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Many autistic children suffer from chronic constipation. Gut mobilization was obtained  administering polyethylene glycol (PEG) at the dose of 6.9 g/d once a day for 6 months in an  open trial involving 21 chronically constipated autistic children 2-8 years old, followed  prospectively for 6 months. Children diagnosed with Autism Spectrum Disorder by DSM-5 and  confirmed by ADOS-2 criteria, were evaluated before (T0), 1 month (T1), and 6 months (T2)  after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol  concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors,  anxiety, and hyperactivity. Chronic constipation is common among children with ASD and is associated with more severe  anxiety, hyperactivity, irritability and repetitive behaviors. Young autistic children with  chronic constipation display higher urinary and foecal concentrations of p-cresol, an  aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute  p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic  behaviors, while blunting social interaction. This study was undertaken to prospectively  assess the behavioral effects of gut mobilization in young autistic children with chronic  constipation, and to verify their correlation with urinary p-cresol. To this aim, 21  chronically constipated autistic children 2-8 years old were evaluated before (T0), 1 month  (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores,  urinary p-cresol concentrations, and behavioral scores for social interaction deficits,  stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization was obtained  administering PEG (6.9 g/d once a day) for 6 months. A progressive, statistically significant  decrease in all behavioral symptoms was recorded over the six-month study period. Urinary  p-cresol levels displayed variable trends, mainly increasing at T1 and decreasing at T2.  These results support gut mobilization as a simple strategy to at least partly ameliorate ASD  symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children.  These beneficial effects likely involve multiple mechanisms. Inclusion Criteria:  -  Fulfilling DSM-5 diagnostic criteria for Autism Spectrum Disorder  -  Chronic constipation, namely unsatisfactory defecation characterized by difficult and  infrequent passage of lumpy and hard stools during at least the previous 3 months, as  reported by parents based on the Bristol Stool Scale Exclusion Criteria:  -  ASD constipated children already treated with laxatives

The primary objective of this study is to evaluate the safety and efficacy of two doses of  CNTX-6970 for the treatment of pain related to OA of the knee compared to placebo. CNTX-6970  is being developed as a new treatment for chronic pain, including painful osteoarthritis of  the knee. The study will employ a randomized, allocation-concealed, multicenter, placebo-controlled,  multi-period crossover design (Schmid et al, 2018). This multi-period crossover randomized,  controlled trial allows comparability and assessment of efficacy through repeated exposures  within each subject to the active treatment and a control (placebo) in randomized sequence.  Such multi-period crossover designs are ideal for treatments with rapid onset of action and  short half-life such as the asset under study here. We have strived to minimize the  complexity of this powerful design by using only 2 blocks with 2 periods each. The modest  additional complexity of the proposed multi-period crossover design, compared to a  parallel-groups design, is justified by the marked improvement in efficiency. The gains in  efficiency afforded by the multi-period crossover design allow a substantial reduction in  sample size without sacrificing statistical power. For example, our simulation experiments  (with sample sizes ranging from 30 to 50, carryover effects ranging from 0 to 0.2, and an  effect size of 0.4) indicated that the parallel design yields statistical power ranging from  0.20-0.25, whereas our proposed 2-block multi-period crossover design yields power ranging  from 0.9-1.0.  The trial will compare an active treatment vs. placebo. Each arm of the study will employ a  multi-period crossover design with two blocks. Each block will consist of two treatment  periods with each period lasting 6 weeks. Treatment assignments (active drug versus placebo)  will be randomized for each patient to the two periods within each block. The period length  of 6 weeks was chosen based on several considerations: (i) Most efficacious analgesic drugs  demonstrate separation from placebo by 6 weeks; (ii) The decision to move CNTX-6970 forward  to Phase 3 will require a clinically meaningful separation from placebo by 6 weeks; (iii) In  this Phase 2 study, implementing a treatment block longer than 6 weeks would make the overall  design more challenging and burdensome by extending the duration of overall testing beyond 6  months; (iv) Recent meta-analyses suggest that anti-inflammatory treatments such as NSAIDs  reach peak effects on pain within a 4-week timeframe in patients with knee osteoarthritis,  and multiple RCTs have specifically demonstrated efficacy for celecoxib at 2-6 weeks (Osani  et al, 2020).  The comparison with celecoxib is used to evaluate "assay sensitivity," i.e., to assess the  study protocol's ability to demonstrate superiority of an established efficacious treatment  (celecoxib 100mg BID). In this study, the placebo will consist of inactive tablets identical  to the active treatment tablets. Treatment assignments (active drug versus placebo) will be  randomized for each patient to the two treatment periods within each block Inclusion Criteria:  1. Individuals between 45 and 80 years of age (inclusive) at the time of the Screening  Visit.  2. Willing to use a mobile smart device during the study period. Individuals who do not  have access to a mobile device will be provided with one for the duration of the study  and trained in its use.  3. Can understand the nature of the study and protocol requirements and is willing to  comply with study drug administration requirements and discontinue prohibited  concomitant medications.  4. Provides written informed consent to participate in the study using a form approved by  the institutional review board (IRB).  5. Is capable of communicating with the site personnel, able to complete subject-reported  outcome measures and can be reliably rated on assessment scales (in the opinion of the  Site Investigator).  6. Radiography of both knees with a posterior-anterior, fixed-flexion view taken during  the Screening visit. The Index knee must show evidence of chronic OA with a K-L  Grading Scale of 2 or 3. Such evidence will be provided by a central reading of the  radiography of both knees from an expert radiologist of the CCC of EPPIC-Net.  7. Moderate to severe pain in the Index knee associated with OA and stable for a minimum  of 6 months prior to Screening in the opinion of the investigator.  8. Confirmation of OA of the index knee: American College of Rheumatology (ACR)  diagnostic criteria.  9. Subjects must have failed 2 or more prior therapies. Failure is deemed to be  inadequate relief in the opinion of the investigator. A therapy may be deemed to have  been inadequate because of one or more of the following:  1. unacceptable adverse events (AEs);  2. inadequate response, or loss of response for chronic OA knee pain or  -  pain in the index knee was minimally improved, not improved, or was worse  and/or  -  function, and/or stiffness in the index knee was minimally improved, not  improved, or was worse  3. medical condition resulting in contraindication to the standard of care  appropriate to the severity of the index knee OA pain. "Therapies" include, but  are not limited to, each of the following:  -  nonsteroidal anti-inflammatory drugs (NSAIDs) (including topical), opioids,  duloxetine, other systemic therapy, IA corticosteroids, IA viscosupplements  -  physical therapy or bracing.  10. A mid-to-high level summed pain score (0-50) for the Index knee on the WOMAC-A pain  subscale, which will be completed by the subject every 3 days (+/-1 day window) during  the 14-day Screening period (5 times - screening days 0, 3, 6, 9, 12).Subject must  complete all 5 screening WOMAC-A pain subscales. Criteria for pain intensity  requirements are specified in Appendix IV: Unblinded Information. This is only  available to unblinded study team members and will be assessed centrally.  Additionally, eligibility per study pain intensity requirements will be confirmed by  the CCC before a SAFER interview is scheduled.  11. Body mass index (BMI) of ≤ 37 kg/m2.  12. Females not of childbearing potential - defined as post-menopausal for at least 1  year, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or  hysterectomy) - or practicing at least one of the following medically acceptable  methods of birth control throughout the study period:  1. Hormonal methods such as oral, implantable, injectable, or transdermal  contraceptives for a minimum of 1 full cycle (based on the subject's usual  menstrual cycle period) before study drug administration;  2. Total abstinence from sexual intercourse since the last menses before study drug  administration;  3. Intrauterine device;  4. Double barrier method (condoms, sponge, diaphragm, with spermicidal jellies or  cream).  13. Male subjects capable of fathering a child must be willing to use barrier methods to  avoid a pregnancy during the study. Male condoms with or without a spermicide coating  are acceptable, as some women are allergic to spermicide.  14. Willing and able to understand the study requirements, abide by the study  restrictions, complete the study procedures, independently record responses on the  pain scales and make daily/weekly entries using the NEForm (section K1), and  independently communicate meaningfully with study personnel.  15. Willing to refrain from illicit drug use during the study, and to have illicit drug  testing at screening and at later time points, if illicit drug use is suspected during  the study. Illicit drug use is defined as the use of any medication or substance that  is outside the prescribed use of a medical professional, including medications that  are prescribed but are not being used as prescribed. Cannabinoid use is exclusionary  for this trial, regardless of reason for use.  16. Subjects must stop taking any current analgesic medications at the time of initial  Screening and agree to take only the allowed rescue medication for OA knee pain  (acetaminophen; 325mg x 2 tablets PO, QID, PRN) from the time of screening through  study completion, and agree to use no topical medications for OA knee pain during the  trial. Subjects must also stop taking any medication known to impact pain, even if  taken for other indications, e.g. duloxetine for depression.  17. Complete the SAFER (State, Assessibility, Face and Ecological Validity and the Rule of  the 3 Ps [persistent, pervasive, pathological]) interview and receive a passing score  which will be administered by a remote telephone rater to confirm pain history with  knee OA, eligibility per study pain intensity requirements, screening EMA score, and  medication history.  18. The end of day EMA Alert #5 is completed on at least 5 out of the 7 days in the  screening period. This is the last alert of the day and includes the daily NRS  question.  19. Patient-reported daily NRS (for average pain over the last 24 hours) meets the  criteria specified in "Appendix IV: Blinded Information" during the 7-day screening  period. The algorithm is only available to unblinded study team members and will be  assessed centrally. Additionally, screening NRS scores will be confirmed by the CCC  before a SAFER interview is scheduled.  20. Completed at least 3/5 daily EMA alerts on days 6 and 7 of screening. Exclusion Criteria:  1. Any form of joint replacement surgery of the index knee at any time, or open surgery  of the index knee/knee joint in the past.  2. Prior arthroscopic surgery of the index knee within 3 months of Screening.  3. Any painful conditions of the index knee due to disease other than OA. For example,  periarticular or referred pain involving the index knee, or from joint disease other  than OA associated with the index knee.  4. Other chronic pain anywhere in the body that is equal or greater in intensity or  impairment than index knee pain or that requires the use of analgesic medications  including, but not limited to, local painful areas, myofascial pain syndromes,  fibromyalgia, genetic, metabolic abnormalities, hematologic or neuropathic pain, and  any acute or chronic pain that may interfere with the study pain assessments by the  subject.  5. Secondary OA of the index knee due to acute or recurrent traumatic injury.  6. Significant current or past instability (e.g., cruciate ligament tear or rupture or  previous repair) or misalignment (>10 degrees varus or valgus) of the index knee.  7. Documented history of neuropathic arthropathy in the knee.  8. Imaging finding of bony fragmentation in the index knee (radiographic, computed  tomography, or magnetic resonance imaging).  9. Physical/occupational/chiropractic therapy for the lower extremities or acupuncture  for the lower extremities within 30 days of Screening, or need for such therapy during  the study.  10. Plans to have surgery, or other invasive procedures, or intra-articular (IA)  injections while participating in the study.  11. Current use of opioids for any condition.  12. Use of pain medication (including non-steroidal anti-inflammatory drugs, medical  cannabinoids/ CBD oil) less than 5 days before screening (acetaminophen is allowed) or  any time throughout the study.  13. Corticosteroid injection in the index knee within 90 days of Screening or during study  participation.  14. Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of  Screening or any time during study participation.  15. History of clearly documented allergic reaction to celecoxib (Celebrex®), or to sulfa  drugs.  16. Knee effusion requiring aspiration of the index or contralateral knee at time of  screening.  17. Radiofrequency ablation (RFA) of the knee within 2 years prior to screening.  18. Presence of any medical condition or unstable health status that, in the judgment of  the investigator, might adversely affect the safety of the subject or the conduct of  the study, or negatively affect the resulting data, including chronic conditions that  are likely to alter the rate of healing or are likely to result in safety  complications unrelated to the study medication, or significant compromise to key  organ systems.  19. Has a malignancy or has received treatment for malignancy at any time, with exception  of resected basal cell carcinoma and squamous cell carcinoma of the skin within the  past 5 years.  20. Ulcer or open wound anywhere in the region of the index knee.  21. Clinically significant abnormal laboratory results at the Screening Visit (in the  opinion of the investigator), or significant organ disease that would put the subject  at undue risk or affect the ability of the subject to participate in the trial.  22. Use of an investigational medication within 30 days of Screening, or 5 pharmacokinetic  or pharmacodynamic half-lives (whichever is longer) or scheduled to receive such an  agent while participating in the current study.  23. Has any of the following characteristics:  1. active or historic substance use disorder within the previous year as defined by  the Diagnostic and Statistical Manual for Mental Health Disorders, fifth edition,  or  2. urine drug screen is positive for a substance of abuse and participant is unable  to provide a valid prescription from a medical professional.  24. Has moderate to severe depression or anxiety, as indicated by a score ≥ 11 on either  subscale of the Hospital Anxiety or Depression Scale (HADS).  25. Has a positive pregnancy test at the Screening Visit.  26. Has ongoing litigation for workers compensation.  27. Known history or symptoms of long QT syndrome.  28. Male has a QRS interval >120 ms and QTcF ≥460 ms OR female has a QRS interval ≥120 ms  and QTcF ≥480 ms at Screening or Baseline.  29. Has moderate to severe congestive heart failure (New York Heart Association [NYHA]  class III and class IV).  30. Has a history of symptomatic cardiovascular disease.  31. K-L Grade 1 or 4 OA in the index knee.  32. Current therapy with any immunosuppressive therapy, including corticosteroids (>5  mg/day of prednisone).  33. Moderate to severe hepatic impairment at the Screening Visit, as defined by any of the  following:  1. AST and ALT values that are ≥1.5 times ULN; or  2. Total bilirubin > 1.2 mg/dL; or  3. Direct (conjugated) bilirubin > 0.3 mg/dL.  34. Moderate to severe renal impairment at the Screening Visit, as defined by either:  1. An estimated glomerular filtration rate [eGFR] < 45 mL/min; or  2. A serum creatinine level > 1.3 mg/dL).  35. Use of CYP3A4 inhibitors (e.g., grapefruit juice, omeprazole, pantoprazole) or CYP3A4  inducers (e.g., carbamazepine, rifampin, St. John's wort) within 7 days prior to the  Baseline Visit or any time during study participation.  36. Use of CYP2C9 inhibitors (e.g., amiodarone, fluconazole) or CYP2C9 inducers (e.g.  carbamazepine, rifampin, St. John's Wort) within 7 days prior to the Baseline Visit or  any time during study participation.  37. Use of P-glycoprotein inhibitors (e.g., atorvastatin, azithromycin, carvedilol) within  7 days prior to the Baseline Visit or any time during study participation.  38. Is classified as a poor metabolizer via the CYP2C9 pathway as determined by genetic  testing (CYP2C9 genotyping).  39. Has chronic or active infection(s) at the time of the Screening Visit.  40. Has clinically significant pulmonary disease such that medical treatment is required  (e.g. COPD, asthma).  41. Has any of the following blood counts:  a. Monocyte count < 0.5 % of white blood cells b. Platelet count , or i. Females (sex  at birth): < 125,000/µL ii. Males (sex at birth): < 150,000/µL c. Hemoglobin: i.  Females (sex at birth): < 11.5 grams/dL ii. Males (sex at birth): < 13.0 grams/dL

The psychological health of military members is a critical element of force health protection  and readiness. Frequent deployments and high operations tempo at home strain the  relationships and families of today's military more than ever before (e.g., Karney & Crown,  2007). Since 2001 the likelihood of divorce in the Air Force increased with the number of  days that Airmen were deployed (Karney & Crown, 2007). Distressed relationships not only  adversely affect members' adjustment and readiness (e.g., Hoge et al., 2006) but also are  centrally implicated in suicides (i.e., relationship problems are the precipitating event in  51% of Air Force suicides, Kindt, 2009) and domestic violence (Pan, Neidig, & O'Leary, 1994).  Unfortunately, traditional sources of marriage counseling available to service members are  largely underutilized. The MC brings a fresh perspective that helps normalize relationship  help-seeking and in turn reach larger numbers of distressed couples early. The partnering of  MC and integrated primary care appears to be an ideal combination of behavioral health  innovations that has the potential to measurably enhance relationship health for the military  services. The most challenging community problems faced by senior military leaders are closely linked  to the quality of marriage relationships. These include family violence, spouse maltreatment,  and suicide. Half (51%) of the service members who either completed or attempted suicide from  2008 to 2010 had a history of a failed intimate relationship, and for nearly one-third (30%)  this failure had occurred within 30 days of the self-harm event. Relationship distress not  only affects marriages but is also associated with depression, substance abuse, work role  impairment and lowered children's health. Despite the potential high costs of chronic marital  distress, very few couples seek therapy. In a recent Air Force study, only 6% of Airmen in  distressed relationships reported making use of couple counseling after returning from  deployment. Indeed, distressed couples wait an average of 6 years before seeking help, at  which point their relationship likely has deteriorated dramatically.  Thus, there is a substantial need in the military for early detection and preventative care  for deteriorating couples before serious and irreversible relationship damage has occurred.  There are currently no widely available means to fill this need. Mild-to-moderately  distressed couples may view therapy as reserved for only the most severely distressed  couples, and thus delay seeking treatment until its efficacy is seriously diminished by the  chronicity and severity of the accumulated relationship dysfunction.  The Marriage Checkup (MC) addresses this issue by providing a less-threatening option for  couples to seek early preventative care before they have begun to identify as distressed.  Intended to be the relationship health equivalent of the annual physical or dental checkup,  the MC is a 4 to 5 hour assessment and feedback intervention. This brief intervention  includes assessment of the couple's relationship history, strengths, and concerns and  provides individualized feedback to the couple with a list of options addressing the couple's  primary concerns. Studies conducted with civilian samples have shown that couples receiving  MC demonstrate significant and lasting improvement across a range of marital health  variables. In addition, MC has been shown to attract couples across the distress continuum  and be perceived by couples as more accessible than traditional therapy.  In recognition of the limited reach and potential stigma of tertiary mental health treatment,  the military services and the Department of Veterans Affairs have implemented collaborative  care models in primary care. In a collaborative care model, mental health providers are  embedded into the primary care setting and serve as integrated behavioral health consultants  (IBHCs) to the medical providers. The IBHC provides brief, focused assessments and  interventions for patients referred by their primary care provider. Marital problems are a  common reason for primary care providers to refer patients to IBHCs, yet there has been no  effort toward development of marital interventions suitable for primary care. MC's design as  a brief "check-up" model for marriage help appeared particularly well-suited to primary care.  Therefore, the investigators conducted a pilot study to adapt MC for use with military  couples in Air Force primary care clinics (FWR20120054H).  In our pilot study the original MC was adapted for military couples and fit into the  fast-paced environment of primary care. Military specific content for the assessment tools in  the Marriage Checkup were developed. In addition, the team developed and piloted a protocol  to use when only one member of the couple is available to come in for a Marriage Checkup,  given the likelihood that some partners seeking an MC may have a partner who is currently  deployed or otherwise unable/unwilling to participate in an in-person checkup. Finally, the  Marriage Checkup was streamlined to fit within a Primary Care setting. More specifically, it  was re-formatted into three 30-minute sessions. Session 1 consisted of the couple's  relationship history and each partner's primary strengths, Session 2 focused on each  partner's primary concern, and Session 3 is dedicated to feedback for the couple. IBHCs  working in primary care were then trained to offer the intervention within a  quasi-experimental research design in which pre-post changes were evaluated within subjects.  To date, twenty-two couples and one individual (N = 45; at least one partner in each couple  was active duty) at two primary care sites have completed the MC. A multilevel modeling  analysis indicated statistically significant pre-post changes for all study variables at both  two weeks and two months, with effect sizes in the moderate range. Relationship satisfaction  (B = .54, p = .003, B = .55, p = .004), distress (B = .75, p < .001, B = .58, p = .003) and  intimacy (B = .43, p < .017, B = .47, p = .014) were significantly improved. In addition,  couples completed a questionnaire measuring their level of satisfaction with the MC  intervention itself. The scale ranged from 1(not at all) to 5 (very much), and across the  questions the average response was 4.33 immediately post checkup and 4.05 at the one-month  follow-up, indicating that couples were satisfied with their Marriage Checkup experience. The  results of the pilot study provide preliminary evidence suggesting that the MC can be  effectively adapted to a military population, and successfully used by behavioral health  consultants (BHCs) working in an integrated primary care clinic.  The overall purpose of the proposed study is to build on pilot study findings by conducting a  randomized trial of the military-adapted Marriage Checkup (MC) delivered in primary care by  Integrated Behavioral Health Consultants (IBHCs). The primary outcomes of interest are  marriage health (e.g., greater satisfaction, deeper intimacy) and community reach (e.g.,  attracts couples at-risk for marital deterioration who otherwise would not be seeking  treatment). There are three specific objectives of the study, the first being to conduct a  randomized trial comparing MC for use in military primary care clinics to a wait list control  condition. Second, examine the effects of MC participation on relationship health at one  month and six months post-treatment follow-up. Lastly, to determine whether the MC is  successful at reaching couples at risk for marital deterioration who would otherwise be  unlikely to seek traditional couple counseling.  This study will investigate two research hypotheses. The first hypothesis being that Military  couples who participate in the Marriage Checkup (MC) for primary care will demonstrate  positive relationship health trajectories for intimacy, acceptance, and relationship  satisfaction over the course of six months when compared to couples in a wait-list control  condition. A randomized control trial with 215 civilian couples demonstrated significant  increases in relationship satisfaction, intimacy, and acceptance both in the short term and  at two-year follow-up for treatment couples compared to no-treatment control couples.  Emerging evidence further suggests that the primary mediator of improvements in marital  health is the effect of the MC on increasing the level of intimate connection between  spouses. In addition, the MC worked to affect both distal (i.e., depression) and specific  (i.e., time together, sexual satisfaction and communication) outcomes. The second hypothesis  is that the MC will attract military couples at-risk for marital deterioration who are  otherwise not seeking relationship treatment. The MC is designed to significantly lower the  barriers to couple help seeking. The MC is very brief and is advertised as an informational  marital health service rather than therapy, intended for all couples who are interested in  learning more about their strengths and areas of concern. The MC has been shown to attract a  broad range of couples across the range of satisfaction from relationally satisfied to  severely distressed and has been shown to successfully attract couples who would not  otherwise seek any kind of relationship intervention.  The randomized trial will be conducted at four military primary care clinics. Three sites  will be Wilford Hall Ambulatory Services Center (WHASC) in San Antonio, Texas, 359th Medical  Operations Squadron (359 MDOS) in San Antonio, Texas, and Malcolm Grow Medical Clinics and  Surgery Center (MGMCSC), Joint Base Andrews, in Maryland. The remaining site will be  recommended by the Air Force Chief of Behavioral Health Optimization (co-investigator Maj Liz  Najera).  Individuals and couples who express an interest in participating in the study will be  scheduled by the on-site study coordinator with the IBHC to receive a more thorough  explanation of the study purpose and requirements of participation. Potential participants  will have the opportunity to ask questions about the study prior to making a decision to  participate. Potential participants will be told that the MC involves three appointments with  the IBHC within a four week period and completion of take-home relationship questionnaires to  aid the BHC in assessing their relationship. At the third IBHC appointment the participants  will receive feedback on the clinical questionnaires and interview results and be given a  list of possible strategies for improving their relationship that has been tailored to their  unique situation. For the purposes of the research, potential participants will be informed  that they will be contacted approximately one month and six months later and asked to log  onto a study website to re-complete surveys about their relationship. They will also complete  surveys that ask their opinion of the MC including what they thought was most helpful and how  it could be improved further.  This first contact will also include the standard brief clinical screening conducted by the  IBHC for all referrals. During this screening the IBHC will also assess for the presence of  any study exclusion factors. If at the conclusion of this first IBHC contact the potential  participant expresses interest in participating and meets the inclusion and exclusion  criteria, they will then meet with the Research Assistant to review and complete the informed  consent documents for study participation and the baseline questionnaires.  The study will use a randomized two-group research design in which participants are randomly  assigned after signing the informed consent document to either receive the MC right away or  be placed on a 7-month wait list condition. All participants will complete study measures at  baseline, eight weeks (1 month post-treatment for those assigned first to the MC condition)  and 28 weeks (six months post-treatment for those assigned first to the MC condition).  Participants assigned to the 7-month wait-list condition will be offered the MC at the  completion of the 6-month follow-up measures. Inclusion Criteria:  -  Potential participants will be active duty and/or their active duty or Department of  Defense (DoD) beneficiary spouses (adults >= 18 years old) who present to the IBHC in  primary care with relationship concerns or questions following referral from their  primary care manager or in response to study advertisements. Potential participants  will be eligible for enrollment whether both partners are participating in-person or  only one partner. Study participants do not have to be married; enrollment is open to  active duty or who are not married but in committed romantic partnerships Exclusion Criteria:  primary care behavioral health, i.e., patients greater than mild risk for self-harm,  patients with current alcohol dependence, psychotic disorder, significant dissociative  disorder, or moderate or severe brain injury. Civilians along with potential  participants that cannot understand, speak or read English will be excluded.

The aim of this study is to investigate the effects of intermittent theta burst stimulation  primed with continous theta burst stimulation (cTBS), on top of a standard robot-assisted  training (RAT) on improving the upper limb motor functions of stroke survivors and to explore  potential sensorimotor neuroplasticity with electroencephalography (EEG). Intermittent theta burst stimulation (iTBS) delivered to the affected primary motor cortex  (M1) appears to enhance the brain response to rehabilitative intervention in patients with  stroke. However, its clinical utility is highly affected by the response variability. New  evidence has reported that preceding iTBS with a priming session of continuous theta burst  stimulation (cTBS), may stabilize and even boost the facilitatory effect of iTBS on the  stimulated M1, via metaplasticity. The aim of this study is to investigate the effects of  iTBS primed with cTBS, on top of a standard robot-assisted training (RAT) on improving the  upper limb motor functions of patients with chronic stroke and to explore potential  sensorimotor neuroplasticity with electroencephalography (EEG). A three-arm randomized  controlled trial (RCT) will be performed with an estimated total of 36 patients with subacute  or chronic stroke. All participants will be randomly allocated to receive 10-session  intervention of different TBS protocols (i.e., cTBS+iTBS, sham cTBS+iTBS and sham cTBS+sham  iTBS), delivered for 3-5 sessions per week, lasting for 2-3 weeks. All participants will  receive a 60-minute standard RAT after each stimulation session. Primary outcome will be  Fugl-Meyer Assessment-Upper Extremity scores (FMA-UE). Secondary outcomes will be Action  Research Arm Test (ARAT), kinematic outcomes generated during RAT as well as and EEG. Inclusion Criteria:  -  with a diagnosis of a unilateral ischemic or hemorrhagic stroke;  -  with stroke onset more than 6 months;  -  from 18 to 75 years old;  -  with mild to moderate impairment of upper limb functions due to stroke, measured using  the Hong Kong Version of the Functional Test for the Hemiplegic Upper Extremity  (FTHUE-HK) from level 2 to level 7;  -  be able to understand verbal instruction and follow one-step commands;  -  be able to give informed consent to participate; Exclusion Criteria:  -  any contraindications to rTMS/TBS, such as unstable medical condition, history of  epileptic seizures, metal implants in vivo (eg, pacemaker, artificial cochlear, and  implant brain stimulator), and a history of receiving craniotomy;  -  previous diagnosis of any neurological disease excluding stroke;  -  presence of any sign of cognitive problems (Abbreviated mental test Hong Kong version  < 6/10);  -  patients with extreme spasticity in any hemiplegic upper limb joint (Modified Ashworth  score > 2) or severe pain that hinder the upper limb motor training;  -  with other notable impairment of the upper limb affected by stroke, eg, recent  fracture, severe osteoarthritis, congenital upper limb deformity  -  any sign of anxiety or depression, as assessed by the Hospital Anxiety and Depression  Scale.  -  concurrent participation in an upper limb rehabilitation program or a medicine trial.

Primary Objective:  To demonstrate the vaccine seroresponse sufficiency of meningococcal serogroups A, C, Y, and  W following the administration of a booster dose of meningococcal Polysaccharide (Serogroups  A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine:  -  In Group 1 participants who were first vaccinated with 1 dose of MenACYW Conjugate  vaccine 3-6 years before the booster dose.  -  In Group 2 participants who were first vaccinated with 1 dose of Menveo vaccine  (meningococcal [Groups A, C, Y and W135] Oligosaccharide Diphtheria CRM197 Conjugate  vaccine) 3-6 years before the booster dose.  Secondary Objective:  To describe:  -  The vaccine seroresponse, seroprotection (serum bactericidal assay using human  complement [hSBA] titer greater than or equal to [>=]1:8), and antibody responses  (geometric mean titers [GMTs]) of meningococcal serogroups A, C, Y, and W measured using  hSBA in serum specimens collected 6 days (±1 day) after vaccination in a subset of 50  participants per group (Groups 1 and 2).  -  The vaccine seroresponse, seroprotection (hSBA titer >=1:8), and antibody responses  (GMTs) to serogroups A, C, Y, and W measured using hSBA on Day (D)0 (pre-vaccination)  and D30 (+14 days) after vaccination with MenACYW Conjugate vaccine alone (Groups 1 and  2).  -  The antibody persistence (GMTs and vaccine seroprotection; hSBA titer >=1:8) of  meningococcal serogroups A, C, Y, and W before a booster dose in participants who  received either MenACYW Conjugate vaccine or Menveo vaccine 3-6 years earlier.  -  The antibody persistence (GMTs and vaccine seroprotection; hSBA titer >=1:8) of  meningococcal serogroups A, C, Y, and W in participants who received either a single  dose MenACYW Conjugate vaccine (participants randomized to MET59 Groups 1, 3, and 4) or  Menveo vaccine (participants assigned to MET59 Group 2), as part of study MET50, or  MET43 (participants randomized to MET59 Groups 1, 3 and 4).  -  To describe the vaccine seroresponse, seroprotection (hSBA titer >=1:8), and antibody  responses (GMTs) to the antigens present in MenACYW Conjugate vaccine, when MenACYW  Conjugate vaccine was given concomitantly with meningococcal serogroup B (MenB) vaccine  (Groups 3 and 4), compared to those when it was given alone (Group 1). Study duration per participant was approximately 6 months including: 1 day of screening and  vaccination, 1 or 2 additional visits at Day 6 and Day 30, 2 phone calls and a safety  follow-up/end of study visit, at Day 8 and Day 180 after vaccine administration,  respectively.  Safety assessment included solicited reactions within 7 days after vaccination, unsolicited  adverse events (AEs) up to 30 days after vaccination, serious adverse events (SAEs)  throughout the study. Inclusion Criteria:  -  Aged >= 13 to less than (<) 26 years on the day of inclusion.  -  Participants participated in and completed study MET50 (MET50 Groups 1, 2, or 3 only)  or study MET43 (MET43 Groups 1, 2, or 3 only).  -  For MET59 Group 2 only (Menveo vaccine-primed participants only; enrichment  population): participants had a documented record of having received 1 dose of Menveo  vaccine 3-6 years earlier either as part of a clinical trial or as routine  vaccination. Participants who participated in MET50 Group 4 can be enrolled if they  fulfill this criterion.  -  Participants aged 13 to < 18 years: assent form had been signed and dated by the  participant and informed consent form (ICF) had been signed and dated by the parent or  guardian.  -  Participants aged >=18 (or legal age of majority, if different from 18 years of age)  to < 26 years: ICF had been signed and dated by the participants.  -  Participant aged 13 to < 18 years: both the participant and parent or guardian were  able to attend all scheduled visits and complied with all trial procedures.  -  Participants aged >=18 (or legal age of majority, if different from 18 years of age)  to < 26 years: able to attend all scheduled visits and complied with all trial  procedures. Exclusion Criteria:  -  Participant was pregnant, or lactating, or of childbearing potential and not using an  effective method of contraception or abstinence from at least 4 weeks prior to the  first vaccination until at least 4 weeks after the last vaccination. To be considered  of non-childbearing potential, a female must be pre-menarche, or post-menopausal for  at least 1 year, or surgically sterile.  -  Participation in the 4 weeks preceding the trial vaccination or planned participation  during the present trial period in another clinical trial investigating a vaccine,  drug, medical device, or medical procedure.  -  Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or  planned receipt of any vaccine before Visit 3 (Day 30) except for influenza  vaccination, which might be received at least 2 weeks before study investigational  vaccine.  -  Receipt of immune globulins, blood or blood-derived products in the past 3 months.  -  Receipt of any meningococcal vaccine including a licensed or investigational MenACWY  vaccine or MenB vaccine since participation in study MET50 or MET43.  -  Menveo vaccine-primed participants only (enrichment group for Group 2): receipt of  more than 1 dose of Menveo vaccine or vaccination with another licensed or  investigational MenACWY vaccine or with a licensed or investigational MenB vaccine.  -  Known or suspected congenital or acquired immunodeficiency; or receipt of  immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy,  within the preceding 6 months; or long-term systemic corticosteroid therapy  (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).  -  History of meningococcal infection, confirmed either clinically, serologically, or  microbiologically.  -  At high risk for meningococcal infection during the trial (specifically but not  limited to participants with persistent complement deficiency, with anatomic or  functional asplenia, or participants travelling to countries with high endemic or  epidemic disease).  -  Known systemic hypersensitivity to any of the vaccine components, or history of a  life-threatening reaction to the vaccines used in the trial or to a vaccine containing  any of the same substances.  -  Personal history of Guillain-Barré syndrome.  -  Personal history of an Arthus-like reaction after vaccination with a tetanus  toxoid-containing vaccine within at least 10 years of the proposed study vaccination.  -  Verbal report of thrombocytopenia, contraindicating IM vaccination.  -  Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion,  contraindicating IM vaccination.  -  Current alcohol abuse or drug addiction.  -  Chronic illness (e.g., Human immunodeficiency viruses, hepatitis B, hepatitis C) that,  in the opinion of the investigator, was at a stage where it might interfere with trial  conduct or completion.  -  Moderate or severe acute illness/infection (according to investigator judgment) on the  day of vaccination or febrile illness (temperature >= 100.4 degree Fahrenheit). A  prospective participant should not be included in the study until the condition had  resolved or the febrile event had subsided.  -  Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first  blood draw.  -  Identified as an Investigator or employee of the Investigator or study center with  direct involvement in the proposed study, or identified as an immediate family member  (i.e, parent, spouse, natural or adopted child) of the Investigator or employee with  direct involvement in the proposed study.  The above information was not intended to contain all considerations relevant to a  participant's potential participation in a clinical trial.

Adequate nutritional support is an essential element for achieving favourable outcomes in  critically ill patients. Therefore, an accurate determination of patients' energy needs is  required to optimize nutritional support and reduce the harmful effects of under- and  over-feeding. Currently, indirect calorimetry is considered as a gold standard for measuring  energy expenditure during critical illness.  This randomized study aims to investigate the impact of indirect calorimetry guided nutrition  therapy on clinical outcomes such as ICU. Mortality, hospital mortality, duration of  mechanical ventilation, length of I.C.U./hospital stay and mascle wasting. The investigators  hypothesis that nutrition therapy guided by IC will improve clinical outcomes in severely ill  patients This is a single-blind randomized control study. Eligible participants are randomly assigned  within 24 hrs of ICU. admission in two groups  -  Intervention group: The calorie needs will be determined by indirect calorimetry.  -  Control group: a routine standard weight-based equation (20-25kcal/kg ideal body  weight/day) will be used to estimate the energy requirements of critically ill patients.  Daily energy and protein data will be recorded for a maximum of 12 evaluable days  (nutritional days) or until death or discharge from ICU.while outcome data will be collected  for a maximum of 28 days. Inclusion Criteria:  -  Adult patients aged over 18 years old  -  Critically ill patients with me ical ventilation  -  Expected to have an ICU. stay of more than (3) days Exclusion Criteria:  -  Requirement for inspired oxygen content (FiO2) greater than 0.6  -  Patients on high-frequency ventilation  -  Patients with chest tubes that leak air/ Bronchopleural fistula  -  Patients with incompetent tracheal cuff  -  Patients inhaled nitric oxide therapy  -  Patients receiving continuous renal replacement therapy (CRRT) during IC measurement  -  Patients with pregnancy  -  Patients with burn injury  -  Patients infected with human immunodeficiency virus (HIV)  -  Patients with severe liver disease (Child-Pugh score C)  -  seizure activity  -  patients suffering from significant head trauma (GCS <8)  -  Patients with paraplegia and quadriplegia

This study is a longitudinal and prospective study of the natural history of infantile  neuroaxonal dystrophy (INAD). After obtaining informed consent, the study participants' relevant medical records will be  collected and reviewed for this study. Next, a clinic visit will be scheduled with the  patient's family and an observing MD/DO/MBBS from a sponsor site to confirm and clarify  information in the medical records.  A baseline evaluation of clinical status will also be performed during this visit to serve as  visit one in this longitudinal, prospective natural history study. Subsequent visits will  take place every 6 months, for up to 24 months. Key components of this prospective study at  each visit include a neurodevelopment exam tailored for INAD, application of the CHOP-INTEND  neurodevelopment scale, the Hammersmith infant neurological examination and the modified  Ashworth spasticity scale as well as collection of monthly parental severity scoring and  monthly home videos of activities of daily living (ADLs).  Data from this study will be pooled and presented in aggregate, without identification of  individual subjects. Inclusion Criteria:  -  Male or female 18 months to 10 years of age  -  Medical history consistent with the symptoms of classic INAD (onset of symptoms  between the ages of 6 months and 3 years)  -  Homozygous or compound heterozygous PLA2G6 variants  -  Signed informed consent form (ICF) prior to entry into the registry Exclusion Criteria:  -  Diagnosis of atypical NAD (ANAD)  -  Additional underlying diagnosis with features that overlap with INAD  -  Unwilling or unable to allow medical record review  -  Unwilling or unable to participate in serial assessments every 6 months (including  deceased patients)

Contraception among women in France has evolved considerably and has become a frequent reason  for consultation in general practice in view of the growing shortage of gynaecologists  practising in towns.  Intrauterine devices (IUDs) are the leading reversible contraceptive method used in the  world, but only 20.7% of women in France were using them in 2010.  In practice, in France, use of the IUD is still "reserved" for older women or those who have  already had children, despite medical recommendations.  In this study the investigator will investigate whether clear information about the mode of  action and insertion/withdrawal of IUDs would dispel these misconceptions of patients. Contraception among women in France has evolved considerably and has become a frequent reason  for consultation in general practice in view of the growing shortage of gynaecologists  practising in towns.  Intrauterine devices (IUDs) are the leading reversible contraceptive method used in the  world, but only 20.7% of women in France were using them in 2010.  In practice in France, the use of IUDs is still "reserved" for older women or those who have  already had children, despite medical recommendations. Indeed, there is a certain feeling of  mistrust towards the IUD as a contraceptive method. Sometimes the patient's reasons for  refusal were unclear or misconceptions and prejudices prevailed.  Various research studies and theses have identified the various obstacles to the use of the  IUD as a contraceptive. Today it would be interesting to evaluate whether a short  presentation of the IUD during a consultation would lead to a better acceptance of women to  use it as a possible contraceptive method.  In this study the investigators will investigate whether clear information about the mode of  action and insertion/removal of IUDs would dispel these misconceptions of patients. Inclusion Criteria:  -  Any woman aged 18 years and over who comes to a family planning centre  -  Having expressed her free and informed written consent  -  Affiliated to a social security scheme Exclusion Criteria:  -  Women under 18 years of age  -  Woman with an IUD  -  Woman who has had an IUD before  -  Woman whose reason for consultation of the day is the insertion of an IUD  -  Menopausal woman  -  Woman who is infertile for any reason  -  Illiterate woman or woman who does not read French  -  Refusal to participate in the protocol  -  Incapable of age.  -  Pregnant or breastfeeding women  -  Vulnerable persons and protected persons as provided for in the Public Health Code  Public Health Code (articles L. 1121-5 to L.1121-8 and L.1122-1-2).

The study design is an observational, longitudinal study with data collected online via a  computer-assisted survey. Subjects will be recruited through non-probability snowball  sampling.  Objectives:  1. to document the prevalence of injuries and medical complications arising from kink  activities  2. to document how healthcare is utilized by kink-involved people  3. to document the health outcomes particular to a large sample of kink-involved people  4. to test whether the centrality of kink identity and degree of community belongingness  affect injuries, health outcomes, and healthcare utilization In 2016, TASHRA conducted the first ever health survey of the U.S. kink community, examining  issues of injuries, risky behavior, health status, and healthcare access and utilization, and  patient satisfaction. It included measures of kink identity centrality, coming out, and kink  community involvement as predictive factors.  The findings provided a broad map of possible health disparities in a manner that was  intended to direct future research. As such, several included measures did not ask any  further questions to collect more detail of the context of health disparities or injuries, or  their impact on the participant.  The 2016 Kink Health Survey was an anonymous online survey that collected data from  kink-involved people, from April 2016 to October 2016 (six month window). 1,118 individuals  completed the survey. The results indicated the following (Sprott, Randall, Smith & Woo,  2021):  -  The percentage of people who reported past experiences of kink-related injury : 13.5%  -  The percentage of people who reported delaying or avoiding healthcare because of  perceived stigma: 19.0%.  -  Past negative experiences with healthcare clinicians increased the odds of delaying or  avoiding care significantly, with those participants four times more likely to  avoid/delay care compared to participants who did not have negative experiences.  -  A significant portion of participants had not disclosed their kink identity or behavior  with their physical healthcare clinician (58.3%), nor with their therapist or mental  healthcare clinician (49.6%).  The following health disparities were noted:  -  4.1% of the sample reported being HIV positive. This is approximately 10x the national  average.  -  24% reported having attempted suicide at some point in their lives. This is  approximately 5x the national average.  -  17.98% reported having PTSD. This is 2.6x the national average.  The current proposal, the International Kink Health Survey, proposes to follow up and expand  on the previous 2016 survey in the following ways:  -  to expand the collection of data beyond the United States, to other English-speaking  populations  -  to clarify the timing of health status measures and health disparities in relation to  the initiation of kink activities  -  to expand measures of stigma and discrimination, paying closer attention to questions of  multiple minority status and intersectionality, and their relation to health status and  health disparities  -  to collect more in-depth information on kink community involvement, paying attention to  online activities as part of community involvement in light of the COVID-19 pandemic  -  to collect more fine-grained information about injuries or medical complications that  arise from engagement in kink scenes/activities  -  To collect more fine-grained information about suicidal behavior, mental health  hospitalizations, and peoples' perceptions of the role of kink in relation to these  mental health challenges  -  to measure future intentions to disclose kink involvement to healthcare providers  The current proposed study will also address asexual people who engage in kink/BDSM behaviors  (bondage, sadomasochism, and power exchange). The 2016 Kink Health Survey included this  sexual orientation group, and we will continue to address this group.  The study design is an observational, longitudinal study with data collected online via a  computer-assisted survey. Subjects will be recruited through non-probability snowball  sampling. Interested individuals will initially be screened for inclusion criteria. All  completed questionnaires will be reviewed to ascertain whether inclusion criteria are met or  exclusion criteria are met. Those who meet the inclusion criteria will be sent a message  asking them to read and sign the Informed Consent form if they wish to enroll in the study.  Those who meet the exclusion criteria or who do not complete an Informed Consent form after 3  contacts will have their information on the screening questionnaire in Ripple de-identified.  In order to characterize the prescreening sample for reporting purposes, the de-identified  data will be retained and may be analyzed. If they provide their consent, prospective  participants will be considered enrolled in the study and will be sent email invitations to  fill out survey instrument 1, and then every week sent an email to fill out survey instrument  2, and so on, as appropriate.  IKHS Survey Instrument 1:  Demographics Kink Behaviors Kink Fantasies Kink/Sexual Desire  IKHS Survey Instrument 2:  Future Disclosure COVID  IKHS Survey Instrument 3:  Kink Injury  IKHS Survey Instrument 4:  Physical Health  IKHS Survey Instrument 5:  Mental Health  IKHS Survey Instrument 6:  Healthcare Utilization  IKHS Survey Instrument 7:  Sex Work Consent Violations Kink and Past Trauma Stigma Family Support Sexual Shame and Pride  Scale  IKHS Survey Instrument 8:  Adverse Childhood Events / Sensation-Seeking Alcohol / Drug Inclusion Criteria:  1. Successful completion of screening checklist to indicate one of the following  conditions:  1. recurring, long-standing fantasies that focus on kink, in areas such as: power  exchange (Dominant/submissive roles), bondage, sadomasochism, or fetish  activities. By fetish, we mean a type of sexual desire in which gratification  depends on or is significantly increased by particular objects, clothing items,  parts of the body, or types of persons.  2. OR currently engaging, or have engaged in the past, in consensual kink activities  such as power exchange (Dominant/submissive roles), bondage, sadomasochism, or  fetish activities.  2. Age of majority in the legal jurisdiction (geographic location) where the survey is  taken (usually age 18)  3. English-language proficiency sufficient to understand the study instruments  4. Completion of an electronically signed and dated informed consent form Exclusion Criteria:  People who respond "no" to the following question on the screening checklist  -  I am familiar with the importance of consent and I endorse negotiation and safe words  or safe signals in my sexual or kink play  -  Clearly fraudulent use of the internet survey, such as: evidence of non-human data  entry via an internet "bot", duplicative or prank data entry that entails  contradictory or clearly fraudulent data.  -  Any condition that, in the professional judgement of the Principal Investigator,  should exclude an individual from participation in the study.

Dry eye disease (DED) in less severe forms are very common, and should ideally be treated  outside hospitals, eg., through primary care services and exploiting holistic therapies such  as traditional medicine. This will keep the care affordable and accessible despite a large  burden of care.  Postmenopausal women, compared to others in the population, have a higher incidence of DED.  Large-scale epidemiological studies done in the United States have shown that the rate of DED  in women over 50 years old is nearly double that in men over 50, at 7% and 4%, respectively.  Studies have demonstrated that there is a hormonal etiology behind this group's  susceptibility to DED, although the precise hormonal imbalance and mechanistic pathway for  DED are still unclear.  A significant number of women seen at the dry eye clinic are post-menopausal, and very  symptomatic, though many do not have the corneal epitheliopathy evidenced by dye staining.  Such patients are not likely to benefit from conventional prescription drugs for dry eye,  such as cyclosporine and corticosteroids. Hormonal replacement therapy for menopausal women  has not been universally accepted, and there may be an increased risk of carcinomas, on the  other hand, topical hormonal therapy for dry eye is not widely available, and still  controversial, so there is a definite unmet need for new therapeutic modalities to treat dry  eye in post-menopausal women.  Traditional Chinese Medicine (TCM) is a form of complementary medicine that aims to treat yin  or yang deficiency syndromes, using modalities like herbs, acupuncture or moxibustion.  Menopause in women, particularly in Asia, has been linked to yin-deficiency, in one study,  73% of Chinese post-menopausal women suffered from kidney yin-deficiency. A review of  randomized controlled trials of TCM treatment showed that certain modalities like soy and  phytoestrogens have been useful in the treatment of syndromes in menopause, such as hot  flushes. The overall hypothesis is that the Traditional Chinese Medicine (TCM) modality of a specific  herbal formulation can improve the symptoms and signs of post-menopausal dry eye in women,  and objectively, these improvements are associated with improvement of dry eye symptoms, and  alteration of levels of tear eicosanoids or cytokines.  TCM in the treatment of dry eye A meta-analysis of TCM in treatment of Sjogren's syndrome  showed that TCM is promising but there were some flaws in the studies reviewed.  Jiang et al, in particular has found that mistletoe, in combination with  carboxymethylcellulose eyedrops were effective in reducing dry eye symptoms and signs,  compared to normal saline eyedrops, in post-menopausal women.Unfortunately, the authors did  not compare the effect of this combination with carboxymetholycellulose eyedrops, a commonly  used artificial tear, per se.  In postmenopausal women, dry eye is not only more common, but the symptoms may be  confused/related to mood changes like depression and anxiety, and sleep disorders, all of  which were linked to the post-menopausal state, where there may be yin deficiency.  Recently the investigators found acupuncture to be useful in the treatment of elderly people  with lung-kidney yin-deficiency type of dry eye in Singapore. In addition, TCM Practitioners  in Singapore were interested in the treatment of dry eye. However, no study has evaluated the  use of TCM herbs in peri-menopausal patients with dry eye in robust way.  Previous studies by the senior TCM collaborator, Prof Wei QP has concluded that steaming  treatment by (Wei's Qi Ju Gan Lu Formula) combined with sodium hyaluronate eye drops could  improve the objective indexes like TBUT and corneal staining as well as subjective symptoms  in peri-menopausal patients with aqueous tear deficiency dry eye of liver and kidney  deficiency. Prof Wei has also studied treatment of dry eye through oral medication (with the  method of strengthening the water element to nourish wood element under the TCM perspective)  combined with artificial tears, and concluded that the prescription can effectively treat dry  eyes by promoting the tear secretion and prolonging BUT. Recently, the investigators have  also discovered that herbal medication have a trend to lower the tear levels of inflammatory  proteins (journal under review). Hence, this current study intends to follow-up with the  effectiveness of oral medication of (Wei's Qi Ju Gan Lu Formula) for patients suffering from  peri/ post-menopausal dry eye disease of the "Liver-Kidney yin deficiency" pattern  differentiation.  1.1.1 Rationale for the Study Purpose Clinical significance Traditional Chinese Medicine  (TCM), when combined with psychotherapy, has been shown to be effective in targeting  yin-deficiency in the treatment of menopause, although the effect of such treatment on dry  eye symptoms has not been specifically investigated.  If TCM is effective in the treatment of post-menopausal women, it can be implemented at the  primary care level, so relieving the specialist centers of this type of patients, thereby  saving health-care costs. Inclusion Criteria:  1. Age 40-79 years old women  2. Peri and Post-menopausal women  3. Chief complaint of participant should be consistent with dry eye symptoms based on  SPEED Questionnaire, with a score of > 6 (Appendix 5)  4. History of presenting TCM score symptoms:  4.1. TCM dry eye assessment score (Appendix 3) The pattern deviation can be determined  if 3 or more main symptoms are present (one of which is a localized eye symptom and  one of which is a system symptom), together with at least one accompanying symptom.  4.2 Liver-Kidney yin deficiency assessment score (Appendix 4) This form is to  determine the extent of Liver-Kidney Yin Deficiency (assessed at SCHMI).  Any score<14 will not satisfy the criterion for Liver Kidney Yin Deficiency and will  not be recruited. This detailed TCM score will also be a secondary outcome measure in  the analysis of pre/post herbal treatment (see below).  5. Clinical signs:  5.1. Tear break up time (TBUT) ≤10s or Schirmer I test ≤10mm/5 mins  6. Normal renal and liver function at baseline, i.e., all parameters within the reference  value Exclusion Criteria:  1. Currently or intention to use hormonal therapy (eg. cancer patients who is on  tamoxifen)  2. Currently pregnant or breastfeeding  3. Hysterectomy procedure done previously  4. Removal of cysts or polyp procedure done previously  5. Requirement to wear contact lens, and having worn such lenses in week preceding  eligibility  6. Glaucoma, significant cataract, age related macular degeneration or other ophthalmic  disease, eg. Extraocular muscle palsies, facial paralysis, ectropion, entropion,  trichiasis  7. Requirement of any eyedrops other than artificial tears.  8. Previous eye surgeries including LASIK (within 6 months) or punctal plugs in-situ  9. Autoimmune systemic diseases: Steven-Johnson syndrome, Sjogren's syndrome, Rheumatoid  Arthritis, Lupus  10. Systemic disease requiring regular medication (except hypertension and lipidemia)

Evidence support that pathogenic bacteria are not only responsible for periodontal  destruction but also contributes to systemic inflammatory burden either directly or  indirectly through increase in pro-inflammatory cytokines. Scaling and root planing (SRP)  with or without local antibiotics contributes to reduced systemic inflammation. However,  studies also reported insignificant changes in systemic inflammation after SRP. It may be due  to incomplete control of periodontal inflammation. Systemic antibiotics proves to beneficial  in treatment of severe periodontitis. Systemic antibiotics along with SRP results in  improvement of vascular health and systemic inflammation. However, till date no study has  been done to evaluate the role of systemic antibiotics as an adjunct to SRP on systemic  inflammatory markers. In this randomized control study impact of adjunctive use of systemic  antibiotics along with SRP on systemic inflammation would be assessed in periodontitis  patients. Periodontitis is characterized by microbially-associated, host-mediated inflammation that  results in loss of periodontal attachment. Periodontal bacteria possess a plethora of  virulence factors that induce cells to produce inflammatory mediators at the gingival level.  Periodontitis is associated with bacteraemia that arises from perturbation of ulcerated  periodontal tissues by simple acts of tooth brushing, eating and also during periodontal  interventions disseminating whole bacteria and their products and toxins such as LPS.  Virulence factors and bacteria itself interact with the host immune system and initiate  inflammatory responses.  Moreover, bacteria may persist at distal sites disseminating virulence factors that act as  soluble antigens thereby provocation leucocytes, endothelial cells and hepatocytes to respond  to bacteria/virulence factors with secretion of pro-inflammatory immune mediators [cytokines,  chemokines, C-reactive protein (CRP)]. With continued exposure, soluble antigens react with  circulating specific antibody to form immune complexes that further amplify inflammation at  sites of deposition.  In industrialized countries, approximately 50% of the adult population suffers from moderate  or severe periodontitis. Basic periodontal therapy usually comprises mechanical debridement  of the teeth. It is the disruption of biofilm, followed by lifelong maintenance therapy.  Traditional periodontal therapy involves elimination of periodontopathogens by mechanical  debridement, such as scaling and root planing (SRP) and surgical procedures in conjunction  with proper plaque control.  Because of the infective nature of periodontitis, pharmacologic agents have been advocated as  adjuncts in the non-surgical treatment of periodontal infection. The rationale for the  adjunctive use of antibiotics is to exert an antimicrobial effect at sites inaccessible to  mechanical therapy, and possibly to suppress periodontal pathogens. Moreover, absence of  specific periodontal pathogens seems to have a negative predictive value for further  attachment loss. Therefore, one objective of periodontal treatment might be to suppress or  eliminate certain subgingival periodontal pathogens. Adjunctive antibiotics have been  suggested to improve treatment outcomes in patients with severe chronic periodontitis and  aggressive periodontitis.  Because of amoxicillin and metronidazole's proven ability to suppress periodontal pathogens,  such as A. actinomycetemcomitans and black pigmented bacteria from periodontitis lesions and  other oral sites, it is the first choice of many clinicians, especially for the treatment of  advanced A. actinomycetemcomitans-associated periodontitis. These pathogenic bacteria are not  only restricted to oral cavity, but are associated with disease implication in other parts of  the body.  Evidence support that pathogenic bacteria are not only responsible for periodontal  destruction but also contributes to systemic inflammatory burden either directly or  indirectly through increase in pro-inflammatory cytokines. Scaling and root planing with or  without local antibiotics contributes to reduced systemic inflammation. However, studies also  reported insignificant changes in systemic inflammation after SRP. It may be due to  incomplete control of periodontal inflammation. Systemic antibiotics proves to beneficial in  treatment of severe periodontitis. Systemic antibiotics along with scaling and root planing  results in improvement of vascular health and systemic inflammation. However, till date no  study has been done to evaluate the role of systemic antibiotics as an adjunct to scaling and  root planing on systemic inflammatory markers.  In this randomized controlled clinical trial, impact of adjunctive use of systemic  antibiotics along with scaling and root planing on systemic inflammation would be assessed in  periodontitis patients.  Material and methods:  The present randomized clinical trial will be conducted in Department of Periodontics and  Oral Implantology, Post Graduate Institute of Dental Sciences, Rohtak. The study protocol is  according to the ethical standards of Helsinki Declaration 1975 as revised in 2013.  Study population:  Periodontally healthy individuals (PH) and stage III periodontitis patients of age 35-45  years will be recruited from outpatient department of Periodontics and Oral Implantology. The  patients will be enrolled after obtaining an informed consent.  Experimental design: This randomized clinical trial consists of two parallel groups based  intervention in periodontitis patients:  Periodontal parameters:  At baseline, periodontal parameters plaque index (PI), gingival index (GI), bleeding on  probing (BOP), probing pocket depth (PPD), clinical attachment loss (CAL) will be assessed at  six sites (disto-buccal, mid-buccal, mesio-buccal, mesio-lingual, mid-lingual and  disto-lingual) per tooth excluding third molars in all groups. Periodontal inflamed surface  area (PISA) will then be calculated. Periodontal examination would again be done during  recall visit after 2nd month in test group (TG) and control group (CG).  Periodontal therapy:  After recording periodontal parameters at baseline, oral hygiene instructions would be given  and scaling and root planing (SRP) would be done in both treatment groups (TG and CG). TG  will be given amoxicillin and metronidazole, 500mg and 400mg respectively (AMX+MTZ) to be  taken thrice daily for 7 days. Patients will inform about any self-perceived side-effects of  the medications. Any adverse effects from antibiotic intake and compliance, as reported by  patients, will be recorded throughout the study period. TG and CG would be recalled after  1stand 2nd month of SRP. At recall visit after 1 month, oral hygiene instructions will be  re-enforced and supportive periodontal therapy would be provided.  Blood collection and serum analysis:  For assessing markers of systemic inflammation, serum samples will be collected from  venipuncture in antecubital fossa after an overnight fasting.  Serum samples would be analyzed for systemic markers at baseline and after 2 months of  periodontal treatment in TG and CG.  Parameter of systemic inflammation that would be assessed:  • High sensitive C-reactive protein (hs CRP)  Blood parameters that would be assessed: Total leukocyte count(TLC), differential leukocyte  count (DLC), neutrophil lymphocyte ratio, platelet count, mean platelet volume (MPV),  platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), red blood cell count  (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular  hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution  width (RDW)  Blood parameters that would be assessed: triglyceride (TG), total cholesterol (TC),  low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), very  low-density lipoprotein cholesterol (VLDL)  Anthropometric parameter that would be measured: Body Mass Index (BMI) calculated as  weight/height2 (Kg/m2) at baseline. Inclusion Criteria:  -  • Systemically healthy individuals  -  Presence of at least 20 teeth excluding third molars.  -  PH individuals defined as <10% bleeding sites with probing depths ≤3mm.  -  Periodontitis criteria:  Stage III periodontitis with ≥30% teeth involved and bleeding on probing with >30% sites  involved. Exclusion Criteria:  -  Confirmed or assumed allergies or hypersensitivity reactions to amoxicillin and/or  metronidazole.  -  Alcohol consumers.  -  History of systemic medication affecting the periodontal conditions, e.g. steroids,  immune suppressants, antibiotics, anti-inflammatory drugs, statins, lipid lowering  drugs, anti-convulsants, anti-coagulants, anti-hypertensives or any other host  modulatory drugs within 6 months of commencing the study.  -  Had received any periodontal treatment in the previous 12 months.  -  Undergoing or require an extensive dental or orthodontic treatment.  -  Pregnant or breastfeeding women.  -  Current or former users of tobacco in any form.

Curative management of locally resectable invasive adenocarcinomas located in the cephalic  region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a  pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major  surgery that often leads to major complications including approximately 20% of relevant  clinical postoperative pancreatic fistula.  Postoperative complications following pancreaticoduodenectomy can lead to early  discontinuation of the complete oncologic strategy, i.e., chemotherapy for malignancy is  performed in only about a third of patients who experienced a grade C fistula.  A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that  involves the complete and definitive resection of all pancreatic tissue, eliminating any risk  of postoperative pancreatic fistula but is associated with unavoidable endocrine  insufficiency and potentially severe metabolic complications, such as "brittle diabetes".  Total Pancreatectomy following by intraportal Islet AutoTransplantation (TPIAT) can prevent  "brittle diabetes" and improve the quality of life. The endocrine islets can be isolated from  the pancreatic surgical specimen with standardized procedures and transplanted in the liver  through intraportal infusion, in absence of immunosuppression and allow adequate control of  glucose metabolism with a reduced need for exogenous insulin and an effective graft function  in 70% of cases at 3 years Thereby, the investigators hypothesize that total pancreatectomy  with intraportal Islet autotransplantation rather than classical pancreaticuduodenectomy, in  patients with high-risk of postoperative fistula will increase the rate of complete access to  adjuvant chemotherapy, while maintaining an adequate metabolic control. Curative management of locally resectable invasive adenocarcinomas located in the cephalic  region of the pancreas (pancreas, duodenum and ampulla of Vater) requires a  pancreaticoduodenectomy followed by adjuvant chemotherapy. Pancreaticoduodenectomy is a major  surgery that often leads to major complications including approximately 20% of relevant  clinical postoperative pancreatic fistula. Severe postoperative pancreatic fistulas (grade C)  require reoperation or lead to organ failure and/or mortality. In an extensive international  registry study of pancreaticoduodenectomy procedures, chemotherapy for malignancy was  performed in only about 33% (on time in 7% and delayed in 25.6 % of patients) and never  delivered in about 67,4 % of patients who experienced a grade C fistula. Therefore,  postoperative complications following pancreaticoduodenectomy can lead to early  discontinuation of the complete oncologic strategy.  A total pancreatectomy rather than a pancreaticoduodenectomy is an alternative procedure that  involves the complete and definitive resection of all pancreatic tissue, eliminating any risk  of postoperative pancreatic fistula.  Total pancreatectomy could represent a major shift in the surgical management of patients  with a high-risk of postoperative fistula by eliminating the life-threatening risk associated  with fistula and by increasing the opportunity to initiate and to complete adjuvant  chemotherapy without delay.  However, total pancreatectomy is associated with unavoidable endocrine insufficiency and  potentially severe metabolic complications, such as "brittle diabetes".  Total Pancreatectomy with intraportal Islet AutoTransplantation (TPIAT) is currently  performed in patients with chronic pancreatitis under chronic pain failing endoscopic  treatment and dependent on long-term opioid treatment.  Therefore, islet autotransplantation following total pancreatectomy can prevent "brittle  diabetes" and improve the quality of life.  The endocrine islets can be isolated from the pancreatic surgical specimen with standardized  procedures and transplanted in the liver through intraportal infusion, in absence of  immunosuppression and allow adequate control of glucose metabolism with a reduced need for  exogenous insulin and an effective graft function in 70% of cases at 3 years  Thereby, the investigators hypothesize that total pancreatectomy with intraportal Islet  autotransplantation rather than classical pancreaticuduodenectomy, in patients with high-risk  of postoperative fistula will increase the rate of complete access to adjuvant chemotherapy,  while maintaining an adequate metabolic control. Inclusion Criteria:  confirmation to plan an exit of the protocol if the pancreas does not finally appear with a  high-risk of CR-POPF.  -  Age ≥ 18 years  -  Locale resectable invasive adenocarcinomas located in the cephalic region of the  pancreas documented by endoscopic ultrasonography with fine-needle aspiration biopsy  -  pancreatic adenocarcinoma;  -  duodenal adenocarcinoma;  -  ampullary adenocarcinoma;  -  and IPMNs with adenocarcinoma degeneration;  -  A potentially curative strategy with primary tumor resection approved by a  multidisciplinary expert team  -  A high-risk of CR-POPF  1. Suspected during preoperative evaluation by the presence of 2 or more of the  following criteria (screening criteria of inclusion) : sex male;an obesity (BMI ≥  30 kg/m2);a main pancreatic duct diameter ≤ 3 mm on preoperative endoscopic  ultrasonography a visceral obesity (i.e. a visceral fat area > 84 cm2) ; a  sarcopenia (i.e. a skeletal muscle index < 43 cm2/m2 in men with a BMI of <25  kg/m2 or <53 cm2/m2 in men with a BMI of ≥25 kg2/m2, and <41 cm2/m2 in women)  2. and validated during intraoperative evaluation (finale inclusion) by a  probability score above or equal to 20% on the validated updated alternative  Fistula Risk Score ua-FRS for pancreaticoduodenectomy (ua-FRS) based of pancreas  texture, duct size, BMI, sex .  -  Women of childbearing potential should only be included after a confirmed menstrual  period, and a negative highly sensitive urine or serum pregnancy test and must agree  to be subjected to a monthly pregnancy test (urine or blood) until the end of the  relevant systemic exposure to chemotherapy agents, in accordance with current CTFG  recommendations (Recommendations related to contraception and pregnancy testing in  clinical trials);  -  Women of child-bearing potential and male subjects must agree to use a birth control  methods which may be considered as highly effective (failure rate of less than 1% per  year ) as recommended by the CTFG (Cinical Trials Facilitation and Coordination Group,  version 1.1). These recommandations related to contraception and pregnancy testing in  clinical trials suggested such method (see below) that will be use during chemotherapy  exposure for included women of child-bearing potential and woman of child-bearing  potential when partner of included male : combined (estrogen and progestogen  containing) hormonal contraception associated with inhibition of ovulation (oral,  intravaginal or transdermal) ; progestogen-only hormonal contraception associated with  inhibition of ovulation (oral, injectable or implantable) ; intrauterine device (IUD)  ; intrauterine hormone-releasing system ( IUS) ; bilateral tubal occlusion;  vasectomised partner ;sexual abstinence For included male partner of a women of  child-bearing potential, contraception with condom.  Contraception will be perform during the relevant systemic exposure to chemotherapy agents  and will be extended by 6 months for women of childbearing potential and by 1 month for men  included as recommended by the CTFG  -  Patient covered by a health insurance system  -  Patient who provides a written informed consent to participate to the study Exclusion Criteria:  -  Patient will be screened and excluded if they present a preoperative diabetes defined  by a stimulated C-peptide < 0.5 ng/mL relative to blood glucose > 2 g/dL, at 2 hours  in post prandial  -  Patients with a known or highly suspected genetic syndrome associated with a risk of  pancreatic adenocarcinoma: familial pancreatic cancer, multiple familial melanoma,  Peutz-Jeghers syndrome, hereditary chronic pancreatitis, cystic fibrosis, familial  breast Ovarian Cancer, Lynch syndrome, adenomatous polyposis family, Li Fraumeni  syndrome, Multi-endocrine disorder type I;  -  Multifocal pancreatic adenocarcinomas identified during preoperative evaluation;  -  Performance status and comorbidity profile inappropriate for a major abdominal  surgery;  -  Contraindication for autologous islet intraportal transplantation  -  Current or indicated/scheduled neoadjuvant chemotherapy;  -  Extra pancreatic metastasis identified during preoperative evaluation (high-definition  cross-sectional imaging with thorax-abdomen-pelvis multi-detection computed tomography  or abdominal MRI with T1, T2 and diffusion weighted sequences) or during  intraoperative assessment (clinical examination and ultrasonography);  -  Need for complex vascular reconstructions (endovascular treatment or release of the  arcuate ligament will be not considered as complex vascular reconstructions), major  vein reconstructions will exclude the patients because of the over-risk of portal  thrombosis following islet intraportal infusion.  -  evident macroscopically or biologically proved post biliary drainage pancreatitis that  jeopardize islet isolation  -  Known infection or positive serology performed at screening for human immunodeficiency  virus (HIV) infection, Hepatitis B or C virus infection, HTLV infection or syphilis  infection.  -  Active infection for SARS-CoV-2 virus (positive PCR), which will require rescheduling  of the intervention 30 days later.  -  Pregnant or breastfeeding woman  -  Dihydropyrimidine dehydrogenase total deficiency  -  Ethics / regulatory criteria :  -  Person unable to understand purposes, benefits and risks of the study and/or  unable to provide a written informed consent.  -  Person unable to comply with the whole study schedule.  -  Person not covered by a health insurance system.  -  Person kept in detention and/or receiving psychiatric medical care and/or  patients admitted in a social or medical sanatorium.  -  Person in an emergency situation.

Intra-abdominal pressure (IAP) needed to create sufficient workspace during laparoscopic  surgery affects the surrounding organs with ischemia-reperfusion injury and a systemic immune  response. This effect is related to postoperative recovery, pain scores, opioid consumption,  bowel function recovery, morbidity and possibly mortality. In clinical practice standard  pressures of 12-16mmHg are applied instead of the lowest possible IAP, but accumulating  evidence shows lower pressure pneumoperitoneum (PNP) (6-8mmHg) to be non-compromising for  sufficient workspace, when combined with deep neuromuscular blockade (NMB) in a vast majority  of patients. Therefore, low impact laparoscopy, meaning low pressure PNP facilitated by deep  NMB, could be a valuable addition to Enhanced Recovery After Surgery (ERAS) Protocols.  The use of low pressure PNP may also reduce hypoxic injury and the release of DAMPs and  thereby contributing to a better preservation of innate immune function which may help to  reduce the risk of infectious complications.  The participants will be randomly assigned to one of the experimental groups with low impact  laparoscopy or one of the control groups with standard laparoscopy. Intra-abdominal pressure (IAP) needed to create sufficient workspace during laparoscopic  surgery affects the surrounding organs with ischemia-reperfusion injury and a systemic immune  response. This effect is related to postoperative recovery, pain scores, opioid consumption,  bowel function recovery, morbidity and possibly mortality. Therefore, low impact laparoscopy,  meaning low pressure PNP facilitated by deep NMB, could be a valuable addition to Enhanced  Recovery After Surgery (ERAS) Protocols.  The use of low pressure PNP may also reduce hypoxic injury and the release of DAMPs and  thereby contributing to a better preservation of innate immune function which may help to  reduce the risk of infectious complications.  The participants will be randomly assigned to the experimental group 1: low impact  laparoscopy (low pressure (8 mmHg) and deep NMB (PTC 1-2)); 8 mmHg IAP after trocar  introduction for perfusion measurement or the experimental group 2: low impact laparoscopy  (low pressure (8 mmHg) and deep NMB (PTC 1-2)); 12 mmHg IAP after trocar introduction for  perfusion measurement, or control group 1: standard laparoscopy (standard pressure (12 mmHg)  and moderate NMB (TOF 1-2)); 8 mmHg IAP after trocar introduction for perfusion measurement,  or control group 2: standard laparoscopy (standard pressure (12 mmHg) and moderate NMB (TOF  1-2)); 12 mmHg IAP after trocar introduction for perfusion measurement.  ICG injection will take place with starting pressure to quantify parietal peritoneum  perfusion, and a parietal peritoneal biopsy will be taken. At the end of surgery, a second  parietal peritoneum biopsy will be taken.  NB: After introduction of the camera trocar, insufflation of carbon dioxide is titrated to an  IAP of 8mmHg in group A and C, and 14 mmHg in group B and D. After placement of the last  trocar the injection of ICG and video registration of peritoneum will take place, and a  peritoneal biopsy will be taken. There after surgery will take place with an IAP of 14mmHg in  the control groups (C and D), and an IAP of 8mmHg in the experimental groups (A and B). In  the control groups (C and D)  Pre- and postoperative a few questionnaires will be taken and blood withdrawals to evaluate  the quality of recovery, and the immune response. Inclusion Criteria:  -  - Age ≥ 18 years  -  Undergoing elective robot assisted radical prostatectomy (RARP)  -  Obtained informed consent Exclusion Criteria:  -  Laparoscopic radical prostatectomy without robot assistance  -  Insufficient control of the Dutch language to read the patient information and to fill  out de questionnaires  -  Neo-adjuvant chemotherapy  -  Chronic use of analgesics or psychotropic drugs  -  Use of NSAID's shorter than 5 days before surgery  -  Severe liver- or renal disease  -  Neuromuscular disease  -  Hyperthyroidism or thyroid adenomas  -  Deficiency of vitamin K dependent clotting factors or coagulopathy  -  Planned diagnostics or treatment with radioactive iodine < 1 week after surgery  -  Indication for rapid sequence induction  -  BMI >35kg/m2  -  Known of suspected hypersensitivity to ICG, sodium iodide, iodine, rocuronium or  sugammadex  -  Use of medication interfering with ICG absorption as listed in the summary of product  characteristics (SPC); anticonvulsants, bisulphite compounds, haloperidol, heroin,  meperidine, metamizol, methadone, morphium, nitrofurantoin, opium alkaloids,  phenobarbital, phenylbutazone, cyclopropane, probencid

The purpose of this study is to investigate brain activity during current visual and auditory  tasks for balance control. The participants will perform cognitive, gait, and balance  measures before the data collection to exclude people with neurological disorders. The  participants will wear VR headset which provides visual tasks. The participants will need to  maintain balance while performing concurrent visual and auditory tasks. The brain activities,  reaction time, and eye-tracking data will be collected during doing our experimental tasks. Virtual reality (VR), defined as an interactive system including computers and media  peripherals, creates an environment similar to a real-world and also provides audio and video  feedback to users. Recently, the virtual reality technology is able to make a headset  displaying 360 degrees VR environment and locate the headset in the space. This improvement  of VR technology significantly reduces the cost of VR equipment and enhances the application  of VR technology in the field of balance assessment and treatment.  Optic flow (OF) has been used to study the effect of visual input on balance control. Most of  the studies displayed OF on a screen rather than using 360 degrees visual field environment.  Therefore, the subjects could obtain reference inputs for balance adjustment. The new VR  headset makes it possible to play OF in a 360-degree visual field in which the subject will  not able to obtain any reference inputs rather than using somatosensory and/or vestibular  systems. It is unclear how the effect of aging and attention relocation affects postural  control with concurrent visual and auditory attention tasks. In this study, fNIRS will be  used to detect the brain activity of healthy adults in the prefrontal and temporal-parietal  junction as they complete concurrent cognitive and visual tasks displayed by a VR headset.  This work will focus on age and test positions (sitting vs standing). As age can play a role  in brain activation levels, the investigators will compare results among younger adults  (25-35 years), older adults (65-85 years), and older adults with the risk of falls. All the  subjects will undergo concurrent auditory reaction time tasks and visual tracking tasks. The  investigators will compare the brain images from the test conditions between the age groups  and investigate if brain activity differs during the performance of reaction time tasks and  visual tacking tasks. The goal of this study is to examine the effect of concurrent visual  and auditory tasks on brain activation and postural control. Inclusion Criteria:  -  must not have any vestibular, orthopedic or neurological disorders, knee or hip  replacements, reports of dizziness, low visual acuity (corrective vision less than  20/40) or require the use of an assistive device for ambulation.  -  Right-handed Exclusion Criteria:  -  Healthy group: have a low fall risk profile based on current available clinical  balance and gait assessment tools, such as the MiniBEST and STEADI fall risk  self-assessment tool and normal cognitive status using the Montreal Cognitive  Assessment (MoCA > 26/30)  -  Fall risk group: other medical issues rather than balance problems

The primary objectives of this study are to evaluate the efficacy of DTX401 to reduce or  eliminate dependence on exogenous glucose replacement therapy to maintain euglycemia and to  maintain or improve the quality of glucose control. Study DTX401-CL301 is a phase 3, randomized, double-blind, placebo-controlled study to  determine the efficacy and confirm the safety of DTX401 in patients 8 years and older with  glycogen storage disease type Ia (GSDIa). Participants will be randomized 1:1 to DTX401 or  placebo group, and followed closely for 48 weeks. At week 48 eligible participants will cross  over and receive DTX401 if they had previously received placebo or placebo if they had  previously received DTX401, and will be followed closely for an additional 48 weeks. After  completion of week 96 or early withdrawal, participants will be offered enrollment into a  Disease Monitoring Program (DMP) where they will be followed for at least 10 years post  DTX401 infusion. Inclusion Criteria: None Exclusion Criteria: None

The aim of this study is to examine the effectiveness of nurse- led program on psychosocial  problems and quality of life in stroke patients. This randomized controlled trial will be  conducted in Stroke Center in Istinye University Liv Hospital-Bahcesehir. Eligible  participants will be randomly allocated to either the control group (receiving usual care/  routine follow-up group) or the intervention group (receiving nurse-led psychosocial  program). A nurse- led program will be implemented for the management of psychosocial  problems following a comprehensive evaluation. Then, the effect of this program on  psychosocial problems and quality of life will be evaluated in the 1st and 3rd months after  discharge. The aim of this study is to examine the effectiveness of nurse- led program on psychosocial  problems and quality of life in stroke patients. This randomized controlled trial will be  conducted in Stroke Center in Istinye University Liv Hospital- Bahcesehir. Patients who meet  the criteria will be randomized into the intervention group or control group. All patients  will be assessed at discharge by use of following tools: National Institutes of Health Stroke  Scale (NIHSS), modified Rankin Scale, Functional Independence Measure (FIM), Montreal  Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep  Quality Index (PSQI). A nurse coordinated multidisciplinary program aiming to improve  psychosocial problems has been developed and will be applied to the patients in the  experimental group. This nurse-led program will start at discharge and continue for three  months. The control group will be applied usual care. Two groups will be compared at baseline  and at the 3rd month after discharge in terms of psychosocial variables and quality of life. Inclusion Criteria:  -  Be literate  -  Have a clinical diagnosis of ischemic stroke  -  History of any preceding cerebral vascular event  -  Capable of giving informed consent Exclusion Criteria:  -  Age ≤ 18 years  -  Have a mental disorder that will prevent cognitive evaluation  -  Have an impaired consciousness (confusion, delirium, etc.)  -  History of any type of cognitive decline  -  Have severe neurologicial deficit  -  Severe aphasia  -  Living in a nursing home  -  Known malignant disease or other chronic disease with poor prognosis and a low life  expectancy

Oral squamous cell carcinoma (SCC) produces a higher prevalence and more severe pain than all  other cancers. Orofacial pain is one of the most common initial symptoms of oral cancer and  often leads to the diagnosis of oral cancer. However, the character, severity, and unique  features of oral cancer widely differ between patients. There is currently no effective and  lasting treatment available to alleviate suffering from oral cancer pain.  A significant obstacle to effectively treating cancer pain is that the relative contributions  of nociceptive mediators and their mechanisms of action (i.e., responsible receptors) are  largely unknown. There is, therefore, a critical need to define the neurobiologic mechanisms  responsible for oral cancer pain. Without such information, the promise of non-opioid therapy  for the treatment of oral cancer pain will remain unfulfilled.  The primary objective of this study is to define and quantify the phenotype of oral cancer  pain in patients, by comparing mechano- and chemosensitivity in oral cancer patients with  healthy subjects. Pain will be stimulated on the site of cancer in 40 oral cancer patients  and on the tongue in 40 healthy volunteers utilizing chemical sensitivity and mechanical  sensitivity tests. Oral squamous cell carcinoma (SCC) is the sixth most common cancer worldwide. The majority of  patients with oral SCC suffer from severe, chronic, function-induced pain. Despite the  severity of pain in many patients, the presentation of oral cancer pain is variable. Opioids  are the only treatment available for oral cancer pain. Opioids are often ineffective and  associated with tolerance, constipation, somnolence, respiratory depression, and addiction,  which is now a national crisis.  The current hypothesis for the etiology of oral cancer pain, which is based on clinical  studies utilizing questionnaires and preclinical studies, is that cancer cells and cells  within the microenvironment produce mediators that activate and sensitize nociceptors.  Published and preliminary data indicate that cancer-secreted mediators induce mechano- and  chemosensitivity. For example, preliminary clinical studies demonstrate that oral cancer  patients experience preoperative sensitivity to capsaicin (i.e., chemosensitivity) and report  greater functional (i.e., mechanosensitivity) pain. Capsaicin activates transient receptor  potential vanilloid 1 (TRPV1). TRPV1 is activated by temperatures above 43°C and endogenous  lipid metabolic products. Mice deficient in TRPV1 respond to mechanical stimuli, suggesting  that TRPV1 is not involved in the detection of mechanical stimulation. By contrast, TRP  ankyrin repeat 1 (TRPA1), co-localized with TRPV1, is responsive to mechanical stimuli, in  addition to irritants such as allyl isothiocyanate (AITC). Both TRPV1 and TRPA1 have been  reported to play important roles in orofacial pain. Improved knowledge of the contribution of  TRPV1 and TRPA1 to oral cancer pain holds considerable promise for the development of novel,  non-opioid treatment strategies that specifically address the unique pain experience of  individual patients.  There is a lack of published data characterizing the sensory phenotype of tumor-related  cancer pain, which has significant implications for understanding the underlying  pathophysiological mechanisms of cancer pain. Quantitative sensory testing can provide  insight into the mechanism(s) responsible for pain. In this proposal, we will test our  hypothesis that the quality of pain experienced by oral cancer patients is dependent on the  level of activation of specific channels on nociceptors. We will perform mechanical (von Frey  testing) and chemical sensitivity tests (sensitivity to capsaicin, TRPV1 agonist, and AITC  (TRPA1 agonist) on oral cancer patients, and compare the sensitivities to healthy subjects.  For cancer patients, we will administer the validated University of California San Francisco  (UCSF) Oral Cancer Pain Questionnaire to evaluate the correlation between mechanical and  chemical thresholds with relevant aspects of pain.  We propose that the quality of pain experienced by oral cancer patients is quantifiable and  dependent on the level of sensitization and activation of specific channels on nociceptors. Inclusion Criteria:  -  Biopsy-proven squamous cell carcinoma (SCC) of the oral cavity that requires surgical  resection  -  Lesion is at least 1 cm in greatest surface dimension  -  In good general health as evidenced by medical history Exclusion Criteria:  -  History of prior surgical, chemotherapeutic, or radiation treatment for head and neck  cancer  -  Pregnancy or lactation  -  Clinically and/or histologically proven oral pre-cancer, oral cancer  -  Pregnancy or lactation

Background:  - People respond differently when asked about their values. They also respond differently  when they learn about how their actions affect their lives and health. Researchers want to  learn more about these differences. This can help them improve public health messages.  Objective:  - To see how people respond differently to questions about their values and to information  about alcohol and breast cancer.  Eligibility:  Study 1  - Women age 18 and older.  Study 2 & Study 3  -Women and men aged 18 and older to take part in these studies if they do not meet the US  recommendations of eating 5 or more servings of fruits and vegetables per week.  Design:  -  This study will take place online.  -  Participants will be randomly assigned to a group that will complete a certain task.  -  Researchers will ask participants to complete 2 small studies:  -  Values Study. Some participants may write briefly about a value that is important to  them or to someone they are close to. Some participants will complete a short  questionnaire instead of the writing exercise.  -  Study 1:  Alcohol and Breast Cancer Study. Participants will read a health message. This will be about  the link between alcohol use and increased breast cancer risk. Participants will then answer  questions about what they read and their beliefs about alcohol and breast cancer.  -Study 2:  Fruit and Vegetable Consumption and Health Study. Participants will read a health message  about the fruit and vegetable consumption. Participants will then answer questions about what  they read and their beliefs about fruit and vegetable consumption.  -Study 3:  Fruit and Vegetable Consumption and Health Study. Participants will read a health message  about the fruit and vegetable consumption. Participants will then answer questions about what  they read and their beliefs about fruit and vegetable consumption. Complete a follow-up  survey that will be emailed to you through the mTurk system a week after you complete the  main study.  -  Both studies in either Study 1, Study 2 and Study 3 should take about 30 minutes. Self-affirmation, a process by which individuals reflect on cherished personal values is a  potent means of augmenting the effectiveness of threatening health communications.  Individuals tend to be defensive against information suggesting their behavior puts them at  risk for disease or negative health. Previous evidence suggests that self-affirmation may  reduce defensiveness to threatening health information, increasing openness to the message  and resulting in increased disease risk perceptions, disease-related worry, intentions to  engage in preventive behavior, and actual behavioral change. Understanding the mechanisms  that explain these robust effects would yield evidence important for dissemination, including  ways to refine self-affirmation interventions and make them more potent, which could change  the ways that public health messages are constructed. Thus, we aim to elucidate potential  mechanisms underlying the effectiveness of self-affirmation, including self-activation,  general affirmation, and domain-specific affirmation. In study 1, female human subjects will  be randomly assigned to one of eleven affirmation or self- activation conditions. Following  the affirmation or activation task, subjects will read about the documented link between  alcohol and breast cancer. Finally, they will be asked a series of questions about their  intentions to reduce drinking, their perceived risk of breast cancer, and their worry about  breast cancer. Study 2 will replicate study 1, but in a different behavioral domain (physical  activity) and a different sample (both males and females who do not meet physical activity  recommendations). Study 3 will extend Studies 1 and 2 by examining whether the most effective  self-affirmations identified in these studies produce short-term increases in fruit and  vegetable consumption. Drawing on previous research, we hypothesize these inductions will be  effective to the degree that they involve a self-affirmation, but will not be effective if  they involve only other-affirmation or self-activation. Inclusion Criteria:  Study 1:  Amazon mTurk workers will be invited to participate if they are women over the age of 18.  They will also be screened to meet alcohol consumption inclusion criteria. Women will be  eligible to complete the study if they drink seven or more drinks per week (consistent with  the alcohol consumption level the health message links to increased breast cancer risk  (which is based on evidence in the extant breast cancer risk literature). If women report  drinking 7 or more drinks in a sitting, they will be eligible regardless of how many times  they drank in the past year. If they report drinking less than 7 drinks in a sitting, an  average will be calculated to determine whether they meet inclusion criteria. For example,  women who report drinking twice per week on average, and who drink an average of 4 drinks  in a sitting, would be eligible for the study.  Study 2:  Prolific participants will be invited to take part in the study if they are over the age of  18. They will also be screened to meet fruit and vegetable consumption inclusion criteria.  Individuals will be eligible to complete the study if they eat fewer than 5 servings of  fruits and vegetables per day, on average (consistent with the consumption level the health  message, and consistent with US consumption recommendations).  Study 3:  Amazon mTurk workers will be invited to participate if they are over the age of 18. They  will also be screened to meet fruit and vegetable consumption inclusion criteria.  Individuals will be eligible to complete the study if they eat fewer than 5 servings of  fruits and vegetables per day, on average (consistent with the consumption level the health  message, and consistent with US consumption recommendations). Exclusion Criteria:  Study1  All men, and women who report a lower threshold of alcohol consumption, will be excluded.  Study 2  All individuals who report a higher threshold of physical activity will be excluded  Study3  All individuals who report a higher threshold of fruit and vegetable. consumption, will be  excluded. All individuals who participated in Studies 1 and 2 will be excluded.

