Validation of the Wider Outcomes Survey for Teachers (WOST): a measure for assessing the behaviour, relationships and exposure to bullying of children and young people with special educational needs and disabilities (SEND)

The Wider Outcomes Survey for Teachers (WOST) is a teacher informant-report questionnaire developed to aid the assessment of behaviour difficulties, quality of relationships and exposure to bullying among students identified with special educational needs and disabilities (SEND). This study examines the psychometric properties of the WOST in a validation sample representing 6164 students with SEND (mean age 12 years) drawn from 481 primary and secondary schools across England. Results showed favourable internal consistency using Cronbach's alpha and acceptable model fit using confirmatory factor analysis, both of which were invariant to broad categorisations of SEND. Practical utility and construct validity were also established by testing two theoretically derived hypotheses. The measure is therefore tentatively supported as a useful tool for assessing the wider outcomes of students with SEND

An Intervention for Pulmonary Rehabilitators to Develop a Social Identity for Patients Attending Exercise Rehabilitation: A Feasibility and Pilot Randomised Control Trial Protocol

Background: Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators practice. This study aims to pilot and feasibly explore a social identity group- management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. Methods: This is a two center, randomized cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre and post exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants’ contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. Discussion: This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention’s effectiveness for improving HRQoL for COPD patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02288039. Date 31st October 2014

Emotional self-efficacy, conduct problems, and academic attainment: Developmental cascade effects in early adolescence

The study is amongst the first of its kind to utilise developmental cascade modelling in order to examine the inter-relations between emotional self-efficacy, conduct problems, and attainment in a large, nationally representative sample of English adolescents (n = 2,414, aged 11 years). Using a 3-wave, longitudinal, cross lagged-design, we tested three cascading hypotheses: adjustment erosion, adjustment fortification, and academic incompetence. A fourth hypothesis considered the role of shared risk. Results supported small effects consistent with the cascade hypotheses, and a small but significant effect was found for shared risk. Strengths and limits of the study are considered alongside a discussion of the implications for these findings

The impact of trial stage, developer involvement and international transferability on universal social and emotional learning programme outcomes: a meta-analysis

This study expands upon the extant prior meta-analytic literature by exploring previously theorised reasons for the failure of schoolbased, universal social and emotional learning (SEL) programmes to produce expected results. Eighty-nine studies reporting the effects of school-based, universal SEL programmes were examined for differential effects on the basis of: (1) stage of evaluation (efficacy or effectiveness); (2) involvement from the programme developer in the evaluation (led, involved, independent); and (3) whether the programme was implemented in its country of origin (home or away). A range of outcomes were assessed including: social-emotional competence, attitudes towards self, pro-social behaviour, conduct problems, emotional distress, academic achievement and emotional competence. Differential gains across all three factors were shown, although not always in the direction hypothesised. The findings from the current study demonstrate a revised and more complex relationship between identified factors and dictate major new directions for the field

Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis

Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity

African sleeping sickness is a disease found in sub-Saharan Africa that is caused by the single-celled parasite Trypanosoma brucei. The drugs used widely now to treat infections are 50 years old and notable for their toxicity, emphasizing the need for development of new therapeutics. In the search for potential drug targets, researchers typically focus on enzymes or proteins that are essential to the survival of the infectious agent while being distinct enough from the host to avoid accidental targeting of the host enzyme. This work describes our research on one such trypanosome enzyme, hexokinase, which is a protein that the parasite requires to make energy. Here we describe the results of our search for inhibitors of the parasite enzyme. By screening 220,223 compounds for anti-hexokinase activity, we have identified new inhibitors of the parasite enzyme. Some of these are toxic to trypanosomes while having no effect on mammalian cells, suggesting that they may hold promise for the development of new anti-parasitic compounds

Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream

The Good Behaviour Game intervention to improve behavioural and other outcomes for children aged 7–8 years: a cluster RCT

