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Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation. For this phase 2, single centre, open-label, adaptive, safety and efficacy randomised clinical trial, we included adults aged 18–75 years presenting to the University of Minnesota Medical Center (MN, USA) with OHCA and refractory ventricular fibrillation, no return of spontaneous circulation after three shocks, automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System, and estimated transfer time shorter than 30 min. Patients were randomly assigned to early ECMO-facilitated resuscitation or standard ACLS treatment on hospital arrival by use of a secure schedule generated with permuted blocks of randomly varying block sizes. Allocation concealment was achieved by use of a randomisation schedule that required scratching off an opaque layer to reveal assignment. The primary outcome was survival to hospital discharge. Secondary outcomes were safety, survival, and functional assessment at hospital discharge and at 3 months and 6 months after discharge. All analyses were done on an intention-to-treat basis. The study qualified for exception from informed consent (21 Code of Federal Regulations 50.24). The ARREST trial is registered with ClinicalTrials.gov, NCT03880565. Between Aug 8, 2019, and June 14, 2020, 36 patients were assessed for inclusion. After exclusion of six patients, 30 were randomly assigned to standard ACLS treatment (n=15) or to early ECMO-facilitated resuscitation (n=15). One patient in the ECMO-facilitated resuscitation group withdrew from the study before discharge. The mean age was 59 years (range 36–73), and 25 (83%) of 30 patients were men. Survival to hospital discharge was observed in one (7%) of 15 patients (95% credible interval 1·6–30·2) in the standard ACLS treatment group versus six (43%) of 14 patients (21·3–67·7) in the early ECMO-facilitated resuscitation group (risk difference 36·2%, 3·7–59·2; posterior probability of ECMO superiority 0·9861). The study was terminated at the first preplanned interim analysis by the National Heart, Lung, and Blood Institute after unanimous recommendation from the Data Safety Monitoring Board after enrolling 30 patients because the posterior probability of ECMO superiority exceeded the prespecified monitoring boundary. Cumulative 6-month survival was significantly better in the early ECMO group than in the standard ACLS group. No unanticipated serious adverse events were observed. Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment. National Heart, Lung, and Blood Institute.

\"Why are some technologies such as fiberglass vaulting poles and hinged skates accepted in sport while performance-enhancing drugs are forbidden? Yes, performance-enhancing drugs are against the rules, but the people who play and govern sport create those rules; rules can be changed. Should we level the playing field by allowing all competitors to use drugs that allow them to run faster or longer, leap higher, or lift more? In this provocative exploration of what draws us to sport as participants and spectators, Good Sport argues that the values and meanings embedded within our games provide the guidance we need to make difficult decisions about fairness and performance-enhancing technologies. Good Sport reveals what we care about in sport. It describes how the reckless use of biomedical enhancements undermines those values. Implicit in sport's history, rules and practices are values and meanings that provide a sturdy foundation for an ethics of sport that celebrates natural talents and dedication. The way a sport adapts to innovations in equipment, tactics and players makes visible its values and meanings. Performance-enhancing drugs distort the connection between natural talents, the dedication to perfect those talents, and success in sport. Through understanding the fundamental role of values and meanings, we can see not just what we champion in the athletic arena but more broadly what we value in human achievement\"-- Provided by publisher.

Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1β and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.

Medical therapy often consists of multiple stages, with a treatment chosen by the physician at each stage based on the patient's history of treatments and clinical outcomes. These decisions can be formalized as a dynamic treatment regime. This article describes a new approach for optimizing dynamic treatment regimes, which bridges the gap between Bayesian inference and existing approaches, like Q-learning. The proposed approach fits a series of Bayesian regression models, one for each stage, in reverse sequential order. Each model uses as a response variable the remaining payoff assuming optimal actions are taken at subsequent stages, and as covariates the current history and relevant actions at that stage. The key difficulty is that the optimal decision rules at subsequent stages are unknown, and even if these decision rules were known the relevant response variables may be counterfactual. However, posterior distributions can be derived from the previously fitted regression models for the optimal decision rules and the counterfactual response variables under a particular set of rules. The proposed approach averages over these posterior distributions when fitting each regression model. An efficient sampling algorithm for estimation is presented, along with simulation studies that compare the proposed approach with Q-learning. Supplementary materials for this article are available online.

A collection of speeches, articles, poetry, book excerpts, and political cartoons from the American antiwar tradition beginning with the War of 1812 offers the full range of the subject's richness and variety, with contributions from such notables as Daniel Webster, Mark Twain, Andrew Carnegie, and Patrick Buchanan.

Cyclization provides a general strategy for improving the proteolytic stability, cell membrane permeability and target binding affinity of peptides. Insertion of a stable, non-reducible linker into a disulphide bond is a commonly used approach for cyclizing phage-displayed peptides. However, among the vast collection of cysteine reactive linkers available, few provide the selectivity required to target specific cysteine residues within the peptide in the phage display system, whilst sparing those on the phage capsid. Here, we report the development of a cyclopropenone-based proximity-driven chemical linker that can efficiently cyclize synthetic peptides and peptides fused to a phage-coat protein, and cyclize phage-displayed peptides in a site-specific manner, with no disruption to phage infectivity. Our cyclization strategy enables the construction of stable, highly diverse phage display libraries. These libraries can be used for the selection of high-affinity cyclic peptide binders, as exemplified through model selections on streptavidin and the therapeutic target αvβ3. Cyclization provides a general strategy for improving peptide proteolytic stability, cell membrane permeability and target binding affinity. Here the authors develop a cyclopropenone-based proximity-driven chemical linker for the site-specific cyclization of phage-displayed peptides.

يتناول كتاب (استخدام نتائج التقييم الوطني للتحصيل التعليمي) والذي قام بتأليفه (توماس كليغان، فينسنت غريني، ت. سكوت موري) في حوالي (163) صفحة من القطع المتوسط المحتويات التالية : الفصل الأول : العوامل المؤثرة على استخدام وعدم استخدام نتائج التقييم الوطني، الفصل الثاني : الإبلاغ عن التقييم الوطني : التقرير الرئيسي، الفصل الثالث : الإبلاغ عن التقييم الوطني : أدوات أخرى لإبلاغ نتائج التقييم ... إلخ.

Patients receiving thrice-weekly hemodialysis have two 1-day intervals and one 2-day interval between treatments. This study shows that the risks of death and cardiovascular events leading to hospital admission are increased during the long (2-day) interdialytic interval. Although some progress has been made in the past two decades, survival rates among patients receiving hemodialysis in the United States remain among the lowest in the world. 1 As in most countries, maintenance hemodialysis in the United States is typically performed three times per week, with two 1-day intervals and one 2-day interval between dialysis sessions. Depending on scheduling, the vast majority of patients do not receive dialysis between Friday and Monday or between Saturday and Tuesday. Patients with end-stage renal disease have a limited capacity to maintain homeostasis in the presence of metabolic and volume-related deviations from normal ranges, . . .