CD40mAb adjuvant induces a rapid antibody response that may be beneficial in post-exposure prophylaxis

Active vaccination can be effective as a post-exposure prophylaxis, but the rapidity of the immune response induced, relative to the incubation time of the pathogen, is critical. We show here that CD40mAb conjugated to antigen induces a more rapid specific antibody response than currently used immunological adjuvants, alum and monophosphoryl lipid A™

Making Memorial Student-Ready: Reflections on the First Year Success Experience

In eleven short chapters faculty, academic advising staff and student union representatives discuss aspects of Memorial’s First Year Success Program (piloted as a Teaching Learning Framework initiative 2012-2017). Teaching approaches, curriculum content and policy rationales are covered in a broad view of how and why students identified as least likely to succeed at university can be academically supported. Contributors identify the singular importance of the community that First Year Success provided them and its student participants

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Global political responsibility for the conservation of albatrosses and large petrels

Migratory marine species cross political borders and enter the high seas, where the lack of an effective global management framework for biodiversity leaves them vulnerable to threats. Here, we combine 10,108 tracks from 5775 individual birds at 87 sites with data on breeding population sizes to estimate the relative year-round importance of national jurisdictions and high seas areas for 39 species of albatrosses and large petrels. Populations from every country made extensive use of the high seas, indicating the stake each country has in the management of biodiversity in international waters. We quantified the links among national populations of these threatened seabirds and the regional fisheries management organizations (RFMOs) which regulate fishing in the high seas. This work makes explicit the relative responsibilities that each country and RFMO has for the management of shared biodiversity, providing invaluable information for the conservation and management of migratory species in the marine realm

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Using shared goal setting to improve access and equity : a mixed methods study of the Good Goals intervention in children's occupational therapy

Peer reviewedPublisher PD

Associations with drug use and sexualised drug use among women who have sex with women (WSW) in the UK: Findings from the LGBT Sex and Lifestyles Survey

Introduction Studies indicate that women who have sex with women (WSW) report greater levels of drug use than heterosexual women, but globally few studies have looked at sexualised drug use among WSW. This study investigated the factors associated with drug use and sexualised drug use (SDU) among WSW. Methods Potential participants across the UK were invited to take part in a cross-sectional anonymous online survey between April-June 2018. The LGBT Sex and Lifestyles Survey recruited participants through Facebook advertising and social media posts from community organisations. Multivariate logistic regression was used to compare WSW who had engaged in any drug use in the past 12 months with those who had not, and those who engaged in sexualised drug use in the past 12 months with those who engaged in other drug use. Results: 1501 WSW could be included in the analyses (mean age = 28.9, 97% white ethnicity). Any drug use was reported by 39% of WSW (n = 583), 44% of which (17% of total, n = 258) reported SDU. Factors associated with drug use were identifying as queer (aOR = 1.86, 95%CI 1.08, 3.23), younger age (aOR = 0.96, 95%CI 0.95, 0.98), being born outside the UK (aOR = 1.75, 95%CI 1.15, 2.66), recent sexual assault (aOR = 2.35, 95%CI 1.43, 3.86), > = 5 female sexual partners (aOR = 3.81, 95%CI 1.81, 8.01), and psychological distress (aOR = 1.75, 95%CI 1.15, 2.67). SDU was associated with identifying as bisexual (aOR = 2.55, 95%CI 1.69, 3.86), > = 5 female sexual partners (aOR = 4.50, 95%CI 1.91, 10.59), and highest education achieved at 16 or lower (aOR = 2.46, 95%CI 1.24, 4.90). Conclusions: Some WSW may have negative experiences in relation to drug use and SDU. Harm reduction and health services that provide services for WSW should be aware of potentially compounding factors related to drug use, such as sexual assault and psychological distress, providing a safe and LGBT-friendly environment to discuss these issues

Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

With an incidence of ~1 in 800 births, Down syndrome (DS) is the most com- mon chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA 21 that directly contribute to cognitive de fi cits remain incompletely understood. Here, we found that the HSA21- encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued de fi cits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes