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Abstract Background Conduct disorders (CD) are among the most frequent psychiatric disorders in children and adolescents, with an estimated worldwide prevalence in the community of 2–4%. Evidence-based psychological outpatient treatment leads to significant improvement in about two-thirds of cases. However, there seems to be considerable variation in rates of CD diagnoses and implementation of evidence-based interventions between nations. The aim of this study was to compare administrative prevalence and treatment patterns for CD in children and adolescents seen in health care systems across four Western countries (Denmark, Germany, Norway, and the USA). Methods Cross-sectional observational study using healthcare data to identify children and adolescents (aged 0–19 years) with an ICD-10 code for CD within the calendar year 2018. Within each country’s study population, the prevalence of CD, psychiatric comorbidity, psychopharmacological treatment, and psychiatric hospitalisation was calculated. Results The prevalence of diagnosed CD differed 31-fold between countries: 0.1% (Denmark), 0.3% (Norway), 1.1% (USA) and 3.1% (Germany), with a male/female ratio of 2.0–2.5:1. The rate of psychiatric comorbidity ranged from 69.7 to 86.1%, with attention-deficit/hyperactivity disorder being most common. Between 4.0% (Germany) and 12.2% (USA) of youths with a CD diagnosis were prescribed antipsychotic medication, and 1.2% (Norway) to 12.5% (Germany) underwent psychiatric hospitalisation. Conclusion Recognition and characteristics of youths diagnosed with CD varied greatly by country. In some countries, the administrative prevalence of diagnosed CD was markedly lower than the average estimated worldwide prevalence. This variation might reflect country-specific differences in CD prevalence, referral thresholds for mental health care, diagnostic tradition, and international variation in service organisation, CD recognition, and availability of treatment offers for youths with CD. The rather high rates of antipsychotic prescription and hospitalisation in some countries are remarkable, due to the lack of evidence for these therapeutic approaches. These findings stress the need of prioritising evidence-based treatment options in CD. Future research should focus on possible reasons for inter-country variation in recognition and management of CD, and also address possible differences in patient-level outcomes.

Abstract Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are ‘fixed’ or ‘reversible’. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.

Abstract Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib’s efficacy in breast cancer models. Nine breast cancer patient–derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%–2.6% and 1.5%–2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

Abstract Background Social and economic costs associated with antisocial behaviour are well-established, but little is known about the potential costs savings/benefits of secure attachment in this high-risk group. We aimed to provide the first test of attachment quality as a distinct predictor of economic costs. Methods 111 adolescents (10–17 years of age, M = 15.0, SD = 1.6; 71% male) referred to young offender services due to high levels of antisocial behaviour were included. Costs were measured by detailed service-use interview, and attachment security to mother and father elicited through the Child Attachment Interview. The level of antisocial behaviour and callous-unemotional traits were assessed. Cost predictors were calculated using generalised linear models. Results Mean 12-months service costs were £5,368 (sd 5,769) per adolescent, with justice system and educational service costs being the main components. After adjusting for covariates, economic costs were predicted by attachment quality to fathers, with a difference of £2,655 per year between those with secure (£3,338) versus insecure attachment (£5,993); significant cost effects were not found for attachment quality to mothers. Higher levels of callous-unemotional traits, lower verbal IQ, higher levels of antisocial behaviour, and older age were also significant cost predictors. Conclusions Secure attachment to fathers is a predictor of reduced public cost in adolescents with severe antisocial behaviour. This novel finding for severely antisocial youth extends previous findings in less antisocial children and underscores the public health and policy benefits of good caregiving quality and the value of population-level dissemination of evidence-based interventions that improve caregiving quality.

Previous research has explored the importance of effective course advising to academic success. Course advising that is student-focused and takes a “whole-of-student” approach has been found to be especially important for students that have historically been minoritised in tertiary education. This includes students who are Indigenous, first-in-family, or from low socio-economic backgrounds. However, no research, to our knowledge, has investigated how Pacific students and staff envision course advising. Given Pacific students are among the fastest growing academic cohort in New Zealand and Australia, it is important for universities to understand how to foster Pacific student success. This research involved a series of talanoa (conversations) with both Pacific students and staff to better understand the current role of course advising in student decision-making, future hopes for the development of course advising, and suggestions to improve Pacific support in course advice. Understanding the perspective of Pacific students and staff helps to highlight the current gaps in course advising systems and encourages universities to acknowledge the importance of relationship building, the development of cultural competencies, and increasing Pacific representation in the course advising process. Results support reassessing course advising systems to help improve retention rates of Pacific students. ... How Can Course Advising Better Support Pacific Student Success? by Marea S. Colombo, Ruthie E. Holmes, Cameron D. Young & Stephen Scott is licensed under CC BY 4.0

Objectives Criminal offending and re-offending comes at a significant social and economic cost. Offending prevention therefore presents a high priority policy area. Low educational attainment is a known risk factor for offending, but little is understood about how changes in school performance over time might be associated with offending. Methods We investigated this in a large sample of n~4.3 million pupils using an administrative data linkage between two routinely-collected national datasets: the National Pupil Database (NPD) and the Police National Computer (PNC). First, we conducted growth mixture modelling using NPD data over three statutory testing years (School Years 2, 6 and 11). We then investigated the association between membership of these trajectories and subsequent conviction or caution for any criminal offence between Year 11 and age 21. Results We derived five school performance trajectories: (1) Average Consistent (n=3,497,167, 81.0%), (2) Average Increasing (n=66,383, 1.5%), (3) Average Declining (n=373,117, 8.6%), (4) Low Increasing (n=98,805, 2.3%), and (5) Low Consistent (n=281,964, 6.5%). The Average Declining group had the highest proportion of individuals who went on to be convicted or cautioned for any first offence up to age 21 (9.8%), followed by the Low Consistent (8.5%), Low Increasing (5.6%), Average Consistent (4.2%) and Average Increasing (1.5%) groups. Furthermore, as the number of offending days between Year 11 and age 21 increased (indicating repeat offending), the likelihood of having been in the Average Declining or Low Consistent groups also increased. We will also present findings from multilevel models accounting for school clustering, different offence types, and interactions. Conclusion Tentatively, findings suggest that changes in school performance could help to identify pupils who are struggling and at increased risk of criminal justice involvement, and therefore might be in need of additional support.

BackgroundThe HIV epidemic remains a major public health concern, particularly among youths living with HIV. While the availability of antiretroviral therapy has significantly improved the health outcomes of people living with HIV, there is growing evidence that youths living with HIV may be at increased risk of cardiovascular disease. However, the underlying mechanisms linking HIV and cardiovascular disease among youths living with HIV remain poorly understood. One potential explanation is that HIV-related biomarkers, including detectable viral load (VL) and low cluster of differentiation 4 (CD4) lymphocyte counts, may contribute to increased cardiovascular risk. Despite the potential importance of these biomarkers, the relationship between HIV-related biomarkers and cardiovascular risk among youths living with HIV has been understudied. ObjectiveTo address this gap, we examined whether detectable VL and low CD4 lymphocyte counts, both of which are indications of unsuppressed HIV, were associated with cardiovascular risk among youths living with HIV. MethodsWe analyzed electronic health record data from 7 adolescent HIV clinics in the United States (813 youths living with HIV). We used multivariable linear regression to examine the relationship between detectable VL and CD4 lymphocyte counts of ≤200 and cardiovascular risk scores, which were adapted from the gender-specific Framingham algorithm. ResultsIn our study, nearly half of the participants (366/766, 47.8%) had detectable VL, indicating unsuppressed HIV, while 8.6% (51/593) of them had CD4 lymphocyte counts of ≤200, suggesting weakened immune function. We found that those with CD4 lymphocyte counts of ≤200 had significantly higher cardiovascular risk, as assessed by Cardiac Risk Score2, than those with CD4 lymphocyte counts of >200 (P=.002). After adjusting for demographic and clinical factors, we found that for every 1000-point increase in VL copies/mL, the probability of having cardiovascular risk (Cardiac Risk Score2) increased by 38%. When measuring the strength of this connection, we observed a minor effect of VL on increased cardiovascular risk (β=.134, SE 0.014; P=.006). We obtained similar results with Cardiac Risk Score1, but the effect of CD4 lymphocyte counts of ≤200 was no longer significant. Overall, our findings suggest that detectable VL is associated with increased cardiovascular risk among youths living with HIV, and that CD4 lymphocyte counts may play a role in this relationship as well. ConclusionsOur study highlights a significant association between unsuppressed HIV, indicated by detectable VL, and increased cardiovascular risk in youths living with HIV. These findings emphasize the importance of implementing interventions that address both VL suppression and cardiovascular risk reduction in this population. By tailoring interventions to meet the unique needs of youths, we can promote overall well-being throughout the HIV care continuum and across the life span. Ultimately, these efforts have the potential to improve the health outcomes and quality of life of youths living with HIV. International Registered Report Identifier (IRRID)RR2-10.2196/11185

