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Adoptive cell therapy (ACT), such as chimeric antigen receptor (CAR) T-cell therapy, has demonstrated promising therapeutic effects with potentially non-monotonic dose-response curves. Building upon the i3 + 3 design for cytotoxic agents [1], we propose a new method - joint i3 + 3 (Ji3 + 3) that takes into account of both safety and efficacy outcomes in making dosing recommendations. This allows for efficient dose escalation and identification of biological optimal dose of ACTs which may not be cytotoxic. The Ji3 + 3 design is rule based, easy to understand for clinicians, and is simple to implement. Simulation results show that Ji3 + 3 outperforms existing designs when monotonic dose-response assumption is violated, and still achieves comparable performance when the assumption holds. The simplicity and superior operating characteristics make Ji3 + 3 a good candidate for phase I/II ACT dose-finding trials in the clinical community when toxicity and efficacy are both considered as binary endpoints.Exit-site infections (ESIs) increase the risk of developing peritoneal dialysis (PD) peritonitis and PD technique failure. There are no clear guidelines on how to monitor exit site (ES) after ESI with Staphylococcus aureus or Pseudomonas. We report on a 1-year observational study of 23 patients who developed an ESI with one of these serious pathogens. After completing initial antibiotic treatment, swabs were taken every month for 3 months. Primary treatment cure occurred in 19/23 (83%). Colonization of ES after primary cure occurred in 8/19 (42%) patients. In the eight colonized patients, five had subsequent PD technique failure due to infections. By contrast, during an average follow-up period of 7.2 months, none of the 11 patients who were proven noncolonized developed PD technique failure from infections; HR (colonized vs. noncolonized) = 10.89, 95% CI 2.6-45.43, p less then 0.05. In conclusion, colonization significantly increased the risk of catheter loss. Increased surveillance and aggressive treatment may ameliorate this risk.Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2. Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against COVID-19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach. Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3' hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3'-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host. Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against COVID-19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19.This study aimed to describe anthropometry and incidence, nature and causes of match injuries in women's international rugby sevens and to compare these with results reported previously for men's international rugby sevens. The study comprised an 8-season, prospective study of World Rugby's women's Sevens World Series. Over the eight seasons, the overall incidence of injury was 105.6 (95% CI 96.0 to 116.3) injuries/1000 player-match-hours with a mean injury severity of 53.4 (95% CI 46.9 to 59.9) days-absence. There were no statistically significant trends for backs or forwards in the incidence (backs p = 0.470; forwards p = 0.242) or mean severity (backs p = 0.098; forwards p = 0.544) of injuries sustained over the 8-season period. Head/face (20.8%), knee (19.7%), ankle (11.3%) and shoulder/clavicle (8.4%) were the most common injury locations while ligament sprain (31.7%), concussion (15.6%), haematoma/bruise (11.5%) and fracture (11.5%) were the most common types of injury sustained. Being-tackled (35.4%), tackling (26.3%), collisions (13.8%) and rucks (8.8%) were the match events responsible for most injuries. The study indicates that injury burden in women's international rugby sevens (5,640 days-absence/1000 player-match-hours; 95% CI 5,123 to 6,209) is similar to that reported previously for men's international rugby sevens (5,263 days-absence/1000 player-match-hours; 95% CI 5,000 to 5,540).In this paper, we outline a systematic testing programme developed to help identify excellence in youth basketball players. We examine the links between biological maturation and training experience with anthropometry, body composition, physical performance, technical and tactical skills from five age-cohorts, and characterize, in detail, facets of their environment. In total, 238 young basketball players aged 11-15 years, clustered into five age-cohorts (11, 12, 13, 14, 15 years) were recruited. We assessed measures across three domains (1) biological [anthropometry, body composition, biological maturation and physical performance]; (2) skill/game proficiency [technical skills and tactical skills]; and (3) contextual [family support, coach knowledge and competence and club context]. selleck chemicals llc The data were analysed using one-way ANOVAs and multivariate analysis of covariance adjusting for biological maturation and training experience. We report significant differences favouring older basketball players on most biological and skill/game proficiency variables.