhibit kidney hypoxia by MRI that strongly  associates with IR and mitochondrial dysfunction. Moreover, our preliminary single-cell RNA  sequencing (scRNA-seq) data from kidney biopsies demonstrate upregulated tubular expression  of HIF1α in adults with T1D vs. healthy controls. The investigators propose to build a unique  new longitudinal kidney biopsy cohort (N=100) spanning the critical duration of T1D over  which DKD initiates and progresses (5-30 years). Participants will be enrolled from our  existing CROCODILE study (adding longitudinal follow-up to completed kidney biopsies and  baseline data and biosample acquisition) and from new enrollment at the University of  Colorado and University of Washington. Normative kidney biopsy data will be provided from our  existing cohort of healthy controls (N=20) and the Kidney Precision Medicine Project (KPMP).  The investigators will implement state-of-the-art molecular (scRNA-seq) and morphometric  interrogation of kidney tissue and rigorous metabolic phenotyping to include kidney magnetic  resonance imaging (MRI), direct measurements of glycemia (continuous glucose monitoring),  intraabdominal fat (dual-energy X-ray absorptiometry), estimation of insulin sensitivity by a  T1D-validated equation, and (in a subset) GFR (iohexol clearance) and renal plasma flow  (p-aminohippurate clearance). Participants will be followed longitudinally for DKD outcomes.  A subset of 20 participants will undergo repeat kidney biopsies and associated procedures 3  years after baseline kidney biopsy. Inclusion Criteria:  -  Age ≥ 18 years at enrollment (rationale: this study focuses on determinants of early  DKD over the course of T1D in adults)  -  T1D duration >5 and ≤ 30 years (rationale: DKD in T1D rarely manifests prior to 5  years of disease duration; longstanding T1D above > 30 years subject to survivorship  bias)  -  HbA1c <11% (rationale: HbA1c ≥ 11% exceeds the average HbA1c at most academic center  and would limiting the generalizability of our study findings) Exclusion Criteria:  -  T2D and monogenic diabetes (rationale: our study focuses on T1D)  -  Recent diabetic ketoacidosis, i.e., <1 month (rationale: safety and insulin resistance  and tubular dysfunction of DKA can confound study findings)  -  eGFR < 30 ml/min/1.73m2 or dialysis treatment (rationale: to reduce the likelihood of  identifying secondary pathways that are not specific to kidney injury from T1D)  -  Kidney transplant recipients (rationale: molecular confounding from immunosuppression)  -  Kidney biopsy contraindications (rationale: safety - kidney biopsy):  -  Evidence of bleeding disorder or complications from bleeding  -  Use of aspirin, Nonsteroidal anti-inflammatory drugs (NSAIDS) or other blood  thinner that cannot be safely stopped for a sufficient time before and after the  biopsy to avoid additional risk of bleeding.  -  INR > 1.4  -  Hemoglobin (Hgb) < 10 mg/dL (Colorado) [altitude]  -  Hemoglobin (Hgb) < 9 mg/dL (Washington)  -  Platelet count < 100,000 / µL  -  Uncontrolled or difficult to control hypertension (> 150/90 mmHg at the day of  biopsy)  -  Single kidney (either by history, documented by prior imaging or ultrasound  performed prior to the biopsy)  -  Kidney size: One or both kidneys < 8 cm  -  Hydronephrosis or other important renal ultrasound findings such as significant  stone disease  -  Any evidence of a current urinary tract infection as indicated on day of biopsy  -  Clinical evidence of non-diabetic renal disease  -  Positive urine pregnancy test or pregnancy

To determine whether there is higher incidence of skewed X chromosome inactivation(SXCI) in  the recurrent miscarriage(RM) population compared with normal population, and verify the  existing hypothesis of the possible genetic mechanisms underlying the association between  SXCI and RM. Recurrent spontaneous abortion (RSA), defined as 2 or more consecutive pregnancy losses  before 20-22 weeks of gestation, is a multifactorial disorder that affects about 5% of all  couples.In up to 50% of women who have experienced RSA, the cause still remains unexplained,  with genetic problem proposed as a main cause. X chromosome inactivation (XCI) is a  physiological phenomenon in female mammals for 'dosage compensation' of X-linked genes with  males. A normal female is mosaic, with about one-half of her somatic cells expressing the  paternal derived X and the remainder of her cells using maternal X. In some situations,  however, the inactivation is not random, resulting in a female having most or even all her  somatic cells inactivating the same X chromosome from either paternal or maternal resource,  which is known as skewed X-chromosome inactivation (SXCI).Evidence of an association between  skewed X chromosome inactivation (SXCI) and idiopathic recurrent spontaneous abortion (RSA)  is conflicting. This is a single-center observational case-control trial to determine whether  there is higher incidence of skewed X chromosome inactivation(SXCI) in the recurrent  miscarriage(RM) population compared with normal population, and verify the existing  hypothesis of the possible genetic mechanisms underlying the association between SXCI and RM. Inclusion Criteria:  -  1) regular menstrual cycles and normal level of E2, P, FSH, LH, T, RPL in the early  follicular phase; 2) no history of gynecologic or other pelvic operations; 3) no  history of hormone medicine application in the last 3 months; 4) no history of poison  contact; 5) normal uterine and adnexal ultrasonography; 6) TORCH(-), chlamydia(-),  mycoplasma(-), normal leucorrhoea routine, anti-phospholipid antibody (-), antinuclear  antibody(-); 7) for the couple, no blood type incompatibility or ABO antibody IgG≤1：64  and normal blood chromosome analysis; 8) condoms are used for contraception. Exclusion Criteria:  -  1) BMI<18.5 or >24.9; 2) hydrosalpinx without operation; endometriosis; polycystic  ovary syndrome; adenomyosis; uterine leiomyomata(submucous myoma or non-submucous  myoma which size was exceed 4cm and/or with the compressed endometrium);uterine cavity  lesions(such as uterine malformation, intrauterine adhesions, the septate uterus,  endometritis etc); 3) the former abortion is because of luteal phase defect without  treatment; 4) FSH≥12IU/L or AMH<1.2ng/ml 5) thyroid dysfunction or increased CA125  level; 6) acute inflammation of genitourinary system or STD carriers; 7) unable to  comply with the study procedures.

This phase IV clinical trial investigates the impact of prostate cancer treatment,  specifically androgen deprivation therapy (ADT), on the heart and coronary vessels among men  with localized, non-metastatic prostate cancer undergoing definitive radiation therapy and  concomitant ADT. Recently, cardiovascular toxicity from hormone therapy that is routinely  used for prostate cancer (e.g. leuprolide) has emerged as a concern, yet studies identifying  who is at risk and the mechanism of cardiac damage are lacking. Additionally, a new hormone  therapy drug, relugolix, has recently been Food and Drug Administration (FDA)-approved and  may reduce toxicity to the heart. This trial intends to investigate the mechanism of  cardiovascular toxicity from ADT, investigate the mechanism by which relugolix reduces  cardiovascular toxicity, and identify predictive biomarkers to improve individualized  risk-assessment for cardiovascular toxicity from ADT. PRIMARY OBJECTIVES:  I. Identify and compare the association of gonadotrophin releasing hormone (GNRH)-agonist  leuprolide versus GNRH-antagonist relugolix with coronary atherosclerosis and progression in  men with prostate cancer.  II. Determine the relationship between leuprolide versus relugolix with downstream immune  effector response that is implicated in atherosclerosis.  II. Determine how pre-existing genomic alterations associated with proinflammatory immunity  impact development of CV toxicity following GNRH-agonist (GNRHa) versus relugolix.  III. Identify imaging biomarkers associated with increased risk of CV toxicity from ADT  OUTLINE: Patients undergoing radiation therapy alone as part of their standard treatment are  assigned to Arm I. Patients undergoing radiation therapy and ADT as part of their standard  treatment are randomized to Arm II or Arm III.  ARM I: Patients undergo definitive radiation therapy in the absence of disease progression or  unacceptable toxicity.  ARM II: Patients undergo radiation therapy as in Arm I and receive leuprolide subcutaneously  (SC) or intramuscularly (IM) every 3 or 6 months. Treatment continues for 6 to 24 months  (depending on cancer risk) in the absence of disease progression or unacceptable toxicity.  ARM III: Patients undergo radiation therapy as in Arm I and receive relugolix orally (PO)  once daily (QD) for 6 to 24 months (depending on risk) in the absence of disease progression  or unacceptable toxicity. Inclusion Criteria:  -  Men >= 18 years old  -  Non-metastatic prostate cancer  -  Non-metastatic, biochemically recurrent prostate cancer  -  Plan to undergo curative-intent pelvic radiation therapy with or without ADT Exclusion Criteria:  -  Metastatic prostate cancer requiring > 24 months of ADT  -  Prior exposure to androgen deprivation therapy  -  Prior exposure to chemotherapy or immunotherapy

The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics and  preliminary antitumor activity of docetaxel for injection (albumin-bound) in different dose  regimens in patients with advanced solid tumors. This study will be conducted in two stages. The first stage (Stage I) is a dose-escalation  study. A classic 3+3 design will be used to determine the maximum tolerated dose (MTD) and  the recommended phase 2 dose (RP2D). Patients will receive the docetaxel for injection  (albumin-bound) until disease progression, or intolerable toxicity, or other reasons for  termination of the study. All dose-escalation decisions will be based on the safety data  generated from the current highest dose group.  In the cohort-expansion study (Stage Ⅱ), patients with a potential to have better response to  the study drug will be recruited. Patients will receive the docetaxel for injection  (albumin-bound) at the recommended phase 2 dose (RP2D) and follow the treatment regimen  established in Stage I. Inclusion Criteria:  1. Patients aged ≥18, ≤75 years (subject to the date when the informed consent form is  signed) and voluntarily signed the informed consent form.  2. Histologically or cytologically confirmed diagnosis of advanced or metastatic solid  tumors, for which standard therapy either does not exist or has proven to be  ineffective, intolerable or unacceptable for the patient.  3. At least one measurable lesion according to RECISTv1.1.  4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status score of  0-1.  5. Patients with estimated survival time of ≥ 3 months.  6. Main organ function meets the following criteria within 7 days before treatment (no  medical supportive treatments such as blood component transfusion, human granulocyte  colony-stimulating factor (G-CSF), thrombopoietin (TPO), interleukin-11, and  erythropoietin (EPO) within 2 weeks before baseline examination):  Absolute neutrophil count ≥1.5×10^9/L; Platelets ≥100×10^9/L; Hemoglobin ≥90 g/L or  ≥5.6 mmol/L; Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 50 mL/min;  Liver function: total bilirubin≤ 1.0 × ULN, ≤ 1.5 × ULN for patients with liver  metastasis or liver cancer; alanine aminotransferase (ALT) and aspartate  aminotransferase (AST) ≤ 1.5 × ULN, ≤ 2.5 × ULN for patients with liver metastasis or  liver cancer.  7. Fertile patients must use contraceptive measures (such as intrauterine device [IUD],  contraceptive pill or condom) during the study period and within 6 months after the  end of the study, and men should avoid sperm donation; Women of childbearing age must  have negative serum pregnancy test within 7 days before study enrollment, and must be  non-lactating women. Exclusion Criteria:  1. Patients with central nervous system metastasis or meningeal metastasis, accompanied by  the following conditions:  1. Patients with clinical symptoms related to central nervous system metastasis or  meningeal metastasis;  2. New lesions in the brain or progression of the original lesions on imaging from the  end of brain radiotherapy or surgery to the first administration;  3. Central nervous system metastasis with cortical alcohols, radiotherapy, dehydration  drugs and other drugs for symptoms control within the last two weeks;  4. Patients has brain stem (midbrain, pons, medulla oblongata) metastasis;  5. Other evidence shows that the patient's central nervous system metastasis or meningeal  metastasis has not been controlled, which is not suitable for inclusion according to  the judgment of the researcher.  2. Known human immunodeficiency virus (HIV) test positive or known history of acquired  immunodeficiency syndrome (AIDS), history of organ transplantation, history of serious  autoimmune diseases judged by the researchers to be unsuitable for inclusion.  3. HCV antibody (+) or active hepatitis B (HBsAg positive and HBV DNA > 500 IU/mL) and  uncontrolled active infection (those who must receive systematic anti infection treatment,  or those with unexplained body temperature > 38 ℃ (axillary temperature) before  administration).  4. Patients have a history of serious cardiovascular diseases, including but not limited  to:  1. Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia  requiring clinical intervention and third-degree atrioventricular block;  2. History of myocardial infarction, angina pectoris, angioplasty, coronary artery bypass  surgery;  3. Patients with prolonged QT/QTc interval (QTcF > 480 ms, Fridericia's formula: QTcF =  QT/RR^0.33, RR = 60/heart rate) by ECG during the screening period;  4. left ventricular ejection fraction (LVEF) ≤ 50% by echocardiography (ECHO) or  multi-gated acquisition (MUGA) during the screening period;  5. Heart failure with New York Heart Association (NYHA) Classification of Class Ш and  above;  6. Poorly controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic  blood pressure ≥ 95 mmHg despite optimal treatment);  7. Previous or current cardiomyopathy;  8. Patients with severe pulmonary hypertension or a history of pulmonary embolism within  6 months.  5. Patients with a third space effusion (e.g., pleural effusion, ascites, or pericardial  effusion) that is difficult to control, who, in the judgment of the investigator, are not  suitable for the study.  6. Allergic history to taxane or any excipients of the study drug (CTCAE 5.0 grade ≥ 3  grade).  7. Adverse reactions from the previous anti-tumor treatment have not yet recovered to ≤  level 1 based on CTCAE 5.0 (except for the toxicity without safety risk judged by the  investigator, such as alopecia).  8. Patients who have previously received docetaxel containing regimen and progressed during  treatment or within 6 months after treatment.  9. Patients who have undergone major organ surgery (excluding puncture biopsy) or  significant trauma within 4 weeks before the first dose of the investigational drug, or who  need to undergo elective surgery during the study period.  10. The time between the last anti-tumor treatment and the first medication meet the  following time interval: anti-tumor treatment such as chemotherapy, radiotherapy (except  local radiotherapy for pain relief), targeted therapy, immunotherapy and other clinical  research drugs within 4 weeks before the first administration; oral fluorouracils, small  molecule targeted drugs and traditional Chinese medicine with anti-tumor indications within  2 weeks before the first administration.  11. Patients who have received corticosteroid (prednisone > 10 mg/day or equivalent) or  other immunosuppressive therapies within 2 weeks before the first dose of the  investigational drug, except for the following: a. use of topical, ocular, intra-articular,  nasal and inhaled glucocorticoids; b. short-term use of glucocorticoids for prophylaxis  (such as prevention of contrast agent allergy).  12. Patients who have used potent inhibitors or inducers of CYP3A4 within 2 weeks before  the first dose of the investigational drug.  13. Patients with alcohol or drug dependence. 14. Patients have clear history of  neurological or psychiatric disorders, including epilepsy and dementia.  15. The researcher believes that the patient has other reasons that affect the safety or  compliance, or is not in the best interests of the subject and is not suitable to  participate in this clinical study (for example, eye diseases, venous thrombosis, etc.,  which affect the safety according to the judgment of the researcher).

The Swiss Patient Registry for DMD/BMD and SMA was launched in 2008 in order to give Swiss  patients access to new therapies. It was founded with the financial support of several  patient organizations and research foundations. Since 2008, children, adolescents and adults  with DMD, BMD and SMA are registered with the help of all major muscle centers in  Switzerland. After nearly ten years of activity, the Swiss Patient Registry for DMD/BMD and  SMA implemented several adaptations in 2018 to meet current and future expectations of  patient's organizations, health authorities and research organizations. Background:  The 'Swiss registry for neuromuscular disorders' (Swiss-Reg-NMD) collects medical information  from people with neuromuscular disorders. It is led by specialized physicians from all over  Switzerland and located at the Institute of Social and Preventive Medicine (ISPM) in Bern.  The registry includes children and adults living or treated in Switzerland who are diagnosed  with Duchenne-Becker Muscular Dystrophy (DMD/BMD), Spinal Muscular Atrophy (SMA) and recently  also merosin-deficient muscular dystrophy also called LAMA2-related muscular dystrophy (MDC1A  respectively LAMA2).  The Swiss Registry for neuromuscular disorders was initially founded in 2008 to give Swiss  patients with a neuromuscular disease access to new therapies. In 2018, the registry was  reorganized to meet new legal requirements and expectations of patients and research  organizations. The Swiss Ethics Commission approved the project (project ID: 2018-00289,  observational study, risk category A).  NMDs are rare diseases with few patients scattered across the country. A national patient  registry with a centralized registration facilitates the participation of Swiss patients in  therapeutic trials and the creation of Swiss trial sites.  Objectives:  Primary objectives of the Swiss-Reg-NMD project are:  1. Establish a representative population-based Swiss cohort of children, adolescents and  adults with NMDs  2. Provide epidemiological data to investigate the incidence, prevalence, spectrum of  diagnosis, survival rates and mortality of NMDs in Switzerland  3. Provide a platform for clinical research:  1. Offer a resource to recruit Swiss patients in current and future national and  international therapeutic trials or observational studies  2. Offer a resource to facilitate the establishment of therapeutic trial sites in  Switzerland  3. Answer questions in the following areas: health, health care, social-,  educational-, professional-, economic aspects, and quality of life  4. Offer a resource for post-marketing surveillance (effects and side effects of  therapies/treatments)  4. Provide a platform for communication:  1. Promote the exchange of knowledge between clinics, researchers, therapists and  national and cantonal health authorities in particular regarding standards of care  2. Facilitate national and international collaborations, in particular with the  international registry of TREAT-NMD and the upcoming Swiss Registry for Rare  Diseases  Inclusion/exclusion criteria:  All children, adolescents and adults living or treated in Switzerland who are diagnosed with  a NMD. The diagnosis needs to be confirmed, whenever possible, by genetic testing, or at  least by biopsy and/or electroneuromyography, according to international standards for the  diagnosis of the given NMD. Once the diagnosis is established, there is no specific exclusion  criteria.  Currently, patients with SMA, DMD/BMD, merosin-deficient muscular dystrophy also called  LAMA2-related muscular dystrophy (MDC1A respectively LAMA2) and Collagen 6 related muscular  dystrophy are included.  Procedure:  After a NMD diagnosis, the treating physician informs the patient and the parents (if the  patient is still a child) during a consultation in a clinic or practice in writing and orally  about the Swiss-Reg-NMD. The patient/parents who wish to participate sign the consent form  and the patient is registered in the Swiss-Reg-NMD. If the patient/parents do not wish to  participate, only a minimal anonymous data set is recorded.  The following data will be collected:  -  Medical data  -  Data from questionnaires for patients and families  -  Data from links to routine statistics and other medical registries  Clinical data (report of new cases and follow-up reports): NMD subtype, severity, and  associated conditions; Comorbidities; Medical care and medication; Therapies; (Serious)  adverse events; Hospitalisations; Motor Function Assessments; Socio-demographic  characteristics.  Questionnaire data: We will collect data through questionnaires with a focus on (but not  exclusively):  -  Health related questions like nutrition, sleep, pain  -  Health behaviours (e.g., physical activity, smoking)  -  Medical equipment use (type, usage, satisfaction)  -  Treatments and therapies: frequency, intensity, start, types  -  Quality of life and participation (involvement in a life situation)  -  Social-economic factors  -  Education (early childhood education, school, professional integration)  -  Patient/caregiver reported outcomes  -  Needs and concerns of persons with NMDs and their families  Routine data and linkages: e.g. Federal Statistical Office (e.g. birth registry, cause of  death statistics, hospital statistics); Swiss National Cohort (socioeconomic data, family  information); other medical registries (e.g. rare disease registry); Communities of residence  (vital status, date of death, address).  Funding:  Schweizerische Muskelgesellschaft; ASRIMM, Association Suisse Romande Intervenant contre les  Maladies neuromusculaire; MGR, Associazione malattie genetiche rare della svizzera italiana;  fsrmm, schweizerische stiftung für die erforschung der muskelkrankheiten; SMA Schweiz;  Duchenne Schweiz; Avexis; Biogen; Novartis; Pfizer, PTC Therapeutics; Roche; Sarepta.  Data protection:  Data generation, transmission, storage and analysis of health related personal data within  this project will follow strictly the current Swiss legal requirements for data protection.  Data analyses will always be done using pseudonymised datasets. Health related personal data  captured during this project are strictly confidential. Project data shall be handled with  uttermost discretion and only be accessible to authorized personnel. Direct access to source  documents will be permitted for purposes of monitoring, audits or inspections. The data  protection concept of ISPM ensures the secure handling of all sensitive data at ISPM and  within Swiss-Reg-NMD. The Swiss-Reg-NMD team is responsible for the implementation and  compliance with the confidentiality and data security measures. Inclusion Criteria:  -  Children, adolescents and adults diagnosed with a NMD  -  Who are living or treated for a NMD in Switzerland, and  -  Who gave informed consent Exclusion Criteria:  -  None if diagnosis is confirmed, whenever possible, by genetic testing, or at least by  biopsy and/or electroneuromyography, according to international standards for the  diagnosis of the given NMD.

The study aim is to look at the effect of the regular use of inhaled corticosteroids on the  response and received from mepolizumab treatment which you are receiving or had received  before. Examine the outcomes of 250 patients who have been treated with mepolizumab within BRSAS and  compare the adherence to ICS in the responders and non-responder groups. If confirmed that  non-adherence to ICS was related to poor response to mepolizumab, steps then will be  undertaken to better monitor and enhance adherence to ICS to improve patients outcomes and  response to mepolizumab treatment.  This study will rely on retrospective analysis of medically existing data within the service  ,the adherence to ICS treatment will be measured using the prescription possession ratio  "PPR" Data is available in the patients' GP records and forms part of the routine clinical  practice of the severe asthma clinic to monitor adherence to ICS treatment.  For a significant number of patients ,such data will be already available within patient  medical records held at University Hospitals Birmingham NHS Foundation Trust (UHB), however  missing data is expected and in such cases GP surgeries will be contacted to obtain the PPR.  Patients will be asked to agree to access to GP records as part of the informed consent  process. Inclusion Criteria:  -  Patients of 18 years of age or higher  -  Patients commenced on mepolizumab within the BRSAS network  -  Patients who have at least 1 mepolizumab injection and with at least 3 months  follow-up data from the time of treatment initiation  -  Patients must be able and willing to give informed consent to participate in the study  . An Interpreter will be provided for those patients where English is not their first  language. Exclusion Criteria:  -  Refusal or inability to provide informed consent

Phase 2 Study Investigating the Efficacy of AMT-101 in Subjects with Chronic  Antibiotic-resistant Pouchitis A Phase 2 12-week, Randomized, Double-blind, Placebo-controlled Study Investigating the  Efficacy of AMT-101 in Subjects with Chronic Antibiotic-resistant Pouchitis Inclusion Criteria:  • Chronic or recurrent pouchitis Exclusion Criteria:  -  Known gastrologic, or systemic condition that may compromise severity or diagnosis of  disease.  -  History or current evidence of colonic or abdominal abnormalities.  -  Previous exposure to AMT-101 or similar and known hypersensitivity to AMT-101 or its  excipients.

Multicentre, national, observational, retrospective and prospective study.  The BLITZ-COVID19 study aims at describing the epidemiology of admissions to Italian  Cardiology Intensive Care Units in the COVID-19 infection pandemia, the main aspects of the  clinical management of inpatients, their short-term outcome, the absorption of resources  related to their admission. The BLITZ-COVID19 study, aims at describing the epidemiology of admissions to Italian  Cardiology Intensive Care Units .  The study is observational, multicentre, national and involves the collection of clinical  data, both retrospectively and prospectively, using a web-based system. In conducting the  study, no drugs are tested, nor are diagnostic tests or non-pharmacological therapies  performed other than those that each participating cardiologist decides to perform following  the rules of normal clinical practice. Diagnostic procedures and pharmacological and  non-pharmacological therapies habitually prescribed for cardiovascular pathologies, which are  the object of hospitalization, and those used in the event of a COVID-19 infection, will be  recorded in the database. Inclusion Criteria:  - All patients aged ≥18 years admitted with any diagnosis to one of the participating ICU Exclusion Criteria:  - Refuse to signe consent

The prolonged β-lactam Antibiotics intravenous infusion strategy has emerged as the standard  treatment for sepsis despite its unknown efficacy. The investigators will conduct a  prospective, multi-center, cluster randomized controlled clinical trial. The investigators  aimed to compare the clinical efficacy and prognosis of prolonged β-lactam antibiotics  intravenous infusion versus short-term intravenous infusion in ICU patients with early  sepsis. The investigators expect to recruit 40 branch centers and enroll at least 2600  patients with sepsis. Sepsis and septic shock can lead to high morbidity and mortality. The mortality of sepsis is  related to inappropriate antibiotic treatment strategy. Due to the pathophysiological  characteristics of patients with sepsis, the pharmacokinetics of antibiotics have changed,  and antibiotic treatment strategies applied to general mild and severe infections may not be  suitable for those patients. The relevant international guidelines recommend that antibiotic  treatment for patients with sepsis should base on pharmacokinetic/pharmacodynamic principles,  but this recommendation is based on low-level clinical evidence.  β-lactam antibiotics, including penicillins, cephalosporins, carbapenems and so on, are the  most widely used antibacterial drugs in clinical practice. The best predictive parameter of  those antibiotic bactericidal activity is the time during which the free drug concentration  exceeds the target microbial MIC value (fT >MIC). According to Monte Carlo approach and  clinical studies, as a PK/PD target value, an effective bactericidal effect can be achieved  if fT>MIC reaches more than 40%; fT>MIC reaches more than 60%-70% can achieve the maximum  bactericidal effect, which can be used in the treatment of severe cases. For severe infection  and prevention of bacterial resistance, fT>MIC needs to reach 90%-100%.  The results of clinical studies have proved that improper or inadequate initial empiric  antibiotic treatment is an independent risk factor that affects the therapeutic effectiveness  and prognosis of severe infections. Important reasons for the lower-than-expected antibiotic  treatment effect in severely ill patients include at least the following two factors: (1)  Changes in the pathophysiological state of severely ill patients on drug metabolism, such as  capillary leakage leading to increased drug distribution volume. As well as the high  excretion and low obstruction hemodynamic characteristics of sepsis, increased renal blood  flow leads to high excretion of water-soluble drugs, which often reduces the effective plasma  concentration of the drug; (2) ICU infection of pathogenic bacteria has increased drug  resistance and increased MIC. The above factors lead to the decrease of drug fT>MIC, which  affects the efficacy of antibiotics. In recent years, the optimization of PK/PD-guided  time-dependent antimicrobial treatment programs have confirmed that the administration method  of prolonging the infusion time or continuous infusion can maintain a good steady-state blood  drug concentration, prolong fT> MIC, and improve clinical curative effect, and can reduce the  amount of antibiotics.  The main problems with PK/PD-guided antimicrobial therapy are: (1) Lack of convincing large  sample clinical research results; (2) It has not been confirmed which subgroup (such as the  sepsis severity, drug-resistant patterns of pathogens, immunocompetence) can be benefited  from this strategy; (3) It is not clear whether the method of prolonged infusion can be  applied in all kinds of β-lactam antibiotics .  This study adopts multi-center, openness, cluster randomization method to group, and  eliminates the bias caused by factors such as the treatment environment in a single ward  through the multi-center study; through Uniform training realizes the standardization of drug  delivery methods to eliminate researchers' human bias in treatment operations and  observations. At the same time, the regional randomization method sets the drug delivery  method for a certain research center in a certain research phase to be determined, which  eliminates the operational error and observation bias when the researcher needs to face  multiple drug delivery programs at the same time. It can greatly reduce research costs and  human bias, and more reliably obtain the impact of PK/PD-guided antibiotic treatment on the  prognosis of patients and the impact of bacterial resistance in the entire ward. Inclusion Criteria:  1. Patients in ICU who need to be treated with β-lactam antibiotics for clinical  diagnosis of infection;  2. Meet the diagnostic criteria of sepsis 3.0 in the previous 24h;  3. At assessment of eligibility, treating doctor expects patient to need treatment in ICU  beyond the next calendar day. Exclusion Criteria:  1. The infection is diagnosed clinically, but the acquired pathogens are not sensitive to  the study drug;  2. Has a history of allergies to study drugs;  3. Those who have a serious condition and the expected survival time is less than 72  hours.  4. Receipt of potential study medication for > 24 hours before randomization.  5. Pregnancy  6. Death is deemed imminent and inevitable.  7. Receiving palliative or supportive treatment only at the time of assessment for  eligibility.  8. Treating doctor not committed to provision of advanced life-support, including any of  mechanical ventilation, dialysis and vasopressor administration for at least the next  48 hours.  9. Consent not gained for study participation and entry under a waiver-of-consent not  approved by the jurisdictional human research ethics committee.

Several studies seem to indicate that emotional attention and change-related attention are  impaired in ASD. The goal of this study is to identify the relationships between those two  types of automatic attention in visual and auditory modalities in subjects with ASD compared  to healthy controls and also, over the course of development (children, adults). In order to  achieve this goal, the investigators will use complementary techniques (EEG and MRI-based  techniques (fMRI, DTI)). Autism Spectrum Disorders (ASD) are characterized by major handicap in social interaction and  in daily life adaptation. The orienting response towards potentially relevant events involves  automatic attentional mechanisms that would be elicited mainly by two classes of biologically  important stimulations: novel stimuli and emotional stimuli. The neural basis of emotional  and change-related attention in ASD will be explored by investigating brain reactivity in  both visual and auditory modalities, during tasks mixing emotional and non emotional stimuli. Inclusion Criteria:  -  No past history of central nervous system disorders  -  Written consent  -  Affiliated to the National Health Insurance  -  Do not participate to another biomedical research  -  For ASD group: Children with autism spectrum disorder (DSM-V criteria) and adults with  high-functioning autism  -  For healthy subjects: No past history of difficulties in early childhood for  acquisition of walk, language or reading and no psychiatric disorders Exclusion Criteria:  -  Abnormal corrected vision  -  Abnormal audition  -  Not stabilized psychoactive treatment or treatment that can modify electrogenesis  -  Infectious or metabolic diseases  -  Epilepsies  -  Impossibility to participate to the whole study  -  For subjects participating to the MRI recordings: MRI counter-indications (pace-makers  ...), claustrophobia or a positive pregnancy test

The practice of a physical activity, even moderate, plays an important role in the prevention  and the management of the main chronic non-communicable diseases (cardiovascular diseases,  certain cancers, diabetes, obesity, osteoporosis ...) as well as by improving psychological  health. Several studies have shown that physical activity has a positive impact on the  economy of companies via the reduction of absenteeism and the improvement of productivity.  However, it seems important to individualize these recommendations in order to prescribe the  best possible dose of physical activity for each individual. In this project, the  investigators want to test the physical qualities of employees in order to prescribe the best  possible dose of physical activity with the ultimate goal of improving quality of life. Physical activity (PA) is one of the major determinants of health. Indeed, the practice of a  physical activity, even moderate, plays an important role in the prevention and the  management of the main chronic non-communicable diseases (cardiovascular diseases, certain  cancers, diabetes, obesity, osteoporosis ...) as well as by improving psychological health.  The effects are beneficial regardless of age, gender and state of health. Moreover, in  addition to the well-being of employees, several studies have shown that physical activity  has a positive impact on the economy of companies via the reduction of absenteeism and the  improvement of productivity. Today, the World Health Organization (WHO) prescribes 150 min of  physical activity per week regardless of the person's profile (active employee, employee  working in his office, construction worker, etc.).. In this project,the investigators  therefore want to test the physical qualities of employees in order to prescribe the best  possible dose of physical activity with the ultimate goal of improving quality of life. Inclusion Criteria:  -  Sedentary people  -  Affiliate to health care organism  -  Subject who gave their consent Exclusion Criteria:  -  People with degenerative disease  -  Pregnant women  -  Cardiovascular trouble  -  Subject who are not able to understand the proceeding of the study or to give their  consent

Evaluate efficacy and safety of ADI-PEG 20 in patients with genotype WWOX-GG and HCC Safety will be evaluated by laboratory tests, vital sign measurements, physical examinations  and subject medical history which will be performed to detect new abnormalities and any  deterioration in pre-existing conditions.  Efficacy will be determined by overall survival, progression free survival, pharmacodynamics  (peripheral blood arginine and citrulline levels) and immunogenicity (antibodies to ADI-PEG  20). Inclusion Criteria:  1. Prior diagnosis of HCC confirmed by radiology, histology, or cytology.  2. Prior treatment with at least 1 systemic agent for Child-Pugh A subjects. However,  Child-Pugh B7 subjects without prior systemic treatment may be enrolled, if they are  not eligible for any approved systemic therapies.  3. WWOX genotype GG.  4. Measurable disease using RECIST 1.1. At least 1 measurable lesion must be present.  5. Child-Pugh (cirrhosis status) score class A-B7.  6. Barcelona Cancer of the Liver (BCLC) stage C.  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment.  8. Expected survival of at least 3 months.  9. Age >20 years.  10. Fully recovered from prior surgery, radiation, or chemotherapy, and none within 2  weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.  11. Female subjects and male subjects must be asked to use appropriate contraception for  both the male and female for the duration of the study and for 35 days after last dose  of ADI-PEG 20. Male partners of female subjects and female partners of male subjects  must agree to use two forms of contraception or agree to refrain from intercourse for  the duration of the study if they are of childbearing potential. Females of  childbearing potential must not be pregnant at the start of the study, and a serum  human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into  the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy  must be performed according to GCP before this subject is deemed eligible. Females not  of childbearing potential must be post-menopausal (defined as cessation of regular  menstrual period for at least 12 months).  12. Informed consent must be obtained prior to study initiation.  13. No concurrent investigational studies are allowed.  14. Total bilirubin < 3.0 mg/dL and no evidence of bile obstruction.  15. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper  limit of normal range.  16. Serum albumin level ≥ 3.0 g/dl.  17. Prothrombin time (PT)-international normalized ratio (INR): PT <3 seconds above  control or INR <1.7.  18. Absolute neutrophil count (ANC) >1,500/μL.  19. Platelets >50,000/μL.  20. Serum uric acid ≤ 8 mg/dL (with or without medication control).  21. Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine >1.5  x the upper limit of normal range, then the creatinine clearance must be ≥ 40 mL/min.  22. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such  treatment, except for interferon.  23. Encephalopathy - none or mild (grade 1 or 2, by Child-Pugh classification); lactulose  of other supportive care allowed.  24. Ascites - absent or slight (by Child-Pugh classification); diuretic therapy allowed Exclusion Criteria:  1. Candidate for potential curative therapies (i.e., resection or transplantation) or  eligible for approved systemic therapies according to the labeling of such drugs.  2. Prior allograft transplantation including liver transplantation.  3. Subjects who have not fully recovered from toxicities associated with previous HCC  loco-regional or systemic therapies, except for Grade 1 alopecia.  4. Serious infection requiring treatment with systemically administered antibiotics at  the time of study entrance, or an infection requiring systemic antibiotic therapy  within 7 days prior to the first dose of study treatment.  5. Pregnancy or lactation.  6. Expected non-compliance.  7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active  infection, symptomatic congestive heart failure (New York Heart Association Class III  or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit  compliance with study requirements.  8. Subjects with history of another primary cancer, including co-existent second  malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b)  curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no  known active disease present or in the opinion of the investigator will not affect  patient outcome.  9. Subjects who had been treated with ADI-PEG 20 previously.  10. History of uncontrolled seizure disorder not related to underlying cancer.  11. Allergy to pegylated compounds.  12. Allergy to E. coli drug products (such as GMCSF).  13. Bleeding esophageal or gastric varices within the prior three months, except if banded  or treated.  14. Uncontrolled ascites (defined as not easily controlled with diuretic treatment).  15. Having received any blood transfusion, blood component preparation, erythropoietin,  albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days  prior to screening laboratories or after screening laboratories have been obtained  until week 1 visit.  16. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.

COVID-19 or coronavirus disease 2019 is an emerging infectious disease. The disease was first  identified in China and then spread worldwide; hence, declared as a global pandemic on March  11, 2020 by World Health Organization (WHO). The pandemic is posing formidable challenges to  healthcare systems and humanities worldwide resulting in morbidities and mortalities  unthought of. Rapidly accumulating clinical evidence on COVID-19 paved the way for an  extensive and prompt characterization of the acute phase of the disease. The clinical  presentation is generally that of a respiratory infection with a symptom severity ranging  from a mild common cold-like illness, to a severe viral pneumonia leading to acute  respiratory distress syndrome that is potentially fatal. Characteristic symptoms include  fever, cough, and dyspnoea, although some patients may be asymptomatic. Complications of  severe disease include, but are not limited to, multi-organ failure, septic shock, and acute  respiratory distress syndrome. The COVID-19 infection fatality rate is between 0.5 and 1  percent and the remaining affected patients will mostly recover but need convalescent care.  However, discharge should not be considered as the final point of overcoming coronavirus and  till date evidence on sequelae of the COVID-19 recovered patients is very limited. COVID-19  is a complex multisystem disease that affects pulmonary function, as well as renal,  cardiovascular, and neuropsychiatric health, metabolic derangement; and nutritional status.  The extent to which these alterations may persist remains obscure, till date evidence on long  term sequelae of the COVID-19 recovered patients is very limited. Some of the aftereffects of  it may have a profound impact on 'recovered' patients in the future.  Long-term morbidities were observed in survivors of severe acute respiratory syndrome but it  is unidentified whether experience from SARS is applicable to COVID-19. The SARS-CoV-2  infection is severe in older, immune deficient people and who have any pre-existing medical  conditions. Hence, it is imperative to comprehend the possible long-term sequelae of the  COVID-19 recovered patients, and if they will develop any other harmful illnesses. This study  would help us to understand the in-depth prognosis and sequelae of the disease, as well as  help to uncover to what extent would COVID-19 recovered patients require post-acute care to  recuperate from any further infections or multi-organ damage. Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, known as severe acute  respiratory syndrome coronavirus 2 (SARS-CoV-2). From December 2019, it has rapidly spread  across China and many other countries. COVID-19 pandemic is posing formidable challenges to  healthcare systems and humanities worldwide resulting in morbidities and mortalities  unthought of.  The first case of COVID-19 was officially detected in Bangladesh on March 8, 2020. As of  December 10, 2020, according to the Institute of Epidemiology, Disease Control and Research  (IEDCR), there are 485,965confirmed COVID-19 cases in Bangladesh with 6,967 related deaths  and the Case Fatality Rate (CFR) is 1.38%. The overall attack rate is 1,639 per 1 million.  Regarding age distribution, 27% of cases were between 31 and 40 years old, 21% in the age  group of 21 and 30 years, 19% were between 41 and 50 years, and 15% were in the age group of  51 and 60 years Regarding geographical distribution, 64% of reported confirmed cases were  from the Dhaka district, followed by 5.7%in Chattagram district. Case doubling time is 5 days  for both the Dhaka and Chattagram district.  COVID-19 is a complex multisystem disease that affects pulmonary function, as well as renal,  cardiovascular, and neuropsychiatric health, coagulation derangement as well as nutritional  status A significant proportion of patients who survive from COVID-19 may have the  possibility to get impairment in their overall health status after their recovery. The extent  to which these alterations may persist remains obscure. Some of the aftereffects of it may  have a profound impact on 'recovered' patients in the future This study would help us to  understand the in-depth prognosis and sequelae of the disease, as well as help to uncover to  what extent would COVID-19 recovered patients require post-acute care to recuperate from any  further infections or multi-organ damage.  This is a prospective cohort study which will be done in Dhaka hospital of icddr,b and BSMMU.  We will include all patients aged ≥ 18 years who have COVID-19, confirmed by  reverse-transcriptase polymerase-chain-reaction assay (RT-PCR), following their discharge  from Dhaka hospital or outpatient clinic or inpatient wards of BSMMU. Baseline data of  prognostic importance, including demographic, social information, lifestyle factors, medical  history, underlying comorbidities, anthropometric measurements, clinical, laboratory, imaging  and treatment records will be collected using a standard case report form. A detailed  clinical examination including measurement of vital signs, blood pressure, pulse oximetry,  anthropometric measurements, neurological, pulmonary, cardiovascular system examination will  be performed by trained research physicians at enrollment and at each follow-up visit. We  will perform routine laboratory assays including complete blood count (CBC), serum alanine  transaminase (ALT), serum creatinine, fasting capillary blood glucose using glucometer and  urine routine examination. We will also perform ECG, echocardiography, chest X-ray and  pulmonary function test. Additional tests will be done as and when required such as RT-PCR  test in nasopharyngeal specimen, as well as fasting blood sugar, glycated haemoglobin, MRI/CT  scan of brain etc. Thyroid function tests such as FT4, FT3 and TSH and C peptide will be  performed at 5 month follow-up time point along with other routine investigations.  Participants will be followed up at at 3,5,9,12 ,18 ,24-month time points following discharge  from hospital or OPD, and at any time they have a complain. Inclusion Criteria:  -  Age ≥ 18 years  -  Participants categorized as mild, moderate and severe/critical disease according to  the classification of WHO and the national guideline on COVID-19 case management  published by the DGHS [28], Bangladesh and discharged from the hospital or outpatient  clinic  -  Participants residing within Dhaka city corporation area  -  Willing to participate in this study  Same as exposed group except that they are not exposed to SARS-CoV-2 infection as evident  by negative RT-PCR test. Other criteria for comparison group are given below.  -  Participants will be included if the RT-PCR test is negative during enrollment  -  Age ≥ 18 years  -  Participants residing within Dhaka city corporation area  -  Willing to participate in this study Exclusion Criteria:  -  Participants will be excluded if they have a history mental illness before COVID-19  -  Participants with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant  clinical symptoms in the preceding fourteen days will be excluded.  -  Participants residing outside the Dhaka city corporation area and not willing to  participate in the study  • Participants with any known co morbidities including obesity will be excluded

Virtual reality (VR) has reported benefits of engagement, immersion, and motivation in  rehabilitation and has been proposed to be a solution for long-term engaging rehabilitation  methods. However, the use of VR within the multiple sclerosis (MS) population is not widely  investigated, and even less with regards to upper limb function. The main aim of this study  is to assess the feasibility of using the Oculus Quest VR headset and games for improving  upper limb function within the MS population. Recruited people with MS will be randomly  assigned to either an eight week intervention using VR games that have been designed by  co-production with people with MS and MS-specialists; or to a control group of usual care.  All participants will undertake testing at baseline, four weeks and eight weeks for multiple  outcomes measures related to upper limb and motor function. After completion of the  intervention, participants who undertook VR intervention will complete a survey regarding the  usability of the games, and some individuals will be invited to interviews to express their  experience of using VR and any suggestions for improvement for potential future trials. The aim of this study is to investigate the feasibility of an eight-week intervention of  co-produced virtual reality (VR) games delivered using the Oculus Quest for improving the  upper limb function of people with MS. This study is also a randomised controlled trial with  two arms, one group will undergo the intervention using VR and the other will be a control  group.  This study aims to recruit up to 30 people with MS who have some degree of self-reported  upper limb mobility difficulties from MS clinics in NHS Lanarkshire and MS Revive, a third  sector in Glasgow. Participants will be randomly allocated to a group: an eight week  intervention study using VR and exercise games or a control group of usual care. All groups  will have assessments at baseline, week 4 and week 8. However, only the VR intervention group  will undertake the USE questionnaire and only a select number of participants in the VR group  will participate in the semi-structured interviews.  The VR intervention group will involve participants travelling to a research site twice a  week for eight weeks and each session will be approximately 30 minutes. This 30-minute  intervention will include participating in game play and the participant using the game's  interface (e.g. navigating through menus, selecting which games to play). The games for the  intervention will involve facilitating and replicating upper limb movements: pushing buttons  for the interface; individual finger movement; grasp and release and one game includes  holding a controller for elbow flexion and extension (see table). The intervention group will  undergo exercises in a fully immersive VR environment using the Oculus Quest VR headsets. For  health and safety reasons participants will complete their programme whilst seated.  The control group will not receive a specific exercise programme but will be asked to  continue with their usual care, which could generally include any ongoing physiotherapy or  occupational therapy support or none whatsoever. Any ongoing physiotherapy or occupational  therapy (NHS or non-NHS) will be recorded, detailing the exercises and frequency. After  completion of the week 8 assessment, participants within the control group will be offered  the opportunity to take part in a 30-minute session trialling the VR games. Inclusion Criteria:  -  Confirmed diagnosis of multiple sclerosis.  -  Degree of self-reported hand or upper limb impairment which interferes with some  activities of daily living (ADL) (e.g. dressing, eating, grooming).  -  Objective upper limb impairment, in at least one hand, as determined by a Nine Hole  Peg Test (see Section Outcome Measures) of 2 standard deviations of more above the  published normative values depending on age and sex.  -  Must be able to travel to a research site. Exclusion Criteria:  -  If they have had a relapse in the last three months  -  Subjective cognitive problems resulting in them being unable to use the equipment or  participate in virtual reality.  -  Visual problems such that they cannot see the visual display within the headset (this  does not include participants who have glasses that are enough to correct eyesight  issues)  -  Have a current eye infection.  -  Have any significant co-existing neurological or orthopaedic conditions affecting the  upper limb.  -  Are unable to understand verbal or written explanations of the study or are unable to  speak or understand English.  -  Individuals who are currently enrolled in any clinical trials will be excluded, but  those who have previously taken part in research and other trials will be eligible.

Rehabilitation is crucial in the treatment of people with Parkinson's disease (PD) as it can  ameliorate motor and non-motor impairments, improving their clinical profile and quality of  life. Considering the complex biological processes occurring in PD brain, the identification  of accessible and measurable biomarkers to monitor the events induced by intensive  rehabilitation would help in i)testing rehabilitation effectiveness, ii)improving the design  of clinical trials and iii)personalizing the rehabilitation strategies by the prediction of  patients' responsiveness. The objective of this project is the validation of Raman analysis  of saliva and salivary extracellular vesicles (EV) for the differential diagnosis of  Parkinson's disease (PD) and atypical Parkinsonism. The proposed diagnostic method can be  integrated in the preliminary assessment and monitoring of the patient by providing a quickly  and repeatable measurable biomarker. In the end, this will bring tothe personalization of the  rehabilitation path and provide an indication on the outcome of the rehabilitation treatment. Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such  as bradykinesia, tremor, rigidity and postural instability. An accurate rehabilitation  program designed considering the specific characteristics of the patient allows you to  maximize the effect of drug therapy, improve the patient's quality of life, while also  limiting secondary complications related to the progression of the disease. At the time of  diagnosis, however, it is particularly important to be able to quickly identify individuals  with idiopathic Parkinson's and distinguish them from those who have an atypical form of  Parkinsonism, such as Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA),  Corticobasal Degeneration (CBD) and Dementia with Lewy bodies (DLB). Atypical Parkinsonisms  are in fact progressive diseases that share some signs and symptoms with PD, however these  patients do not respond as effectively to drug therapy since the cellular and degenerative  mechanisms that characterize them are very different. For these reasons, their early  identification is particularly important to identify the best pharmacological and  rehabilitative path for each patient.  To ensure a more accurate patient profiling that takes into account the individual complex  clinical picture, the discovery of a biomarker that can be periodically measured in an easily  accessible biofluid would allow for better patient stratification, monitoring of the course  of the disease and careful study of the effects of the pharmacological and rehabilitation  program as well as its personalization, with a view to precision medicine designed, defined  and built on the patient.  The Laboratory of Nanomedicine and Clinical Biophotonics (LABION) of Fondazione Don Gnocchi  has been working for years on using innovative methods such as Raman spectroscopy to identify  biomarkers of neurodegenerative diseases in easily accessible biological fluids, such as  blood and saliva. Raman Spectroscopy (RS) allows to obtain a specific and complete  characterization of a specific fluid in a rapid, sensitive and non-destructive way, without  particular procedures for the preparation of the sample to be analyzed. In RS the entire  spectrum obtained from the sample is used as a highly specific "fingerprint" for the selected  sample (eg saliva, blood, serum, cerebrospinal fluid) which represents the diagnostic  biomarker. The Raman analysis of saliva has already demonstrated the possibility of profiling  patients with progressive pathologies with good accuracy and, specifically, of distinguishing  subjects suffering from amyotrophic lateral sclerosis compared to subjects with other types  of neurodegenerative diseases.  At the same time, LABION has verified the possibility of characterizing by Raman  spectroscopy, the extracellular vesicles (EV) circulating in the blood of patients with PD.  Since 2017, LABION has been working on the biochemical study of circulating EVs in the serum  of PD patients by analyzing the EVs in spectroscopy and the ability of RS to identify a  specific biochemical profile of blood vesicles that correlates with clinical scales has been  demonstrated. UPDRS III and Hoehn and Yahr. The analysis of the EVs present in the saliva of  patients with PD could help to understand the origin of biochemical alterations in the saliva  as well as identify even more specific markers.  Raman spectroscopy is therefore proposed as a useful method for the rapid and comprehensive  biochemical characterization of saliva and the vesicular component present within it, without  the use of staining and labeling procedures.  The objective of this project is the validation of a specific Raman molecular signature for  the different experimental groups, which can lead to the determination of a biomarker useful  for the differential diagnosis of people with PD compared to subjects with atypical  Parkinsonism, through the analysis of a biological fluid that is not invasive, thus filling  the current lack of a measurable biomarker for rapid differential diagnosis and for  monitoring the evolution of the diseases.  The rapid identification and differential diagnosis of subjects with Parkinson's disease and  atypical parkinsonisms will allow to promptly identify the optimal pharmacological and  rehabilitative therapy for each subject, leading to a significant improvement in the quality  of life for the patient and, in the future, an increased probability slowing the progression  of the disease.  SAMPLE COLLECTION: Saliva collection from all the selected subjects will be performed  following the Salivette (SARSTEDT) manufacturer's instructions. Saliva will be obtained from  all subjects after an appropriate lag time from feeding and teeth brushing. Pre-analytical  parameters (i.e. storage temperature and time between collection and processing), dietary and  smoking habit will be properly recorded. Briefly, the swab will be placed in the mouth and  chewed for 60 seconds to stimulate salivation. Then the swab will be centrifuged for 2  minutes at 1,000 g to remove cells fragments and food debris. Collected samples will be  stored at -80° C.  SAMPLE PROCESSING: For the Raman analysis, a drop of each sample will be casted on an  aluminium foil in order to achieve the Surface Enhanced Raman Scattering (SERS).  EV ISOLATION: different isolation methods will be tested for effective EV isolation. Purified  EVs will be then concentrated and analysed by means of standard techniques and by Raman  spectroscopy following a previously optimized protocol for blood EVs. The experimetal  settings will be adapted to the salivary EVs, considering variations in substrate,  acquisition time, etc.  DATA COLLECTION: Salivary and EV spectra will be acquired using an Aramis Raman microscope  (Horiba Jobin-Yvon, France) equipped with a laser light source operating at 785 nm and 532  nm. The instrument will be calibrated before each analysis using the reference band of  silicon at 520.7 cm-1. Raman spectra will be acquired in the region between 400 and 1600 cm-1  for saliva, 500-1800 nad 2600-3200 cm-1 for EVs using a 50x objective. The software package  LabSpec 6 (Horiba Jobin-Yvon, France) will be used for the acquisition of spectra.  DATA PROCESSING: All the acquired spectra will be baseline corrected and normalized by unit  vector using the dedicated software LabSpec 6. The contribution of the substrate will be  removed from each spectra, if necessary. The statistical analysis to validate the method,  will be performed using a multivariate analysis approach. Principal Component analysis (PCA)  will be performed in order to reduce data dimensions and to evidence major trends. The first  20 resultant Principal Components (PCs) will be used in a classification model, Linear  Discriminant Analysis (LDA), to discriminate the data maximizing the variance between the  selected groups. The smallest number of PCs will be selected to prevent data overfitting.  Leave-one-out cross-validation and confusion matrix test will be used to evaluate the method  sensitivity, precision and accuracy of the LDA model. Mann-Whitney will be performed on PCs  scores to verify the differences statistically relevant between the analysed groups.  Correlation and partial correlation analysis will be performed using the Spearman's test,  assuming as valid correlation only the coefficients with a p-value lower than 0.05. The  statistical analysis will be performed using Origin2018 (OriginLab, USA).  ROC Curve will be calculated to assess thediagnostic potential of the method. Inclusion Criteria:  For Pakinson's disease: diagnosis following "MDS clinical diagnostic criteria for  Parkinson's disease" (Postuma et al. Movement Disorders vol. 30 1591-1601, 2015), with  Hoehn&Yahr between 1 and 3.  The diagnosis of Progressive Supranuclear Palsy will be made according to the criteria of  the Movement Disorders Society (Höglinger et al. Mov. Disord. 32, 853-864, 2017). The  diagnosis of Corticobasal Syndrome will be made according to the 2013 Armstrong criteria  (Armstrong et al. Neurology 80, 496-503, 2013).  The diagnosis of multiple system atrophy will be made according to the Gilman criteria of  The diagnosis of Behavior Disorder in REM phase will be made according to the criteria of  the "International Classification of Sleep Disorders, Third Edition (ICSD-3)". Exclusion Criteria:  For all the experimental groups considered and for healthy controls, subjects with  concomitant chronic and / or inflammatory diseases of the oral cavity, other systemic  diseases (eg anemia, cardiovascular or respiratory diseases), oncological or infectious  diseases will be excluded.  Vascular parkinsonisms, monogenic parkinsonisms will also be excluded as well as iatrogenic  parkinsonisms, parkinsonisms secondary to exposure to known neurotoxins; parkinsonisms  secondary to tumor lesions; parkinsonisms due to normotensive hydrocephalus; subjects with  a form of dementia, severe speech disorders and other psychiatric and / or neurological  pathologies.

To assess the safety, immunogenicity and preliminary efficacy of 3D189 in patients with  hematological malignancies. This is a phase 1, open-label, non-comparative, multicenter study of 3D189 (also known as  galinpepimut-S), a multivalent peptide vaccine targeting Wilms Tumor-1 (WT1), for maintenance  immunotherapy in patients with WT1-positive hematological malignancies, including patients  with acute leukemia (AL) patients in complete remission (CR), or multiple myeloma (MM),  non-Hodgkin lymphoma (NHL) or higher-risk myelodysplastic syndrome (MDS) patients who have  received at least first-line standard therapy and recently achieved CR or partial remission  (PR), if the latter is the best achievable response for the patient. Inclusion Criteria:  -  Subjects must be willing and able to understand and provide signed informed consent  for the study.  -  Male or female patients ≥ 18 years of age on the day of signing informed consent.  -  Have a histologically or cytologically confirmed hematological malignancy and have  achieved complete remission (CR) or partial remission (PR) after at least one line of  standard therapy, and are not suitable for hematopoietic stem cell transplant (HSCT)  for the following reasons: a) not eligible for HSCT due to intercurrent medical  conditions; b) lack of an available HLA-matched donor for allogeneic HSCT; c) not able  to accept HSCT for financial reasons; d) without a potential indication for HSCT (e.g.  having a relatively favorable prognosis or low risk of relapse). However, patients who  have previously received autologous HSCT but remain MRD+ or in remission after salvage  therapy for post-transplant relapse are allowed to be recruited.  Including the following 4 types of hematological malignancies:  1. Acute Leukemia (AL): including acute myeloma leukemia (AML) and acute lymphoblastic  leukemia (ALL), in morphological complete remission with complete or incomplete blood  count recovery (CR or CRi), and having completed any planned post-remission therapy;  2. Myelodysplastic Syndrome (MDS): Revised International Prognostic Scoring System  (IPSS-R) risk score > 3.5, having achieved CR or PR following prior therapy;  3. Multiple Myeloma (MM): having achieved stringent complete response (sCR), CR or very  good partial response (VGPR), or PR if deeper response cannot be obtained from  adequate therapy.  4. Non-Hodgkin Lymphoma (NHL): preference for patients with diffuse large B-cell lymphoma  (DLBCL) and follicular lymphoma (FL) who have achieved CR or PR following prior  therapy.  -  Have a documented WT1 positive disease. This is defined as detectable presence of  WT1 transcript via real-time quantitative polymerase chain reaction (RT-PCR) in  patients'bone marrow or peripheral blood samples, or WT1 expression by  immunohistochemistry (IHC) in archived (paraffin embedded, unstained slides) or  freshly biopsied tumor tissues from bone marrow or lymph nodes or extranodal  lesions ( for NHL patients).  -  Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.  -  Estimated life expectancy ≥ 6 months.  -  The interval between the last antitumor therapy (including surgery, radiotherapy  and systemic therapy) and the first study treatment must be at least 4 weeks, and  the toxicity of the previous therapies have recovered to ≤ grade 1 [according to  the Common Terminology Criteria for Adverse Events (CTCAE) 5.0], except for  toxicity such as alopecia, which in the judgment of the investigator is not a  safety risk.  -  Have adequate organ and bone marrow function, defined as follows:  1) Blood count (participants must not have received transfusion of blood products or  hematopoietic growth factors within 14 days prior to this test): hemoglobin (Hb) ≥ 9.0  g/dL; neutrophil (NEUT) ≥ 1.0×109/L; platelet (PLT) ≥ 50×109/L; 2) Liver function: alanine  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ×ULN (upper limit of  normal); but for subjects with liver metastasis, ALT or AST ≤ 5×ULN; total bilirubin (TBIL)  ≤ 1.5 × ULN, or TBIL > 1.5 × ULN, but direct bilirubin (DBIL) ≤ 1.0 × ULN; 3) Renal  function: serum creatinine ≤ 1.5 × ULN or endogenous creatinine clearance rate ≥ 50 ml/min  (Cockcroft-Gault formula); 4) Coagulation: international normalized ratio (INR) ≤ 1.5,  activated partial thromboplastin time (APTT) ≤ 1.5 ×ULN, unless subjects are receiving  anticoagulant therapy as long as INR or APTT is within the therapeutic range of intended  use of anticoagulants; 5) Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%  by echocardiography.  • Subjects (including partners) must agree to use an adequate method of contraception,  starting with the screening visit through 4 months after the last dose of study treatment. Exclusion Criteria:  -  Previously treated with any therapy targeting WT1.  -  Have known hypersensitivity to peptide biologics, or to immune adjuvants Montanide  and/or GM-CSF.  -  Subjects with acute promyelocytic leukemia (APL or M3).  -  Presence of central nervous system (CNS) invasion and/or carcinomatous meningitis;  participants with previously cured brain or meningeal metastasis can be allowed.  -  Have undergone prior allogeneic HSCT, or plan to perform HSCT during the study period.  -  Received live vaccine within 4 weeks prior to the first dose of study treatment.  -  Currently participate in or have participated in a study of an interventional agent or  device within 4 weeks prior to the first dose of study treatment.  -  Have a known additional malignancies within the past 5 years, with the exception of  cured skin basal cell carcinoma or cervical cancer in situ or other carcinoma in situ.  -  Have an active autoimmune disease or any disease that requires long-term use  (including use within 4 weeks prior to the first dose of study drug) of systemic  corticosteroids (at doses greater than 10 mg daily of prednisone equivalent) or any  other form of immunosuppressive agents, hormone replacement therapy for adrenocortical  insufficiency, hypopituitarism, hypothyroidism, or type I diabetes mellitus is not  considered a form of systemic treatment and is allowed.  -  Have a diagnosis of primary immunodeficiency disease, or acquired immunodeficiency  syndrome, or a positive test for human immunodeficiency virus (HIV).  -  Presence of active tuberculosis.  -  Have a history of a severe cardiovascular disease such as class III or IV heart  failure [New York Heart Association (NYHA) criteria], myocardial infarction or stroke,  unstable arrhythmia or unstable angina within 6 months prior to start of study  treatment.  -  QTcF interval tested during the screening period ≥ 450 msec (for male subjects) or ≥  470 msec (for female).  -  Have an acute severe infection requiring systemic therapy during the screening period.  -  Positive for HBsAg and HBV DNA ≥ 103 IU/ml; or positive for HCV antibodies and HCV RNA  level is above the detection limit.  -  Are pregnant or breastfeeding, or have a positive serum pregnancy test during the  screening period (for female subjects of childbearing potential).  -  Have a known psychiatric or substance abuse disorder that would interfere with the  participant's ability to cooperate with the requirements of the study.  -  Any condition, therapy or laboratory abnormality that, in the opinion of the  investigator, might affect the participant's compliance, pose an unwarranted high risk  to the participant, or interfere with the interpretation of the study results.

The aim of this study is to examine the performance of determining the sarcopenia by  anthropometric measurements (mid-upper arm circumference and calf circumference) added to the  SARC-F questionnaire developed as a screening tool for the risk of sarcopenia in the  community-dwelling older adults. The risk of sarcopenia of the individuals over 65 years of  age who applied to the Geriatrics Department of Ege University Medical Faculty Hospital  Internal Diseases Department. was determined by the SARC-F questionnaire, muscle mass was  established by bioelectrical impedance analysis, muscle strength was assessed by handgrip  strength, physical performance was assessed by a 4-meter walking test and presence of  malnutrition was assessed with an MNA-long form. For the diagnosis of sarcopenia; old (EWGSOP  1) and revised (EWGSOP 2) diagnostic criteria of Sarcopenia Study Group in Elderly  Individuals of the European Union Geriatric Medicine Association were used. New parameters  were obtained by adding calf circumference (SARC-CC) and mid-upper arm circumference  (SARC-MUAC) measurements were added separately and together (SARC-CC-MUAC) to the SARC-F. For  the calf circumference cut-off points of <31 cm and <33 cm and for the mid-upper arm  circumference cut-off points of <25 cm and <31 cm were used for the sensitivity and  specificity analyses. The population of the research is individuals aged 65 and over who applied to Ege University  Medical Faculty Hospital Internal Diseases Department, Geriatrics BD Outpatient Clinic. For  statistical power analysis; When α=0.05 and the power of the study are 0.80, the minimum  number of samples required for the study was determined as 190. The relevant sample size was  calculated with the G-Power 3.0.8 package program.  Data collection tools:  1. General information collection form: Investigator collect data about age, gender,  chronic diseases, economic status, etc of participants  2. Measurement of Muscle Mass, Muscle Strength, and Gait Speed Body composition analysis  was determined by electrical bioimpedance using the Tanita MC-780 multi-frequency  segmental Body Composition Analyzer (Tanita Corporation, Tokyo). The appendicular  skeletal muscle mass (ASM) was calculated with the Janssen equation for EWGSOP criteria  and Sergi equation for EWGSOP 2 criteria. The appendicular muscle mass index (ASMI) was  calculated based on the equation: ASM(kg) /height (m2).  Muscle strength (kg) was assessed with the Takei Grip Strength Dynamometer®. Handgrip  strength (HS) measurements were made with the subjects in a sitting position, with the  elbow and wrist in full extension, three times with an interval of five seconds on both  hands, and the highest value among the measurement results was used for analysis.  Gender-specific cut-offs were used to define low muscle strength (30 and 20 kg in males  and females) for EWGSOP criteria, and (27 and 16 kg in males and females) for EWGSOP 2  criteria. Usual gait speed (m/s) was performed by the subjects walking 4 m with usual  speed and ≤0.8 m/s was defined as low walking speed.  3. Anthropometric measurement:  In all participants, height was measured using a stadiometer to the nearest 0.1 cm,  weight was measured unclothed to the nearest 0.1 kg using a calibrated balance scale.  Body mass index (BMI) was calculated by the weight (kg)/height (m2) equation.  The calf circumference (CC) of participants was measured with an inflexible tape  measure, in the sitting position, with the knee flexed to 90º, and the circumference of  the widest part of the calf. Both the standard CC cut-off (<31 cm) and  population-specific cut-off (<33 cm) were used and compared in SARC-CalF analysis. Mid  upper arm circumference (MUAC) was measured in a stand position, the mid-point of the  participant's left upper arm- located between the acromion and olecranon- was marked  when the elbow bent to a 90o angle and measured with the inflexible tape around the  marked midpoint with the participant's arm hung down naturally.  4. Screening of sarcopenia risk and assessment of sarcopenia SARC-F, SARC-CalF, and  SARC-MUAC were used for screening sarcopenia risk. For the SARC-F total score of ≥4,  SARC-CalF ≥11, and SARC-MUAC≥11 were defined as positive sarcopenia risk. Investigator  used EWGSOP and EWGSOP 2 criteria for sarcopenia diagnosis.  5. Statistic analysis: SPSS 25.0 (SPSS Statistics; IBM, Armonk, NY) and MedCalc Statistical  Software 19.1.6-free trial (MedCalc Software, Ostend, Belgium) statistical package  programs were used for statistical analysis. The level of significance was defined as  p<0.05.  For categorical variables, the data were presented as numbers (percentage). Continuous  variables with normal or skewed distribution were presented as mean (standard deviation) or  median (interquartile range), respectively. Group differences were investigated using the  t-test for normally distributed data and the Mann-Whitney test for skewed data and the X2 or  Fisher's exact test for categorical data was used. Using EWGSOP and EWGSOP 2 criteria as the  reference standard, the investigator calculated the diagnostic value of the SARC-F,  SARC-CalF- 31, and SARC-CalF-33 [sensitivity, specificity, positive predictive value (PPV),  negative predictive value (NPV), and accuracy] for identifying sarcopenia. A receiver  operating characteristics (ROC) curve was used to compare the overall accuracy of SARC-F,  SARC-CalF-31, and SARC-CalF-33. The area under the ROC curve (AUC) and 95% confidence  interval (CI) were calculated.  The exclusion criteria are as follows: an implanted pacemaker, severe mental illness, unable  to walk, severe heart failure, severe renal failure, clinically visible edema, and unable to  communicate.  Participants in which all the evaluations in the research protocol were carried out and  answered all the questions. Inclusion Criteria:  participants who applied to the geriatrics outpatient clinic for any reason Exclusion Criteria:  Participants with an implanted pacemaker, severe mental illness, unable to walk, severe  heart failure, severe renal failure, clinically visible edema, and unable to communicate.

This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind,  placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus  placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR.  Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post  hospitalization and a positive COVID-19 testing. The study is planned to include 4 cohorts, with enrolled patients being randomized 1:1 in a  blinded manner on Day 1, following screening, to F-652 or placebo as follows:  -  Cohort 1 (sentinel cohort): Four patients will receive either dose level 1 F-652 or  placebo. Upon completion of sentinel, the Data Monitoring Committee will evaluate the  safety and tolerability data of the sentinel patients and determine if it is acceptable  to dose the remaining patients in this dosing group in Cohort 2.  -  Cohort 2: Fourteen patients will receive either dose level 1 F-652 or placebo. Upon  completion of Cohort 2, the DMC will convene and review all available safety data to  determine if the study can proceed to the next dose level.  -  Cohort 3 (sentinel cohort): Four patients will receive either dose level 2 F-652 or  placebo. Upon completion of sentinel dosing, the DMC will evaluate the safety and  tolerability data of the sentinel patients and determine if it is acceptable to dose the  remaining patients in this dosing group in Cohort 4.  -  Cohort 4: Sixteen patients will receive either dose level 2 F-652 or placebo. Treatment  will begin on Day 1 following randomization. Patients assigned to active drug will  receive a total of 2 doses of F-652 (1 IV infusion on Day 1 and 1 IV infusion on Day 8).  Patients assigned to placebo will receive identical IV infusions of placebo vehicle on  Days 1 and 8. All patients will receive available supportive and antiviral therapies as  standard of care. Efficacy will be assessed on Days 15 and 29. Patients will be followed  for safety until Day 60.  The primary efficacy endpoint is the proportion of patients with a ≥2-point increase in the  National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale from  baseline to Day 29.  The secondary efficacy endpoints include the proportion of patients with a ≥2-point increase  in the NIAID 8-point ordinal scale from baseline to Day 15, mortality rate by Days 15 and 29,  percentage of patients who have recovered and discharged from the hospital by Days 15 and 29,  and percentage of patients progressed to severe/critical disease by Day 15.  The safety endpoints include all cause treatment-emergent adverse events (TEAEs) and serious  adverse events (SAEs); change from screening (baseline) in clinical symptoms and abnormal  vital signs, abnormal laboratory tests; and relationship of any AEs with F-652 treatment.  The exploratory endpoints include time to negative SARS-CoV-2 PCR test from randomization;  and changes in pharmacodynamic parameters. Inclusion Criteria:  -  Willing to provide informed consent and able to comply with protocol requirements  -  18 years or older  -  Has a COVID-19 diagnosis confirmed by PCR  -  Hospitalized within 5 days and meets the following criteria at screening:  Peripheral capillary oxygen saturation (SpO2) ≤ 93% on room air or SpO2 ≥93% on ≤10 liters  per minute of supplemental oxygen via nasal cannula  -  Radiographic (chest X-ray, computed tomography scan, or ultrasound) evidence of  bilateral pulmonary infiltrates consistent with SARS-CoV-2/COVID-19  -  Clinical symptoms consistent with COVID-19 per Investigator judgement  -  Body mass index between 18 to 40 kg/m2  -  If of reproductive potential, willing to abstain or agree to the use of highly  effective contraception Exclusion Criteria:  -  Respiratory failure at screening  -  History of heart failure  -  History of COPD or bronchial asthma  -  Active TB or history of TB of the following types  -  Uncontrolled arrhythmia within 3 months prior to randomization  -  Heart disease of the following types  -  Moderate to severe renal insufficiency  -  Abnormal white cell and platelet counts  -  History of transplantation of vital organs (e.g., heart, lung, liver, and/or kidney);  -  Malignant tumor  -  Uncontrolled systemic or local autoimmune or inflammatory disease besides SARS-CoV-2  -  Unhealed wounds, active gastric ulcer, had surgery  -  Received other investigational therapeutic products  -  Used interferon therapies  -  History of HIV infection, hepatitis B, and/or hepatitis C  -  Known serious allergic reaction or hypersensitivity to components of F-652  -  Pregnant or breastfeeding  -  History of drug abuse or use of narcotics  -  Treated with immunomodulators or immunosuppressants  -  Other conditions resulting in increased risk

The primary objective of this study is to evaluate whether the management of colorectal  cancer (CRC) patients with 5-fluorouracil (5-FU) exposure optimization testing reduces 5-FU  related toxicities and improves outcomes compared to the current standard of care. A  secondary objective is to characterize the variability of 5-FU levels among CRC patients  managed with 5-FU exposure optimization testing and the impact of such management on 5-FU  plasma levels and drug doses during the course of chemotherapy. This is a multi-center retrospective matched cohort study of early and late stage CRC  patients who received 5-FU doses determined using body surface area (BSA) and in patients who  underwent pharmacokinetically (PK)-guided 5-FU dose monitoring and adjustment. A  retrospective chart / electronic medical record review of colorectal cancer patients treated  with infusional 5-FU regimens between May 1, 2009 and December 31, 2013, satisfying the  inclusion/exclusion criteria, will be performed. In this multi-center study, patients who  underwent PK-testing during at least two different 5-FU administrations will be matched to  patients who received doses based on their BSA, treated at the same institution. Matching for  selection of the BSA cohort at each site will be done using the following criteria (based on  factors that may influence 5-FU metabolism): age, gender, disease stage, prior chemotherapy  treatment, and 5-FU containing treatment regimen being used. Each patient will be assigned a  random five-digit Study ID number to protect patient confidentiality. Minimal medical  history/demographics data will be collected from the patient's medical records / clinic chart  using paper case report forms (CRFs). The data to be collected from each patient's records  will include: patient demographics (i.e. gender, age, height, and race), colorectal cancer  diagnosis (i.e. date of primary diagnosis, tumor stage, grade, histology and phenotype, and  date of metastatic diagnosis and sites of metastases if applicable), use of prior therapies  for treatment of CRC, 5-FU containing regimen details throughout the 5-FU treatment (i.e.  weight, BSA, ECOG status, doses of each drug used in the regimen, and 5-FU infusion  start/stop dates and times), 5-FU PK testing results (if applicable), concomitant procedures  and medications, CBC and chemistry testing results, adverse events experienced during 5-FU  therapy regimen, and tumor response and follow-up information. Patients will not be contacted  for the purposes of this study and a waiver of HIPAA authorization will be requested from the  appropriate IRB. Once data has been collected and monitored, all records tying the random  Study ID number to a specific patient at the sites will be destroyed, rendering all  information de-identified. Inclusion Criteria:  -  Male or female patients 18 years of age or older.  -  Patients with histologically confirmed colorectal cancer who were treated with an  infusional 5-FU regimen between May 1, 2009 and December 31, 2013.  -  PK-Guided Cohort: Patients monitored with 5-FU PK-testing at a minimum of two  administrations of 5-FU throughout the course of a single infusional 5-FU containing  treatment regimen.  -  BSA Cohort: Patients who received infusional 5-FU doses calculated based on their BSA. Exclusion Criteria:  -  Patients less than 18 years of age.  -  Patients with concurrent treatment of other active malignancies.  -  Patients that underwent radiation therapy concurrently with chemotherapy.

The effect of therapeutic touch applied to hemodialysis patients on the level of loneliness  and hopelessness is being investigated. It encourages nurses to practice therapeutic touch. Chronic diseases are a challenging process that affects human life physiologically and  psychologically. Chronic Renal Failure, which shows a significant increase in the world and  in our country, also affects human life in every aspect. Hemodialysis treatment is used with  a high rate in the treatment of patients diagnosed with End Stage Renal Failure.  Hemodialysis patients experience loneliness and hopelessness during their difficult and  compulsory treatmet. Fear of being alone is an important problem affecting the patient's  compliance with treatment. In addition, the other problem these patients experience is  hopelessness. Hopelessness is an important factor that affects the patient's expectations for  the future and the process of solving problems.  Therapeutic touch is a complementary and alternative treatment method. It is stated that this  treatment method, which is successfully used by nurses, is good for loneliness and  hopelessness. This method, which will be used on hemodialysis patients, is aimed to get away  from the problems of loneliness and hopelessness.  In this study, two scales will be used to measure the loneliness and hopelessness levels of  hemodialysis patients. Patients will fill in UCLA Loneliness Scale and BECK Hopelessness  Scale.  Nurses should not ignore the problems of loneliness and hopelessness in hemodialysis  patients. Therapeutic touch treatment method wil lprovide nurses the holistic caregiver role  for the feelings of loneliness and hopelessness experienced by the patients. When the  literature is scanned, this study is unique because it has not been done before on  hemodialysis patients. Inclusion Criteria:  -  Having hemodialysis treatment for at least 3 months,  -  Cognitive patients,  -  Having a score of UCLA> 20 and BECK≥4 scoring,  -  Involved in the work with us. Exclusion Criteria:  • Patients using traditional treatment for the disease were not included in the study.

This intervention pilot feasibility study will assess the impact of auricular acupressure as  an additional non-pharmacologic therapy for infants at risk for developing Iatrogenic  Withdrawal Syndrome (IWS) in the Pediatric Cardiac Intensive Care Unit (PCICU) of Monroe  Carrell Jr Children's Hospital at Vanderbilt (MCJCHV). The investigators will recruit 40  healthy, 34 weeks gestational age or older infants exposed to prolonged medications (greater  than 5 days) for cardiac procedures that may cause withdrawal upon cessation such as opioids,  benzodiazepines, or other sedative medications. Participants will receive the auricular  acupressure in addition to the standard of care such as clustered nursing care, touch,  position change, environmental controls, holding, and swaddling. This intervention pilot feasibility study will assess the impact of auricular acupressure as  an additional non-pharmacologic therapy for infants at risk for developing Iatrogenic  Withdrawal Syndrome (IWS) in the Pediatric Cardiac Intensive Care Unit (PCICU) of Monroe  Carrell Jr Children's Hospital at Vanderbilt (MCJCHV). The investigators will recruit 40  healthy, 34 weeks gestational age or older infants exposed to prolonged medications (greater  than 5 days) for cardiac procedures that may cause withdrawal upon cessation such as opioids,  benzodiazepines, or other sedative medications. Participants will receive the auricular  acupressure in addition to the standard of care such as clustered nursing care, touch,  position change, environmental controls, holding, and swaddling. Within 24 hours of  implementing a weaning protocol, acupressure will be applied to three designated points of  one ear following the NADA protocol acupuncture technique while also incorporating the  Near-Term Infant (NTI) conceptual framework identified elements (see figure 3). Acupressure  will be administered via stickers that are adhesive to the skin like a Band-Aid (see figure  1). These stickers include a vaccaria plant seed in the center that applies continuous light  pressure on the designated points. This form of acupressure was selected as it is organic and  does not contain metal which may interfere with emergency medical care such as imaging. After  the initial 24 hours of application, stickers will be removed, the infant's skin will be  assessed for any disruption such as bruising or discoloration, and the stickers will be  rotated to the infant's other ear at the same NADA protocol auricular sites. Acupressure  stickers will be removed and applied to the opposite ear every 48 hours until withdrawal  symptoms improve (1). Withdrawal symptoms are measured every 6 hours with the enhanced  Withdrawal Assessment tool (WAT) as part of the standard of care. Upon completion of the  weaning regimen, infants with a score of less than or equal to 3 or less than 2 above  baseline with no more than 2 rescue medication doses in 24 hours will have the acupressure  removed. Inclusion Criteria:  -  Infants, 34 weeks or greater gestation  -  Exposure to opioids and/or benzodiazepine medications for 5 days or more  -  Beginning a stable wean  -  Maternal age of 18 or older Exclusion Criteria:  -  Hemodynamic instability  -  Transfer to another facility prior to completion of the weaning regimen  -  Death

Evaluation of a workplace intervention to implement supported wellbeing centres in a  healthcare workplace during and after the COVID-19 pandemic.  Mixed-Methods Evaluation study - including collection of service use monitoring data, online  survey and qualitative interviews. Project Aims:  1. To describe the cost, reach and usage of the Staff Wellbeing Centres  2. To gather insight into experiences of those who access the facility ('service users') as  well as those of support workers ('wellbeing buddies').  3. To identify any facilitators, obstacles or barriers to accessing the facility.  4. To identify perceptions of facility users and non-users towards the value of the  facilities during and after the coronavirus pandemic.  5. To establish recommendations for longer-term sustainability of the wellbeing centres.  Interviews will be conducted with up to 45 interview participants (10-15 Wellbeing Buddies,  25-30 Staff).  Online survey will be conducted - all Nottingham University Hospitals National Health Service  (NHS) staff invited to take part (>14,000).  The survey will include measures of mental wellbeing (Warwick-Edinburgh Wellbeing Scale,  14-item - license received), and single items measures of job stressfulness, job  satisfaction, presenteeism, turnover intentions and work engagement. Inclusion Criteria:  -  National Health Service staff which includes employees, volunteers or healthcare  students, as well as bank staff (all have access to the Staff Wellbeing Centres).  -  Ability to give informed consent. For survey element: Ability to access the internet  (to complete the online survey) For interview element: Ability to attend an individual  interview. Exclusion Criteria: • Inability to communicate in spoken English.

Summary Rationale: The diaphragm is a dome-shaped muscle which separates the thoracic cavity  from the abdomen. In patients with diaphragm paralysis the treatment (surgery versus  non-invasive ventilation) is based on physician preference, not sound scientific evidence.  Clearly studies are needed to guide a scientific decision making.  Objective: In this pilot study the investigators will evaluate if participants are willing  and able to participate in a randomized trial. Secondly this pilot study is also needed to  know the clinical relevant effect of both therapies on EQ-5D_5L, the latter being the primary  outcome. Finally, it will show the investigators the costs of both therapies form a societal  perspective.  Study design: open-label, multi center randomized controlled trial / pilot Study population:  20 participants >18 year and diagnosed with a unilateral of bilateral diaphragm paralysis  resulting from phrenic nerve injury.  Intervention: 10 participants for surgical plication and 10 participants for nocturnal  non-invasive ventilation.  Main study parameters/endpoints: The primary question is whether the intended cost  effectiveness / cost utility study is feasible. In the investigators opinion the intended  study is feasible if at least 50% of the participants fulfilling the inclusions criteria are  randomized in this pilot study.  The second goal of the preparatory study is to describe the effect of both plication and NIV  on the endpoints of the intended efficiency study. The intended primary endpoint is quality  of life as measured by the EQ-5D-5L questionnaire. Secondary endpoints are; the Medical  Research Council (MRC) dyspnoea scale, the Diaphragmatic Paralysis Questionnaire, Borg  dyspnoea score, Endurance Shuttle Walk Test (ESWT), spirometry in both sitting and supine  position, a polysomnography and transcutaneous measurement of carbon dioxide an oxygen  saturation at night. INTRODUCTION AND RATIONALE  The diaphragm is a dome-shaped muscle which separates the thoracic cavity from the abdomen.  It is the most important muscle of respiration innervated by the phrenic nerves. While many  diseases might interfere with its function (1), in the intended study the investigators will  focus on diaphragm paralysis due to phrenic nerve injury. Two types of diaphragm paralysis  can be distinguished: unilateral and bilateral. Patients with unilateral paralysis perceive  exertional dyspnea, have an impaired exercise capacity and orthopnea.(2) Patients with a  bilateral paralysis usually have more symptoms and might even develop respiratory failure.  (3) In addition, all patients with a diaphragm paralysis may have poor sleep quality, as the  diaphragm is the only active respiratory muscle during REM sleep. (4) Currently, two  treatment approaches for patients with diaphragm paralysis are used in clinical practice:  surgical diaphragm plication and nocturnal non-invasive ventilation (NIV). Plication is a  minimal invasive surgical procedure that aims to stiffen the diaphragm and such limits  dysfunctional (paradoxical movement) excursions of the paralytic diaphragm. The procedure is  performed in ±70 patients per year in the Netherlands. NIV is a non-invasive mode of positive  pressure ventilatory assistance; through a facial mask the ventilator supports patient  breathing effort. Patients with diaphragm paralysis use their ventilator mainly during night  time, to improve quality of sleep and such to reduce day time symptoms. In the Netherlands,  home mechanical ventilation is very well organized, as care is delivered by only 4  specialized centers. NIV for diaphragm paralysis is started in around 50 patients yearly.  Currently, both plication and nocturnal NIV appear beneficial and both options are covered by  health care insurance. However, it is unknown which intervention is most beneficial from a  patient perspective. For instance, comparison on patient relevant outcome measures and  complications between these treatment approaches is unknown. In addition, patients with  diaphragm paralysis may develop severe symptoms, limiting daily activities including ability  to perform their professional work. To assess the overall impact of this a detailed cost  analysis is necessary to compare both treatments from a societal perspective. A solid cost  effectiveness / cost utility study will reveal which therapy is the best option from a  societal perspective.  This preparatory study will be set up as a randomized pilot study to evaluate if patients are  willing and able to participate in this trial. Question is, are participants willing to  participate, are they willing to travel to the other institute and are they able to comply  with the follow-up measurements. Participants referred to either one of the therapies might  be biased towards that therapy and the questions is whether well informed about both  therapies, they are willing to participate. To know what clinical effect of both therapies is  relevant the EQ-5D-5L is used. It is unknown whether there is a significant difference on the  outcome between both therapies. A search in trial registries did not reveal any study with  similar research questions. Based on the outcomes of this preparatory study a power analysis  can be performed for the seminal study. Due to the acute origin of a diaphragm paralysis  patients get suddenly severely impaired which is interfering enormously with their lives. As  this is often happening in middle aged patients they often have to discontinue professional  activities. This means that the potential impact of this disorder is huge from patient and  societal perspective and needs to be assessed.  As both therapies are completely different for invasiveness, the investigators need to  compare the side effects and possible complications. Possible complications of the surgery  are infection, bleeding and abdominal pain while the well know side effects of ventilatory  support are leakage of the mask, aerophagia and a-synchrony between breathing pattern of the  patient and the ventilator. As this is also an important outcome of this pilot study  participants will be closely monitored from the start of therapy and there will be a  telephone call after 2 months Inclusion Criteria:  -  >18 years  -  diagnosed with a unilateral or bilateral diaphragm paralysis based on isolated phrenic  nerve injury.  Unilateral or bilateral diaphragm paralysis is defined as follows: complaints of dyspnea  and / or orthopnea combined with a drop in VC of more than 15% when change from upright to  supine position and a positive sniff test during fluoroscopy or ultrasonography. A positive  sniff test means that the diaphragm stands still or even moves in cranial direction  (paradoxical movement ) during the sniff inspiratory maneuver.  -  Ability to provide written consent  -  Time between diagnosis and treatment should be at least 1 year Exclusion Criteria:  -  Patients diagnosed with a unilateral or bilateral diaphragm paralysis due to a more  systemic neurological or neuromuscular disorder like for example Amyotrophic Lateral  Sclerosis ,  -  Hypercapnia during daytime (PaCO2 > 6.0 kPa)  -  Radiotherapy of the thorax  -  Contra indication for diaphragm surgery.

Idiopathic inflammatory myopathies lead to important functional limitations resulting from  the loss of muscle strength and endurance, especially in the hip and shoulder, which leads to  a significant loss of quality of life for patients. The aim of this study is to correlate the  "Myositis Functional Index-3 (FI-3)" with muscle function assessed by computerized isokinetic  dynamometry, electromyography and magnetic resonance through an observational study; and to  compare the effects of a repetitive task training program with a resistance exercise program  through an interventional study in patients with inflammatory myopathies. It is expected that  FI-3 will present a good correlation with muscle function assessed by computerized isokinetic  dynamometry and electromyography, given its reduced cost and less time spent on evaluation.  It is also expected to demonstrate that repetitive task training is as efficient and safe as  resistance exercises. Idiopathic inflammatory myopathies lead to important functional limitations resulting from  the loss of muscle strength and endurance, especially in the hip and shoulder, which leads to  a significant loss of quality of life for patients. PURPOSE: to correlate the "Myositis  Functional Index-3 (FI-3)" with muscle function assessed by computerized isokinetic  dynamometry, electromyography and magnetic resonance through an observational study; and to  compare the effects of a repetitive task training program with a resistance exercise program  through an interventional study in patients with inflammatory myopathies. METHODS: this is an  observational cross-sectional study for the observational study and an interventional  study/randomized clinical trial for the interventional study. The study will be held at the  Cassiano Antônio de Moraes University Hospital (HUCAM) and at the Interprofessional Health  Clinic (CEIS) of the Federal University of Espírito Santo (UFES), located in the city of  Vitória, Espírito Santo. Patients will come from the Rheumatology Service of HUCAM For the  observational study, 30 patients with inflammatory myopathies and 15 healthy individuals  matched for age and sex. For the interventional study, the 30 patients evaluated in the  observational study will be randomized into two intervention groups. To participate in the  research, patients must have a diagnosis of polymyositis or dermatomyositis (Bohan and Peter  criteria); age ≥18 years; duration of disease since diagnosis for more than six months;  stable medication ≥3 months; chronic inactive or mildly active but stable myositis for at  least 3 months prior to observation; HAQ≥0.5. They may not have serious cardiac or pulmonary  conditions; severe osteoporosis; unable to exercise; neoplasm; cognitive disorders; and acute  or chronic infection. Healthy individuals must be age and sex matched with patients and may  not have severe cardiac or pulmonary conditions; severe osteoporosis; unable to exercise;  neoplasm; cognitive disorders; and acute or chronic infection. Patients will be evaluated in  two moments: before starting the training programs and after 12 weeks. Healthy individuals  will be evaluated only once. The data from the evaluations carried out before starting the  training programs will be used for the analysis of the observational study. Participants will  be evaluated for variables: muscle endurance (Functional Index-3 and isokinetic dynamometry),  muscle strength (Manual Muscle Test 8 and isokinetic dynamometry), muscle activation  (electromyography), muscle damage (magnetic resonance imaging of thigh muscles),  cardiopulmonary capacity (6-minute walk test), pain (visual analogue scale), functional  capacity (Health Assessment Questionnaire), quality of life (SF-36), disease activity (PGA,  SGA, MDAAT, creatine phosphokinase and aldolase) and disease damage (MDI). In addition,  demographic and clinical data such as date of birth, age, sex, self-reported race-color,  marital status, occupational status, weight, height, date of first symptoms, date of  diagnosis, comorbidities and medications in use will also be collected. The training program  will last 12 weeks, twice a week in person with the supervision of physiotherapists and once  a week at home. Each session will last 60 minutes. The resistance training group will perform  traditional resistance exercises with an intensity of 30%-60% of a voluntary repetition  maximum and 1 to 2 sets of 10 repetitions each exercise. The repetitive task training group  will carry out exercises involving upper and lower limbs. To determine the  clinical-demographic characterization of the study population, descriptive statistics (mean  and standard deviation) will be used; the correlation analysis will be performed using the  Pearson or Spearman correlation coefficient; the comparison between the group of patients and  the control group of healthy individuals will be performed using the t test or Mann-Whitney  test; the comparison before and after the training programs will be performed using the  t-test or Mann-Whitney; the comparison between groups will be performed using ANOVA; the  normality test to be used will be the Shapiro-Wilk and the results will be considered  significant for P<0.05. EXPECTED RESULTS: It is expected that FI-3 will present a good  correlation with muscle function assessed by computerized isokinetic dynamometry and  electromyography, given its reduced cost and less time spent on evaluation. It is also  expected to demonstrate that repetitive task training is as efficient and safe as resistance  exercises. Inclusion Criteria:  -  diagnosis of polymyositis or dermatomyositis (Bohan and Peter criteria)  -  age ≥18 years  -  duration of disease since diagnosis for more than six months  -  stable medication ≥3 months  -  chronic inactive or mildly active but stable myositis for at least 3 months prior to  observation  -  Health Assessment Questionnaire (HAQ) ≥0.5 Exclusion Criteria:  -  serious cardiac or pulmonary conditions  -  severe osteoporosis  -  unable to exercise  -  neoplasm  -  cognitive disorders  -  acute or chronic infection

The goal of this study is to establish a prospective observational cohort of adult patients  with microscopic colitis and collect clinical information and specimens over the course of  their treatment. This information will be used in order to establish a patient registry with  detailed clinical data and a specimen repository for future research as well as to  specifically identify genetic and molecular characteristics associated with microscopic  colitis. Microscopic colitis (MC) is a chronic relapsing disease of the colon, characterized by watery  non-bloody diarrhea, usually normal colonoscopic findings, and typical histology findings. It  is frequently accompanied by abdominal pain, nocturnal diarrhea, and mild weight loss. The  incidence of MC has increased significantly over recent years with a 2010 study reporting  U.S. incidence for MC as 19.7 per 100,000 person-years. MC comprises two major histological  subtypes: collagenous colitis (CC), characterized by a distinctive thickened band of  subepithelial collagen (>10-20um), and lymphocytic colitis (LC), with an increased number of  intraepithelial lymphocytes (>20 lymphocytes per 100 epithelial cells).  Although the exact etiology of MC remains largely unknown, a few observational studies have  suggested associations with autoimmune disorders (e.g. celiac disease, and thyroid  disorders), cigarette smoking status, and medications such as non-steroidal anti-inflammatory  drugs (NSAIDS), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors  (SSRI), and statins. In addition to environmental factors, recently studies indicate that  genetics and specific infectious organisms may also play a role in development of the  disease. A recent study revealed a seasonal incidence pattern of lymphocytic colitis,  suggesting a potential link to an infectious or allergic component. Further, one study  demonstrated an association between collagenous colitis and persistent colonic C. difficile  infection. Additionally, while familial occurrence of MC has been reported, suggesting a  genetic predisposition, the roles of specific genetic factors have not been described.  Finally, recent studies demonstrate an association between MC and various autoimmune  disorders including celiac disease, autoimmune thyroid disease, and Sjören's syndrome,  indicating that MC may be part of a broader spectrum of autoimmune disorders. Despite these  findings, few studies have investigated the role of genetic, infectious, and immunological  factors in the development and progression of MC.  Budesonide is the only treatment for MC that appeared to be effective in randomized  controlled trials, with remission rates of 80%. However, recurrence of clinical symptoms  following withdrawal of treatment is not uncommon. Thus, further investigation of the  molecular mechanisms underlying MC is needed in order to obtain targeted and sustainable  treatment.  Analysis of clinical specimens obtained by colonoscopy from individuals affected with MC over  the course of their treatment offers a promising method by which to improve our understanding  of MC. Profiling of genetic and molecular characteristics such as changes in gut flora,  colonic mucosal immune profiles, and genetic factors over the course of treatment would  provide powerful insight into the role of these factors in the pathophysiology of the disease  which may ultimately lead to better treatments. Additionally, identification of disease  biomarkers can aid in developing disease monitoring and surveillance strategies.  Here, we propose to establish a cohort of individuals with suspected microscopic colitis  undergoing diagnostic colonoscopy at the Massachusetts General Hospital (MGH) to identify  genetic and molecular characteristics associated with the progression of this disease. This  study will elaborate on findings from a medical record review of patients with microscopic  colitis treated at MGH from 2002 to 2014. In addition to medical records, genetic and  molecular characteristics of colonic samples will be examined to determine their influence on  treatment response and outcomes. Inclusion Criteria:  -  Ability to give informed consent  -  Ability and willingness to comply with all patient visits and study-related procedures  -  Ability to understand and complete all study-related materials and questionnaires  -  Patients ages 18 or older with suspected microscopic colitis  -  Patients that have been previously treated for microscopic colitis that are being seen  for possible relapse will also be included Exclusion Criteria:  -  Inability to provide informed consent  -  Inability or unwillingness to comply with all patient visits and study-related  procedures  -  Inability to understand and complete all study-related materials and questionnaires  -  Patients with a known diagnosis of Inflammatory Bowel Disease or colorectal cancer  -  Patients with a known bleeding disorder, acute disease, or those that are awaiting  transplantation  -  Patients who have taken antibiotics in the last two weeks  -  Female subjects who are pregnant or nursing

Comparison of the effects of CYT107 vs Placebo administered by intra-muscular route (IM) at  10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19  patients Approximately forty-eight (48) participants will be randomized 1:1 to receive  (a) Intramuscular (IM) administration of CYT107 at 10 μg/kg followed, after 72hrs of  observation, by 10 μg/kg twice a week for 3 weeks (maximum 7administrations adjusted to  patient's length of stay in the hospital) or (b)Intramuscular (IM) placebo (normal saline) at  the same frequency. The aim of the study is to test the ability of CYT107 to produce an  immune reconstitution of these patients and observe possible association with a clinical  improvement.  This cohort excludes oncology patients on treatment Inclusion Criteria:  1. A written, signed informed consent, or emergency oral consent, by the patient or the  patient's legally authorized representative, and the anticipated ability for  participant to be re-consented in the future for ongoing Study participation  2. Men and women aged ≥ 25 - 80 (included) years of age  3. Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at  two time points at least 24 hours apart, following HOSPITALIZATION:  4. Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at  >4L per minute nasal cannula or greater to keep saturations >90%, non-invasive  positive pressure ventilation (e.g., BIPAP), or patients intubated / ventilated for  respiratory failure  5. Confirmed infection with COVID-19 by any acceptable test available / utilized at each  site  6. Willingness and ability to practice contraception regardless of the gender of the  patient during 5 months after last drug exposure  7. Private insurance or government / institution financial support (through CMS or other) Exclusion Criteria:  1. Pregnancy or breast feeding  2. ALT and/or AST > 5 x ULN  3. Known, active auto-immune disease;  4. Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy  within last 3 months and/or ongoing  5. Patients with past history of Solid Organ transplant  6. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral  load  7. Hospitalized patients with refractory hypoxia, defined as inability to maintain  saturation >85% with maximal available therapy for >6 hours  8. Patients receiving any agent with immune suppressive effects, other than steroids at  dosages less than 300 mg/day equivalent hydrocortisone and/or anti-IL-6R treatments  like Tocilizumab or Sarilumab or anti-IL-1 treatment like Anakinra which should  preferably be minimized  9. Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission  10. Patients showing an increase of the NEWS2 score by more than 6 points during the  screening/ baseline period (48 to 72 hrs prior to first administration)  11. Patients under guardianship

Clinical and comparative evaluation of the treatment results of arthroscopic reconstruction  of the medial meniscus of the knee joint using the Fast Fix and FiberStitch systems. The main goal of the project is to evaluate the results of medial meniscus traumatic injury  suturing. Further (detailed) objectives are: to compare the results obtained in the study  groups of suturing the medial meniscus with the use of two systems: Fast Fix (smith & nephew)  and Fiber Stitch (arthrex). The results refering to the operated limb will be compared in  both groups between themselves and furthermore with the results of clinical and biomechanical  studies on non-operated limbs. Inclusion Criteria:  -  Isolated MM damage.  -  Operation performed only in arthroscopy technique.  -  No any knee intervention earlier.  -  No other pathology in the anatomical area.  -  Patient informed consent to participate in research Exclusion Criteria:  -  Age under 18 years old or above 35 years old.  -  Any knee intervention performed earlier.  -  Any other pathology in the anatomical area identified during preoperative diagnostics.  -  Any damage in the area of the second knee joint.  -  Failure complying the same treatment protocol rigor.

This research will contribute to therapeutic technology to support bereaved parents who have  experienced a perinatal loss. The proposed mobile application would accomplish this objective  by providing a series of therapeutic modules to provide parents with tools to normalize their  grief and additional coping skills to support the grieving process. The investigators will develop grief processing and healing activities for bereaved parents,  via an iterative formative development process with stakeholder input. The investigators will  embed the core intervention components in administrative, provider, and client interfaces  which will comprise the prototype Walk with Me (WWM) intervention.  The investigators will evaluate its feasibility and initial efficacy of WWM in a  within-subjects pre-post design study. The investigators will provide the mobile-based  provider component for use by HCPs who work in the partner hospital. HCPs will have access to  training videos and bereaved parent content. After training, the HCPs will recruit 52  bereaved parents.  HCPs will obtain consent from bereaved parents who express interest in the study to share  their contact information with the research team. Parents who wish to participate will  provide consent for their own participation in the study. After consent, parents will  complete the baseline survey via the Qualtrics online assessment form and then be provided  download access to the WWM prototype. At 4 and 8 weeks, parents will be administered  post-treatment surveys. This design will allow the investigators to evaluate baseline to  follow-up change in the proposed study outcomes and acceptability of the prototype WWM  program.  Baseline and post-treatment surveys will measure bereaved parents traumatic stress, grief  intensity, grief, grief management self-efficacy, and care experiences. The post-survey  questionnaire will contain measures of usability, as well as any difficulties experienced or  problems made worse. Demographics will be collected at the baseline assessment. Project staff  will follow-up with parents as needed to encourage survey completion in a timely manner. Inclusion Criteria: None Exclusion Criteria:  * Non-English speakers are excluded. The WWM program will first be developed in English and  its feasibility established.

Gastric Adenocarcinoma (GAC) accounting for the major percentage of all stomach malignancies  is associated with a poor overall survival of 25-30% despite the advancement in treatment  strategies. Several factors associated with tumor microenvironment (TME) are thought to play  an important role in tumorigenesis and acquired chemoresistance to therapies that are not  otherwise addressed by the comprehensive molecular classification of GAC given by TCGA and  ACRG. In the present study investigators intend to do transcriptome profiling of GAC tumor  tissue and adjacent normal tissue to investigate differentially expressed genes between the  two in relation to TME which might help in identification of gene signatures that are  clinically relevant with survival outcome in Gastric Adenocarcinoma. This study on Gastric adenocarcinoma is retrospective as well as prospective that will be  conducted at SGPGIMS, Lucknow, India. Patients undergoing gastric resection at the department  of surgical gastroenterology who are diagnosed with GAC based on the endoscopic biopsy in the  department of pathology will be recruited for the study. For the retrospective part of study,  cases will be selected based on histological findings retrieved from hospital information  system and patient records.  For sample collection, surgically resected fresh specimens will be collected in RNAlater and  stored at -80⁰C. Archived formalin fixed paraffin embedded (FFPE) tissue blocks for  retrospective cases will be retrieved and reviewed histopathologically. After a confirmed  diagnosis of GAC, tissues will be processed to obtain tumor and normal tissue for  experimental part.  RNA from the tumor and normal area will be extracted from FFPE blocks and fresh tissue  specimens. Whole transcriptomic next generation sequencing will be performed after successful  quality check, library preparation and amplification. The gene expression data obtained from  sequencing will be bioinformatically analyzed to elucidate differential gene expression  between tumor and adjacent normal tissue in relation to TME. The significantly differentially  expressed genes between the tumor and normal areas will be annotated and identified using  bioinformatic packages for gene annotation. Using statistical analysis, the differentially  expressed genes will be correlated with the patient's clinical features and outcome to  identify TME genes with significant prognostic value. Inclusion Criteria:  -  Patients with origin of tumor in distal part of stomach  -  Patients who underwent Total or partial Gastrectomy after Biopsy examination  -  Availability of follow up in Radiotherapy or Gastro department  -  Availability of FFPE gastrectomy specimen tissue of selected cases in Histopathology Exclusion Criteria:  -  Patients with origin of tumor in proximal part of stomach  -  Patients with only biopsy available  -  Patients whose follow-up is not available  -  Unavailability of FFPE tissue blocks

Data about transgender medical care, especially the gender-affirming hormone therapy (GAHT)  is extremely insufficient in China. Few evidence exists in the physical and psychological  effects of the hormonal treatment in Chinese transgender population. CGAHT is designed to  describe the social and mental condition of transgender people who are seeking for formal  GAHT, and to investigate the physical and psychological effects of GAHT on this population in  China. CGAHT will be conducted in one of the main transgender medical centers in Chinese mainland.  Participants who are seeking for the start of GAHT will be enrolled from clinical visitors.  Before GAHT, participants will be interviewed with questionaries about their life experience,  gender identity and social economic conditions. Evaluations on mental and physical health  will be performed at baseline and during the GAHT. Participants will be followed up to 12  months. GAHT will be given to transgender people according to the protocol recommended by the  international guideline (doi: 10.1210/jc.2017-01658) . Inclusion Criteria:  -  Transgender men and women  -  Meet criteria of Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition)  for gender dysphoria  -  Aged between 18 to 40 years  -  People desire to start the GAHT  -  No previous history of gender-affirming interventions  -  Having full ability to make informed consent  -  Dextromanual Exclusion Criteria:  -  Disorders of sex development  -  Who has fertility demand but have not made fertility preservation  -  With contradictions of GAHT  -  Comorbid diseases are not under control  -  Alcohol or drug abuse  -  Hormonal and chromosomal disorders  -  History of gender affirming surgery  -  Current psychiatric disorders  -  History of brain trauma or neurological pathologies  -  Current use of medications with psychotropic effects within two weeks (antipsychotic  or antiepileptic agents, lithium, benzodiazepines or opioid analgesics)  -  Claustrophobia  -  Implanted metal and medical devices (pacemakers, ceramic teeth, etc.),  -  Tattoos or eyebrow tattooing (heavy metal dye)

PURPOSE: … The aim of this study will be conducted to investigate the therapeutic efficacy of  Aerobic exercise versus whole-body vibration on fatigue, functional capacity and quality of  life in patients with systemic lupus erythematosus  RESEARCH QUESTION:  The problem of the study will be designed in a questioner form " which is more effective  Aerobic Exercise or Whole-Body Vibration on Fatigue, Functional Capacity And Quality Of Life  In Patients With Systemic Lupus Erythematosus? Procedures of the study:  The assessment procedures  1. Measuring of functional capacity and health-related quality of life in Systemic Lupus  Erythematosus patients by:  The Systemic Lupus Erythematosus Quality of Life (SLEQOL) questionnaire SLEQoL is a  40-item questionnaire that was developed and validated in an English-speaking cohort of  SLE patients in Singapore and it assesses the quality of life of Systemic Lupus  Erythematosus (SLE) patients across six domains including physical functioning,  occupational activities, symptoms, treatment, mood and self-image.  Arabic version of the SLEQOL The questionnaire which is a reliable and valid specific  instrument for measuring the quality of life of Egyptian SLE patients, cross-cultural  adaptation and validation of SLEQoL has been performed in Arabic (Egypt). Each domain  score varies from 1 to 7, with higher scores indicating poorer quality of life. The  total scores of the questionnaire vary between 40 and 280.  The Arabic version of the SLEQOL is used to measure health-related quality of life in  Systemic Lupus Erythematosus patients pre-treatment (pre-test) and after 6 weeks  (post-treatment 1) and after 12 weeks of the study (post-treatment 2).  2. Measuring of functional capacity in Systemic Lupus Erythematosus patients by:  Health Assessment Questionnaire(HAQ)  HAQ has been reported as the best tool targeting functional disability. Moreover, the  validity and reliability of the HAQ have been confirmed in several ethnic groups. It  contains 20 questions grouped into eight subscales (dressing and grooming, arising,  eating, walking, hygiene, reach, grip, activities). The response categories are "without  any difficulty" (score = 0),"with some difficulty" (score = 1), "with much difficulty"  (score = 2), and "unable to do" (score = 3). The highest score for any question  determines the score for the subscale in question. The use of any assistive device or  any other person's help was given a score of 2. The HAQ disability index was calculated  as the sum of the scores for various subscales, divided by the number of subscales  responded to, and results in a score between 0 and 3.  The Arabic- Health Assessment Questionnaire(HAQ) The Arabic HAQ is a reliable and valid  instrument that can be self-administered to Arabic patients to evaluate their functional  disability.  The Arabic HAQ is used to measure functional capacity in Systemic Lupus Erythematosus  patients pre-treatment (pre-test) and after 6 weeks (post-treatment 1) and after 12  weeks of the study (post-treatment 2).  3. Measuring of fatigue in Systemic Lupus Erythematosus patients by:  Fatigue severity scale The Fatigue severity scale (FSS) is a self-reported questionnaire It  consists of 9 statements that rate the severity of the patient's fatigue symptoms in terms of  how these symptoms affect motivation, exercise, physical function, and activities of daily  living. Reflecting on their condition, patients score each item from 1 to 7, based on the  extent, to which they agree or disagree with each statement (1 = strong disagreement, 7 =  strong agreement). The FSS can be scored either by obtaining a total score or by calculating  a mean score across all 9 items, with higher scores indicating more severe fatigue. The most  appropriate tool to measure fatigue in SLE. The FSS is widely used in clinical practice and  research and has been translated into several languages.  Arabic version of the FSS-Arabic (FSS-Ar) The development of an Arabic version of the  FSS-Arabic (FSS-Ar) and its validation would be of great value, as it would allow clinicians  and researchers to investigate the incidence and impact of fatigue associated with it.  The Arabic version of the FSS-Arabic (FSS-Ar) is used to measure fatigue in Systemic Lupus  Erythematosus patients pre-treatment (pre-test) and after 6 weeks (post-treatment 1) and  after 12 weeks of the study (post-treatment 2).  Therapeutic procedures:  This current study will be designed to determine which is more effective aerobic exercise or  whole-body vibration on fatigue, functional capacity and quality of life in patients with  systemic lupus erythematosus so the treatment protocol will be applied through the following  steps and phases:  Therapeutic intervention for the study will be started at the same time for all groups of the  study as follows;  1. Aerobic exercise  Exercise Program:  -  The program will consist of three 50-minute exercise sessions weekly over 12 weeks.  -  Each exercise session included graded treadmill machine walking and stepping  exercises. Maximal exercise tolerance test (Bruce protocol) will be performed on  the preceding day of the exercise program. Maximum heart rate is calculated by the  formula (220 -age).  -  The graded treadmill machine walking exercise will be started with a 5-minute  warm-up period with the intensity of about 40% of maximum heart rate followed by a  30-minutes training phase. The training intensity will be arranged at about 70-85%  of maximum heart rate and ended with a 5-minute cool-down period with the intensity  of about 40% of maximum heart rate. Exercising sessions will be comprised of  warming up (stretching, turning joints, and walking slowly), the main program  (treadmill machine walking), and cooling down (stretching, turning joints, and  walking slowly).  -  The second part of the exercise program will be 10 minutes of stepping exercise at  a speed of 96 beats per minute using a 20-cm-high bench, with rest after the first  5 minutes.  2. Whole-body vibration (WBV)  -  Whole-body vibration apparatus (model power plate-my5tm, made in the United States)  with frequency 30-40Hz and 2 mm of amplitude will be used for whole-body vibration  program by reciprocating vertical displacements on the left and right side of a  fulcrum.  -  The subjects will stand on a whole-body vibrator and they will be vibrated in a  squat positioning.  -  The subjects will exercise for 16 minutes (1 min vibration with 8 iterations and 1  min break between each iteration), 20, and 24 minutes in the first week to the  third week, the fourth week to the sixth week, and the seventh week to the eighth  week respectively and also to the end of the study after 12 weeks.  -  The WBV group performed a training program 3 times a week with at least one day  between each session for 12 weeks.  Treatment procedure Interventions  Participants were randomly assigned to:  -  Group A (GA) (Aerobic exercise group): Will receive aerobic exercise: (graded treadmill  machine walking and stepping exercises). The second part of the exercise program will be  10 minutes of stepping exercise at a speed of 96 beats per minute using a 20-cm-high  bench, with rest after the first 5 minutes. Three sessions per week for 12 weeks.  -  Group B (GB) (Whole-body vibration (WBV) group): will receive whole-body vibration with  frequency 30-40Hz and 2 mm of amplitude will be used for the whole-body vibration  program by reciprocating vertical displacements on the left and right side of a fulcrum.  The WBV group performed a training program 3 times a week with at least one day between  each session for 12 weeks. Inclusion Criteria:  -  Criteria for selecting the patients include the following:  -  This study turned will be done on 68 patients.  -  Age range between 25-45 years.  -  Female patients with a diagnosis of Systemic Lupus Erythematosus (SLE).  -  A follow-up of 12 months.  -  Clinical and treatment stability during the 6 previous months.  -  Not performing regular exercise.  -  All patients enrolled in the study will have their informed consent Exclusion Criteria:  -  The subjects are excluded from the study if they will meet one of the following  criteria;  -  Have had biological treatment in the previous 6 months.  -  A background of clinical cardiovascular disease in the previous year.  -  Present contraindications to performing the exercise.  -  Other associated rheumatic diseases, pregnancy, active acute or chronic  infection.  -  Acute renal failure, cardiac or pulmonary involvement.  -  Have a depressive disorder.  -  Undergo total hip replacement.  -  Diabetes, cancer.

This is a phase II, mono institutional, non comparative study, evaluating adjuvant  capecitabine in patients affected by KRAS mutated Pseudomyxoma peritonei treated with  cytoreductive surgery and HIPEC.  Patient will be treated with 8 cycles of the study regimen that include:  Capecitabine 1250 mg/m2 PO BID day 1-14 q21 days A previous phase II study evaluated the combination of systemic concurrent mitomycin C and  capecitabine in advanced unresectable PMP.  Fifteen out of 39 patients benefited from chemotherapy in the form of either reductions in  mucinous deposition or stabilisation of progressive pretreatment disease determined on CT  scan. Notably, two patients, originally considered unresectable, underwent potentially  curative cytoreductive surgery. One-year and two-year tumour-related survival rates for the  40 patients were 84% and 61%, respectively.  FOLFOX-4 chemotherapy was evaluated on 20 patients with unresectable or recurrent PMP,  obtaining a 20% response rate and a 65% disease control rate, 2 patients originally  considered unresectable underwent complete cytoreduction. Median PFS and median OS were 8  months and 26.2 months respectively.  In a retrospective review of MCP (mucinous cancer peritonei) patients who had undergone  CRS/HIPEC with or without perioperative systemic chemotherapy (any regimen), postoperative  chemotherapy was associated with longer PFS (13.6 months) compared to pre-operative treatment  (6.8 months, P < 0.01) and CRS/HIPEC alone (7.0 months, P = 0.03).  The OS of patients treated with systemic chemotherapy after previous CRS and HIPEC appeared  to be associated with the length of PFS after primary treatment (p=0.04).  KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at  univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS  mutations were independently associated with PFS (P = 0.012).  This is the rationale that induced us to carry out an evaluation and feasibility assessment  of an adjuvant approach with oral capecitabine in patients affected by KRAS mutated PMP with  extensive peritoneal disease, after cytoreductive surgery and HIPEC.  Twenty-eight cases (intention to treat) will be recruited in 3 years and followed-up for 2  years. Currently, the annual PMP case-volume submitted to CRS-HIPEC amounts approximately 25  in our center. Considering that approximately 65-70% of cases could present the KRAS mutated  status, we will accrue 28 patients over the study period. With such a sample size, we  estimate that the study power is of 76% in case of a 40% relative reduction in the hazard of  PFS. We assumed an exponential distribution of event times, a baseline median PFS of 27  months, and the use of a one-sided test at the 10% significance level, a choice justified by  the exploratory nature of the study.  Given the low level of evidence on the tolerance of Capecitabine alone in the systemic  treatment of PMP, an independent safety board will perform a strict monitorization of the  adverse events in the subset of first 10 recruited cases.  Twenty-eight cases (intention to treat) will be recruited in 3 years and followed-up for 2  years. Currently, the annual PMP case-volume submitted to CRS-HIPEC amounts approximately 25  in our center. Considering that approximately 65-70% of cases could present the KRAS mutated  status, we will accrue 28 patients over the study period.[6] With such a sample size, we  estimate that the study power is of 76% in case of a 40% relative reduction in the hazard of  PFS. We assumed an exponential distribution of event times, a baseline median PFS of 27  months [6], and the use of a one-sided test at the 10% significance level, a choice justified  by the exploratory nature of the study.  This study should be completed after 36 months enrolment, followed by 2 years of follow up.  It is understood that these accrual rates are based on reasonable planning expectations.  Response to treatment has to be assessed after four cycles of treatment by using the same  techniques used at baseline.(At baseline, each tumor lesions will be categorized in  measurable or nonmeasurable; The measurable lesion can have longest diameter >20mm with  conventional techniques (CT scan) or >10 mm with spiral CT scan;the non measurable lesions  include the lesions with longest diameter <20 mm with conventional techniques (CT scan) or  <10 mm with spiral CT scan and truly non measurable lesions;tumor lesion that are situated in  a previously irradiated area might not be considered measurable).  Written informed consent must be obtained prior to the patients undergoing any study-specific  procedures.Tumor assessment (TC/RMN abdomen plus TC thorax and PET) should be made within 28  days before treatment start.  Clinical assessment will be made up to 17 days before treatment start and includes:  demographic data, medical history, electrocardiogram (ECG), CEA and Ca19.9 determination,  pregnancy test, height, weight, vital signs (body temperature, blood pressure, pulse/heart  rate), ECOG Performance Status, haematology, blood chemistry: bilirubin total and direct,  AST/ALT, alkaline phosphatase, albumin, LDH, serum creatinine and estimated creatinine  clearance (calculated using Cockcroft and Gault formula), glucose, electrolytes (sodium,  potassium, calcium).  Study Medication: Capecitabine is available in the form of film-coated tablets in two  strengths 150 mg and 500 mg. Capecitabine is to be administered orally twice daily within 30  minutes after the end of a meal (breakfast, dinner). Tablets should be swallowed with water  (and not fruit juices). For capecitabine the investigator must calculate the body surface  area (m2) of the patient. If there is a 10% decrease in body weight comparing to baseline,  the BSA will be recalculated. If the calculated BSA is >2.2 m2, the doses to be given to the  patients will be calculated according to BSA = 2.2 m2. No ideal body weight should be used  for the calculation of BSA.  The drug is commercially available. At the discretion of the principle investigator it is  possible to administer modest pre and post chemotherapy hydration, the same principle applies  with regard to the preventive anti-emetic treatment to be carried out at the same time as the  therapy and, if needed, at home.  The working out of the dosage of the drug to be administered must be done at the beginning of  the treatment taking the body surface into account which in turn has to be worked out with  respect to patient's weight and height.  At the end of the entire protocol program tumor assessment will be performed every 3 months,  during follow up visit for the first two years, then from third to fifth year and until  evidence of relapse or death. After relapse, follow up visit will continue until patient's  death in order to collect survival data. Inclusion Criteria:  -  Patients submitted to a complete cytoreductive surgery and subsequent HIPEC for PMP  -  Histological diagnosis of pseudomyxoma peritonei (PMP)  -  Assessment of KRAS mutation positivity on surgical sample  -  Age >= 18 years and <76 years  -  Performance Status (ECOG <2)  -  Adequate organ function including the following:  -  Adequate bone marrow reserve: WBC count >3.0x109/L, absolute neutrophyl count  >1.5x109/L, platelet count >100x109/L, and hemoglobin >10 g/dL  -  Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase,  and alanine transaminase < 2.5 xULN  -  Renal: Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL  -  Patients compliance and geographic proximity that allows for adequate follow-up  -  Patients must sign an informed consent document (ICD)  -  Male and female patients with reproductive potential must use an approved  contraceptive method. Exclusion Criteria:  -  Previous systemic chemotherapy and/or biological therapy  -  Administration of other experimental drugs during the study  -  Pregnancy and breast-feeding  -  Serious or uncontrolled medical pathologies or active infections that would jeopardize  the possibility of receiving the investigated treatment  -  Disorders that could influence the absorption of capecitabine (e.g. malabsorption),  intestinal occlusion, Crohn's disease or ulcerative colitis  -  Psychiatric disorders, neurologic disease or other conditions that would make it  impossible to comply with the protocol procedures.  -  Positive anamnesis with regard to other neoplastic diseases except for the ones that  have been cured for more than 5 years

This was a multi-center Phase II study investigating the efficacy and safety of reinfusion of  tisagenlecleucel in pediatric and young adult patients with acute lymphoblastic leukemia  (ALL) who were treated with tisagenlecleucel and experience B cell recovery. This trial was a phase II, open label, multi-center trial to determine the efficacy and  safety of tisagenlecleucel re-infusion in pediatric and adolescent young adult (AYA) patients  with acute lymphoblastic leukemia (ALL) experiencing loss of B cell aplasia. Loss of B-cell  aplasia is defined as: peripheral blood (PB) absolute B lymphocyte count ≥ 50/µL, OR PB B  lymphocyte ≥ 10% of the total lymphocytes. B-cell aplasia is defined as PB absolute B  lymphocyte count <50/µL.  The study had the following phases for all patients: Screening, Treatment and Follow-up. The  total duration of the study was about 12 months. After tisagenlecleucel re-infusion, efficacy  was assessed at months 1, 3, 6, and End of Study at which time blood samples were obtained.  The study stopped early due to slow enrollment into the trial. The rate of enrollment made  the trial no longer feasible to continue.  The patients were able to voluntarily withdraw from the study for any reason, at any time.  Patients who received commercial tisagenlecleucel had to be followed for up to 15 years  post-infusion. Patients could have been followed under the Center for International Blood and  Marrow Transplant Research (CIBMTR) cellular therapy registry if consented for participation.  For patients who do not provide consent for participation in the Center for International  Blood and Marrow Transplant Research (CIBMTR) registry, adverse events were to be reported  for 15 years or until the patient enrolls in the registry. Inclusion Criteria:  -  Signed informed consent must be obtained prior to participation in the study  -  Must have an additional dose of unexpired, commercial tisagenlecleucel available and  prescribed by a physician in the course of medical practice  -  Age up to and including 25 years  -  Patients must have CD-19+ Leukemia  -  Patients who were previously treated with tisagenlecleucel and present with evidence  of B-cell recovery as defined by: Peripheral blood (PB) absolute B lymphocyte count ≥  50/µL, OR PB B lymphocyte ≥ 10% of the total lymphocytes Exclusion Criteria:  -  Prior gene therapy other than tisagenlecleucel  -  Prior adoptive T cell therapy other than tisagenlecleucel  -  Active CNS involvement by malignancy  -  Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at  screening  -  HIV positive test within 8 weeks of screening

This research study is evaluating a drug called clofarabine as a possible treatment for  Langerhans Cell Histiocytosis (LCH) and and other histiocytic disorders. This research study is a Phase II clinical trial. Phase II clinical trials test the  effectiveness of an investigational intervention, to learn whether the drug works in treating  a specific disease, in this case, clofarabine to treat LCH.  "Investigational" means that the intervention is still being studied. It also means that the  FDA (the U.S. Food and Drug Administration) has not yet approved clofarabine for your  disease.  Clofarabine is a chemotherapy drug that has been used and is approved by the FDA for the  treatment of leukemia in children and adults. Information from other research studies  suggests that this drug may also be effective in participants with LCH and other histiocytic  disorders. Inclusion Criteria:  -  Prior diagnosis of Langerhans Cell Histiocytosis (stratum 1) or LCH-related disorder  (stratum 2) established by standard diagnostic criteria and confirmed histologically.  -  Evidence of active disease (histological confirmation of reactivation or progression  is not required).  -  Performance Score > 70% (use Lansky score for age < 16 and Karnofsky score for age =  >16).  -  Patients of all ages will be eligible.  -  Provide signed written informed consent.  -  In stratum 1, patients must have failed one prior systemic chemotherapy regimen. In  stratum 2, RDD patients must have failed treatment with corticosteroid. ECD patients  who have confirmed BRAF V600E mutation must have failed treatment with a BRAF  inhibitor or are not considered to be eligible for such treatment.  -  There is no limitation of amount or the type of prior therapy or drugs.  -  Female patients of childbearing potential must have a negative serum pregnancy test  within 14 days prior to enrollment. Male and female patients must use an effective  contraceptive method during the study and for a minimum of 6 months after study  treatment.  -  Capable of understanding the investigational nature, potential risks and benefits of  the study, and able to provide valid informed consent.  -  Participants must have adequate marrow functions as defined below, except those with  involvement of hematopoietic system for whom these criteria can be waived:  -  Absolute neutrophil count ≥ 750 cells/µL  -  Platelets ≥75,000/µL  -  Participants must have adequate organ functions as defined below:  -  Total bilirubin ≤ 2.5x institutional upper limit of normal  -  AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal unless it is  related to involvement by LCH  -  Adequate renal function defined as:  -  Pediatric Population (patients < 18 years): Creatinine within normal limits or  calculated creatinine clearance greater than or equal to 90 ml/min/1.73 m2 as  calculated by the Schwartz formula for estimated glomerular filtration rate (GFR)  where GFR (ml/min/1.73 m2) = k x Height (cm)/serum creatinine (mg/dl). k is a  proportionality constant which varies with age and is a function of urinary  creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55  children and adolescent girls; and 0.70 adolescent boys.  -  Adult Population (patients >= 18 years): Serum creatinine less than or equal to  1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular  filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the  Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73  m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient  is female) x (1.212 if patient is black), where serum creatinine is measured in  mg/dL.  -  Alkaline phosphatase ≤ 2.5 x institutional upper limit of normal Exclusion Criteria:  -  Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for  nitrosoureas or mitomycin C) prior to entering the study or those who have not  recovered from adverse events due to agents administered more than 2 weeks earlier.  Corticosteroid treatment is allowed.  -  Participants may not be receiving any other investigational agents targeting  Histiocytosis.  -  Clofarabine is excreted primarily by the kidneys. Therefore, drugs with known renal  toxicity (e.g.vancomycin, amphotericin B, acyclovir, cyclosporin, methotrexate,  tacrolimus) should be avoided to the extent possible during the 5 days of clofarabine  treatment in each cycle or, if required, administered cautiously and with close  monitoring.  -  Use of alternative medications (e.g., herbal or botanical that could interfere with  clofarabine) is not permitted during the entire study period.  -  Uncontrolled intercurrent illness including, but not limited to ongoing or active  infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac  arrhythmia, or psychiatric illness/social situations that would limit compliance with  study requirements.  -  Pregnant women are excluded from this study because clofarabine is a nucleoside analog  with the potential for teratogenic or abortifacient effects. Because there is an  unknown but potential risk of adverse events in nursing infants secondary to treatment  of the mother with clofarabine, breastfeeding should be discontinued if the mother is  treated with clofarabine. These potential risks may also apply to other agents used in  this study.  -  Individuals with a history of a different malignancy are ineligible except for the  following circumstances. Individuals with a history of other malignancies are eligible  if they have been disease-free for at least 5 years and are deemed by the investigator  to be at low risk for recurrence of that malignancy. Individuals with the following  cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer  in situ, and basal cell or squamous cell carcinoma of the skin.  -  Patients with a history of prior hematopoietic stem cell transplantation (HSCT),  elevated conjugated serum bilirubin at study entry, uncontrolled systemic fungal,  bacterial, or other infection, a history of hepatitis B or C infection or a history of  cirrhosis.  -  Individuals who are known to be HIV-positive on combination antiretroviral therapy are  ineligible because of the potential for pharmacokinetic interactions with clofarabine.  In addition, these individuals are at increased risk of lethal infections when treated  with marrow-suppressive therapy. Appropriate studies will be undertaken in  participants receiving combination antiretroviral therapy when indicated.

The purpose of this study is to determine the overall safety of adoptive immunotherapy when  given after chemotherapy for AML/MDS. Adoptive immunotherapy means using an infusion of cells  from a donor to help fight cancer. The donor cells will be either from the umbilical cord  blood (UCB) of a newborn baby or they will be cells collected from a relative  (haplo-identical cells).  The 2 cohorts that were discussed - adoptive immunotherapy with either UCB or haplo-identical  stem cells - will be analyzed separately.  Preliminary data from other centers has suggested that adoptive immunotherapy with cells from  a relative is an effective approach that may improve remission rates and survival in AML and  MDS, because they exert anti-cancer effects of their own (so called graft vs leukemia  effects) and possibly because they hasten recovery of cell counts from chemotherapy. The  Investigators are interested in confirming these data, but also in testing umbilical cord  blood cells for the same purpose. Preliminary data indicate that umbilical cord blood cells  may have more powerful graft vs leukemia effects and cause fewer side-effects. This is a phase 2 trial to evaluate the safety of adoptive immunotherapy with Non-Inherited  Maternal Antigen (NIMA) compatible, Inherited Paternal Antigen (IPA) targeted CBU or with  haplo-identical stem cells after conventional induction therapy for very high risk Acute  Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).  The study has 2 cohorts - patients in cohort 1 will receive CBU cells as adoptive  immunotherapy. Patients in cohort 2 will receive haplo-identical cells. Both cohorts will be  evaluated separately and no formal statistical comparison between cohorts will be performed.  There will be approximately 20 patients in each cohort, and a 95% confidence interval for the  proportion of patients experiencing grade III-IV GVHD complications or unexplained prolonged  myelosuppression complications in each cohort can be constructed to be within +/- 13.1% of  the observed complication proportions. This calculation assumes an expected prevalence of  each of these complication proportions of no greater than 10%.  After 10 patients are enrolled in each group, the incidence of the above-defined  life-threatening complications will be assessed. If more than one patient out of 10 enrolled  patients (i.e., greater than 10%) in a cohort experiences either of these complications, the  cohort will be stopped for safety.  All potential recipients will have complete HLA typing and determination of HLA antibodies.  An appropriate umbilical cord blood unit (CBU) will be identified or in the absence of an  appropriate CBU, a haplo-identical donor will be identified.  Treatment will be as per the treating physician's choice..  The umbilical cord graft or haplo-graft will be administered between 24 - 72 hours after the  completion of the chemotherapy regimen.  The Graft Selection Algorithm is as follows:  1. CBU Unit 5/6 Matched - 1 NIMA match with patient  2. CBU Unit 5/6 Matched - Shared IPA target(s) with patient  3. Haplo-identical relative  4. CBU Unit 4/6 Matched - 1-2 NIMA matches with patient  5. CBU Unit 4/6 Matched - Shared IPA target(s) with patient  Within 42 days of transplant, the recipient's pre-treatment evaluation includes: medical  history and physical examinations, Eastern Cooperative Group Oncology Group (ECOG) score,  complete blood count (CBC), HLA antibodies, and cytomegalovirus (CMV) antibody testing.  Patients will continue with the therapy specified in this protocol until one of the following  occurs:  -  Achievement of protocol endpoint complete remission (CR) or CR with incomplete platelet  recovery (CRp) after induction and cellular therapy;  -  Failure to achieve CR or CRp; or,  -  Extraordinary Medical Circumstances: If, at any time the constraints of this protocol  are detrimental to the patient's health and/or the patient no longer wishes to continue  protocol therapy, remove the patient from protocol treatment. In this event.  After removal from protocol therapy, patients will continue to be followed for survival and  disease status. Samples for correlative studies will continue to be collected every two  months until one year after cell infusion. Inclusion Criteria:  1. Patients must be 18 years of age or older  2. Patients with a confirmed diagnosis of AML or MDS, according to World Health  Organization (WHO) classification (excluding acute promyelocytic leukaemia) with  recurrent or refractory disease as defined below.  1. For AML:  1. Primary induction failure (PIF) after ≥ 2 cycles of chemotherapy.  2. First relapse.  3. Relapse refractory to salvage chemotherapy  4. Second or subsequent relapse.  2. For MDS, either refractory anemia with excess blasts (RAEB) I or RAEB II who  failed at least one chemotherapy regimen including either cytarabine or a  hypomethylating agent.  3. Patients must have Karnofsky Performance score of ≥70  4. Women of child-bearing potential must have a negative serum or urine pregnancy test  within 2 weeks prior to treatment start  5. Patients must be capable of understanding and complying with protocol requirements,  and must be able and willing to sign a written informed consent form Exclusion Criteria:  1. Persistent clinically significant toxicities from previous chemotherapy  2. Known positive status for human immunodeficiency virus (HIV)  3. Pregnant and nursing patients  4. Uncontrolled intercurrent illness including, but not limited to, uncontrolled  infection, or psychiatric illness/social situations that would limit compliance with  study requirements  5. Impairment of hepatic or renal function to such an extent that the patient, in the  opinion of the investigator, will be exposed to an excessive risk if entered into this  clinical study  6. Active heart disease including myocardial infarction within previous 3 months,  symptomatic coronary artery disease, arrhythmias not controlled by medication, or  uncontrolled congestive heart failure. Any New York Heart Association (NYHA) grade 3  or 4.  7. Any medical condition which in the opinion of the investigator places the patient at  an unacceptably high risk for toxicities

The current study is designed to test nationally whether patients' outcomes and utilization  of services can be improved through symptom monitoring via patient-reported outcomes between  visits. This is a cluster RCT at approximately 50 sites where randomization will occur in a 1:1 ratio  at the site level (not at the individual patient level). Therefore, approximately 25 sites  will be randomized to the PRO-TECT intervention arm (patient-reporting of symptoms), and  approximately 25 sites will be randomized to the control arm (usual care delivery).  Approximately 1200 patients will be enrolled. Specifically:  PROCEDURES AT ALL SITES (CONTROL SITES AND INTERVENTION SITES):  -  Site staff (CRA and Nurse Champion required) will attend the site initiation webinar  with UNC staff, including training for the PRO-Core online data management system and  orientation to the symptom management guidelines.  -  At enrollment, all participants will be given a booklet with patient-level symptom  advice and a link to the content online.  -  All participants will receive compensation for participation, mailed to them as gift  cards by UNC.  -  CRAs will train all participants how to complete outcomes questionnaires for the trial  using the PRO-Core online system. Participants will be given a choice to complete these  in clinic or from home online, or if necessary via paper in clinic (with the CRA  entering the data into PRO-Core). If the patient does not self-complete this  information, the CRA will contact them to collect the information and then enter it into  PRO-Core. The outcomes questionnaires will be completed at baseline; and at month 1 (+/-  2 weeks); and at months 3, 6, 9, and 12/off-study (+/- 4 weeks each), and will be  available in English, Spanish, or Mandarin Chinese. At each time point, the CRA will  contact the participant to remind them about the upcoming questionnaire and offer help.  -  Chart abstraction will be conducted by CRAs at baseline and at off-study for each  participant, with data entered into the PRO-Core system. Date of death information will  additionally be abstracted at 18 and 24 months, and possibly later per the UNC study  team.  -  CRAs will be asked to complete a feedback survey (entered by the CRA into the PRO-Core  online system) and may be asked to participate in a brief telephone debriefing and/or  site visit.  -  Accrual will be monitored in a weekly teleconference between the UNC team and site CRAs.  ADDITIONAL PROCEDURES AT INTERVENTION SITES ONLY:  -  At baseline, CRAs will also train patients to self-report symptoms and physical  functioning using the PRO-Core system weekly for up to a year, with a choice to do this  online or via an automated telephone system (patient choice), and a choice of English,  Spanish, or Mandarin Chinese.  -  Whenever a concerning symptom is reported, an automated "email alert" notification will  be sent to the site CRA. The CRA will forward the email alert to the responsible  clinical nurse (or other covering clinician) and CC the site's Nurse Champion. Within 72  hours, the CRA will document what action(s), if any, were taken by the nurse in response  to the alert (entered by the CRA into a form in the PRO-Core system).  -  A symptom report will be printed/generated by the site CRA whenever the patient has a  clinic visit, and will be given to the oncologist and nurse caring for the patient. Inclusion Criteria:  1. Adults (21+) with metastatic cancer of any type (EXCEPT leukemia or indolent [slow  growing] lymphoma)  2. Receiving outpatient systemic cancer treatment for non-curative/palliative intent,  including chemotherapy, targeted therapy, or immunotherapy.  3. Enrolled at any point in their treatment trajectory, meaning during any line of  treatment, and at any point during a course or cycle of treatment.  4. Can understand English, Spanish, and/or Mandarin Chinese. Exclusion Criteria:  1. Cognitive deficits that would preclude understanding of consent form and/or  questionnaires.  2. Current participation in a therapeutic clinical trial (because these often involve PRO  questionnaires and intensive monitoring).  3. Patients being treated with curative intent (e.g., adjuvant chemotherapy for breast,  lung, or ovarian cancer; primary curative therapy for testis cancer or lymphoma).  4. Receiving hormonal therapy only (e.g., tamoxifen or aromatase inhibitors in breast  cancer; androgen deprivation therapy in prostate cancer; or octreotide in  neuroendocrine cancers)  5. Indolent lymphomas (due to their prolonged time courses that may be minimally  symptomatic).  6. Leukemias (time courses inconsistent with other tumor types in chronic and acute  leukemias).  7. Does not understand English, Spanish, or Mandarin Chinese.

The Aim of This Study is to Determine the Minimum Effective Volume of Local Anesthetic  (Ropivacaine 0.5%) Required to Produce an Effective Ultrasound-guided Supra-anterior Superior  Iliac Spine Fascia Iliaca Compartment Block（SASIS-FICB） for Surgical Anesthesia in 90% of  Patients Scheduled for Elective Surgery of One Lower Limbs. The study is based on biased coin design, and the volume of Local Anesthetic (Ropivacaine  0.5%) for the next patient is determined by the result of the last one. In the case of block  failure, the volume will be increased by 2.5ml. Conversely, block success will result in  either a reduction in volume by 2.5ml (probability 11%) or no change in volume (probability  89%). A blinded assistant will assess sensory and motor blockade in each nerve territory (  the femoral, obturator and lateral femoral cutaneous nerves) at 5-min intervals up to 30 min  after completion of the block. Finally, MEV90 is calculated by isotonic regression. Inclusion Criteria:  -  patients undergoing hip/knee surgery Exclusion Criteria:  -  age <18 years  -  body mass index >35  -  inability to consent to the study  -  allergy to local anesthetics  -  a history of liver or renal insufficiency, coagulopathy  -  clinical evidence of peripheral neuropathies, abnormalities of sensory or motor  function of the FN, ON or LFCN.

The aim of this study was to compare the effects of Neuromuscular Integrative Action (NIA)  and Pilates exercises on physical fitness and psychological effects in sedentary women. 20-45  years old 43 sedentary females were randomly divided into Pilates and NIA groups. The  6-Minute Walking Test (6MWT), the Sit and Reach Test, and the Static Plunk Test durations  were used for the physical fitness level assessment at baseline and at the end of trainings.  In addition, the Rosenberg Self-Esteem Scale, the Beck Anxiety Inventory, and the SF-36 were  used to evaluate the psycho-somatic symptoms and health-related quality of life of the  participants. Both groups received 60-min exercise sessions 2 days a week for 8 weeks. Participant Healthy female volunteers between the ages of 20 and 45 who performed desk jobs 8  hours a day and with a sedentary lifestyle were included in this study. This is a parallel  group randomized comparative study aimed to compare the effects of NIA and Pilates on  physical fitness and psychological status. This study was conducted at …………. University  School of Physical Therapy and Rehabilitation in 2017. Participants were excluded if  participants had a risk of pregnancy, using pacemakers or metal implants in participiants'  body, had an active athlete history, had any health problems preventing them performing  exercises. Written informed consent was obtained from all participants, and participants  signed the form approved by the ………………….. University Clinical Research Ethics Committee  (020/55134) prior to participation in the study.  Randomization of the volunteers were screened for eligibility and signed an informed consent  form. Then, participants were randomized to Pilates and NIA groups using the sealed envelope  method. An identification number (i.e., 1-54) was allocated to each volunteer. Each number  was written on a separate piece of folded white paper and placed into an opaque envelope. The  randomization process was performed by picking a random number from the sealed envelope to  allocate each volunteer to either the intervention or control group.  Outcomes Measures This is a prospective, single-blinded, randomized-comparative study, and it  involved twice time at pre and post 8-week exercise program. Assessments were performed at  the baseline and after eight weeks of intervention. The dependent variables were flexibility,  cardiovascular endurance, Abdominal Strength-Endurance, Balance Assessment, self-esteem,  anxiety, and quality of life. BMI was measured with a Tanita BC 418 (Tanita Corp., Tokyo,  Japan), which is a segmental professional body analysis monitor measuring the impedance  generated during the passage of an electric current of 50 kHz, 0.8 mA through tissues.  Psychological Status Rosenberg Self-Esteem Scale The Rosenberg Self-Esteem Scale was  developed by Morris Rosenberg and the validity and reliability studies of the Turkish version  of the scale were performed by Çuhadaroğlu. The Rosenberg self-esteem scale is a 10-item  scale that assesses global self-worth by measuring both positive and negative feelings about  the self. Each item has a 4- point Likert scale ranging from strongly agree to strongly  disagree. Higher scores indicate higher self-esteem. The scale was used for self-esteem  measurement.  Quality of Life Assessment Short Form Health Survey is a questionnaire assessing the quality  of life of the subjects. Short Form Health Survey examines eight different parameters,  namely, Functional Capacity, Physical Aspects, Bodily Pain, General Health, Vitality, Social  Aspect, Emotional Aspect, and Mental Health domains. A higher score indicates a better  quality of life.  Beck Anxiety Inventory The Beck Anxiety Inventory is a 21-item self-report questionnaire for  assessing the severity of anxiety. The Beck Anxiety Inventory assesses the grade of anxiety  using 21 questions. A higher score indicates more severe anxiety and depression.  Fatigue A Visual Analogue Scale was applied to assess the severity of perceived fatigue. The  Visual Analogue Scale is a 10-cm scale that evaluates the severity of fatigue in the previous  week.  Physical Fitness Assessment Flexibility Assessment The Sit and Reach Test was used to  evaluate the flexibility of the participants. The participants were placed in a long sitting  position with straight legs. Participants were asked to lean forward four times and reach  forward on the board. At the end of the fourth reach, the distance obtained after  participants waited for two seconds was recorded in centimeters (cm).  Cardiovascular Endurance Assessment The cardiorespiratory endurance of the participants was  evaluated with the 6 Minute Walk Test. The test was conducted by measuring the distance the  participants could walk in a 20-meter corridor with a fast and firm walk. At the beginning of  the test, the heart rate and blood pressure of the participants were measured with a pulse  meter heart rate monitor. Before the test, the fatigue levels of the participants were  assessed by taking the perceived difficulty levels according to the Borg Rating of Perceived  Exertion. After the test, evaluations were repeated.  Abdominal Strength-Endurance Assessment Muscle strength and endurance of the abdominal  muscles were evaluated by sit-up tests. The participants were placed on participants' back,  hips and knees in flexion, with the plantar side of the foot on the bed. The arms were  positioned according to the strength of the rectus abdominus muscle and participants were  asked to perform trunk flexion for 60 seconds consecutively. The number of trunk flexions  completed was recorded. Static abdominal strength and trunk stabilization were evaluated  using a static plank test. Individuals assumed a position with the elbows on the ground with  the fingertips touching the ground and the hip raised from the ground, and the knee, hip, and  trunk were in a parallel line, the maximum time participants could keep this position was  recorded. During the test, the participant was asked not to disturb the horizontal position  of the trunk.  Balance Assessment The balance of the participants was evaluated with the Functional Reach  Test. The test measures dynamic balance and core stabilization. The participants were asked  to stretch participants' hands forward while standing and reach from that distance without  stepping forward and without support. The distance participants reached was recorded in cm.  Interventions The NIA and Pilates programs were implemented by one of the researchers (AU)  with trainings and qualifications in both approaches. The trainings were carried out for 60  minutes, 2 days a week, for 8 weeks. Each session was performed by a Pilates instructor with  a 10-year of Pilates training experience. NIA sessions were also performed by the same  instructor (AA), and she had a 1-year NIA training experience. The participants were asked  not to participate in any other physical activity program during the study. Prior to training  sessions, a familiarization period of practice was conducted to introduce the participants  with the methods and techniques.  Pilates Mat Exercise Protocol The Pilates Mat exercise group followed an eight-week exercise  program. The exercise protocol of this study was designed by the researchers. According to  previous reports, 6 to 8 weeks of Pilates training has positive effects on physical and  psychological health. As the program advanced, 20-cm diameter mini soft balls, Pilates rings,  65 cmdiameter soft gymnastic balls, and rubber bands were used in this order as materials in  Pilates exercises. After an initial warm-up exercises at a slow pace for 10 minutes, Pilates  exercises with and without equipment were performed for 40 minutes. The exercises ended with  a 10-minute recovery and stretching exercises for relaxation of all muscle groups  Neuromuscular Integrative Action Protocol NIA includes nine basic movement forms, 13  principles, and 52 basic moves. The nine movement forms were derived from martial arts, dance  arts, and the healing arts of the Alexander Technique, Feldenkrais Method, and Yoga. The 13  principles specify areas related to fitness, personal growth, and lifestyle. Centered on the  joy of movement, participants focus on, for example, being sensitive to personal rhythms,  making the correct movement choices, and experiencing positive changes in daily life. The  moves of NIA are used to engage all body areas, improve fitness, and facilitate self-healing.  Instrumental music, which plays throughout each 60-min session, is an integrative part of  NIA, and the melody and beat of the music used are directly associated with the movements.  For instance, the feet and the legs follow a pattern that maps directly on to the drum beat  of a particular song, while the arms and the upper body express the melody of the rest of the  instruments, such as the guitar, violin, or the singer's voice. Visual imagination is  stimulated in NIA as the movements pertaining to the choreography relate a particular image  or symbol. Inclusion Criteria:  -  20-45 years  -  Healthy Females volunteers performed desk jobs 8 hours a day and with a sedentary  lifestyle Exclusion Criteria:  -  pregnancy,  -  using pacemakers or metal implants in their body,  -  had an active athlete history, had  -  any health problems preventing them performing exercises

IBI110 is an investigational drug under evaluation for treatment of small cell lung cancer.  The purpose of the study was to assess the Efficacy and Safety of IBI110 in combination with  Sintilimab and chemotherapy with untreated ES-SCLC. This Phase II, multicenter, open-lable study is designed to evaluate the safety and efficacy  of IBI110 (anti-lymphocyte activation gene 3 [LAG-3] monoclonal antibody) and sintilimab  (anti-programmed death 1 [PD-1] antibody) in combination with intravenous (IV)  cisplatin/carboplatin plus (+) etoposide (EP) in treatment naïve patients with  extensive-stage small cell lung cancer (ES-SCLC) . Sixty eligible subjects will be enrolled  and randomized in a 1:1 ratio to the experimental arm or the control arm. The experimental  arm will be IBI110+ sintilimab + EP Q3W for 4 cycles, followed by IBI110+ sintilimab Q3W  until disease progression. The control arm will be sintilimab + EP Q3W for 4 cycles, followed  by sintilimab Q3W until disease progression. Inclusion Criteria:  1. Patients must have the ability to understand and voluntarily sign informed consent;  2. Age: over 18 years old;  3. Expected survival period ≥ 3 months;  4. Histologically or cytologically confirmed ES-SCLC (according to the Veterans Lung  Administration Lung Study Group, VALG staging);  5. No prior systemic treatment for ES-SCLC;  6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1;  7. At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging  (MRI) per Response Eval -uation Criteria in Solid Tumors version 1.1 (RECIST v1.1)  criteria;  8. Adequate hematologic and end organ function. Exclusion Criteria:  1. Have been previously exposed to any antibody or drug of immune-mediated therapy,  including but not limited to LAG-3, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4),  anti-PD-1, anti-PD-L1 antibodies.  2. Have received systemic treatment with Chinese herbal medicine or immunomodulatory  drugs with anti-tumor indications (including thymosin, interferon, interleukin, except  for local use to control pleural effusion) within 2 weeks prior to the first  administration of study drug.  3. Have active or uncontrolled central nervous system (CNS) metastases and/or spinal cord  compression and/or carcinomatous meningitis, or history of leptomeningeal carcinoma.  Subjects with a history of radiotherapy or surgery for brain metastases and  asymptomatic CNS metastases at the time of screeing are eligible if they meet all of  the following criterias: have measurable lesions outside the CNS; do not have  midbrain, pons, meninges, medulla oblongata or spinal cord metastases; do not have  evidence of new or enlarged brain metastases after treatment for brain metastases, and  corticosteroids and anticonvulsants treatments have been discontinued for at least 14  days prior to the study treatment. Subjects with asymptomatic brain metastases can be  included if the brain metastases have been treated with radiotherapy and above  mentioned criterias are all met.  4. Are expected to require any other antineoplastic therapy while in study (PCI is  allowed).  5. Have received administration of live attenuated vaccines within 4 weeks prior to the  first administration of study drug or anticipation that such a live attenuated vaccine  will be required during the study.

To determine whether a heterologous vaccination regimen in individuals with no known previous  history of COVID-19 is non-inferior to that observed with counterpart regimens currently in  use in Argentina among persons aged 21 to 65 years The Covid-19 disease caused by the SARS-COV 2 virus has caused a pandemic with more than 180  million cases worldwide and more than 4 million deaths. In Argentina, this pandemic has had a  significant impact, with about 4.5 million cases and about 95,000 deaths. In no more than  nine months, medical science developed different vaccines to prevent new cases and mitigate  this pandemic.  At the time of the presentation of this research protocol, there are four vaccines for the  prevention of COVID-19 approved for emergency use by the National Administration of  Medicines, Food and Medical Technology (ANMAT). Argentina recently received a donation of 3.2  million doses of Moderna (mRNA-1273) vaccine from the US government. This vaccine was  approved for emergency use in the context of the pandemic. All require the administration of  two doses with an administration interval of at least 21 days.  All these vaccines were designed to be used with a homologous two-dose regimen. However, for  both logistical and biomedical reasons, the need to use vaccines in heterologous regimens  (one dose of one vaccine and a second dose of another vaccine) is emerging worldwide. The  efficacy and safety of this type of regimen has not yet been demonstrated.  In Argentina, there are a large number of people who currently have one dose of Gam-COVID-Vac  vaccine and who - even after a period of ≥21 days - have not received the second component.  At the same time, the provision of the second component of the Gam-COVID-Vac vaccine is  delayed due to production and distribution logistics.  As of 08/02/2021, among the universe of people vaccinated with Gam-COVID, residents of CABA,  vaccinated in establishments in the City of Buenos Aires - and excluding deceased and  infected people - there were a total of 332,291 people with one dose and ≥22 days since the  first dose was administered. In a context of high viral circulation, it is desirable to try  to vaccinate as much of the population as possible with a full schedule in the shortest  possible time. In addition, new variants of SARS-COV2 virus possessing the E384K genomic  variant such as the gamma strain (formerly Manaus), the beta strain (known as South African)  and the Delta strain (also known as Indian) have the ability to evade the immune system and  therefore most laboratories that have developed vaccines recognise that the efficacy of the  vaccines requires two doses.  This study will attempt to determine whether administration of a heterologous regimen  combining a first dose of Gam-COVID-Vac the repetition of the first component of the  Gam-COVID-Vac vaccine (rAd26) or the administration of an RNA vaccine (mRNA-1273) resulted in  a non inferiority result that the classic and recomended protocol based on two dosis of  Gam-COVID-Vac (rAd26-rAd5) .  The present protocol is therefore oriented to respond to a practical management need and to  guarantee the best possible protection to the population through two doses, which is what is  considered worldwide as "complete vaccination" according to WHO for the vaccines used by  Argentina. The proposed protocol is a pragmatic and public health oriented clinical trial,  whose primary objective is to establish whether there are indicators that allow the  implementation of a heterologous vaccination scheme. For this, a surrogate endpoint will be  used, which is immunogenicity measured by the presence of antibodies against protein S. In  addition, the safety of the combination will be evaluated in terms of monitoring  self-reported and non-self-reported clinical events by patients. Inclusion Criteria:  -  Persons who have received a dose of Gam-COVID-Vac more than 30 days and:  -  Age > 21 and <66 years.  -  Both genders.  -  Who have voluntarily agreed to participate in the clinical trial and have provided  informed consent. Exclusion Criteria:  -  Known history of COVID in the 6 months prior to study inclusion.  -  Known or suspected immunocompromised status by the study investigator for any cause.  -  Use of oral or parenteral corticosteroids in the last 30 days.  -  Known history of allergy to any vaccine.  -  History of anaphylaxis.  -  Pregnant or lactating women.  -  Known history of autoimmune diseases.  -  Persons under treatment for any neoplastic disease within the last 6 months.  -  Any serious illness or condition at the discretion of the study investigator  (including but not limited to the presence of chronic obstructive pulmonary disease,  heart failure, poorly controlled hypertension, poorly controlled diabetes, renal  failure).  -  Planned medical procedures within two months of randomisation.  -  Previous vaccination within the last 30 days with any vaccine.  -  Known participation in an ongoing clinical trial.  -  Ongoing acute illness.  -  Fever (≥37.8 C) at the time of randomisation.

A Prospective, Multicenter, Non-Randomized Study of the Aerin Medical Vivaer ARC Stylus for  Nasal Airway Obstruction The primary objective of this post-market study is to continue to evaluate the effectiveness  of the Vivaer® ARC Stylus for treating the nasal valve area to improve symptoms in those  diagnosed with nasal airway obstruction using validated questionaires. Inclusion Criteria:  Eligible subject will meet all the following:  -  1. Age 18 or older 2. Willing and able to provide informed consent 3. Willing and able  to comply with the study protocol 4. Seeking treatment for nasal obstruction 5. NOSE  score of ≥ 60 at Baseline 6. Nasal valve is a primary or significant contributor to  the subject's nasal obstruction as determined by the study investigator (based on  clinical presentation, physical examination, nasal endoscopy, etc.) and the subject  has a positive response to any of the following temporary measures (based on patient  history or office exam):  -  Use of external nasal dilator strips (e.g., Breathe Right Strips)  -  Q-Tip test (manual intranasal lateralization)  -  Use of nasal stents  -  Cottle Maneuver (manual lateral retraction of the cheek) Exclusion Criteria:  Eligible subjects will NOT meet any of the following:  1. Prior surgical treatment of the nasal valve  2. Rhinoplasty, septoplasty, inferior turbinate reduction or other surgical nasal  procedures within the past six months  3. Medical conditions which in the opinion of the treating physician would predispose the  subject to poor wound healing or increased surgical risk.  4. Known or suspected to be pregnant or is lactating.  5. Any adjunctive surgical nasal procedure planned on the same day or within 24 months  after the Vivaer procedure.  6. Current participation in any study or participation in any study less than 6 weeks  before study date 1.  -

The main objective of this study is to determine whether 24/7 hybrid closed-loop insulin  delivery under free living conditions applying faster insulin aspart (FiAsp) is superior to  24/7 hybrid closed-loop insulin delivery applying standard insulin aspart in very young  children with type 1 diabetes.  The closed-loop system consists of three components: the continuous glucose monitor (CGM),  the insulin pump and a smartphone Application, or App, that translates, in real-time, sensor  glucose levels received from the glucose monitoring device and calculates the amount of  insulin to be delivered by the coupled insulin pump.  This is a double-blind, multi-centre, randomised, crossover design study, involving a run-in  period followed by two 8-week study periods during which glucose levels will be controlled by  a hybrid closed-loop system using either standard insulin aspart or faster insulin aspart in  random order.  Participants aged 2-6 years with type 1 diabetes on insulin pump therapy will be recruited  through paediatric diabetes outpatient clinics at participating clinical centres. Enrolment  will target up to 30 children (aiming for 6-14 participants per centre) to allow for dropouts  during run-in.  Prior to the use of study devices, participants and parents/guardians will receive  appropriate training by the research team on the safe use of the study pump and CGM device,  and the hybrid closed-loop insulin delivery system. Parents/guardians at nursey/school may  also receive training by the study team if required. Participants will have regular contact  with the study team during the study including 24/7 telephone support. Parents/guardians will  be asked to complete validated questionnaires at the start and end of the study to assess  quality of life measures including sleep.  The primary outcome is the between group difference in time spent in target range between 3.9  and 10.0 mmol/l as recorded by CGM during the study. Secondary outcomes are time spent with  glucose levels above and below target, as recorded by CGM, and other CGM-based metrics.  Safety evaluation comprises assessment of the frequency and severity of hypoglycaemic  episodes and diabetic ketoacidosis (DKA). Purpose of clinical trial:  To compare hybrid closed-loop applying faster insulin aspart to hybrid closed-loop applying  standard insulin aspart over 8 weeks.  Study objectives:  The study objective is to compare hybrid closed-loop glucose control using faster insulin  aspart with hybrid closed-loop control using standard insulin aspart in very young children  with type 1 diabetes.  1. EFFICACY: The objective is to assess the ability of a hybrid closed-loop system applying  faster insulin aspart to maintain CGM glucose levels within the target range from 3.9 to  10.0 mmol/l, in comparison to a hybrid closed-loop system applying standard insulin  aspart in very young children with type 1 diabetes.  2. SAFETY: The objective is to evaluate the safety of closed-loop glucose control using  faster insulin aspart compared to standard insulin aspart in terms of episodes and  severity of hypoglycaemia, frequency of diabetic ketoacidosis (DKA) and nature and  severity of other adverse events.  3. UTILITY: The objective is to determine the acceptability and duration of use of the  closed-loop system.  4. HUMAN FACTORS: The objective is to assess emotional and behavioural characteristics of  parents/guardians and their response to the closed-loop system and clinical trial using  validated surveys.  Participating clinical centres:  1. Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge  2. John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford  3. Nottingham Children's Hospital, Nottingham  4. Alder Hey Children's Hospital, Liverpool  Sample Size:  24 children randomised (6-14 participants per centre).  Maximum duration of study for a subject:  6 months  Recruitment:  Participants will be recruited through the paediatric diabetes outpatient clinics at  participating clinical centres (see above). Enrolment will target up to 30 participants  (aiming for 6-14 participants per centre), to allow for dropouts during run-in.  Consent:  Written informed consent will be obtained from all parents/guardians.  Screening and baseline Assessment:  Eligible participants will undergo a baseline assessment including a blood sample for the  measurement of HbA1c. Height and weight will be recorded. Validated questionnaires will be  completed by parents/guardians.  Pre-Study Training and Run-in:  Training sessions on the use of the study CGM, insulin pump and hybrid closed-loop insulin  delivery will be provided by the research team. During the closed-loop training session,  parents/guardians will operate the system under the supervision of the clinical research  team. Participants and parents/guardians will use the study CGM, insulin pump, and hybrid  closed-loop insulin delivery during a 2-4 week run-in period. For compliance and to assess  the ability of the participant to use the study devices safely, at least 8 days of CGM data  need to be recorded and safe use of study insulin pump and hybrid closed-loop insulin  delivery demonstrated during the last 14 days of the run-in period. The CGM data will also be  used to assess baseline glucose control and may be used for treatment optimisation as  necessary.  Competency Assessment:  Competency on the use of study pump,study CGM and hybrid closed-loop insulin delivery will be  evaluated by the research team. Training may be repeated if required.  Randomisation:  Eligible participants will be randomised using randomisation software to the initial use of  faster insulin aspart with the hybrid closed-loop system or to standard insulin aspart with  the hybrid closed-loop system for 8 weeks before crossing over to the other treatment arm.  1. Faster insulin aspart with hybrid closed-loop:  Participants and their parents/guardians will use the hybrid closed-loop system with  faster insulin aspart for 8 weeks at home. The participant, parents/guardians and the  research team will be blinded to the intervention.  Crossover assessment:  At the end of the first study arm, validated questionnaires will be completed by the  parents/guardians.  2. Standard insulin aspart with hybrid closed-loop:  Participants and their parents/guardians will use the hybrid closed-loop system with standard  insulin aspart for 8 weeks at home. The participant, parents/guardians and the research team  will be blinded to the intervention.  Study contacts:  Participants and parents/guardians will be contacted 24 hours after starting each study arm  to ensure there are no concerns regarding the study devices. Participants will be contacted  by the study team (email/phone) 2 and 4 weeks after the start of each study arm in order to  record any adverse events, device deficiencies, and changes in insulin settings, other  medical conditions and/or medication.  In case of any problems related to the technical devices or diabetes management, participants  and parents/guardians will be able to contact a 24-hour telephone helpline to the local  research team. The local research team will have access to central 24 hour advice on  technical issues.  End of study assessments:  Height and weight will be recorded. Validated questionnaires will be completed by  parents/guardians. Participants will resume usual care using their pre-study insulin pump.  Procedures for safety monitoring during trial:  Standard operating procedures for monitoring and reporting of all adverse events will be in  place, including serious adverse events (SAE), serious adverse device effects (SADE) and  specific adverse events (AE) such as severe hypoglycaemia.  A data safety and monitoring board (DSMB) will be informed of all serious adverse events and  any unanticipated serious adverse device effects that occur during the study and will review  compiled adverse event data at periodic intervals.  Criteria for withdrawal of subjects on safety grounds:  A participant and parent/guardian may terminate participation in the study at any time  without necessarily giving a reason and without any personal disadvantage. An investigator  can stop the participation of a participant after consideration of the benefit/risk ratio.  Possible reasons are:  1. Serious adverse events  2. Serious protocol violation  3. Non-compliance  4. Failure to satisfy competency assessment  5. Decision by the investigator, or the Sponsor, that termination is in the participant's  best medical interest  6. Allergic reaction to insulin Inclusion Criteria:  1. Age between 2 and 6 years (inclusive)  2. Type 1 diabetes as defined by WHO for at least 6 months [WHO definition: 'The  aetiological type named type 1 encompasses the majority of cases which are primarily  due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those  cases attributable to an autoimmune process, as well as those with beta-cell  destruction for which neither an aetiology nor a pathogenesis is known (idiopathic).  It does not include those forms of beta-cell destruction or failure to which specific  causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']  3. Insulin pump user (with or without continuous glucose monitoring or flash glucose  monitoring system) for at least 3 months, with parent/guardian good knowledge of  insulin self-adjustment as judged by the investigator  4. Treated with U-100 rapid or ultra-rapid acting insulin analogue  5. Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory  6. Able to wear glucose sensor  7. Able to wear closed-loop system 24/7  8. The parent/guardian is willing to follow study specific instructions  9. The parent/guardian is proficient in English Exclusion Criteria:  1. Physical or psychological disease likely to interfere with the normal conduct of the  study and interpretation of the study results as judged by the investigator  2. Untreated coeliac disease or thyroid disease based on local investigations prior to  study enrolment  3. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic  corticosteroids  4. Known or suspected allergy to insulin  5. Parent/guardian's lack of reliable telephone facility for contact  6. Parent/guardian's severe visual impairment  7. Parent/guardian's severe hearing impairment  8. Medically documented allergy towards the adhesive (glue) of plasters or subject is  unable to tolerate tape adhesive in the area of sensor placement  9. Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located in  parts of the body which could potentially be used for localisation of the glucose  sensor)

The study investigates the associations of ambulatory electrodermal activity (EDA)  measurements with mental well-being at work, especially job burnout. Appropriate statistical  methods are applied to predict burnout with EDA measurements combined with self-report  surveys on emotional valence. The aim of the study is to complement burnout research by considering ambulatory  electrodermal activity (EDA) measurements as part of the identification and definition of the  burnout phenomenon. Previous studies have shown that assessment methods for the physiological  identification of burnout do not yet exist and that more information on the physiological  markers of burnout is needed. The study also complements the understanding of how and in what  cases ambulatory measurements of EDA can be justified, for example, as an occupational health  care tool.  The study investigates the association between ambulatory EDA measurements and mental  well-being, especially job burnout, and the potential of the measurements in supporting  better mental health at work. According to research the EDA measurements alone do not always  provide sufficient information and often context related information is needed to improve the  interpretation of the measurement. Therefore, the EDA measurements are complemented with the  self-reported emotional valence.  The state of mental well-being is defined using Peter Warr's model of affective well-being.  The model proposes that two dimensions of emotion, arousal and emotional valence, together  can provide information / be used to describe one's affective well-being at work. The model  is further based on the circumplex model of affect.  Previous studies of EDA have shown that the measurement method has a potential role in  assisting the diagnosis of some mental disorders, such as anxiety and depression. However,  the measurements have been largely tied to laboratory settings and have not been able to be  utilized in everyday life. The development of health and well-being technology has brought to  the market methods for measuring the electrical conductivity of the skin, which are suitable  for ambulatory measurements, but whose suitability must be critically assessed.  Within this study it is hypothesized that the average variation of the sympathetic nervous  system activity measured with EDA and combined with a self-reported emotional valence is  associated with mental well-being at work, as burnout measured with the Burnout Assessment  Tool (BAT-12), anxiety measured with Generalized Anxiety Disorder (GAD-7) Scale, depression  measured with Beck Depression Inventory (BDI-21), and job engagement measured with Utrecht  Work Engagement Scale (UWES-9).  The study is longitudinal, consisting of four measurement periods at six-month interval. One  measurement period of EDA and valence is two weeks. EDA and emotional valence are recorded  with a commercially available Moodmetric smart ring and Moodmetric mobile app. EDA is  measured with using the Moodmetric index which is calculated from the EDA raw signal produced  by the Moodmetric smart ring. EDA and valence measurements are then compared with BAT-12,  GAD-7, BDI-21, UWES-9 that measure burnout, anxiety, depression, and job engagement  respectively. The survey data (BAT-12, GAD-7, BDI-21, and UWES-9) is gathered after every  two-week measurement period is over. 150 voluntary knowledge workers from three Finnish  companies are invited to participate in the study. Inclusion Criteria:  -  Healthy volunteers, but they may have mental health issues  -  Employed by one of the target organizations in the beginning of the study  -  Informed consent in a written form by the study subject Exclusion Criteria:  -  Nickel sensitivity

The project PeptiClear aims to investigate whether the blood-brain-barrier (BBB) and the  glymphatic system are compromised in atypical neurodegenerative diseases, and whether  Alzheimer´s disease (AD)-related copathology, vascular lesions or sleep disturbances modify  the clinical picture or structural and/or functional features of the diseases. It is well established for the frequent sporadic (non-genetic) variant of Alzheimer´s disease  (AD) that not the overproduction of a specific protein (Amyloid-beta - Aβ) is a major cause  but rather the insufficient clearance of this protein from the central nervous system. On one  hand, under physiological conditions, the interplay of the several cell types (cerebral  endothelial cells, perivascular mural cells (pericytes), glial cells (astrocytes and  microglia) and neurons) regulates the neuronal and glial cell environment and is crucial for  cell function and survival. On the other hand, Aβ aggregates lead to BBB damage and  activation of microglial cells. The BBB facilitates the clearance of proteins such as Aβ via  the cerebrovascular system, but its association with other intracerebral Aβ drainage systems,  such as the glympathic system, remains to be clarified. As the glymphatic system is mainly  active during sleep, sleep disturbances could influence the clinical course. Concerning  atypical neurodegenerative diseases, it is not clear whether tau or alpha-synuclein  (alpha-syn) deposits also have a potential to damage the BBB. In AD Aβ aggregation and  vascular changes give rise to insufficient protein clearance and thus contribute to AD  pathogenesis in a synergistic fashion. However the role of copathology in atypical  neurodegenerative diseases - which mainly consists of Alzheimer-related changes and vascular  pathology - is elusive and remains to be clarified.  The prospective study cohort (N ~80) will include patients with Lewy Body spectrum disease,  progressive supranuclear palsy, corticobasal syndrome and frontotemporal dementia. All study  participants will undergo a detailed clinical and neuropsychological assessment according to  a standardised protocol (i.a. magnet resonance imaging (MRI), positron emission tomography  (PET), cerebrospinal fluid (CSF), actigraphy). Inclusion Criteria:  -  Diagnosis of Atypical Parkinsonian Disorders or Frontotemporal Dementia  -  Able to provide written informed consent  -  Unchanged pharmacotherapy within 4 days prior to the study specific assessments  -  Fluent in German Exclusion Criteria:  -  Unable to give informed consent or has a legal guardian  -  Other severe mental disorder, e.g. schizophrenia or bipolar affective disorder  -  Clinically relevant depression  -  Acute suicidality  -  Current alcohol, drug or medication abuse  -  History of severe traumatic brain injury within 3 months prior to inclusion  -  Structural lesions of the basal ganglia or brain stem  -  Severe neurological disorder including (but not limited to) epilepsy, systemic  disorders, stroke, repeated transient ischaemic attacks, increased brain intracranial  pressure, normal pressure hydrocephalus  -  Severe medical disorders including (but not limited to) heart failure, respiratory  failure, uncontrolled severe arterial hypertension  -  Electronic implants (e.g. cardiac pacemaker) or other MRI contraindication  -  Renal failure > stage 3 (GFR < 30 mL/min)  -  Pregnancy  -  Unresolved malignancies within two years prior to inclusion  -  Severe current infections or other chronic or systemic disorders  -  Other circumstances which preclude participation based on the investigator's judgement

Effect of Integrated Neuromuscular Training on Explosive Strength, Speed and Endurance of  Medium Fast Bowler in Cricket Integrated neuromuscular training (INT) is a combination of functional movement training and  specific strength, balance, speed, sensitivity, and isometric training, which aims to evaluate  and prevent sports injury and improve sports performance. Neuromuscular control defects are  mainly manifested as decreases in muscle strength, explosive power, or abnormal activation  patterns. INT is defined as a conceptual training program that incorporates general (e.g.,  fundamental movements) and specific strength and conditioning tasks (e.g., resistance,  balance, agility, plyometric) to improve injury resilience and to enhance sporting and motor  skill performance. The majority of studies in youth examining neuromuscular training  strategies to improve performance and injury prevention include multiple components (for  example, balance, strength, plyometric, agility, speed, coordination. INT sessions are  characterized by short bursts of physical activity interspersed with brief rest periods.  the purpose of this study is to find the effect of integrated neuromuscular training on  explosive strength, speed and endurance of medium fast bowler in cricket Inclusion Criteria:  -  Medium fast bowlers  -  Players playing cricket for > 1 year  -  Players engaging in cricket ≥ 3 days in a week Exclusion Criteria:  -  History of any injury in past 6 months.  -  Those players having musculoskeletal, neurological, cardiorespiratory problems  -  Those players who have any medical condition

This study aims to evaluate antithrombotic activities of novel yoghurt drink in healthy adult  volunteers This randomized controlled, double-blinded crossover study aims to investigate the  antithrombotic activities of a novel yoghurt drink in healthy adult volunteers. It is  anticipated that the novel drink containing beneficial polar lipids will reduce platelet  aggregation in participants and consequently decrease the onset of cardiovascular disease.  In Phase I, the subjects will provide blood samples after overnight fasting and then take  either a yoghurt drink (YD) or placebo (that does not contain polar lipids) daily for 4  weeks. Following this period, they will again provide blood samples. Then, after a 2-week  washout period in which the subjects do not take any yoghurt or placebo drink , Phase II of  the clinical trial will commence. This is the crossover phase in which subjects who took YD  will now be given a placebo drink, and vice versa, over 4 weeks. A total of 80 blood samples  will be collected for analysis. Inclusion Criteria:  -  Healthy adults Exclusion Criteria:  -  Volunteers need to be off medication and off any dietary supplements.  -  Subjects must not have any blood clotting disorders or dyslipidaemia.  -  Dairy intake needs to be within a normal range of 1-2 portions a week.  -  Unwilling to follow the study requirements.

When there is space present between our teeth orthodontically we have the ability to close  them through many methods. Using braces as our treatment modality this study will be  investigating how efficient a new orthodontic wire is in closing tooth space. This new  material is trade-named GUMMETAL and claims to have many benefits to treating patients  orthodontically. We will be exploring its efficiency in space closure compared to an industry  standard (stainless steel). We predict that the stainless-steel orthodontic wire will be more  efficient at space closure than the new GUMMETAL wires. This will be a randomized pilot split-mouth clinical trial of patients with spaces ≥ 3mm  distal to the maxillary canines in need of closure through sliding mechanics. The sample  consists of adolescent patients regardless of Angle's molar malocclusion who are receiving  comprehensive full fixed appliance orthodontic treatment. Preformed conjoint archwires half  being GUMMETAL and the other half SS, will be utilized. Each patient will have one side of  the maxilla randomly allocated into the SS or GUMMETAL treatment group. The study will follow  a split-mouth design to reduce the confounding variables from patient to patient on space  closure mechanics. The maxillary arch in each subject will be randomized into a SS side or GM  side using a random number generator. Spaces will be measured at; T0 is initial records, T1  is initiation of space closure, T2 will be 4 weeks after the initiation of space closure, T3  is another 4 weeks of space closure evaluation and T4 will be the final evaluation of space  closure after 4 weeks from T3, via 3D intraoral scans of maxillary arches. Space measurement  and calculations will utilize 3Shape software to measure the distance of canine movement  based off the distal surface. Sliding mechanics will be activated through NiTi coil springs  from the maxillary canines to the maxillary molars. The force will be standardized to 150 gms  and will be measured each visit. The same provider will activate the NiTi coil spring for  retraction, along with data collection. Superimposition of scans will be utilized to assess  outcome measures. Inclusion Criteria:  -  Full permanent dentition (except third molars)  -  Good general and oral health  -  Bilateral spaces 3 >/= mm distal to the maxillary canines  -  Normal and hypodivergent growth pattern  -  Any dental malocclusion  -  Good Oral Hygiene Exclusion Criteria:  -  Systemic diseases or syndrome  -  Abnormalities in teeth size and/or shape  -  Previous orthodontic treatment  -  Anti-inflammatory medication  -  Craniofacial anomalies  -  Hyperdivergent growth pattern  -  Periodontal disease / attachment loss exceeding 25% of root length  -  Significant pre or in-treatment root resorption

The incidence of atrial fibrillation (AF) after lung resection varies between 12% and 30%  after lobectomy and 23%-67% after pneumonectomy. The average time of onset of AF after lung  resection is 2-3 days. AF after pulmonary resection can cause symptoms, hemodynamic  instability, and stroke.Furthermore, AF following pulmonary resection may triple the mean  duration stay in the intensive care unit and increase the total length of hospital stay by  2-9 days, with an increased in associated hospitalization costs.lastly, AF after lung  resection has been associated with an increased risk of mortality , although the arrhythmia  is more likely to be a consequence of other associated cardiopulmonary complications, rather  than the main cause of death.  our study aim to assess the role of intra operative dexmedetomidine in reduction of early  postoperative atrial fibrillation in patients undergoing thoracic non cardiac surgeries.  Objectives:  1. To evaluate possible efficacy of intraoperative dexmedetomidine in reduction of  postoperative atrial fibrillation in patients undergoing thoracic non cardiac surgeries  2. To determine the incidence of new-onset atrial fibrillation after thoracic non cardiac  surgeries in patients given intra operative dexmedetomidine This a randomized control trial is designed to include (350) patients ASA physical status II  patients ranging from(18) to(70)years old scheduled for thoracic non cardiac surgeries  Patients meeting the inclusion criteria will be randomly assigned to receive either :  Group I : dexmedetomidine: (n=175) dexmedetomidine will be administered as a bolus dose,  before the surgical incision with 1mcg/kg iv over 10 minutes followed by infusion rate of 0.5  μg/kg per h and stopped at the end of operation.  GroupII: normal saline placebo:(n=175) similar bolus and infusion volumes of normal saline  will be administered as dexmedetomidine group  Anesthesia management  Preoperative procedures:  Full history and investigation will be taken in the form of CBC, blood sugar ,liver function  tests. Kidney function tests ,electrolytes and coagulation profile Preoperative awake supine  trans thoracic echocardiograms will be performed before operation using a 2.5/2.0- MHz  transducer for imaging and Doppler echocardiography. Preoperative 12-leads will be performed  to all patients. On arrival of the patient to the operating theatre and before induction of  anesthesia, all standard monitors will be applied, including heart rate (HR), ECG, oxygen  saturation (SpO2), end-tidal CO2, arterial blood pressure (systolic, diastolic, and MAP), and  temperature, arterial catheter will be inserted in the radial artery for continuous blood  pressure monitoring and frequent blood gas analysis. Initial readings of all these monitors  will be taken and recorded before starting any drug infusion. After securing IV access by 20G  cannula, all patients will be premedicated with 0.05mg/kg midazolam for anxiety, antibiotic  50mg/kg.  Intraoperative procedures:  Induction of general anesthesia will be done by fentanyl 2ug/kg/ iv, 2mg \kg propofol, and  0.5mg\kg atracurium to facilitate endotracheal intubation. Anesthesia maintenance will be  achieved with endotracheal tube with suitable size, 1.2 minimum alveolar concentration of  isoflurane, volume controlled mode ventilation, respiratory rate will be adjusted according  to Et CO2 to range between 35-40 mmHg, a tidal volume of 6-8 ml/kg and mixture of gases in  proportion 50% oxygen and 50% air, with PEEP 5 cm H2O and0.1 mg\kg atracurium every 30  min.10mg morphine intravenous will be given after induction and intubation.  Intervention Dexmedetomidine will be administered as a bolus dose, before the surgical  incision with 1mcg/kg iv in 100 ml saline solution over 10 minutes followed by infusion rate  of 0.5 μg/kg per h infusion via syringe pump during surgery and stopped at the end of  operation. Similar bolus and infusion volumes of normal saline will be administered in the  Control group (placebo) However, anaesthesiologists will be permitted to reduce dose of the  study drug as necessary to preserve haemodynamic stability(systolic blood pressure decrease  more than 20% from the baseline or\ and heart rate less than 60 ). with occurence of  bradycardia and \or hypotension it will be managed by the attending anesthesiologist  according to standard institutional guidelines and drug infusion rate will be decreased to  the half. if bradycardia or hypotension persisted, drug infusion will be unblinded, stopped  and reported as a serious side effect occured with drug infusion .By the end of surgery,  anaesthesia will be discontinued ,patient will be reversed by neostigmine 0.05mg\kg and  atropine0.02mg\kg, extubation will be done and patient will be transferred to post  anaesthesia care unit (PACU).  Postoperative  1. Postoperative analgesia will be started with continuous infusion of 30 mg morphine  associated with 180 mg ketorolac in 250 ml of normal saline at 5 ml /h and paracetamol  infusion 1 g every 6 h. Additional bolus dose of 0.04mg/kg if vas exceed or equal 4 and  it will be repeated if pain exist every 6 hours. All patients will be continuously  monitored by 5-leads ECG and pulse oximeter(oxygen saturation) .12-leads ECG will be  performed in occurence of tachycardia or arrythmia for the first 72 hours. Diagnoses of  atrial fibrillation in the cardiac ICU will be made by clinicians who will be masked to  group allocation. Atrial fibrillation will be defined by: clinician diagnosis;  documented arrhythmia lasting at least 5 min ( supraventricular tachyarrhythmia  characterized by uncoordinated atrial activation .Electrocardiographic findings include  the replacement of the normal consistent p waves with oscillatory or fibrillatory waves  of different sizes amplitudes and timing with narrow QRS complex unless other conduction  abnormalities exist ( e.g. bundle branch block , accessory pathways). The ventricular  response is often rapid and between 90 and 170 beats per minute and it will be  documented by 12- lead ECG.  2. Post operative haemodynamic will be assessed (heart rate , ,systolic and diastolic blood  pressure every 2 hours or with the occurrence of dysrhythmia)  3. Serial cardiac enzymes concentration (CK MB , Troponin ) will be measured every 6 h to  rule out myocardial infarction. Inclusion Criteria:  1. Gender both males and females  2. ASA Class II  3. Age 18-70 years  4. Patients undergoing thoracic non cardiac surgeries(lobectomy, pneumonectomy, and  esophagectomy). Exclusion Criteria:  A. Hypersensitivity or known allergy to dexmedetomidine. b.Patients with Sick-sinus  orWolff-Parkinson-White syndromes; atrioventricular block atrial fibrillation within 30  days; a permanent pacemaker; used amiodarone or dexmedetomidine within30 days.  c. Patients with echocardiographic finding of an ejection fraction <30% and left atrial  diameter more than 45mm and use of beta blockers or statins.  d. Liver and renal impairment(elevated liver enzymes (ALT, AST two to three fold), CRF ) e  .Emergency operations ,video assisted thoracic surgeries and operation for spontaneous  pneumothorax

The purpose of this study is to compare the positive and negative effects of Dex4® tablets,  as an alternative form of fast acting carbohydrate, compared to the current standard  diagnostic test, glucose beverage. The investigators hypothesis that because of their  availability in solid, chewable form, variety of flavours and lack of carbonation, Dex4®  tablets may result in fewer side effects than glucose beverage and provide an equivalent  carbohydrate challenge for diagnosis of gestational diabetes. The project is a population-based, prospective randomized crossover study. Women who fall  into the screen positive group of the 50g GCT (1 hour serum glucose of 7.8-11 mmol/L) will be  offered participation in the study. 28 participants will be recruited and will be randomly  assigned using a pre-populated allocation table to take either the standard OGTT test (75g of  glucose beverage) first or the alternative OGTT test (21 Dex4® tablets) first. The first test  will be referred to as OGTT-1 and the second test will be referred to as OGTT-2. After  completing OGTT-1 at the first test appointment, a questionnaire about pregnancy, health,  diet and exercise habits, and side effects from the first test will be completed by the  participant (Questionnaire A). After completing OGTT-2 at their second test appointment, a  questionnaire about side effects from the second test and test preference will be completed  by the participant (Questionnaire B). Each woman will complete both tests within one week and  each subject will serve as their own control. Results will be kept blinded in the case report  forms until both OGTT tests are done. Serum glucose will be measured using the same  internationally standardised glucose-oxidase method (RocheDiagnosis) in the Sunnybrook  Biochemistry lab. After serum glucose measurement, all results will be sent to the research  team but only the standard of care glucose beverage test data will appear in electronic (or  classical) medical records and be used for GDM diagnosis.  The participant population consists of 28 pregnant women between 24-28 weeks' gestation who  have screened positive for gestational diabetes on the 50g glucose challenge test. The main  drawback to participation is that women will have to undergo two fasting, 1 hour and 2 hour  glucose values within one week. Risks involved with participating in the study include:  possibility of pain, bruising, swelling or infection related to drawing blood, allergic  reaction symptoms such as itching, facial swelling and anaphylaxis upon consumption if the  participant has an allergy to corn based products such as dextrose. These risks will be  minimized by screening patients for dextrose allergy before having them sign the informed  consent form.  The benefit may not be directly to the patient as they will still need to complete the  standard 75g glucose beverage test but they will be contributing to new knowledge on  alternatives to the standard test that may benefit other pregnant women, including  themselves, in the future.  The ultimate goal of this project is to improve women's health by 1) allowing more women to  be screened for GDM and 2) providing an equivalent glucose beverage alternative with fewer  side effects, making the screening process more comfortable for patients who cannot tolerate  glucose beverage. Improving the tolerability of the test is important because there is  growing evidence that GDM significantly increases the risk of short and long term adverse  consequences for both the fetus and the mother (10,11). Accurate diagnosis may allow women to  implement preventative measures such as a healthy lifestyle, which has shown to be effective  in preventing T2DM in women with previous GDM (19,20). There have been recent quality control  issues with the commercially available glucose beverage product (16), so this alternative  test could become the standard test if the dose calibration is found to be more reliable.  Primary objective 1 (PO-1): to determine if Dex4® tablets is equivalent to glucose beverage  for use in the 2-hr 75g OGTT in pregnant women between 24-30 weeks gestation who have  screened positive for GDM.  Secondary objective (SO-1): to determine if women have fewer side effects and prefer the  standard (glucose beverage) OGTT test or the alternative (Dex4® tablets) OGTT test Inclusion Criteria:  -  Positive 50g GCT result between 7.8-11.0 mmol/L  -  Female  -  Singleton pregnancy  -  Informed consent obtained and signed Exclusion Criteria:  -  Use of steroids, terbutaline, or metformin within the last 4 weeks  -  Previous diagnosis of diabetes type 1 or 2 outside of pregnancy or diagnosis with any  form of diabetes prior to 20 weeks of pregnancy  -  Allergy to any ingredients (including the non-medicinal ingredients) in Dex4® tablets  or Glucodex solution

Insomnia is a common and distressing symptom for patients on hemodialysis (HD), and there is  evidence for a much larger impact on the health of patients. Chronic insomnia is disrupted  sleep that occurs at least three nights per week and lasts at least three months.  The SLEEP-HD study is a randomized open-label clinical trial to compare two types of  treatment for insomnia in participants who have end-stage renal disease on HD, and who have  been diagnosed with chronic insomnia. The two types of treatment involved in the study are  Cognitive Behavioral Therapy for Insomnia (CBT-I) or treatment with a drug (trazodone vs  placebo).  126 participants will be enrolled who are undergoing HD in two study locations (Seattle,  Washington and Albuquerque, New Mexico). Most HD patients have significant impairments in quality of life, largely from the high  frequency of disabling symptoms. Insomnia is one of the most frequently reported symptoms and  studies of HD patients and/or other populations suggest that it is a significant contributor  to other common symptoms and poor health outcomes. There are unique contributors to chronic  insomnia in HD patients and these include the biologic effects of residual uremia after  partial correction as is achieved with current dialysis technology, maladaptation to  treatment schedules, and patients' napping during treatments.  There is a compelling need to identify effective treatments for insomnia in HD patients and  the interventions being studied in this clinical trial, telehealth cognitive behavioral  therapy for insomnia (CBT-I) and trazodone, have a strong scientific premise. If telehealth  (web-based) CBT-I is effective for insomnia in HD patients, it will make a treatment that is  presently inaccessible available to patients. Trazodone is widely used but the data on  efficacy for insomnia are limited; no such data exist for HD patients.  SLEEP-HD is a parallel group randomized controlled trial wherein 125 HD patients with chronic  insomnia, treated in community-based dialysis facilities in Seattle and Albuquerque, will be  randomized 1:1:1 over 31 months to 6-week treatment with telehealth CBT-I, trazodone, or  medication placebo. Inclusion Criteria:  -  Undergoing thrice-weekly maintenance hemodialysis for ≥ 3 months  -  Able to speak English  -  ISI score ≥ 10 at pre-screening with sleep disturbances for ≥ 3 nights per week for ≥  3 months Exclusion Criteria:  -  Severe cognitive impairment on Mini-COG cognitive test (score < 3)  -  Severe depression assessed by Patient Health Questionnaire (PHQ)-2 and if appropriate,  PHQ-9  -  Suicidal Ideation  -  Alcohol abuse on CAGE alcohol assessment questionnaire (score ≥ 2) or substance abuse  on Drug Abuse Screening Test (DAST)-10 questionnaire (score > 5)  -  Severe restless leg syndrome  -  Treatment with trazodone in the past one month  -  Known allergy to trazodone (self-report or by chart review)  -  Current treatment with monoamine oxidase inhibitors or in the preceding 14 days  -  Current treatment with linezolid (self-report or by chart review)  -  Current treatment with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole,  clarithromycin, voriconazole), or known to prolong QT interval including Class 1A  antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g.,  amiodarone, sotalol), antipsychotic medications (ziprasidone, chlorpromazine,  thioridazine), and quinolone antibiotics  -  Pregnancy, or lactation, or women of childbearing potential not willing to use  adequate birth control  -  Life Expectancy < 3 months  -  Expected to receive a kidney transplant or transition to home dialysis (peritoneal  dialysis or home hemodialysis) within 6 months  -  Any other condition that, in the opinion of the investigator, should preclude patient  participation in the clinical trial

Lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH) are the most common  urological problem among men. monopolar transurethral resection of the prostate (TURP), in  which the enlarged prostate tissue is resected piece by piece using a monopolar electrode,  has been the gold standard since the 1970s. It can substantially improve the maximal flow  rate (Qmax), urinary symptoms (International Prostate Symptom Score, IPSS), and  health-related quality of life (QOL), with long-term efficacy compared to medications or  other minimally invasive treatments.4 5 However, monopolar TURP is a risky procedure because  of the likelihood of severe complications such as massive bleeding or transurethral resection  (TUR) syndrome.6 Therefore, it is of paramount importance to develop minimally invasive  surgical techniques with outcomes similar to those of monopolar TURP, but with fewer side  effects. Therefore, new energy system with different surgical methods developed after 2000s.  Among all, Enucleation methods was proved to have better Qmax and IPSS after surgery than  vaporization and resection methods. However, the risk of short-term transient incontinence  was higher in enucleation than in resection methods.  Hence modified methods such as upside down, apical preservation methods, defining the limits  of dissection proximal to external sphincter prior to enucleation of prostate were developed  in order to reduce transient incontinence. Besides, the necessity of preoperative urodynamic  study and biofeedback training, investigate the risk factors of transient incontinence are  important issues. The study using prospective cohort design recruit 300 BPH patient receiving  enucleation methods. To investigate the risk factors of transient incontinence and establish  model to predict the incontinence. Besides we will evaluate different surgical methods and  treatment methods to improve transient incontinence and the long-term results of different  enucleation methods. Lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH) are the most common  urological problem among men. Approximately one-third of men over the age of 50 are affected  by this problem. Surgical intervention is the most effective treatment for BPH, with around  100,000 procedures carried out annually in the United States. Of all surgical treatments,  monopolar transurethral resection of the prostate (TURP), in which the enlarged prostate  tissue is resected piece by piece using a monopolar electrode, has been the gold standard  since the 1970s. It can substantially improve the maximal flow rate (Qmax), urinary symptoms  (International Prostate Symptom Score, IPSS), and health-related quality of life (QOL), with  long-term efficacy compared to medications or other minimally invasive treatments. However,  monopolar TURP is a risky procedure because of the likelihood of severe complications such as  massive bleeding or transurethral resection (TUR) syndrome. Therefore, it is of paramount  importance to develop minimally invasive surgical techniques with outcomes similar to those  of monopolar TURP, but with fewer side effects.  Since the 2000s, new energy systems for BPH surgical interventions quickly became popular,  including systems that use bipolar energy and various laser systems, such as the holmium  laser, potassium-titanyl-phosphate (KTP) laser, thulium laser, and diode laser. The trend in  BPH surgical therapy has shifted from monopolar TURP to laser therapies and bipolar TURP over  the past 10 years. Bipolar energy can be used to incise, resect, and vaporize prostate tissue  using different electrodes. Holmium and thulium laser beams are mainly absorbed by water and  act as incisional lasers. The KTP laser is selectively absorbed by hemoglobin and debulks  prostate tissue through vaporization. The diode laser is absorbed by water and hemoglobin can  therefore vaporize and incise prostate tissue. These new methods all use normal saline  instead of distilled water to avoid hyponatremia. They can be further divided into three  types according to their treatment principles: resection methods (resection of prostate  tissue piece by piece), vaporization methods (vaporization of excessive prostate tissue), and  enucleation methods (peeling the enlarged prostate from the prostate capsule).  Enucleation methods was proved to have better Qmax and IPSS after surgery than vaporization  and resection methods. In a network meta-analysis, enucleation methods, including bipolar  enucleation of prostate , holmium, thulium, and diode laser enucleation of prostate, yielded  greater Qmax values at 6-12-months after surgery than did the resection and vaporization  methods, and the difference could still be observed at 24-36 months after treatment. The  advantages of the enucleation over vaporization methods were mainly observed in large  prostates. Enucleation methods also achieved better IPSS than resection and vaporization  methods, although the difference was not statistically significant. The new methods were  generally safer than monopolar TURP. They were less likely to require patient transfusion,  cause blood clot tamponade, lead to postoperative hemoglobin decline, or cause TUR syndrome.  However, the risk of short-term transient incontinence was higher in enucleation than in  resection methods. Compared with resection methods, enucleation methods had more events of  short-term transient urinary incontinence than resection methods. (odds ratio (OR)=1.91, 95%  Confidence interval (CI); 1.35 to 2.71) Liu et al compared bipolar enucleation with bipolar  TURP and found that after Foley removal, the incontinence rate was higher in enucleation than  in resection at 24 hours (35.6 % vs 18.9%, p<0.01) and one week (20% vs 7.8%, p<0.05).28  There was no difference after two weeks postoperatively (3.3% vs 2.2 % at 2 weeks).  Xu et al retrospectively reviewed 1288 patient receiving bipolar enucleation and found that  older age and large prostate volume were associated with postoperative stress urinary  incontinence. Besides, operation time and blood loss were also reported as risk factors.  Hence many authors used modified methods such as upside down, apical preservation methods,  defining the limits of dissection proximal to external sphincter prior to enucleation, in  order to reduce postoperative urinary incontinence. Besides pelvic floor exercise was  demonstrated to shorten the periods of stress urinary incontinence. However, the role of  pelvic floor exercise in enucleation methods in BPH patients are unclear. These questions  need further investigations.  6、study aim： To investigate the risk factors of transient incontinence and establish model to  predict the incontinence. Besides we will evaluate different surgical methods and treatment  methods to improve transient incontinence and the long-term results of different enucleation  methods.  7、material and methods： I. study design: prospective cohort study II. . We plan to invite 300  patients whom received enucleation (laser or bipolar) surgery for BPH during 2020 march to  2022 march in National Taiwan University Hospital yun-lin branch to participate this study.  We adopted usual care and collect patient's preoperative, intraoperative and postoperative  data. The preoperative data include age, comorbidities, medication history, urodynamic  parameters and urinary questionnaire. Intraoperative data include operative methods,  operative time and surgical complications. Postoperative parameters include urinary  questionnaire such as International Consultation on Incontinence Questionnaire-Urinary  Incontinence Short Form (ICIQ-SF), 4-time use pad questionnaire, IPSS, 7-item Overactive  Bladder Symptom Score (OABSS) and urodynamic parameters.  III. Outcome measure  1. Maximum urinary flow rate (Qmax) Prostate volume (TRUSP) , post-voiding residual urine  (PVR ) at baseline, 3, 6, 12, and 24-month follow-up visits，pressure-flow study at  baseline.  2. If incontinence and using pad, then biofeedback, ICIQ-SF, 4-item use pad questionnaire  every week until incontinence cured. Videourodynamic study if incontinence persisted  after post-op one month  3. IPSS, OABSS instruments, flow, TRUSP and PVR will be scored per instructions for each  instruments collected at baseline and at baseline, 3, 6, 12, and 24-month follow-up  visits  4. Pre-operative parameters: Age, BMI, comorbidities (DM, Hypertension, heart disease,  neurologic disease)  5. Op parameters: op methods, enucleation and morcellation time  6. Complication: using modified clavien-dindo classification classification grade 1-4 Inclusion Criteria:  -  Subject has diagnosis of lower urinary tract symptoms due to benign prostatic  enlargement causing bladder outlet obstruction  -  Clinical investigator has documented in the subject's medical record that in his/her  judgment the subject is a surgical candidate  -  Subject is 40 to 90 years of age  -  Subject has an IPSS score greater than or equal to 12 measured at the baseline visit  -  Subject has medical record documentation of a maximum urinary flow rate (Qmax) less  than 15ml/s  -  Subject is classified as American Society of Anesthesiologists (ASA) I, II or III Exclusion Criteria:  -  Subject has a life expectancy of less than 2 years  -  Subject has an active infection (eg, urinary tract infection or prostatitis)  -  Subject has a diagnosis of, or has received treatment for, chronic prostatitis or  -chronic pelvic pain syndrome (eg, non-bacterial chronic prostatitis)  -  Subject has been diagnosed with a urethral stricture or bladder neck contracture  -  Subject has history of lower urinary tract surgery (eg, TURP, laser, urinary  diversion, artificial urinary sphincter, penile prosthesis)  -  Subject has diagnosis of stress urinary incontinence that requires treatment or daily  pad/device use  -  Subject has diagnosis of prostate cancer and receive cancer treatment  -  Subject has a history of carcinoma in situ (CIS), Ta Grade 2, Ta Grade 3 or any T1  stage bladder cancer

To determine the immediate effects on the abdominal musculature, assessed by ultrasound  (RUSI), due to the application of electrostimulation using whole body electrostimulation  together with physical exercise in healthy people and to compare with the application of  local EMS in the abdominal area and the same physical exercise session. The same intervention  is carried out for the control group as the WB-EMS group but simulated. Evaluation of the immediate changes in the thickness of the abdominal muscles (Transversus  abdominis, Internal and External Oblique and Rectus abdominis) and in the Interrectus  distance after the physical exercise session together with whole body electrostimulation or  local electrostimulation assessed by ultrasound (RUSI) in healthy people. Inclusion Criteria:  -  Healthy participants  -  Good medical history without injury or chest pain in the past year  -  No surgeries in the previous year. Exclusion Criteria:  -  Upper body mass index 30 Kg/m2  -  Level of professional or elite sports activity  -  Hyperventilation / hypercapnia and score above 23 points on the Nijmegen questionnaire  -  Present any contraindication regarding the WB-EMS/EMS  -  Viral o bacterial infections  -  Arterial circulatory disorders, advanced arteriosclerosis  -  Women during their menstrual period  -  Type I diabetes, hemophilia, bruises, bleeding, cognitive deficit, fibromyalgia,  congenital diseases with muscle-skeletal alterations at the level of the back and  lower extremities, scoliosis, protrusion or disc herniation, medication consumption,  abdominal surgeries (scars or keloids), abdominal muscle injury.  -  Presence of chronic low back, hip or thigh pain

The investigators conduct a large-scale randomized controlled trial in Finland by sending  three types of information letters to households to examine whether the reminder letters  affect healthcare use. All letters remind of the importance of seeking care to treat  potential health problems.  This study has two primary objectives are: to evaluate the effects of an information nudge  reminding on the importance of diagnosing and treating health problems and to evaluate the  effects of additionally providing information on the fact that primary care nurse visits have  become exempt from copayments. Main outcomes include the number of primary care nurse visits  and general practitioner (GP) visits in a six-month follow-up. This study has two main objectives: (i) to evaluate the effect of an information nudge  reminding on the importance of diagnosing and treating health problems and (ii) to evaluate  the effect of providing information on the fact that primary care nurse visits have become  exempt from co-payments. Inclusion Criteria:  -  Residency in one of the 25 target municipalities as of September 15, 2021.  -  Born in 1966 or earlier (aged 55 or more at the end of 2021).  -  Living in a household with a maximum of three individuals aged 55 or above. Exclusion Criteria:  -  Individuals living in households (postal address) with more than three individuals  aged 55 and above.

This was a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare  the safety, tolerability, and antiviral activity of EIDD-2801 (molnupiravir) versus placebo  as measured by SARS-CoV-2 viral RNA detection in symptomatic adult outpatients with COVID-19. This was a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare  the safety, tolerability, and antiviral activity of molnupiravir versus placebo as measured  by SARS-CoV-2 viral RNA detection in symptomatic adult outpatients with COVID-19. The study  was a multicenter trial that was conducted in the United States.  In this study, 204 participants were randomized and 202 received molnupiravir or placebo  orally twice a day (BID) for 5 days. The study enrolled participants in 5 parts with each  part evaluating molnupiravir doses of either 200 mg BID, 400 mg BID, or 800 mg BID. Doses  were chosen based on emerging virology and safety data from this and ongoing studies. New  dose groups were started after the selected dose had been studied for safety in a Phase 1  study. Inclusion Criteria:  1. Able to provide informed consent prior to initiation of any study procedures.  2. ≥18 years of age at Screening.  3. Study treatment is expected to begin within ≤168 hours from first symptom onset.  4. Ability to swallow pills.  5. Documentation of confirmed active SARS-CoV-2 infection, as determined by a molecular  or non-molecular ("rapid") test conducted at any clinic or laboratory that had a  Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent from  a sample collected ≤96 hours prior to study entry.  6. Was experiencing at least one of the following SARS-CoV-2 infection symptoms at the  time of enrollment: fever (could be subjective including feeling feverish or having  chills) OR signs/symptoms of respiratory illness (including but not limited to upper  respiratory congestion, loss of sense of smell or taste, sore throat OR lower  respiratory illness - cough, shortness of breath).  7. Agreed to not participate in another interventional clinical trial for the treatment  of SARS-CoV-2 during the study period (28 days) unless hospitalized.  8. Agreed to not obtain investigational medications outside of the molnupiravir study.  9. Agreed to the sampling detailed in the schedule of evaluations and to comply with  study requirements including contraception requirements.  10. A female participant was eligible to participate if she was not pregnant or  breastfeeding and at least one of the following conditions applied:  -  Was not a woman of childbearing potential (WOCBP) OR  -  Was a WOCBP and using a contraceptive method that is highly effective (a low user  dependency method OR a user-dependent method in combination with a barrier  method), or was abstinent from heterosexual intercourse as their preferred and  usual lifestyle (abstinent on a long-term and persistent basis), as described in  Appendix 2 of the study protocol during the intervention period and for at least  50 days after the last dose of study intervention. The investigator evaluated the  potential for contraceptive method failure (ie, noncompliance, recently  initiated) in relationship to the first dose of study intervention.  -  A WOCBP must have had a negative highly sensitive pregnancy test (serum or urine)  within 24 hours before the first dose of study intervention.  -  Additional requirements for pregnancy testing during and after study intervention  were provided in the study protocol.  -  The investigator was responsible for review of medical history, menstrual  history, and recent sexual activity to decrease the risk for inclusion of a woman  with an early undetected pregnancy.  -  Contraceptive use by women was to be consistent with local regulations regarding  the methods of contraception for those participating in clinical studies.  -  Given the elevated risk of venous thrombotic events in patients hospitalized with  COVID-19 (Benson et al, 2020; Spratt et al, 2020), estrogen-containing  contraceptives could not be started to fulfill the contraceptive requirement of  this study at any time during participant's participation. If contraceptives were  interrupted as standard of care management of COVID-19 patients and resumed at a  later time point, such as at hospital discharge, then abstinence was practiced  for the defined period of back-up contraception per the contraceptive product  labeling. After this period, contraceptive use had to adhere to the guidance in  Appendix 2 of the study protocol.  11. Male participants were eligible to participate if they agreed to the following during  the intervention period and for at least 100 days after the last dose of study  intervention:  -  Refrained from donating sperm  PLUS either:  -  Were abstinent from heterosexual intercourse as their preferred and usual lifestyle  (abstinent on a long term and persistent basis) and agreed to remain abstinent.  OR  -  Had to agree to use contraception unless confirmed to be azoospermic (vasectomized or  secondary to medical cause [Appendix 2 of the study protocol]) as detailed below:  -  Agreed to use a male condom plus partner use of an additional contraceptive  method when having penile-vaginal intercourse with a WOCBP who was not pregnant.  Note: Men with a pregnant or breastfeeding partner had to agree to remain  abstinent from penile-vaginal intercourse or use a male condom during each  episode of penile-vaginal penetration.  -  Contraceptive use by men was to be consistent with local regulations regarding  the methods of contraception for those participating in clinical studies. Exclusion Criteria:  1. Need for hospitalization or immediate medical attention in the clinical opinion of the  study investigator.  2. Hemoglobin <10 g/dL in men and <9 g/dL in women.  3. Platelet count <100,000/ µL or received a platelet transfusion within 5 days prior to  enrollment.  4. Was on dialysis or has an estimated glomerular filtration rate <30 mL/min/1.73 m^2  5. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >3x upper limit normal  (ULN).  6. History of or current hospitalization for COVID-19. Note: Individuals hospitalized and  then discharged, even if only hospitalized for 1 day, were excluded.  7. History of kidney disease as evidenced by estimated creatinine clearance value <30  mL/min.  8. History of significant liver disease in the opinion of the site investigator or active  hepatitis B or active hepatitis C. Human immunodeficiency virus (HIV) that is advanced  (CD4<200/mm^3) and/or on treatment with nucleos(t)ide analogues.  9. Use of therapeutic interventions with possible anti-SARS-CoV-2 activity within 30 days  prior to study entry, (e.g., remdesivir, lopinavir/ritonavir fixed dose combination,  ribavirin, chloroquine, hydroxychloroquine, and convalescent plasma), or participation  in a clinical trial involving any of these drugs whether for treatment or prophylaxis.  10. Receipt of a SARS-CoV-2 vaccination prior to study entry.  11. Known allergy/sensitivity or any hypersensitivity to components of molnupiravir, or  its formulation.  12. Active drug or alcohol use or dependence that, in the opinion of the site  investigator, would interfere with adherence to study requirements.  13. History of recent (within the past 3 months) hemorrhagic cerebrovascular accident) or  major bleed.  14. Presence of a condition, that in the opinion of the investigator, would place the  subject at increased risk from study participation.

The goal of this study is to provide a new treatment approach for schoolage children with  ADHD, which could facilitate the EF developing well to achieve better outcome. ADHD in preschoolers has become established as a valid psychiatric disorder with  characterized core deficits of executive function (EF). The EF impairments occurred in  preschool period could persist to childhood, adolescent and adulthood, causing extensive and  deep damage of individual's academic and career achievement, social function, and peer  relationship. Although medication showed significant effectiveness in controlling the core  symptoms of ADHD, it failed to help patients master compensatory strategies to cope with  functional impairments in learning and life events. The family intervention program for  school-age ADHD children is still rare, and it is a blank field in China. At present, most of  these related studies have not integrated task training in realistic scenarios with parent  training, and lack of randomized and controlled Settings, which makes the effect of  intervention less convincing. Therefore, the investigators conduct this randomized and  controlled study to find out the therapeutic efficacy of Family-based Executive Function  Training for Schoolage Children with ADHD, and follow the subjects to observe whether the  therapeutic efficacy would persist. In the mean time, the investigators also observe the  factors which can influence the therapeutic efficacy. The goal of this study is to provide a  new treatment approach for schoolage children with ADHD, which could facilitate the EF  developing well to achieve better outcome. Inclusion Criteria:  1. meet both the criteria of ADHD based on the interview by the CDIS and clinical  diagnosis with DSM-5;  2. full-scale IQ estimated bythe Wechsler Intelligence Scale for Children-Revised Form  (WISC-R) above 80;  3. their parents volunteered to participate in this study. Exclusion Criteria:  1. child with severe mental disorder or physical disease that might interfere the  assessment and intervention, such as Autistic Spectrum Disorder(ASD), Schizophrenia,  epilepsy, traumatic brain injury, etc.;  2. parents with severe mental illness, such as schizophrenia, mood disorder (period of  onset), etc..

This project will be Randomized control trial conducted to check the effects of percussive  massage treatment with theragun on pain and muscle length on post exercise delayed onset  muscle soreness (DOMS) of calf muscles in healthy population so that we can have best  treatment option for people with delayed onset muscle soreness, duration will be of  6months,purposive sampling will be done, subject following eligibility criteria from kasrat  health and fitness club, will randomly allocated in two groups, baseline assessment will be  done, group A will be treated with 5 minutes of percussive massage and 5 minuties of static  stretching exercises, while group B will be managed with 5 minutes of static stretching  exercises only. Assessment will be done via, Numeric Pain Rating Scale(NPRS), Short-Form  McGill Pain Questionnaire (SF-MPQ) and goniometric measurements of passive ankle dorsi  flexion for calf muscle length at baseline before intervention and immediately post  intervention data will be analyzed by using SPSS version 25 Percussive therapy is a form of soft tissue manipulation the same thing that a massage  therapist does during a massage, and is intended to reduce muscle soreness and increase  muscle length. The aim of the current study is to determine the effects of percussive massage  with theragun and static stretching exercises on muscle length and pain of calf muscles on  post exercise (DOMS) delayed onset muscle soreness. It will be a randomized control trail,  where initial screening will be done as per the inclusion criteria of healthy female gym  users with minimum one week of joining time and developed post-exercise DOMS and ages ranged  from 20 to 30 years. Participants with the history of lower leg injuries, any type of  neuromuscular disorder and elite level of fitness will be excluded. All the study  participants will perform 15 minutes treadmill, 15 minutes stationary bicycle at day one.  After 24 hours participants with positive DOMS will be randomly place into experimental and  control groups. Experimental group will be treated with 5 minutes of percussive massage and 5  minutes of static stretching exercises, while the control group will be managed with 5  minutes of static stretching exercises only. Participants in both the groups will be assessed  on Numeric Pain Rating Scale and Short-Form McGill Pain Questionnaire for pain and degree of  passive ankle dorsi flexion for calf muscle length at baseline before intervention and  immediate 24 hours, 48 hours and 72 hours after the completion of treatment session. Inclusion Criteria:  Healthy Females will be included Participant's age will be between of 20-30 years Who  develops post exercise DOMS after 15 minutes treadmill, 15 minutes stationary bicycle Exclusion Criteria:  Subject with history of lower extremity injuries Any history type of muscular disorder  Elite level of fitness excluded in this study

The traditional Chinese herbal medicine Triptolide Wilfordii has displayed remarkable effect  on the treatment of autoimmune diseases such as rheumatoid arthritis. Now that  immunosuppression therapy has recently become a new strategy for HIV infection, it's  reasonable to expect the anti-inflammatory effect of Triptolide Wilfordii in HIV infected  patients. So we designed a randomized, double-blinded, placebo-controlled study to explore  the efficacy and safety of Triptolide Wilfordii in new-onset HIV infection. Acquired immune deficiency syndrome(AIDS) is a severe fatal disease caused by HIV infection.  Despite viral suppression achieved, antiretroviral therapy(ART) cannot ameliorate HIV-induced  immune activation and the consequent non-AIDS complications including cardiovascular, renal,  hepatic diseases. Recently, immunosuppression therapy has become the focus since it can  suppress exorbitant immune activation and inflammation so as to reduce the risk of non-AIDS  cardiovascular and central neural system complications. Triptolide Wilfordii is a traditional  Chinese herbal remedy and has long been used in the treatment of autoimmune diseases such as  rheumatoid arthritis. Moreover, a recent study has shown that Triptolide Wilfordii combined  with ART is associated with increased CD4 T cell counts and reduced immune activation in  immunological non-responders, who were defined as patients with CD4 cell counts<350 cells/μl  despite over 2 years of ART. Hence we expect Triptolide Wilfordii to bring up similar  improvement in treatment naïve HIV infection. This randomized, double-blinded,  placebo-controlled study is designed to investigate the safety and efficacy of Triptolide  Wilfordii and hopefully provide evidence for a new treatment strategy. Inclusion Criteria:  -  18~65 years old;  -  Male or female;  -  Good adherence and promise to follow-up;  -  Inform Consent signed;  -  Positive for HIV antibody test or serum HIV-RNA positive for 2 times or more; Exclusion Criteria:  -  Present opportunity infection defined according to national AIDS treatment guideline  or active opportunistic infection(not stable within 14 days ) within 3 months before  recruitment or AIDS-related carcinoma;  -  Hemoglobin (HGB) < 9 g/dl, white blood cell (WBC) < 3000/ul, granulin (GRN) < 1500  /ul, platelet (PLT) < 75000 /ul, Cr >1.5x upper limit of normal (ULN), ALT or AST or  alkaline phosphatase (ALP) >3x ULN, total bilirubin (TBIL) >2x ULN;  -  Pregnancy or breastfeeding;  -  Woman with pregnancy plan;  -  Severe organ dysfunction;  -  Administration of immunosuppressor, immunomodulator(including thymocin) or systemic  cytotoxic drugs within 6 months before recruitment.

This project examines the feasibility of a smartphone-based intervention to reduce obesity  and breast cancer risk among Chinese women in China. The proposed intervention is to use the  mobile application and an activity tracker device to promote a healthier lifestyle and  physical activity. The intervention will be tailored to the participants' behaviors, personal  needs, and preferences. The aim is to reduce abdominal obesity and improve healthy lifestyle  behaviors in premenopausal women with children in order to reduce the growing cancer burden  in China. Cancer presents a major disease burden across the globe. The incidence and mortality of  gynecologic cancers have increased significantly in China over the last two decades with  breast and endometrial cancer as leading causes of death in women in China. Obesity,  especially abdominal obesity, and unhealthy lifestyles are major risk factors for breast and  endometrial cancer. A high risk group for obesity is mothers with dependent children as they  have high levels of stress and family responsibilities that prevent regular engagement in a  healthy lifestyle and early screening activities. Because reducing postmenopausal abdominal  obesity is very difficult and because of the significant increased risk for gynecologic  cancers in obese postmenopausal women, interventions that aim to reduce abdominal obesity and  improve healthy lifestyle behaviors in premenopausal women with children are critical to  reducing the growing cancer burden in China. A smartphone-based intervention provides a  promising platform for obesity and cancer prevention. In this proposed study, the research  team will modify the Healthy Mothers Healthy Children: Technology-Based Intervention to  Prevent Obesity, which was developed by the principal investigator. The proposed intervention  (titled "The Smartphone-Based Cancer and Obesity Prevention Education Program for Chinese  Women: SCOPE-Chinese Women") is a smartphone-based, data-driven, and individually tailored  intervention. It includes 12 weekly educational modules and six bi-weekly tailored messages  delivered via WeChat, a popular communication app in China. The intervention will also be  tailored to the participants' behaviors, personal needs, and preferences. The overall goal of  this proposed study is to assess the feasibility and estimate the preliminary efficacy of the  SCOPE-Chinese Women intervention using a randomized control study design (RCT). The following  aims will be addressed.  Aim 1: To assess the feasibility of the smartphone-based lifestyle intervention (i.e.,  SCOPE-Chinese Women).  Aim 2: To estimate the preliminary efficacy of the SCOPE-Chinese Women intervention on the  primary outcome (waist circumference) and secondary outcomes (body mass index, self-efficacy,  food intake, physical activity, and metabolic risk) between the intervention and control  groups at baseline, 3 months, and 6 months.  Aim 3: To understand participants' acceptance, barriers to adherence, and recommendations for  intervention. Inclusion Criteria:  Participants must:  -  Be female  -  Be at least 18 years old  -  Have a waist circumference great than 80 cm  -  Own a smartphone  -  Be able to read Chinese and speak Mandarin  -  Be premenopausal  -  Have a child between the age of 1 and 18 years old Exclusion Criteria:  Women are excluded from the study if they:  -  Are pregnant  -  Gave birth less than 12 months prior to enrollment date  -  Have an acute or life-threatening disease (e.g., renal failure).

This study aims to assess the effect of a parent-administered intervention program based on  MIT-PB in preterm with abnormal general movements during the preterm period. We will describe  the short and long-term differences between infants exposed to MIT-PB and infants who follow  current standard care. The quasi-experimental design has been planned to assess the effect of a physiotherapy  program carried out in neonatal intensive care and at home during the first months of life.  Preterm babies born before 32 weeks gestational age (GA) and/or with less than 1500g showing  an abnormal General Movement Assessment (GMA) at 34-36 weeks will be included.  Standardized tests will be performed at baseline, at term, 44 weeks post-menstrual age (PMA),  54 weeks PMA, 6 months, and 12 months.  A qualitative study has been designed to assess the physiotherapy performance and parents'  experience.  Two different Hospitals with similar care protocols and sizes will recruit the sample  (n=138). The Intervention group (n=69) will be located at Hospital Josep Trueta of Girona and  the control group (n=69) will be located at Hospital Parc Taulí of Sabadell (Barcelona). Inclusion Criteria:  -  Preterm infants born before 32w GA and less than 1500g weight.  -  Infants who show Abnormal General Movements (CS-PR pattern) at 34-36w postmenstrual  age (PMA).  -  Families able to understand/speak Catalan, Spanish or English.  -  Families willing to participate who have the informed consent Exclusion Criteria:  -  Infants with congenital abnormalities and/or genetic disorders  -  Infants with invasive ventilation or Continuous Positive Airway Pressure (CPAP) at 36  weeks PMA.  -  Infants with Normal General Movements at 34-36 w PMA.  -  Families not willing to participate.

Quasi-experimental pre-post analysis of the rate of high-value and low-value care services  between states that expanded Medicaid and states that did not expand Medicaid January 1,  2014, for adult ambulatory visits, using visit-level survey data from the National Ambulatory  Medical Care Survey January 1, 2012 - December 31, 2015. Data Source: Visit level data obtained from the National Ambulatory Medical Care Survey  (NAMCS) between January 1, 2012-December 31, 2015.  Identification of Observations (Visits) for Primary Analysis: Adult visits in states that did  expand Medicaid January 1, 2014 (experimental group) and states that did not expand Medicaid  January 1, 2014 (control group). Eight Medicaid expansion states (experimental group):  Arizona, California, Illinois, Massachusetts, New Jersey, Ohio, Washington Five states that  did not expand Medicaid (control group): Florida, Georgia, North Carolina, Texas, Virginia.  Visits will be included only if they could receive a low value service (visits for back pain,  headache, general medical exam, URI) or high value service (visits with patients who have  CAD, DM, CVD, Depression, CHF, Osteoporosis and no exclusion to receive the indicated high  value service) when evaluating low value service counts and high value service counts  respectively as opposed to all adult visits regardless of the opportunity to receive a high  value or low value care service (e.g. visit for hand pain and none of the high or low value  areas above.)  Identification of Observations (Visits) for Secondary Analyses: Medicaid patient  subpopulation will be defined as those visits for primary analysis that are coded with  Medicaid as a pay type for the visit. "New" Medicaid patient subpopulation will be defined as  those visits for primary analysis that are coded with Medicaid as a pay type, have not seen  before, to a provider who is accepting new patients and accepts Medicaid for new patients.  Create Indicator Variables for Primary and Secondary Outcome Analyses: Develop a set of low  value and high value services with distinct inclusion and exclusion criteria for each  service. Create indicator variable for each high value and low value service. Low value care  measures (Imaging for Low Back Pain, Opioid for Low Back Pain, Opioid for Headache, Imaging  for Headache, Antibiotic for Upper Respiratory Infection, General Medical Examination with  ECG ordered, General Medical Examination with Urinalysis ordered.) High value care measures  (Antiplatelet for CAD, Beta Blocker for CAD, Statin for CAD, Anticoagulation for Atrial  Fibrillation, Statin for DM, Antiplatelet CVD, Treatment for Depression, Beta Blocker for  CHF, ACE/ARB/ARNI for CHF, Treatment for Osteoporosis)  Analysis: Evaluate for pre-intervention (Medicaid Expansion) parallel trends (This has  already been established). Then perform pre-post difference-in-differences analyses of  primary and secondary outcomes between the experimental group (states that expanded Medicaid)  and control group (states that did not expand Medicaid). Regression analysis will be  performed to adjust for respondent age, sex, race/ethnicity, number of chronic illnesses, and  clinic rural/urban location. Stratified models based on payer type will allow for analyses of  the Medicaid population. Perform sensitivity analyses of primary and secondary outcomes. Inclusion Criteria:  Criteria: <18 years old, visits before 01/01/2012, visits after 12/31/2015 Exclusion Criteria: None

This study will aim to recruit at least 70 children who participated in the iMAP2 study whose  mothers received a pertussis vaccine in pregnancy as part of the iMAP2 trial and at least 15  children born to mothers who did not receive a pertussis vaccine in pregnancy. Blood samples  will be obtained prior to and one month after the routine preschool booster vaccination and  vaccine responses compared between children whose mothers received one of two pertussis  vaccines or no pertussis vaccine in pregnancy. Children will be vaccinated with the routine  booster vaccines by the study team on the same visit as the pre-vaccination bloods are taken. In the UK, all pregnant women are offered a whooping cough-containing vaccine during  pregnancy. This protects newborn infants against whooping cough, but there have been some  concerns that this vaccination in pregnancy may affect the response to childhood  vaccinations.  A preceding study called immunising Mums Against Pertussis 2 (iMAP2) was conducted involving  pregnant women randomised to receive one of two different whooping cough-containing vaccines,  with a control group also recruited, and the antibody levels in their infants were measured  at age 2, 5 and 13 months.  This study, immunising Mums Against Pertussis 3 (iMAP3), is a follow up study of children who  participated in iMAP2, to investigate the sustained impact of whooping cough vaccination in  pregnancy on childhood vaccine responses.  This study will investigate the antibody levels in these children before and after the  routine pre-school booster (DTaP/IPV vaccination) vaccine. It will help the Department of  Health continue to ensure the best protection is offered to the population.  Those eligible for the study are children who participated in the iMAP2 study who have  reached the age for pre-school booster vaccination (from age 3 years 4 months).  The study period will be approximately 4-6 weeks with two study visits. The first visit will  take place when the child is around 3 years and 4 months of age. After informed consent a  blood sample will be obtained followed by administration of the pre-school booster vaccine.  At the second visit another blood sample will be obtained. These blood tests will measure the  level of protective antibody against the components of the pre-school booster vaccine. Visits  will take place either in the child's home or at a suitable clinical setting within the study  team's sites.  The study will be run by St. George's, University of London, in collaboration with St  George's University Hospitals NHS Foundation Trust, Oxford Vaccine Group and Bristol  Children's Vaccine Centre. Inclusion Criteria:  -  Age eligible for routine pre-school booster vaccinations (i.e. from 3 years and 4  months of age)  -  Participated in the iMAP2 trial  -  Informed consent by a parent or legal guardian Exclusion Criteria:  -  Permanent exclusion criteria:  -  Fulfil any of the contraindications to vaccination specified in The Green Book on  Immunisation  (https://www.gov.uk/government/organisations/public-health-england/series/immunis  ation-against-infectious-disease-the-green-book)  -  Received any additional pertussis containing vaccine after the routine 16 week  booster  -  Previous or concurrent participation in an interventional study other than iMAP2  if, in the opinion of the investigator, this may influence the objectives of this  study  -  Temporary exclusion criteria:  -  If the child has an axillary/aural temperature ≥ 38°C then vaccination and blood  sampling will be postponed until resolution of fever. If the child is acutely  unwell, vaccination will be postponed until resolution  -  If the child is receiving antibiotics (other than long term prophylaxis)  vaccination should be postponed until 48 hours after the conclusion of the course

The study aims to evaluate the efficacy of a cognitive behavioural and psychoeducational  intervention in patients with insomnia and diagnosed with a schizophrenic disorder. Patients will be recruited by consecutive non-probabilistic sampling at the Outpatient Mental  Health Centre of Nou Barris in Barcelona and subsequently randomised into 2 groups, control  and intervention. Presence and severity of insomnia will be assessed through the following  measurement instruments: ISI for presence and severity, PSQI for sleep quality and EQ-5D for  health-related quality of life. Patients in intervention will attend 6 group sessions with  cognitive behavioural and psychoeducational intervention and the control group will carry out  the usual follow-up. Pre-post, 6-month and 9-month assessments will be analysed. Inclusion Criteria:  -  Insomnia disorder (ISI scale)  -  Schizophrenic disorder Exclusion Criteria:  -  Presence of severe psychopathological alteration  -  Inability to understand the Spanish language or difficulties writing or reading

This study evaluates the safety and immunogenicity of the BPZE1 live, attenuated pertussis  vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares  BPZE1 vaccine vs Boostrix vaccine vs both BPZE1 and Boostrix vaccines. This is a  multi-center, randomized, placebo- and active-comparator-controlled study in healthy,  school-age children with a 6-month safety follow-up after the first vaccination. This multi-center, randomized, placebo- and active-comparator-controlled study evaluates the  safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent  nasopharyngeal colonization and pertussis disease. Healthy school-age children will be  randomly assigned to 1 of 3 different study treatment groups to receive the intranasal BPZE1  vaccine, the intramuscular Boostrix vaccine, or both. Subjects will first receive the  intranasal vaccine (BPZE1 or placebo) using a small, cone-shaped device that attaches to a  syringe and sprays the vaccine into the nose. After a 10-minute waiting period, subjects will  receive the intramuscular vaccine (Boostrix or placebo) in the upper arm. As this is the  first study in school-age children, a staggered enrollment is planned with the first 45  subjects in the older age group of 11-17 years designated as the safety lead-in cohort. After  reactogenicity results from the first 7 days after vaccination of the safety lead-in cohort  are reviewed by the safety monitoring committee, the remainder of the subjects will be  enrolled. Subjects who choose to take part in a small sub-study of revaccination/attenuated  challenge will receive BPZE1 intranasal vaccine (open-label) 3 months after the first  vaccination. Safety will be monitored for 6 months after the first vaccination. Inclusion Criteria: None Exclusion Criteria: None

This research is being done to determine the safety and tolerability of timolol in the  treatment of acne and rosacea. The investigators will also look for specific biomolecular  changes in acne or rosacea skin when it is exposed to timolol.  Timolol is approved by the Food and Drug Administration (FDA) for the treatment of glaucoma.  In dermatology, it has been used as a treatment to decrease the size of vascular (blood  vessel) malformations in infant skin. Timolol is not approved for use in acne or rosacea and  its use in this study is investigational.  Many people with rosacea have telangiectasias which are small, red dilated blood vessels on  the skin. They also suffer from flushing and acne-like lesions. Better treatments than those  currently available are desired.  Acne vulgaris, or acne, is another chronic inflammatory and very common skin disease that  affects about 8 out of 10 young adults and adolescents. Signs of acne include papules and  blackheads that are often called primary lesions because they represent an active form of the  disease. There are also secondary lesions that can form later; they are known as acne scars Rosacea affects roughly 16 million Americans who desire better treatments than those  currently available. Acne vulgaris, another chronic inflammatory skin disorder, mainly  affects teenagers but also affects 20-40% of adults. Investigating potential new treatments  will not only satisfy a clinical need, but also offers the opportunity to learn about the  pathogenesis of the disease and skin biology. The purpose of this study is to investigate the  possible role of timolol as a therapy for the erythema and papules associated with acne and  rosacea. It has been shown that timolol is beneficial and safe to treat infantile  hemangiomas. The investigators hypothesize that it may also be safe and effective in the  treatment of acne and rosacea.  In a single experiment where the test case was the PI (a practicing physician), the  investigators treated his rosacea with timolol for this off-label indication and have noticed  an improvement in flushing and an unexpected improvement in acneiform eruptions associated  with the rosacea. After 30 days, less flushing and acneiform lesions were noted on the  treated right side compared to the left side . Similarly, at 60 days after treatment, as  visualized by infrared imaging, significantly less inflammation and flushing was noted on the  treated right side even outside of episodes of flushing. The improvement was durable, such  that after a 60 day washout, improvements were still noted. In summary, during testing of the  PI as a case subject, timolol appeared effective, safe, and with some disease-remissive  effects.  Our aim is to conduct a 16 week split-face pilot study with up to 30 patients who have a  diagnosis of either inflammatory acne or rosacea to assess whether timolol maleate  effectively reduces erythema, flushing, telangiectasias, and/or papules. The investigators  also propose to biopsy a subset of our study patients to examine the biological activity in  the skin before and after treatment. The investigators are particularly interested in  studying epigenetic DNA methylation abnormalities in these conditions at baseline to compare  to normal subjects and as a result of therapy. Inclusion Criteria:  -  In the opinion of the investigator, must be medically able to undergo the  administration of study material  -  Be able to comprehend the informed consent document and provide consent for  participation  -  Females of childbearing potential must:  -  Not be pregnant by subjective report  -  agree to not become pregnant or breastfeed for the period of the study through 1  month after completion of the study  -  be willing to use a reliable form of contraception during the study  -  Be willing and able to comply with the scheduled visits and other study procedures for  the duration of the study.  -  Be willing not to take any other medicine for acne or rosacea during the study  -  Acne specific inclusion criteria:  o 10-100 noninflammatory, 20-50 inflammatory lesions (nose excluded)  -  Rosacea specific inclusion criteria:  -  History of frequent flushing  -  Skin erythema - Positive (not negative) chromometer minimum reading difference  when subtracting nonaffected reading from affected reading.  Goal would be greater than 1 unit difference between red areas. For example, the red area  (average 17.7 Chroma Meter a) and nonaffected areas (average 14.1 Chroma Meter a), yields  in an optimum scenario greater than 3 point difference in this example (in subjects with  average Chromometer L value averaging 56.6-59.6). Example from (Helfrich et al., 2015).  o Presence of inflammatory papules Exclusion Criteria:  -  Having received any investigational drug within 30 days prior to study entry  -  An allergy history to any study materials including any beta-blockers.  -  Pregnant, lactating, or trying to become pregnant  -  Severe depression  -  Hypotension or history  -  Bradycardia or history  -  History of Cardiac Heart Failure  -  History of Myocardial infarction  -  History of heart arrhythmia  -  Asthma or Bronchospasm or history  -  Rosacea specific exclusion criteria:  Recent topicals within 3 weeks Oral rosacea medications such as antibiotics within 3 weeks  • Acne specific exclusion criteria: nodular acne man with beard which interferes with  clinical evaluation history of Accutane Oral contraceptive pills changes last 3 months  Topical retinoid within 4 weeks Cosmetic procedures (like facial or peels) for 4 weeks  Photodynamic therapy , laser therapy or microdermabrasion for 4 weeks Other topicals or  oral acne medications such as antibiotics within 3 weeks  o Biopsy volunteer specific exclusion criteria: History of keloids History of hypertrophic  scars Allergy to lidocaine or epinephrine

Tetrahydrocannabidiol (THC) is the psychoactive chemical in cannabis that makes people high.  This study aims to dissect acute impairment of various forms of memory and learning by THC in  cannabis compared to placebo. Impairment will be assessed via a short cognitive test battery  and then subjects will complete four tasks in the fMRI scanner. The protocol below is designed to begin dissecting acute impairment of various forms of  memory and learning by THC in cannabis compared to placebo, in a 2-session per subject  double-blind, random assignment, placebo-controlled counterbalanced design in young to  middle-aged adults. The purpose of these experiments is to gather important pilot data to  demonstrate proof of principle for a planned NIDA submission of a P50 center application that  will examine cannabis's differential effects on the neural circuit underpinnings these  various cognitive domains across the lifespan in much more detail. In other words, these  pilot data will show NIDA that the investigators' methods and approaches work and are  suitable for use in their proposed center grant application. Unlike in the planned P50, in  these small-scale pilot studies the investigators are only concerned with comparing these  disrupting effects using a single dose of THC versus placebo, without exploration of age,  sleep, or sex-related differential effects or of different dose-related effects.  Tasks tapping each of the major cognitive memory-related domains will be performed in the MRI  scanner, to reveal the relevant underlying circuitry and its disruption by drug using  functional MRI. Although each of the fMRI tasks is already implemented in the investigators'  lab in other contexts, the investigators have never studied alteration of the fMRI tasks by  THC. Neither have other investigators elsewhere used this approach. It is also important to  point out that the dose of active THC to be administered is the same as that already used  safely in the investigators' IRB-approved driving studies, one which subjects state  subjectively (a blind to actual dose information) makes them feel moderately intoxicated, and  similar to the amount that they would consume themselves recreationally.  The study will consist of 3 days (screening visit and 2 dose days). In a randomized,  counterbalanced, double-blind study, investigators will administer high THC marijuana or  placebo marijuana using paced inhalation through a vaporizer. Following administration,  subjects will provide subjectively-rated CNB intoxication using a verbal analog scale, a  short cognitive test battery, then complete 4 fMRI paradigms within ~1.5 hours: a) MSDM task,  b) MID task, c) RISE task, and d) Treadway Effort/Reward task. These tests will be  counterbalanced across subjects and sessions to minimize order and fatigue effects. Inclusion Criteria:  -  18-55 years old  -  Right handed  -  CNB use within past 2 years and felt "high" when used  -  Able to read, speak, and understand English  -  Able and willing to provide written informed consent, and willing to commit to study  protocol. Exclusion Criteria:  -  Current marijuana tolerance, desire to cut down, or cravings to sue during periods of  abstinence.  -  Strongly left-handed  -  Positive screen for drug or alcohol (except CNB) on test day will result in  rescheduling the appointment  -  History of adverse effects with CNB  -  CNB users who are abstaining  -  Report of any psychotic disorder in a first degree relative  -  IQ < 80 on the Wechsler Abbreviated Scale of Intelligence  -  Inability to comprehend written instructions using the WRAT-4 reading achievement test  -  Pregnant, breastfeeding, and ineffective birth control methods.  -  Unable or unsafe to have an MRI  -  Serious medical, neuro-ophthalmological, or neurological illness (e.g. cancer, seizure  disorders, encephalopathy  -  History of head trauma with loss of consciousness > 30 minutes or concussion lasting  30 days.  -  Focal brain lesion seen on structural MRI  -  Any medical/neurological condition that could compromise neurocognitive performance  (e.g. epilepsy, multiple sclerosis, fetal alcohol syndrome).  -  Anyone deemed unsafe to study personnel for any reason

The purpose of this study is to determine the efficacy and safety of BCX9930 monotherapy for  the treatment of PNH compared to continued C5 inhibitor therapy in adult PNH patients with  residual anemia despite treatment with a C5 inhibitor. This is a randomized, active comparator-controlled, open-label, parallel-group, 2-part study.  Parts 1 and 2 will be conducted in the same subjects.  Part 1 of the study is designed to evaluate the efficacy, safety, and tolerability of oral  BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in subjects with PNH  with inadequate response to their current C5 inhibitor therapy. Subjects will be randomized  to either discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5  inhibitor therapy for the 24-week randomized treatment period. The primary efficacy and  safety analyses will be based on Part 1.  Part 2 of the study is designed to evaluate the long-term safety, tolerability, and  effectiveness of BCX9930 monotherapy when administered through Week 52. All subjects in Part  2 will receive BCX9930. Subjects who are randomized to BCX9930 monotherapy in Part 1 will  continue to receive BCX9930 in Part 2. Subjects who are randomized to C5 inhibitor therapy in  Part 1 will discontinue that therapy at the Week 24 visit and receive BCX9930 in Part 2. Inclusion Criteria:  -  Male or female, aged ≥ 18 years old  -  Body weight ≥ 40 kg  -  Documented diagnosis of PNH  -  Currently being treated with a stable C5 inhibitor regimen  -  Documentation of current vaccinations against Neisseria meningitidis and Streptococcus  pneumoniae or willing to start vaccination series  -  At screening: PNH clone size of ≥ 10% and hemoglobin ≤ 10.5 g/dL Exclusion Criteria:  -  Known history of or existing diagnosis of hereditary complement deficiency  -  History of hematopoietic cell transplant or solid organ transplant or anticipated  candidate for transplantation  -  Myocardial infarction or cerebrovascular accident within 30 days prior to screening,  or current and uncontrolled clinically significant cardiovascular or cerebrovascular  condition  -  History of malignancy within 5 years prior to the screening visit  -  Active bacterial, viral, or fungal infection or any other serious infection within 14  days prior to screening  -  Treatment with anti-thymocyte globulin within 180 days prior to screening  -  Initiation of treatment with an erythrocyte or platelet growth factor, or danazol  within 28 days prior to screening  -  Receiving iron supplementation with an unstable dose in the 28 days prior to screening

We propose a double-blind randomized controlled trial to evaluate the effect of intravenously  administered morphine at surgery conclusion on acute postoperative pain in patients  recovering from craniotomy surgery. Participating adults having craniotomy surgery will be  randomized in a 1:1 ratio to intraoperative intravenous administration of 0.08 mg/kg morphine  at dura closure, or a matching placebo. After confirming eligibility, patients will be approached by one of the study researchers for  potential participation. After a thorough explanation, written informed consent will be  obtained.  General anesthesia will be induced with propofol (2-3 mg/kg), and either remifentanil (1  mcg/kg) or fentanyl (2 mcg/kg). Lidocaine (1 mg/kg) and rocuronium (0.6 mg/kg) will be  allowed and left to the discretion of the caregivers. Anesthesia will be maintained with  infusions of propofol and remifentanil, and titrated to maintain hemodynamic goals and  evaluation of anesthesia depth by somatosensory or motor evoked potentials according to  clinical requirements. Ketamine and fentanyl administration will not be allowed at the  maintenance phase. No additional IV opioids will be allowed during surgery. Other analgesics  such as dipyrone and non-steroidal anti-inflammatory agents (such as diclofenac) will not be  allowed during surgery or during PACU stay. At dura closure, patients will be randomized by a  web-based randomization service in a 1:1 ratio. The intervention group will receive 0.08  mg/kg intravenous morphine (0.08 ml/kg), while the control group will receive 0.08 ml/kg 0.9%  NaCl. The research solution (morphine/0.9% NaCl) will be administered via IV infusion over  ten minutes. Randomization and study drug preparation will be performed by a research  team-member, uninvolved in data collection, analysis, or patient care.  Both groups will receive acetaminophen (1 gr) at dura closure. Steroids and other anti-emetic  medications will be allowed. Remifentanyl and propofol infusions will be discontinued at the  end of the surgery during wound dressing. All patients will have orders for intravenous  morphine administration in PACU for breakthrough pain as acceptable and according to the  orders prescribed by anesthesiologist assigned for the case/the attending anesthesiologist in  PACU. The research team/protocol does not interfere with morphine administration during PACU  stay. All caregivers will be blinded to treatment allocation.  Patient's monitoring at the operating room and during transportation to the PACU will be done  by the anesthesiologist assigned for the case. Patient's monitoring during PACU stay will be  done by the PACU team and according to the patient's clinical status according to PACU  protocol. Patients will be followed during PACU stay by a study team member blinded to the  treatment allocation. The study team member will measure and record pain score (NRS),  sedation score (Ramsay score) and PONV at admission to PACU and 30 minutes after admission to  PACU. The research team, according the research hypothesis is interested in measuring pain  (via NRS) while the patient is fully conscious and alert. Additional data regarding the  surgery, anesthesia, recovering from anesthesia and PACU stay will be collected retroactively  from computer system data (metavision, chameleon).  Demographic and clinical data will be collected on the day of surgery. Surgical and  anesthetic data, laboratory results, details regarding side effects, time of first morphine  requirement, total morphine consumption in PACU, and pain scores (NRS) at POD1 and POD2 will  be collected from computerized patient files. Inclusion Criteria:  -  Informed consent.  -  Scheduled for elective craniotomy for resection of supra-tentorial intracranial tumor  that requires cranium sawing, dural opening and excision of tumor, under general  anesthesia.  -  Age 18 - 80 years.  -  American Society of Anesthesiologists' physical status I-III.  -  Body mass index (BMI) under 35 kg/m2. Exclusion Criteria:  -  Pregnant or current breastfeeding patients.  -  Patients unable to provide informed consent or in need of a legal authorized  representative.  -  Patients with neurological disorders preventing a good understanding of the pain  numerical reporting scale (NRS) before surgery.  -  Patients with pre-operative aphasia.  -  Patients with chronic pain or chronic use of opioids.  -  Patients with current alcohol or drug abuse.  -  Expected delayed extubation.  -  Patients with documented allergy to opioids or acetaminophen.  -  Preoperative Glasgow Coma Scale <15.

Depression and metabolic disorder (MetD) are two of the most common and debilitating  disorders worldwide, occurring with significant rates of comorbidity. This is a major  clinical challenge as the outcomes of both conditions are worsened. Studies have uncovered  that depression and metabolic disorder are associated with chronic, low-grade inflammation.  In brain circuit level, patients with depression are characterized with aberrant  frontostriatal (FS) circuit connectivity and reduced activity level that also associated with  metabolic comorbidity. In neurotransmitter level, the dopaminergic pathway, that could be  feedback regulated by immune and metabolic factors, has long been known to involve in  emotional and metabolic homeostasis. More importantly, this dopamine (DA) input is critical  to shaping the FS circuit-level dynamic connectivity and plasticity. Therefore, this study  hypothesizes that inflammatory and metabolic dysregulations on DA transmission link to the  aberrant FS function that cause mood and metabolic syndromes. To clarify the underlying  mechanisms, 90 patients who meet the DSM-5 diagnostic criteria of major depressive episode in  either major depressive disorder or bipolar disorder are planned to be recruit. FS functional  connectivity and activation, before and after receiving 10 Hz repetitive transcranial  magnetic stimulation (rTMS) to left dorsolateral prefrontal cortex will be measured. Then  systemically analyze participants' clinical symptomology, neurocognitive function,  inflammation and metabolic status. Possible correlations between indices, the effects of rTMS  and differences between groups will be tested. Results could provide a chance for further  understanding the pathophysiology of depression with MetD and comparing between unipolar and  bipolar depression, and developing brain circuit based non-invasive brain stimulation  personalized treatment for depression with MetD to achieve a better outcome. Depression and metabolic disorder (MetD) are two of the most common and debilitating  disorders worldwide, occurring with significant rates of comorbidity. This is a major  clinical challenge as the outcomes of both conditions are worsened. Studies have uncovered  that depression and metabolic disorder are associated with chronic, low-grade inflammation.  In brain circuit level, patients with depression are characterized with aberrant  frontostriatal (FS) circuit connectivity and reduced activity level that also associated with  metabolic comorbidity. BD patients also showed functional anomalies in the VS and FS circuits  with reduced neural flexibility of hedonic signaling in response to stress. The dysfunctional  FS circuits also link to the metabolic comorbidities in patients with mood disorders.  Regarding metabolic control, the FS functional connectivity changes affect food craving. And  the altered reciprocal loop from the medial prefrontal cortex could regulate eating behavior  and metabolic disturbance. In neurotransmitter level, the dopaminergic pathway, that could be  feedback regulated by immune and metabolic factors, has long been known to involve in  emotional and metabolic homeostasis. More importantly, this dopamine (DA) input is critical  to shaping the FS circuit-level dynamic connectivity and plasticity. Disruptions in the  dopamine (DA) system have been observed in psychiatric disorders. MDD might involve DA  reductions that could result from either diminished DA release from presynaptic neurons or  impaired signal transduction, either due to changes in receptor number or function and/or  altered intracellular signal processing. Therefore this study hypothesizes that inflammatory  and metabolic dysregulations on DA transmission link to the aberrant FS function that cause  depression and MetD. To clarify the underlying mechanisms, unipolar and bipolar depression  patients will be enrolled to measure the FS functional connectivity and activation, before  and after receiving 10 Hz repetitive transcranial magnetic stimulation (rTMS) to left  dorsolateral prefrontal cortex. Then systemically analyze participants' clinical  symptomology, neurocognitive function, inflammation and metabolic status. Possible  correlations between indices, the effects of rTMS and the possible differences between  unipolar and bipolar depression patients will be tested. Results could provide a chance for  further understanding the pathophysiology and better treatment of depression with MetD,  finding biomarkers for subgrouping depression between unipolar depression and bipolar  depression, predicting outcomes to brain circuit based personalized rTMS treatment for  depression with MetD.  The specific aims of the project are:  Aim 1: To find the biological homogeneousness among depression with MetD by investigate the  associations between (1) FS circuit connectivity and clinical (mood and metabolic) symptoms,  and (2) FS circuit activation and clinical (mood and metabolic) symptoms in both unipolar and  bipolar depressed individuals.  Aim 2: To confirm the role of FS in depression with MetD by applying rTMS to test its effects  on (1) clinical symptoms, (2) FS circuit activation, (3) FS circuit connectivity and (4) find  predictors for the rTMS treatment response.  Aim 3: To study the bidirectional inflammatory and metabolic feedback regulations of the DA  transmission in FS circuit in depression with MetD by investigate the associations between  (1) FS circuit activation, and (2) FS circuit connectivity and systemic inflammatory/  metabolic regulators both before and after rTMS treatments. Inclusion Criteria:  -  (1)Signed informed consent by patient or legal representative;  -  (2) male or female patient aged ≧20 and ≦70 years;  -  (3) a diagnosis of MDD or BD according to DSM criteria made by a specialist in  psychiatry;  -  (4) a total score of at least 18 in the Hamilton Rating Scale for Depression (HDRS) at  the screening stage;  -  (5) patient or a reliable caregiver can be expected to ensure acceptable compliance  and visit attendance for the duration of the study. Exclusion Criteria:  -  (1) women of childbearing potential, not using adequate contraception as per  investigator judgment or not willing to comply with contraception for the duration of  the study;  -  (2) females who are pregnant or breast-feeding;  -  (3) other major DSM 5 diagnoses other than mood disorders, except for tobacco use  disorder and anxiety disorder;  -  (4) current evidence of an uncontrolled and/or clinically significant medical  condition, e.g. patients with extensive area of ischemic bruise, multiple sclerosis,  cardiac, hepatic and renal failure that would compromise patient safety or preclude  study participation;  -  (5) history of seizure or epilepsy;  -  (6) history of neurological diseases or traumatic brain injury;  -  (7) history of brain lesion, having received neurosurgery, meningitis or encephalitis;  -  (8) exacerbation of symptom severity, presenting severe suicidal ideation or self harm  behavior during the screen or study period;  -  (9) presence of devices, e.g. pacemakers, cochlear prosthesis, neuro-stimulators,  magnetic cochlear prosthesis, intracranial/intraocular metallic fragments;  -  (10) patient has received electroconvulsive therapy (ECT) within 3 months prior to the  first intervention of the treatment;  -  (11) skin lesion at local site receiving rTMS stimulation;  -  (12) those who cannot tolerate the side effects or ever developed sleep disorder while  receiving rTMS therapy.

The purpose of this study is to evaluate the clinical utility of the StatStrip Lactate,  Hemoglobin and Hematocrit Hospital Meter System in the testing of whole blood specimens from  patients in hospital settings by CLIA waived operators, over a period of at least twenty  days. The specimens shall include capillary (obtained by fingerstick), and venous whole  blood. The study will also evaluate the use of a Fingerstick Blood Contamination Barrier for  capillary sampling from the fingertip. This submission to the FDA is intended for a Point of  Care (POC), CLIA waived device for whole blood capillary and venous lactate, and hemoglobin  and hematocrit measurements. The study will be conducted at three (3) different healthcare settings (hereafter referred to  as "testing sites") in POC sites/departments, by at least nine (9) CLIAW operators (at least  3 in each healthcare setting), over a period of at least twenty days at each healthcare  setting. Examples of hospital departments include (but are not limited to) Emergency  Department (ED), Intensive Care Unit (ICU), Pediatric Intensive Care Unit (PICU), Surgical  Intensive Care Unit (SICU), Medical Intensive Care Unit (MICU), Cardiac Intensive Care Unit  (CICU), Operating Room (OR), where point-of-care lactate, hemoglobin and hematocrit testing  can be utilized.  Each site will recruit at least 120 patients for a total of 360 adult patients in all three  (3) sites for each of the tests and specimen types. An attempt will be made to enroll 50%  males and 50% females.  Each Study Subject will provide:  1. Two (2) capillary whole blood fingerstick specimens  1. One Lactate capillary test using the Fingerstick Blood Contamination Barrier  2. One Hb/Hct capillary test following traditional fingerstick protocol  2. One (1) venous whole blood specimen obtained by venipuncture collected in a lithium  heparin tube or heparinized syringe:  1. One lactate venous test  2. One Hb/Hct venous test Inclusion Criteria:  -  Adult subjects (over or equal to 18 years old) with ordered hemoglobin and hematocrit Exclusion Criteria:  -  Pediatric

Due to the generally poor prognosis, with no chance of long-term survival, health related  quality of life is a very important objective in the treatment of patients with pancreatic  cancer. The non-interventional, prospective, multicentre PARAGON study is desinged to  evaluate the health-related quality of life in patients with metastatic pancreatic cancer, by  analyzing the course of QoL throughout all applied therapy lines for patients with pancreatic  adenocarcinoma, measured according to EORTC scoring manual and patient reported outcome. Pancreatic cancer is often diagnosed at an advanced stage, because most of the patients have  no symptoms until the cancer metastasized. In the majority of study cases pancreatic cancer  research focuses on therapy outcomes and prognosis. With poor prognosis and no chance of  long-term survival, quality of life becomes a very significant purpose of pancreatic cancer  care.  The PARAGON study is designed to see a bigger picture by acquiring data on quality of life  (QoL) and further outcome of patients with localized, locally advanced and metastatic  pancreatic cancer and moreover to establish a sample collection for future biomarker  analysis.  The multicenter, prospective, permanent, register study PARAGON collects outcome data,  patient reported outcomes (PRO), and tumor tissues of pancreatic cancer patients of both  sexes and ages over 18 at approx. 80 German study sites. Patients diagnosed with pancreatic  adenocarcinoma planned for (or recently started with) neoadjuvant, adjuvant or 1st line  therapy can be included into the study.  The data assessment includes data on demography, basic parameters, anamnesis, comorbidities,  therapies, outcome and survival data as well as patient reported outcome in QoL at baseline  and every 8 weeks.  PARAGON's first objective is to determine the course of QoL throughout all applied therapy  lines for patients with pancreatic adenocarcinoma, measured according to EORTC scoring manual  and patient reported outcome. Secondary outcome measurements are e.g. progression-free,  disease-free and overall survival according to treatment line. Inclusion Criteria:  -  Written informed consent and signed data protection form before any study specific  intervention, including screening, will be done  -  Age ≥ 18 years  -  Histologically or cytologically confirmed pancreatic adenocarcinoma  -  Systemic neoadjuvant, adjuvant, 1st line systemic therapy is planned or recently  started (within last 14 days) Exclusion Criteria:  -  Patients who are unable to consent because they do not understand the nature,  significance and implications of the study  -  Patients who are unable to understand or fill out the QoL survey  -  Patients in 2nd or further treatment lines that have not been documented for 1st line  therapy within the study

The uterine manipulator is a device commonly used in minimally invasive hysterectomy surgery  for endometrial cancer. However, without substantial evidence to support its use, surgeons  are required to make decisions about its use based only on their personal choice and surgical  experience.  A retrospective study demonstrated how uterine manipulator use in early-stage endometrial  cancer (FIGO I-II) for minimally invasive surgery was associated with a worse oncologic  outcome in patients with uterus-confined endometrial cancer (FIGO I-II) who underwent  minimally invasive surgery.  The main objective of this study is to prospectively confirm the results obtained  retrospectively, assessing the relapse rate in these patients related to the use or not of a  uterine manipulator during the endometrial surgery. Secondary, the presence of risk factors  that contraindicate the use of the uterine manipulator will also be evaluated. The primary treatment for early-stage endometrial cancer is surgery, performing a total  hysterectomy and bilateral salpingo-oophorectomy with surgical staging if it is indicated.1  The National Comprehensive Cancer Network and European Society of Gynaecological Oncology  Consensus recommend minimally invasive approaches (laparoscopic/robotic) in patients with  disease limited to the uterus, according to evidence reported from randomized prospective  studies (GOG-LAP2 trial).2 This approach leads to lower operative morbidity and a shorter  hospital stay compared to open surgery, without compromising oncologic outcomes.3 The uterine  manipulator is a device commonly used in minimally invasive gynecologic hysterectomy for  benign disease. It is inserted vaginally through the cervical canal into the endometrial  cavity. It facilitates the uterus mobilization during the surgery, generating tension on the  main supporting elements of the uterus to improve surgical field exposure and provide a  landmark for the colpotomy.4  With the introduction of minimally invasive approaches in gynecological oncology treatments,  this uterine device has been utilized for endometrial and cervical cancers, with controversy  regarding its influence on the spread of tumoral cells and the risk of recurrence. Recently,  the LACC trial showed a worse than expected oncological outcome after a laparoscopic/robotic  approach in early stage cervical cancer.5 One of the hypotheses generated was that the  uterine manipulator might influence this worse prognosis.6 The retrospective European Succor  study found the use of a manipulator was associated with a decrease in disease-free survival  in cervical cancer in the minimally invasive group.7 Therefore, there are reasonable doubts  about the uterine manipulator's safety in hysterectomy performed due to cancer.  In endometrial cancer, the presence of the uterine device in a cavity lined with neoplastic  tissue leads to a potential tumor-manipulator interaction. Multiple mechanisms are  potentially involved in this relationship but are poorly understood, however, the concept of  uterus-confined disease is important to evaluate these interactions.8 Nonetheless, we have  limited evidence from retrospectives studies about the uterine manipulator in endometrial  cancer surgery, in which no impact of the uterine manipulator's use on oncological outcome  has been found.9-12 To date, it remains a controversial conclusion that the theoretical tumor  manipulation has no clear impact on oncological prognosis in endometrial cancer.  As is already known in other gynecological tumors (such as early-stage epithelial ovarian  cancer or morcellation in unexpected uterine sarcoma), when the confined disease is exposed  to the peritoneal cavity, the oncological outcome worsens.29 Therefore, the concept of  organ-confined disease is an essential idea to understand our results. In early-stage  endometrial cancer, the myometrium acts as a containment barrier, which may be iatrogenically  injured by the uterine manipulator.  The MUCEI study by Padilla et al. suggests that the use of a uterine manipulator is  associated with worse oncological outcomes in patients with uterus-confined endometrial  cancer (FIGO I-II) at the time of surgery; it also presented a lower recurrence-free survival  and lower overall survival, regardless of the type of manipulator with no differences in the  pattern of recurrence.  The study observed a worse prognosis when the uterine manipulator was used in patients with  the uterine-confined disease (FIGO I-II), not present in those patients with the no-confined  disease (FIGO III) at the time of surgery. These results support the concept that the uterine  manipulator might act in breaking the uterine-confined disease and worsen the oncological  outcomes.  The different potential interferences may explain the alteration of the myometrial barrier by  the uterine device. Therefore, two hypotheses are presented to explain this relationship  between the uterine manipulator and endometrial cancer.  The first is the macroscopic injury hypothesis. During the insertion of any uterine  manipulator (with or without balloon) and its use (especially in the atrophic uterus), the  manipulator´s shank may weaken the myometrium, iatrogenically leading to uterine rupture and  the opening of the tumor to the peritoneal cavity and surgical field.30,31 The uterine  rupture is rarely reflected in surgical reports, and it has not been considered in previous  analyses. Machida et al. showed a 0.4-1% perforation rate with a balloon manipulator,32 thus,  other factors could be involved.  The second hypothesis is the microscopical pathway of dissemination. The uterine device  generates a significant increase in pressure inside the endometrial cavity, generating global  distension according to Pascal´s principle, which is additionally increased by the maintained  push needed during uterine mobilization and colpotomy.33 This increased pressure might be  involved in the improved ability of tumor cells to exceed the myometrial barrier, spreading  outside the uterus cavity by a passive effect through the fallopian tubes and lymphovascular  space.34  Methodology Prospective and non-randomized multicenter descriptive and analytical study in  which the characteristics of the patients, the details associated with the surgery, and the  oncological results will be studied depending on the use or not of the uterine manipulator.  The non-randomization is due to the fact that the procedure to be evaluated is  surgeon-dependent, so the criteria for the use of the uterine manipulator or not will depend  on the surgeon according to the protocol of his center. In other words, inclusion in the  study does not modify the surgical practice in the patient.  Inclusion criteria include women with endometrial cancer diagnosed with stage I-II in a  previous pre-surgical biopsy, the surgery has been performed and there are complete data on  surgery, pathological anatomy, and follow-up.  Exclusion criteria include any patient with suspected disease beyond the uterus in the  preoperative assessment or confirmed during surgical exploration. Cases without pathological  confirmation of endometrial cancer in the final surgical specimen, or final histology of  atypical hyperplasia/endometrial intraepithelial neoplasia will not be accepted.  Patients with open surgery, conversion to laparotomy, or vaginal hysterectomy alone will also  be excluded.  The surgical variables collected will be: use of uterine manipulator (the type of uterine  manipulator and classification of subtypes with or without intrauterine balloon), sealing of  the fallopian tubes, surgical staging, intraoperative complications, surgical time and  hospital stay. Collection of postoperative complications by Clavien-Dindo Classification. The  final histological data of the surgery will be collected according to the type and grade of  the tumor according to the WHO classification, the invasion of the myometrium, the presence  of invasion of the lymphovascular space, sentinel (+/- ultrastaging) and the number of pelvic  lymph nodes. and para-aortic. The Bokhman dual classification of endometrial cancer will be  used. and tumors were classified by FIGO staging. Finally, data on adjuvant treatment  (vaginal brachytherapy, external beam radiation (ERBT), and chemotherapy scheme), follow-up  time, relapse time, and type and pattern of relapse. Inclusion Criteria:  1. - Women with endometrial cancer diagnosed with stage I-II.  2. - Previous pre-surgical biopsy with a diagnosis of endometrial cancer.  3. - The surgery has been performed and there are complete data on surgery, pathological  anatomy, and follow-up of at least 2 years. Exclusion Criteria:  -  Any patient with suspected disease beyond the uterus in the preoperative assessment or  confirmed during surgical exploration. Cases without pathological confirmation of  endometrial cancer in the final surgical specimen or final histology of atypical  hyperplasia/endometrial intraepithelial neoplasia will not be accepted.  Patients with open surgery, conversion to laparotomy, or vaginal hysterectomy alone will  also be excluded.

Lung transplantation (LTx) remains the gold standard for treating patients with irreversible  end-stage pulmonary disease. Of the major organs transplanted, survival in LTx recipients  remains the lowest (mean 5 years). Despite improvements, primary graft dysfunction (PGD), as  defined by respiratory insufficiency and edema up to 72 hours post LTx, remains the leading  cause of early mortality and contributes to the development of chronic lung allograft  dysfunction (CLAD) which is the leading cause of late mortality (2). PGD develops within the  first 72 hours after LTx. The development of CLAD increases quickly with cumulative incidence  of 40-80 % within the first 3-5 years. There is a general lack of efficient treatments for  PGD and CLAD. Prevention of PGD is therefore of crucial importance and has a direct impact on  survival.  The present study is a randomized controlled pilot study which aims to compare patients  undergoing LTx with and without the utilization of cytokine adsorption. Early intolerance to the newly transplanted lung starts at the time of transplantation and  results in PGD driven by an intense inflammatory response. Cytokines play a critical role as  signaling molecules that initiate, amplify, and maintain inflammatory responses both locally  and systemically. The use of cytokine filtration devices to target middle- and low-molecular  weight molecules has been shown to reduce levels of a diverse number of cytokines. These  results have been demonstrated in the in vitro reduction of pathogen-associated molecular  pattern molecules (PAMPS) and damage associated molecular patterns (DAMPS) as well as in in  vivo studies involving orthotopic heart transplantation and kidney transplantation. Cytokine  adsorption has been used successfully in clinical applications to both heart and kidney  transplantation.  The present study is a randomized controlled pilot study which aims to collect preliminary  data on the efficacy of a medical device through the comparison of patients undergoing LTx  with and without cytokine adsorption. Inclusion Criteria:  -  Double lung transplantation  -  Single organ failure Exclusion Criteria:  -  Re-transplantation  -  Drug abuse  -  Kidney failure  -  Liver failure  -  Diabetes mellitus

The main objective is to co-design and assess the practicality of group-based Pelvic floor  muscle training (PFMT) programme in pregnant women. The co-design of the PFMT programme will  involve the stakeholder meeting. The feasibility of the group-based Pelvic floor muscle  training (PFMT) programme will be achieved by using ICIQ-SF questionnaire before  intervention, the completion time of the intervention and 42-day after delivery. Pregnant  women with or without UI at Nanjing maternity and child health care hospital will be offered  to participate if they meet the criteria of the research. Participants will be randomized  into two groups, interventions and control group that gets standard care at the hospital. The  intervention group will meet the midwife to receive supervised group-based PFMT once a month  for 4 months in groups. Doing correct PFMT during pregnancy can help women to prevent or  decrease the risk of developing UI in pregnancy and postnatal period. This study is to co-design and assess the practicality of group-based Pelvic floor muscle  training (PFMT) programme in pregnant women.  PFMT has been recommended as the first-line treatment for stress urinary incontinence and the  other types of urinary incontinence (UI), however, it was not well implemented in many  countries due the lack of human resource and financial support. Compared to individual PFMT  supervision, which is commonly conducted in hospital with additional fees, delivering PFMT in  groups can help more women. Therefore, this study is to codesign and investigate the  feasibility of group-based PFMT programme.  The first phase is to co-design the group-based PFMT programme: The stakeholders will be  involved in this phase. The stakeholder development group will purposively sample both health  professionals and pregnant women with or without UI. The stakeholder development group  members will include the principal researcher, two pregnant women without UI, two pregnant  women with a history of UI, two midwives (one of the midwives will help the principal  researcher to deliver the training session), two physiotherapists. Data from group meetings  will be digitally audio-recorded following consent and notes will be taken during the  meeting. The data will be analyzed to identify the content and mode of delivery of the  group-based PFMT programme along with potential barriers and facilitators.  The second phase is implementation and evaluation of the group-based PFMT programme  (randomised controlled feasibility study): Participants will be randomized into two groups,  intervention and control group. The control group gets standard care at the hospital. The  interventional group gets supervised group-based PFMT. The intervention will be teaching the  participants to do PFMT in groups. The intervention will help women to identify their pelvic  floor muscles and then guide them how to contract the pelvic floor muscle correctly (the  detail of the intervention will be discussed and determined in phase 1 of this project). The  core outcome measures are likely to include self-reported UI, which is commonly used in  studies and is able to evaluate the effectiveness of PFMT intervention in pregnant women, and  UI severity which may be assessed by ICIQ-SF (a validated questionnaire which both assesses  the severity of urinary loss and quality of life impact). The adherence to the programme may  be assessed by attendance records from the group-based training sessions and completion of a  training diary which includes the frequency and duration the participants self-report doing  the exercises. The training diary will be submitted to the principal researcher after the  training sessions. Inclusion Criteria:  1. Nulliparous women who are aged 18 years and older;  2. Gestational ages of 19-24 weeks;  3. With or without the symptom of UI;  4. Singleton fetus  5. Capable of giving valid informed consent Exclusion Criteria:  1. Women with pregnancy complications or urine tract infection  2. Women with previous UI symptoms before pregnancy  3. High risk of preterm labour  4. Women with previous urogenital surgery or diseases which may interfere with pelvic  floor muscle strength, for example, pelvic organ prolapse, neurological disorders,  diabetes.

The purpose of this trial is to investigate whether previously reported benefit of Tranexamic  acid in pediatric orthopedic surgeries could be recapitulated in bone tumor surgeries or not  through a double blinded randomized controlled trial done in children cancer hospital 57357. Resection of bone tumors is commonly associated with considerable intra and post-operative  blood loss due to extensive soft tissue dissection, multiple bone osteotomies, prolonged  operative time. The intraoperative use of limb tourniquet to reduce bleeding may not be  applicable in all situations e.g. arm, thigh and pelvic surgeries. The use of cell savers for  auto transplantation of blood is not preferred in cancer surgeries. Antifibrinolytic drug are  currently used to reduce perioperative blood loss in a variety of orthopedic surgeries.  Currently, the most common agents used are EACA and TXA. A third agent, aprotinin, was  withdrawn from the market in 2007 owing to safety concerns noted in several studies,  suggesting an increased risk of death and renal dysfunction in patients undergoing cardiac  surgery. Slow to adopt in obstetric population, TXA became popular for patients with  hereditary bleeding disorders for whom menorrhagia, frequent spontaneous nose bleeds, or  dental procedures could be life threatening. With strong record as an effective and safe  medicine, TXA has earned its place on the World Health Organization List of Essential  Medicines as an important drug needed in every health system. More recently, its use has  expanded to treat or prevent excessive blood loss from trauma and major surgery, including  cardiac, orthopedic, and hepatic procedures. TXA, a lysine analogue, reversibly binds to the  plasminogen lysine receptors and thereby blocks plasminogen from binding to fibrin (tPA can  only activate fibrin-bound plasminogen and produce plasmin responsible for cleaving fibrin  molecule and dissolving the blood clot) TXA has been extensively studied in joint replacement  surgeries specifically total knee replacement, scoliosis surgery, and in trauma surgeries.  The question of efficacy of TXA in these surgeries was addressed in multiple prospective  randomized studies and subsequent meta-analysis. Main concern regarding increased risk of DVT  was negated in several of these studies. The American Academy of Orthopedic Surgeons provides  a strong recommendation for the use of any administration of TXA for joint arthroplasty and  states that it does not seem to increase the risk of thromboembolic or myocardial  complications. Junlong Zhong et al. in 2019 published a systematic review and meta-analyses  on 2500 pediatric patients undergoing corrective surgery for idiopathic scoliosis. They  concluded that TXA was effective in reducing surgical time, intraoperative blood loss and  blood transfusion without increasing complications. Levack et al. Published in 2020 a  randomized controlled trial on role of TXA in reducing blood loss and transfusion in  pediatric patients undergoing a periacetabular osteotomy. They concluded that TXA reduced  blood loss by 293ml and reduced frequency of allogenic transfusions by 73%.  The purpose of this trial is to investigate whether previously reported benefit of Tranexamic  acid in pediatric orthopedic surgeries could be recapitulated in bone tumor surgeries or not  through a double blinded randomized controlled trial done in children cancer hospital 57357. Inclusion Criteria:  1. Malignant bone tumor of the femur and finished neoadjuvant chemotherapy  2. Candidate for resection and reconstruction by prosthesis. 3- Age 4-18 years. Exclusion Criteria:  1. Anatomic location other than femur de  2. Reconstruction other than prosthesis  3. Allergy to TXA  4. Previous history of DVT  5. Previous history of renal dysfunction  6. Congenital or acquired coagulopathy.  7. Congenital or acquired cardiomyopathy.  8. Previous history of convulsions.

This retrospective study was conducted on patients with frontal sinus leaks came to ENT  departments of Al-Azhar University Hospital, New Damietta, Egypt, for a period of five years. All patients in this study were evaluated during the follow-up period. Patients' age, sex,  occupation, residence, and telephone number were recorded for each participant for  demographic purposes. General and local examinations were also performed preoperatively as  usual.  Medical history, surgical approach, leakage site, complications, reconstruction technique,  and follow-up were recorded.  All cases were treated by endonasal endoscopy  -  Complete sphenoethmoidectomy.  -  Draf type IIa, IIb, and III according to defect location.  -  Defect less than 3 mm closed by a plug of fat and facia lata or middle turbinate mucosa.  -  Defect more than 3 mm closed by underlying facia lata, underlying cartilage, and overlay  facia lata. Inclusion Criteria:  -  patients who underwent endoscopic frontal sinus repair. Traumatic or spontaneous  patients with a CSF leak at a minimum of six months not responding to conservative  measures were included. Exclusion Criteria:  -  Known malignancy or patients with frontal leak due to extensive tumor resection or  intracranial injury

This is a retrospective, mono centric, exploratory study to assess the incidence of a genomic  alteration: NTRK gene fusion, in adult gliomas and brain metastases. Retrospective mono centric study of medical data (clinical, histological, molecular and  imaging) from medical records and analysis of available excisional tissue samples. Inclusion Criteria:  -  Adult male or female subject;  -  Glioma or brain metastasis operated on in our institution, histologically confirmed  (WHO classification 2016);  -  Subject with a frozen tumour sample < 5 years old;  -  Subject for whom all clinico-radiological data are available;  -  Subject affiliated to a health insurance scheme;  -  Subject who has been informed of the research and who has not indicated his opposition  to the use of his medical data and who has signed a consent for the use of his tumour  sample. Exclusion Criteria:  -  Patient under legal protection, guardianship or deprived of liberty by judicial or  administrative decision  -  Biological samples not available and/or in insufficient quantity for analysis

Our main aim for this study was to evaluate the long-term outcome comparisons between sural  artery and Supramalleolar flap in the reconstruction of extensive defects of non-weight  bearing regions of foot and ankle. The patients' information were collected through medical  records and analyzed through SPSS In this article we intend to present our experience comparing a series of the two types of  flaps in terms of viability, coverage of defect, cosmetic appearance, and functions of foot  and ankle based on self-designed Tool . This Tool contains 4 parameters i.e., Activity of  daily living, coverage of defect, cosmetic appearance of Skin post flap, and Weight bearing  status. A score was given to each parameter and on the basis of these scores, Long term  outcome were analyzed of each patient Inclusion Criteria:  -  Only defects of foot and ankle around dorsum and perimalleolar areas were included. Exclusion Criteria:  -  The defects reconstructed with other local flaps and free flaps were excluded from  this review

This is a monocentric, randomized, open-label, single-dose, three-cycle, partial replicate  clinical study designed to evaluate the pharmacokinetic profile and bioequivalence of  HMPL-523 Tablets produced by two different manufacturers in healthy subjects. This is a monocentric, randomized, open-label, single-dose, three-cycle, partial replicate  clinical study designed to evaluate the pharmacokinetic profile and bioequivalence of  HMPL-523 Tablets produced by two different manufacturers in healthy subjects. This study  plans to enroll 39 healthy Chinese subjects who will be randomized (1:1:1) into one of three  sequence groups (Test [T]/Reference[R]/R group, RTR group and RRT group) to receive a single  dose in each cycle with a washout period of at least 7 days, where T is the test product  [i.e., HMPL-523 Tablets manufactured by Hutchison MediPharma (Suzhou) Limited.], and R is the  reference product (i.e., HMPL-523 Tablets manufactured by WuXi STA).  The study includes three periods expected to last for 2 months: screening period, treatment  period (for three cycles), and follow-up period Inclusion Criteria:  1. Subjects can communicate well with investigators, must be voluntary and sign the ICF,  and agree to comply with the requirements in the study protocol;  2. Healthy male and female subjects aged 18-55 years (inclusive);  3. Weight ≥50 kg, Body Mass Index (BMI) between 19-26 kg/m2 (inclusive);  4. Subjects with good health condition  5. Subjects of childbearing potential must promise to use reliable contraceptive  measures. Exclusion Criteria:  1. History or clinical characterization of clinically significant metabolic/endocrine,  hepatic, renal, hematological, pulmonary, immune, cardiovascular, gastrointestinal,  genitourinary, neurological, or psychiatric diseases within 3 months prior to the  screening period and in the screening period (judged by investigators);  2. creatinine clearance estimated using Cockcroft-Gault formula [(140-age) × body weight  (kg) × gender correction factor] /[0.818×Scr (umol/L)] (male: 1.00, female: 0.85) < 80  mL/min;  3. History of gastrointestinal surgery, kidney surgery, cholecystectomy and other  surgeries that might affect drug absorption or excretion judged by the investigator;  4. History of serious allergy (e.g., drug allergy) and acute allergic rhinitis or food  allergy, in particular allergy to the active ingredient or excipient of study drug,  within two weeks prior to screening;  5. Previous history of hypertension;  6. Systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg;  7. Female subjects who have a positive pregnancy test;  8. Subjects who smoked >10 cigarettes per day within 3 months prior to screening, or are  unable to quit smoking completely during the study;  9. Subjects who drank on a regular basis within 6 months prior to the study, i.e.,  drinking more than 14 units of alcohol per week (1 unit =360 mL beer or 45 mL liquor  with 40% alcohol or 150 mL wine);  10. Subjects with drug abuse (including but not limited to Morphine,  3,4-methylenedioxy-methamphetamine (MDMA), methamphetamine, tetrahydrocannabinolic  acid, Ketamine, Cocaine or subjects whose urine drug abuse screen showed positive);  11. Use of blood products within 2 months before screening; donation of blood (including  blood component) or loss of blood ≥400 mL within 3 months prior to screening, ≥200 mL  within 1 month prior to screening, or plan to donate blood or blood component during  the study or within 1 month after end of the study;  12. Subjects who have a fear of needles, hemophobia or whose venous blood is hard to  collect;  13. Positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody  (HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV)  antibody, or treponema pallidum antibody;  14. Use of any prescription drug and Chinese herbal tonic within 30 days prior to the  first dose;  15. Use of any over-the-counter drug (including but not limited to vitamins, prophylactic  treatments, plant health products, etc.) within 14 days prior to the first dose;  16. Having participated in clinical trials for other drugs/medical devices within 3 months  prior to screening;  17. Having consumed foods, juices and beverages containing alcohol, grapefruit, bigarade  and caffeine within 72 hours prior to the first dose;  18. Subjects vaccinated with a live-attenuated vaccine within 8 weeks prior to screening  or planning to get vaccinated during participation of this clinical trial;  19. Previous history of serious gastrointestinal disease, such as dysphagia, active  gastric ulcer, inability to take drugs orally or absorption disorder for oral drugs;  20. Subjects who have special requirements for diet and cannot comply with uniform diet;  21. Lactating female subjects;  22. According to the investigator's judgment, the subjects had any other disease or status  that might affect the normal completion of the study or the evaluation of the study  data, or had any other condition that was not suitable for the study.

This study main objective is to evaluate the safety and efficacy of the UltraSight AI  Guidance software. The investigational product is a software that guides the user to capture  a high quality ultrasound image. The study will include healthcare professionals, not  specialized in echocardiography, who will perform echocardiography by using UltraSight AI  Guidance software, on subjects in the medical centers cardiac units. This pivotal study is a multi-center, multi-reader multi-case (MRMC) study, designed to  assess the quality of the clips obtained by novice users when using the UltraSight AI  Guidance software. Prior to the study start, there will be a pre-study training phase for  training the novice users.  During the study, eligible subject will undergo the echocardiography examination twice on a  single study visit (same day): once by one of the novice users when using the UltraSight AI  Guidance software, and once by an expert sonographer without the aid of the software.  Each novice user will perform the examination on at least 20 subjects (with the aim that the  number of examinations by each novice will be similar). All examinations will be sent to  multiple Board certified cardiologists for their quality evaluations. Inclusion Criteria:  1. Age 18 and older  2. Subjects willing and able to give written informed consent. Exclusion Criteria:  1. Emergency (non-elective) admission within 24 h prior to participating in the study  2. Female subjects who are pregnant (women of childbearing potential will perform a urine  pregnancy test)  3. Unable to lie as required in all the classic positions for standard TTE exam: supine  on back / left decubitus  4. Subjects who currently participate a clinical trial, involving interventional cardiac  devices.  5. Subjects who have prior Echo exam with description of Low/Poor quality exam in the  echo report  6. Subjects with BMI above 40  7. Subjects experiencing a known or suspected acute cardiac event  8. Subjects with severe chest wall deformity as per previous medical records and physical  examination  9. Subjects who have undergone pneumonectomy  10. Subjects whose anatomy does not lend itself to yield diagnosable standard  echocardiography clips (i.e. situs inversus with dextrocardia, single ventricle  anatomy due to congenital heart disease, etc.).  -  A woman is of childbearing potential if she is postmenarchal, has not reached a  postmenopausal state (≥12 continuous months of amenorrhea with no identified  cause other than menopause), and is not permanently infertile due to surgery  (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as  determined by the investigator (e.g., Müllerian agenesis.).

At present, there is conflicting evidence regarding outcomes in patients with septic shock  receiving weight-based vasopressor (WBVP) versus non-weight-based vasopressor (NWBVP) dosing  strategies. At MCMC, a weight-based strategy is in place whereas MDMC, MMMC and MRMC  currently utilize a non-weight-based dosing strategy. Obese patients (BMI > 30) receiving  either strategy may potentially be receiving substantially more or less vasopressor exposure  compared to their non-obese (BMI < 30) counterparts. Determining total vasopressor exposure  and assessing clinical outcomes would benefit our institution and others by providing optimal  vasopressor dosing strategies in obese and non-obese patients. There is a difference in  clinical outcomes between patients receiving weight-based and non-weight-based vasopressor  dosing strategies. There is a difference in total vasopressor exposure between obese and  non-obese patients utilizing WBVP and NWBVP strategies. Vasopressors are a mainstay of therapy for patients with septic shock to achieve and maintain  hemodynamic stability.1 Both weight-based and non-weight-based dosing recommendations exist  with no clear evidence that one is better than the other.3-10 However, in light of the  obesity epidemic and emerging evidence regarding the dangers of excessive catecholamine  exposure, an evaluation of dosing practices is warranted. The aim of this study is to  determine whether clinical outcomes differ between patients receiving weight-based and  non-weight-based vasopressor dosing strategies for septic shock. This is a multicenter,  retrospective chart review. Patients admitted to MDMC and MCMC from 4/1/2017-8/31/2019 will  be identified through the electronic medical record utilizing ICD codes for sepsis and septic  shock. Patients meeting study inclusion criteria will be analyzed as described below.  Outcomes will be assessed between patients receiving WBVP and NWBVP with planned subgroup  analysis in each group between patients with BMI < 30, 30-49, and > 50. Inclusion Criteria:  -  ICU admission  -  Medical admission type  -  Received NE, epinephrine (EPI), phenylephrine (PE), or dopamine (DA) for septic shock  -  Received NE/EPI/PE/DA for > 24 hours  -  Age ≥ 18 years Exclusion Criteria:  -  Non-sepsis indication for vasopressors  -  Surgical or trauma admission type  -  ICU length of stay < 24 hours  -  Pregnant

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex  for production of human IL-12. IL-12 is a protein that can improve the body's natural  response to disease by enhancing the ability of the immune system to kill tumor cells and may  interfere with blood flow to the tumor.  The main purpose of this study is to evaluate the safety and tolerability of a single tumor  injection of Ad-RTS-hIL-12 given with oral veledimex in the pediatric population. Eligible patients will be stratified to one of two arms, according to clinical indication for  tumor resection. Pediatric patients who are scheduled for craniotomy and tumor resection will  receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be  administered by free-hand injection. Patients will continue on oral veledimex for 14 days.  This arm has been completed and is currently closed to enrollment.  Pediatric patients with diffuse intrinsic pontine glioma (DIPG) will receive Ad-RTS-hIL-12 by  stereotactic injection and then will continue on oral veledimex for 14 days.  The study is divided into three periods: the screening period, the treatment period and the  follow-up period. Inclusion Criteria:  1. Male or female subjects ≤ 21 years-of-age with the demonstrated ability to swallow  capsules whole and who are willing to provide access to previously obtained biopsy  results  2. Provision of written informed consent and assent, when applicable, for tumor  resection, stereotactic surgery, tumor biopsy, sample collection, and/or treatment  with study drug prior to undergoing any study-specific procedures  3. Arm 1: Evidence of recurrent or progressive supratentorial tumor, which has shown a >  25% increase in bi dimensional measurements by MRI or is refractory with significant  neuro deterioration that is not otherwise explained with no known curative therapy,  not in direct continuity with the ventricular system (e.g., there is physical  separation between the tumor and ventricle, the tumor does not open directly into the  ventricular system).  Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the  pons included and without evidence of dissemination. Subjects should be ≥ 2 weeks and  ≤ 10 weeks post standard focal radiotherapy (ie, dose of 5400 to 5960 cGy and maximum  dexamethasone of 1 mg/m2/day)  4. At the time of registration, subjects must have recovered from the toxic effects of  previous treatments, as determined by the treating physician.  1. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks  2. Other cytotoxic agents: 3 weeks  3. Nitrosoureas: 6 weeks  4. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks  5. Vaccine-based and/or viral therapy: 3 months  5. On a stable or decreasing dose of dexamethasone for the previous 7 days  6. Able to undergo standard MRI scans with contrast agent before enrollment and after  treatment  7. Have age-appropriate functional performance:  1. Lansky score ≥ 40 or  2. Karnofsky score > 50 or  3. Eastern Cooperative Oncology Group (ECOG) score ≤ 2  8. Have adequate bone marrow reserves and liver and kidney function, as assessed by the  following laboratory requirements:  1. Hemoglobin ≥ 8 g/L  2. Absolute lymphocyte count ≥ 500/mm3  3. Absolute neutrophil count ≥ 1000/mm3  4. Platelets ≥ 100,000/mm3 (untransfused [> 5 days] without growth factors)  5. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age  6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age  7. Total bilirubin < 1.5 x ULN for age  8. International normalized ratio (INR) and activated thromboplastin time within  normal institutional limits  9. Male and female subjects of childbearing potential must agree to use a highly reliable  method of birth control (expected failure rate < 1% per year) from the Screening visit  through 28 days after the last dose of study drug. Women of childbearing potential  must have a negative pregnancy test at screening. Exclusion Criteria:  1. Radiotherapy treatment prior to the first veledimex dose:  1. Focal radiation ≤ 4 weeks  2. Whole-brain radiation ≤ 6 weeks  3. Cranio-spinal radiation ≤ 12 weeks NOTE: Subjects in Arm 2 (ie, with DIPG) must  be ≥ 2 weeks and ≤ 10 weeks after standard focal radiotherapy (dose of 5400 to  5960 cGy and maximum dexamethasone of 1 mg/m2/day)  2. Subjects with clinically significant increased intracranial pressure (eg, impending  herniation or requirement for immediate palliative treatment) or uncontrolled seizures  3. Subjects whose body surface area (BSA) would expose them to < 75% or > 125% of the  target dose  4. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection  (eg, human immunodeficiency virus [HIV], hepatitis)  5. Use of systemic antibacterial, antifungal, or antiviral medications for the treatment  of acute clinically significant infection within 2 weeks of first veledimex dose.  Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile  prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is allowed  perioperatively  6. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first  dose of study drug  7. Other concurrent clinically active malignant disease, requiring treatment  8. Nursing or pregnant females  9. Prior exposure to veledimex  10. Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450)  3A4 within 7 days prior to veledimex  11. Use of heparin or acetylsalicylic acid (ASA). The use of systemic heparinization, or  any ASA containing medications, is prohibited during active dosing with veledimex.  Prophylactic heparin SC, per institutional protocol, or heparin when used for  maintaining patency of an access port of a PICC line is permitted.  12. Presence of any contraindication for a neurosurgical procedure  13. Unstable or clinically significant concurrent medical condition that would jeopardize  the safety of a subject and/or their compliance with the protocol

Comparative study of nasal stents and nasal packing in patients undergoing septoplasty To investigate the safety and effectiveness of nasal stent in clinical application by  comparing and observing the clinical effect and comfort of nasal stent and merocel sponge  applied in nasal septoplasty. Methods: patients with nasal septal deviation were selected and  randomly divided into nasal stent group (experimental group) and merocel sponge group  (control group) according to the packing method. The hemostasis effect, comfort and  complications of the two groups were compared during the packing period. Inclusion Criteria:  -  Clinical diagnosis of septal deviation  -  Post septoplasty surgery Exclusion Criteria:  -  Pregnant or lactating women;  -  Allergic to Nickel

This is an observational study based on a population-based EHR database. This observational study based on a population-based EHR database in Yinzhou district of  Ningbo city in China is to estimate incidence rates of seizures (including febrile seizures),  urticaria and angioedema, apnea, and fever among Chinese children after receiving Prevenar  13. In addition, a validation study including validation of International classification of  diseases, tenth revision (ICD-10) codes or ICD-10 code based algorithm for identifying all  safety outcomes of interest and a prospective cohort study in a sub-population of the main  study will be conducted in order to offset the potential biased results from the main study  because of potential misclassification of the safety outcomes of interest due to miscoding  and/or undercoding of ICD-10 codes used to identify these safety outcomes in the EHR  database. Inclusion Criteria:  To be eligible for the main study, children in Yinzhou population-based EHR database must  be aged 1 to 24 months and receive at least one dose of 13vPnC between May 1st, 2017 and  July 24th, 2020 where the first dose is received before or on July 24th, 2020 since a 7-day  post-vaccination follow-up for each dose in each child receiving 13vPnC is needed. For the  prospective cohort in a sub-population of the main study, eligible children for the main  study must receive the first dose of 13vPnC between August 1st, 2018 and July 24th, 2020  and an informed consent must be obtained from parents/legal guardians. Exclusion Criteria: There are no exclusion criteria for this study.

A prospective observational cohort study investigating physiological parameters vs biological  markers of whole blood in septic and non-septic pregnant woman to predict systemic immune  health The altered physiology of pregnancy makes the signs and symptoms of sepsis less distinctive  in the pregnant population. This can lead to both over treatment (with antibiotics) and late  identification of sepsis. The progression of sepsis can be rapid in this population,  resulting in severe morbidity and mortality. The mortality associated with sepsis in the  general population is over 10%, while septic shock can increase this figure up to 30%. A  study looking at maternal mortality due to sepsis recognised that the time from the onset of  infection to death was less than 24 hours in 50% of patients. A review of the literature  shows that half of the fatal cases of maternal sepsis could have been prevented with early  detection of sepsis.  The unmet need is therefore a diagnostic bedside tool that can be performed on women  identified as high risk via physiological parameters. The tool needs to be quick and easy to  use whilst accurate at diagnosing sepsis.  Study Objectives  To evaluate the effectiveness of physiological parameters in predicting maternal sepsis.  To evaluate the effectiveness of alternative biomarkers in diagnosing maternal sepsis  including a genomic sepsis-test.  Investigation of the systemic immune health of women undergoing an uncomplicated pregnancy  and labour. Inclusion Criteria:  Pregnant with viable pregnancy confirmed on ultrasound at dating scan and over 18 years of  age Able to provide informed consent (a translation service will be provided for women  where English is not the first language);  Women recruited into Cohort B will have deferred consent taken to avoid interference with  clinical care. Exclusion Criteria:  -  Pregnant woman under the age of 18 or wishing not to consent, withdrawing consent or  lacking capacity.