BackgroundDigital strategies and broadened eligibility criteria may optimize the enrollment of youth living with HIV in mobile health adaptive interventions. Prior research suggests that digital recruitment strategies are more efficient than traditional methods for overcoming enrollment challenges of youth living with HIV in the United States. ObjectiveThis study highlights the challenges and strategies that explain screening and enrollment milestones in a national web-based adherence protocol for youth living with HIV. MethodsBaseline data from a national web-based HIV adherence protocol for youth living with HIV, collected from July 2018 to February 2021, were analyzed. A centralized recruitment procedure was developed, which used web-based recruitment via Online Master Screener; paid targeted advertisements on social media platforms (eg, Facebook and Reddit) and geosocial networking dating apps (eg, Grindr and Jack’d); and site and provider referrals from Subject Recruitment Venues and other AIDS service organizations, website referrals, and text-in recruitment. ResultsA total of 3 distinct cohorts of youth living with HIV were identified, marked by changes in recruitment strategies. Overall, 3270 individuals consented to screening, 2721 completed screening, 581 were eligible, and 83 completed enrollment. We examined sociodemographic and behavioral differences in completing milestones from eligibility to full enrollment (ie, submitting antiretroviral therapy and viral load data and completing the baseline web-based survey). Those with the most recent viral load tests >6 months ago were half as likely to enroll (odds ratio 0.45, 95% CI 0.21-0.94). Moreover, eligible participants with self-reported antiretroviral therapy adherence (SRA) between 50% and 80% were statistically significant (P80%. ConclusionsThe findings add to our knowledge on the use of digital technologies for youth living with HIV before and during the COVID-19 pandemic and provide insight into the impact of expanding eligibility criteria on enrollment. As the COVID-19 pandemic continues and the use of and engagement with social media and dating apps among youth living with HIV changes, these platforms should continue to be investigated as potential recruitment tools. Using a wide variety of recruitment strategies such as using social media and dating apps as well as provider referral mechanisms, increasing compensation amounts, and including SRA in enrollment criteria should continue to be studied with respect to their ability to successfully recruit and enroll eligible participants. International Registered Report Identifier (IRRID)RR2-10.2196/11183

La teoría y la investigación sobre el apego se utilizan en muchos contextos aplicados, incluidos los juzgados de familia, pero hay malentendidos muy extendidos y que a veces dan lugar a aplicaciones erróneas. El objetivo de este documento de consenso es, por lo tanto, mejorar la comprensión, contrarrestar la desinformación y dirigir el uso de la teoría del apego por parte de los juzgados de familia en la dirección de un apoyo basado en la evidencia, especialmente en lo que respecta a la protección de niñas y niños y las decisiones sobre su custodia. El artículo se divide en dos partes. En la primera abordamos los problemas relacionados con el uso de la teoría y la investigación sobre apego en los juzgados de familia, analizando las causas de tales problemas. Para ello examinamos las aplicaciones de la teoría del apego en los juzgados de familia en el marco del concepto de interés superior de niños y niñas, analizamos los malentendidos relacionados con la teoría del apego e identificamos los factores que han obstaculizado su adecuada aplicación. En la segunda parte ofrecemos recomendaciones para la aplicación de la teoría y la investigación sobre apego. Para ello establecemos tres principios del apego: la necesidad de niñas y niños de cuidadoras y cuidadores habituales que no maltraten, el valor de la continuidad de cuidados de calidad suficientemente buena y los beneficios de las redes de relaciones de apego. También analizamos la idoneidad de las evaluaciones de los estilos de apego y del comportamiento de los cuidadores para fundamentar la toma de decisiones de los juzgados de familia. Llegamos a la conclusión de que las evaluaciones de quienes cuidan deberían ocupar un lugar central. Aunque no hay consenso entre nosotros sobre el uso de las evaluaciones del estilo de apego para fundamentar las decisiones sobre custodia y protección infantil, dichas evaluaciones son actualmente las más adecuadas para orientar y dirigir las intervenciones de apoyo. Por último, proporcionamos orientaciones para guiar la futura colaboración en la investigación interdisciplinaria.

Background: Looked-after children are at risk of suboptimal attachment patterns and reactive attachment disorder. However, access to interventions varies widely and there are no evidence-based interventions for this disorder. Objectives: (1) To adapt an existing video-feedback intervention to meet the specific needs of foster children in the UK with reactive attachment symptoms, (2) to conduct a case series to road-test the treatment manual and study procedures, (3) to conduct a scoping study of the key hurdles in a pilot trial and (4) to conduct a pilot randomised controlled trial of the adapted intervention to determine the feasibility of a future full-scale trial. Design: This was a mixed-methods study. The adapted treatment manual was developed with expert input and tested on a small case series. Qualitative interviews with key stakeholders were used in the scoping study in preparation for the trial and later with foster carers who received the new intervention. The final stage was a feasibility and pilot randomised controlled trial of the new intervention, compared with usual care. Researchers assessing the outcomes were blinded to group assignment. Setting: The study was set in outpatient child and adolescent mental health services and partner social services departments. Sites included urban and rural/semirural areas. Participants: Participants were foster carers with children aged ≤ 6 years presenting with difficulties in the domain of reactive attachment disorder. Key stakeholders included children’s services managers and mental health service practitioners in the scoping study. Foster carers who received the modified intervention participated in qualitative interviews. Intervention: The video-feedback intervention to promote positive parenting and sensitive discipline is an extensively evaluated and effective treatment approach. This intervention was modified (based on the adapted version for foster care in the Netherlands) to suit the needs of young children with reactive attachment symptoms in foster care in the UK and was delivered to improve the sensitive responding of foster carers, foster carer–child relationships and child outcomes. The modified intervention was delivered in-home by trained mental health professionals over a period of 4–6 months. Main outcome measure: The main outcome was reactive attachment symptom scores on the Disturbances of Attachment Interview. Results: A series of minor changes to the intervention programme were introduced, which focused on improving its suitability for the UK foster care context. Challenges in recruitment meant that, despite numerous modifications to the protocol and the inclusion of additional sites, only 30 families (target, n = 40) were recruited to the randomised controlled trial (15 allocated to each group). However, most other trial parameters were deemed feasible and acceptable, particularly the high levels of data and treatment completeness. All randomised families were available for baseline analyses, but two in the treatment arm were not available for post-treatment analyses. The revised intervention was positively received by practitioners and foster carers. Limitations: Only three-quarters of the target sample size was recruited. Furthermore, the sites’ own exclusion of potential participants and the low return rates of screening questionnaires raise the possibility of non-randomness of non-responses. Conclusion: A larger-scale trial may be feasible, but only if recruitment barriers can be overcome. Dedicated resources to support recruitment within local authorities and wider inclusion criteria are recommended. Central resourcing of intervention capacity to supplement NHS staff is also recommended. Trial registration: This trial is registered as ISRCTN18374094. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 35. See the NIHR Journals Library website for further project information.

BackgroundHIV mobile health (mHealth) interventions often incorporate interactive peer-to-peer features. The user-generated content (UGC) created by these features can offer valuable design insights by revealing what topics and life events are most salient for participants, which can serve as targets for subsequent interventions. However, unstructured, textual UGC can be difficult to analyze. Interpretive thematic analyses can preserve rich narratives and latent themes but are labor-intensive and therefore scale poorly. Natural language processing (NLP) methods scale more readily but often produce only coarse descriptive results. Recent calls to advance the field have emphasized the untapped potential of combined NLP and qualitative analyses toward advancing user attunement in next-generation mHealth. ObjectiveIn this proof-of-concept analysis, we gain human-centered design insights by applying hybrid consecutive NLP-qualitative methods to UGC from an HIV mHealth forum. MethodsUGC was extracted from Thrive With Me, a web app intervention for men living with HIV that includes an unstructured peer-to-peer support forum. In Python, topics were modeled by latent Dirichlet allocation. Rule-based sentiment analysis scored interactions by emotional valence. Using a novel ranking standard, the experientially richest and most emotionally polarized segments of UGC were condensed and then analyzed thematically in Dedoose. Design insights were then distilled from these themes. ResultsThe refined topic model detected K=3 topics: A: disease coping; B: social adversities; C: salutations and check-ins. Strong intratopic themes included HIV medication adherence, survivorship, and relationship challenges. Negative UGC often involved strong negative reactions to external media events. Positive UGC often focused on gratitude for survival, well-being, and fellow users’ support. ConclusionsWith routinization, hybrid NLP-qualitative methods may be viable to rapidly characterize UGC in mHealth environments. Design principles point toward opportunities to align mHealth intervention features with the organically occurring uses captured in these analyses, for example, by foregrounding inspiring personal narratives and expressions of gratitude, or de-emphasizing anger-inducing media.

Abstract Background Parenting programmes aim to alleviate behavioural problems in children, including conduct disorder. This study was part of a multi-phase mixed-methods project seeking to extend the reach of parenting programmes for the treatment of conduct problems through developing an evidence base to inform a personalised approach. It explored the narratives of parents of children with behavioural and conduct problems about parenting programmes to identify how such programmes could be personalised in order to extend their reach to parents and children who do not currently benefit. Methods Face-to-face semi-structured interviews with a purposive sample of 42 parents, who had different experiences of parenting programmes. Interviews were conversational and informed by a topic guide. Analysis of transcripts of audio-recorded interviews drew on inductive thematic approaches and was framed largely within a phenomenological perspective. Results Parents’ accounts demonstrated three themes: 1) a personalised approach needs to include the child; 2) a supportive school matters; and, 3) the programme needs to feel personal. Parents were more likely to have a positive experience at a parenting programme, and for their child to demonstrate positive behavioural changes, when they felt their concerns were validated within the group and they also felt supported by the child’s teachers. Parents whose children had been assessed prior to undertaking the programme were also more likely to perceive the programme to be beneficial, compared to parents who felt their child’s individual issues were never considered. Conclusions Our findings point to the potential for personalised approaches to extend the reach of parenting programmes to parents and children who do not currently benefit from such programmes. Important in personalising parenting programmes is assessing children before parents are referred, to directly work with children as well as parents, and to work collaboratively with parents and children to identify which families are most suited to group support or one-to-one support and how this may change depending on circumstances.

The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evaluating their potential anti-inflammatory activity. Fourteen chemical derivatives of carvone were synthesized, purified and their chemical structures confirmed. Noncytotoxic concentrations of the test compounds were selected based on the resazurin reduction assay. Among the tested compounds, four significantly reduced the lipopolysaccharides-induced protein levels of the inducible isoform of the nitric oxide synthase and nitric oxide production and showed a dual effect on pro-IL-1 protein levels in the Raw 264.7 cell line. The Ligand Express drug discovery platform was used to predict the targets of the test compounds, and an enrichment analysis was performed to group the different biological processes and molecular and cellular functions of the tested compounds. Moreover, Ligand Express also predicted that all chemicals evaluated have intestinal and blood–brain barrier permeability, do not inhibit P-gp and do not interact with major receptors. Although presenting anti-inflammatory and some advantageous ADME properties, the tested compounds still have low potency and specificity but may provide novel structures the further chemical modification of which may yield more promising drugs.

Background and objectives: Studies suggest that individual student-reported connection to school is associated with better mental health. However, there is less evidence for associations between schools’ overall school climate and the mental health of their students. This may reflect limitations in which mental health outcomes have been examined. We conducted a large longitudinal study in schools, hypothesising that we would find associations at both the student and school levels between student-reported positive school climate, and reduced student conduct and emotional problems and improved mental wellbeing. Methods: We tracked students in 20 English secondary schools from near the end of the first year of secondary school (age 11/12) over 3 years using reliable measures of school climate and mental health. Results: We found associations between student-level reports of positive school climate at baseline, and reduced conduct and emotional problems and better mental wellbeing at 3-year follow-up adjusting for various potential confounders. We also found some evidence of adjusted associations between baseline school-level measures of overall positive climate and better student mental health at follow-up. However, these student- and school-level associations reduced considerably when also adjusting for baseline mental health. Conclusions: Our findings suggest that there are associations between school climate and student mental health at both the student and school level but these associations are complex and not necessarily causal.

The timing of flowering plays a critical role in determining the productivity of agricultural crops. If the crops flower too early, the crop would mature before the end of the growing season, losing the opportunity to capture and use large amounts of light energy. If the crops flower too late, the crop may be killed by the change of seasons before it is ready to harvest. Maize flowering is one of the most important periods where even small amounts of stress can significantly alter yield. In this work, we developed and compared two methods for automatic tassel detection based on the imagery collected from an unmanned aerial vehicle, using deep learning models. The first approach was a customized framework for tassel detection based on convolutional neural network (TD-CNN). The other method was a state-of-the-art object detection technique of the faster region-based CNN (Faster R-CNN), serving as baseline detection accuracy. The evaluation criteria for tassel detection were customized to correctly reflect the needs of tassel detection in an agricultural setting. Although detecting thin tassels in the aerial imagery is challenging, our results showed promising accuracy: the TD-CNN had an F1 score of 95.9% and the Faster R-CNN had 97.9% F1 score. More CNN-based model structures can be investigated in the future for improved accuracy, speed, and generalizability on aerial-based tassel detection.

Background: Behaviour problems emerge early in childhood and place children at risk for later psychopathology. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. Design: A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. Setting: Health visiting services in six NHS trusts in England. Participants: A total of 300 at-risk children aged 12–36 months and their parents/caregivers. Interventions: Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. Main outcome measures: The primary outcome was the Preschool Parental Account of Children’s Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children’s Symptoms. Results: In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children’s Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen’s d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children’s conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval –1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval –0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval –0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval –0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval –0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children’s Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children’s Symptoms was 1.73 [95% confidence interval –0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval –0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval –0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval –0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval –0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval –0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children’s Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children’s Symptoms. Limitations: The proportion of participants with graduate-level qualifications was higher than among the general public. Conclusions: VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. Trial registration: Current Controlled Trials ISRCTN58327365. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

In the absence of empirical and conceptual considerations of the negotiation of leadership in teams doing community-based research, this article adds to the leadership literature by offering a critical reflection on positioning and collaborative teams in the context of one interdisciplinary, co-productive, cross-generational and international research project. The project focused on youth and community resilience to drought in South Africa. Fourteen co-researchers reflected on their experiences of leadership within the project, using a collectively developed questionnaire. Findings uniquely highlight wider ethical considerations when youth and novice researchers are included in research teams. A strong emphasis on cultural responsiveness was found; with local and culturally led leadership seen to positively influence both processes and outcomes. Reflections suggest collaboration may be approached as an “ethos” and aided by transformational leadership theories and methodologies. Findings may be especially relevant to research teams, funders, and ethical bodies.

The Plasmodium falciparum protein VAR2CSA allows infected erythrocytes to accumulate within the placenta, inducing pathology and poor birth outcomes. Multiple exposures to placental malaria (PM) induce partial immunity against VAR2CSA, making it a promising vaccine candidate. However, the extent to which VAR2CSA genetic diversity contributes to immune evasion and virulence remains poorly understood. The deep sequencing of the var2csa DBL3X domain in placental blood from forty-nine primigravid and multigravid women living in malaria-endemic western Kenya revealed numerous unique sequences within individuals in association with chronic PM but not gravidity. Additional analysis unveiled four distinct sequence types that were variably present in mixed proportions amongst the study population. An analysis of the abundance of each of these sequence types revealed that one was inversely related to infant gestational age, another was inversely related to placental parasitemia, and a third was associated with chronic PM. The categorization of women according to the type to which their dominant sequence belonged resulted in the segregation of types as a function of gravidity: two types predominated in multigravidae whereas the other two predominated in primigravidae. The univariate logistic regression analysis of sequence type dominance further revealed that gravidity, maternal age, placental parasitemia, and hemozoin burden (within maternal leukocytes), reported a lack of antimalarial drug use, and infant gestational age and birth weight influenced the odds of membership in one or more of these sequence predominance groups. Cumulatively, these results show that unique var2csa sequences differentially appear in women with different PM exposure histories and segregate to types independently associated with maternal factors, infection parameters, and birth outcomes. The association of some var2csa sequence types with indicators of pathogenesis should motivate vaccine efforts to further identify and target VAR2CSA epitopes associated with maternal morbidity and poor birth outcomes.

