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  The dense clustering of glycans creates an unfavorable environment for the interaction of otherwise neutralizing antibodies. [...]critical regions on EBOV GP, such as the receptor-binding site, are hidden under layers of glycan. [...]host BST-2 is incorporated in the membrane of the nascent virion and forms a protein tether to prevent viral release. [...]it may be worthwhile to explore the role of the transmembrane domain of EBOV GP in BST-2 antagonism.

\"Lifting its name from the Persian word for \"herbs,\" Sabzi is a collection of more than 80 accessible, plant-forward recipes that celebrate the best of Mediterranean, Middle Eastern, and South Asian flavors. From bountiful salads to fragrant soups, colorful mezze, and heart-warming mains, Yasmin invites home cooks to eat better for the health of people and the planet, while staying connected to the traditional food cultures that make us who we are.\" -- Provided by publisher.

In E. coli , the FtsEX-EnvC system regulates two of the three division-associated amidases that break the peptidoglycan layer during bacterial division. Structural and mechanistic studies have revealed a detailed molecular mechanism for amidase activation in which an ABC transporter and its periplasmic partner reversibly activate periplasmic amidases under direction of the cytoplasmic cell division machinery. This paper explores structural features of EnvC that underpin autoinhibition and the activation mechanism. The FtsEX-EnvC system serves as a powerful example of a Type VII ABC transporter that uses transmembrane conformational changes to drive work in the periplasmic space.

Use of patient-reported outcomes (PROs) and patient and public engagement are critical ingredients of pragmatic trials, which are intended to be patient centered. Engagement of patients and members of the public in selecting the primary trial outcome and determining the target difference can better ensure that the trial is designed to inform the decisions of those who ultimately stand to benefit. However, to the best of our knowledge, the use and reporting of PROs and patient and public engagement in pragmatic trials have not been described. The objectives of this study were to review a sample of pragmatic trials to describe (1) the prevalence of reporting patient and public engagement; (2) the prevalence and types of PROs used; (3) how its use varies across trial characteristics; and (4) how sample sizes and target differences are determined for trials with primary PROs. This was a methodological review of primary reports of pragmatic trials. We used a published electronic search filter in MEDLINE to identify pragmatic trials, published in English between January 1, 2014 and April 3, 2019; we identified the subset that were registered in ClinicalTrials.gov and explicitly labeled as pragmatic. Trial descriptors were downloaded from ClinicalTrials.gov; information about PROs and sample size calculations were extracted from the manuscript. Chi-squared, Cochran-Armitage, and Wilcoxon rank sum tests were used to examine associations between trial characteristics and use of PROs. Among 4,337 identified primary trial reports, 1,988 were registered in CT.gov, of which 415 were explicitly labeled as pragmatic. Use of patient and public engagement was identified in 39 (9.4%). PROs were measured in 235 (56.6%): 144 (34.7%) used PROs as primary outcomes and 91 (21.9%) as only secondary outcomes. Primary PROs were symptoms (64; 44%), health behaviors (36; 25.0%), quality of life (17; 11.8%), functional status (16; 11.1%), and patient experience (10; 6.9%). Trial characteristics with lower prevalence of use of PROs included being conducted exclusively in children or adults over age 65 years, cluster randomization, recruitment in low- and middle-income countries, and primary purpose of prevention; trials conducted in Europe had the highest prevalence of PROs. For the 144 trials with a primary PRO, 117 (81.3%) reported a sample size calculation for that outcome; of these, 71 (60.7%) justified the choice of target difference, most commonly, using estimates from pilot studies (31; 26.5%), standardized effect sizes (20; 17.1%), or evidence reviews (16; 13.7%); patient or stakeholder opinions were used to justify the target difference in 8 (6.8%). Limitations of this study are the need for trials to be registered in ClinicalTrials.gov, which may have reduced generalizability, and extracting information only from the primary trial report. In this study, we observed that pragmatic trials rarely report patient and public engagement and do not commonly use PROs as primary outcomes. When provided, target differences are often not justified and rarely informed by patients and stakeholders. Research funders, scientific journals, and institutions should support trialists to incorporate patient engagement to fulfill the mandate of pragmatic trials to be patient centered.

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials.

Two commonly performed surgical interventions are available for severe (grade II–IV) haemorrhoids; traditional excisional surgery and stapled haemorrhoidopexy. Uncertainty exists as to which is most effective. The eTHoS trial was designed to establish the clinical effectiveness and cost-effectiveness of stapled haemorrhoidopexy compared with traditional excisional surgery. The eTHoS trial was a large, open-label, multicentre, parallel-group, pragmatic randomised controlled trial done in adult participants (aged 18 years or older) referred to hospital for surgical treatment for grade II–IV haemorrhoids. Participants were randomly assigned (1:1) to receive either traditional excisional surgery or stapled haemorrhoidopexy. Randomisation was minimised according to baseline EuroQol 5 dimensions 3 level score (EQ-5D-3L), haemorrhoid grade, sex, and centre with an automated system to stapled haemorrhoidopexy or traditional excisional surgery. The primary outcome was area under the quality of life curve (AUC) measured with the EQ-5D-3L descriptive system over 24 months, assessed according to the randomised groups. The primary outcome measure was analysed using linear regression with adjustment for the minimisation variables. This trial is registered with the ISRCTN registry, number ISRCTN80061723. Between Jan 13, 2011, and Aug 1, 2014, 777 patients were randomised (389 to receive stapled haemorrhoidopexy and 388 to receive traditional excisional surgery). Stapled haemorrhoidopexy was less painful than traditional excisional surgery in the short term and surgical complication rates were similar between groups. The EQ-5D-3L AUC score was higher in the traditional excisional surgery group than the stapled haemorrhoidopexy group over 24 months; mean difference −0·073 (95% CI −0·140 to −0·006; p=0·0342). EQ-5D-3L was higher for stapled haemorrhoidopexy in the first 6 weeks after surgery, the traditional excisional surgery group had significantly better quality of life scores than the stapled haemorrhoidopexy group. 24 (7%) of 338 participants who received stapled haemorrhoidopexy and 33 (9%) of 352 participants who received traditional excisional surgery had serious adverse events. As part of a tailored management plan for haemorrhoids, traditional excisional surgery should be considered over stapled haemorrhoidopexy as the surgical treatment of choice. National Institute for Health Research Health Technology Assessment programme.

To advance understanding of doctoral student experiences and the high attrition rates among Science, Technology, Engineering, and Mathematics (STEM) doctoral students, we developed and examined the psychological profiles of different types of doctoral students. We used latent class analysis on self-reported psychological data relevant to psychological threat from 1,081 incoming doctoral students across three universities and found that the best-fitting model delineated four threat classes: Lowest Threat , Nonchalant , Engaged/Worried , and Highest Threat . These classes were associated with characteristics measured at the beginning of students’ first semester of graduate school that may influence attrition risk, including differences in academic preparation (e.g., amount of research experience), self-evaluations and perceived fit (e.g., sense of belonging), attitudes towards graduate school and academia (e.g., strength of motivation), and interpersonal relations (e.g., perceived social support). Lowest Threat students tended to report the most positive characteristics and Highest Threat students the most negative characteristics, whereas the results for Nonchalant and Engaged/Worried students were more mixed. Ultimately, we suggest that Engaged/Worried and Highest Threat students are at relatively high risk of attrition. Moreover, the demographic distributions of profiles differed, with members of groups more likely to face social identity threat (e.g., women) being overrepresented in a higher threat profile (i.e., Engaged/Worried students) and underrepresented in lower threat profiles (i.e., Lowest Threat and Nonchalant students). We conclude that doctoral students meaningfully vary in their psychological threat at the beginning of graduate study and suggest that these differences may portend divergent outcomes.