Does gender matter? A cross-national investigation of primary class-room discipline.

© 2018 Informa UK Limited, trading as Taylor & Francis GroupFewer than 15% of primary school teachers in both Germany and the UK are male. With the on-going international debate about educational performance highlighting the widening gender achievement gap between girl and boy pupils, the demand for more male teachers has become prevalent in educational discourse. Concerns have frequently been raised about the underachievement of boys, with claims that the lack of male ‘role models’ in schools has an adverse effect on boys’ academic motivation and engagement. Although previous research has examined ‘teaching’ as institutional talk, men’s linguistic behaviour in the classroom remains largely ignored, especially in regard to enacting discipline. Using empirical spoken data collected from four primary school classrooms in both the UK and in Germany, this paper examines the linguistic discipline strategies of eight male and eight female teachers using Interactional Sociolinguistics to address the question, does teacher gender matter?Peer reviewedFinal Accepted Versio

Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

Acknowledgments We are grateful to the Ian Fraser Cytometry Centre and our Mass Spetrometry and qPCR Facilities for help with the flow cytometry, glutathione and qRT-PCR assays, respectively. We also thank our many colleagues in the CRISP Consortium and in the medical mycology and systems biology communities for insightful discussions. Funding: This work was supported by the CRISP project (Combinatorial Responses In Stress Pathways), which was funded by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk): AJPB, KH, CG, ADM, NARG, MT, MCR. (Research Grants; BB/F00513X/1, BB/F005210/1-2). AJPB and JQ received additional support from the BBSRC (Research Grants; BB/K016393/1; BB/K017365/1). NARG and AJPB were also supported by the Wellcome Trust (www.wellcome.ac.uk), (Grants: 080088; 097377). AJPB was also supported by the European Research Council (http://erc.europa.eu/), (STRIFE Advanced Grant; ERC-2009-AdG-249793). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Mapping trends in insecticide resistance phenotypes in African malaria vectors

Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6,423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from the Anopheles gambiae complex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across sub-Saharan Africa from 2005 to 2017, with mean mortality following insecticide exposure declining from almost 100% to less than 30% in some areas, as well as substantial spatial variation in resistance trends

Adjuvant trastuzumab duration trials in HER2 positive breast cancer - what results would be practice-changing? Persephone investigator questionnaire prior to primary endpoint results.

Trastuzumab Duration questionnaire. The questionnaire that was completed by the oncologists. (PDF 476 kb

The development of a risk-adjustment strategy to benchmark emergency medical service (EMS) performance in relation to out-of-hospital cardiac arrest in Australia and New Zealand

Introduction: The aim of this study was to develop a risk adjustment strategy, including effect modifiers, for benchmarking emergency medical service (EMS) performance for out-of-hospital cardiac arrest (OHCA) in Australia and New Zealand. Method: Using 2017–2019 data from the Australasian Resuscitation Outcomes Consortium (Aus-ROC) OHCA Epistry, we included adults who received an EMS attempted resuscitation for a presumed medical OHCA. Logistic regression was applied to develop risk adjustment models for event survival (return of spontaneous circulation at hospital handover) and survival to hospital discharge/30 days. We examined potential effect modifiers, and assessed model discrimination and validity. Results: Both OHCA survival outcome models included EMS agency and the Utstein variables (age, sex, location of arrest, witnessed arrest, initial rhythm, bystander cardiopulmonary resuscitation, defibrillation prior to EMS arrival, and EMS response time). The model for event survival had good discrimination according to the concordance statistic (0.77) and explained 28% of the variation in survival. The corresponding figures for survival to hospital discharge/30 days were 0.87 and 49%. The addition of effect modifiers did little to improve the performance of either model. Conclusion: The development of risk adjustment models with good discrimination is an important step in benchmarking EMS performance for OHCA. The Utstein variables are important in risk-adjustment, but only explain a small proportion of the variation in survival. Further research is required to understand what factors contribute to the variation in survival between EMS

Trastuzumab-associated cardiac events in the Persephone trial.

BACKGROUND: We report cardiac events in the Persephone trial which compares 6-12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of 2500 patients, aged 22-82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04-1.90)), and not for 6-month patients (OR 1.28 (0.91-1.79)). CONCLUSIONS: We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care.National Institute of Health Research Health Technology Assessment (NIHR HTA) Programme UK. Funding reference number - 06/303/98This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/bjc.2016.35

Comparing Breast Cancer Multiparameter Tests in the OPTIMA Prelim Trial: No Test Is More Equal Than the Others

Background: Previous reports identifying discordance between multiparameter tests at the individual patient level have been largely attributed to methodological shortcomings of multiple in silico studies. Comparisons between tests, when performed using actual diagnostic assays, have been predicted to demonstrate high degrees of concordance. OPTIMA prelim compared predicted risk stratification and subtype classification of different multiparameter tests performed directly on the same population. Methods: Three hundred thirteen women with early breast cancer were randomized to standard (chemotherapy and endocrine therapy) or test-directed (chemotherapy if Oncotype DX recurrence score >25) treatment. Risk stratification was also determined with Prosigna (PAM50), MammaPrint, MammaTyper, NexCourse Breast (IHC4-AQUA), and conventional IHC4 (IHC4). Subtype classification was provided by Blueprint, MammaTyper, and Prosigna. Results: Oncotype DX predicted a higher proportion of tumors as low risk (82.1%, 95% confidence interval [CI] = 77.8% to 86.4%) than were predicted low/intermediate risk using Prosigna (65.5%, 95% CI = 60.1% to 70.9%), IHC4 (72.0%, 95% CI = 66.5% to 77.5%), MammaPrint (61.4%, 95% CI = 55.9% to 66.9%), or NexCourse Breast (61.6%, 95% CI = 55.8% to 67.4%). Strikingly, the five tests showed only modest agreement when dichotomizing results between high vs low/intermediate risk. Only 119 (39.4%) tumors were classified uniformly as either low/intermediate risk or high risk, and 183 (60.6%) were assigned to different risk categories by different tests, although 94 (31.1%) showed agreement between four of five tests. All three subtype tests assigned 59.5% to 62.4% of tumors to luminal A subtype, but only 121 (40.1%) were classified as luminal A by all three tests and only 58 (19.2%) were uniformly assigned as nonluminal A. Discordant subtyping was observed in 123 (40.7%) tumors. Conclusions: Existing evidence on the comparative prognostic information provided by different tests suggests that current multiparameter tests provide broadly equivalent risk information for the population of women with estrogen receptor (ER)–positive breast cancers. However, for the individual patient, tests may provide differing risk categorization and subtype information

Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Background: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings: A5164 was a randomized strategy trial of ‘‘early ART’’ - given within 14 days of starting acute OI treatment versus ‘‘deferred ART’’ - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) [greater than or equal to] 50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications

OPTIMA: A prospective randomized trial to validate the predictive utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in early breast cancer

Background: Multi-parameter gene expression assays (MPAs) are widely used to estimate individual patient residual risk in hormone-sensitive HER2-negative node-negative early breast cancer, allowing patients with low risk to safely avoid chemotherapy. Evidence for MPA use in node-positive breast cancer is limited. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) aims to validate MPA’s as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population