Let us now praise famous students: A qualitative study of high school students with learning disabilities

This study used qualitative methodology in order to gain understanding of the school lives of high school students with learning disabilities in the areas of reading and writing. Two resource room sections of students were observed, using methods of participant observation over a year long period and four case studies of students from these sections were conducted. Classroom work of all students was studied and special education files of those chosen as case studies were reviewed. Students and school personnel involved in the education of the students were interviewed. Research findings suggested that, despite years of intervention, high school students with learning disabilities in this study continued to have severe reading and writing difficulties. These difficulties pervaded their school lives, negatively impacting all academic areas, social interactions and personal development. Difficulties experienced by the students were exacerbated by issues involving ways in which their differences marginalized them, language development, academic disengagement, problems seeing relationships between actions and consequences, and limited expectations for their present and future lives

A rapid review of innovations for attraction, recruitment and retention of social care workers, and exploration of factors influencing turnover within the UK context

Context: The UK social care sector has come under increased pressure to combat workforce shortages. With international recruitment of professionals impacted by Brexit and the COVID-19 pandemic, social care is in need of innovations to attract, recruit and retain staff. Objectives: This review aimed to identify (1) innovations to attract, recruit, and retain social workers (professionals working with children and adults to protect them from harm, often as case managers) and the wider social care workforce (workers providing direct practical support to children and adults with their daily activities) and (2) factors influencing staff turnover in the UK context. Method: Pre-defined inclusion criteria were developed using the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) framework. Searches were conducted across three databases and 32 key United Kingdom third sector and government organisations from 2001. In total, 1,835 citations were retrieved and 40 met the eligibility criteria (13 for social workers and 28 for social care workforce). Thematic analysis was used to explore the data and presented across two evidence maps. Findings: Evaluation evidence was only available for a small portion of innovations identified. Practice learning, fast-track graduate programmes, and apprenticeships may support the retention of social workers, while pre-employment training, national recruitment campaigns, care work ambassadors, and values-based recruitment could help attraction, recruitment, and retention of the wider social care workforce. Limitations: Most of the included studies were conducted pre-pandemic and mainly relied on descriptive and explorative methodologies. Implications: Future policy initiatives should include an evaluation strategy from the outset to develop a more extensive evidence base. Funding bodies should offer schemes supporting research in this area

An inventory of supranational antimicrobial resistance surveillance networks involving low- and middle-income countries since 2000.

Low- and middle-income countries (LMICs) shoulder the bulk of the global burden of infectious diseases and drug resistance. We searched for supranational networks performing antimicrobial resistance (AMR) surveillance in LMICs and assessed their organization, methodology, impacts and challenges. Since 2000, 72 supranational networks for AMR surveillance in bacteria, fungi, HIV, TB and malaria have been created that have involved LMICs, of which 34 are ongoing. The median (range) duration of the networks was 6 years (1-70) and the number of LMICs included was 8 (1-67). Networks were categorized as WHO/governmental (n = 26), academic (n = 24) or pharma initiated (n = 22). Funding sources varied, with 30 networks receiving public or WHO funding, 25 corporate, 13 trust or foundation, and 4 funded from more than one source. The leading global programmes for drug resistance surveillance in TB, malaria and HIV gather data in LMICs through periodic active surveillance efforts or combined active and passive approaches. The biggest challenges faced by these networks has been achieving high coverage across LMICs and complying with the recommended frequency of reporting. Obtaining high quality, representative surveillance data in LMICs is challenging. Antibiotic resistance surveillance requires a level of laboratory infrastructure and training that is not widely available in LMICs. The nascent Global Antimicrobial Resistance Surveillance System (GLASS) aims to build up passive surveillance in all member states. Past experience suggests complementary active approaches may be needed in many LMICs if representative, clinically relevant, meaningful data are to be obtained. Maintaining an up-to-date registry of networks would promote a more coordinated approach to surveillance

A rapid review of innovations for attraction, recruitment and retention of social care workers, and exploration of factors influencing turnover within the UK context

Context: The UK social care sector has come under increased pressure to combat workforce shortages. With international recruitment of professionals impacted by Brexit and the COVID-19 pandemic, social care is in need of innovations to attract, recruit and retain staff. Objectives: This review aimed to identify (1) innovations to attract, recruit, and retain social workers (professionals working with children and adults to protect them from harm, often as case managers) and the wider social care workforce (workers providing direct practical support to children and adults with their daily activities) and (2) factors influencing staff turnover in the UK context. Method: Pre-defined inclusion criteria were developed using the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) framework. Searches were conducted across three databases and 32 key United Kingdom third sector and government organisations from 2001. In total, 1,835 citations were retrieved and 40 met the eligibility criteria (13 for social workers and 28 for social care workforce). Thematic analysis was used to explore the data and presented across two evidence maps. Findings: Evaluation evidence was only available for a small portion of innovations identified. Practice learning, fast-track graduate programmes, and apprenticeships may support the retention of social workers, while pre-employment training, national recruitment campaigns, care work ambassadors, and values-based recruitment could help attraction, recruitment, and retention of the wider social care workforce. Limitations: Most of the included studies were conducted pre-pandemic and mainly relied on descriptive and explorative methodologies. Implications: Future policy initiatives should include an evaluation strategy from the outset to develop a more extensive evidence base. Funding bodies should offer schemes supporting research in this area

Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis

ACKNOWLEDGMENTS We thank Karl Kuchler for the C. albicans superoxide dismutase mutants used in this study. This work was funded by a Medical Research Council Doctoral Training Program studentship to M.A.C.I.; Wellcome Trust Grants 089930 to J.Q., 080088 to A.J.P.B., and 097377 to J.Q., A.J.P.B., and L.P.E.; Biotechnology and Biological Sciences Research Council Grants BB/K016393/1 to J.Q. and BB/F00513X/1 and BB/K017365/1 to A.J.P.B.; European Research Council STRIFE Advanced Grant ERC-2009-AdG-249793 to A.J.P.B.; and Wellcome Trust and Royal Society Sir Henry Dale Fellowship 098375/Z/12/Z to K.J.W. and E.T. The funders had no role in study design, data collection, or interpretation or the decision to submit the work for publication.Peer reviewedPublisher PD

Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria.

Indirect clinical measures assessing anti-malarial drug transmission-blocking activity in falciparum malaria include measurement of the duration of gametocytaemia, the rate of gametocyte clearance or the area under the gametocytaemia-time curve (AUC). These may provide useful comparative information, but they underestimate dose-response relationships for transmission-blocking activity. Following 8-aminoquinoline administration P. falciparum gametocytes are sterilized within hours, whereas clearance from blood takes days. Gametocytaemia AUC and clearance times are determined predominantly by the more numerous female gametocytes, which are generally less drug sensitive than the minority male gametocytes, whereas transmission-blocking activity and thus infectivity is determined by the more sensitive male forms. In choosing doses of transmission-blocking drugs there is no substitute yet for mosquito-feeding studies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention