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RecA-mediated homologous recombination (HR) is a key mechanism for genome maintenance and plasticity in bacteria. It proceeds through RecA assembly into a dynamic filament on ssDNA, the presynaptic filament, which mediates DNA homology search and ordered DNA strand exchange. Here, we combined structural, single molecule and biochemical approaches to characterize the ATP-dependent assembly mechanism of the presynaptic filament of RecA from Streptococcus pneumoniae (SpRecA), in comparison to the Escherichia coli RecA (EcRecA) paradigm. EcRecA polymerization on ssDNA is assisted by the Single-Stranded DNA Binding (SSB) protein, which unwinds ssDNA secondary structures that block EcRecA nucleofilament growth. We report by direct microscopic analysis of SpRecA filamentation on ssDNA that neither of the two paralogous pneumococcal SSBs could assist the extension of SpRecA nucleopolymers. Instead, we found that the conserved RadA helicase promotes SpRecA nucleofilamentation in an ATP-dependent manner. This allowed us to solve the atomic structure of such a long native SpRecA nucleopolymer by cryoEM stabilized with ATPγS. It was found to be equivalent to the crystal structure of the EcRecA filament with a marked difference in how RecA mediates nucleotide orientation in the stretched ssDNA. Then, our results show that SpRecA and EcRecA HR activities are different, in correlation with their distinct ATP-dependent ssDNA binding modes.

Initial and continuing teacher education are increasingly making use of remote and blended modes of education. Conducted in the summer of 2020 during the COVID-19 pandemic, this rapid review brings together literature and evidence to inform planning for remote and blended teacher education during restrictions in face-to-face teaching activity. The review consists of three main parts: first, a descriptive framework of modes of remote and blended teacher education; second, an exploratory review of the affordances and limitations of remote and blended approaches connecting the literature on effective teacher education with reviews of remote and blended approaches; third, a rapid review of evidence on the efficacy of remote and blended approaches, including of a small number of studies comparing these to face-to-face equivalents. We conclude that remote and blended teacher education is likely to become an increasingly important part of the teacher education landscape and there are plausible theoretical reasons suggesting that it can be effective with suitable design. However, we find too few studies presenting robust evidence to enable firm conclusions to be drawn on the relative effectiveness of modes and approaches. The review provides a foundation for further research and practice in this area.

ObjectiveThe effect of physical activity on the risk of developing knee osteoarthritis (OA) is unclear. We undertook this study to examine the relationship between recreational physical activity and incident knee OA outcomes using comparable physical activity and OA definitions.MethodsData were acquired from 6 global, community-based cohorts of participants with and those without knee OA. Eligible participants had no evidence of knee OA or rheumatoid arthritis at baseline. Participants were followed up for 5-12 years for incident outcomes including the following: 1) radiographic knee OA (Kellgren-Lawrence [K/L] grade ≥2), 2) painful radiographic knee OA (radiographic OA with knee pain), and 3) OA-related knee pain. Self-reported recreational physical activity included sports and walking/cycling activities and was quantified at baseline as metabolic equivalents of task (METs) in days per week. Risk ratios (RRs) were calculated and pooled using individual participant data meta-analysis. Secondary analysis assessed the association between physical activity, defined as time (hours per week) spent in recreational physical activity and incident knee OA outcomes.ResultsBased on a total of 5,065 participants, pooled RR estimates for the association of MET days per week with painful radiographic OA (RR 1.02 [95% confidence interval (95% CI) 0.93-1.12]), radiographic OA (RR 1.00 [95% CI 0.94-1.07]), and OA-related knee pain (RR 1.00 [95% CI 0.96-1.04]) were not significant. Similarly, the analysis of hours per week spent in physical activity also showed no significant associations with all outcomes.ConclusionOur findings suggest that whole-body, physiologic energy expenditure during recreational activities and time spent in physical activity were not associated with incident knee OA outcomes.

ObjectiveTo examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes.MethodsWe used longitudinal data from the Multicenter Osteoarthritis Study, a community-based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes.ResultsAmong the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16-3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87-5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit.ConclusionSubchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease.

ObjectivesTo examine whether foot and/or ankle pain increases the risk of knee OA.DesignWe utilised longitudinal data from the Multicentre Osteoarthritis Study (MOST); a community-based cohort of risk factors for knee OA. Participants without frequent knee pain (clinic visit only) and radiographic knee OA (RKOA) at baseline and, with no evidence of inflammatory musculoskeletal disease and a history of knee-related surgery were followed for up to 84-months for incident outcomes; i) RKOA (Kellgren-Lawrence (KL) ≥2), ii) symptomatic RKOA (RKOA and frequent pain in the same knee) and iii) frequent knee pain only. At baseline, ankle and foot symptoms were assessed, with knee radiographs and symptoms also assessed at 30, 60 and 84-months. Our exposures included baseline ankle, foot, and ankle and foot pain (participant-level). Associations between foot and/or ankle pain and incident outcomes were assessed using multiple logistic regression, with adjustment for participant characteristics and ankle/foot pain.ResultsNo statistically significant associations were observed between ankle, foot and, ankle and foot pain and incident RKOA, respectively. Ankle pain with (2.30, 95% CI 1.13 to 4.66) and without foot pain (OR: 2.53, 95% CI 1.34 to 4.80) were associated with increased odds of incident symptomatic RKOA and frequent knee pain. No statistically significant associations were observed between foot pain and these outcomes.ConclusionsAnkle pain should be a focus point, more so than foot pain, in the management of knee OA. Future studies should include additional ankle joint-specific symptom questions to better elucidate the knee OA biomechanical pathway.

ObjectiveUse of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA.MethodsWe used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren-Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW.ResultsOf 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = -0.042, 95% CI -0.08, -0.0004). No other associations were observed.ConclusionsIn current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

Replication studies in education are relatively rare. Of the few which are conducted, many are conceptual rather than direct replications. With so few replication studies, and many of those that are attempted producing null results, the scientific status of the evidence base for educational policy and practice is in question. Replicating Makel and Plucker's review of the education replication literature, conducted in 2014, this paper presents a mapping review looking at rates of replication in education research from 2011 to 2020. We provide an overview of the number of replication studies by replication type, year, outcome, authorship, and journal. Our results are consistent with those of Makel and Plucker, revealing very low but gradually increasing rates of replication study in education. We discuss the role of replication in producing a robust and trustworthy evidence base for policy and practice, and some of the challenges in operationalising definitions of replication we encountered.

ObjectiveWith adults working to older ages, occupation is an important, yet less modifiable domain of physical activity to consider in the risk of knee osteoarthritis (OA). This study aimed to investigate the association between predominant lifetime occupation and prevalent knee OA.DesignParticipant-level data were used from five international community-based cohorts: Johnston County Osteoarthritis Project, the Hertfordshire Cohort Study, the Multicenter Osteoarthritis Study, the Tasmanian Cohort Study and Framingham Osteoarthritis Study. Self-reported predominant occupation was categorized into sedentary, light, light manual and heavy manual levels. Cross-sectional associations between predominant lifetime occupation and knee OA outcomes including prevalence of radiographic knee OA (RKOA), symptomatic RKOA and knee pain, were assessed using logistic regression, accounting for cohort clustering.ResultsData for 7391 participants were included. 24.7% reported sedentary lifetime occupation, 30.0% light, 35.9% light manual and 9.4% heavy manual. 43.3% presented with RKOA, 52.1% with knee pain and 29.0% with symptomatic RKOA. There was over a two-fold increase in the odds of having RKOA, knee pain and symptomatic RKOA in those whose with heavy manual compared to sedentary occupations ((odds ratio (OR): 2.14; 95% confidence interval (CI): 1.79, 2.58), (OR: 2.19; 95% CI: 1.78, 2.70), (OR: 2.41; 95% CI: 1.94, 2.99) respectively).ConclusionThis large international multi-cohort study demonstrated an association of heavy manual work with RKOA, symptomatic RKOA and knee pain. Measures that protect workers and are designed to reduce heavy manual related activities remain a priority to reduce the risk of knee OA.

ObjectivesTo examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults.MethodsWe used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations).ResultsHeavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression.ConclusionHeavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

Feedback is an integral part of education and there is a substantial body of trials exploring and confirming its effect on learning. This evidence base comes mostly from studies of compulsory school age children; there is very little evidence to support effective feedback practice at higher education, beyond the frameworks and strategies advocated by those claiming expertise in the area. This systematic review aims to address this gap. We review causal evidence from trials of feedback and formative assessment in higher education. Although the evidence base is currently limited, our results suggest that low stakes-quizzing is a particularly powerful approach and that there are benefits for forms of peer and tutor feedback, although these depend on implementation factors. There was mixed evidence for praise, grading and technology-based feedback. We organise our findings into several evidence-grounded categories and discuss the next steps for the field and evidence-informed feedback practice in universities.

A significant proportion of pupils move school during their school career for reasons other than standard structural moves between educational stages. Little is known about the underlying causes of these moves and the characteristics and experiences of mobile pupils are challenging to research. There is currently a large disconnect between the macro level of system structures, data and policy and the individual experiences and journeys of mobile pupils. This article brings together international literature around school mobility and mobile pupils, with analyses of the English National Pupil Database (NPD), tracking a cohort from age 5 to 16, to better understand when school moves occur and the characteristics of mobile pupils. Findings reveal a sizable underlying rate of moves in England of about 1.5-2% per term and identify differences in mobility related to disadvantage, school phase, ethnic group and SEND status. The predictive power of the data, however, is low, highlighting the need for more research, policy and practice in this area to better understand individual mobility circumstances. By bringing together the literature and the data, the article concludes with a discussion of what is known about school mobility and recommends further areas for research into the characteristics, experiences and outcomes of mobile school pupils.

This paper presents findings from an exploratory review of the literature on school approaches and current issues within European schools in relation to migrant children with Special Educational Needs (SEN). 13 papers were identified and analysed and three key 'journeys' reflecting the developing and negotiated nature of family and school experiences and practices were identified: the family journey, the school journey and the journey into SEN. The findings emphasise the importance of professionals acknowledging cultural and individual diversity, not only by considering the cultural backgrounds of migrants, but also by critically understanding their own cultural framework and how they use it in their work with families. The review provides a useful reference for future research in this area and for professionals working with diverse communities, by highlighting common practices to be aware of, and by providing evidence that more training is needed of school staff in how to manage and understand migration and diversity in relation to children with SEN.

Policy reform around the globe has increased the autonomy that schools enjoy in spending on resources. This reform assumes that schools face strong incentives to use their resources to maximise pupil attainment and that they know best how to spend their money to achieve this aim. This study provides evidence of the relationship between governance and how schools choose to spend their money. It uses data for all state-funded secondary schools in England for the academic years 2009/10, 2011/12 and 2015/16. This enables a comparison of schools operating under three forms of governance: local authority maintained schools (LAMs); schools operated as a single 'academy' trust outside local authority control (SATs); or those in a network of academy schools governed by a multi-academy trust (MATs). The data provide no support for claims that academy schools will spend less on administration or that networks of schools will enjoy economies of scale. The data do show that academy schools spent proportionately less on teacher salaries and educational support, and more on back office costs, after taking account of pupil characteristics.

Objectives: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis. Methods: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.1 (>7000 SOMAmers/proteins). An optimised approach to standardisation was developed. Technical confounders and batch-effects were identified and adjusted for. Poorly performing SOMAmers and samples were excluded. Variance in the data was determined by principal component (PC) analysis. Results: A synovial fluid standardised protocol was optimised that had good reliability (<20% co-efficient of variation for >80% of SOMAmers in pooled samples) and overall good correlation with immunoassay. 1720 samples and >6290 SOMAmers met inclusion criteria. 48% of data variance (PC1) was strongly correlated with individual SOMAmer signal intensities, particularly with low abundance proteins (median correlation coefficient 0.70), and was enriched for nuclear and non-secreted proteins. We concluded that this component was predominantly intracellular proteins, and could be adjusted for using an 'intracellular protein score' (IPS). PC2 (7% variance) was attributable to processing batch and was batch-corrected by ComBat. Lesser effects were attributed to other technical confounders. Data visualisation revealed clustering of injury and OA cases in overlapping but distinguishable areas of high-dimensional proteomic space. Conclusions: We have developed a robust method for analysing synovial fluid protein, creating a molecular and clinical dataset of unprecedented scale to explore potential patient subtypes and the molecular pathogenesis of OA. Such methodology underpins the development of new approaches to tackle this disease which remains a huge societal challenge. [ABSTRACT FROM AUTHOR]

The authors report outcomes of an evaluation of a 'video club' intervention to improve the feedback and dialogic teaching practice of 91 teachers from 11 primary schools in England. Participating teachers worked collaboratively in a sequence of six video clubs over a six-month period. To understand teacher engagement they examine videos of video club meetings; online platform use metrics; surveys; selected videos of classroom practice; focus groups; and interviews. They evaluate change in teachers' thinking and practice using survey results for participants compared to a comparison group of non-participating teachers at the intervention schools. The survey includes a new instrument for gathering evidence of teachers' thinking and practice in feedback. The results suggested changes in thinking and practice for teachers who self-reported as engaging highly with the intervention. They conclude by discussing the potential of video technology within professional development and the challenges of researching changes in thinking and practice.

In the outer space down to the altitudes routinely flown by the larger commercial aircrafts, radiation is a serious problem for the microelectronics circuits. The 88-Inch Cyclotron at Lawrence Berkeley National Laboratory is a sector-focused cyclotron and is the home of the Berkeley Accelerator Space Effects Facility, where the effects of energetic particles on sensitive microelectronics are studied with the goal of designing electronic systems for the space community. The paper will describe the flexibility of the facility and its capabilities for testing the bombardment of the electronics by heavy ions, light ions, and neutrons.

A compositional effect is when pupil attainment is associated with the characteristics of their peers, over and above their own individual characteristics. Pupils at academically selective schools, for example, tend to out-perform similar-ability pupils who are educated with mixed-ability peers. Previous methodological studies however have shown that 'phantom' compositional effects can arise purely from measurement error. Through simulations using English National Pupil Database data, this paper demonstrates that moderate rates of measurement error in baseline scores can produce a systemic bias in value-added ('Progress') scores that favours higher ability pupils. This bias is large enough to explain the ostensibly superior performance of selective 'grammar' schools that is seen in the English data and create an appreciable bias across the school performance distribution. This paper describes how such biases can arise from 'regression attenuation' and discusses the more general methodological implications of the results. The paper concludes that the consequences of baseline measurement error on school value-added scores is greatly mitigated by controls for school-level prior attainment, but that the English 'Progress' value-added measures, as they do not control for prior attainment at school-level, are seriously biased and that the observed 'grammar school effect' is likely to be largely or wholly spurious.

This study examines parental choice preferences following the introduction of the Free Schools policy in England. It reports on two phases of data collection: first, the analysis of factors that Free School and non-Free School parents reported as important in informing their choices; and, second, findings from semi-structured interviews with parents of children attending a Free School. The findings show that Free School parents' choices were mostly influenced by similar factors to those of parents elsewhere. There were, however, some notable exceptions, particularly in relation to school size, ethos and curriculum. The analyses also highlight how the lack of information available led parents to use proxies to assess potential academic quality and school suitability for their child. The tensions that exist for parents in exercising choice within this new context and the implications for school intakes and diversity within the system are discussed.

Background: Personal protective equipment (PPE) is an essential component of safely treating suspected or confirmed SARS-CoV-2 patients. PPE acts as a barrier to heat loss, therefore increasing the risk of thermal strain which may impact on cognitive function. Healthcare workers (HCWs) need to be able to prioritize and execute complex tasks effectively to ensure patient safety. This study evaluated pre-cooling and per-cooling methods on thermal strain, thermal comfort and cognitive function during simulated emergency management of an acutely unwell patient.Methods: This randomized controlled crossover trial was run at the Clinical Services Department of the Medical Research Unit The Gambia. Each participant attended two sessions (Cool and Control) in standard PPE. Cool involved pre-cooling with an ice slurry ingestion and per-cooling by wearing an ice-vest external to PPE.Results: Twelve participants completed both sessions. There was a significant increase in tympanic temperature in Control sessions at both 1 and 2 h in PPE (p = 0.01). No significant increase was seen during Cool. Effect estimate of Cool was −0.2°C (95% CI −0.43; 0.01, p = 0.06) post 1 h and −0.28°C (95% CI −0.57; 0.02, p = 0.06) post 2 h on tympanic temperature. Cool improved thermal comfort (p < 0.001), thermal sensation (p < 0.001), and thirst (p = 0.04). No difference on cognitive function was demonstrated using multilevel modeling.Discussion: Thermal strain in HCWs wearing PPE can be safely reduced using pre- and per-cooling methods external to PPE.