This is a double-blind, placebo-controlled phase 2b trial in which 54 MSM who use meth will  be randomly assigned (2:1) to receive 12 weeks of as-needed intermittent oral naltrexone 50  mg enhanced with an EMA-informed EMI platform, or receive as-needed placebo with EMA-informed  EMI. The 12-week treatment period is consistent with other pharmacotherapy trials for  substance use disorders. The proposed sample size is also consistent with other phase 2b  trials for substance use treatment. Upon enrollment, participants will complete daily EMA  assessments and weekly visits for behavioral surveys and urine testing for meth metabolites,  study drug dispensing and computer-based counseling for substance use. Safety laboratory  assessments and vital signs will be completed monthly. Efficacy (Specific Aims 1-3) will be  assessed upon trial completion as measured by proportion meth-positive urine samples; PrEP  and ART adherence by drug levels and viral load testing; and sexual risk behavior data  accounting for PrEP use and viral suppression. Methamphetamine (meth) use is very common among men who have sex with men (MSM), particularly  MSM living with HIV. Meth use among HIV-negative and HIV-positive MSM is up to 13 and 34  times more prevalent than in the general U.S. adult population, respectively. Meth use is  independently associated with HIV-related sexual risk behaviors among MSM and can function as  a barrier to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) adherence.  Thus, effective interventions to reduce meth use may also function as an important HIV  prevention and care intervention by reducing meth-related HIV risk behavior, and optimizing  ART and PrEP adherence. MSM comprise two-thirds of the new infections in the United States.  Despite this continued domestic HIV epidemic and the high prevalence of meth use among MSM,  few interventions have proven efficacious for MSM who use meth. The investigators seek to  address this gap by evaluating the efficacy of intermittent oral naltrexone enhanced with an  ecological momentary intervention (ION+EMI) for meth use treatment. Naltrexone, a µ-opioid  receptor antagonist, is a promising agent for MSM who use meth. Meth is rapidly metabolized  to amphetamine in the bloodstream and daily naltrexone has shown efficacy in reducing  amphetamine urine-positivity and relapse. Oral naltrexone is inexpensive and has few  toxicities, but the standard daily regimen for naltrexone hampers compliance as patients  frequently neglect to take the medication. Alternate regimen schedules have been proposed to  increase efficacy and expand the population that may benefit from this pharmacologic agent.  One alternative approach is the targeted administration of intermittent oral naltrexone  (ION), whereby individuals are instructed to take the medication as needed in anticipation of  substance use, after exposure to triggers of substance use, or during periods of craving.  Administration of naltrexone prior to exposure to amphetamines significantly attenuated  amphetamine craving in 4 trials. Additionally, emerging evidence suggests that ecological  momentary interventions (EMI) that respond to in-the-moment contexts can lead to positive  health behaviors, such as increasing medication dosing. EMI are particularly well-suited to  enhancing as-needed dosing of naltrexone because anticipation of meth use and meth craving in  a natural setting changes within a person from moment to moment, and the detection of these  momentary fluctuations can support the delivery of just-in-time messages to encourage  medication use to prevent participants from proceeding from craving to meth use. A pilot  study led by our research team on ION found that meth-using MSM who use at least 1 day per  week had significantly greater reductions in meth-using days when treated with as-needed  naltrexone, compared to placebo. Moreover, naltrexone participants had greater reductions in  serodiscordant receptive anal intercourse and serodiscordant condomless receptive anal  intercourse, compared to placebo. In the pilot, participants reported taking study drug 64%  of the days that they craved or anticipated meth use. Participants also completed ecological  momentary assessments (EMA) with a 74% response rate, indicating that real-time assessments  are feasible and acceptable. To build on the results of this study and 4 other naltrexone  trials, the investigators propose to evaluate intermittent naltrexone to treat meth in a  phase 2b efficacy trial supplemented by an EMA-informed EMI that responds to a participant's  real-time craving levels or anticipated meth use to provide in-the-moment medication  reminders when participants would most benefit from naltrexone. The investigators hypothesize  that pairing ION with EMI will further amplify reductions in meth use by providing  just-in-time reminders for naltrexone to optimize adherence, thereby interrupting the  progression from craving to meth use. Inclusion Criteria:  -  cisgender male (male gender and sex assigned at birth)  -  age 18-70 years* (naltrexone's tolerability and safety has been demonstrated among  older adults up to age 70)  -  self-reported condomless anal sex with men or missing Pre-Exposure Prophylaxis or  antiretroviral therapy doses due to meth use in the prior three months while under the  influence of meth  -  self-reported meth use at least weekly  -  mild, moderate or severe meth use disorder  -  positive meth sample via sweat patch or urine testing during screening  -  interested in reducing meth use  -  no current acute illness requiring prolonged medical care  -  no chronic illness that is likely to progress clinically during trial  -  able and willing to provide informed consent and adhere to visit schedule  -  current CD4 count ≥ 200 cells/mm3; or CD4 count of 100-199 cells/mm3 and HIV viral  load < 200 copies/mL (if living with HIV)  -  baseline complete blood count, total protein, albumin, glucose, alkaline phosphatase,  creatinine, blood urea nitrogen test, and electrolytes without clinically significant  abnormalities as determined by study clinician in conjunction with symptoms, physical  exam, and medical history Exclusion Criteria:  -  any psychiatric (e.g., depression with suicidal ideation) or medical condition that  would preclude safe participation  -  known allergy or prior adverse reaction to naltrexone  -  current use of any opioids or a known medical condition which currently requires or  may likely require opioid analgesics  -  opioid-positive urine test at screen/enrollment visits (naltrexone can induce opioid  withdrawal)  -  moderate or severe liver disease (aspartate aminotransferase test, alanine  aminotransferase test, or total bilirubin > 3 times upper limit of normal)  -  impaired renal function (creatinine clearance < 60 ml/min)  -  currently participating in another intervention research study with potential overlap  -  severe alcohol use disorder as determined by structured clinical interview for DSM-5  criteria  -  any condition that, in the PI and/or study clinician's judgment interferes with safe  participation or adherence to study procedures

Light to moderate sedation is recommended during surgery with spinal anesthesia . This study  is exploring which sedation drug is better, midazolam or dexmedetomidine for transurethral  resection of bladder and prostate in patients with or without high risk for obstructive sleep  apnea (OSA). Patients were divided in two groups regarding OSA risk, and each group received  midazolam or dexmedetomidine for sedation. Investigators observed intraoperative  complications of airway and factors that are disturbing surgeon(movement due to participants  coughing and restlessness) because one could puncture bladder or prostate and cause  perforation. All participants were premedicated with diazepam 5mg 12 hours and 1 hour before surgery.  Thromboprophylaxis (enoxaparin 4000-6000 IU) depending on the body weight was given at least  12 hours before surgery.  Participants were divided by STOP-BANG(Snoring history, Tired during the day, Observed stop  breathing while sleep, High blood pressure, BMI more than 35 kg/m2, Age more than 50 years,  Neck circumference more than 40 cm and male Gender) questionnaire into one of two groups:  high OSA and low&medium OSA. Each group was then allocated by permuted block randomisation  into midazolam or dexmedetomidine group. The randomisation list was obtained from R program.  The group allocations were contained in closed envelope that were opened before surgery after  the completed enrollment procedure.  Participants got IV cannula with switch for continuous intravenous infusion in operating  theatre. Non invasive monitoring (electrodes for ECG, blood pressure cuff and pulse oximeter)  was placed before induction of spinal anesthesia. Skin was disinfected and 40mg of 2%  Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used  and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied.  Participants were then positioned in uniform lithotomy position and 9cm pillow was inserted.  After sensory block, defined as the absence of pain at T10 dermatome, was induced by  needle-tip test by the anaesthesiologist, the surgery was initiated.  Time after subarachnoid block was T0 and sedation with midazolam or dexmedetomidine was  started via continuous intravenous infusion. Midazolam was started with 0.25 mg/kg of ideal  body mass, and dexmedetomidine with 0.5 ug/kg through 10 minutes. Every 10 minutes sedation  level was observed with Ramsay sedation scale (RSS). Drug was titrated to achieve RSS of 4 or  5 (closed eyes and patient exhibited brisk or sluggish response to light glabellar tap or  loud auditory stimulus). Independent blinded doctor was assessing RSS level, vital parameters  and signs of airway obstruction every 10 minutes. Every 10 minutes systolic, diastolic and  mean arterial pressure(MAP) were noticed along with heart rate, oxygen saturation by pulse  oximetry(SpO2), RSS level and adverse intraoperative events: snoring as sign of airway  obstruction, cough and restlessness as disturbing factors to surgeon. If peripheral oxygen  fell below 90% supplemental oxygen was delivered by facemask with reservoir bag at flow of 10  L/min. End tidal carbon dioxide(CO2)was measured for detection of possible apnea. If  oxygenation was still inadequate chin lift and jaw thrust maneuver were performed and  oropharyngeal airway was inserted if needed. If heart rate fell below 50 bpm atropine 0.1  mg/kg was given and if systolic blood pressure fell below 100 mmHg(or MAP < 65 mmHg)  ephedrine 5mg bolus was given. Total crystalloid infusion volume was noticed at the end of  surgery. All measurements were performed every 10 minutes and 1 hour after surgery in urology  intensive care. High risk OSA participants underwent cardiorespiratory polygraphy at Center  for sleep medicine Split. Inclusion Criteria:  -  elective transurethral resection of bladder and prostate  -  American Society of Anesthesiologists (ASA) physical status classification system: I,  II, III Exclusion Criteria:  -  regional anesthesia contraindications  -  American Society of Anesthesiologists (ASA) physical status classification system: IV  -  Atrioventricular cardiac block II and III degree  -  Psychotic disorders  -  Participants with tracheostomy  -  Dementia  -  Allergy on Dexmedetomidine or Midazolam

This is a prospective clinical study aiming to investigate on the transplacental antibody  transmission post Covid-19 infection during pregnancy. Covid -19 infection has been a significant public health burden as it shifted the paradigm of  infectious diseases aiming to control the spread and enhance public immune protection. The  introduction of Covid -19 vaccination in December 2020 aimed to combat the infection, thus  tremendously helping to flatten the disease worldwide. Channeling the vaccine for the  obstetrics field is one of the hallmark strategies to reduce maternal morbidity and  mortality. The efficacy of vaccination for the pregnant lady has been established. However,  fetus protection via transmission of the antibody during pregnancy is still uncertain.  Therefore, this study aims to consolidate further evidence of transplacental antibody  post-maternal vaccination aiming for fetal protection following delivery. Inclusion Criteria:  -  term pregnancies at 37 weeks or more  -  vaccinated 2 doses  -  in labour Exclusion Criteria:  -  unvaccinated  -  preterm labour less than 37 weeks  -  multiple pregnancies

The primary objectives of this study are to examine sleep, exercise, and nutrition in  prostate cancer. The primary objective of this study is to determine whether exposure to a website with  recommendations about sleep and lifestyle for patients with prostate cancer and caregivers  leads to an improvement in sleep and healthy lifestyle. Inclusion Criteria:  1. Adult U.S. male age >18 with prostate cancer OR  2. Adult U.S. male or female >18 who is a family member/partner/caregiver of a prostate  cancer patient AND  3. Telephone and internet access AND  4. Able to read, comprehend, and sign informed consent in English AND  5. Perceived deficits in sleep, nutrition, and/or physical activity Exclusion Criteria:  1. Age <18 years  2. Not English proficient  3. No or irregular access to the same telephone number and/or mailing address  4. No or less than weekly access to the internet  5. Patients who do not have a diagnosis of prostate cancer  6. Caregivers/family members for a condition other than prostate cancer  7. Mental or cognitive impairment that interferes with ability to provide informed  consent  8. Surgery within the past 6 weeks or planned within the next 3 months (must wait until  cleared to participate)  9. Other restrictions or upcoming events that affect sleep, physical activity or  nutrition (e.g. doctor's orders)

In this study, it is assumed that grip strength is associated with pelvic floor muscle  strength. And the outcome of pelvic floor function can be predicted by referring to the  status of pelvic floor muscle strength through the value of grip strength, which is  labor-saving, time-saving and more convenient for evaluating pelvic floor muscle function.  Moderate physical activity and increase the overall strength can activate the potential  mechanism of pelvic floor muscle contraction at the same time may be a "core muscles" overall  effect, that core muscles mainly includes transverse abdominal muscle, pelvic floor muscles  and the muscles around the back, these muscles in the body movement to spontaneous  collaboration contract pelvic floor muscles, enhancing pelvic floor muscle function, thus  reducing the incidence of pelvic floor dysfunction. This study is a cross-sectional observational study, planned to enroll 2942 participants from  Gynecology Outpatient Clinic. Uniformly trained physicians as investigators to collect  indicators from questionnaires and physical examinations.  Questionnaires may contain general information which include the patient's age, height, body  weight before pregnancy and childbirth, weight gain during pregnancy, gestational age,  pregnancy time, production time, high palace, delivery mode, neonatal birth weight, body  length, blood sugar, blood fat, whether or not to use during pregnancy, childbirth, labor,  perineal laceration, forceps midwifery, episiotomy and epidural data, pelvic floor cognition  degree, physical activity levels, pelvic floor dysfunction score, pelvic floor functional  impact score and sexual function score (including the prenatal and postnatal participants).  Physical examinations will be performed without the results of the questionnaire, including  stress tests, pelvic floor POP-Q staging, pelvic floor muscle strength by palpation, vaginal  relaxation degree, grip strength value, rectus abdominis separation, waist circumference,  waist-hip ratio, etc.  Through univariate analysis of the general data of the patients, the related factors of  female PFD were obtained, and the independent influencing factors of PFD were found by binary  Logistic regression analysis (the dependent variable in this study was a dichotomous  variable). The ROC curve was used to evaluate the predictive value of patients' overall  strength level, physical activity level, body shape and other indicators on PFD outcome. Inclusion Criteria:  -  Gynecological outpatient clinic patients  -  In good condition and able to actively cooperate  -  Agree to conduct the study.  -  Age range: 18 to 65 years old Exclusion Criteria:  -  Patients who has a history of pelvic surgery or has had pelvic floor functional  diseases  -  Patients who do not have sex  -  Pregnancy  -  Patients who have serious medical diseases  -  Patients with cardiac dysfunction or wear pacemakers  -  Patients with neurological diseases and cognitive impairment who are difficult to  cooperate with the study

The purpose of this study is to evaluate the safety of pharmacopuncture by observing any  adverse events that may occur after pharmacopuncture treatment in with spinal joint disease  hospitalized patients at 7 Korean medicine hospitals and analyzing blood test results. This study was an registry observational study, and was conducted in 7 Korean medicine  hospitals (160 patients at Jaseng Korean medicine Hospital, 140 patients at Daejeon Jaseng  Hospital of Korean Medicine, 140 patients at Bucheon Jaseng Hospital of Korean Medicine, 140  patients at Haeundae Jaseng Korean medicine Hospital, 140 patients at Kyunghee University of  Korean medicine Hospital, 140 patients at Kyung Hee University of Korean Medicine Hospital at  Gangdong, and 140 patients at Dongguk University Bundang Oriental Hospital). Inclusion Criteria:  -  Inpatients with diagnosed spinal joint disease  -  Patients who received pharmacopuncture treatment during hospitalization  -  Patients who are 19 years of age or older and less than 70 years old  -  Patients who agreed to participate in the clinical study and voluntarily given written  informed consent Exclusion Criteria:  -  Patients with difficulty or refusal to give sign written informed consent  -  Patients for whom the researchers judge participation in the clinical study to be  difficult

This is a pilot study to assess the feasibility, acceptability and appropriateness of  delivery of the investigational "MedViewer" intervention in adult patients living with HIV  who have been prescribed antiretroviral (ARV) medications. The Medviewer uses Infra-red (IR)  matrix-assisted laser desorption electrospray ionization (MALDESI) technology for mass  spectrometry imaging (MSI) to analyze patient hair samples to provide information on ARV  adherence in real-time.  The study has two different groups of participants: the patients, and their clinician  providers. This study is part of a larger research program that is investigating a novel non-invasive  approach to rapidly quantify ARV concentrations and provide evidence of drug ingestion. The  ultimate goal is to provide clinicians and patients feedback on ARV adherence. Infra-red (IR)  matrix-assisted laser desorption electrospray ionization (MALDESI) technology for mass  spectrometry imaging (MSI) is used to visualize and quantify ARV concentrations in hair. The  IR-MALDESI MSI has been labeled the "MedViewer".  Patient participants will be scheduled for the sampling visit to correspond with their next  appointment at the University of North Carolina (UNC) Infectious Disease (ID) clinic. Patient  participants will be asked to arrive to their clinic appointment at least two hours prior to  the scheduled time to be consented and enrolled. If eligible and enrolled in the study,  patient participants will have a small hair sample (5 strands) plucked from a discrete  location on the back of their head. Patient participants will also have a small blood sample  collected. The results from the MedViewer test will be provided to both the patient and their  provider, in order to facilitate a discussion around medication adherence. After receiving  the results, all participants will complete a brief questionnaire about their experience with  the MedViewer.  As this is a feasibility study, results from the Medviewer test will not be used to make  clinical decisions related to care.  Major changes after the start of enrollment:  1. Removed the term "real-time" throughout the document-Pertinent feasibility endpoints now  use "delivery of the report to the designated research staff member within 2 hours of  initiation of hair processing" rather than "…within 2 hours of hair sample collection"  2. Removed mitra sampling for the remaining 15 participants in cohort A. Now stated as  "blood sample will be collected for 10 participants in Group A and a subset of  participants in Group B." After Mitra is analyzed for the first 10 participants in Group  B, we will reevaluate to determine if additional samples are needed to validate hair  samples.  3. V1 and V2 study activities will be conducted virtually (except hair collection and  in-person patient provider clinic visits) to minimize in-person contact. Consent and  screening will be conducted virtually using videoconferencing via zoom on computer,  tablet or phone. All questionnaires (patient baseline, patient post-visit, patient  endline, provider baseline, provider post-visit, and provider endline) will be conducted  virtually through REDCap (emailed to participant or verbally administered via phone or  videoconferencing). Hair collection will be conducted by research staff at remote  locations to limit time in clinic. Implementation of the intervention will now be  allowed in the setting of telehealth clinical visits between patient and provider in  addition to in-person clinical visits. MedViewer reports will be sent to providers via  secure email. All remaining V2s will be conducted virtually. Hair and blood samples will  not be collected.  4. Consenting will take place up to 3 days before scheduled clinic appointment with  provider. Hair sample will be collected by research staff at a remote location in the 3  days between consent and the scheduled provider visit. MedViewer report will be  discussed between patient and provider (or patient and pharmacist, if needed) within 4  weeks of hair sample collection.  5. Interviewer-administered portions of the baseline questionnaire have been modified.  Health Literacy measure (Newest Vital Sign) removed. ART adherence Visual Analog Scale  modified to allow for remote self-administration.  6. Maximum duration on study extended by 6 months for providers (increased from 10 to 16  months). Provider sample size range reduced (from 20-30 to 16-30)  These changes were implemented on November 5, 2020 in a Letter of Amendment (LOA) to  ENLIGHTEN Protocol Version 2. The LOA detailed changes made to the protocol due to the  COVID-19 Pandemic. Inclusion Criteria:  Patient participants:  -  Documentation of HIV-1 infection by means of any one of the following:  1. Documentation of HIV diagnosis in the medical record by a licensed health care  provider;  2. OR HIV-1 RNA detection by a licensed HIV-1 RNA test demonstrating >1000 RNA  copies/mL;  3. OR any licensed HIV screening antibody and/or HIV antibody/antigen combination  test confirmed by a second licensed HIV test such as a HIV-1 Western blot  confirmation or HIV rapid Multispot antibody differentiation test.  -  At least 18 years of age on the day of consent.  -  Documentation of HIV viral loads over 2-year period prior to screening.  -  Has been a patient at the UNC ID clinic for at least 90 consecutive days prior to the  date of enrollment in the study (i.e. attended first appointment at the UNC ID Clinic  at least 90 days prior to the date of enrollment in the study).  -  Has attended at least one HIV appointment at the UNC ID clinic within the 365 days  prior to the date of enrollment in the study.  -  Has been prescribed one of the ARV medications eligible in this study (Dolutegravir,  Emtricitabine) by a UNC provider for at least 90 days prior to the date of enrollment  in the study.  -  Has an HIV appointment scheduled at the UNC ID clinic during the enrollment period of  the study with a medical provider enrolled in the study.  -  Evidence of a personally signed and dated informed consent form indicating that the  participant has been informed of all pertinent aspects of the study.  -  Has stated willingness and availability to comply with all study procedures for the  duration of the study.  -  Literate in English.  -  Has at least 1.0 cm of natural caput hair.  -  As enrollment will occur in a stratified manner based on 2 viral load strata, (n = 25  for patients with undetectable viral loads, n = 25 for those with detectable viral  loads), once a stratum quota is reached, patients whose viral loads fall within that  stratum will not be eligible to participate in the study.  Provider participants:  -  Medical provider (including, but not limited to: attending physician, ID fellow, nurse  practitioner, physician assistant, or a designated HIV Care pharmacist) for UNC ID  clinic patients living with HIV.  -  Provides medical care for patients at the UNC ID clinic at least one half-day per week  (i.e. 4 hours per week).  -  Evidence of a personally signed and dated informed consent form indicating that the  participant has been informed of all pertinent aspects of the study.  -  Has stated willingness and availability to comply with all study procedures for the  duration of the study. Exclusion Criteria:  Patient participants:  -  Previous participation in the study UNC 11530- Formative Sub-Study for Novel Mass  Spectrometry Imaging Methods to Quantify Antiretroviral Adherence.  -  Deemed, by medical provider in UNC ID clinic, too ill, or other relevant reason, to  participate in the study.  -  Prior history of clinically significant alteration of the gastrointestinal system or  drug absorption capability, including but not limited to: gastrectomy, total colectomy  -  Any chemical hair treatment with dye, bleach, or relaxers within the past 4 weeks  prior to sampling  Provider participants:  -  Not willing or able to participate in any of the provider training sessions for this  study or any form of make-up training session with research team.

This study is open-label, two arms, multi-centered, phase 2b clinical trial to determine the  efficacy, safety, and immunogenicity of booster vaccination (TURKOVAC) against Covid-19.  The primary aim of the study is to evaluate the efficacy of a booster dose of TURKOVAC  vaccine administered to subjects who have passed at least 90 days and at most 240 days after  the second dose of the first course of Comirnaty (Code name: BNT162b2) vaccine. This phase 2b study aims to determine the efficacy, safety, and immunogenicity of a booster  dose of TURKOVAC vaccine administered to subjects who have passed at least 90 days and at  most 240 days after the second dose of the first course of Comirnaty (Code name: BNT162b2)  vaccine.  Efficacy will be evaluated by spike-specific antibody response and neutralizing antibody  levels on days 0, 28 (all subjects), 48, 84 and 168 days (50% of subjects).  For the booster dose, subjects will be assigned open-label according to randomization (1:1)  for 2 different arms. Comparing the efficacy, safety, and immunogenicity results of different  series of TURKOVAC vaccines (TURKOVAC-Koçak and TURKOVAC-Dollvet) produced in different  production facilities are the secondary objectives of the study.  The booster dose vaccine arms are as follows:  -  TURKOVAC-Koçak  -  TURKOVAC-Dollvet Inclusion Criteria:  1. Subjects willing and able to give signed informed consent to participate in study,  2. Healthy male or female aged 18 - 59 years (including both groups),  3. Subjects who were vaccinated with Comirnaty (Code name: BNT162b2) for 2 doses and who  had a minimum of 90 days and a maximum of 240 days after the second dose,  4. Subjects with a minimum of 28 days and a maximum of 42 days between 1st and 2nd dose  of Comirnaty (Code name: BNT162b2) vaccines,  5. Female subjects of childbearing potential and male subjects of to have child potential  who are willing to ensure that they or their partner use effective contraception  continuously from 1 month before vaccination to 3 months after booster vaccination,  6. In the opinion of the investigator, subjects capable and willing to comply with all  study requirements,  7. Subjects are willing to agree to abstain from donating blood during the study. Exclusion Criteria:  1. Administration of any vaccine (registered or investigational) other than study  intervention within 30 days before and after each study vaccine (one week for  authorized seasonal flu vaccine or pneumococcal vaccine),  2. Known history of SARS-CoV-2 infection,  3. Pre-or planned use of another vaccine or product likely to affect the study (e.g.  adenovirus vectored vaccines, any coronavirus vaccine),  4. Subjects who were pregnant at the time of enrollment or who plan to become pregnant  within the first 3 months following vaccination and who are breastfeeding,  5. Subjects with fever (above 38°C) at the time of vaccination and/or up to 72 hours  before (subjects may be screened again after acute condition has resolved),  6. Administration of immunoglobulins and/or any blood product within 3 months prior to  vaccination,  7. Any confirmed or suspected immunosuppressive or immunodeficiency state; asplenia;  recurrent severe infections and use of immunosuppressants (less than ≤14 days) in the  last 6 months, excluding topical steroids or short-term oral steroids,  8. Possible history of allergic disease or reaction (e.g. to the active substance) by any  component of the study vaccines,  9. Any history of anaphylaxis,  10. Current cancer diagnosis or treatment (excluding basal cell carcinoma of the skin and  cervical carcinoma in situ),  11. History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet  disorder), or prior history of significant bleeding or bruising following  intramuscular injections or venipuncture,  12. Continued use of anticoagulants such as coumarins and related anticoagulants (i.e.  warfarin) or new oral anticoagulants (e.g. apixaban, rivaroxaban, dabigatran and  edoxaban),  13. Cerebral venous sinus thrombosis, antiphospholipid syndrome, or a history of  heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2),  14. Suspected or known current alcohol or drug addiction,  15. Any other significant disease, disorder or finding that could significantly increase  the subject's risk for participation in the study, affect the subject's ability to  participate in the study, or impair the interpretation of study data; severe and/or  uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease,  liver disease, kidney disease, endocrine disorder, and neurological disease  (mild/moderate well-controlled comorbidities are permitted),  16. History of active or previous autoimmune neurological disorders (e.g. multiple  sclerosis, Guillain-Barre syndrome, transverse myelitis) (Bell's palsy will not be an  exclusion criterion),  17. Subjects with severe renal impairment or liver failure,  18. Subjects who will undergo scheduled elective surgery during the study,  19. Subjects with a life expectancy of less than 6 months,  20. Subject who participated in another clinical trial study involving an investigational  product in the past 12 weeks,  21. In case of clinical necessity, a COVID-19 PCR (polymerase chain reaction) test will be  requested from the subjects, and subjects who are positive will be excluded from the  study,  22. Known history of SARS-CoV-2 infection,  23. Acute respiratory disease (moderate or severe illness with or without fever).  (Subjects may be screened again after acute condition has resolved),  24. Fever (greater than 37.8°C as measured by ear) (Subjects can be enrolled again after  acute condition improves),  25. Insufficient level of Turkish to perform the informed consent, except where briefing  by an independent witness can be provided and is available.

Study objective: To clarify the risk of exposure to indirect contact and transmission of  environmental objects during digestive endoscopy diagnosis and treatment for patients and  medical staff, simulating by using Vitamin B2 solution.  Study design: This is a case-only research. In the study, the object surface of the digestive endoscopy room is preliminarily analyzed,  and several key exposure units, such as potential high-frequency touch areas such as the  surface of the bed unit, are screened and defined. A fluorescence photographing system is  arranged in the digestive endoscopy room, and the exposure unit before treatment is  photographed with the best excitation wavelength of the fluorescent marker as the light  source, to get the experimental background reference. Then, patients undergoing digestive  endoscopy in the same endoscopy work unit (usually half a day) are selected. Before entering  the digestive center, the hands of patients are fluorescently marked with vitamin B2 mixed  hand sanitizer 1ml (vitamin B2 0.12mg/ml). Then, the doctors and nurses give routine care and  procedure. Based on the fluorescence tracing and detection methods, the indoor light source  is turned off after each selected endoscopy work unit, and the fluorescence residue on the  surface of key exposed units is photographed. The environmental surfaces touched by the  patient are sampled by the wiping method. The dosage is detected by the Fluoro Max-4®  fluorophotometer (HORIBA, Japan), which is quantified as a cumulative mass (μg) over all the  exposure time. Inclusion Criteria:  -  During the study period, patients who were treated in the digestive endoscopy center  of Beijing Union Medical College Hospital and planned to undergo gastroscopy. Age and  gender are not limited temporarily. Exclusion Criteria:  -  Allergic to medical non-toxic fluorescent agent: Vitamin B2 aqueous solution.  -  Poor general condition, including severe cardiopulmonary disease, difficult to  tolerate examination, and coagulation disorders.  -  Patients with contraindications to endoscopy.

Necrotizing soft-tissue infections (NSTI) are rare and life-threatening bacterial infections  characterized by subcutaneous tissue, fascia or muscle necrosis. Few prospective studies have  been performed and our current knowledge on NSTI is mostly derived from retrospective single  center studies. The "SKin and soft tissue necrotizing INfections in the ICU" (SKIN-ICU) study  is a multinational prospective non-interventional cohort study that will include patients  admitted to the ICU/intermediate care unit for NSTI or not.  The objectives of the study are :  1. To assess hospital (i.e., ICU and hospital mortality) and medium-term (day-90 mortality,  functional outcomes and health-related quality of life scores, HR-QoL) outcomes  2. To report the clinical presentation and microbiological epidemiology of NSTI and  identify independent prognostic factors of mortality and altered quality of life Necrotizing soft-tissue infections (NSTI) are rare and life-threatening bacterial infections  characterized by subcutaneous tissue, fascia or muscle necrosis. The mortality of NSTIs is  high, ranging from 9% in non-selected patients to up to 30% in the most severe forms  requiring intensive care unit (ICU) admission .  With an incidence of 4/100 000 persons per year, initial misdiagnosis is frequent, with no  reliable diagnostic test available, frequently leading to a delayed surgical debridement of  infected tissues, one of the main modifiable prognostic factors. According to international  recommendations, any cutaneous infection associated with the failure of one or more organs or  showing a dramatic deterioration must include the diagnosis of NSTI for consideration, even  if there is no local sign of the condition being severe. The diagnosis is confirmed by  identifying during surgery deficient tissue, sometimes necrotic, which comes away easily in  the fingers and by the presence of the typical, foul-smelling "dishwasher" exudate.  The early management of NSTIs is challenging and requires a coordinated and multidisciplinary  approach. Treatment of NSTIs consists of early broad-spectrum antimicrobial therapy together  with emergency and aggressive surgical debridement including excision of all necrotic and  infected tissues. Few prospective studies have been performed and our current knowledge on  NSTI is mostly derived from retrospective single center studies.The few randomized  therapeutic trials testing interventions in this setting have been disappointing, in part  because of the difficulty to identify subgroups for individualized treatments. A large  international study aimed at collecting granular data on the clinical presentation,  microbiology, management and outcomes of patients with NSTI admitted in the ICU and involving  a large number of centers and countries is thus desirable to improve our knowledge on this  devastating condition.  The "SKin and soft tissue INfections in the ICU" (SKIN-ICU) study is a multinational  prospective non-interventional cohort study that will include patients with NSTI admitted or  not to the ICU/intermediate care unit and aim at addressing the following points: 1) Hospital  (i.e., ICU and hospital mortality) and medium-term outcomes (three- and six-month survival,  functional outcomes and health-related quality of life scores, HR-QoL); and 2) Clinical  presentation and microbiological epidemiology of NSTI. Inclusion Criteria:  -  Age > 18 years  -  Patient with surgically-confirmed NSTI (i.e., macroscopic appearance of tissue during  surgery revealing swollen, dull gray tissues with a thin, brownish exudate with or  without necrosis) Exclusion Criteria:  -  Patient deprived of liberty by judicial or administrative decision or patient under  guardianship  -  Expressed opposition to project's participation at the project

Problematic Internet Use (PIU) and Unsafe Internet Use (UIU) are the two main potential  negative consequences of children's online activities. Parents have a vital role in reducing  these consequences and shaping a safe digital environment. Parental Vigilant Care (PVC) is a  systematic approach that integrates active and restrictive mediation practices, in which  parents regulate their involvement according to the alarm signs the parents detect.  This study is a randomized controlled trial designed to assess the efficacy of the PVC parent  training. Families were randomly assigned to either (1) PVC group (2) Technological Parental  Monitoring group (3) combining both group parental training and installation of filtering  devices (PVC + TPM) or (4) Control group. BACKGROUND: One of the most disturbing phenomena regarding the digital age is Problematic  Internet Use (PIU) among adolescents (12-16). PIU is defined as a functioning impairment due  to: (1) internet excessive use that may lead to the neglect of developmental tasks, or (2)  unsafe use which includes viewing inappropriate content, abusive encounters, or commercial  exploitation. Clinical and research experience shows that parental involvement plays a  critical role in reducing risk behaviors among adolescents in various domains. Despite the  ample literature regarding parental involvement, few studies have evaluated the efficacy of  parental involvement on adolescents' PIU in reducing functional impairment and designing a  safe digital environment. One of the most investigated theoretical approaches in this field  is Parental Monitoring (PM). PM is defined as a set of parental practices that aim to monitor  and supervise adolescent activities. Despite evidence that PM is effective in reducing risk  behaviors among adolescents, PM also has some drawbacks. Studies have demonstrated that it  may be perceived as rigid parental control, thereby damaging internalization of parental  presence, and potentially sabotaging adolescents' growing independence and autonomy. In the  digital world, rigid PM can be defined as using filtering and surveillance applications that  enable parents to closely monitor and enforce strict rules regarding their child's internet  use. This approach is defined as in the current study as "Technological Parental Monitoring"  (TPM). On the other hand, "Parental Vigilant Care" (PVC), is theoretically conceptualized as  an alternative parental involvement approach that addresses the weaknesses of PM. By  implementing PVC principles, parents develop a positive and non-judgmental dialogue with  their children regarding domains the participants are concerned about. Additionally, parents  determine their level of active involvement in a flexible manner, specific to the risks  presented by their children. By executing decisive and consistent parental involvement,  parents strengthen their presence in their children's digital world, therefore, reducing PIU  by internalization of safe digital behavior.  OBJECTIVES: The current study aims to examine the efficacy of using digital parental control,  according to TPM approach, in comparison with flexible integration of positive parental  presence with setting boundaries, according to PVC approach. These approaches will be  compared in light of the following outcomes: (1) increasing effective parental involvement in  PIU of their adolescent children, (2) reducing PIU and improving adolescent's functioning,  and (3) internalizing parental values regarding safe digital activities by children, in order  to maintain a parental presence over time.  METHOD: To examine these objectives, a randomized controlled trial was conducted.  Sample size calculation: To assess sample size, the investigators used G-Power software,  assuming type 1 error of 5%, power 80%, and analysis of variance, repeated measures with  three measurement points, a moderate effect size of time X group interaction (µ2 = .15). The  minimum sample size required to meet these assumptions was 134 participants. The final sample  consisted of 157 adolescents, in addition to their parents (one parent for each adolescent),  yielding a total sample size of 314 participants.  Two-hundred and 297 parents and their children (12-16 y/o) were randomly assigned to four  groups: (1) Group parental training according to PVC approach; (2) installation of filtering  devices on adolescents' mobile phones and setting them for reducing time use and prohibiting  inappropriate content (TPM); (3) combining both group parental training and installation of  filtering devices (PVC + TPM) and (4) control group that did not receive any intervention.  Three types of measures were used: (A) Self-reported questionnaires completed by parents:  Parental Helplessness for Internet Supervision, Internet Parental Styles, Norms for Unsafe  Internet Behaviour, Parental Knowledge of the child's online activities, Family Environment  and Adolescent's Functioning (B) Self-reported questionnaires completed by adolescent:  Problematic Internet Use and unsafe internet behavior (C) Cellular internet usage retrieved  directly from adolescents' mobile devices including total time online, as well as time by  specific contents (video games, pornography, gambling, YouTube and social networking sites).  The self-report questionnaires were gathered at three time points - before intervention (T1),  immediately after termination of intervention (T2) and after 8 weeks follow-up (T3). The  online activities data were gathered continuously for 12 weeks (a baseline week, 3 weeks of  intervention and 8 weeks of follow-up).  Data Analysis:  Data were analyzed using SPSS version 25. First, descriptive statistics were produced using  means and standard deviations for all variables. Group comparisons on demographic variables  were conducted using chi-square tests for categorical variables and t- tests for continuous  variables. Intervention effects were examined using intent-to-treat analyses. The groups were  compared with self-reported measures using repeated measures Analysis of Covariance,  examining interaction effect between time (within-subject) and group (between-subject). In  these analyses, the expectation to benefit from treatment was controlled. Post-hoc  corrections were used for to further examine the significant two-way interactions, and  depicted the effect sizes using Cohen's d's both between baseline (T0) and post-intervention  (T1), and also between post-intervention (T1) and follow-up (T2). Time of online activity was  analyzed using Multi-Level Modeling (MLM) since average daily time online per-week (12 weeks)  was nested in the child's group (PVC vs. Control). In addition, to examine the persistence of  improvement achieved during intervention, change in average time online between intervention  period (3 weeks) and the follow-up period (8 weeks) was tested. Inclusion Criteria:  -  Functioning deterioration of the child (age 12-16) due to online activity in the past  6 months in at least one of the following domains: school, social relationships,  participation in family activities, sleeping patterns, and mood (according to parents'  self-report).  -  The child owns a mobile phone. Exclusion Criteria:  -  A psychiatric diagnosis of the child  -  A significant personal crisis in the previous 12 months (e.g., divorce, loss of a  significant person)  -  A parental control application is installed on their children's mobile phones.

This is a multi-center, randomized, double-blind, placebo-controlled clinical trial to  evaluate two polypore mushrooms, Fomitopsis officinalis and Trametes versicolor (FoTv), to  treat COVID-19-positive outpatients with mild-to-moderate symptoms assigned to  self-quarantined and home management. The study aims to establish the safety and feasibility  of the use of FoTv vs placebo in 66 total subjects. Despite biomedical advances, medical intervention for COVID-19 is largely limited to  vaccinations and supportive care during the later stages of disease. While antiviral,  anti-inflammatory, and antimalarial options have been explored for later stages of disease,  fewer studies have been conducted on medications to reduce the risk of outpatient cases  progressing to severe disease. Therefore, it is important that we broaden the search to  include agents outside of our usual pharmacopeia. Integrative Medicine offers several  promising therapeutics that are available today and warrant investigation.  Some of the botanicals used for their possible immune modulating functions include polypore  mushrooms. Among these, Turkey Tail (Trametes versicolor) has a long history of use for its  immune supporting properties. An RCT examining the effects of Trametes versicolor in breast  cancer patients detected increases in lymphocyte counts and natural killer cell functional  activity (Torkelson et al, 2012 and Benson et al, 2019) both of which are key to host  COVID-19 response. Further investigations into other relevant mushroom species demonstrated  that Agarikon (Fomitopsis officinalis) can strongly induce an array of differential cytokine  responses associated with both immune-activation and resolution of host defense- induced  inflammatory reactions (unpublished). This homeostatic effect deserves attention for COVID-19  given the high mortality rate associated with cytokine storm.  This is a multi-center, randomized, double blind, placebo-controlled clinical trial to  evaluate two polypore mushrooms, Fomitopsis officinalis and Trametes versicolor (FoTv), to  treat COVID-19-positive outpatients with mild-to-moderate symptoms assigned to  self-quarantined and home management. This study aims to establish the safety and feasibility  of the use of FoTv vs placebo in 66 total subjects. Subsequent trials will evaluate Chinese  herbal medicine as well as the efficacy of FoTv in a larger study population. Inclusion Criteria:  -  Positive COVID-19 diagnosis within the prior 72 hours  -  Age 18 years and older  -  Women of childbearing potential must have a negative urine or serum hCG. Women of  childbearing potential must have a negative serum pregnancy test at screening and  agree to use contraception throughout the study period.  -  Capable of documenting vitals, symptoms, and study product intake daily and  communicating this information to the study team  -  Willing to avoid alcohol, cannabis, and dairy products during the study period. Exclusion Criteria:  -  Any of the following symptoms which, according to the CDC, require hospitalization:  1. Trouble breathing  2. Persistent pain or pressure in the chest  3. New confusion or inability to arouse  4. Bluish lips or face  -  Current use of investigational agents to prevent or treat COVID-19  -  Known liver disease (ALT/AST >3x ULN or diagnosis of cirrhosis)  -  Known renal disease (eGFR < 60 ml/min) or acute nephritis.  -  Uncontrolled hypertension (SBP>140 or DBP>90 while on medications)  -  Pregnant or breastfeeding women

DYNAMIC AF is an observational, prospective, multi-center, non-randomized registry designed  to obtain real world clinical experience of radiofrequency (RF) ablation for the treatment of  paroxysmal (PAF) and persistent (PsAF) atrial fibrillation ablation. Patient assessments will  occur at pre- procedure, procedure, 12 weeks, 6 months and 1 year post ablation. Dynamic AF is a prospective, observational, multi-center, non-randomized registry designed to  obtain real world clinical experience associated with the use of Abbott technologies for AF  ablation. Future technologies may be included as they become available in the market. The  registry population will include patients with symptomatic PAF or PsAF that meet all  eligibility criteria, who, in the opinion of the investigator, are candidates for AF  ablation.  All patients will be treated with commercially approved catheters and the ablation procedure  will be conducted based on the current standard of care. Participation in the registry does  not influence treatment decisions. All consecutive patients presenting at the institution  considered for an RF ablation procedure for symptomatic PAF or PsAF should be screened by the  investigator or designated member of the research team for study eligibility  The primary purpose of this registry is to assess procedural efficiencies as well as long  term procedural safety and effectiveness of RF ablation in the treatment of patients with  paroxysmal or persistent atrial fibrillation. The registry will utilize real world clinical  data obtained from the use of commercially available technologies under the authority of a  health care practitioner within a legitimate practitioner-patient relationship.  To support the objective of the registry, both patient information and procedure data will be  collected. Patient-related data will be collected at a pre ablation office visit, a 12-week  post ablation office visit, interim arrhythmia recurrence monitoring at 6- and 12-month post  ablation and a 12-month post ablation office visit. Procedure related data collection will  include procedural workflow and acute, mid and late onset procedure or device related  complications. Inclusion Criteria:  -  Patients with symptomatic, refractory or intolerant to at least one Class I or III  AAD, paroxysmal atrial fibrillation (AF episode terminating spontaneously within 7  days) or symptomatic, refractory or intolerant to at least one Class I or III AAD,  persistent AF (continuous AF sustained beyond 7-days and less than 1-year) who, in the  opinion of the investigator, are candidates for ablation for AF. Refusal to take AADs  for any reason is considered intolerant for the purposes of this protocol.  -  Plans to undergo an RF catheter ablation procedure using an ablation catheter  manufactured by Abbott  -  De Novo ablation unless it is a repeat procedure for a subject whose index procedure  is also included in the registry  -  18 years of age or older  -  Able and willing to participate in baseline and follow up evaluations for the full  length of the registry Exclusion Criteria:  -  Pregnant women  -  Individual who cannot read or write, or those who cannot legally consent for  themselves  -  Participating in another clinical trial or has participated in a clinical trial within  30 days prior to screening that may interfere with this registry.  -  Long-standing persistent AF (continuous AF sustained >=1 year)  -  Previous left atrial surgery for atrial fibrillation  -  Having a repeat ablation, unless the subject's index ablation procedure is also  included in the registry  -  In the opinion of the investigator, any known contraindication to an ablation  procedure or to any device or drug required for use during an ablation procedure as  assessed by the investigator

Macrophage surface markers (CD80, CD163 and CD206) will be evaluated in periodontally healthy  gingiva, healthy peri-implant mucosa, and periodontitis and peri-implantitis lesions. Soft tissue biopsies obtained from clinically healthy gingiva, healthy peri-implant mucosa,  Stage III Grade C periodontitis lesions and peri-implantitis lesions will be evaluated.  Healthy peri-implant samples are obtained from submerged implants during exposure surgery.  Healthy gingiva samples are obtained from individuals receiving crown lengthening,  gingivectomy or tooth extraction as excess tissue during the corresponding treatment. Samples  from peri-implantitis and periodontitis (pocket depth ≥6 mm, bleeding on probing+) are  obtained during initial periodontal treatment / debridement procedure with a single stroke at  the pocket wall.  The samples will be grinded and ultrasonicated. Western blotting will be used for  determination of CD80, CD163 and CD206 in biopsy specimens. ImageJ will be used for intensity  analysis of the bands. Inclusion Criteria:  -  diagnosed with generalized Grade C Stage III periodontitis  -  diagnosed with peri-implantitis  -  periodontally healthy individuals with dental implants in the primary healing period  -  periodontally healthy individuals who are in need of crown lengthening / gingivectomy  or extraction Exclusion Criteria:  -  systemic disease  -  smoking / former smokers  -  regular medicine intake  -  antibiotic or anti-inflammatory medicine intake in the last 3 months  -  pregnancy or lactation

This study is a prospective evaluation of the Hydrus Microstent for the treatment of Primary  Angle Closure (PAC) and Primary Angle Closure Glaucoma (PACG) with adjunctive cataract. A  total of 20 subjects will be successfully treated with one Hydrus device after completion of  cataract extraction with phacoemulsification followed by IOL replacement (HMS cohort), and 10  eyes will be treated with phacoemulsification cataract extraction and IOL replacement only  (PCS group). Since cataract surgery is standard of care for this condition, eligible fellow  eyes from the HMS cohort may be enrolled into the PCS group. To avoid selection bias in this  non-randomized study, the first 20 consecutive qualifying subjects will be treated with  Hydrus and the next 10 consecutive qualifying eyes will be treated with cataract surgery  only. The objective of this study is to assess the effectiveness of the Hydrus Microstent for  lowering intraocular pressure in patients with PAC or PACG. The addition of the Hydrus is  expected to lower IOP and medication dependency, and thus reduce the risk of progression of  glaucoma. The PCS group will provide a control group to assess the magnitude of the Hydrus  treatment effect on IOP, medications, and safety.  Upon successfully meeting the study inclusion/exclusion criteria at both the screening and  baseline visits, the subject will be scheduled for surgery. Follow up will be continued for 1  year post surgery, and will include assessments of the subject's IOP, ocular health, and  visual acuity status. Visits will be conducted at 1, 7, 30, 90, 180, and 365 days.  A 20% drop in IOP in response to therapy is considered clinically meaningful. The study  treatment will be considered successful if a patient can obtain this response in IOP using  the same or a fewer number of medications as pre-operative baseline. Inclusion Criteria:  Pre-Operative Inclusion Criteria  1. Male and Female patients at least 40 years of age.  2. An operable age-related cataract with visual impairment or glare, eligible for  phacoemulsification.  3. Subjects with diagnosed primary angle-closure (PAC; defined as appositional or  synechial irido-trabecular contact of 90 degrees or more on gonionscopy) OR primary  angle-closure glaucoma (PACG; defined as PAC with documented glaucomatous optic  neuropathy and/or reproducible glaucomatous visual field defect), and on > or = 1  glaucoma medication with IOP > or = 21mmHg at both preoperative visits.  4. PAC or PACG subjects that are newly diagnosed, or unmedicated (newly diagnosed or  non-compliant patient not using medication for > 30 days), with IOP > or = 24mmHg at  both preoperative visits.  The subject is able to understand the requirements of the study and is willing to provide  written informed consent, follow study instructions, and comply with all study procedures.  Intraoperative Inclusion Critera  1. An intact and centered capsulorhexis.  2. An intact posterior capsular bag.  3. A well-centered IOL implant placed in the capsular bag.  4. A clear view and visualization of the angle with direct gonioscopy.  5. No evidence of zonular dehiscence/rupture (uncomplicated cataract extraction) Exclusion Criteria:  1. Pseudophakia in the intended study eye  2. All forms of glaucoma other than primary angle-closure (i.e. all open-angle glaucoma  including primary open-angle, pseudoexfoliative, or pigmentary glaucoma; neovascular,  uveitic, traumatic, steroid induced, lens induced, or glaucoma associated with  increased episcleral venous pressure; congenital or developmental glaucoma).  3. Secondary angle-closure glaucoma  4. Advanced glaucoma, defined as visual field mean deviation worse than -15 dB, or  cup-to-disc ration > or = 0.9.  5. Visual field depression within the central 5 degrees of fixation, on pattern deviation  probability plot.  6. Eyes with an anticipated need for incisional glaucoma surgery (e.g. trabeculectomy or  tube shunt) within the 12-month follow-up period.  7. Central corneal thickness >620 or <490 microns.  8. Axial length < or = 19 mm (nanophthalmos).  9. Previous incisional glaucoma surgery in the study eye, including trabeculectomy, tube  shunt, and non-penetrating procedures such as deep sclerectomy, viscocanalostomy or  canaloplasty.  10. Plateau iris syndrome.  11. History of complicated intraocular surgery.  12. Previous MIGS surgery in the study eye.  13. Proliferative diabetic retinopathy.  14. Previous surgery for retinal detachment.  15. Clinically significant corneal dystrophy (e.g. Fuch's Dystrophy).  16. Best-corrected visual acuity in the fellow eye worse than 20/200.  17. Previous corneal surgery.  18. Previous refractive surgery.  19. Degenerative visual disorders such as exudative age-related macular degeneration.  20. Clinically significant ocular inflammation or infection within thirty days prior to  screening.  21. Uncontrolled systemic disease that in the opinion of the investigator would put the  subject's health at risk and/or prevent the subject from completing all study visits.  22. Pregnant or nursing females.

The study intends to establish proof of concept for a fractional dose schedule under  conditions of natural exposure in children 5-17 months old at first vaccination. The study  also aims to establish the role of third dose spacing in a fractional dose schedule, describe  the effect of an earlier full fourth dose at Month 14 and describe the effect of multiple  fractional or full yearly doses. The current study intends to establish proof of concept (POC) for a fractional dose schedule  under conditions of natural exposure. The study will be conducted in children 5-17 months old  at first vaccination living in areas of mid to high malaria transmission, in line with the  age group recommended by the World Health Organization (WHO) for the implementation of the  RTS,S/AS01E vaccine. Results from this study will be critical in informing future  possibilities for the development of vaccine-based strategies which, in combination with  other interventions, may contribute to the malaria elimination agenda. Inclusion Criteria:  -  Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will  comply with the requirements of the protocol (e.g. return for follow-up visits).  -  Signed or thumb-printed and witnessed informed consent obtained from the  parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.  Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by an  independent witness.  -  A male or female between, and including, five and 17 months of age at the time of the  first vaccination.  -  Healthy subjects as established by medical history and clinical examination before  entering into the study.  -  Previously received three documented doses of diphtheria, tetanus, pertussis,  hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine. Exclusion Criteria:  -  Child in care.  -  Use of a drug or vaccine that is not approved for that indication (by one of the  following regulatory authorities: Food and Drug Administration [FDA; USA] or European  Union member state or WHO [with respect to prequalification]) other than the study  vaccines during the period starting 30 days before the first dose of study vaccines  (Day -29 to Day 0), or planned use during the study period.  -  Any medical condition that in the judgment of the investigator would make  intramuscular injection unsafe.  -  Chronic administration (defined as more than 14 days in total) of immunosuppressants  or other immune-modifying drugs during the period starting six months prior to the  first vaccine dose. For corticosteroids, this will mean prednisone (0.5 mg/kg/day (for  pediatric subjects) or equivalent. Inhaled and topical steroids are allowed.  -  Planned administration/administration of a vaccine not foreseen by the study protocol  in the period starting seven days before each dose and ending seven days after each  dose of vaccine administration.  -  Concurrently participating in another clinical study, at any time during the study  period, in which the subject has been or will be exposed to an investigational or a  non-investigational vaccine/product (pharmaceutical product or device).  -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on  medical history and physical examination (no laboratory testing required).  -  Family history of congenital or hereditary immunodeficiency.  -  History of any reaction or hypersensitivity likely to be exacerbated by any component  of the vaccines.  -  History of anaphylaxis post-vaccination.  -  History of any, or documented, serious adverse reaction to rabies vaccination.  -  Contraindication to rabies vaccination (Rabipur is contraindicated in subjects with an  history of a severe hypersensitivity to any of the ingredients in the vaccine. Note  that the vaccine contains polygeline and residues of chicken proteins, and may contain  traces of neomycin, chlortetracycline and amphotericin B).  -  Major congenital defects.  -  Serious chronic illness.  -  Children with a past history of a neurological disorder or atypical febrile seizure (a  febrile seizure is atypical if it meets one of the following criteria: not associated  with fever; lasts > 5 minutes; focal (not generalized); followed by transient or  persistent neurological abnormality; occurs in a child < 6 months of age).  -  Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥  37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal  route.  Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection)  without fever may, be enrolled at the discretion of the investigator.  -  Administration of immunoglobulins and/or any blood products during the period starting  three months before the first dose of study vaccine or planned administration during  the study period.  -  Moderate or severe malnutrition at screening defined as weight for age or weight for  height Z-score < -2.  -  Hemoglobin concentration < 8 g/dl at screening.  -  Same sex twins (to avoid misidentification).  -  Maternal death.  -  Prior receipt of an investigational malaria vaccine.