Background Universal, school-based behaviour management interventions can produce meaningful improvements in children’s behaviour and other outcomes. However, the UK evidence base for these remains limited.Objective The objective of this trial was to investigate the impact, value for money and longer-term outcomes of the Good Behaviour Game. Study hypotheses centred on immediate impact (hypothesis 1); subgroup effects (at-risk boys, hypothesis 2); implementation effects (dosage, hypothesis 3); maintenance/sleeper effects (12- and 24-month post-intervention follow-ups, hypothesis 4); the temporal association between mental health and academic attainment (hypothesis 5); and the health economic impact of the Good Behaviour Game (hypothesis 6). Design This was a two-group, parallel, cluster-randomised controlled trial. Primary schools (n = 77) were randomly assigned to implement the Good Behaviour Game for 2 years or continue their usual practice, after which there was a 2-year follow-up period. Setting The trial was set in primary schools across 23 local authorities in England. Participants Participants were children (n= 3084) aged 7–8 years attending participating schools. Intervention The Good Behaviour Game is a universal behaviour management intervention. Its core components are classroom rules, team membership, monitoring behaviour and positive reinforcement. It is played alongside a normal classroom activity for a set time, during which children work in teams to win the game to access the agreed rewards. The Good Behaviour Game is a manualised intervention delivered by teachers who receive initial training and ongoing coaching. Main outcome measures The measures were conduct problems (primary outcome; teacher-rated Strengths and Difficulties Questionnaire scores); emotional symptoms (teacher-rated Strengths and Difficulties Questionnaire scores); psychological well-being, peer and social support, bullying (i.e. social acceptance) and school environment (self-report Kidscreen survey results); and school absence and exclusion from school (measured using National Pupil Database records). Measures of academic attainment (reading, standardised tests), disruptive behaviour, concentration problems and prosocial behaviour (Teacher Observation of Child Adaptation Checklist scores) were also collected during the 2-year follow-up period. Results There was no evidence that the Good Behaviour Game improved any outcomes (hypothesis 1). The only significant subgroup moderator effect identified was contrary to expectations: at-risk boys in Good Behaviour Game schools reported higher rates of bullying (hypothesis 2). The moderating effect of the amount of time spent playing the Good Behaviour Game was unclear; in the context of both moderate (≥ 1030 minutes over 2 years) and high (≥ 1348 minutes over 2 years) intervention compliance, there were significant reductions in children’s psychological well-being, but also significant reductions in their school absence (hypothesis 3). The only medium-term intervention effect was for peer and social support at 24 months, but this was in a negative direction (hypothesis 4). After disaggregating within- and between-individual effects, we found no temporal within-individual associations between children’s mental health and their academic attainment (hypothesis 5). Last, our cost–consequences analysis indicated that the Good Behaviour Game does not provide value for money (hypothesis 6).Limitations Limitations included the post-test-only design for several secondary outcomes; suboptimal implementation dosage (mitigated by complier-average causal effect estimation); and moderate child-level attrition (18.5% for the primary outcome analysis), particularly in the post-trial follow-up period (mitigated by the use of full information maximum likelihood procedures). Future work Questions remain regarding programme differentiation (e.g. how distinct is the Good Behaviour Game from existing behaviour management practices, and does this makes a difference in terms of its impact?) and if the Good Behaviour Game is impactful when combined with a complementary preventative intervention (as has been the case in several earlier trials).Conclusion The Good Behaviour Game cannot be recommended based on the findings reported here. Trial registration This trial is registered as ISRCTN64152096. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 7. See the NIHR Journals Library website for further project information

Coaching Models of School-Based Prevention and Promotion Programmes: A Qualitative Exploration of UK Teachers' Perceptions

There has been increased interest in recent years regarding the utility of imported universal prevention and promotion (P&P) programmes in UK schools, many of which have a coaching model attached. However, there have been relatively few studies exploring the cultural transferability and social validity of these models, even though evidence suggests that these factors are important to the successful implementation of the programmes, and thus the achievement of the intended outcomes. The aim of the current study was to explore the coaching practices that teachers report experiencing, and to further understanding of the perceived benefts of these coaching practices to teachers. The sample consisted of 33 teachers implementing one of two universal, school-based P&P programmes, Good Behavior Game and Promoting Alternative Thinking Strategies as part of large-scale, randomised controlled trials. Qualitative, semi-structured interviews were conducted, and data were analysed thematically utilising a hybrid approach. Teachers typically reported engaging in six distinct practices with their coaches. While the majority of these practices were in line with coaching literature, there were some discrepancies between intended coaching practices and teachers’ reports. The coaching practices were generally perceived to be acceptable to teachers. Two unanticipated practices, validation and motivation, appeared to be of particular value to teachers, although these are not currently a prominent feature in existing coaching models. The fndings provide implications for improving the development of socially valid coaching models for UK schools