This study will compare the effects of fractionated CO2 laser plus topical steroids versus  topical steroids alone in treatment of lichen sclerosus. Vulvar lichen sclerosus is a common benign skin condition which causes pain and itching.  Topical steroids have been the main treatment. A recent study showed that fractionated CO2  laser treatment is non inferior and actually may improve subjective symptoms compared to  topical steroids with no serious safety or adverse events. Because steroids reduce risk of  vulvar cancer in patients with lichen sclerosus, the investigators hypothesize that steroids  in addition to the fractionated laser will provide greater symptom relief while still  allowing patient the benefits of steroid treatment. Inclusion Criteria:  -  women with biopsy proven lichen sclerosus and significant symptoms based on Skindex-29  scores >21 Exclusion Criteria:  -  prior vaginal mesh or pelvic radiation  -  active genital infection  -  Current or past gynecologic malignancy

The purpose of this study is to determine which method is most effective for teaching the  kettlebell swing: verbal cueing, physical constraints, or a combination of the two. There is a method of teaching and learning movement and exercise skills known as the  constraint-led approach. This method of movement learning has the learner exploring and  experimenting different variations of an exercise by self-organizing around a set of given  constraints of the individual, environment and task (Newell 1986, Moy & Renshaw 2020, chow et  al. 2011). Individual constraints are qualities about the person performing the task such as  their arm length and height. Environmental constraints regard the environment where the task  is being performed and include factors such as lighting and temperature. Finally, the task  constraints are qualities about the movement and exercises being performed such as asking  someone to do a half squat onto a box instead of a full bodyweight squat in the air. This  constraints way of teaching movement has the movement educator as a guide or architect that  shapes the qualities of the task the learner must navigate.  The kettlebell swing was chosen as the primary exercise for this study due to its efficacy  and practicality as a functional movement pattern. Current literature suggests that  kettlebell swings may elicit an increase in strength measured in the form of a deadlift  exercise, which may have carry over to activities of daily living, such as bending over to  lift a box with proper form (Maulit et al, 2017). In a 2016 study, Edinborough et al.  examined the proposed implications that repeated kettlebell swings could be used as a  practical tool to increase endurance capacity of the lumbar extensor complex. The  investigators of this study found that after a 60 second bout of continuous kettlebell  swings, participants demonstrated a reduction in isometric strength, demonstrating fatigue of  this musculature. The implications of this study suggest that kettlebell swings may increase  the fatigue threshold of the lumbar extensor musculature, which may provide protective  measures regarding the development of musculoskeletal conditions such as low back pain, as a  decrease in activation of these associated muscles may be apparent during periods of fatigue. Inclusion Criteria:  -  Subjects between the ages of 18 and 55 years.  -  Subjective rating of 3/5 or less on confidence with kettlebell swings. Exclusion Criteria:  -  Inability to read and write in English.  -  Previous injury to the lower extremity that prevents normal squatting motion.  -  Physical Activity Readiness Questionnaire suggesting inability to safely participate  in exercise.

The baseline infusion rate during surgery for pediatric patients still is the 'Holliday and  Segar' rule (also known as the 4/2/1 rule) The question arises if this rule is not outdated,  since it was calculated based on the caloric need of the pediatric population, calculated for  cow milk. The study tends to validate the use of bio impedance measurements for registering  fluid shifts in the pediatric surgical patients. The Body Composition Monitor (BCM, Fresenius Medical Care, Germany) is the first device that  determines individual fluid status and body composition in an easy and objective way. The  technology uses bioimpedance spectroscopy (BIS) to determine total body water (TBW) and  extracellular water volume (ECW).It measures at 50 frequencies over a range from 5 to 1000  kHz to determine the electrical resistances of the total body water and the extracellular  water. While high-frequency current passes through the total body water, low-frequency  current cannot penetrate cell membranes and thus flows exclusively through the extracellular  water.  To obtain the clinically relevant output parameters, two advanced physiological models are  used in the BCM: a volume model, describing electrical conductance in a cell suspension  enabling the total body water and extracellular water as well as the intracellular water  (ICW) to be calculated, and a body composition model calculating the three principal body  compartments overhydration, lean tissue and adipose tissue from ECW and TBW information.  The measurement is a non-invasive and accurate method that is easy to apply and results are  obtained within just two minutes. It has been extensively used in patients with kidney  disease receiving dialysis, both in adult and pediatric patients. However, bio impedance  spectrometry has not yet been tested in the perioperative setting.  This is a single-center pilot study to evaluate if bio impedance measurement is a workable  tool to determine fluid shifts in the pediatric population after a surgical procedure was  performed under general anesthesia. Patients will be seen preoperatively by an  anesthesiologist which is standard of care upon surgery under general anesthesia and  eligibility will be evaluated. Informed consent will be asked and has to be signed by the  accompanying parent or legal guardian. Where possible, care will be taken to inform the child  itself about the content of the study and to get a written acknowledge. There are no other  investigations necessary for this research. All patients on the day of surgery will be fasted  as by the guidelines of the European Society of Anesthesia. For patients in daycare surgery,  measurements with BCM will be performed preoperatively and postoperatively before ending the  IV line on the ward. For inpatient hospitalisation, measurements by BCM will be performed  preoperatively, postoperatively 6 hours after induction and postoperatively 24 h after  induction.. Age, gender, height, weight and blood pressure are registered in the device  before starting the measurement. If the quality calculated by BCM is < 60%, the measurement  will be repeated again and only good quality measurements will be used.  Data are collected on chip cards by the BCM. Data can be transferred to a personal computer  for further analysis with the Fluid Management Tool (FMT). Site requirements is the  availability of a low electronic surrounding for correct measurement. After discharge of the  hospital no further follow up assessments regarding this study are needed. Inclusion Criteria:  -  Scheduled for elective surgery or investigation under general anesthesia  -  Day care or inpatient hospitalisation Exclusion Criteria:  -  If sedation is needed instead of general anesthesia  -  Critically ill patients for urgent surgery  -  Patients who cannot lie still for performing correct measurements on the bio impedance  monitor  -  No informed consent obtained

This is a prospective, double-blind, placebo-controlled, randomized clinical trial to assess  the effects of daily 4-gram marine omega-3 polyunsaturated fatty acid (MO3PUFA), through  treatment with AMR101 (VASCEPA, icosapent ethyl) on the tumor immune microenvironment and gut  microbiome in patients who are diagnosed with colorectal cancer or with a colorectal mass or  polyp suspected to be a cancer or advanced adenoma and will undergo surgical resection or  interventional endoscopy at the Massachusetts General Hospital (MGH). It uses the novel  "window-of-opportunity" clinical trial design to take advantage of the window of time between  cancer/mass/polyp diagnosis and surgery to examine the effect of therapeutic agents on tumor  pathologic and molecular features unperturbed by prior therapies. This research study is evaluating the effect of AMR101, as a chemopreventive agent to reduce  risk of colorectal cancer in individuals with a history of colorectal cancer, colorectal mass  or polyp(s).  AMR101 is made of marine omega-3 fatty acid, which is a family of natural substances found in  the oil of certain fish, such as salmon and mackerel. Marine omega-3 fatty acid cannot be  produced in sufficient amount by the human body and has to be obtained through diet or  supplemented to maintain normal function in the body.  The U.S. Food and Drug Administration (FDA) has not approved AMR101 as a treatment for any  disease. AMR101 is commercially available in the US as VASCEPA (icosapent ethyl).  The research study procedures include screening for eligibility and study treatment including  evaluations and follow up visits during which participants will complete a lifestyle  questionnaire and a nutritional survey. A drug diary will be provided to be completed.  Measurements will be taken, and blood and stool specimens will be collected. Tumor,  colorectal mass, or polyp tissue will be collected for research purposes at the time of  surgery or interventional endoscopy.  AMR101 administered daily, orally for up to 30 days and it is expected that 36 participants  will take part in this study. Inclusion Criteria:  Participants must meet the following criteria on screening examination to be eligible to  participate in the study:  Participants have histologically confirmed adenocarcinoma of the colon that is localized,  with no evidence of distant metastasis (stage I, II, or III), and for which surgical  resection of the primary tumor is being planned;  OR  Participants may have a colon biopsy that is suspicious for adenocarcinoma if clinical  and/or endoscopic findings strongly support the presence of malignancy, and if surgical  resection is being planned. NOTE: In the unlikely event that the final pathology of the  surgical resection specimen is consistent with high-grade adenoma or dysplasia, the patient  will not be considered ineligible and collected research samples will still be utilized.  OR  Participants have a diagnosis of a colorectal mass or polyp suspected to be a cancer or  advanced adenoma at the most recent colonoscopy and are being referred to an advanced  endoscopist to undergo interventional endoscopy within 30 days.  Age >= 18 years  This study will only include adult participants because colorectal carcinogenesis in  children is more likely to be related to a cancer predisposition syndrome with distinct  biological mechanisms compared with sporadic colorectal cancer in adults.  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)  Patients must be sufficiently healthy to undergo surgery/interventional endoscopy.  The effects of AMR101 on the developing human fetus are unknown. For this reason, women of  child-bearing potential and men must agree to use adequate contraception (hormonal or  barrier method of birth control; abstinence) prior to study entry and for the duration of  study participation. Should a woman become pregnant or suspect she is pregnant while  participating in this study, she should inform her treating physician immediately.  Subjects must be able and willing to follow study procedures and instructions.  Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria:  Participants who exhibit any of the following conditions at screening will not be eligible  for admission into the study.  Prior systemic or radiotherapy treatment for colorectal cancer.  Participants who are receiving any other investigational agents.  Concurrent use of other anti-cancer therapy, including chemotherapy agents, targeted  agents, biological agents, immunotherapy, or investigational agents not otherwise specified  in this protocol.  Inability or unwillingness to swallow pills.  History of malabsorption or uncontrolled vomiting or diarrhea, or any other disease that  could interfere with absorption of oral medications.  History of allergic reactions attributed to fish or compounds of similar chemical or  biologic composition to MO3PUFA.  Currently using or have used any fish oil supplement at any dose more than once per week  within the last month.  Regularly consuming more than three servings of fish per week.  Known bleeding tendency/condition (e.g. von Willebrand disease)  Current use of anticoagulants or antiplatelet therapies, including aspirin and other  nonsteroidal anti-inflammatory drugs (NSAIDs, including Ibuprofen [Advil, Motrin], Naproxen  [Aleve, Anaprox DS, Naprosyn], and Celecoxib [Celebrex]), Heparin, Warfarin, Dalteparin  sodium, Bivalirudin, Argatroban, Lepirudin, Heparin Sodium, Heparin/Dextrose, and an  unwillingness or inability to discontinue anticoagulants.  Any 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, in the opinion of the  investigator, may increase the risks associated with study participation or study  treatment, limit compliance with study requirements, or interfere with the interpretation  of study results.  Pregnant or breastfeeding.  The effects of AMR101 on the developing human fetus are unknown. For this reason, women of  child-bearing potential must agree to use adequate contraception (hormonal or barrier  method of birth control; abstinence) prior to study entry and for the duration of study  participation. Should a woman become pregnant or suspect she is pregnant while she is  participating in this study, she should inform her treating physician immediately.  Similarly, lactating women are excluded from this study because there is an unknown but  potential risk of adverse events in nursing infants secondary to treatment of the mother  with AMR101. Consequently, breastfeeding should be discontinued if the mother is enrolled  on the study.  Presence of synchronous (at the same time) malignancy for which the patient is currently  receiving active treatment.  Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or  chronic hepatitis B infection.  Participants with these infections are ineligible because they are at increased risk of  significant complications in the perioperative period, and because fresh tissue from  patients with these infections cannot be harvested for research purposes, per institutional  policy. Appropriate studies will be undertaken in participants receiving combination  antiretroviral therapy when indicated.  Inclusion of Women and Minorities  Women and minorities will be eligible for this study without alteration in eligibility  criteria. Enrollment of these underrepresented populations to this trial will be  encouraged.

To evaluate the efficacy and safety of adjunctive pimavanserin compared to placebo in  subjects with major depressive disorder who have an inadequate response to antidepressant  therapy Two separate studies, idential in design, were planned and initiated under 2 protocol IDs and  NCTs, i.e. study ACP-103-54 (NCT03999918) and ACP-103-059 (NCT03968159). In March 2020,  recruitment of new patients was paused due to the emerging coronavirus disease 2019  (COVID-19) pandemic. At that point in time, about half of the planned patients had been  randomized. The Sponsor decided to combine the 2 identically designed trials, with a  prespecified combined statistical analysis plan. As a result, both trials were closed and  proceeded with database lock and statistical analysis of the combined data. No further  patients were enrolled.  This entry now includes the combined data of studies ACP-103-054 and ACP-103-059. Inclusion Criteria:  1. Adult patients, aged 18 years and above  2. A clinical diagnosis of major depressive disorder (MDD)  3. Is being treated with one of the following SSRI or SNRI antidepressants:  1. Citalopram  2. Escitalopram  3. Paroxetine  4. Fluoxetine  5. Sertraline  6. Duloxetine  7. Venlafaxine  8. Desvenlafaxine  9. Venlafaxine XR  4. Inadequate response to SSRI/SNRI antidepressant treatment is confirmed  5. If the subject is female, she must not be pregnant or breastfeeding. She must also be  of non-childbearing potential OR must agree to use acceptable methods of contraception Exclusion Criteria:  1. Has a history of psychotic disorder or is currently being treated or requires  treatment for post-traumatic stress disorder, acute stress disorder, panic disorder,  or obsessive compulsive disorder  2. Has current evidence of delirium or an unstable neurological, cardiovascular,  respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder,  including cancer or malignancies that would affect the patient's ability to  participate in the program  3. Has a known history or symptoms of long QT syndrome  4. Is determined to be inappropriate for the study for any reason  Additional inclusion/exclusion criteria apply. Patients will be evaluated at screening to  ensure that all criteria for study participation are met. Patients may be excluded from the  study based on these assessments (and specifically, if it is determined that their baseline  health and psychiatric condition do not meet all pre-specified entry criteria).

Due to COVID-19, the routine treatment for dementia, Cognitive Stimulation Therapy (CST), is  currently suspended in multiple countries. Access to treatment is, therefore, paramount. The  investigators seek to bridge the current treatment gap with a virtual and individual form of  CST, called Virtual Individual Cognitive Stimulation Therapy (V-iCST). This psychosocial  intervention was adapted from the key principles of CST and developed within the Medical  Research Council (MRC) framework for complex interventions. The investigators aim to evaluate  the feasibility and acceptability of V-iCST in a Randomized Controlled Trial.  This is a feasibility randomized controlled trial (RCT) for Virtual Individual Cognitive  Stimulation Therapy (V-iCST), an evidence-based teletherapy for people with mild to moderate  dementia. This psychosocial intervention is adapted from a routine and established dementia  treatment, Cognitive Stimulation Therapy, and developed within the Medical Research Council  (MRC) framework for complex interventions. Dementia, a global epidemic, affects 50 million individuals worldwide. Cognitive Stimulation  Therapy (CST) is the only non-pharmacological therapy recommended by the UK government to  improve cognition for mild to moderate dementia. It is delivered in over 85% of National  Health Services (NHS) services and is offered in 34 countries. Unfortunately, this routine  treatment is suspended due to lockdown, even though people with dementia are  disproportionately affected by COVID-19. Accessible treatment is a pressing need. Virtual  Individual Cognitive Stimulation Therapy (V-iCST) aims to bridge this treatment gap as an  evidence-based treatment for dementia, developed within the Medical Research Council (MRC)  Framework for complex interventions using principles of CST. There may still be a demand for  V-iCST post-pandemic because those with sensory impairments and lack of transport provision  may prefer a virtual and individual treatment. The investigators aim to 1) design V-iCST; 2)  evaluate V-iCST in a feasibility Randomized Controlled Trial (RCT). A sample of 34  participants will be recruited. Seventeen will be allocated to V-iCST, and 17 to treatment as  usual (TAU), the control group. Data will be collected pre-and post-test. Dementia prevalence  is projected to reach 152 million worldwide by 2050. Therefore, accessible treatment is  paramount during the pandemic and beyond. Inclusion Criteria:  1. Diagnosis of dementia, according to the DSM-IV  2. MoCA - BLIND ≥ 2  3. Age ≥ 18  4. Ability to communicate in English  5. Ability to complete outcome measures  6. Capacity to consent  7. Consent to video-conferencing  8. Access to video-conferencing Exclusion Criteria:  1) Illness and disability that affects participation (as deemed by researcher)

The research question is whether a single fraction of preoperative radiosurgery can reduce  the incidence of leptomeningeal disease 12 months following resection of a brain metastasis  (BM) as compared with 5 fractions of postoperative stereotactic radiotherapy. Neurosurgical resection of a brain metastasis in patients with a diagnosis of cancer may be  indicated however the recurrence rate approximates 50% and adjuvant radiotherapy is standard.  Single fraction postoperative stereotactic radiosurgery (SRS) has been widely adopted as a  standard therapy as it achieves equivalent survival and prevents loss of neurocognitive  function as compared with whole brain radiotherapy and improves cavity local control rates as  compared with observation. Hypofractionated stereotactic radiotherapy in 3 to 5 fractions  (hfSRT) is also used in the postoperative setting.  Nodular leptomeningeal disease (nLMD) is a recognised pattern of failure after postoperative  SRS and hfSRT. A 16.9% incidence of nodular LMD was seen after surgery and a similar  incidence of 11%-28%is reported following postoperative SRS in retrospective series. These  data suggest that postoperative SRS/hfSRT have no significant effect on the development of  LMD following surgery.  The incidence of LMD following single fraction preoperative SRS is only 6.1% according to the  largest retrospective series. Preoperative SRS takes advantage of the easier delineation of  an intact BM and sterilizes tumor cells disseminated at surgery. Side effects are minimized  by a smaller planning margin, a dose reduction and resection of the irradiated volume. In  addition, there is no delay to systemic therapy due to wound healing/complications.  Furthermore, a single fraction offers patient convenience.  This trial will randomise and compare intracranial outcomes between single fraction  preoperative SRS and 5 fraction postoperative hFSRT. Inclusion Criteria:  1. Provision of signed and dated informed consent form  2. Stated willingness to comply with all study procedures and availability for the  duration of the study  3. Age ≥18  4. Karnofsky performance status ≥60  5. Histological diagnosis of a malignant primary or metastatic tumour  6. Ability to take steroids  7. No contraindication to magnetic resonance imaging (MRI)  8. MRI-diagnosis of a clearly demarcated contrast-enhancing brain metastasis up to 4.0 cm  diameter indicated for neurosurgical resection (tumorboard decision). Up to 3 other  brain metastases suitable for primary radiosurgery/ stereotactic radiotherapy  9. Survival estimated by primary clinician > 12 months  10. Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL Exclusion Criteria:  1. Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma  2. >10 mm midline shift, effacement of the 4th ventricle or other sign of raised  intracranial pressure requiring urgent decompressive surgery  3. More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm.  4. More than 1 metastasis requiring resection  5. Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated  then resected with the metastasis)  6. Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT)  7. Prior resection of a primary or secondary brain tumor  8. Prior diagnosis of a non-meningioma brain tumor  9. Prior radionuclide therapy within 30 days  10. Prior anti-VEGF therapy within 6 weeks  11. Unable to tolerate radiosurgery immobilization and treatment  12. Inability to give informed consent  13. Pregnancy or lactation  14. Females of reproductive potential not willing to use effective contraception for at  least 6 months after radiotherapy  15. Males of reproductive potential not effective contraception for 3 months after  radiotherapy  16. Lack of likely compliance with protocol and follow-up

This is an open-label, multicenter, observational study evaluating GI symptoms in  relapsing-remitting multiple sclerosis (RRMS) patients who switch from dimethyl fumarate  (DMF) to Bafiertam®. This is an open-label, multicenter, observational study evaluating GI symptoms in  relapsing-remitting multiple sclerosis (RRMS) patients who switch from dimethyl fumarate  (DMF) to Bafiertam® (monomethyl fumarate).  Adult patients with a diagnosis of RRMS receiving continuous treatment with DMF monotherapy  and who are experiencing GI symptoms will be eligible to enroll in the study.  Patients will be identified and screened by chart review and invited to report GI Symptoms  for one baseline week using a study app downloaded on their own smartphone/tablet. During  this week, patients will continue their currently prescribed and remaining DMF treatment and  will record their GI symptoms daily using the app.  At the end of the Baseline Period, patients will be asked to cease administration of the DMF,  and to commence self-treatment with Bafiertam® 95 mg capsules twice a day (total daily dose  of 380 mg) approximately 12 hours apart the following day for 28 days. They will be required  to continue to record their GI symptoms each day.  On Day 28; End-of Study [EOS]) the patient's diary will be reviewed, adverse events (AE)  recorded, and drug accountability performed.  Following EOS patients will be asked if they wish to continue Bafiertam® treatment. Those  patients who elect to continue will be contacted one month and two months after EOS to  ascertain if they remain on Bafiertam®. Inclusion Criteria: None Exclusion Criteria: None

This is a study of the safety and efficacy of MDMA-assisted therapy in people with war or  terrorism-related posttraumatic stress disorder (PTSD). Posttraumatic stress disorder (PTSD) occurs after experiencing a traumatic event or events.  PTSD is a public health problem that causes a great deal of suffering. This study will  examine whether two six to eight-hour long sessions of 3,4-methylenedioxymethamphetamine  (MDMA)-assisted therapy scheduled three to five weeks apart are safe, and whether combining a  fully therapeutic dose of MDMA with psychotherapy, compared with a low ("active placebo")  dose of MDMA, will reduce PTSD symptoms, with symptoms measured four times, twice during the  study, and during two follow-up assessments six and twelve months after the second  experimental session. People who received the active placebo dose of MDMA can then take part  in an "open label" study continuation, with the participant receiving a fully active dose of  MDMA on two more six to eight hour-long psychotherapy sessions. Open-label means that the  participants and the researchers know that the participant will receive the fully active dose  of MDMA. People who receive the full dose of MDMA, and anyone who received low-dose MDMA and  does not undergo the open-label study continuation will have PTSD symptoms measured six and  twelve months after the second fully active or low dose MDMA session. People who take part in  the open label study continuation have their PTSD symptoms checked six and 12 months after  the second open label MDMA-assisted session.  MDMA is a substance that has unique effects that make it well suited to intensive therapy.  MDMA may belong to a new class of drugs, called entactogens, that produce feelings of  closeness to others, empathy, well being, and insightfulness. Currently, MDMA is scheduled in  the US and Israel, and doctors and therapists cannot give it to people outside of research  studies like this one. Anecdotal reports of therapy conducted before MDMA was made illegal  suggest that MDMA-assisted therapy may benefit people with PTSD, and there is an ongoing  placebo-controlled study of MDMA-assisted therapy in people with crime or war-related PTSD  occurring in the US.  This study will look at MDMA-assisted therapy in 12 individuals aged 18 years or older  diagnosed with PTSD that arose out of war or terrorism-related trauma, with PTSD symptoms not  improving after trying at least one treatment. Eight of 12 participants will be assigned to  receive the full dose of MDMA, and four will be assigned to receive a low or "active placebo"  dose of MDMA during each of two experimental sessions. People will be assigned to full or  low-dose MDMA "by chance," as by flipping a coin. The fully active dose consists of an  initial dose of 125 mg MDMA and a supplemental dose of 62.5 mg given 2 to 2.5 hours later.  The active placebo dose consists of an initial dose of 25 mg MDMA and a supplemental dose of  12.5 mg.  The study will last approximately four months, and will include two sixty minute long  introductory therapy sessions, two active placebo or fully active dose MDMA-assisted therapy  sessions, a sixty to ninety minute long therapy session 24 hours after each experimental  session, and one to two hour-long therapy sessions occurring weekly between the first and  second experimental session, and between the second experimental session and the end of the  study.  PTSD symptoms will be measured at the start of the study and eight weeks (two months) after  the second experimental session. PTSD symptoms are assessed six and twelve months after the  second experimental session in people who do not take part in the open-label study  continuation. People who take part in the open-label study continuation will have their PTSD  symptoms measured six and twelve months after the second MDMA-assisted therapy session. Inclusion Criteria:  -  Diagnosis of Posttraumatic stress disorder arising from war or terrorism-related  events.  -  PTSD still remains after at last one treatment, with treatment including psychotherapy  or pharmacotherapy.  -  May meet criteria for a mood disorder.  -  Must be at least 18 years old.  -  Must be able to stop taking psychiatric medication from the start of the study until  the two-month follow-up.  -  May continue seeing an outside therapist during the study, but cannot increase the  length or frequency of treatments.  -  Must be able to follow all the rules and instructions relating to the experimental  session, including restrictions on food and substance (alcohol and drug) consumption  -  Must be willing to stay overnight in the clinic after each experimental session until  the non-drug session occurring the next morning.  -  Must be willing to be contacted by one of the researchers on a daily basis for a week  after each experimental session.  -  If a woman of childbearing potential, must have a negative pregnancy test and must  agree to use an effective form of birth control.  -  Must be able to speak and read Hebrew. Exclusion Criteria:  -  Cannot have a non-war or non-terrorism event as significant contributor to PTSD  symptoms.  -  Cannot have history of or be diagnosed with psychotic disorder or bipolar affective  disorder - 1.  -  Cannot be diagnosed with dissociative identity disorder, an eating disorder with  active purging or borderline personality disorder.  -  Cannot have evidence or history of significant hematological, endocrine,  cerebrovascular, cardiovascular, coronary, pulmonary, renal, gastrointestinal,  immunocompromising, or neurological disease, including seizure disorder. (People with  hypothyroidism who are on adequate and stable thyroid replacement will not be  excluded).  -  Cannot have uncontrolled hypertension, peripheral vascular disease, hepatic disease  (with or without abnormal liver enzymes), or history of hyponatremia or hyperthermia.  -  Cannot weigh less than 50 or more than 105 kg.  -  Cannot have used "Ecstasy" more than five times during lifetime or in the past six  months.  -  Cannot present a serious suicide risk or be likely to require hospitalization during  the course of the study.  -  Cannot require ongoing concomitant therapy with a psychotropic drug.  -  Cannot meet DSM-IV criteria for substance abuse or dependence for any substance save  caffeine or nicotine in the past 60 days.  -  Unable to give adequate consent.

Secondary peritonitis is a frequent abdominal emergency that is still associated with a high  morbidity and mortality rate due to surgical site infections (SSI) and sepsis. Early surgical  source control is crucial to avoid sepsis and worse outcomes. The current randomized  controlled trial aims to investigate the effect of peritoneal lavage with super-oxidized  solution (SOS) on SSI and mortality in patients undergoing emergency surgery for secondary  peritonitis. The investigators hypothesize that peritoneal lavage with SOS reduces the  incidence of SSI and mortality in this patient population. Secondary peritonitis is a frequent abdominal emergency that is associated with significant  morbidity and complications, especially surgical site infections (SSI). If not treated  promptly and efficiently, secondary peritonitis may progress from a contained abdominal  infection to systemic disease, i.e., sepsis and eventually septic shock. Early surgical  source control is crucial to avoid sepsis and worse outcomes. Super-oxidized solution (SOS)  has been shown to have a strong antimicrobial activity while being safe for medical use in  humans.  This randomized controlled trial (RCT) will investigate the effect of peritoneal lavage with  SOS vs. the current standard solution (Ringer's lactate) on SSI and mortality in patients  undergoing emergency abdominal surgery (EAS) for secondary peritonitis. The hypothesis of  this study is that peritoneal lavage with SOS during EAS will reduce the incidence of SSI and  mortality.  Patients scheduled for EAS with secondary peritonitis due to suspected hollow-viscus  perforation, anastomotic insufficiency, or abdominal abscess, including patients with the  named abdominal emergencies as a complication after elective surgery, will be assessed for  eligibility. All patients included will be treated according to the current standard of care  for secondary peritonitis. This includes the insertion of intravenous lines, start of  antibiotic therapy, infusion of crystalloid solutions, monitoring of vital signs, and EAS.  EAS will be performed by laparoscopy or laparotomy, or started laparoscopically with a  conversion to laparotomy during the operation.  Randomization will take place during EAS after the surgical procedure including regular  peritoneal lavage have been performed. If a hollow-viscus perforation, anastomotic  insufficiency, or abdominal abscess is encountered intraoperatively, patients will be  randomized and undergo additional peritoneal lavage with either SOS (SOS group) or Ringer's  lactate (control group).  In the SOS group, the abdominal cavity will be irrigated with 2 liters of SOS (Micodacyn60®),  followed by aspiration of the product and abdominal closure. In the control group, the  abdominal cavity will be irrigated with two liters of Ringer's lactate solution, followed by  aspiration of the solution and abdominal closure. The only difference in treatment between  the two groups will be the additional peritoneal lavage with SOS or Ringer's lactate at the  end of the procedure. After surgery, there will be no difference in the further management of  the SOS and control group.  The primary outcome of this RCT will be the incidence of SSI and mortality as a composite  outcome at 30 days postoperatively.  Secondary outcomes will be in-hospital and 30-day mortality, surgical site infections within  30 days, the time to occurrence of the primary outcome, sepsis as defined by the Sepsis-3  guidelines at 24 h, 48 h, and 7 days postoperatively, septic shock as defined by the Sepsis-3  guidelines at 24 h, 48 h, and 7 days postoperatively, organ dysfunction over time (14 days,  as measured by the SOFA and/or qSOFA scores), biomarkers of inflammation over time (14 days,  including C-reactive protein, white blood cell count, and body temperature), postoperative  fascial dehiscence at 30 days postoperatively, intestinal fistula at 30 days postoperatively,  re-intervention for postoperative complications within 30 days postoperatively, days to first  postoperative bowel movement, and total hospital and Intensive Care Unit length of stay. Inclusion Criteria:  -  Secondary peritonitis due to suspected hollow viscus perforation, anastomotic  insufficiency, and/or abdominal abscess (including patients with the named abdominal  emergencies as a complication after elective surgery)  -  Scheduled emergency surgery with peritoneal lavage  -  Age over 18 years  -  Written informed consent Exclusion Criteria:  -  Pregnancy (will be ruled out using beta-hCG testing)  -  Patients with primary or tertiary peritonitis

The VetASSIST study is a randomized clinical trial testing whether receiving virtual health  coaching from Veteran peers improves the physical and mental health-related quality of life  of Veterans with multiple chronic health conditions and complex healthcare needs. VetASSIST  will test the efficacy of an intervention that matches Veteran patients with multimorbidty  with Veteran health coaches who will provide education, resources, guidance and support to  help them manage their physical and mental health over the course of a year. The study objective is to evaluate the effectiveness of a virtual, Veteran peer-led  self-management support program (VetASSIST) to improve health related quality of life (HRQoL)  for Veterans with multimorbidity compared to usual care. The investigators will conduct a  type 1 hybrid effectiveness-implementation randomized controlled trial of the intervention  among VA Puget Sound patients with multimorbidity. Trained peer health coaches will virtually  meet one-on-one with patients to assist in daily self-management by providing information;  identifying patients' values and preferences; helping them set goals in alignment with their  values and preferences and problem-solve barriers to those goals; modeling skills for  effective management; providing social support; linking them to clinical care and community  resources; and addressing self-management barriers. Veterans with multimorbidity will be  randomized to receive the peer health coaching intervention or usual care. Outcomes will be  assessed remotely at baseline and 12 months.  Specific aims are: 1) Test the effect of VetASSIST, compared to usual care, on the primary  outcome of baseline to 12-month change in physical HRQoL, and secondary outcomes of mental  HRQoL and health care utilization; 2a) Describe differences between VetASSIST and usual care  on baseline to 12-month changes in intermediate outcomes reflecting the functions of peer  support and intervention targets (self-efficacy, patient activation, health behaviors, social  support, perceived access to care, patient-provider communication, and shared  decision-making); 2b) Examine whether intermediate outcomes mediate intervention-associated  differences in HRQoL; 3) Evaluate feasibility of translating VetASSIST into practice,  including evaluation of per patient intervention costs and barriers and facilitators to  implementation. Inclusion Criteria:  -  Veteran VA Puget Sound patient with >=1 primary care visit within last year  -  Complex multimorbidity (>=3 chronic conditions in >=3 body systems based on AHRQ  Chronic Condition Index)  -  Meets >=2 criterion from NICE multimorbidity guidelines:  -  1) diagnosis of a mental and physical health condition,  -  2) frailty based on JEN Frailty Index, confirmed with self-reported PRISMA-7  score,  -  3) one or more visits to the VA emergency department within the past 12 months,  -  4) 10 or more regularly prescribed medications,  -  5) difficulties managing treatment defined by a score of at least 22 on the  self-reported Multimorbidity Treatment Burden Questionnaire Valid e-mail address  -  Reliable access to the Internet  -  Access to a device (personal/VA supplied) compatible with the VA video conferencing  platform  -  Agree to participate in the health coaching sessions and surveys if assigned to  intervention group Exclusion Criteria:  -  Not fluent in English, severe hearing loss, no phone access  -  Dementia or cognitive impairment (diagnosis or six-item cognitive screener score >=2)  --Pregnant or planning to become pregnant in the next 6 months  -  End stage renal disease and on dialysis  -  Receipt of palliative or hospice care  -  Enrollment in VA Home Based Primary Care  -  Living in a care facility (nursing home or assisted living)  -  Behavior flags in the VA electronic health record  -  Active treatment for non-skin cancer diagnosis

The primary objective is to determine whether in patients with CIPN pain, treatment with  Qutenza has the same effect as treatment with duloxetine 60 mg daily. Rationale: Painful polyneuropathy occurs in approximately 20-40% of patients after the  chemotherapy treatment and has a negative influence on quality of life. To our knowledge, no  previous randomized study examined Qutenza in patients with CIPN, and no study compared  Qutenza to duloxetine. We hypothesize that the effect of Qutenza on the severity of pain and  its impact on functioning is the same as that of duloxetine in patients with CIPN, as  measured by the numeric rating scale (NRS).  Objective: The primary objective is to determine whether in patients with CIPN pain,  treatment with Qutenza has the same effect as treatment with duloxetine 60 mg daily.  Study design: The study is a pragmatic randomized controlled trial.  Study population: Patients who have been treated with chemotherapy in the last 5 years to 3  months and with CIPN grade 1 or higher according to the NCIC-CTC (National Cancer Institute  of Canada-Common Toxicity Criteria). The patients are ≥ 18 years of age and have to  experience painful neuropathy longer than 3 months with mean (1 week) pain score of ≥4.  Intervention: The affected extremity or extremities will be treated with Qutenza (179mg)  according to normal procedures of the hospital and as recommended by the manufacturer.  Patients randomized to duloxetine will start with duloxetine 30 mg per day. After 1 week the  dose of duloxetine will be increased, if tolerated, to 60 mg per day for a period of 12  weeks.  Main study parameters/endpoints: The primary endpoint will be average pain reduction at week  12 after start of treatment as measured by the NRS (Numeric Rating Scale). Furthermore  secondary objectives will be: pain interference as measured by the BPI (Brief Pain  Inventory), side effect profile, quality of life, patient satisfaction, pain at 6 weeks after  the start of treatment.  Nature and extent of the burden and risks associated with participation, benefit and group  relatedness: Patients will visit the research location for a screening visit to determine  whether the patient fits the in- and exclusion criteria. After the baseline visit patients  will be randomized to either receive Qutenza or duloxetine.  All patients will fill in questionnaires (either digital or on paper) before starting  treatment with Qutenza or duloxetine (T=0), after 6 weeks of treatment (T=6) and after 12  weeks of treatment (T=12) to obtain the primary and secondary endpoints. All patients will be  followed for a total period of 12 weeks. In the first week of treatment patients fill in a  questionnaire with side effect profile on a daily basis after 2 weeks patients will fill in a  questionnaire on a weekly base. Castor will be used to send the 'side effect questionnaire'.  Since both treatments are commonly used in the treatment of neuropathic pain and are both  registered for that indication, no serious complications and no additional burden other than  normal treatment are expected. Inclusion Criteria:  -  Age ≥ 18 years of age  -  Presence of CIPN grade 1 or higher according to the NCIC-CTC  -  Mean pain (1 week) score of ≥ 4  -  Treatment with chemotherapy in the last 5 years to 3 months ago  -  Able to give oral and written informed consent  -  Painful neuropathy longer than three months Exclusion Criteria:  -  Peripheral neuropathy from other causes (e.g. carpal/tarsal tunnel syndrome,  radiculopathy, spinal stenosis, brachial plexopathy)  -  Leptomeningeal carcinomatosis  -  Severe depression or use of anti-depressant medication  -  Psychiatric disorders which can interfere with cooperation  -  Abnormal renal (< GFR 30) or liver function tests (> 2 times normal value)  -  Severe heart failure as determined by the cardiologist  -  Allergy for duloxetine or capsaicin  -  Skin diseases in hands and/or feet, damaged skin  -  The presence of uncontrolled/untreated hypertension  -  Concomitant use of medication that may interact with duloxetine such as fluvoxamine,  ciprofloxacin and enoxacin  -  Active cancer treatment (such as radiotherapy or chemotherapy)  -  Active cancer  -  Previous treatment with Qutenza or duloxetine for CIPN  -  Any condition that by the judgement of the investigator might interfere with the  investigation

This is a study to assess if 162 mg of aspirin will decrease rates of preeclampsia in  pregnant patients compared to 81 mg of aspirin. After screening to meet inclusion criteria, pregnant patients at the Family Medicine Clinic  will be asked to take 162 mg aspirin daily for 6 months, starting at about 12 weeks gestation  and continued until the end of pregnancy. They will be monitored every 4 weeks until week 28,  then every 2 weeks until week 36, and then weekly from week 36 on. Participants will be  screened at these visits for medication compliance (taking, missed doses, side effects, etc).  Patients will be subject to lab work as is routinely indicated for preeclampsia.  At the end of the study period, accumulated study data will be compared with historical data  from the Family Medicine Clinic on rates of preeclampsia and outcomes in patients taking 81  mg for preeclampsia prevention. Inclusion Criteria:  -  Any pregnant patient at Peoria FMC  -  Hx of pre-eclampsia  -  Multifetal gestation  -  Chronic hypertension  -  Type 1 or 2 diabetes  -  Autoimmune disease  -  Renal disease  -  Nulliparity  -  Obesity  -  Family Hx of pre-eclampsia  -  Sociodemographic characteristics  -  Age >= 35 years of age  -  Personal history factors (LBW, SGA, > 10-year pregnancy interval, adverse pregnancy  outcomes Exclusion Criteria:  -  At high risk of side effects from ASA therapy  -  Hx of hemorrhagic stroke  -  Hx of GI bleed, G6PD  -  Liver disease  -  NSAID or Salicylate allergy)  -  Patients confirmed to be not compliant with therapy

This is a first-in-human, Phase I, multicenter, open label, dose escalation study to evaluate  the DLTs and MTD and to determine the recommended Phase 2 dose (RP2D) of CPX-POM administered  IV in patients with any histologically- or cytologically-confirmed solid tumor type. The study will initially employ an accelerated escalation design, with a single patient  enrolled in each cohort (i.e., Single-Patient Cohorts). The initial patient will receive  CPX-POM at a starting dose of 30 mg/m2. Doses will be escalated (doubling), until a ≥Grade 2  toxicity (with the exception of alopecia), is encountered. Subsequently that and all  subsequent cohorts will follow a classical "3+3" dose escalation design.  Note: Fosciclopirox is the generic name for CPX-POM. Inclusion Criteria:  1. Patient is male or female aged ≥18 years.  2. Patient provided signed and dated informed consent prior to initiation of any study  procedures.  3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0  (fully active, able to carry out all pre-disease activities without restriction) or 1  (unable to perform physically strenuous activity but ambulatory and able to carry out  work of a light or sedentary nature).  4. Patient has a predicted life expectancy of ≥3 months.  5. Dose escalation cohorts only: Patient has adequate renal function (creatinine ≤1.5 ×  the upper limit of normal [ULN]) or a glomerular filtration rate (GFR) of ≥50  mL/min/1.73 m^2). Expansion cohort only: Patient has a GFR of ≥30 mL/min/1.73 m^2.  6. Patient has adequate hepatic function, as evidenced by a total bilirubin ≤1.5 × ULN,  aspartate transaminase (AST), and /or alanine transaminase (ALT) ≤3 × ULN or ≤5 ×ULN,  if due to liver involvement by tumor.  7. Patient has adequate bone marrow function, as evidenced by hemoglobin ≥9.0 g/dL in the  absence of transfusion within the previous 72 hours, platelet count ≥100×10^9cells/L,  and absolute neutrophil count (ANC) ≥1.5×10^9 cells/L.  8. Patient has no significant ischemic heart disease or myocardial infarction (MI) within  6 months before the first dose of CPX-POM and currently has adequate cardiac function,  as evidenced by a left ventricular ejection fraction of >50% as assessed by  multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and corrected QT  interval (QTc) <470 msec by Fridericia (QTcF). The eligibility of patients with  ventricular pacemakers for whom the QT interval may not be accurately measurable will  be determined on a case-by-case basis by the Sponsor in consultation with the Medical  Monitor.  9. Patient and his/her partner agree to use adequate contraception after providing  written informed consent through 3 months after the last dose of CPX-POM, as follows:  1. For women: Negative pregnancy test during Screening and at Day 1 of each  treatment cycle and compliant with a medically-approved contraceptive regimen  during and for 3 months after the treatment period or documented to be surgically  sterile or postmenopausal.  2. For men: Compliant with a medically-approved contraceptive regimen during and for  3 months after the treatment period or documented to be surgically sterile. Men  whose sexual partners are of child-bearing potential must agree to use 2 methods  of contraception prior to study entry, during the study, and for 3 months after  the treatment period.  10. Patient is willing and able to participate in the study and comply with all study  requirements. Exclusion Criteria:  Patients who meet any of the following exclusion criteria are not to be enrolled in this  study  1. Patient has a history of risk factors for torsade de pointes (e.g., heart failure,  hypokalemia, family history of long QT syndrome) or requires the use of concomitant  medications that prolong the QT/QTc interval during study participation. Patients  should not receive anti-emetic medications before and following Dose 1 of Cycle 1 for  each treatment cohort. However, anti-emetics such as ondansetron or granisetron that  have a mild QTc prolonging effect are allowed starting with Dose 2 of Cycle 1, if used  with caution and attention to the approved labelling.  2. Patient has an abnormal cardiac appearance/heart size, as evidenced by chest X-ray or  computed tomography (CT) scan.  3. Patient has an uncontrolled or severe intercurrent medical condition (including  uncontrolled brain metastases). Patients with stable brain metastases either treated  or being treated with a stable dose of steroids/anticonvulsants, with no dose change  within 4 weeks before the first dose of CPX-POM and no anticipated dose change, are  allowed. The decision to exclude a patient from the study for an uncontrolled or  severe intercurrent medical condition will be made by the Principal Investigator.  Examples could include epilepsy, resistant infection, or any other neurological  disease that would make clinical assessment difficult.  4. Patient underwent major surgery within 4 weeks before the first dose of CPX-POM or  received cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy,  biologic or immunotherapy, etc.) or an drug or device within 4 weeks (6 weeks for  mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is shorter)  before the first dose of CPX-POM. A minimum of 10 days between termination of the  investigational drug and administration of CPX-POM is required. In addition, any  drug-related toxicity, with the exception of alopecia, should have recovered to ≤Grade  1.  5. If female, patient is pregnant or breast-feeding.  6. Patient has evidence of a serious active infection (e.g., infection requiring  treatment with intravenous antibiotics).  7. Patient has active Hepatitis A infection.  8. Patient known human immunodeficiency virus (HIV) or Hepatitis B or C infection, as  such patients may be at increased risk for toxicity due to concomitant treatment and  disease-related symptoms may preclude accurate assessment of the safety of CPX POM.  9. Patient has an important medical illness or abnormal laboratory finding that, in the  Investigator's opinion, would increase the risk of participating in this study.  10. Patient is taking warfarin.  11. Patient has a history of other malignancy treated with curative intent within the  previous 5 years with the exception of adequately treated non-melanoma skin cancer or  carcinoma in situ of the cervix. Patients with previous invasive cancers are eligible  if the treatment was completed more than 5 years prior to initiating current study  treatment, and there is no evidence of recurrent disease.  12. Patient has known allergy or hypersensitivity to components of CPX-POM.  13. Patient is taking any iron replacement therapy administered IV, IM, or orally due to  the potential for loss of anticancer activity due to drug and metabolites chelating  iron.

A prospective randomized controlled double-blinded study will be conducted on 90 patients  assigned randomly into three equal groups, After obtaining approval of the medical and ethical committee of Menoufia University & Nasser  Institute for Research and Treatment, an informed and written consent from the patients, a  prospective controlled randomized double blinded study will be performed  Sample size:  MedCalc® version 12.3.0.0 program "Ostend, Belgium" was used for calculations of sample size,  statistical calculator based on 95% confidence interval and power of the study 80% with α  error 5%, According to a previous study (13), showed that the duration of tourniquet time in  group A was mean 51.60±5.157 and Group B was mean 53.80±4.773, with p-value >0.05, while  Quality of block of excellent in group A 83.3% and group B 90%, it turns out that there is  success in the group B compared to group A, but there is no difference. So it can be relied  upon in this study, based on this assumption, sample size was calculated according to these  values produced a minimal samples size of 86 cases were enough to find such a difference.  Assuming a drop-out ratio of 5%, the sample size will be 90 cases, subdivided into three  groups 30 cases in each group. Patients will be randomly categorized into three equal groups  (30 patients each): The patients will be randomly allocated to one of these three groups,  using a computer-generated sequence of random numbers and a sealed envelope technique. Inclusion Criteria:  -  Patients of ASA class I and II.  -  Patients of either sex.  -  Patients aged between 20-70 years.  -  Patients scheduled for forearm and hand surgery lasting for about 60 minutes. Exclusion Criteria:  -  Patient with known hypersensitivity to any study medications.  -  Patient with Severe peripheral vascular disease and neurological disease.  -  Where use of tourniquet will be either not possible or contraindicated.  -  Patient with Hemolytic diathesis specially sickle cell anemia, epilepsy, diabetes  mellitus, hypertension, cardiovascular disease like myocardial infarction, cardiac  arrhythmias, heart block and altered mentation.  -  Procedures lasting for more than 90 min will be also not considered.  -  Therapy with adrenergic receptor antagonist, calcium channel blocker and ACE  inhibitors.  -  Patient with impaired liver function.

The purpose of the study is to learn how different dietary interventions affect microbiota  diversity in pregnant women and the transmission of microbiota to their infants during  pregnancy, birth, and postpartum. This research study aims to understand the relationship of dietary fiber, fermented foods,  and the microbiome, specifically during pregnancy and postpartum. We know that the  composition of the microbiome can have an important effect on our overall health, and a  greater variety will confer more health benefits. Research suggests that maternal microbiota  play an important role in the development of their offspring's microbiota during pregnancy,  childbirth, and breastfeeding. The purpose of this study is to assess how diet impacts  maternal microbiome during pregnancy and their infant's microbiome up to about two years  postpartum.  Potential pregnant participants will be recruited during their first trimester up to 22  weeks. After completion of the baseline visit and sample collection, they will be randomized  to start a diet high in fiber, high in fermented foods, high in both fiber and fermented  foods, or a usual care group. Participants will be asked to provide blood, stool, vaginal  swab, and breast milk samples periodically throughout the study. Cord blood will be collected  after childbirth, and infant blood from a heel stick will be collected twice. They will also  be asked to fill out online questionnaires and perform dietary recalls with study diet  assessors. Inclusion Criteria:  -  > 18 years of age  -  Singleton pregnancies  -  Recruit during the first trimester and up to 22 weeks of pregnancy.  -  Healthy subjects willing and able to provide blood, stool, vaginal swab, and breast  milk samples.  -  Must be able to provide signed and dated informed consent. Exclusion Criteria:  -  Pre-pregnancy BMI greater than 40  -  Blood pressure SBP: > 160 mmHg -OR- DBP: > 90 mmHg  -  Kidney disease  -  Liver disease  -  Anemia  -  Symptomatic gallstones  -  History of bariatric surgery  -  Acute disease at time of enrollment (i.e. flu or gastroenteritis). May delay sampling  until subject recovers.  -  Chronic, clinically significant, unstable (unresolved, requiring on-going changes to  medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic  or renal functional abnormality, as determined by medical history  -  History of active uncontrolled gastrointestinal disorders or diseases including:  -  Inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe),  Crohn's disease (mild-moderate-severe), or indeterminate colitis;  -  Irritable bowel syndrome (IBS) (moderate-severe);  -  Persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic  diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or  Helicobacter pylori infection (untreated)  -  Any confirmed or suspected condition/state of immunosuppression or immunodeficiency  (primary or acquired) including HIV infection.  -  Surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in  the past five years. Any major bowel resection at any time.  -  Confirmed or suspected autoimmune disease  Medications:  -  Weight loss medications  -  Regular high dose aspirin  -  Regular use of prescription opiate pain medication  If taken in the past 2 months:  -  Systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous,  intramuscular or oral)  -  Corticosteroids (intravenous, intramuscular, oral, nasal or inhaled)  -  Cytokines  -  Methotrexate or immunosuppressive cytotoxic agents  Diet & Lifestyle:  -  Recent history of chronic excessive alcohol consumption defined as more than five  1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or  five 5-ounce servings of wine per day; or > 14 drinks/week.  -  Regular/frequent use of smoking or chewing tobacco, e-cigarettes, cigars or other  nicotine-containing products  Maternal chronic medical conditions:  -  Pre-gestational diabetes (T1 or T2)  -  History of gestational diabetes  -  On medication that is an immune modulators or chronic steroid use  -  Hyperemesis gravidarum  Pregnancy history:  -  Preterm birth  -  Recurrent pregnancy loss

This study was designed to assess the bioequivalence of Olanzapine tablets of two different  manufacturers and to investigate the safety and tolerability of Olanzapine tablets of two  different manufacturers. A comparative, open-label, randomized, two-period, two-treatment, two-sequence, two-way  crossover clinical trial to evaluate the bioequivalence of single doses of test product  Olanzapine film-coated tablets 5 mg (JSC Farmak, Ukraine) and reference product Zyprexa®  coated tablets 5 mg (Eli Lilly, Nederland B V) in healthy, adult male and female subjects  under fasted conditions.  During each period 22 blood samples were taken in each Study Period: prior to dosing (-1.0)  and 1.0, 2.0, 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 10.0, 12.0, 14.0,  16.0, 24.0, 48.0 and 72.0 hours after IMP administration. Inclusion Criteria:  1. Healthy males and non-pregnant and no breast-feeding females ), ≥18 and ≤55 years of  age ) (on the day of Informed Consent). Caucasian race.  2. Non-smoker or past-smoker (who has stopped smoking at least 6 months before the first  dosing).  3. Body Mass Index (BMI) 18.5 to 30.0 kg/m2, inclusive and body weight between 50 kg and  100 kg (on the day of screening).  4. Subject was available for the whole study and has provided his/her written informed  consent.  5. Subjects in good health, as determined by screening medical history, physical  examination, vital signs assessments (pulse rate, systolic and diastolic blood  pressure, and body temperature) and 12-lead ECG. Minor deviations outside the  reference ranges were acceptable, if deemed not clinically significant by the  Investigator.  6. All laboratory screening results within the normal range. Minor deviations outside the  reference ranges were acceptable, if deemed not clinically significant by the Clinical  Investigator.  7. Acceptance of use of contraceptive measures during the whole study by both female and  male subjects ). Exclusion Criteria:  1. Gastrontestinal, renal or hepatic diseases and/or pathological findings present or in  history, which might interfere with the drug pharmacokinetics. Any pre-existing  disease or condition (e.g. hemicolectomy) for which it can be assumed that absorption,  distribution, metabolism and excretion of the IMP will be affected.  2. An unusual diet, for whatever reason (e.g. low-sodium), for four weeks prior to  receiving the study drug. In any such case subject selection was at the discretion of  the Principal Investigator.  3. History, presence or known risk of narrow-angle glaucoma.  4. Acute or chronic diseases and/or clinical finding which may interfere with the aims of  the study or with the drug's safety, tolerability, bioavailability and/or  pharmacokinetics of the IMP.  5. Previous liver disease or elevations in serum transaminases ALT or AST ≥ 1.0 ULN at  the screening.  6. History of kidney disease and with impaired renal function.  7. Known hypersensitivity or idiosyncratic reaction to olanzapine or to any of its  excipients or any drug or any substance.  8. Hereditary problems of galactose intolerance, total lactase deficiency or  glucose-galactose malabsorption.  9. Any history or presence of asthma (including aspirin-induced asthma) or nasal polyp or  NSAII induced urticaria.  10. Presence of out-of-range cardiac interval on the ECG at screening or other clinically  significant abnormalities, unless deemed non-significant by the Investigator.  11. Clinically significant illness within 28 days before the first dosing, including major  surgery.  12. Any significant clinical abnormality, including a positive result of HBsAg and/or HCV  and/or HIV test during screening procedure.  13. Positive result of blood pregnancy test at screening or positive urine pregnancy test  at check-in or breast-feeding or lack of results of pregnancy test.  14. Positive results of drugs in urine at screening and at check-in.  15. Positive result of alcohol breath test at screening and at check-in.  16. Positive result of urine cotinine test at screening.  17. Serious mental disease and/or inability to cooperate with clinical team.  18. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of  90-140 mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out  of the range of 50-100 bpm during the screening procedure.  19. Body ear temperature is out of the range of 35.7-37.6° C at screening and at check-in.  20. Orthostatic hypotension during the screening procedure.  21. Drug, alcohol (of ≥ 40 g per day pure ethanol), solvents or caffeine abuse.  22. Use of organ-toxic drugs or systemic drugs known to substantially alter liver  metabolism within 90 days before the first dosing.  23. Use of any prescription medication for a period of 28 days before the first dosing.  24. Use of any OTC (over-the-counter) medication including vitamins, herbal medications  and food supplements less than 14 days before the first dosing.  25. Getting a tattoo, body piercing or any cosmetic treatment involving skin piercing  within 90 days before the screening unless evaluated by Investigator as  non-significant for inclusion in the study.  26. Donation or loss of at least 500 mL of blood within 90 days or donation of plasma or  platelets within 14 days before the first dosing.  27. Subjects who have any clinically significant abnormal laboratory safety findings (upon  repeat testing, 1 repeat assessment is acceptable) previously or at screening.  1. Anaemia (haemoglobin below 120 g/L for women and 130 g/L for men)  2. Leukopenia (value of WBC below 4.00*10_9/L) and/or neutrophilopenia (value of NEU  below 2.0 *10 9/L  3. Thrombocytopenia (value of platelets below 150*10_9/L).  28. Less thay 30 days between exit procedure in previous study and the first dosing in  this study.

OCTAV is a medical device class I, CE marked, based on a new technique for high-resolution  imager (cell) internal microstructures of all types of biological tissues in vivo or ex vivo,  to a depth of penetration 800 .mu.m. It allows to explore the epidermis, the dermo-epidermal  junction and middle dermis in a totally non-invasive (direct contact with the tissue without  sampling). At the coming of the patient in Dermatology for resection / biopsy of the tumor (usual  practice), for the study, an image of the tumor will be performed with the OCTAV device  (about 5 minutes) for the study. Then, according to usual practice, resection / biopsy will  be performed.  This study aims to validate the clinical relevance of this device to characterize the 3 main  skin cancers and to obtain the necessary data for the implementation of future clinical  trials. Inclusion Criteria:  -  Patient with a cutaneous lesion suspicious for melanoma, basal cell carcinoma,  squamous cell carcinoma, requiring a surgical excision  -  Consent form signed  -  Major patient  -  Aged between 18 to 40 years  -  Consent form signed  -  Patient of the dermatology department with non-pathological forearm skin Exclusion Criteria:  -  Allergy or intolerance to immersion oil (used for microscopy)  -  If female, pregnant or breast-feeding  -  Patient unable to stand still for 60 seconds  -  Skin lesions located near patient eyes (<3 cm)  FOR CONTROL GROUP  -  Allergy or intolerance to immersion oil (used for microscopy)  -  If female, pregnant or breast-feeding  -  Patient unable to stand still for 60 seconds

To assess the prevalence of renal disease in a pediatric population of patients with celiac  disease by looking for the presence of hematuria and/or proteinuria. In this study the investigators seek to quantify the prevalence of urine sediment  abnormalities in children with celiac disease to assess whether there is value in screening  for renal disease in this population. Celiac disease (CD) is frequently accompanied by a  variety of extra-digestive manifestations, making it a systemic disease rather than a disease  limited to the gastrointestinal tract. CD belongs to the group of autoimmune diseases, a  significantly increased prevalence of other autoimmune diseases (AD) has been reported in  individuals with CD and their first-degree relatives, and a significantly increased  prevalence of CD has been documented in individuals with other AD. The association between CD  and other ADs may be explained by a shared pathogenic basis, involving genetic susceptibility  as in type 1 diabetes (T1D), similar environmental triggers, increased intestinal  permeability, and possibly by undiscovered mechanisms. Many of the extraintestinal  manifestations of CD involve the kidney. Urolithiasis and crystal-induced renal disease,  nephrogenic ascites, increased risk of end-stage renal disease, and membranoproliferative  glomerulonephritis type 1 are associated with CD. However, little is known about the risk of  kidney disease in individuals with CD, and it would be interesting to assess the prevalence  of urine sediment abnormalities in a pediatric population at diagnosis and during follow-up.  No previous studies have examined the risk of renal disease, and there are currently no  recommendations for screening for renal involvement in patients with CD.  One of the renal conditions that particularly attracts our attention is IgA nephropathy  (NIgA). First, studies suggest a common pathogenic basis between this nephropathy and CD and  second, it is one of the most common primary glomerulonephritis in children and adolescents  worldwide. NIgA usually progresses to end-stage renal disease (ESRD) within 20 years; the  median age of patients starting dialysis ranges from 40 to 50 years. Cohort studies with  extensive follow-up show that 10-13% of children eventually reach ESRD within 10 years and  20-30% within 20 years. In more than half of cases, NIgA is asymptomatic (microscopic  hematuria) and is diagnosed after an incidental finding of hypertension, subnormal glomerular  filtration rate, hematuria, and/or proteinuria in children and adults. Renin-angiotensin  system inhibitors have shown effective results in reducing the progression of kidney damage  in young NigA patients with moderate proteinuria.  In view of its potential severity, the arguments in favor of its association with CD, its  generally asymptomatic clinical presentation, and the usefulness of its early detection, it  seems interesting to us to evaluate the prevalence of urinary abnormalities characteristic of  NigA in children with celiac disease. The results of this study could have an impact on the  prevention of renal disease in patients with celiac disease. Inclusion Criteria:  -  children with Celiac Disease Exclusion Criteria:  -

Brown adipose tissue (BAT) burns excess calories to produce heat in response to environmental  cold. Rapidly growing evidence from rodent and human studies suggests that the presence and  activation of brown fat are far more beneficial for whole body metabolism and cardiometabolic  health than previously appreciated. Despite the clear associations between brown fat and  metabolic health, we lack both: cost-effective means of detecting brown fat in humans as well  as comprehensive insights into how brown fat facilitates metabolism on a molecular level in  humans.  Emerging evidence suggests that the benefits of brown fat activation are mediated, at least  in part, by secretion of specific molecules into the bloodstream which signal to  metabolically active organs such as skeletal muscle, liver and brain. A number of these  so-called brown adipokines (or BATokines) have now been discovered in mice and shown to  positively impact glucose homeostasis, liver and muscle function. Human deep-neck brown fat  biopsies reveal that >1000 molecules could potentially be secreted from brown fat, and >400  are released by human brown fat cells in a dish, representing a major opportunity for  discovery of high translational value.  Here, we aim to identify a screen of first potential blood biomarkers of brown fat in healthy  young humans. This will be achieved by analyzing plasma proteins in subjects with 'inactive  brown fat' (warm) and 'activated brown fat' (3-hr cold exposure, cooling vests) using  high-throughput technologies (SOMAscan and O-link) to identify temperature-sensitive brown  fat-enriched molecules. This preliminary data will guide a larger follow up study in which we  envision studying lean and obese (insulin sensitive and insulin resistant) subjects of  various age groups and race/ethnicity. Human BATokines identified here will become primary  targets for manipulation in experimental animals to assess their therapeutic potential  against obesity, T2D, and associated diseases. Additionally, since current methods of brown  fat detection in human rely on deep neck biopsies or costly 18-FDG-PET/CT scans,  identification of blood biomarkers of brown fat would offer a cost-effective and non-invasive  alternative for prediction of metabolic health in humans. Fat plays a fundamental role in regulating metabolic health due to its capacity to store  excess calories (white adipose tissue; WAT) or burn them to produce heat (brown adipose  tissue, BAT). While white fat cells are located in deposits beneath the skin (subcutaneous)  or around the internal organs (visceral) and expand with obesity, brown fat cells reside  predominantly in the deep neck area and have evolved to turn fuel into heat (a process termed  thermogenesis) when activated by environmental cold. This calorie-burning property of BAT  suggest it is a type of 'good fat' which may protect us from conditions such as obesity. A  wealth of mouse data confirms that activation of BAT via cold exposure provides significant  health benefits to experimental animals, including protection from diet-induced obesity and  improved glucose metabolism. BAT has only recently been detected in adult humans, which has  led to efforts to understand its physiology and investigate whether its activity can be  manipulated to treat metabolic diseases. Notably, in addition to storing or burning fat,  adipose tissue secretes a large number of hormone-like factors into the bloodstream, known to  affect blood glucose levels and insulin sensitivity (adiponectin, adipsin) as well as  appetite and energy expenditure (leptin). Although many such factors have been identified in  white fat, little is known about the proteins secreted from brown fat, particularly in  humans.  In a recent study of 52,000 patients with 18-FDG-PET/CT scans to identify the presence of  brown fat, we found that BAT+ individuals had significantly reduced odds of type 2 diabetes  (T2D), coronary artery disease, and congestive heart failure, compared to matched individuals  who did not have brown fat. A smaller independent study demonstrated that short-term  activation of BAT with cooling jackets significantly improved insulin sensitivity in T2D  patients. These findings collectively reveal that BAT carries extraordinary potential to  impact metabolic health in humans.  Metabolic benefits linked with BAT cannot be explained by the generation of heat  (thermogenesis) alone. Emerging evidence suggests that BAT secretes specific molecules into  the bloodstream. A number of these so-called brown adipokines (or BATokines) have now been  discovered in mice and shown to positively impact whole body glucose metabolism and liver  function, reducing the susceptibility to metabolic disease. However, the 'secretome' of brown  fat has not been well studied in humans, and hence the relevance of these BATokines to our  physiology remains unclear. In support of this unexplored research avenue, gene expression  data from deep-neck BAT biopsies reveal that >1,000 molecules could potentially be secreted  from BAT in humans, and 431 were identified as being released from human BAT cells in a dish,  but a comprehensive validation of these proteins in blood samples of participants with  activated BAT is lacking.  The aim of this study is to identify a panel of plasma proteins induced by activation of  brown fat in young healthy human participants and provide pilot data for a larger biomarker  study. We will employ novel unbiased multiplex tools to identify up to 7,000 unique proteins  of various abundances, in subjects before and after cooling. Using these data, we will be  able to identify common circulating factors that correlate with BAT activation, and  subsequently compare them with pre-existing gene expression data to find polypeptides  secreted, shedded or otherwise released specifically by BAT. While this study will focus on  the identification of proteins, we also have the potential to survey small molecule  metabolites secreted into the circulation. This list of BATokines will become instrumental  for validation and retro-translation of mouse data from our lab and the larger scientific  community interested in the metabolic benefits conveyed by BAT. In addition to the discovery  of potential therapeutic targets, the blood screen may become a valuable data platform for  clinical biomarkers of brown fat. Since current methods of BAT detection in human rely on  deep neck biopsies and/or costly 18-FDG-PET/CT scans, identification of blood factors that  circulate proportionally to BAT activity or correlate with the presence or amount of BAT  would offer a cost-effective, non-invasive alternative in human participants. Inclusion Criteria:  -  Age between 18 and 28  -  BMI >20 and < 25 Exclusion Criteria:  -  Diabetes type I or II (self-report)  -  Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism,  thyroiditis) (self-report)  -  Diagnosis with cancer including skin cancer (self-report)  -  Diagnosis or evidence of Raynaud's Syndrome or systemic sclerosis (self report)  -  Previously or currently diagnosed with SARS-Cov-2 infection/COVID-19 (secondary to  unknown immune responses)  -  Any vaccine administration within two weeks preceding the study procedure  -  Currently pregnant  -  Currently taking any prescribed medication other than oral contraceptives  -  Treatments for weight loss or any other supplements that may alter weight or  metabolism are not acceptable (vitamins are acceptable)  -  Has consumed nicotine (smoking, inhaling, ingesting) within the last within the last 6  months  -  Has used illicit drugs within the last 6 months  -  Any medical, psychological, or social condition that, in opinion of principle  investigators, would jeopardize the health or well-being of the participant during the  study procedure or integrity of the data

Epipage 2 (Epidemiological study on small gestational ages) is a prospective population-based  national cohort implemented to better understand the short, mid and long term future of  premature children.  This study was launched on 28 March 2011 by the researchers of the EPOPé team (Perinatal,  Obstetric and Pediatric Epidemiology Research) of the Epidemiology and Biostatistics Research  Centre (INSERM U1153), in collaboration with the Inserm 1027 Unit (Epidemiology and Analysis  in Public Health: risks, chronic diseases and handicaps) and medical teams of public health  and research in 25 French regions.  The study focuses on children born before 35 weeks of amenorrhea.  3 follow-up steps for children included in the cohort have already been completed at 1, 2 and  5 and a half years of age. Currently, nearly 4,000 children are still eligible for follow-up.  Since the children are 9 years old, the follow-up steps are shared with those set up in  another birth cohort, the Elfe cohort (Étude Longitudinale Française depuis l'Enfance,  (www.elfe-france.fr) ), as part of the RE-CO-NAI project.  The RE-CO-NAI project is a research platform on cohorts of children followed since birth in  order to be able to study in a global and multidisciplinary way the major issues of the  health, development and socialization of children.  This RE-CO-NAI project was funded by the EQUIPEX 2011 call for projects as part of future  investments.  This protocol, which is part of the RECONAI project, concerns the fully shared follow-up  phase, proposed in the 10th year for the children of the two cohorts. The objectives of this new follow-up phase are to study:  -  the relationships between prematurity, early growth and cardiometabolic disorders  -  the relationship between parenting educational skills and children's quality of life  -  the factors influencing children's puberty development  -  the factors influencing the child's fitness and motor skills  Study design:  The 10 and a half year follow-up phase is a Category 2 Human Person Research (IHRP 2).  Study population The study population corresponds to all children who have participated in  the Epipage 2 cohort since birth and whose parents did not wish to stop follow-up in the  study. In total, nearly 4,000 children will be invited to participate in this new follow-up  phase.  Methodology:  This follow-up phase will take place in 3 steps:  1. A telephone interview with one of the parents living regularly with the child. Parents  will be asked to answer several questions concerning their family situation, the school  (homework, school support), the health, sleep and nutrition of the child, the general  health and mental health of the parent interviewed, the employment situation, the living  conditions and educational practices of the family.  2. The home visit of the families of an investigator who will propose to the families  several activities:  -  An interview with the child about his relations with his siblings, his comrades,  his involvement in domestic activities and an estimate of his quality of life;  -  A physical examination measuring some of the child's health parameters and  including tests of physical fitness and motor skills;  -  A test of the child's cognitive abilities;  -  A parent self-administered questionnaire including a parent's cognitive abilities  test (self-administered);  3. Biological samples from the child (blood, urine, saliva hair) Inclusion Criteria:  -  Children initially included in the Epipage 2 study,  -  Not lost to follow up (i.e. having participated in at least one of the Epipage 2  surveys since the age of 1 year),  -  Neither parent has expressed a definitive refusal to participate in the follow-up  study. Exclusion Criteria:  -  Refusal of the investigation by one of the two parents or holders of parental  authority,  -  Residence abroad

This phase I trial aims to determine if it is safe to use palliative radiotherapy and  lurbinectedin at the same time to treat small cell lung cancer that has spread outside of the  chest and that has grown after being treated with chemotherapy (extensive stage).  Lurbinectedin kills tumor cells by blocks a process called transcription that small cell lung  cancer relies on to survive. It also damages the deoxyribonucleic acid (DNA) of tumor cells,  which is similar to the way radiation kills tumor cells. Palliative radiotherapy is a routine  medical treatment for patients who have lung cancer that has spread to other parts of the  body (metastatic), and is used to relieve symptoms caused by cancer or to patients from  developing symptoms. This trial may help doctors understand if treating patients with  lurbinectedin and palliative radiotherapy at the same time would make them both work better  than either one alone or if they could cause more side effects for patients when given  together. PRIMARY OBJECTIVE:  I. To describe the safety in terms of palliative radiation therapy (RT) in combination with  uninterrupted lurbinectedin in patients with extensive stage-lung small cell carcinoma  (ES-SCLC).  SECONDARY OBJECTIVES:  I. To determine the feasibility of delivering palliative RT in combination with  lurbinectedin.  II. To evaluate the preliminary efficacy of RT plus (+) lurbinectedin, as assessed by:  IIa. Radiographic response rates. IIb. Pain response rates. IIc. Progression free survival  (PFS). IId. Overall survival (OS). III. To assess patient-reported toxicities to palliative  RT + lurbinectedin.  EXPLORATORY OBJECTIVE:  I. To explore the dose-volume relationships between irradiated bone marrow and hematologic  toxicity.  OUTLINE:  Patients undergo palliative RT over 5 or 10 treatment fractions at the discretion of the  treating physician daily for 21 days. Patients also receive lurbinectedin intravenously (IV)  over 1 hour on day 1 of each cycle. Cycles of lurbinectedin repeat every 21 days in the  absence of disease progression or unacceptable toxicity.  After completion of palliative RT, patients are followed up at 1, 3, 6, and 12 months. Inclusion Criteria:  -  Age >= 18 years  -  Eastern Cooperative Oncology Group (ECOG) performance status =< 3  -  Patients with pathologically confirmed ES-SCLC who are receiving lurbinectedin or are  candidates for lurbinectedin therapy after progression on first-line systemic therapy  (either chemotherapy [platinum etoposide] or chemoimmunotherapy) at the discretion of  the treating medical oncologist.  -  Metastatic bone or visceral/lung metastatic disease as assessed computed tomography  (CT), magnetic resonance imaging (MRI), bone scan or positron emission tomography  (PET)/CT within 90 days prior to RT on this study.  -  Patients with treated brain metastases are eligible but must require < 10 mg of  dexamethasone daily or its glucocorticoid equivalent. Brain metastases will not be  treated in the context of this protocol.  -  Absolute neutrophil count (ANC) >= 1,500/cells/mm^3  -  Platelets >= 100,000/cells/mm^3  -  Hemoglobin > 7.0 g/dL  -  Total Bilirubin ≤ 1.5 ULN  -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN (=< 5.0x  ULN for liver involvement)  -  Alkaline phosphatase =< 2.5x ULN (=< 5.0x with documented liver or bone metastases)  -  Based on its mechanism of action, lurbinectedin could cause harm when administered to  a pregnant woman. Taken together with the known teratogenicity of RT, female of  child-bearing potential (FCBP) must have a negative serum or urine pregnancy test  prior to starting protocol therapy. A female of childbearing potential (FCBP) is a  sexually mature woman who: 1) has not undergone a hysterectomy or bilateral  oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive  months (i.e., has had menses at any time in the preceding 24 consecutive months.  -  FCBP and men must agree to use adequate contraception (hormonal or barrier method of  birth control; abstinence) prior to study entry and for the duration of study  participation and 6 months after the final dose of lurbinectedin. Should a woman  become pregnant or suspect she is pregnant while she or her partner is participating  in this study, she should inform her treating physician immediately. Men treated or  enrolled on this protocol must also agree to use adequate contraception prior to the  study, for the duration of study participation, and 4 months after completion of  lurbinectedin administration. FCBP who are currently breastfeeding must discontinue  during and up to 2 weeks after the final dose of lurbinectedin.  -  Completion of all previous cancer-directed therapies (excluding lurbinectedin) for the  treatment of cancer >= 3 weeks before the start of study therapy.  -  Willingness and ability of the subject to comply with scheduled visits, drug  administration plan, protocol-specified laboratory tests, other study procedures, and  study restrictions.  -  Evidence of a personally signed informed consent indicating that the subject is aware  of the neoplastic nature of the disease and has been informed of the procedures to be  followed, the experimental nature of the therapy, alternatives, potential risks and  discomforts, potential benefits, and other pertinent aspects of study participation. Exclusion Criteria:  An individual who meets any of the following criteria will be excluded from participation  in this study:  -  Pregnancy or breastfeeding within 2 weeks  -  Patients may not enroll in both safety cohorts  -  Patients who have received prior RT will be permitted to enroll. However, the  metastases treated on this study must be > 2 cm from the following previously  irradiated structures:  -  Spinal cord previously irradiated to > 40 Gy (delivered in =< 3Gy/fraction)  -  Brachial plexus previously irradiated to > 50Gy (delivered in =< 3Gy/fraction)  -  Small intestine, large intestine, or stomach previously irradiated to > 45Gy  (delivered in =< 3Gy/fraction)  -  Brainstem previously irradiated to > 50Gy (delivered in =< 3Gy/fraction)  -  Lungs previously irradiated with prior V20Gy > 35 percent (delivered in =<  3Gy/fraction)

TP-3654 is an oral PIM inhibitor. This is a Phase 1, open-label, dose-escalation, safety,  pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum  tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-3654 in patients with  advanced solid tumors. Primary Objective:  • To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral  TP-3654 in patients with advanced solid tumors.  Secondary Objectives:  -  To establish the pharmacokinetic (PK) profile of orally administered TP-3654  -  To observe patients for any evidence of antitumor activity of TP-3654 by objective  radiographic assessment  -  To study the pharmacodynamic effects of TP-3654 therapy  -  To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-3654 Inclusion Criteria:  -  1. Have a histologically confirmed diagnosis of advanced metastatic, progressive or  unresectable solid tumor  2. Be refractory to, or intolerant of, established therapy known to provide clinical  benefit for their condition.  3. Have 1 or more tumors measurable or evaluable as outlined by modified Response  Evaluation Criteria in Solid Tumors (RECIST) v1.1  4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than  or equal to 2  5. Have a life expectancy greater than or equal to 3 months  6. Be greater than or equal to 18 years of age  7. Have a negative pregnancy test (if female of childbearing potential) and not  currently nursing  8. Have acceptable liver function:  a. Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless associated  with Gilbert's syndrome b. Aspartate aminotransferase (AST/SGOT), alanine  aminotransferase (ALT/SGPT) and alkaline phosphatase less than or equal to 2.5x upper  limit of normal (ULN) *If liver metastases are present, then less than or equal to 5x  ULN is allowed.  9. Have acceptable renal function:  a. Calculated creatinine clearance greater than or equal to 30 mL/min  10. Have acceptable hematologic status:  a. Absolute Neutrophil Count (ANC) greater than or equal to 1500 x10^9/L b. Platelet  count greater than or equal to 100,000 x 10^9/L c. Hemoglobin greater than or equal to  8 g/dL  11. Have acceptable coagulation status:  1. Prothrombin time (PT) within 1.5 x normal limits  2. Activated partial thromboplastin time (aPTT) within 1.5 x normal limits  12. Be nonfertile or agree to use an adequate method of contraception. Sexually  active patients and their partners must use an effective method of contraception  (hormonal or barrier method of birth control; or abstinence) prior to study entry  and for the duration of study participation and for 3 months (males) and 6 months  (females) after the last study drug dose. Should a woman become pregnant or  suspect she is pregnant while participating in this study, she should inform her  treating physician immediately.  13. Have read and signed the Institutional Review Board (IRB)-approved informed  consent form prior to any study related procedure. (In the event that the patient  is re-screened for study participation or a protocol amendment alters the care of  an ongoing patient, a new informed consent form must be signed.) Exclusion Criteria:  -  1. History of congestive heart failure (CHF), Cardiac disease, myocardial infarction  within the past 6 months prior to Cycle 1 Day 1, left ventricular ejection fraction  <45% by echocardiogram, unstable arrhythmia, or evidence of ischemia on  electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1  2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450  msec in men and >470 msec in women  3. Presence of symptomatic central nervous system metastatic disease or disease that  requires local therapy such as radiotherapy, surgery, or increasing dose of steroids  within the prior 2 weeks.  4. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as  resting 02 saturation of less than or equal to 90% breathing room air). The use of  supplemental oxygen with nasal cannula to reach >90% saturation will not preclude  study participation.  5. Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior  to Cycle 1 Day 1  6. Have active, uncontrolled bacterial, viral, or fungal infections, requiring  systemic therapy  7. Received treatment with radiation therapy, surgery, chemotherapy, or  investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior  to study entry (6 weeks for nitrosoureas or Mitomycin C)  8, Are unwilling or unable to comply with procedures required in this protocol  9. Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis  C. Patients with history of chronic hepatitis that is currently not active are  eligible.  10. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other  conditions) that could compromise protocol objectives in the opinion of the  Investigator and/or the Sponsor  11. Are currently receiving any other investigational agent  12. Have exhibited allergic reactions to a similar structural compound, biological  agent, or formulation  13. Have a medical conditional such as Crohn's disease or have undergone significant  surgery to the gastrointestinal tract that could impair absorption or that could  result in short bowel syndrome with diarrhea due to malabsorption.

This study aims to assess how an at-home COVID-19 frequent testing regimen using the CoV-SCAN  test kit and a paired phone application to help interpret the test result compares to  once-a-week or three-times-a-week polymerase chain reaction (PCR) (molecular) testing to  identify a SARS-CoV-2 infection.  Employees and cast members at Media and Entertainment Company and its affiliates will be  recruited to test whether frequent use of CoV-SCAN will perform as well or better than weekly  molecular testing and at least as well as three-times-a-week molecular testing. Antigen tests are simple to perform, have a rapid turn-around time of 15-30 minutes, and a  lower cost than molecular tests. Because antigen tests do not incorporate an amplification  step, they are intrinsically less sensitive than PCR molecular tests. Nevertheless, several  investigators have examined the feasibility of screening populations of individuals in a low  SARS-CoV-2 infection prevalence situation, such as the workplace or schools, with rapid  antigen tests in place of the molecular tests. Using viral kinetics, knowledge of what level  of viral load is required for transmission of culture-competent virus, test sensitivity and  modeling, they have come to the conclusion that more frequent testing with a test with lower  sensitivity that has a quick turn-around time is better than a test with high sensitivity  with a longer turn-around time. Therefore, the goal of this study is to test the hypothesis  that frequent testing with a relatively sensitive lateral flow antigen test performed at home  using self-collected anterior nasal swabs will be superior to once a week or less PCR testing  and non-inferior to three times a week PCR testing in an employment screening setting with a  relatively low incidence of new SARS-CoV-2 infections. This study aims to assess how an  at-home COVID-19 frequent testing regimen using a Rapid Antigen Screening Test (RAST) and a  phone application to help interpret the test result compares to once-a-week or  three-times-a-week PCR (molecular) testing to identify a SARS-CoV-2 infection. We expect to  recruit up to 4,400 employees and cast members of Media and Entertainment Company and its  affiliates to test whether frequent use of the RAST will perform as well or better than  weekly molecular testing and at least as well as three-times-a-week molecular testing.  Recruitment and the study will continue until at least 31 or at most 148 true positive  SARS-CoV-2 molecular results are reached. Inclusion Criteria:  -  Aged 18 years or older;  -  Have a smartphone;  -  Understand and read English;  -  Will be on one production location for at least three weeks following enrollment to  the study;  -  Will be willing to be contacted by the Study Coordinator after leaving one production  location to facilitate continued access to weekly molecular testing; Exclusion Criteria:  -  Have received any dose of COVID-19 vaccination;  -  Have been diagnosed with COVID-19 infection.

Periodontal disease is a chronic condition affecting the teeth and surrounding support  structures, characterized by tooth loss and alveolar bone loss. Sanative therapy (ST) is the  gold standard non-surgical treatment for periodontal disease and involves mechanically  removing the subgingival bacteria from the periodontal pockets. Regular periodontal  maintenance appointments are needed to maintain periodontal health after ST. Moreover, the  periodontal health of individuals not requiring ST is also dependent on regular hygiene  appointments. Due to Ontario's March 2020 COVID-19-related clinic closure for approximately 3  months along with a reduced numbers of appointments available due to guidelines of  professional bodies and public health beyond this period of time, many appointments were  considerably delayed or cancelled. The effects of this disruption to periodontal health in  male and female patients who have undergone ST and continue with maintenance appointments or  who attend for regular hygiene appointments have not yet been investigated. Sanative therapy (ST) is often the first line of treatment following a diagnosis of  periodontal disease. By mechanically removing the inflammation-inducing bacteria below the  gum line, a more controlled state of periodontal health can be achieved. Improvements in  periodontal health achieved through ST can be maintained long-term with regular maintenance  appointments that aid in preventing further progression of the disease. However, due to the  government-mandated clinic closure in March 2020 of dental offices for all but emergency  in-person care in Canada due to the COVID-19 pandemic, clinics were shut down for  approximately 3 months with a reduced availability of appointments in the following year due  to professional guidelines. Regular hygiene appointments (cleanings) were also considerably  delayed or cancelled. This disruption in routine care, accompanied with the potential  exacerbation of various risk factors for periodontal disease such as stress, diet, physical  activity, and smoking or alcohol use brought on by the pandemic has not yet been investigated  pertaining to the effect on clinical periodontal outcomes. The main objective of this study  is to determine if delays in regularly scheduled maintenance or regular hygiene appointments  caused by COVID-19 impacted clinical periodontal outcomes in male and female patients.  Secondary objectives include retrospectively determining the long-term clinical outcomes of  patients who underwent periodontal therapy or who have had regular hygiene appointments at  the clinic; comparing the long-term periodontal outcomes of patients who undergo maintenance  appointments and those who receive only regular hygiene appointments; and examining whether  there exists a sex-specific response to either treatment. Periodontal outcomes of interest  include probing depth, bleeding on probing, plaque index, and tooth loss. Inclusion Criteria:  -  Have undergone sanative therapy or attend regular hygiene appointments at the clinic  -  Age 19 years or older  -  Willing and able to provide informed consent Exclusion Criteria:  -  Age < 19 years  -  Unable to provide informed consent

Nowadays in France, the standards of hospital rooms are being questioned in view of the  particularities of certain populations admitted to hospitals.  The " Groupement de Coopération Sanitaire des Hôpitaux Universitaires du Grand Ouest " (GCS  HUGO) proposes to improve the quality of geriatric care through the modernisation of hospital  rooms.  The GCS HUGO has launched a project to co-design a hospital room adapted to the elderly,  called "Hospi'Senior", with the help of the "Dependency and Old Age" steering committee. This  committee is made up of experts from HUGO and partner companies.  The Hospi'Senior room is composed of innovative technologies concerning bed equipment (e.g.  bed canopy), autonomous (e.g. lifeline) and assisted mobility (e.g. rail lift system),  lighting (e.g. light guide), communication (touch tablet) and social space (furniture).  The project consists in evaluating the user experience (UX) of :  -  patients hospitalized in the Hospi'Senior room,  -  informal caregivers of patients hospitalized in the Hospi'Senior room,  -  caregivers who have worked in the Hospi'Senior room. The specificities of Hospi'Senior room are multiple and concern in particular :  -  The equipment of the bed :to create a more personalized room: presence of a bed canopy,  orientation of the bed towards the windows, presence of a multifunctional space at the  head of the bed.  -  The autonomous mobility of the patient by facilitating the movements and by preserving  the orientation in time of the patient: ephemeris for the temporal orientation, lifeline  and sliding door.  -  Caregiver-assisted mobility to facilitate patient movements: lifting rail above the bed.  -  Lighting to ensure safe movement, especially during the night: light guide, room light,  window mirrors, bathroom lighting.  -  The digital interface with a touch tablet to improve the occupational and communication  aspects.  -  The socialization space to welcome visitors in the room.  Design:  Step 1: A visit to the room is made to each participant (patients, informal caregivers,  caregivers).  Step 2: no change in care or support for users during hospitalization  Step 3: UX assessment:  -  Patients: collected at the end of the hospitalization,  -  Informal caregivers: collected at the end of the patient's stay,  -  Caregivers: collected after 3 months of using the Hospi'Senior room. Inclusion Criteria:  -  Patient :  -  Being admitted to Hospi'Senior room  -  Informal caregiver :  -  Be the informal caregiver of a patient admitted to Hospi'Senior room (only one  caregiver per patient)  -  Age ≥ 18 years old  -  Able to visit the patient admitted to Hospi'Senior room  -  Caregiver :  -  Age ≥ 18 years old  -  Be a healthcare professional involved in the short-term geriatric unit, from one  of 4 categories:  -  physicians,  -  permanent paramedical caregivers (nurse, nurse's aide, health executive),  -  support paramedical staff (psychologist, neuropsychologist, physiotherapist,  adapted physical activity teacher),  -  technical staff (stretcher bearer). Exclusion Criteria:  -  Patient :  -  Contraindication to participation in the study at the discretion of the medical  team  -  Refusal to participate  -  Poor understanding of the French language  -  Persons deprived of liberty by an administrative or judicial decision, persons  under forced psychiatric care, adults under legal protection or unable to express  their consent  -  Informal caregiver :  -  Refusal to participate  -  Poor understanding of the French language  -  Persons deprived of liberty by an administrative or judicial decision, persons  under forced psychiatric care, adults under legal protection  -  Caregiver :  -  Be a staff in training  -  Less than 3 months seniority in the unit  -  Refusal to participate

The purpose of the proposed research is to determine how changes in kidney dopamine (DA)  activity influence urinary sodium excretion. We will decrease DA activity in the kidney by  inhibiting DA synthesis via carbidopa administration. We want to compare findings in normal  volunteers and in patients with postural tachycardia syndrome (POTS). We will test the null  hypothesis (Ho) that the effects of oral carbidopa administration on urinary sodium excretion  will not differ between patients with POTS and healthy volunteers. We will determine whether inhibition of renal dopamine formation by carbidopa administration  leads to a decrease in urinary excretion of dopamine and sodium and whether the response  differs in POTS and control populations. Carbidopa effects will be compared to those of a  matching placebo, and the sequence of treatments (carbidopa before placebo or placebo before  carbidopa) will be randomized.  Each subject will undergo a complete history and physical examination, including an  electrocardiogram (EKG).  -  After achieving sodium balance on a 200 mEq/day sodium diet, subjects will collect urine  over 24hr for baseline assessment of sodium and catecholamines.  -  On this day, the subjects will be admitted to the CRC.  -  An 18 gauge intravenous catheter will be inserted in order to draw blood.  -  The subjects will fast from 7 pm until after the next morning's testing.  -  In the morning, while still supine after the overnight sleep, heart rate and blood  pressure will be recorded, and blood will be drawn. The subjects will then stand for 10  minutes. Heart rate and blood pressure will be measured at intervals, and an upright  blood sample will be collected.  -  The subjects will be asked to collect their urine to end the 24hr urine collection.  Another 24hr urine collection will be started.  -  Treatment A (Carbidopa 200mg or placebo) will be given orally following the void, at  approximately 7 am. Additional doses will be taken every 6 hours with the last dose at 7  am the following morning.  -  Subjects will be free to follow their normal routine during the day until returning to  the CRC for the night. However, they will need to consume the 200 mEq/day study diet for  each meal, collect all urine, and take study medication on schedule  -  After returning to the CRC, the subjects will fast after 7 pm.  -  In the morning, supine and standing heart rate and blood pressure will be recorded, and  the subjects will be asked to collect their urine to end the 24hr urine collection.  -  The final dose of study medication (Carbidopa 200mg or placebo) will be given orally  following the void, at approximately 7 am.  -  Supine heart rate and blood pressure will be measured and supine blood samples will be  collected hourly for 4 hours after the treatment and at 8 hours after the treatment.  Subjects must rest supine for at least 30 minutes before each blood draw.  -  At 2 hours after treatment, subjects will stand for 10 minutes for upright blood  pressure and heart rate measurements and collection of an upright blood sample, as  described above. Participants will be asked to rate the severity of common orthostatic  symptoms while supine and upright.  -  Urine will be collected for two 4-hour periods after treatment and from 8 hours to 24  hours after treatment.  -  Fixed-sodium study diet will be provided after the 4-hour measurements and in the  evening.  After at least a 1 day washout period, the study will be repeated with Treatment B Inclusion Criteria:  -  Patients diagnosed with POTS by the Vanderbilt Autonomic Dysfunction Center based on  the following stringent criteria: 1) history of daily orthostatic symptoms for at  least 6 months; 2) increase in heart rate (HR) of at least 30 bpm with standing or a  standing HR of at least 120 bpm; 3) absence of orthostatic hypotension (defined as a  fall in blood pressure (BP)>20/10 mm Hg); and 4) absence of conditions, such as  dehydration, substantial weight loss, or systemic illnesses, that could provoke  orthostatic intolerance  -  Upright plasma NE at least 600 pg/mL in patients  -  Non-smoking  -  Free of medications with the potential to influence BP  -  Able and willing to provide informed consent - Exclusion Criteria:  -  Overt cause for postural tachycardia (such as acute dehydration)  -  Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or  screening results  -  Positive urine b-hcg pregnancy test  -  Evidence of cardiac structural disease (by clinical examination or prior  echocardiogram)  -  Hypertension defined as a BP>145/95 (off medications) or need for antihypertensive  medications  -  Evidence of significant conduction system delay (QRS duration >120 ms) on  electrocardiogram  -  Inability to give, or withdraw, informed consent

Visual acuity is the relative ability of the eye to resolve detail that is usually expressed  as the reciprocal of the minimum angular separation in minutes of two lines just resolvable  as separate and that forms in the average human eye an angle of one minute.  Visibly Inc. has developed a method for determining a patient's visual acuity electronically  via a web-based software system that can be self-administered wherever convenient. This  method provides an efficient alternative for people to have immediate access to visual acuity  measurements. The Visibly Digital Acuity Product (VDAP) is a web-based, self-guided software application  intended for use by adults, ages 22 to 40, at home, to evaluate visual acuity with or without  correction. The standalone software application allows the user to interface with the  software via a web browser on two internet-enabled devices:  -  A computer screen (the Display) which displays optotypes  -  A touchscreen mobile device (the Remote) which operates as a remote control and  interface for the user to respond to prompts related to the optotypes appearing on the  Display while standing 10 feet away  The software allows users to view and respond to displayed optotypes and uses the responses  to categorize a user's visual acuity into one of two buckets:  -  20/25 or better  -  Worse than 20/25 Inclusion Criteria:  -  1. Be between 22 and 40 years (inclusive) of age at the time of consent 2. Be able and  willing to provide written informed consent, attend all scheduled visits and comply  with all study procedures Exclusion Criteria:  -  1. Have any of the following conditions (based on subject report):  1. Advanced eye disease in either eye;  2. Poor vision as a result of refractive surgery in either eye;  3. Unable to walk;  4. Unable to hear or follow audio instructions.

To evaluate the relation between thyroid, parathyroid hormones and estimated glomerular  filtration rate in chronic kidney disease . CKD is defined as abnormalities of kidney structure or function, present for >3 months, with  implications for health. CKD is classified based on Cause, GFR category (G1-G5), and  Albuminuria category (A1-A3) .  The global prevalence of CKD is 13.4%, with 10.6% being stages 3-5 ,Over the past 10 years,  the death rate due to CKD has increased by 31.7% .  CKD patients remain sometimes asymptomatic, presenting the complications typical of renal  dysfunction only in more advanced stages. Its treatment can be conservative usually in  patients with glomerular filtration rate above 15 ml/minute without indications of dialysis  or replacement therapy .  In CKD patients the changes of endocrine system levels may arise from several causes as the  kidney is the site of degradation & synthesis of many different hormones .  So thyroid and parathyroid hormones dysfunction has been recognized as common co-morbidity  that is often diagnosed with CKD .  Thyroid hormone is one of the most important hormones in the human body as it regulates  majority of the body's physiological actions .  Parathyroid hormone (PTH) is one of the most important hormones required for the maintenance  of calcium and phosphate homeostasis .  Chronic kidney disease metabolic bone disorder (CKD-MBD) among patients with end stage renal  disease ranges from 33% to 67%, and its severity tends to increase with the progression of  the kidney damage & high mortality rates .  CKD-MBD causes bone abnormalities that affect turnover, volume, mineralization, vascular,  linear growth, and density, and soft tissue calcification . Inclusion Criteria:  -  1. CKD patients 2. Age (18-80 years) 3. Diabetic nephropathy 4. Hypertensive  nephropathy 5. Chronic pyelonephritis 6. Obstructive nephropathy 7. Polycystic kidney  8. Gout nephropathy 9. Nephrosclerosis Exclusion Criteria:  -  1. Patients underage of 18 and above 80 2. Patients with history of thyroidectomy and  parathyroidectomy 3. Patients with history of thyroid and parathyroid disease before  diagnosis of CKD 4. Malignancy

An open-label, dose escalation and expansion clinical trial to evaluate the safety,  tolerability and PK of HMPL-689 in patients with relapsed or refractory lymphomas This is a Phase 1, open-label, multicenter study of HMPL-689 administered orally to patients  with relapsed or refractory lymphoma.  HMPL-689 is a selective and potent small molecule inhibitor targeting the isoform  phosphoinositide 3'-kinase delta (PI3Kδ), a key component in the B-cell receptor signaling  pathway  This study will consist of a dose escalation stage (Stage 1) and a dose expansion stage  (Stage 2).  Dose Escalation Stage (Stage 1):  This stage will end when any of the following criteria is met:  -  The dose level 1 demonstrates an excessive toxicity, ie, 3 dose limiting toxicities  (DLTs) are observed out of the first 3 patients at dose level 1.  -  The maximum sample size is reached.  -  The MTD and/or RP2D is confirmed.  Dose Expansion Stage (Stage 2):  To further characterize the safety and explore the preliminary anti-tumor activity of  HMPL-689 at RP2D, patients with B cell lymphoma will be enrolled in the dose expansion stage. Inclusion Criteria:  1. (ECOG) performance status of 0 or 1;  2. Histologically confirmed lymphoma (tumor types are restricted to CLL/SLL, FL (grade  1-3a), MCL, MZL, LPL/WM, PTCL or CBCL);  3. Patients with relapsed or refractory NHL for whom:  -  Standard of care treatment options no longer exist (Stage 1 only);  -  Standard of care treatment options no longer exist with the exception of  PI3K-delta inhibitors (Stage 2 only);  4. Expected survival of more than 24 weeks. Exclusion Criteria:  Patients who meet any of the following criteria will be excluded from study entry:  1. Primary central nervous system (CNS) lymphoma;  2. Any of the following laboratory abnormalities Absolute neutrophil count; <1.0×10^9/L,  Hemoglobin <80 g/L Platelets <50 ×10^9/L  3. Inadequate organ function, defined by the following:  -  Total bilirubin ≥1.5 times the upper limit of normal (× ULN);  -  AST or ALT > 2.5 × ULN;  -  Estimated creatinine clearance (CrCl) per Cockcroft-Gault;  -  Dose Escalation stage of trial (Stage 1) - CrCl < 40 mL/min;  -  Dose Expansion stage of trial (Stage 2) - CrCl <30 mL/min;  4. International normalized ratio (INR) > 1.5 × ULN, activated partial thromboplastin  time (aPTT) > 1.5 × ULN;  5. Serum amylase or lipase > ULN at screening or known medical history of serum amylase  or lipase > ULN;  6. Patients with presence of second primary malignant tumors within the last 2 years;  7. Clinically significant history of liver disease;  8. Prior treatment with any PI3Kδ inhibitors;  9. Any prior use of the following: cancer therapy within 3 weeks of study treatment, GCSF  within 7 days of screening, steroid therapy or targeted anti-neoplastic intent within  7 days of treatment, any use of strong CYP3A4 inducers within 2 weeks prior to  initiation of study treatment, prior autologous transplant within 6 months of study  treatment, prior allogenic stem cell transplant within 6 months of study treatment;  10. Clinically significant active infection or interstitial lung diseases (including drug  induced pneumonitis);  11. Major surgical procedure within 4 weeks prior to initiation of study treatment;  12. Adverse events from prior anti-neoplastic therapy that have not resolved to Grade less  than or equal to 1, except for alopecia;  13. New York Heart Association (NYHA) Class II or greater congestive heart failure;  14. Congenital long QT syndrome or QTc >470 msec;  15. Currently use medication known to cause QT prolongation or torsades de pointes;  16. History of myocardial infarction or unstable angina within 6 months prior to  initiation of study treatment;  17. History of stroke or transient ischemic attack within 6 months prior to initiation of  study treatment;  18. Inability to take oral medication, prior surgical procedures affecting absorption, or  active peptic ulcer disease;  19. History of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);  20. Patients with ongoing chronic gastrointestinal diseases;  21. Any other diseases, metabolic dysfunction, physical examination finding, or clinical  laboratory finding that, in the investigator's opinion, gives reasonable suspicion of  a disease or condition that contraindicates the use of an investigational drug or that  may affect the interpretation of the results or renders the patient at high risk from  treatment complications.

Pressure ulcer is defined by the European Pressure Ulcer Advisory Panel (EPUAP) and the  National Pressure Ulcer Advisory Panel (NPUAP) as "localized skin and/or skin, usually  arising over bony prominences, caused by pressure alone, or by a combination of shear and  pressure. subcutaneous tissue damage. Pressure ulcer is a painful, costly and preventable  health problem that is frequently encountered especially in geriatrics group and in patients  with limited daily activities or bedridden. It is an undesirable health care problem that is  difficult to treat, but it is possible to prevent the development of pressure ulcers with the  measures to be taken from the beginning of the disease. In order for nurses to fulfill their  role in preventing pressure ulcers, the content of undergraduate education programs needs to  be arranged in a way that will provide them with knowledge and skills in the prevention of  pressure ulcers, diagnosis of risky patients and maintenance of care. In Northern Cyprus,  knowledge and skills related to pressure sores are provided to students in the basic nursing  education curriculum. However, the subject of pressure ulcer in the education programs of  nursing schools differs in terms of content and duration, and most of the hospitals do not  have a standard guide and training program for the prevention of pressure ulcers. In Northern  Cyprus, studies on the knowledge and practices of nursing students to prevent pressure ulcers  are limited. According to the results of a study conducted in Turkey, it has been reported  that a significant portion of nursing students have a positive attitude towards preventing  pressure ulcers, but their general knowledge about preventing pressure ulcers is  insufficient. In another study, it was reported that 70.7% of nursing students encountered  patients with pressure ulcers during hospital practices, but research findings and the  knowledge of nursing students to prevent the development of pressure ulcers were  insufficient. Similarly, in studies conducted with nursing students using different scales,  it has been reported that students' knowledge levels about preventing pressure ulcers are  low. This research was planned in accordance with the randomized controlled research method  in order to determine the knowledge levels and practices of firts year nursing students to  prevent pressure ulcers. The population of the research will be 2nd year students studying at the Faculty of Health  Sciences Nursing Department in the 2021-2022 Academic Year Spring Semester. Since 1st year  students do not have any information about pressure ulcers yet and other classes (3rd, 4th  grade students) have received information about pressure ulcers before, they were excluded  from the study, as this would affect the average scores. The entire population that meets the  criteria for inclusion in the study will be included in the sample. Before starting the  research, the enclosed Informed Consent Form will be distributed to the students and their  consent will be obtained stating that they are willing to participate in the research.  "Student Descriptive Characteristics Questionnaire and "Pressure ulcer Knowledge Assessment  Tool" updated version (PUKAT 2.0) all groups will be collected before and after the training  by face-to-face interview method. Students will be divided into two groups by simple  randomization method. Group distributions will be divided into group 1 and group 2 by drawing  lots. Students who are divided into groups will not know what the group they belong to means  In this case, group 1 students will be included in the research in accordance with the  flipped learning model, and group 2 students will be included in the research in accordance  with the traditional education method. Group 1 students and educational materials (lecture  presentation, video) will be uploaded through the system in accordance with the flipped  learning model, and students will be asked to come prepared to the planned lesson. No  classical presentations will be made to the students, but the education will be carried out  in the form of question and answer discussion, in line with the Flipped Learning model. The  training, consisting of Group 2 students and a Powerpoint presentation, will last 20-30 on  average, and will be given in accordance with the traditional education model. After the  lesson, the questions of the students who have questions will be answered. After obtaining  the necessary ethics committee approval, the data collection phase will begin. Inclusion Criteria:  -  Students who agree to participate in the research,  -  Year 2 students studying at the University's Faculty of Health Sciences, Department of  Nursing. Exclusion Criteria:  -  Students who do not meet the sample selection criteria,  -  Students who fill in the data collection form incompletely.

This study is to find an optimal dose of Imiquimod (IMQ) in the first part (Phase I) and test  the effectiveness of the combination treatment of IMQ, cyclophosphamide (CTX), and  radiotherapy (RT) in patients with skin metastases from breast cancer in the second part  (Phase II). Currently this trial is in its Phase II part. By harnessing the cytocidal and immunostimulatory properties of two local treatment  modalities, RT and IMQ, an effective, adaptive immune response can be generated, resulting in  systemic control of metastatic breast cancer after local treatment of cutaneous metastases.  Additionally, based on investigators' recent preclinical data, the investigators intend to  estimate in patients with metastatic breast cancer, if the addition of immunomodulatory  cyclophosphamide can increase anti-tumor responses.  This trial originally had one treatment arm IMQ/RT(patients were treated with IMQ and RT).  Recent evidence has emerged that the addition of immunomodulatory cyclophosphamide (CTX)  increased anti-tumor responses, therefore the IMQ/RT arm is closed and the trial will  continue with two additional cohorts (CTX/IMQ/RT and CTX/RT) which include cyclophosphamide. Inclusion Criteria:  1. Patients with biopsy-confirmed breast cancer.  2. Patients with at least measurable skin metastases and distant, measurable metastases  (outside of skin) by Response Evaluation Criteria in Solid Tumors (RECIST). For  patients without distant measurable metastases, an area of the skin metastases  designated to not receive local therapy can be substituted. Patients with multiple (>=  2) metastatic sites (skin involvement not required), with at least one site measurable  by RECIST, will be eligible for the CTX/RT cohort.  3. Age >= 18 years.  4. Eastern Cooperative Oncology Group performance status 0-2.  5. Patients must agree to tumor fine-needle aspiration required by protocol.  6. Concurrent systemic cancer therapy (hormones, biologics or chemotherapy) can be  continued if distant metastases are non-responsive (i.e. no complete response or  partial response) on that regimen for >= 8 weeks as assessed by the investigator.  7. Patients must have adequate organ and bone marrow function as defined below:  -  absolute neutrophil count >= 1,300/microliter  -  hemoglobin >= 9.0 grams/deciliter  -  platelets >= 75,000/microliter  -  total bilirubin =< 1.5 X institutional upper limit of normal  -  AST (aspartate aminotransferase) =< 2.5 X institutional upper limit of normal  -  ALT (alanine aminotransferase) =< 2.5 X institutional upper limit of normal  -  creatinine =< 2 X institutional upper limit of normal if patient has chronic  renal insufficiency and creatinine has been stable for > 4 months)  8. Informed consent. Exclusion Criteria:  1. Brain metastases unless resected or irradiated and stable >= 4 weeks.  2. Concurrent treatment with other investigational agents.  3. Patients who have received any local therapy (radiotherapy, high-potency  corticosteroids, intralesional therapy, laser therapy or surgery) other than biopsy to  the target area within 4 weeks prior to first dosing of study agent.  4. Patients who have received hyperthermia to the target area within 10 weeks prior to  first dosing of study agent.  5. Patients with an uncontrolled bleeding disorder.  6. Patients (with skin metastases only) who will be therapeutically anticoagulated with  heparins or coumadin at the time of the biopsy (they are eligible if anticoagulation  can be held prior to biopsy as per investigator). Patients on aspirin and other  platelet agents are eligible.  7. Patients with known immunodeficiency or receiving immunosuppressive therapies.  8. History of allergic reactions to imiquimod or its excipients.  9. Uncontrolled intercurrent medical illness or psychiatric illness/social situations  that would limit compliance with study requirements.  10. Pregnancy or lactation.  11. Women of childbearing potential not using a medically acceptable means of  contraception.

This study will pilot test a brief, scalable intervention called Maisha (Swahili for life),  to address HIV stigma for women presenting to antenatal care in Tanzania and male partners  who accompany them. The intervention will include: 1) a video and brief counseling that  addresses HIV stigma at the start of the ANC visit (prior to HIV testing), and 2) two  stigma-based counseling sessions for individuals who are HIV infected, building on the video  content to provide emotional support, promote acceptance, address stigma, and reinforce care  engagement. The primary intervention outcome is engagement in PMTCT care among women who are  HIV infected. The investigators will also examine HIV stigma outcomes (enacted, anticipated,  internalized) among all groups of participants, including individuals who are already  established on ART and indiviudals who are HIV uninfected. HIV-related stigma has been identified as a significant reason for loss to follow up in  prevention of mother-to-child transmission of HIV (PMTCT) programs. Antenatal care (ANC)  provides a unique and important entry point to address HIV stigma. Stigma-based counseling  during the first ANC visit can promote readiness to initiate or sustain treatment among those  who are HIV infected, and can address stigmatizing attitudes and behaviors among those who  are uninfected. We are proposing to pilot test a brief, scalable intervention called Maisha  (Swahili for life), to address HIV stigma for women and their partners presenting to ANC in  Tanzania. The intervention will include: 1) a video and brief counseling for women and their  partners (if present) that addresses HIV stigma at the start of the ANC visit (prior to HIV  testing), and 2) two stigma-based counseling sessions for women who are HIV infected,  building on the video content to provide emotional support, promote acceptance, address  stigma, and reinforce care engagement, with the opportunity for male partners to attend the  first follow-up counseling session after testing. The primary intervention outcome is  engagement in PMTCT care among women who are HIV infected. As a secondary outcome we will  also look at linkage to HIV care among men who are HIV infected. We will also examine HIV  stigma outcomes (enacted, anticipated, internalized) among all groups of people, including  those who are already established on ART and those who are HIV uninfected. The intervention  content is based on principles of cognitive-behavioral therapy (addressing automatic negative  thoughts about the self, future and the world) to address and mitigate multiple forms of HIV  stigma (internalized, anticipated and enacted). We will conduct a pilot RCT of the  intervention, enrolling all women who attend a first ANC appointment at two clinics in the  Moshi district. If women come to the ANC visit with a male partner, the partner will be  invited to enroll as well. Maisha will be compared to the standard of care HIV counseling. In  addition to a baseline assessment, all participants who are identified as HIV-infected and  their partners will get a follow-up assessment three months after enrollment. A subset of  participants who are identified as HIV-uninfected but who report high levels of HIV  stigmatizing attitudes at baseline will also receive a follow-up assessment three months  after enrollment. Measures will include health outcomes (care engagement, adherence,  depression), stigma outcomes, and HIV disclosure. Quality assurance data will be collected  and the feasibility and acceptability of the intervention and RCT will be described.  Statistical analysis will examine differences between conditions in health outcomes and  stigma measures, stratified by HIV status. We hypothesize that 1) among HIV infected  individuals, individuals receiving the Maisha intervention will report better engagement in  PMTCT care/linkage to HIV care and lower levels of internalized HIV stigma, as compared to  individuals receiving the standard of care, and 2) among HIV uninfected individuals,  individuals receiving the pre-test video and counseling will report lower levels of  stigmatizing attitudes when compared with the control group. Inclusion Criteria:  -  18 years of age or older  -  If female: Pregnant and attending first antenatal care (ANC) appointment for the  current pregnancy at one of the two study sites  -  If male: Accompanying an enrolled woman to her first ANC appointment. Exclusion Criteria:  -  Impaired mental status  -  Does not speak Swahili

Proof of effectiveness of Pascoflair using qantitative measurement of electric brain activity  during examination stress in 40 subjects suffering from test anxiety. A double-blind,  randomized, placebo-controlled, 2-armed, Phase IV study in parallel design. Anxiolytic effects of PASCOFLAIR® shall be tested in subjects suffering from test anxiety  after single intake by aid of a newly developed, validated method consisting of a combination  of eye tracking (following glances) with neurocode tracking (quantitative EEG with a time  resolution of 364 ms). Inclusion Criteria:  -  Healthy male and female subjects.  -  Age between 18 and 40 years (both included).  -  Anxiety questionnaire PAF (pre-selection of subjects) - values above T> 60 are  regarded as conclusive.  -  Inconclusive case history and diagnosis.  -  Subject must be capable of giving informed consent.  -  Acceptance of written consent to participate in the study after education in written  and oral form (informed consent). Exclusion Criteria:  -  Acute or chronic disease with an impact on the study, which becomes obvious by case  history or clinical examination.  -  Clinically relevant pathological findings from clinical and laboratory findings.  -  Presence of clinically relevant pathological EEG features or artifact-free portion of  the screening EEG <30%.  -  Clinically relevant allergic symptoms.  -  Detection of alcohol at the time of initial examination (day SC) or on study day A  (positive alcohol test) or by case history.  -  Detection of drugs (positive drug test) at the time of initial examination (day SC).  -  Consumption of clinically relevant medication during last fourteen days before and  during the active study period based on the notification of the subject or his case  history.  -  Consumption of medication with primarily central action (i.e. psychotropic drugs or  centrally acting antihypertensives).  -  Known intolerance / hypersensitivity (allergy) to plant derived extracts (Passion  flower dry extract) or any of the ingredients of the investigational product  (anamnestic).  -  Presence of a rare, genetic disease such as fructose intolerance, glucosegalactose  malabsorption or sucrase-isomaltase deficiency (anamnestic).  -  BMI (Body Mass Index) <18 or> 32.  -  Consumption of unusual quantities or misuse of coffee (more than 4 cups a day), tea  (more than 4 cups a day) or tobacco (more than 20 cigarettes per day).  -  Smoking on day of A.

The researchers collect treatment-naive H.pylori-positive patients from the outpatient  clinic. The subjects were randomized to receive a 10-day or 14-day course of quadruple  eradication therapy. 6-8 weeks after treatment, the subjects will re-take the 13C-urea breath  test. Calculate the eradication rates, adverse reaction rates, patient compliance and  cost-effectiveness index of each group. The researchers collect treatment-naive H.pylori-positive patients from the outpatient  clinic. If the subject meets the selection criteria but not the exclusion criteria, and signs  an informed consent form, the researchers randomized the subjects in groups: subjects  received a 10-day or 14-day course of bismuth-containing quadruple eradication therapy. The  medication of groups are as follows. 6-8 weeks after the eradication treatment, the subjects  will review the 13C-urea breath test, and the researcher records the results.  After all subjects were tested, the eradication rates, adverse reaction rates, patient  compliance and cost-effectiveness index of each group were calculated.  According to the course of treatment, it is randomized into a 10-day treatment group and a  14-day treatment group. The two groups of bismuth quadruple regimens are the same, as  follows:  Option 1: Amoxicillin + Clarithromycin + Bismuth + Vonoprazan fumarate Option 2: Amoxicillin  + Tetracycline + Bismuth + Vonoprazan fumarate Option 3: Amoxicillin + Metronidazole +  Bismuth + Vonoprazan fumarate Three options are selected according to the hospital's  situation. Inclusion Criteria:  -  Patients aged 18-65.  -  Patients with H.pylori infection (Positive for any of the following: H.pylori culture,  histopathology test, rapid urease test, 13C/14C-urea breath test, stool H.pylori  antigen test).  -  Patients who have never received H. pylori eradication treatment. Exclusion Criteria:  -  Patients with serious underlying diseases, such as liver insufficiency (Aspartate  aminotransferase or alanine aminotransferase greater than 3 times the normal value),  renal insufficiency (Cr≥2.0mg/dL or glomerular filtration rate <50 ml/min),  immunosuppression, malignant tumors, Coronary heart disease or coronary artery  stenosis ≥75%.  -  Patients who are pregnant or lactating or unwilling to take contraceptive measures  during the trial.  -  Patients with active gastrointestinal bleeding.  -  Patients with a history of upper gastrointestinal surgery.  -  Patients allergic to treatment drugs.  -  Patients with medication history of bismuth agents, antibiotics, proton pump inhibitor  and other drugs within 4 weeks  -  Patients with other behaviors that may increase the risk of illness, such as alcohol  and drug abuse  -  Patients whose re-check 13C/14C-urea breath test is negative before the start of the  test.  -  Patients who are unwilling or incapable to provide informed consents.

This in-vivo study investigates early (48h), mature (2 weeks) and long-term (3 months)  biofilm formation and composition on temporary push-on cones (exchangeable conical rings)  made of noble-alloy-based materials (Pagalinor, PA) in comparison to  Titanium-6Aluminum-7Niobium alloy (TAN) presently used in the transmucosal portion of dental  implant abutments. Oral biofilm (dental plaque) consists of bacteria and their metabolic products as well as  saliva components and food residues. It is recognizable as a tough and structured coating on  teeth and artificial surfaces within the oral cavity. Plaque development is a physiological  process that begins immediately after cleaning of the oral surface. If the biofilm is not  removed by daily oral hygiene, it continues to mature while changing the structure and its  microbial composition.  Implant restorations comprise the osseous implant portion predominantly manufactured from  titanium alloys, the transmucosal implant portion (in most implant systems as a separate  abutment), and the clinical crown, which is in most systems extraorally cemented on an  abutment and screw-retained onto the implant. According to current knowledge, microbial  colonization of the implant abutment surface plays a significant role in the aetiology of  peri-implantitis.  This study investigates the antibacterial potential of a temporary push-on cone (conical  ring) that could reduce the risk of bacterial related peri-implant diseases due to decreased  biofilm susceptibility, compared to current available transmucosal materials, in the short-  and long-run. The test material Pagalinor®2 (PA) is an established material in dental  medicine and has proven to accumulate least biofilm in an in-vivo biofilm sampling model  using removable splints. The control material consists of the current transmucosal implant  abutment material Titanium-6Aluminum- 7Niobium alloy (TAN). The push-on rings are designed  for repeated application along the transmucosal implant abutment portion with high precision  fit and will allow biofilm sampling in the natural implant environment. Profound insight into  the native homeostasis of biofilm formation will be obtained and therefore enhance the  knowledge about long-term tissue response. Inclusion Criteria:  -  Informed Consent signed by the subject  -  Presence of one or more bone level titanium implant prior to insertion of the final  restoration  -  No systemic illness  -  No heavy smoking (smoking <10 cigarettes/day)  -  No pregnancy  -  No active periodontitis (probing pocket depth ≤4 mm)  -  No pharmacological treatment or antibiotic therapy during or up to three months before  the study Exclusion Criteria:  -  Systemic illness (e.g. Diabetes)  -  Heavy smoking (smoking >10 cigarettes/day)  -  Known or suspected non-compliance, drug or alcohol abuse  -  Pregnancy  -  Active periodontitis (probing pocket depth >4 mm)  -  Pharmacological treatment or antibiotic therapy during or up to three months before  the study

This repository will consist of clinically derived data and images of patients with  congenital heart disease from the time of birth until they have reached one of the following  outcomes: transition to outpatient care that has not resulted in readmission in 30 days after  hospital discharge, death, weaned off supplementary feeding tubes, or clinic visits  demonstrating clinical stability with their primary cardiologist, or full bi-ventricular  cardiac surgery palliation with improvement in hemodynamic stability. This information will  be collected for clinical evaluation and diagnostic purposes and will continue to be stored  for potential future research application. Approximately 40,000 infants are born each year with congenital heart disease (CHD), a  leading cause of morbidity and mortality in infancy. Progress in surgical, transcatheter, and  medical management of newborn CHD has significantly reduced mortality. The CHAMP app  (separate IRB # 15030113) has helped to transition high-risk infants with single ventricle  congenital heart disease out of the hospital and to second stage cardiac surgery at  Children's Mercy Hospital and across the United States with improved survival. Remote  monitoring technology and telemedicine is a critical tool to aid clinical care for high risk  children with congenital heart disease but has been limited to the single ventricle  population in most cases. The benefits of this tool as a standard of care for other children  transitioning home may include decreased readmissions, improved weight gain, and remote  monitoring for reduced throughput in the emergency room, hospital, and clinic settings. To  improve outcomes beyond mortality and into morbidity with other high-risk patients with  congenital heart disease, future studies must assess morbidities and quality of outcomes with  the application of remote home monitoring with applications like the CHAMP app.  Patients that are discharging from the hospital after complex congenital heart disease  surgery and cardiac catheterization are at high risk of events. Adverse outcomes in the year  after discharge are of similar magnitude to mortality in hospital and are not only with  infants with single ventricle heart disease but may include infants and children that were  hospitalized more than 30 days, readmitted to intensive care unit more than once, smaller  size for age, younger age at surgery, shunt dependent for pulmonary blood flow, congenital  heart disease with complexities such as neurological conditions and supplemental enteral  feedings gastrostomy. Over a 6-year period, 6.7% (514/7976) children experienced adverse  events including mortality in a report from England after initial discharge from cardiac  surgery. In a review of our similar patients from Children's Mercy we have noted a 5.8%  mortality in this population.  There is additional focus on expanding transition care in the pediatric cardiac population  beyond 30 days after discharge as traditionally followed by the Society of Thoracic Surgeons  as a marker of well-state (traditionally 8.3%) and onto 90 days (21% of additional  readmissions) to 1 year after discharge. Children had unplanned hospital readmissions during  the first year after cardiac surgery that were between 31 and 90 days after discharge that  could have possibly been prevented with the aid of remote technology in additional to  ambulatory care by a specialized advanced practice nurse. Higher rates of readmissions were  seen with those in lower socioeconomic areas (through zip codes), living closer to the  hospital (potentially a marker of access to care and rurality), higher STAT category, longer  intubation, and longer ICU length of stay were all markers for higher risk of later  readmission after 31 days of discharge.  Combining the advancements with CHAMP app with the expert care teams with advanced practice  nurses, a new standard of care for an expanded group of high-risk infants and children  transitioning home after cardiac surgery and in-hospital care can be established. The  research and ability to improve the understanding of how this process can be applied to an  expanded population that has been identified as high risk is key for implementation and  sustainability of a high risk transition care program. Inclusion Criteria:  -  • Subjects with congenital heart disease that have been hospitalized for more than 30  days,  -  Subjects being discharged with readmissions more than twice to critical care  areas,  -  Subject with single ventricle physiology that has not been discharged home during  the single ventricle interstage period,  -  Subjects that are less than 18 years of age,  -  Subjects with gastrostomy or nasogastric tubes and congenital heart disease,  -  Subjects with congenital heart disease who are at a high risk for transition to  the home setting and are not currently enrolled in the CHAMP single ventricle  -  Subjects at high risk for events as identified by the Directors of the CATCH app  Repository. Exclusion Criteria:   -  All patients not meeting at least one of the above specified criteria.

ASOP is a prospective cohort study comparing three methods for assessing risk of self-induced  lung injury in patients with acute respiratory failure being managed with pressure-support  ventilation. We will describe the relationship between three different assessment methods for  risk of self-induced lung injury and compare them to a gold standard measurement. Ventilator-induced lung injury (VILI) is known to cause significant morbidity and mortality  in patients with acute respiratory failure. Most studies on VILI have involved the effects of  inappropriate (often excessive) mechanical ventilator settings. More recently, it has been  noted that similar lung damage can be caused by large, patient generated, uncontrolled tidal  volumes and driving pressures, which has been termed "self-induced lung injury," or SILI.  Pressure-support ventilation (PSV) is a common mechanical ventilation mode often used in  patients with active inspiratory efforts to help reduce patient inspiratory work and improve  comfort. PSV effectively allows spontaneously breathing patients to determine their breath  flow-rate and breath duration, eliminating flow and cycle dyssynchrony. However, pressure  support ventilation does not allow for physicians to control tidal volume or driving  pressure. The risk of SILI may thus be increased with PSV.  Several different methods have been proposed to address these challenges. However, to date  none of these methods have been compared to assess for concordance in their ability to  indicate an increased risk of self-induced lung injury. ASOP is a prospective cohort study  comparing three methods for assessing risk of self-induced lung injury in patients with acute  respiratory failure being managed with pressure-support ventilation. Inclusion Criteria:  -  Adult patients age ≥18 years with acute respiratory failure receiving invasive  mechanical ventilation  -  Managed in pressure-support mode of ventilation Exclusion Criteria:  -  Actively undergoing a spontaneously awakening trial or SAT  -  Patient or surrogate is unable to provide informed consent  -  Currently pregnant  -  Currently incarcerated  -  Acute exacerbation of an obstructive lung disease  -  Known esophageal varices or any other condition for which the attending physician  deems an orogastric catheter to be unsafe  -  Esophageal, gastric or duodenal surgical procedures within the last 6 months

The investigators' study aims to study how melanin index (mx) affects the deviation between  SpO2 and SaO2, which becomes generally greater as hypoxia increases. The studies reviewed  grouped individuals by race or have assigned individuals into groups like "dark",  "intermediate", or "light" to describe pigmentation. Both of these methods are neither  standardized nor objective, looking for race identifiers when it is more useful to be  considering skin pigmentation identifiers. Skin pigmentation is a spectrum and it should be  treated as such when trying to characterize relationships involving measurable factors such  as melanin index.  The investigators will similarly measure the deviation between SpO2 and SaO2 however novel in  that the investigators will quantitatively measure skin pigmentation via a light reflectance  measurement device by Photovault. Pulse oximetry is an essential tool within healthcare due to its impressive ability to detect  low oxygen levels even before hypoxia manifests in a patient. Despite being a powerful tool,  pulse oximetry has limitations. It is well known that nail polish or jaundice can interfere  with pulse oximetry readings. This knowledge influences clinical practice in that providers  are aware of the inaccurately low saturation readings associated with nail polish and  jaundice. Alarmingly, several studies have reported that pulse oximetry also fails to read as  accurately for patients who have greater levels of skin pigmentation.  One theory reported by Bickler et al. (2005) and Fiener et al. (2007) suggests that pulse  oximetry accuracy decreases as hypoxia increases, where this deviation is further amplified  in the presence of greater levels of skin pigmentation. Bickler et al. (2005) reported  statistically significant differences in pulse oximeter readings on three different pulse  oximeters. They found a small bias existed at blood oxygen saturations above 80% and  increased as desaturation increased. Specifically, this bias over-estimated blood oxygenation  in Black patients where Bickler et al. reported a bias as much as 8% at very low oxygen  saturation. A similar trend has been reported by others. Clinically, a staggering number of  COVID-19 patients fall victim to "silent" or "apathetic" hypoxemia, exhibiting minimal  symptoms of concern upon presentation, but rapidly experience multi-organ failure and in the  most unfortunate circumstance, death, in less than 48 hours. If not concerned at the moment,  emergency departments suggest patients self-monitor their oxygen saturation at home and  return for further evaluation if they record an oxygenation reading below the COVID-19  protocol threshold. What would be a difference of a couple percentage points of observed  oxygenation levels with a pulse oximeter in patients with more skin pigmentation determines  admission, access to the required care, and risks a delay in the necessary oxygen  supplementation of patients. One paper has even suggested that clinicians should accept 95%  oxygen saturation for Black patients as opposed to a threshold of 92% SpO2 to ensure proper  oxygenation. In January 2021, the World Health Organization included the use of pulse  oximeters to assess and identify patients that would require hospitalization for COVID-19.  However, in February 2021, the FDA cautioned against using pulse oximeter oxygen readings to  diagnose or rule out COVID-19 patients, questioning its reliability in clinically significant  circumstances shortly after the New England Journal of Medicine reported that Black patients  suffered from occult hypoxemia nearly three times as much than White patients.  The investigators' study aims to study how melanin index (mx) affects the deviation between  SpO2 and SaO2, which becomes generally greater as hypoxia increases. The studies reviewed  grouped individuals by race or have assigned individuals into groups like "dark",  "intermediate", or "light" to describe pigmentation. Both of these methods are neither  standardized nor objective, looking for race identifiers when it is more useful to be  considering skin pigmentation identifiers. Skin pigmentation is a spectrum and it should be  treated as such when trying to characterize relationships involving measurable factors such  as melanin index.  The investigators will similarly measure the deviation between SpO2 and SaO2 however novel in  that the investigators will quantitatively measure skin pigmentation via a light reflectance  measurement device by Photovault. Inclusion Criteria:  -  Currently being cared for in the University of Minnesota Masonic Children's Hospital  Intensive Care Unit (ICU)  -  Already have an arterial line in place  -  ICU staff state that it would be a good time to approach possible participants Exclusion Criteria:  -  If members of the research team are unable to access and measure with the Photovault  the area that was measured via pulse oximetry by the care team  -  Patients who do not have SpO2 or SaO2 measurements

Endovascular coiling has become a strategy of choice of intracranial aneurysms due to its  minimally invasiveness. However, there has few prospective randomized controlled studies on  the comparison of therapeutic effect between endovascular coiling and microsurgical clipping,  especially the latter via keyhole approaches, which has been widely used in recent years.  Based on the data of a single center, a randomized controlled study was conducted on patients  with ruptured anterior circulation aneurysms suitable for both endovascular and extravascular  treatment, including endovascular coiling, microsurgical clipping via conventional craniotomy  and keyhole approaches, in order to compare the efficacy of the above strategies and provide  more objective basis for treatment selection for operators. Consecutive patients of a single center will be screened. If spontaneous subarachnoid  hemorrhage (SAH) is confirmed by head computed tomography (CT), a diagnostic CT angiography  (CTA) or digital subtraction angiography (DSA) will be carried out emergently. A patients  harbored a single intracranial aneurysm of anterior circulation that resulted in SAH will be  concerned. Based on the assessment of condition, the patient will enrolled into this study  without indication of decompressive craniectomy. The enrolled patients will be divided  randomly into 3 groups, who experienced endovascular coiling, microsurgical clipping via  conventional craniotomy and via keyhole approaches. All of these treatment will be conducted  by a same senior neurosurgeon. CTA or DSA were followed up regularly. The occlusion rate,  operative period, hospitalization duration and cost, surgical complications were compared and  analyzed. Inclusion Criteria:  -  Single intracranial anterior circulation aneurysm diagnosed by CTA or DSA  -  CT showed that subarachnoid hemorrhage originated from the rupture of the aneurysm and  was confirmed during operation  -  No indication of decompressive craniectomy (Hunt-Hess grade ≤ 4, Glasgow Coma Scale ≥  7, no brain herniation; CT showed midline displacement < 5mm)  -  The aneurysm is suitable for both endovascular treatment and microsurgical clipping Exclusion Criteria:  -  The patients and their families did not agree to join the study  -  Patients with unruptured anterior circulation aneurysms  -  Patients with posterior circulation aneurysms  -  Patients with multiple intracranial aneurysms  -  Those who cannot receive treatment due to serious concomitant diseases

This study is to learn if the combination therapy of capmatinib and neritinib can help to  control metastatic or locally advanced breast cancer. Researchers also want to find the  highest tolerable dose of the combination therapy of capmatinib and neritinib that can be  used in this study drug combinations. The safety of this drug combination and the CELsignia  MP test methodology will also be studied. This is an open-label, phase Ib/II study of neratinib plus Capmatinib in patients with  metastatic breast cancer and metastatic IBC.  Phase 1b - Dose Escalation of Neratinib with Capmatinib This phase of the study will employ  the Bayesian optimal interval (BOIN) design with the 3+3 design run-in, to find the MTD. The  BOIN design is implemented in a simple way similar to the traditional 3+3 design, but is more  flexible and possesses superior operating characteristics that are comparable to those of the  more complex model-based designs, such as the continual reassessment method (CRM). The  maximum sample size for dose escalation is 27. Patients are treated in cohorts of 3,  beginning with Neratinib PO dose level 1 (120 mg, Days 1-7, 160 mg, through end of treatment,  see Table 2) in combination with Capmatinib PO level 1 (400 mg, see Table 3), with a maximum  of 12 patients per dose. The target toxicity rate for the maximum tolerable dose (MTD) is  25%.  Phase II Phase II will be a prospective, open label, interventional study with previously  treated HER2-negative metastatic breast cancer and metastatic inflammatory breast cancer  patients. Subjects receive Capmatinib in combination with neratinib. The MTD determined  during Phase 1b will be used.  This portion of the trial will be conducted to assess the overall response rate (ORR) for  patients treated at the MTD. The target ORR will be 25%, with unacceptable ORR as 5%. We  assess the ORR using the Bayesian optimal phase 2 (BOP2) design (Zhou, Lee and Yuan, 2017).  Up to an additional 29 evaluable subjects with measurable disease will be enrolled. An  interim analysis will be performed when the number of enrolled patients reaches 15. Inclusion Criteria:  1. Signed Informed Consent Form (ICF) and comply with the requirements of the study  protocol  2. Age 18 years  3. ECOG performance status 0-1  4. Confirmed diagnosis of metastatic breast cancer or inflammatory breast cancer  according to international consensus criteria30:  -  Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm  breast, with or without an underlying breast mass  -  Duration: History of such findings no more than 6 months  -  Extent: Erythema occupying at least 1/3 of whole breast  -  Pathology: Pathologic confirmation of invasive carcinoma  5. Patients with metastatic or recurrent IBC which is not amenable to curative treatment  with available local and systemic therapy or metastatic non-IBC after 1-6 lines of  therapies for metastatic disease with at least 2 weeks washout period before the  initiation of study treatment.  6. For Phase Ib, any ER, PR, and HER2 status, For Phase 2, HER2-negative per ASCO/CAP  guidelines and any ER and PR status.  7. For Phase II only, Patients with measurable disease according to the Response  Evaluation Criteria in Solid Tumor (RECIST, v1.1) (local or distant) and at least one  metastatic lesion amendable for biopsy (core or punch)  8. Left Ventricular Ejection Fraction ≥ 50% measured by MUGA scan or Echocardiogram.  9. Abnormal HER-family and c-Met signaling activity based on CELsignia MP Test results  (for phase II patients only).  10. Participants must have adequate organ function including the following laboratory  values at the screening visit. Screening must occur within 28 days prior to the first  dose of study drug. Screening samples for hematology and serum chemistries must be  drawn within 14 days prior to the first dose of study drug  -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without growth factor support  Platelets (PLT) >= 75 x 10^9/L  -  Hemoglobin (Hgb) >= 9 g/dL ( Calculated creatinine clearance (using  Cockcroft-Gault formula) >= 45 mL/min  -  Total bilirubin (TBIL) =< ULN (upper limit of normal) with the following  exception: Patients with known Gilbert disease who have serum bilirubin level =<  3 x ULN may be enrolled Aspartate transaminase (AST) =< 3 x ULN, except for  participants with liver metastasis, who may only be included if AST =< 5 x ULN  -  Alanine transaminase (ALT) =< 3 x ULN, except for participants with liver  metastasis, who may only be included if ALT =< 5 x ULN Alkaline phosphatase (ALP)  =< 5.0 x ULN  -  Asymptomatic serum amylase =< grade 2. Participants with grade 1 or grade 2 serum  amylase at the beginning of the study must be confirmed to have no signs and/or  symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase,  abnormal imaging findings of pancreas, etc.) Serum lipase =< ULN  11. Willing and able to comply with scheduled visits, treatment plan and laboratory tests Exclusion Criteria:  1. Concurrent anticancer therapy within 2 weeks of initiation of study treatment; except:  2. Unstable and symptomatic brain metastasis (Stable disease is defined as CNS  radiographic study 4 weeks from completion of radiotherapy and 2 weeks from  discontinuation of corticosteroids)  3. Adverse events from prior anticancer therapy that have not resolved to Grade 1 (CTCAE  v 5.0) except for alopecia, vitiligo, pain, constipation, diarrhea, or fatigue if  these symptoms existed during screening baseline.  i. Grade 3 or above neuropathy induced from prior treatment, that is not resolved to  grade 2 or below despite best supportive care  4. Known clinically significant liver disease, including active viral, alcoholic, or  other hepatitis; cirrhosis  5. Acute exacerbations of underlying condition within the last 12 months (requiring  psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic  agents, oral calcineurin inhibitors; high potency or oral steroids)  6. Patients with known HIV infection: 1) CD4+ count<350 cells/uL; or 2) had AIDS-defining  opportunistic infections < 12 months  7. Know active hepatitis B (chronic or acute) or hepatitis C infection:  8. Severe infections within 4 weeks prior to study treatment, including but not limited  to hospitalization for complications of infection, bacteremia, or severe pneumonia  9. Signs or symptoms of infection within 2 weeks prior to study treatment per treating  physician and PI judgement.  10. Concurrent oral or IV antibiotics within 5 days prior to study treatment  * Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract  infection or chronic obstructive pulmonary disease) are allowed and eligible so long  as the antibiotic is not prohibited with the study medication (See Tables 8 and 10).  11. Major surgical procedure within 28 days prior to study treatment or anticipation of  need for a major surgical procedure during the course of the study  12. Presence or history of interstitial lung disease or interstitial pneumonitis,  including clinically significant radiation pneumonitis (i.e., affecting activities of  daily living or requiring therapeutic intervention).  13. Long QT syndrome, family history of idiopathic sudden death or congenital long QT  syndrome  14. Clinically significant, uncontrolled heart diseases.  -  Unstable angina within 6 months prior to screening  -  Myocardial infarction within 6 months prior to screening  -  History of documented congestive heart failure (New York Heart Association  functional classification III-IV)  -  Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg  and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without  antihypertensive medication. Initiation or adjustment of antihypertensive  medication(s) is allowed prior to screening  -  Ventricular arrhythmias  -  Supraventricular and nodal arrhythmias not controlled with medication  -  Other cardiac arrhythmia not controlled with medication  -  QTcF (QT interval corrected by Fridericia's formula) ≥ 470 ms on the screening  ECG (as mean of triplicate ECG)  15. Major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) within 4 weeks  prior (2 weeks for resection of brain metastases) to starting study therapy or who  have not recovered from side effects of such procedure.  16. Unable to swallow or absorb study drugs due to impairment of GI function or GI disease  e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption  syndrome  17. Participants receiving treatment with any enzyme-inducing anticonvulsant that cannot  be discontinued at least 1 week before first dose of capmatinib, and for the duration  of the study.  18. Other severe, acute, or chronic medical or psychotic conditions, substance abuse or  laboratory abnormalities that in the opinion of the investigator may increase the risk  associated with study participation, or that may interfere with the interpretation of  study results  19. Pregnant or nursing (lactating) women  20. Women of child-bearing potential, defined as all women physiologically capable of  becoming pregnant, unless they are using highly effective methods of contraception  during dosing and for one month after stopping treatment. Highly effective  contraception methods include:  -  Total abstinence (when this is in line with the preferred and usual lifestyle of  the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,  post-ovulation methods) and withdrawal are not acceptable methods of  contraception  -  Female sterilization (have had surgical bilateral oophorectomy with or without  hysterectomy) total hysterectomy, or tubal ligation at least six weeks before  taking study treatment. In case of oophorectomy alone, only when the reproductive  status of the woman has been confirmed by follow up hormone level assessment  -  Male sterilization (at least 6 months prior to screening). For female subjects on  the study, the vasectomized male partner should be the sole partner for that  subject  -  Use of injected or implanted hormonal methods of contraception or placement of an  intrauterine device (IUD) or intrauterine system (IUS), or other forms of  hormonal contraception that have comparable efficacy (failure rate <1%), for  example hormone vaginal ring or transdermal hormone contraception. Women should  have been stable on the same pill for a minimum of 3 months before taking study  treatment.  21. Sexually active males will not be eligible unless they use a condom during intercourse  while taking drug and for 3 months after stopping treatment and should not father a  child in this period. A condom is required for all sexually active male to prevent  them from fathering a child AND to prevent delivery of study treatment via seminal  fluid to partner. In addition, male participants must not donate sperm for the time  period specified above  22. Participants receiving treatment with the following medications that cannot be  discontinued at least 1 week prior to the start of treatment with study therapy and  for the duration of the study:

In this study, the investigators will be able to estimate the metabolic cost of several  foundational suspension training exercises. Suspension exercise training has become a popular cardiovascular training choice in fitness  centers and athletic performance enhancement facilities. Despite widespread use and growing  popularity, little is known about the metabolic demands of such a training method. Therefore,  the purpose of this study was to quantify the cardiovascular and metabolic cost from various  foundational suspension training exercises in order to contribute to a better planning of  exercise programs in the real world.  Ten healthy young adults were assigned to execute six suspension training exercises (acute  bout) for 30 and 45 seconds. Anthropometric, metabolic, and performance measurements were  conducted at baseline. The metabolic cost was estimated from heart rate, blood lactate,  resting oxygen uptake, exercise oxygen uptake, and excess post-exercise oxygen consumption  measurements using a portable gas analyzer. Inclusion Criteria:  -  Aged between 18 and 35 years  -  Physically active individuals  -  Free of chronic diseases  -  Free of musculoskeletal injuries  -  Nonsmokers Exclusion Criteria:  -  Musculoskeletal injuries  -  Chronic diseases  -  Use of alcohol, caffeine and any type of ergogenic supplements or medication before  (≤6 months) and throughout the study.

This is a randomized, double-masked, placebo-controlled study to determine the safety of pAF  in patients who undergo PRK. Photorefractive Keratectomy (PRK) is a common elective surgery used to correct refractive  errors. We propose that amniotic fluid drops may be beneficial in promoting ocular surface  healing following PRK. Purified amniotic fluid (pAF) contains anti-inflammatory,  anti-microbial and regenerative factors similar to solid amniotic membrane. Individual  patients will be randomized to one of two post-operative drop regimens, control eyes that  will receive placebo saline solution (NaCl 0.9%, Baxter Medical), and study eyes that will  receive pAF four times daily for seven days.  This is a randomized, double-masked, placebo-controlled study to determine  -  the safety of pAF in patients who undergo PRK  -  if pAF hastens re-epithelialization following PRK compared to placebo  -  if pAF reduces post-operative pain following PRK compared to placebo  -  if pAF affects visual outcome following PRK compared to placebo  -  if pAF affects ocular surface staining and corneal regularity following PRK compared to  placebo Inclusion Criteria: None Exclusion Criteria: None

Pulmonary Hypertension (PH) is a disease that is characterized by vasoconstriction of small  vessels of the lung. Many cases do have proliferation of endothelial cells within these  vessels. A possible influence of polymorphisms of genes relevant for inflammatory and  endothelial processes is suspected.  Especially patients with chronic heart failure can develope PH. The reasons therefore are  lacking.  The researchers investigate different polymorphism and the influence of these on pulmonary  artery pressure (measured invasively) in patients with congestive heart failure (CHF) and  patients with primary pulmonary hypertension. The study consists of 3 arms-patients with CHF and PH, patients with CHF without PH and  patients without CHF and PH.  The PH measurement is due to routine catheterization, thereafter we measure different  vasoactive polymorphism. Inclusion Criteria:  -  CHF with or without pulmonary hypertension or  -  patients with normal LVEF and pulmonary hypertension  -  right heart catheterization due to routine  -  informed consent Exclusion Criteria:  -  no right heart catheterization  -  no informed consent  -  elevated pulmonary pressure due to valve diseases or congenital heart disease

The now widely used reference interval for pulse oxygen saturation of the neonate after 24  hours of birth has been developed relying on data from low altitude.It is not suitable for  neonates at high altitude. At present, no reference interval has been established at high  altitude, and the existing studies have many limitations. So this study was designed. Knowledge of the reference interval of pulse oxygen saturation (SpO2) in neonates is crucial  for accurate identification of neonatal hypoxemia. The now widely used standard was derived  from low altitude data, which is not suitable neonates at high altitude. At present, many  scholars have paid attention to this problem. But, previous studies still have some  limitations. For example, they often only focus on a specific altitude. However, with the  increase of altitude, the pulse oxygen saturation decreases in a curve, so their study  results are only suitable for this specific altitude and can not be widely used. Inclusion Criteria:  -  Healthy singleton term infants with no clinical signs and symptoms (e.g., cyanosis,  respiratory distress, heart murmur, etc.). Exclusion Criteria:  -  1. Low birth weight (< 2500 g). 2. Need for oxygen. 3.1 or 5 minute Apgar score < 7.  4. Referred to the neonatal intensive care unit or neonatology department for various  reasons. 5. Neonates discharged within 24 hours of birth. 6. Neonates diagnosed with  congenital diseases in utero. 7. Refusal of consent.

Musculoskeletal injuries (MSKI) and traumatic brain injury (TBI) are the signature injuries  of the ongoing military conflicts. MSKI affect 800,000 Service Members annually and TBI have  impacted more than 350,000 in the past 19 years and account for 22% of all combat casualties.  Concussion, a mild form of TBI, increases MSKI risk in physically active individuals,  including Service Members.  The overall goal of the study is to identify the neuromuscular control mechanisms that  increase MSKI risk following concussion. It is hypothesized that concussed individuals will  display abnormal neuromuscular function that increases MSKI risk, as compared to  non-concussed controls. The study will employ a multi-center, prospective, case-matched  control observational study to identify the differences in neuromuscular function following  concussion that may contribute to increased MSKI risk. Once the neuromuscular control  mechanisms that increase MSKI risk following concussion are identified, targeted risk  mitigation strategies can be developed to reduce MSKI risk. Musculoskeletal injuries are the greatest unsolved public health problem facing the military  and significantly diminish Service member's medical readiness. MSKI affect 800,000 Service  members and result in 25 million limited-duty days annually. Additionally, among civilians  peers, sport-related MSKI affect as many as 12 million people annually. In total, MSKI place  a significant burden on military and civilian populations, with a combined financial burden  of more than $980 billion per year in the US alone.  Traumatic brain injuries (TBI), specifically concussions a mild form of TBI, have been  classified by the National Institutes of Health and Centers for Disease Control as a "serious  health problem" in the US. TBIs have impacted more than 350,000 Service members in the past  19 years. Concussions negatively affect individuals' quality of life, as assessed by patient  report outcome (PRO) psychosocial measures, including worse scores for measures of anxiety,  depression, fatigue, anger, and pain immediately following concussion, as compared to when  they are cleared to return-to-duty/activity (RTD/A).  Musculoskeletal injury (MSKI) risk is increased following RTD/A after concussion. However,  despite the well-documented increased MSKI risk following concussion, the underlying  neuromuscular mechanisms contributing to this increased risk have yet to be definitively  determined. The underlying mechanism contributing to increased MSKI risk is likely a  multifaceted issue that requires a comprehensive study to identify all of the factors.  Understanding the neuromuscular control deficits that persist after concussion and how these  deficits change over time (longitudinally) will greatly expand the existing knowledge of why  individuals are at greater MSKI risk following concussion. Thus, the overall objective is to  elucidate the neuromuscular control mechanisms that contribute to increase MSKI risk  following concussion so that effective MSKI risk mitigation strategies can be developed. The  study team hypothesizes that concussed individuals will display aberrant neuromuscular  control function that increases MSKI risk, as compared to non-concussed controls.  This study will address the following specific aims:  Specific Aim #1: Determine the neuromuscular control factors that differ between concussed  and non-concussed military Service Members and physically active civilians that may  contribute to MSKI risk after concussion.  Hypothesis #1: Concussed individuals will display aberrant neuromuscular functioning (e.g.,  atypical joint loading, slower time to stabilization, lower muscular twitch interpolation)  that increases MSKI risk after reporting asymptomatic as compared to non-concussed controls.  Specific Aim #2: Determine the differences in patient reported outcome (PRO) measures between  military Service Members and physically active civilians with and without concussion.  Hypothesis #2: Concussed individuals will report worse functioning on PRO measures (e.g.,  National Institutes of Health Patient-Reported Outcomes Measurement Information System  [PROMIS] and psychological resiliency) as compared to non-concussed matched controls.  Exploratory Aim #1: Determine the time-dependent changes in neuromuscular control factors  following concussion (initial, 6-week post-initial, 12-week post-initial) for concussed and  non-concussed military Service Members and physically active civilians.  Exploratory Hypothesis #1: Concussed individuals will display greater changes, regressing  toward the non-concussed population, in neuromuscular control (e.g., joint loading, time to  stabilization, muscular twitch interpolation) from initial-to-6-week and initial-to-12-week  measures as compared to non-concussed controls (anticipate non-significant changes).  This is a multi-center prospective, case-matched control observational study to identify the  differences in neuromuscular function following concussion that may contribute to increased  MSKI risk. A convenience sample of concussed Service Members and physically active civilians  who self-report being asymptomatic and gender, age, occupation, and physical activity matched  non-concussed controls will complete the study procedures described below: 1) within 5 days  of being asymptomatic ("initial"); 2) 6 weeks post-initial neuromuscular control assessment  ("6-week post-initial"; ±72 hours); and 3) 12 weeks post-initial neuromuscular control  assessment ("12-week post-initial"; ±72 hours).  Concussed and non-concussed matched control participants will complete the same dynamic  movement assessment, neuromuscular testing, and sensory assessment batteries. Control  participants will complete the battery at the same time intervals as their concussed  counterpart, ± 72 hours. Full-body kinematics will be tracked via stereophotogrammetric  motion capture systems and kinetic measures will be captured via 6-degree-of-freedom force  platforms. Peak isometric strength and voluntary muscle activation, via the interpolated  twitch technique (ITT), and muscular ramp contraction assessment of the dominant and  non-dominant knee extensors and plantar flexors will be assessed via a dynamometer (WRNMMC:  Baltimore Therapeutic Equipment (BTE) Primus RS [Baltimore Therapeutic Equipment, Maryland  and Colorado, USA]; UGA: Biodex System 4 [Biodex Medical Systems, Shirley, New York, USA]).  The sensory assessments will examine proprioception (sensation of joint movement) and light  touch sensation. The proprioception assessments will utilize the three-dimensional motion  capture equipment (closed chain) and the dynamometer (passive joint repositioning). The light  touch sensation will utilize Semmes-Weinstein Monofilaments to assess the participant's  ability to detect various sensory thresholds on the foot. Additionally, study participants  will self-report any MSKI they sustain and psychosocial measures monthly for up to 1-year  following the initial neuromuscular control assessment.  Data and Statistical Analysis Plan  Data will be collapsed across trials for all for multi-trial assessments for each data  collection time point (initial, 6-Week post-initial, 12-Week post-initial). The time from  initial concussion diagnosis until the first data collection time point ("initial"),  over-ground gait velocity, and potentially limb dominance will be utilized as a covariates  for all statistical analyses. Other covariates, including gender, age, occupation, and  physical activity will be explicitly controlled between groups by the matching procedure used  in the study design and will therefore be unlikely to contribute to any observed effects;  however, the study team will evaluate the importance of these variables in each analysis.  These covariates will initially be included in each model, when appropriate; however, if a  covariate accounts for little or no variance (p > 0.2), it will be removed from the models.  For all statistical analyses, statistical significance will be set a priori as α ≤ 0.05.  For Specific Aim #1, generalized linear mixed effects models including the fixed effects of  study group (concussed group; non-concussed control group) and the random (subject-level)  effect of participant will determine whether there is a statistically significant difference  between concussed and non-concussed matched controls in each biomechanical outcome collected  during the movement assessments, while accounting for the aforementioned covariates. Models  will be generated for each movement assessment. Additionally, the models exploring gait  variables will include task complexity (single-task vs dual-task) to determine whether there  is a statistically significant difference in performance in regards to task complexity.  For Specific Aim #2, generalized linear models including group (concussed group;  non-concussed control group) as the independent variable and each PRO as the dependent  variable to determine whether there is a statistically significant difference in  self-reported function and symptoms between concussed and non-concussed matched controls for  each PRO. These models will include similar covariates as were used to analyze Specific Aim  #1. For ordinal outcomes, the study team will use cumulative link models.  For Exploratory Aim #1, generalized linear mixed effects models treating time as both a fixed  effect and including a random slope of time by participant, and fixed effects of group  (concussed and non-concussed matched control), time point (initial, 6-Week post-initial,  12-Week post-initial), the interaction of group and time, as well as other covariates as  previously described will determine whether there is a statistically significant difference  between concussed and non-concussed matched controls in the outcomes of interest over time.  Planned comparisons will evaluate between group differences at each time point. The study  team will also analyze loss to follow up ("attrition"), to identify if any trends in  performance on any of the biomechanical measures or PRO relate to the likelihood of study  dropout. If no trends in missing data are observed, participants with at least one follow-up  session will be included in all analyses. Inclusion Criteria:  Concussed Cohort  -  18-40 years old.  -  Self-reported asymptomatic post-concussion following enrollment into the study and  monitoring of symptoms by research personnel via daily self-reported symptom  questionnaires.  -  Recruited within 5 days following being diagnosed with a concussion, and at least 72  hours prior to self-reporting as asymptomatic.  -  Access to a functional email address and the internet for completion of patient  reported outcomes (PROs) and musculoskeletal injury measures.  Non-Concussed Cohort  -  18-40 years old.  -  Active duty Service members and physically active civilians.  -  No self-report history of concussion within the previous 5 years.  -  No lingering post-concussion signs/symptoms.  -  Same gender as the matched concussed participant.  -  Within ±5% of the matched concussed participant's height, weight, and body mass index.  -  Within ±2 years of age of the matched concussed participant.  -  Participant in the same physical activities (work, recreational sports, average type  [no impact, low-impact, high-impact] and duration of physical activity) Exclusion Criteria:  -  Post-Concussion Cohort AND Healthy Non-Concussed Cohort  -  Unable to read or comprehend the English language.  -  Admitted to the hospital following concussion.  -  Sustained a concussion not related to physical activity participation (e.g.,  blast-related injury, fall from a ladder, motor vehicle accident).  -  Loss of consciousness longer than 30 minutes.  -  Alteration in consciousness longer than 24 hours.  -  Post-traumatic amnesia lasting longer than 1 day.  -  Glasgow Coma Scale below 13.  -  Abnormal brain imaging findings.  -  Sustained a concussion that took longer than 21 days for the individual to report  as asymptomatic.  -  A MSKI within the last 6 months that resulted in altered or missed physical  activity for 3 or more consecutive days.  -  History of MSKI surgery.  -  Pregnant females (will be eligible for participation in the study once medically  cleared to RTD/A by a qualified and licensed healthcare provider following the  end of the pregnancy).  -  Participants will be excluded if they present any known contraindications for  electrical stimulation. These contraindications include conditions such as:  active deep vein thrombosis/thrombophlebitis, any acute injury with concurrent  inflammation, hemorrhagic conditions, impaired circulation, impaired local  sensations, presence of infection (osteomyelitis, tuberculosis), malignancy,  recently radiated tissue, skin disease/damage and/or at-risk skin.  -  Present with any implanted pacemaker, electronic device, or plastic/cement  material

Overuse shoulder injuries such as rotator cuff (RC) tendinopathy are common with a prevalence  estimated to be 14% in the general population of which 23% of the working population with  shoulder problems are sick listed.  RC tendinopathy is a tendon-related pain in the proximal lateral aspect of the upper arm with  weakness, especially during active elevation and external rotation, and painful active range  of motion. The prevalence of RC tendinopathy is highest in the supraspinatus and  infraspinatus tendon.  Exercise therapy is regarded as an effective intervention for symptomatic RC tendinopathy for  reducing pain and disability and improving function. However, the prescription is diverse and  the effectiveness of specific characteristics of exercise programs is unknown. Many  contextual factors and prescription parameters, such as external resistance, training  intensity and frequency, home versus supervised exercises, duration of the program, etc. have  been described. Some of these prescription parameters have been extensively studied, with  some conflicting results. Although some level of resistance seems to matter, as well as  number of sets and repetitions, the 'optimal' level and volume are unclear. Inducing or  allowing pain based on tendon loading during exercises is todays consensus in the treatment  of patellar and achilles tendinopathy using a pain-monitoring model. Although a number of  shoulder studies report that pain either should be avoided or allowed, not one study ever  examined the influence of pain allowance versus pain avoidance during a shoulder exercise  program on patient outcome in terms of pain, physical function and disability.  The purpose of this project is to examine the effect of allowing pain versus avoiding pain  based on tendon loading during an exercise regimen for patients with symptomatic rotator cuff  (RC) tendinopathy. This will be accomplished in a Randomized Controlled Clinical Trial,  comparing the effectiveness on patient reported and objective outcomes of a "pain allowing"  and "pain avoiding" exercise program, performed for 26 weeks. Our hypothesis is that allowing  pain based on tendon loading during exercises would result in a better outcome in pain and  function measured on SPADI (the primary outcome) compared to avoiding pain in patients with  RC tendinopathy. Aim The purpose of this project is to examine the effect of allowing pain versus avoiding  pain based on tendon loading during an exercise regimen for patients with symptomatic rotator  cuff (RC) tendinopathy. This will be accomplished in a Randomized Controlled Clinical Trial,  comparing the effectiveness on patient reported and objective outcomes of a "pain allowing"  and "pain avoiding" exercise program, performed for 26 weeks.  Background Shoulder disorders are the third most common musculoskeletal disorder with a  life-time prevalence in the general population of 30%. Shoulder disorders are often  persistent and recurrent, with 54% of the patients reporting on-going symptoms after 3 years.  RC tendinopathy is regarded as a common source of shoulder pain with prevalence estimated to  be as high as 14% in the general working-age population. About 23% of the working population  with shoulder problems are sick-listed, with a potential individual productivity loss.  RC tendinopathy is a tendon-related pain in the proximal lateral aspect of the upper arm with  weakness, especially during active elevation and external rotation, and painful active range  of motion. The pathoanatomic understanding is extended by classifying tissue irritability and  specific impairments. Tissue irritability is meant to guide intensity of treatment, and  identifying specific impairments guides specific tactics used for intervention. The  prevalence of RC tendinopathy is highest in the supraspinatus and infraspinatus tendon.  Exercise therapy is widely regarded as an effective intervention for symptomatic RC  tendinopathy for reducing pain and disability and improving function. It is well known that  tendon collagen regains formation and tensile strength faster than unstressed collagen, and  that it can take 12 month or longer before it reaches full maturity and strength. However,  the prescription is diverse and the effectiveness of specific characteristics of exercise  programs is unknown. Many contextual factors and prescription parameters, such as external  resistance, training intensity and frequency, home versus supervised exercises, duration of  the program, etc. have been described and are summarized in a systematic review. Some of  these prescription parameters have been extensively studied, with some conflicting results.  Although some level of resistance seems to matter, as well as a number of sets and  repetitions, the 'optimal' level and volume are unclear. The existing studies offer some  preliminary guidance in relation to the development and application of loading in exercise  programs for RC tendinopathy, however there is a gap in literature with respect to allowing  or avoiding pain during shoulder exercises. Inducing or allowing pain based on tendon loading  during exercises is todays consensus in the treatment of patellar and achilles tendinopathy  using a pain-monitoring model.  Although a number of shoulder studies report that pain either should be avoided or allowed,  not one study ever examined the influence of pain allowance versus pain avoidance during a  shoulder exercise program on patient outcome in terms of pain, physical function and  disability.  Hypothesis Allowing pain based on tendon loading during exercises would result in a better  outcome in pain and function measured on SPADI (the primary outcome) compared to avoiding  pain in patients with RC tendinopathy. Inclusion Criteria:  -  Adults aged 18 to 55 years  -  Shoulder symptoms lasting for a minimum of 3 months  -  Clinical diagnosis of rotator cuff (supraspinatus and/or infraspinatus) tendinopathy  -  Clinical diagnosis verified by/ combined with ultrasound Exclusion Criteria:  Patients are excluded if they have  -  resting pain above 4/10 (NPRS)  -  <90 degrees active elevation of the arm  -  had a corticosteroid injection within the previous 12 weeks  -  isolated subscapularis tendinopathy  -  total rotator cuff tear  -  diagnosed AC-joint pathology  -  diagnosed labrum pathology  -  diagnosed glenohumeral joint instability  -  had prior shoulder surgery (all shoulder joints)  -  diagnosed glenohumeral osteo arthrosis (OA) evaluated on x-ray, rheumatoid arthritis  or periarthrosis General exclusion criteria are inability to speak or read Danish,  inability to perform and maintain the physical training, or other conditions  negatively influencing compliance.

Laparoscopic right hemicolectomy D3 dissection or complete mesocolic excision (CME) has  become the standard treatment for right hemi-colon cancer, and the treatment of Henle trunk  is one of the difficulties of the operation. However, there are many variations in the Henle  trunk, and the vein wall is thin. It is very easy to damage the Henle trunk and its branches  during the operation, resulting in massive bleeding, especially for beginners. In addition,  retrospective studies found that for ileocecal or ascending colon tumors, low ligation of  Henle trunk can obtain better lymph node clearance. In the early stage, the investigators  improved the surgical method for ileocecal or ascending colon tumors. An endoscopic linear  stapler was used to disconnect the surrounding tissues of Henle trunk under the guidance of  indocyanine green developer. The retrospective study of small samples found that it can  significantly reduce the incidence of local bleeding, shorten the operation time, and obtain  the same lymph node clearance rate. At present, there is less large-scale randomized  controlled study on the disconnection of Henle trunk with linear stapler for right colon  cancer. In recent years, the were nearly 1000 cases/year of colorectal cancer operated in  department of gastrointestinal surgery of shanghai east hospital. Therefore, the  investigators plan to cooperate with many domestic colorectal cancer treatment centers to  take the lead in carrying out this prospective, multicenter and randomized controlled trail,  to explore the safety and efficacy of linear stapler in the treatment of Henle trunk in  laparoscopic radial hemicolectomy of colon cancer. The investigators hope to provide accurate  clinical evidence for individualized precision treatment of rectal cancer patients. Laparoscopic right hemicolectomy D3 dissection or complete mesocolic excision (CME) has  become the standard treatment for right hemi-colon cancer, and the treatment of Henle's trunk  is one of the difficulties of the operation. The traditional view is that D3 lymph node  dissection should be performed routinely in the right hemicolectomy, that is, the blood  vessels of the right hemi-colon including the Henle trunk and its tributary should be ligated  at the level of superior mesenteric artery and vein, and the lymph nodes should be cleaned.  However, there is a large degree of variation in the anatomy of Henle trunk, which is even  considered as the "fingerprint" of CME in the right colon. Coupled with the thin venous wall,  it is very easy to damage Henle trunk and its branches during operation and resulting in  massive bleeding, especially for beginners. In addition, a retrospective study found that the  lymph node metastasis rate around the middle colonic vein and Henle trunk was less than 5% in  ileocecal or ascending colon tumors. Low ligation in this area can also obtain a better lymph  node resection rate.  Based on the above points, the investigators propose to improve the surgical method in  ileocecal or ascending colon tumors using a combined cephalic caudal approach. When the  accessory right colonic vein is separated from the head and then turned to the caudal side  for upward dissociation. After no metastasis of 203 groups of lymph nodes is confirmed  according to indocyanine green (ICG) development during the operation, the Henle trunk and  its root tissue were resected with a linear stapler. The investigators believe that this  method has the following advantages: 1. The Henle trunk together with the branches could be  effectively disconnect, which can reduce the difficulty of operation and shorten the learning  curve; 2. The incidence of bleeding was reduced. Our preliminary small sample studies have  confirmed that the improved operation does not increase postoperative complications and can  obtain the same oncological prognosis.  This is a prospective, multicenter, randomized, parallel controlled trial designed to  evaluate the safety and efficacy of linear stapler in laparoscopic radical resection of  ascending colon cancer. The total number of patients enrolled in this study is 128, including  64 in the control group and 64 in the experimental group. In the experimental group,  indocyanine green was injected for development during the operation after ileocolic vessel  and the middle colonic vessel were dissected. The tributary vessels of the Henle trunk were  disconnected with a linear stapler if there was no obvious lymph node development, which  means ligated not in the root. Otherwise, they were transferred to the experimental group. In  the control group, the branches of Henle's trunk were dissected according to the conventional  method and clamped at the root. The main research objectives include: 1. Intraoperative  bleeding volume 2. Operation time. Secondary research objectives included: 1. Lymph node  detection rate 2. R0 resection rate 3. Complication rate 4. At least one serious complication  rate within 30 days after resection.  At present, there is less large-scale randomized controlled study on the disconnection of  Henle trunk with linear stapler for right colon cancer. In recent years, the were nearly 1000  cases/year of colorectal cancer operated in department of gastrointestinal surgery of  shanghai east hospital. Therefore, the investigators plan to cooperate with many domestic  colorectal cancer treatment centers to take the lead in carrying out this prospective,  multicenter and randomized controlled trail, to explore the safety and efficacy of linear  stapler in the treatment of Henle trunk in laparoscopic radial hemicolectomy of colon cancer.  The investigators hope to provide accurate clinical evidence for individualized precision  treatment of rectal cancer patients. Inclusion Criteria:  -  Patients with locally advanced colorectal cancer met the following criteria at the  time of enrollment:  1. Adult male and female, aged between 18-75 years  2. Colonoscopic biopsy confirmed colonic adenocarcinoma  3. Before treatment, the tumor was located between ileocecal part and ascending  colon liver area  4. There were no local complications (no complete obstruction, no massive active  bleeding, no perforation and abscess formation) before operation  5. The functions of heart, lung, liver and kidney meet the requirements of operation  and anesthesia  6. Informed consent form be signed Exclusion Criteria:  -  Patients who met the following criteria at the time of inclusion were excluded from  this trial:  1. Previous history of malignant colorectal tumor  2. Patients with intestinal obstruction, intestinal perforation and intestinal  bleeding requiring emergency surgery  3. The primary tumor invades the abdominal wall and / or adjacent organs, resulting  in inability to R0 resection  4. Unresectable lymph node metastasis  5. Recent diagnosis complicated with other malignant tumors  6. Patients who had participated or were participating in other clinical trials  within 4 weeks before enrollment  7. American Society of Anesthesiologists (ASA) physical status classes ≥ grade IV  and / or Eastern Cooperative Oncology Group (ECOG) physical state score ≥ 2  points (see Appendix for details)  8. Patients with severe liver and kidney function, cardiopulmonary function,  coagulation dysfunction or combined with serious basic diseases can not tolerate  the operation  9. Have a history of serious mental illness  10. Pregnant or lactating women  11. Patients with uncontrolled infection before operation  12. Some researchers believe that patients with other clinical and laboratory  conditions should not participate in the trial

A substantial proportion of individuals are left with poor residual functioning of the  affected arm after a stroke. This has a tremendous impact on the quality of life and the  ability for stroke survivors to live independently. While exercise is considered essential to  any rehabilitation program, its benefits are generally far from optimal because of the lack  of proper dosing in terms of intensity. One way to tackle this problem is to develop better  tools that could predict an individual's potential and then adjust the intensity of exercise  accordingly. One such predicting tool exists and consists of using non-invasive brain  stimulation such as transcranial magnetic stimulation (TMS), to assess the integrity of  descending motor pathways originating from the brain. TMS consists of applying a magnetic  wand near the scalp to stimulate brain cells without inducing pain or discomfort. One goal of  the current proposal is to use TMS to test the integrity of the motor pathway in chronic  stroke survivors. The level of responses to TMS will be used to classify participants in  terms of potential for recovery and then, to determine the optimal level of exercise. The  study will also examine the effect of another non-invasive brain stimulation technique called  transcranial Direct-Current Stimulation-tDCS to determine whether it can enhance the response  to strength training exercise in the affected arm. Half of the participants will be trained  with the tDCS on, while the other half will be trained with the stimulator off. The training  program will last 4 weeks; 3X/week. Both clinical and neurophysiological measures will be  performed to determine the impact of the strength training intervention on participants.  Overall, the proposed project is expected to have a positive and significant impact on stroke  survivors' quality of life. The functional impact of impairment to UL following a stroke is critical given the close  association between residual strength at the affected UL and performance in activity  post-stroke. Exercise is a key element to recovery, even in chronic stroke survivors.  However, the response to exercise is quite variable between individuals, reflecting the fact  exercise intervention is often based on stroke survivors' clinical score as opposed to their  potential for recovery. Accordingly, clients with comparable clinical presentations will  often receive a similar intervention, even though they may exhibit very different potential  for recovery. Hence, using a suitable prognostic tool of post-stroke recovery to  individualize interventions based on individual potential for recovery is essential. One such  tool is non-invasive transcranial magnetic stimulation (TMS). TMS elicits motor evoked  potentials (MEP), which in turn provide a measure to conveniently assess the integrity of the  corticospinal pathway. MEP is currently recognized as a good prognosis for post-stroke  potential recovery. Another factor that can improve response to exercise is by modulating the  excitability of sensorimotor circuits in the brain by the use of transcranial Direct-Current  Stimulation (tDCS). Studies have shown that priming the motor cortex with tDCS before or  during an intervention can promote motor recovery in stroke patients.  Goals: 1) To assess if an MEP amplitude stratification, used to guide exercise prescription,  can optimize UL function in chronic stroke survivors; 2) To evaluate whether adding tDCS to a  more individualized exercise intervention can further improve UL function.  Methods: Participants will be stratified based on their MEPs amplitudes at the affected hand.  Within each stratum, participants will be further randomized into two tDCS groups: tDCS real  and tDCS sham. The strength training program will target the affected upper limb and will  last 4 weeks (3 times/week).The tDCS will be applied to an anodal montage during each  training session (12 sessions; 2 mA) for 20 minutes (tDCS real group) or 30 seconds (tDCS  sham group). Inclusion Criteria:  1. have had solely one supratentorial stroke  2. be in a chronic stroke phase (>6 months) Exclusion Criteria:  1. a significant spasticity at the affected upper limb (score > 3 on the modified  Ashworth scale);  2. a significant pain intensity at the affected upper limb (≥ 4/10 on the Visual Analog  Pain Scale);  3. a major sensory deficit (a score ≤ 25/34 on the Nottingham Sensory Assessment);  4. a presence of hemineglect (> 70% of unshaded lines on the same side as the motor  deficit on the Line Cancellation Test);  5. an apraxia (score >2.5 on the Alexander Test);  6. the presence of a neurological disorder other than a stroke;  7. concomitant orthopaedic problems at the affected upper limb and  8. any contraindication to TMS and/or tDCS.

Target question is as the following one:  Does the daily use of a fluoride-free, microcrystalline hydroxyap-atite (HAP) - containing  test toothpaste have a non-inferior caries preventing effect in the permanent dentition  compared to the regular use of a fluoride control toothpaste (1450 ppm F-) with proven caries  preventive efficacy (Walsh et al. 2019)? This multicenter, non-inferiority clinical trial,  randomized, double-blind, active-controlled design, two-armed study evaluates the hypothesis  that the home regular use of a toothpaste containing microcrystalline hydroxylapatite (HAP)  (test toothpaste) provides a caries preventive effect in adults aged 18-45 comparable to the  caries preventive effect provided by the regular use of a fluoridated tooth paste (1450 ppm  -F) (control toothpaste) over observation periods of max. 18 months. Caries development will  be assessed according to the clinical criteria of the Decay Missing Filling Surface Index  (DMFS). Caries-preventing effects of hydroxyapatite toothpastes have been shown in vivo [children and  adolescents] (Schlagenhauf et al. 2019, Paszynska et al. 2021), in situ (Amaechi et al.  2019), and in vitro (Tschoppe et al. 2011). However, to date, the caries-preventing effect of  a hydroxyapatite toothpaste in adults (without orthodontic treatment) has not been  investigated in a clinical trial compared to fluoride toothpastes.  The aim of this clinical trial is to assess in cohorts of adults whether 2 x daily tooth  brushing at home over an observation period of 18 months with a fluoride-free,  microcrystalline hydroxyapatite (HAP) - containing test toothpaste has a non-inferior caries  preventing effect in the permanent dentition compared to the regular use of a fluoride  control toothpaste (1450 ppm F-) with proven caries preventive efficacy (Walsh et al. 2019).  The study is designed as a multicentre, two armed, non-inferiority trial and will be  performed by 2 study centres in Poland. Caries development will be assessed by the Decay  Missing Filling Surface Index (DMFS).  There are planned 4 visits for all subjects included to the project. Description of the 4  visits is presented below.  Visit 1 (Screening and Baseline): Study day 0, informed consent, screening, collection of  baseline data, and study inclusion Subjects potentially suitable for the study will be  informed by the investigator about the nature, sig-nificance, and scope of the clinical trial  according to the requirements described in the written subject information.  Before study inclusion, the willingness of the subjects to properly follow the study protocol  during the complete treatment period of 546 days must be assessed. Only when subjects have  given their written informed consent, he/she will be included as study participant.  Subjects have to meet all inclusion criteria and no exclusion criteria. Unsuitable subjects  with un-treated caries in need of a restoration can become eligible after restorative  therapy.  Once informed consent has been given, an initial examination will take place that covers the  follow-ing aspects:  -  Screening subjects for study eligibility (inclusion and exclusion criteria)  -  Demographic data Assessment of the study parameters has to be done on all teeth in the  following sequence  -  Plaque control record (PCR)  -  Professional tooth cleaning  -  DMFS  -  DIAGNOcam After the analysis of the plaque control record using a plaque-staining  solution (see O' Leary T, Drake R, Naylor, 1972), a professional tooth cleaning will be  performed. Thereafter, no fluoride gel/varnish etc. will be applied.  Finally, the study subjects receive an electric toothbrush with 3 brushing heads (replacement  of the brushing head every 2 months) and the allocated toothpaste (test or control) by a  trained study nurse or dentist not involved in clinical study examinations.  Proper use of the assigned electric toothbrush and the issued toothpaste is also instructed  by this study nurse or a dentist not involved in the clinical study examinations.  Visit 2: Study day 182 (± 28 days at most), 1st follow-up examination 182 days after baseline  visit the following parameters are reassessed:  -  Plaque control record (PCR)  -  Caries status (DMFS) as described for the baseline visit. Subsequently a study nurse or  a dentist not involved in clinical study examinations will hand out 3 new brushing heads  for the electric toothbrush and a new supply of the assigned experimental toothpaste  (test or control) for the next 182 days.  Furthermore, the study nurse will subsequently check the efficacy of the oral hygiene efforts  of the subjects and if PCR will be > 15%, will train again with the subjects an efficacious  brushing tech-nique. Finally, subjects receive a new appointment for visit 3.  Visit 3: Study day 364 (± 28 days at most), 2nd follow-up examination 364 days after baseline  visit the following parameters are reassessed:  -  Plaque control record (PCR)  -  DMFS as described for the baseline visit. Subsequently a study nurse or a dentist not  involved in the clinical study examinations will hand out 3 new brushing heads for the  electric toothbrush and a new supply of the assigned experimental toothpaste (test or  control) for the next 182 days.  Furthermore, the study nurse will subsequently check the efficacy of the oral hygiene efforts  of the subjects and if PCR will be > 15%, will train again with the subjects an efficacious  brushing tech-nique. Finally, subjects receive a new appointment for visit 4.  Visit 4: Study day 546 (± 28 days at most), final visit 546 days after baseline visit the  following assessments are repeated:  -  Plaque control record (PCR)  -  Professional tooth cleaning  -  DMFS  -  DIAGNOcam as described for the baseline visit.  Methods of Determining Efficacy and Safety Methods of Determining Efficacy DMFS-index and  PCR-scores will be determined by clinical examinations of the oral cavity. In addi-tion,  analysis of mineral density using DIAGNOcam will be conducted according to the instructions  of the manufacturer.  Assessments of all clinical findings will be performed only by experienced dentists.  DMFS Index Calculation The DMFS Index (Decayed Missed Filled Surfaces) is one of the most  common methods in oral epidemiology for assessing dental caries prevalence as well as dental  treatment needs among populations.  DMFS Index calculation: There are five surfaces on the posterior teeth: facial, lingual,  mesial, distal, and occlusal. There are four surfaces on anterior teeth: facial, lingual,  mesial, and distal. The third molars are not counted.  -  When a carious lesion or both a carious lesion and a restoration are present, the  surface is listed as a D.  -  When a tooth has been extracted due to caries, it is listed as an M.  -  When a permanent filling is present, or when a filling is defective but not decayed,  this surface is counted as an F. Surfaces restored for reasons other than caries are not  counted as an F.  The total count is 128 surfaces.  DIAGNOcam (KaVo Dental) DIAGNOcam will be used according to the instructions of the  manufacturer. The following classifi-cation will be used (Dent. Med. Probl. 2016, 53, 4,  468-475).  0 = Light transmission unchanged  1. = Shadow visible in enamel  2. = Shadow visible in dentin  Plaque Control Record The Plaque Control Record (O' Leary T, Drake R, Naylor, 1972) is a  simple method of recording the presence of the plaque on individual tooth surfaces.  At the study visits a suitable disclosing solution such as Bismarck Brown, Diaplac or similar  is painted on tooth surfaces. After the subject has rinsed, the investigator (using an  explorer or a tip of a probe) examines each stained surface for soft accumulations at the  dentogingival junction.  After all teeth are examined and scored, the index is calculated by dividing the number of  plaque containing surfaces by the total number of available surfaces.  Plaque Index Calculation = The number of plaque containing surfaces / The total number of  available surfaces Inclusion Criteria:  -  provision of written informed consent  -  age 18-45 years (both men and women)  -  a minimum of 10 healthy molars and premolars (DMFS of these teeth = 0)  -  willing to use an electric (powered) toothbrush Exclusion Criteria:  -  Medical Reasons  -  untreated caries [clinical investigation and analysis with DI-AGNOcam] (→  unsuitable subjects with untreated caries in need of a restoration can become  eligible after restorative therapy)  -  severe periodontitis at the baseline-visit (pocket depth on at least one tooth ≥  5.5 mm)  -  orthodontic treatment  -  known hypersensitivity to one of the ingredients of the tooth-pastes to be tested  -  systemic disorders interfering with salivary function or flow  -  regular medication intake interfering with salivary function or flow  -  Other Reasons:  -  Participation in any other clinical study within the past 3 months or ongoing  -  lack of intellectual or physical ability to conduct the study properly  -  Any other reason that, in the opinion of the investigator, dis-qualifies the  subject from participating in the study

After exiting the RACE trial (NCT02099747) patients will be invited to participate in this  long term follow-up study Patients will be followed up annually, according to standard of care.  All diagnostic and therapeutic intervention will be performed according to standard of care,  at discretion of the treating physician. In particular, during the study no extra Peripheral  blood or Bone Marrow sampling will be performed, in addition to routine sampling for  morphology and karyotype surveillance.  Molecular analysis by Next Generation Sequencing (NGS) will also be collected if the centre  is doing this on a routine basis.  No Investigational Medicinal Product (IMP) or Non-Investigational Medicinal Product (NIMP)  will be given to the patients. Inclusion Criteria:  1. Subject participated in the RACE trial (NCT02099747, EudraCT number: 2014-000363-40)  during which patient received ATGAM, Cyclosporine A with or without Eltrombopag.  2. Subject has provided informed consent to participate in long-term data collection Exclusion Criteria:  None

Many malaria deaths occur in places where people have poor access to preventive and curative  health services. Prompt access to quality health services is critical in the case of severe  childhood diseases, among which severe malaria is particularly frequent in endemic areas. In  communities where parenteral treatment of severe malaria is not available, the World Health  Organization (WHO) recommends administration of a single rectal dose of artesunate (RAS) to  children less than 6 years, followed by immediate referral to an appropriate facility where  the full package of care for severe malaria can be provided.  Many African countries have already endorsed the use of pre-referral RAS. But treatment  guidelines vary widely across these countries and often do not align with the WHO  recommendation. With the impending availability of quality-assured rectal artesunate (QA RAS)  and countries poised to scale-up this intervention, it is critical to investigate the safe  and effective implementation of RAS as part of a continuum of care for severe malaria  patients. To ensure that RAS is well targeted, it is equally urgent to learn more about  frequency, treatment seeking and risk factors for severe malaria at community level. The  CARAMAL project has two major components: the pilot implementation of QA RAS in selected  areas of the Democratic Republic of the Congo (DRC), Nigeria and Uganda, and operational  research on the introduction of QA RAS into established integrated community case management  (iCCM) platforms. The CARAMAL project is funded by Unitaid and coordinated by the Clinton  Health Access Initiative, Inc. (CHAI). UNICEF is responsible for QA RAS implementation. Swiss  TPH in partnership with the local research organizations Akena Associates Ltd. in Nigeria,  Kinshasa School of Public Health in DRC and Makerere University School of Public Health in  Uganda carries out the operational research component to generate evidence for the  responsible implementation of RAS. Finally, the CARAMAL project will generate a better  understanding of severe febrile illness, its management at all levels and key determinants of  health outcomes. Objective(s):  The overall goal of the CARAMAL project is to contribute to reducing malaria mortality in  children globally by improving the community management of suspected severe malaria cases.  The project will contribute to this goal by advancing the development of operational guidance  to catalyse effective and appropriate scale-up of QA RAS as pre-referral treatment of severe  malaria.  Accompanying the pilot roll-out of QA RAS by UNICEF, the CARAMAL project will test whether it  is feasible to introduce QA RAS into established integrated community case management (iCCM)  platforms with only minimal additional supportive interventions and with minimal unintended  consequences such as inappropriate use as artemisinin monotherapy.  Through the research activities described in detail below, the CARAMAL project aims to answer  the following research questions:  I. What are the minimal requirements of a community case management system to ensure that RAS  is an effective part of the continuum of care from the community to a referral facility  (defined as a health care facility equipped for inpatient care of severe malaria)?  II. What are the unintended consequences of scaled implementation, such as adverse drug  reactions, unforeseen costs [5], or unforeseen issues in treatment of malaria at all levels  of care, and how can they be addressed?  III. Is there any use of RAS beyond the recommended guidelines, including full treatment of  severe cases with RAS at community level, and the treatment of uncomplicated malaria with  RAS?  IV. Can the introduction of pre-referral QA RAS reduce severe malaria case fatality ratio  over time under real-world operational circumstances in three distinct settings?  What are the costs and cost-effectiveness of community and peripheral health facility based  RAS?  Study Design:  The CARAMAL project has been designed as a multi-country operational research study  implemented in three highly malaria-endemic countries. It will be based on a before-and-after  plausibility design aligned with the roll-out of QA RAS through established community-based  health care provider systems.  Activity 1: A patient surveillance system (PSS) to assess severe febrile illness/suspected  severe malaria incidence, case fatality rate, and related clinical patterns, diagnoses,  treatment and treatment outcomes from first contact to the point of recovery or death  (baseline and after RAS roll-out) Activity 2: Health care provider surveys (HCPS) to  establish the availability and uptake of QA RAS at all levels, and health providers'  knowledge, attitudes and practices towards RAS (baseline and after RAS roll-out) Activity 3:  Household surveys (HHS) to assess treatment seeking, caretakers' knowledge and attitudes  towards RAS, and malaria intervention coverage at community level (baseline and after RAS  roll-out) Activity 4: An economic evaluation to assess the costs and incremental  cost-effectiveness of implementing RAS at community level compared to the current standard of  care Activity 5: Routine monitoring of process indicators along the entire case management  chain to continuously assess implementation progress of RAS as contextual information for  other outcome indicators  Study Population:  Activity 1, Patient surveillance system:  The PSS will include all children <5 years of age seeking care for a current/recent febrile  illness episode at the level of community based care providers in the study areas, including  Community Health Workers (CHWs) and primary health facilities (HF). All children diagnosed at  that level with severe febrile illness / suspected severe malaria will then be enrolled in  the PSS and tracked at the referral health facility and at the child's home 28 days after  initial diagnosis. In addition, all children <5 years of age seeking care for a severe  febrile illness episode directly at the referral facility will be enrolled to evaluate  treatment seeking, diagnosis, treatment and disease outcome. These children will be excluded  from the case fatality ratio analysis.  Activity 2, Health care provider surveys:  The sampling frame will include all registered providers at all levels operating in the study  areas, including public and private providers. A simple random sampling approach stratified  by provider level (CHW, primary health facility, etc.) will be used to select providers for  the survey.  Activity 3, Household surveys:  Household surveys will include randomly sampled households in the study areas. Households  will be selected using a two-stage random sampling approach (village-household) whereas the  sampling frames will consist of all villages in the study area and all households in the  village, respectively.  In each household, the household heads and parents/caretakers of children < 5 years of age  will be eligible to participate.  Measurements and Procedures:  Activity 1, patient surveillance system:  1. CHW / primary health facility (first contact) According to established routine practice,  the following procedures are performed: children attending a CHW or primary health  facility undergo examination, treatment and referral procedures as per local guidelines.  A rapid malaria test (mRDT) is performed on all children with a history of or acute  fever, including children with symptoms of severe febrile illness / children with danger  signs. The children are then treated as per the applicable national guidelines. Enrolled  children will be assigned a unique study ID.  2. Referral facility Children with severe febrile illness / suspected severe malaria and  either referred to or directly reporting to a referral facility in the study area will  be registered upon arrival in the facility. The study nurse will monitor the case  management of each registered patient and continuously enter study-specific details on  diagnosis and treatment provided throughout the patient's admission into an electronic  case report form.  3. At home (day 28)  All children with severe febrile illness / suspected severe malaria and enrolled into  the patient surveillance system (PSS) by a CHW / primary health facility or at the  referral health facility will be followed up at their home by a member of the research  team. The primary purpose of this visit is to establish the health status of the child  using a structured questionnaire. It will also include a section on the  parent's/caretaker's experience and attitude towards the use of RAS. During the home  follow-up a finger-prick blood sample will be collected from all of children for:  -  mRDT  -  Microcuvette sample for measuring haemoglobin (Hb) concentration In case of the  death of an enrolled child, the research team will attempt to conduct a verbal  autopsy at a later stage.  Activity 2, Health care provider surveys:  4. Health Care Provider Checklist A structured checklist completed to assess the  availability of essential medical supplies (incl. RAS) and equipment, human resource  capacity, infrastructure and documentation.  5. Health Care Provider Questionnaire An interviewer administered questionnaire with  questions pertaining to the health worker's demographics, education and training, work  experience and supervision, type and utility of any work-related training received,  knowledge, attitudes and practices relevant to febrile case management (incl. diagnostic  algorithm and (RAS) treatment guidelines) and intermittent preventive treatment in  infants and pregnancy (IPTi, IPTp), experiences implementing malaria/febrile case  management and prevention guidelines. More in-depth questions will be asked to health  care workers administering RAS as well as different cadres of health workers providing  post-referral treatment, focusing on aspects relevant to the implementation of  pre-referral RAS and post-referral treatment of severe febrile illness.  Activity 3, Household surveys:  Three survey instruments will be completed with participating household heads and/or  household members:  1. Household Questionnaire A structured interviewer administered questionnaire to collect  information about coverage and uptake of mosquito nets behaviour change campaigns and  other malaria control interventions, alongside background demographic information on  each household member as well as indicators of the household's socio-economic status.  2. Treatment Seeking Questionnaire A semi-structured interviewer administered questionnaire  completed with randomly selected household members who are parents or caretakers of a  child <5 years of age. Parents/caretakers of children who reported a febrile illness  (irrespective of severity) in the two weeks prior to the survey will be interviewed  about that specific illness episode. The form collects information about the signs and  symptoms of the illness and subsequent treatment seeking behaviours, including sources  of treatment and types (if any) of drugs administered. Parents/caretakers of children  who did not experience a recent febrile illness will be asked about hypothetical care  seeking behaviour based on specific vignettes (one scenario of mild and one scenario of  severe febrile illness). The form furthermore collects information on the knowledge and  attitudes of the parents/caretakers towards RAS. The parent/caretaker will be asked  about previous experiences with RAS. Parents/caretakers without any previous experience  with RAS will be asked about their attitudes based on a vignette.  3. Prevalence Form / blood sample collection A finger prick blood sample will be taken from  every household member below 5 years of age to assess changes in malaria prevalence and  anaemia over time in the study areas. A short form will accompany each finger-prick  blood sample, recording the individuals' demographic details, recent travel history,  intake of any medicine, the mRDT and Hb measurement result, and any treatment  administered.  Activity 4, Economic evaluation:  Financial and non-financial economic costs will be collected as part of routine project  records over the duration of the study. The evaluation will reflect multiple perspectives  including individual (i.e. patient), societal, and health systems-level (i.e. government).  Activity 5, Routine monitoring of process indicators:  Programmatic records of the implementation of QA RAS by UNICEF will be continuously assessed,  including:  1. RAS needs assessment data and orders  2. Reports from supportive supervision of CHWs  3. CHW monthly reports  4. CHW, health facility registers  Number of Participants:  Activity 1, Patient surveillance system:  The minimum sample size of 6,032 cases of severe malaria in children < 5 years over 24 months  Activity 2: Health care provider surveys:  -  All referral health facilities in the project areas  -  All non-referral health facilities in the study area (Uganda and DRC), while in Nigeria,  a random sample of 40 facilities will be included.  -  40 community health workers (Nigeria and Uganda).  Activity 3: Household surveys 906 household survey responses on treatment-seeking for severe  febrile illness will be required per country and individual survey round.  Study Sites:  -  Three health zones in DRC (Kenge, Kingandu and Ipamu),  -  A subset of local government areas (LGAs) in one state in Nigeria (Adamawa) , and  -  Three districts in Uganda (Apac, Kole and Oyam) Inclusion Criteria:  -  Patient surveillance system:  -  Children < 5 years  -  History of fever plus danger signs indicative of severe febrile illness / suspected  severe malaria, according to local iCCM guidelines  -  Child referred to higher level facility by CHW/primary health facility, or, child  directly attending a referral facility.  Signed full consent form from parent / guardian  Health care provider interview:  -  CHW or health worker at peripheral health facility enrolled in the iCCM referral  system who treats children < 5 years OR  -  Health care provider at referral hospitals treating children < 5 years OR  -  Any other health care provider in project area treating children < 5 years  -  Signed consent form  Household survey:  -  Household head and parent / caregiver of children < 5 years  -  Signed consent form from parent / guardian Exclusion Criteria:  -  Patient surveillance system:  -  Children ≥ 5 years  -  Children with no permanent residence in project area  Health care provider interview:  -  Health workers not treating children < 5 years  -  Health workers outside project area  -  Health workers who do not speak any of the local languages  -  Health workers employed since < 1 month  Household survey:  -  Parents / guardians with no children < 5 years  -  Parents / guardians with no permanent residence in project area  -  Parents / guardians who do not speak any of the local languages

The purpose of this study is to assess the efficacy of droperidol as a treatment of  cannabinoid hyperemesis syndrome. Patients presenting to the Emergency Department with nausea, vomiting and/or abdominal pain  with a significant history of cannabis use and symptoms in a cyclic pattern will be assessed  for study inclusion. After given written informed consent, patients will be treated with  droperidol and diphenhydramine and symptoms will be assessed using a visual analog scale at  time intervals up to 120 minutes. Patient will then be contacted at 24 and 48 hour intervals  to assess symptoms on the same scale. This is a multicenter, prospective interventional study  with results compared to a historical cohort using haloperidol. Inclusion Criteria:  -  aged 18 years of age or older and presenting with cannabis hyperemesis syndrome  requiring intravenous medication. Exclusion Criteria:  -  any patient with a contraindication to the use of droperidol  -  QTc interval on ECG greater than 440 milliseconds for males and greater than 450  milliseconds for females  -  any prisoners  -  pregnant females.

This trial is taking place in Los Angeles, CA at clinics within the UCLA Health System.  Despite the Advisory Committee on Immunization Practices (ACIP) recommendation in 2010 that  all people above 6 months of age should receive an annual flu vaccine, vaccination rates  remain low: at 6m-4.9 yrs. (70%), 5-17.9 yrs. (56%), 18-64.9 yrs. (38%), and >65 yrs. (63%).  The investigators will assess the effectiveness and cost-effectiveness of 1, 2, 3 MyChart R/R  messages as compared to the standard of care control (no messages). Annual epidemics of influenza cause substantial morbidity in the U.S. with up to 40,000  deaths/year and many hospitalizations, emergency and outpatient visits, and significant  costs. Concerns about pandemic influenza elevate the need to prevent flu outbreaks.  Numerous studies, including Cochrane or systematic reviews, and reports by the CDC and the  Task Force on Community Preventive Services, highlight 4 evidence-based strategies to raise  child and adult influenza vaccination rates: 1) increase patient demand by reminder-recall or  education, 2) expand patient access to influenza vaccinations (e.g., flu vaccine clinics), 3)  implement provider strategies such as prompts or standing orders, and 4) use societal  strategies (e.g., reducing costs).  Reminder/recall (R/R), sent by phone, mail or other modality, can improve child and adult  influenza vaccination rates. However, fewer than one-fifth of pediatric or adult primary care  practices utilize patient R/R. Barriers are lack of finances, personnel, and algorithms to  identify eligible patients.  A technological breakthrough that might overcome these barriers involves patient portals--  secure, web-based communication systems, embedded within electronic health records (EHRs),  for patients and providers to communicate with each other via email and the internet. Portals  are used by about half of Americans and half of UCLA patients. Portals can theoretically  improve upon phone, mail or text R/R by adding information such as web links, videos, or  images, allowing patients to schedule their own visits, and linking to the medical chart to  customize messages.  For this randomized control trial, the intent is to evaluate the impact of patient portal  (MyChart) reminder recalls - either 1, 2, or 3 reminders versus the standard of care control  group, specifically in relation to raising influenza vaccination rates among UCLA Health  System's primary care patients aged 6 months and older.  The proposed design of this 4-arm RCT:  1. Standard of care control (no messages)  2. Up to 1 portal R/R messages  3. Up to 2 portal R/R messages  4. Up to 3 portal R/R messages  Hypothesis 1: >1 portal R/R will increase vaccination rates vs. no R/R. Hypothesis 2: More  R/R messages will raise vaccination rates (3R/R > 2R/R > 1R/R > 0R/R).  For the primary analysis, only the data from the randomly selected index patients (1 index  patient per household) will be included.  For relevant study arms, the first R/R message will be sent in October 2018. Inclusion Criteria:  • A patient within the UCLA Health System identified by the system as a primary care  patient per an internal algorithm, with a documented primary care visit within the last 3  years as of 8/1/18. Exclusion Criteria:  • A patient not identified by the UCLA Health System's internal algorithm as a primary care  patient.

This is a Phase III Study to Compare Efficacy and Safety of CT-P17 with Humira in Patients  With Active Rheumatoid Arthritis CT-P17, containing the active ingredient adalimumab, is a recombinant humanized monoclonal  antibody that is being developed as a similar biological medicinal product to Humira. The  purpose of this study is to demonstrate similar efficacy and safety of CT-P17 and Humira in  patients with moderate to severe rheumatoid arthritis when co-administered with methotrexate. Inclusion Criteria:  -  Patient is male or female aged 18 to 75 years old, both inclusive.  -  Patient has had a diagnosis of rheumatoid arthritis according to the 2010 American  College of Rheumatology(ACR)/EULAR classification criteria for at least 24 weeks prior  to the first administration of the study drug . Exclusion Criteria:  -  Patient who has previously received investigational or licensed product; biologic or  targeted synthetic disease-modifying antirheumatic drugs for the treatment of  rheumatoid arthritis and/or a tumor necrosis factor (TNF) α inhibitor for any  purposes.  -  Patient who has allergies to any of the excipients of study drug or any other murine  and human proteins, or patient with a hypersensitivity to immunoglobulin products.

This study will include 5 cohorts of 14 ZIKV and DENV-naïve female subjects, 18 - 40 years of  age (total: up to 70 subjects). Within each cohort, 10 subjects will receive ZIKV and 4  subjects will receive a placebo on Study Day 0. Cohorts 1 and 2 (Dose = 10^2 PFU) will be  enrolled first. Cohorts 3 and 4 may be enrolled if dose escalation criteria are met (Section  3.1.2.3). Enrollment into Cohort 5 may occur if dose escalation criteria are met following  enrollment into Cohorts 3 and 4. Only one ZIKV strain will be evaluated in Cohort 5. This study is a placebo-controlled, double-blind study in normal healthy adult female  subjects 18 - 40 years of age, inclusive, recruited from the metropolitan  Baltimore/Washington, DC and Burlington, VT areas. The purpose of this study is to evaluate  the clinical and virologic response to escalating doses of 2 different ZIKV strains  administered subcutaneously in healthy, ZIKV and DENV-naïve, non-pregnant, female adult  volunteers to identify the most suitable ZIKV strain and dose for use in a ZIKV CHIM. The  ZIKV CHIM will then be used to evaluate the protective efficacy of candidate ZIKV vaccines  prior to evaluation of these candidates in Phase 2 clinical trials. Both ZIKV strains will be  studied at doses of 10^2 PFU and 10^3 PFU. Only one of the ZIKV strains will be studied at a  dose of 10^4 PFU. The ZIKV strain to be studied at 10^4 PFU will be determined following  review of the data from the 10^2 and 10^3 PFU cohorts. Placebo recipients are included in the  study as a control to better assess ZIKV-associated versus non-ZIKV-associated AEs. Inclusion Criteria:  -  Adult ZIKV and DENV-naïve non-pregnant females 18 - 40 years of age, inclusive.  -  Good general health as determined by physical examination, laboratory screening, and  review of medical history.  -  Available for the duration of the study, approximately 26 weeks post-inoculation.  -  Must be able to complete the informed consent process and comprehension assessment  independently and without assistance.  -  Willingness to participate in the study as evidenced by signing the informed consent  document.  -  Willingness to reside in the inpatient unit for 16 days (or longer for safety if  necessary) following receipt of ZIKV or placebo.  -  All subjects: Willingness to use barrier contraception during cervico-vaginal, anal,  and oral intercourse through study day 56 (in accordance with CDC guidance).  -  Female subjects of childbearing potential must be willing to use effective  contraception for the duration of the study. Reliable methods of contraception  include: hormonal birth control* (implantable, hormonal patch, NuvaRing®, oral  contraception, Depo-Provera injection, etc.), surgical sterilization (hysterectomy,  tubal ligation, or tubal coil at least 3 months prior to inoculation), and  intrauterine device. All female subjects will be considered having child-bearing  potential except for those with post-menopausal status documented as at least 1 year  since last menstrual period and females who have sex with females (exclusively) and  have no intention of conceiving a child during the study. Females who are not  considered to be of childbearing potential will not be required to use contraception  other than barrier contraception for the purpose of reducing potential transmission.  -  Volunteers on hormonal birth control must not be on medications or other agents  that decrease the effectiveness of hormonal birth control. Exclusion Criteria:  -  Currently pregnant, as determined by positive beta-human choriogonadotropin (Beta-hCG)  test, breast-feeding or planning to become pregnant during the 6-month duration of the  study.  -  Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,  rheumatologic, autoimmune, or renal disease by history, physical examination, and/or  laboratory studies.  -  Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator  affects the ability of the subject to understand and cooperate with the requirements  of the study protocol.  -  Evidence of recent opiate use based on urine toxicology screen  -  Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC),  ALT, and serum creatinine, as defined in this protocol.  -  Any other condition that in the opinion of the investigator would jeopardize the  safety or rights of a subject participating in the trial or would render the subject  unable to comply with the protocol.  -  Any significant alcohol or drug abuse in the past 12 months which has caused medical,  occupational, or family problems, as indicated by subject history.  -  History of a severe allergic reaction or anaphylaxis.  -  Severe asthma (emergency room visit or hospitalization within the last 6 months).  -  HIV infection, by screening and confirmatory assays.  -  Hepatitis C virus (HCV) infection, by screening and confirmatory assays.  -  Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening.  -  History of Guillain-Barré syndrome (GBS).  -  History of seizure disease or peripheral neuropathy  -  History of any neuroinflammatory disorder i.e. Bell's Palsy, transverse myelitis  -  Any known immunodeficiency syndrome, including that caused by malignancy.  -  Use of anticoagulant medications (use of antiplatelet medication such as aspirin or  non-steroidal anti-inflammatory medication is permitted and will not exclude a subject  from enrollment).  -  Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within  28 days prior to or following inoculation. Immunosuppressive dose of corticosteroids  is defined as ≥10 mg prednisone equivalent per day for ≥14 days.  -  Receipt of a live vaccine within 21 days or a killed vaccine within the 14 days prior  to inoculation or anticipated receipt of any vaccine during the 21 days following  inoculation.  -  Asplenia.  -  Receipt of blood products within the past 6 months, including transfusions or  immunoglobulin or anticipated receipt of any blood products or immunoglobulin during  the 28 days following inoculation.  -  History or serologic evidence of previous ZIKV infection or DENV infection.  -  Previous receipt of a ZIKV or DENV vaccine (licensed or investigational).  -  Anticipated receipt of any investigational agent in the 28 days before or after  inoculation.  -  Subject has definite plans to travel to a ZIKV-endemic or dengue-endemic area during  the study.  -  Previous hypersensitivity to any study product component.  -  Refusal to allow storage of specimens for future research.

The study aims to develop and externally validate a prediction model for the critical  outcomes of COVID-19 patients using predictors which can be easily obtained in clinical  practice, including patients' demographic characteristics, self-reported medical conditions,  and oral health. Background The novel coronavirus disease 2019 (COVID-19) pandemic has presented an important  and urgent threat to global health since its outbreak in December 2019. The COVID-19 does not  only affect the respiratory tract, but also other organs in human body including lungs,  liver, kidney, heart, vessels, and other organs (1). Respiratory failure and acute  respiratory distress syndrome (ARDS) are the most common serious complications of COVID-19  infection (2). The crude mortality rates (CMRs) of COVID-19 varies in different locations,  which ranges from 37.0/100,000 to 167.6/100,000 in several European countries up to 30th  August 2020 (3). The in-hospital mortality of COVID-19 was reported to be 17.1% based on 33  studies from 13,398 patients (4), and it was 2.9 times higher than that of influenza based on  the French national administrative database (5). It was reported that 26% of the COVID-19  patients admitted to ICU with severe status and 31% of the patients who admitted to ICU died  based on 37 studies from 24,983 patients (6).  There are several risk factors on patients' demographic characteristics and underlying  medical conditions which were shown be associated with the critical outcomes of COVID-19 (7).  In addition, poor oral health, in particular periodontitis, was also shown to be associated  with the critical outcomes of COVID-19 (8). Marouf et al. showed that COVID-19 patients with  periodontitis had 8 times higher odds of death and 3.5 times higher odds of ICU admission  than those without periodontitis based on a case-control study (9). This may be because  periodontal disease could enhance cytokine release via altered microflora, expression of  multiple viral receptors, bacterial superinfection, and aspiration of periodontal pathogens  (10). The increased production of pro-inflammatory cytokine, which is referred to as cytokine  storm, is the foremost cause of the adverse events of COVID-19 (10).  Because of the high contagiousness, high ICU admission rate, and high mortality of COVID-19,  it has led to tremendous increases in the demand for hospital beds and shortage of medical  equipment. Therefore, there is an urgent need for a pragmatic risk stratification tool that  allows the early identification of the COVID-19 patients who are likely to be at highest risk  of ICU admission and death (11). This can help clinicians and policymakers make the decisions  on the management and optimize resource allocation. A recent review identified multiple  prediction models which have been developed for prediction of prognosis of COVID-19 patients  (12). Those prediction models varied in their predictors and performance of the models. A  large number of prediction models reflected difficulties in their application in the rapid  risk stratification for general COVID-19 patients at their first intake in hospitals because  some predictors cannot be easily obtained without professional devices or lab tests, such as  C reactive protein, peripheral oxygen saturation, and urea level. Many prediction models  showed moderate performance in aspects of discrimination and calibration, and no benefit to  clinical decision making (12). In addition, the dental variables were not considered the  potential predictors in the previously developed models.  Therefore, the aim of the present study is to develop and externally validate a prediction  model for the critical outcomes of COVID-19 patients using predictors which can be easily  obtained in clinical practice, including patients' demographic characteristics, self-reported  medical conditions, and oral health.  Materials and Methods Participants We include hospitalized patients and outpatients from the  Isala Hospital (Zwolle, the Netherlands) with confirmed COVID-19 who visited the Department  of Oral and Maxillofacial Surgery (OMFS) between March 2020 and May 2021, if they have had a  dental panoramic radiograph (OPG), obtained up to a maximum of 5 years until the end of the  current study. The patients are used to develop the prediction model (derivation cohort).  We also include the hospitalized patients and outpatients from Noordwest Ziekenhuis (NWZ)  (Alkmaar, the Netherlands) with confirmed COVID-19 to externally validate the prediction  model (validation cohort).  Potential predictors  The potential predictors include patients' demographic characteristics, self-reported medical  conditions, and oral health. All the potential predictors are collected at baseline. The  potential predictors are presented below:  Demographic characteristics  -  Gender  -  Age  -  BMI  Medical conditions  -  Smoking  -  Diabetes  -  Hypertension  -  Hypercholesterolemia  -  COPD  -  CVD  -  Chronic kidney disease  -  OSAS  Dental variables (based on OPG)  -  Number of teeth  -  Number of dental implants  Outcome (endpoint) The endpoint of the study is the presence or absence of the critical  outcomes of COVID-19 (dichotomized). The course and outcome of the COVID-19 is classified  into (1) ambulatory; (2) hospitalized; (3) ICU admission or death based on the WHO Clinical  Progression Scale (13). In the study, the critical outcomes are defined as ICU admission or  death, while the non-critical outcomes are defined that patients are ambulatory or  hospitalized without ICU admission.  Statistical analysis The prediction modes will be developed and externally validated.  References  1. Wang X, Fang X, Cai Z, et al. Comorbid Chronic Diseases and Acute Organ Injuries Are  Strongly Correlated with Disease Severity and Mortality among COVID-19 Patients: A  Systemic Review and Meta-Analysis. Research (Wash D C) 2020; 2402961.  2. SeyedAlinaghi S, Afsahi AM, MohsseniPour M, et al. Late Complications of COVID-19; a  Systematic Review of Current Evidence. Arch Acad Emerg Med 2021; 9: e14.  3. Villani L, McKee M, Cascini F, et al. Comparison of deaths rates for COVID-19 across  Europe during the first wave of the COVID-19 pandemic. Front Public Health 2020; 8:  620416.  4. Macedo A, Gonçalves N, Febra C. COVID-19 fatality rates in hospitalized patients:  systematic review and meta-analysis. Ann Epidemiol 2021; 57: 14-21.  5. Piroth L, Cottenet J, Mariet AS, et al. Comparison of the characteristics, morbidity,  and mortality of COVID-19 and seasonal influenza: a nationwide, population-based  retrospective cohort study. Lancet Respir Med 2021; 9: 251-259.  6. Abate SM, Ali SA, Mantfardo B, et al. Rate of intensive care unit admission and outcomes  among patients with coronavirus: a systematic review and meta-analysis. PLoS One 2020;  15: e0235653.  7. Kim HJ, Hwang H, Hong H, et al. A systematic review and meta-analysis of regional risk  factors for critical outcomes of COVID-19 during early phase of the pandemic. Sci Rep  2021; 11: 9784.  8. Botros N, Iyer P, Ojcius DM. Is there an association between oral health and severity of  COVID-19 complications? Biomed J 2020; 43: 325-327.  9. Marouf N, Cai W, Said KN, et al. Association between periodontitis and severity of  COVID-19 infection: a case-control study. J Clin Periodontol 2021; 48: 483-491.  10. Sukumar K, Tadepalli A. Nexus between COVID-19 and periodontal disease. J Int Med Res  2021; 49: 3000605211002695.  11. Knight SR, Ho A, Pius R, et al. Risk stratification of patients admitted to hospital  with covid-19 using the ISARIC WHO Clinical characterization protocol: development and  validation of the 4C mortality score. BMJ 2020; 370: m3339.  12. Wynants L, Calster BV, Collins GS, et al. Prediction models for diagnosis and prognosis  of covid-19: systematic review and critical appraisal. BMJ 2020; 369: m1328.  13. WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection.  A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis  2020; 20: e192-e197. Inclusion Criteria:  -  patients who had a diagnosis of COVID-19 in the hospitals who visited the Department  of Oral and Maxillofacial Surgery (OMFS) between March 2020 and May 2021, if they have  had a dental panoramic radiograph (OPG), obtained up to a maximum of 5 years until the  end of the current study. Exclusion Criteria: None

The study is intended to compare expectant management and on presentation labor induction in  women with premature rupture of membranes.  The means of labor induction and cervical ripening are either oxytocin or dinoprostone.  Expectant management in this obstetrical state means waiting 24 hours from the onset of  rupture of membranes and then commencing labor induction with either oxytocin or dinoprostone  depending on the patient's obstetrical history and cervical condition.  The investigators' hypothesis is that active management will lead to a higher rate of vaginal  deliveries, a shorter interval between the time of rupture of membranes and the time of  delivery, a lower rate of cesarean sections and a better obstetric result for the mother and  the fetus/newborn. In the setting of premature rupture of membranes in term pregnancies, it is customary in  women who are not in active labor to wait for 24 hours before attempting to induce labor. The  means of labor induction used at our medical center are either intravenous oxytocin or  per-vaginal dinoprostone, depending on patient's obstetric history and cervical conditions.  The investigators hypothesize that commencing induction of labor at presentation in these  women by either means of induction will lead to higher rates of vaginal delivery, shorter  intervals between the time of onset of rupture of membranes and the time of delivery and  lower rates of cesarean sections.  The participants in the study, upon signing informed consents, will be randomized to 4  groups-2 groups of expectant management in which labor induction will be commenced after 24  hours with either oxytocin or dinoprostone and 2 groups of active management in which labor  induction will be commenced at presentation with either oxytocin or dinoprostone.  The participants will be followed from the time of presentation with rupture of membranes at  the delivery room and until the time of delivery.  Further obstetric, clinical and demographic information will be acquired from the patient's  electronic medical file for analysis accuracy and sub-analysis. Inclusion Criteria:  -  Term pregnancies >37 weeks of gestation.  -  Certain rupture of membranes.  -  Bishop score < 6.  -  Singleton pregnancies.  -  Vertex presentation.  -  No obstetric or clinical contraindications for labor induction.  -  Reactive non stress test on presentation. Exclusion Criteria:  -  Previous cesarean section.  -  Previous uterine surgeries (Myomectomy etc.).  -  Placenta Previa.  -  Multiple gestation pregnancies.  -  Pregnancies with history of fetal reduction or Intrapartum uterine fetal demise.  -  Known fetal defects/Chromosomal abnormalities.  -  Active genital Herpes.  -  HIV carrier.  -  Contractions that are less than 10 minutes apart.

In this study, doctors want to find out more about why people who lose weight often regain  the weight that they have lost once they resume a regular diet and whether hormones might  play a role in weight regain. The study is divided into two parts, called the meal  replacement period and the follow-up period. The meal replacement period will consist of  drinking a shake for breakfast and lunch and eating a frozen meal for dinner that is calorie  controlled. Individuals will also be asked to eat two servings of fruit and three servings of  vegetables each day. The study will provide the shakes and the frozen entrees, participants  are asked to supply the fruits and vegetables.  Participation in this study will last for up to 35 weeks. There will be 10 in-person visits  and 13 visits by phone or over Zoom over the 35 weeks. Individuals who are found to be eligible to participate will have two study interventions: An  8-week meal replacement therapy period in which they are asked to reduce their BMI by >5%.  Participants will be asked to strictly follow the individually-prescribed eating regimen  which will include meal replacement shakes and/or frozen meals to be used for breakfast and  lunch. For dinner, the study will provide pre-packaged frozen entrée meals to be consumed  with two servings of fruit and three servings of vegetables per day. Meal replacement  compliance will be assessed by requiring participants to maintain a dietary log throughout  the study. The percentage of days for which the protocol was followed (no additional calories  consumed) will serve as the primary metric of compliance.  Participants will also receive a standardized lifestyle/behavioral modification counseling  every 2 weeks throughout the entire study, which will be delivered at each in-person study  visit and via virtual platform of phone when there is no in-person study visit scheduled. The  lifestyle curriculum will incorporate evidence-based behavior change principles including  dietary modification, energy expenditure modification, behavior modification and family  involvement and support. To ensure fidelity and adherence to the delivery protocol, a manual  will be developed for each session that trained staff will follow when administering the  curriculum. Inclusion Criteria:  -  11 to less than 16 years old  -  BMI > 30 kg/m^2 or 95th BMI percentile  -  Tanner stage 2, 3, or 4 Exclusion Criteria:  -  Tanner stage 1 and 5  -  Prior bariatric surgery  -  Current or recent (< 3 months prior to enrollment) use of anti-obesity medication(s)  defined as orlistat, metformin, phentermine, topiramate, combination  phentermine/topiramate, liraglutide, and/or combination naltrexone/bupropion  (monotherapy use of naltrexone or bupropion is not an exclusion)  -  Monogenic and hypothalamic obesity  -  Polycystic ovary syndrome (diagnosed by a physician)  -  Pregnancy or planned pregnancy  -  Current use of supplemental hormones  -  Individuals with a diagnosed eating disorder of anorexia nervosa, bulimia or binge  eating disorder  -  Type 1 or 2 diabetes  -  Treatment with growth hormones  -  Thyroid disease/problem  -  Has had cancer in the last 10 years

To evaluate the performance of Check-Cap Imaging System in healthy volunteers in a variety of  operating scenarios.  The Back recorder unit is the primary module for evaluation The participants DO NOT ingest a  capsule and the capsules do not have any radioactive source 1. st visit - Subjects will be referred to the study by an advertisement in the local media  -  The subjects will receive a preliminary explanation about the study procedure and  required activities. If the subjects agree to participate in the study will be  asked to sign the ICF  -  Subjects will be screened for eligibility according to the inclusion/exclusion  criteria.  -  The date for their participation will be coordinated at their convenience  2. nd visit - Subject will arrive to the company R&D lab and will receive detailed  introduction about the procedure and instruction for the daily activities.  (The total duration of Check-Cap Imaging System study for each subject is up to 4 days).  -  Subjects will receive detailed instructions (verbally and written) about the normal  operation of the C-Scan System and how to handle it during normal daily routine. They  will be asked to document all their daily activity in a personal diary.  -  The C-Scan Track will be attached to their lower back to test its functionality and the  capsule will be attached to their abdomen to test the effect on data transmission during  daily activities.  -  The interference of the back recorder with the cloths (belt, bra etc.) will be monitored  for any discomfort.  -  Subjects will be asked to complete a personal diary which documents the time and  duration of significant activities during the procedure such as meal times, sleeping  times, physical activities etc.  -  Some subjects will be instructed to be stationary during short sessions (10-20-30 min)  and may read, watch TV or use the Internet. The localization data will be collected on a  dedicated portable computer via these detectors.  -  The monitoring routine for each subject will include but not limited to the following  parameters:  -  The well-being of the subject, and his/her daily routine: work, meals, driving,  public transportation, mild sport, shower, sleep, other activities  -  Inquiries about any discomfort caused by the recorder  -  Inquiries about any discomfort or skin irritation caused by the patches.  -  Inquiries about the function of the recorder as indicated by the recorder visual &  indicators  -  Ease of operation of the push buttons positioned on the recorder (reaching to the  lower back with w/out direct vision (mirror)  -  Responding to auditory and visual indicators position on the recorder  -  Some subjects will be asked to continue carrying the back recorder system for few more  days in order to evaluate the effects of the system on their daily activities.  -  A subjective questionnaire will be filled by the subjects following each phase of the  evaluation in order to solicit immediate feedback regarding any discomfort or complaint  During the current development study the plan is to simulate some of these scenarios and  evaluate the functionality of the back-recorder and communication with the capsule  -  Subjects will continue their daily routine: work, sleep, shower, driving in car or  public transportation, sit, stand, walk.  -  Subjects should refrain from active sport such as jogging, physical exercise in the gym,  swimming, sauna, any ball-games, skiing etc.  -  Subjects should refrain from Flights, boat trips or long train travels during the  monitoring procedure  -  Subjects should try and stay away from areas with high electromagnetic fields such as:  High voltage elect. Poles, transformation station, radio and TV transmitter station etc.  -  Subjects should not be examined by CT or MRI (unless it is an emergency)  -  Subjects who are working in an area with high electromagnetic field should not be  examined by the capsule Inclusion Criteria:  -  Male or female between 20 and 75 years of age  -  Subjects who are generally healthy  -  Subjects who fit the following body dimensions:  -  Height: 150-200 cm  -  Weight : 50-140 Kg  -  BMI: 20-35  -  Subjects who are ready to follow the various physical activities such as: walking,  running, sitting, driving, bending etc.  -  Subjects who are free to spend up to 4 days carrying the back recorder system.  -  Sign informed consent Form. Exclusion Criteria:  -  Subjects with cancer or other life threatening diseases or conditions  -  Pregnant women  -  Subjects with cardiac pacemaker or any other implanted or external portable medical  device (i.e. infusion pumps)  -  Bed-ridden or sedentary subjects  -  Subjects who suffer significant movement limitations (who cannot follow the typical  activities of walking, driving, bending, sitting etc.)  -  Morbid Obesity (BMI > 35)  -  Subjects under custodial care  -  Participation in current clinical study or clinical study within 30 days prior to the  procedure

The aim of this study will be to investigate the effect of an opioid-free anesthesia regimen  with a mixture of dexmedetomidine-lidocaine-ketamine in the same syringe versus fentanyl  analgesia in elective thyroidectomies. Recovery parameters and nociception levels throughout  the operation will be evaluated In the usual anesthetic practice opioids are often administered in the perioperative period  for intraoperative analgesia to control the nociceptive pathway of pain and post-surgical  pain management. However, in recent years, opioid Free Anesthesia (OFA) has become  increasingly popular, in which opioid administration is avoided intraoperatively and  minimized or avoided in the postoperative period.  Opioid-free anesthesia (OFA) has been shown to decrease postoperative complications  associated with opioids, include sedation, dizziness, nausea, vomiting, constipation,  physical dependence, tolerance, and respiratory depression.  Therefore, the investigators aim to perform this study to determine a goal-directed approach,  which targets adequate antinociception (e.g., by measuring nociceptive/antinociceptive  balance) that could reduce the negative effects of excessive drug infusion, prevent  postoperative pain and improve patient outcomes. Inclusion Criteria:  -  adult patients  -  American Society of Anesthesiologists (ASA) classification I-II  -  elective thyroidectomy Exclusion Criteria:  -  body mass index (BMI) >35 kg/m2  -  contraindications to local anesthetic administration  -  systematic use of analgesic agents preoperatively  -  chronic pain syndromes preoperatively  -  neurological or psychiatric disease on treatment  -  pregnancy  -  severe hepatic or renal disease  -  history of cardiovascular diseases/ arrhythmias/ conduction abnormalities  -  bradycardia(<55 beats/minute)  -  drug or alcohol abuse  -  language or communication barriers lack of informed consent

This double-blinded clinical randomized trial with a 1:1 recruitment ratio between placebo  and the active group will aim to investigate the effects of intravenously administered iron  in non-anemic iron deficient patients on physical capacity, immunological cells and their  function prior to surgery. A total of 134 patients with colorectalcancer will be included in  the study.  Study outline:  After initial inclusion the patient will undergo baseline testing with cardiopulmonary  exercise test (CPET), then followed by an infusion of a weight dependent dosage of  iron(III)isomaltoside or placebo. Then at the closest possible time to the surgery the  patient will have drawn bloodwork and be re-tested by (CPET). The patient will be followed  after surgery with evaluation of several outcomes including quality of recovery and  complications. Further, the effects of the intervention on the patients immune function will  be evaluated by two different methods: 1) by changes in neutrophil-to-lymphocyte ratio  between baseline and preoperative bloodwork and 2) by evaluation mRNA expression in the tumor  specimen by the Nanostring pancancer immune panel Aim The aim is to investigate the effects of intravenously administered iron in non-anemic  iron deficient patients on physical capacity, immunological cells and their function prior to  surgery.  Study design The study will be performed as a double-blinded clinical randomized trial with a  1:1 recruitment ratio between placebo and the active group. The study will be performed as a  multicenter study with inclusion at Department of Surgery, Zealand University Hospital,  Departement of Surgery, Slagelse Hospital and Department of Surgery, Regionshospital Randers.  The study will need 134 participants, 67 in each arm.  Potential patients will be identified through routine blood samples taken prior to the first  consultation. The samples will contain a complete anemia workup and a white blood cell count.  The clinical guidelines for identifying and treating anemia in patients with colorectal  cancer prior to surgery defines anemia by a hemoglobin ≤ 7 mmol/L for both men and women.  Therefore non-anemic patients are defined by a hemoglobin above 7 mmol/L for both men and  women in this protocol. Patients, who consents to the study, will immediately after the  consultation be randomized and given weight dependent dose of Monofer®  (Iron(III)-Isomaltoside) or placebo. On the day prior to surgery (or closest possible time)  blood samples similar to the previous samples, will be taken, but with two additional blood  samples, which will be stored for later analysis.  At the day of surgery, samples from the invasive front of the removed tumor will be taken and  stored for later analysis by the Nanostring PanCancer Immune panel.  The first 20 patients from the Zealand University Hospital and Slagelse hospital will be  physical tested by CPET prior to randomization and the day prior to surgery.  All patients will receive the same standardized peri- and postoperative care. All clinical  decisions will be at the surgeon's discretion. On the days after surgery until discharge,  daily routine blood samples will be taken, including white blood cell count and an assessment  of the recovery, through the validated and translated questionnaire Quality of Recovery-15  (QoR-15). Discharge will be handled through standardized discharge criteria. After thirty  days after surgery the patient will be contacted by phone for a follow up, concerning  complications after discharge and medical records scrutinized for postoperative events.  Randomization and allocation concealment Randomization to the intervention or placebo group  will be handled through an online block randomization stratificatied by sex, center of  treatment and hemoglobin levels at baseline. Hemoglobin levels at baseline will be divided  into four groups: 7.1-8.0, 8.1-9.0, 9.1-10.0 and ≥10.1. Placebo or MonoFer  (Iron(III)-Isomaltoside) will be administered through identical opaque bags. Placebo will be  an isotonic saline solution. The randomization key will be stored online behind an encryption  key (in EasyTrial), which only will be opened after all testing of primary outcomes have been  concluded. In order to secure double blinding a specific procedure for administration will be  performed outlined in figure 3. When randomization are performed the randomization ID will  have a corresponding closed cardboard box with a label with the randomization ID. The box  will contain everything needed for concealment, equipment for intravenous administration,  isotonic saline solution, and if active also 1000 mg (maximum dosage) MonoFer  (Iron(III)-Isomaltoside). The box will be delivered to a clinical nurse which will mix the  drug and put it into the opaque bag. A project nurse will secure an intravenous catheter,  tape the catheter with opaque tape, put the patients hand through a curtain and leave the  room. The clinical nurse will then administer the drug/placebo behind the curtain. The  project nurse will do the observation of the patient during the infusion and the clinical  nurse will remove the drug/placebo after end infusion. The box will be packed by the Central  Pharmacy of Region Zealand and delivered to each site. All clinical nurses will receive  training prior to initiation of the study in regards to proper mixing and concealment  procedure.  Trial medication, packaging, labeling and administration The trial medication in use for this  trial is weight depended MonoFer (Iron(III)isomaltoside 100 mg/ml) versus placebo which is  isotonic saline, as an one-time dosage administered intravenously in hospital. The weight  depended dosages are as follows: <50 kg bodyweight: 500 mg, 50-59 kg bodyweight: 600 mg,  60-69 kg bodyweight: 700 mg, 70-79 kg bodyweight: 800 mg, 80-89 kg bodyweight: 900 mg, and  ≥90 kg bodyweight 1000 mg Monofer. MonoFer needs to be mixed with isotonic saline just prior  to administration. Thus, in order to secure proper concealment everything needing for mixing  and administration are packed in closed cardboard boxes. The boxes are labelled in  concordance with The Rules Governing Medicinal Products in the European Union Directive  2003/94/EC  Each cardboard box will contain 500 ml isotonic saline infusion fluid, a drop line and an  opaque bag which will cover both the line and the fluid, labeling for the opaque bag, and a  standard operating procedure document detailing handling and allocation concealment procedure  (appendix II: Håndtering af forsøgsmedicin). If allocated to the active group the box will  also contain 10ml MonoFer 100mg/ml.  If the administration are interrupted before the full dosage are administered the actual  dosage given are noted by the clinical nurse and passed on to the project nurse which will  secure the registration without deblinding the patient or research staff. Otherwise the full  dosage of 500 ml will be recorded.  The infusion will be stopped if the patient experiences any adverse effects during the  infusion. A particular reaction called a 'Fishbane reaction' in which the patient develops  reddening of the skin, especially in the face, and truncal myalgia, but without any other  symptoms of an allergic reaction will not be cause termination of the infusion. The Fishbane  reaction is always selflimitating and is not associated with respiratory stridor, edema,  hypotension or tachycardia. In case of a Fishbane reaction the infusion is stopped until the  symptoms have dissipated, then the infusion is restarted, but with double the infusion time.  If the Fishbane reaction reoccurs the infusion is terminated and dosage given registered.  Definition of per protocol Patients are considered per protocol if the patient received full  dosage of placebo or MonoFer, and underwent surgery for a malignant tumor. Inclusion Criteria:  -  Planned for curative intended elective colon or rectum cancer surgery  -  UICC stage I-III (at diagnosis)  -  Hemoglobin > 7.0 mmol/L  -  Serum ferritin <101 microgram/L or transferrin saturation <21% Exclusion Criteria:  -  Chronic kidney failure with need for dialysis  -  Metachronous diagnosed cancer  -  Unable to speak or understand Danish  -  Cognitive impairment e.g. moderate to severe dementia  -  Concurrent severe active bacterial infection  -  Known allergy for Iron(III)isomaltoside  -  Contraindications for intravenous iron (Pofryria, livercirrosis, active hepatitis,  transaminases three times the upper limit, hemosiderosis and hemochromatosis)  -  Withdrawal of informed consent  -  Neoadjuvant chemo or radiation therapy  -  Pregnancy

Last Mile Health (LMH) has partnered with the Liberian Ministry of Health (MOH) to support  the design and implementation of the National Community Health Assistant Program (NCHAP). In  collaboration with MOH, LMH is planning to conduct an impact evaluation in Grand Bassa to  assess the effect of the National Community Health Assistant Program (NCHAP) on health  outcomes, as well as to learn lessons around program operations and implementation. Our  central hypothesis is that Community Health Assistants (CHAs) within the NCHAP will reduce  under 5 mortality, as a result of expanding access to and uptake of health care utilization  in remote communities. We will use a mixed effects discrete survival model, taking advantage  of the staggered program implementation in Grand Bassa districts over a period of 4 years to  compare the incidence of under-5 child mortality between the pre- and post-CHW program  implementation periods. Previous evaluations of the NCHAP in Rivercess and Grand Gedeh counties found significant  increases in uptake of child and maternal health-care services from qualified providers. We  will expand upon those studies to assess the impact of the CHA program after a phased  implementation in an additional county.  The Liberian NCHAP is being rolled out staggered across the eight districts of Grand Bassa  County by the government of Liberia. The practical program implementation is accompanied and  supported by LMH. Starting with program implementation in March 2018, the last district will  be covered by the NCHAP by January 2022. At baseline, midline, and endline LMH will conduct  representative household surveys to assess the interventions uptake and effectiveness on  population health. This programmatic strategy allows us to apply a  effectiveness-implementation hybrid design, where we are using quasi experimental methods on  the intervention's impact on relevant outcomes and program utilization and mixed methods to  assess the implementation process.  The program implementation and data collection takes place in the Grand Bassa county of  Liberia between 2018 and 2022. Measuring an area of 7,936 square kilometres and an overall  population of 224,839 in 2008, the county is predominantly rural. For program roll out the  five administrative districts were subdivided in eight study districts (see Figure 1). The  target population of the NCHA are households in communities with a distance of more than 5 km  from the nearest health facility. According to the 2018 LMH Grand Bassa household survey,  1,733 communities were identified as remote with 23,702 households.  The long-term objective of the NCHA program is to provide community-based health care that  substantially improves population health and is desirable and respectful to the clients it  serves. In pursuit of this objective, our specific research aims for the Grand Bassa causal  impact evaluation is to assess the impact of the NCHA program on under-5 mortality. Inclusion Criteria:  -  Communities >5 km from a health facility  -  Within a household all women 18-49 were interviewed (if possible). Exclusion Criteria:  -

There has been a steep rise in the prevalence of obesity among children and adults in the  United States. The Weigh Smart program, a family based weight management program was  developed in 2005 with significant improvement in the severity of obesity among children in  the Baltimore are participating in the group program with limited impact outside the region  due to transportation. Trial of the group program (nutrition, exercise) delivered via  telehealth through fruit street on the Eastern Shore and Western Maryland with use of  noninvasive lifestyle tracking options (drink water aquarium app for water consumption and  fitbit- steps, sleep monitoring) provides novel options for expansion of family- based  lifestyle intervention to underserved areas. Investigators plan as a pilot study to assess  the sensitivity of noninvasive measures for the detection of sleep apnea (pediatric sleep  questionnaire (PSQ) and fitbit re: sleep data) in comparison to clinically indicated  polysomnography among children with clinical suspicion for sleep apnea. . Trial of the group program (nutrition, exercise) delivered via telehealth through fruit  street to families of overweight and obese children between 7-17 years of age referred from  selected pediatric practices on the Eastern Shore of Maryland and Western Maryland with use  of noninvasive lifestyle tracking options (drink water aquarium app for water consumption and  fitbit charge 3- steps, sleep monitoring) provides novel options for expansion of family-  based lifestyle intervention to underserved areas. Investigators plan as a pilot study to  assess the sensitivity of noninvasive measures for the detection of sleep apnea (pediatric  sleep questionnaire (PSQ) and fitbit charge 3 sleep data) in comparison to clinically  indicated polysomnography among children with clinical suspicion for sleep apnea. Inclusion Criteria:  -  Children who are overweight/obese (7-17 years of age)  -  Children must be referred by selected Maryland Eastern Shore and Western Maryland  pediatric practices to Mount Washington Pediatric Hospital Weigh Smart. Families must  provide informed consent at the weigh smart visit and have access to either a tablet,  laptop or smart phone device to participate. Exclusion Criteria:  -  Children outside of the age range  -  Children not seen by Maryland Eastern Shore or Western Maryland pediatric providers  who are part of the intervention group  -  Children who do not have internet access either by smart phone or tablet to allow  telehealth participation  -  Children who are unwilling to participate in group program and followup local visits

Mechanomyography (MMG) is considered the gold-standard for neuromuscular blockade (NMB)  monitoring. However, it is quite bulky and difficult to use on a routine basis. Therefore,  alternative methods like Acceleromyography (AMG), Electromyography (EMG) and the TOF-CUFF  method have been developed. The aim of this study was to compare the TOF-Cuff monitor and  Electromyography (EMG-NMT module with the CARESCAPE B450 monitor) data following  rocuronium-induced neuromuscular blockade and its reversal. Neuromuscular relaxation of the patient during surgery is necessary for multiple reasons,  such as facilitating intubation or improving the effectiveness of some surgical procedures.  Premature extubation of the patient without having achieved a complete recovery of the NMB  can have deleterious consequences, increasing postoperative complications, especially those  related to the respiratory system. Given this, current guidelines of good clinical practice  recommend the monitoring of pharmacologically induced NMB during general anesthesia. In  addition, monitoring allows confirmation of optimum relaxation before intubation, and allows  for control over re-dose administration and recovery of NMB upon awakening from general  anesthesia.  There are different methods of quantitative monitoring of NMB. The TOF-CUFF monitor uses a  method based on a traditional pressure cuff that incorporates stimulation electrodes. The  placement of the cuff which aligns the stimulation electrodes on the path of the brachial  plexus at the humeral level allows to evaluate the muscular response evoked from the changes  in the cuff pressure, generated by the muscular contraction after the electrical stimulus.  Its main advantage is that monitoring of the NMB is included within the pressure cuff itself,  which is always used in any anesthetic act. Then, when the pressure cuff is placed,  monitoring of the NMB is easily established. This specific design facilitates the task of  anesthesiologists because they do not have to perform any additional preparation for the  monitoring of NMB.  The TOF-CUFF monitor has been validated regarding the mechanomyography, which is considered  the gold-standard for the monitoring of NMB. The main objective of the study is to compare  the values of NMB measured with the TOF-CUFF monitor with NMB values measured with the  CARESCAPE B450 monitor during the pharmacologically induced NMB and evaluate the degree of  equivalence in different situations. Secondary objective is to verify that the design for  joint monitoring of the NMB and NIBP in the TOF-CUFF monitor does not affect the independent  measure of the two variables.  Prospective, single-center, open and controlled observational clinical study. The study is  aimed to be conducted with 40 patients aged between 18 and 65 years. Inclusion Criteria:  -  ASA I-II  -  Patients who give their written informed consent  -  Elective surgery under general anesthesia that according to the anesthetic plan muscle  relaxants will be administered Exclusion Criteria:  -  Patients who refuse to give their informed consent  -  Patients who present any of the contraindications for the devices used in the study  -  Patients who are participating or have participated in a clinical trial during the 4  weeks prior to inclusion  -  Women of childbearing age who do not use effective contraceptive methods, pregnant  women, with suspicion of pregnancy or breast-feeding  -  Patients with the following criteria: upper limb peripheral vascular pathologies, a  difficult airway, myasthenia gravis and other neuromuscular diseases, use of  medication that may alter NMT

To explore the efficacy of venetoclax combined with azacytidine in Myelodysplastic /  myeloproliferative neoplasms（MDS/MPN）, so as to improve the overall survival and treatment  status of MDS/MPN patients. At present, there is no standardized treatment strategy for MDS/MPN. The purpose of our study  is to explore the efficacy of venetoclax combined with azacytidine in the treatment of  MDS/MPN, so as to improve the overall survival and treatment status of patients with MDS/MPN.  After the participants were treated with four cycles of venetoclax combined with azacytidine,  the efficacy was evaluated according to the 2015 adult MDS/MPN response criteria to determine  the disease status. Participants with disease progression and intolerance withdrew from the  study during treatment. Inclusion Criteria:  1. Male or female, Age (years) >= 18；  2. Patients newly diagnosed or previously treated with MDS/MPNs (CMML, MDS/MPN-U, aCML)  according to 2016 WHO diagnostic criteria:  Initial diagnosis: CMML: CPSS-mol intermediate risk 2 and above; aCML; MDS/MPN-U.  Previous treatment: HMA treatment failed.  3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;  4. Liver function: Total bilirubin ≤3 upper limit of normal (ULN); aspartate  aminotransferase (AST) ≤3 ULN; alanine aminotransferase (ALT)≤3 ULN；  5. Renal function#Ccr ≥30 ml/min;  6. Patients who sign the informed consent must have the ability to understand and be  willing to participate in the study and sign the informed consent. Exclusion Criteria:  1. Acute myeloid leukemia  2. Myelodysplastic syndrome  3. Subjects who had previously been treated with Venetoclax  4. Subjects who are known to be allergic to ingredients of the study drug or their  analogues  5. HIV infection  6. HBV-DNA or HCV-RNA positive  7. Subjects with grade 2 or above cardiac failure and those considered unsuitable for  inclusion by the investigator  8. Subjects who are pregnant or breastfeeding  9. Subjects reject to participate in the study