Background: The Systemic Therapy for At Risk Teens (START) trial is a randomised controlled trial of multisystemic therapy (MST) compared with management as usual (MAU). The present study reports on long-term follow-up of the trial (to 60 months). Objectives: The primary objective was to compare MST and MAU for the proportion of young people in each group with criminal convictions up to 60 months post baseline. Secondary outcomes included group comparisons of psychological and behavioural factors. An economic analysis was carried out to determine the cost-effectiveness of MST compared with MAU. Two qualitative studies were conducted to better understand the subjective experiences of the participants. Design: Primary outcomes (collected up to 60 months) were collected using a centralised police database. Secondary outcomes were evaluated using self-report questionnaires completed by both young people and parents or carers at the 24-, 36- and 48-month follow-ups. Research assistants were blind to treatment allocation. Setting: Participants were recruited from participating MST sites in nine areas of England. Secondary outcomes were typically collected within the family home. Participants: A total of 684 families were recruited into the START trial and allocated randomly to a treatment group. Of these, 487 remained in the second phase of the trial. Young people were aged, on average, 13.8 years at baseline, with 63% male and 37% female. Interventions: MST is a manualised programme for young people exhibiting antisocial behaviour and their families that uses principles from cognitive–behavioural and family therapy to provide an individualised approach. MAU content was not prespecified, but consisted of the standard care offered to young people who met eligibility for the trial. Main outcome measures: Young people’s offending was evaluated using the Police National Computer. Secondary measures included validated self-report measures completed by both the young person and their parent or carer. The economic evaluation took a broad perspective and outcomes were assessed in terms of quality-adjusted life-years and offending. Results: No significant differences were found in the proportion of offending between the groups (hazard ratio 1.03, 95% confidence interval 0.84 to 1.26; p = 0.78). No differences were found between the groups on secondary outcome measures, with a few exceptions that did not hold up consistently across the follow-up period. The economic analysis did not find evidence to support the cost-effectiveness of MST compared with MAU. Outcomes from the qualitative studies suggest that families mostly felt positive about MST, and that MST was associated with greater maturity in young men. Limitations: Some intended evaluations were not possible to deliver. Selective attrition may have influenced the nature of the sample size. It is also unclear how representative the MAU services were of reality. Future research: Recommendations are made for the evaluation of MST in populations with more severe behavioural problems, as well as for identifying and testing new moderators. Conclusions: The results of the second phase of the START trial do not support the long-term superiority of MST to MAU, but elements of the intervention may be adapted successfully. Trial registration: Current Controlled Trials ISRCTN77132214 and London South-East REC registration number 09/H1102/55. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 23. See the NIHR Journals Library website for further project information.

Background: We present a rare case of a dichorionic-diamniotic twin pregnancy in a noncommunicating rudimentary uterine horn diagnosed prior to rupture at 12 weeks of gestation. Case: A 33-year-old woman with history of two prior spontaneous abortions presented with a spontaneously conceived dichorionic-diamniotic twin pregnancy. Routine first-trimester screening ultrasound detected an extrauterine twin pregnancy. The patient was admitted for observation and treatment planning. Magnetic resonance imaging (MRI) of the pelvis led to the radiologic diagnosis of suspected abdominal ectopic pregnancy. Exploratory laparotomy led to an intraoperative diagnosis of twin pregnancy within a rudimentary uterine horn, which was removed without incident. Conclusion: This is a rare case of a twin pregnancy contained in a noncommunicating rudimentary uterine horn. The presence of this horn was not detected on ultrasonography or MRI. Keywords: Uterine horn, Mullerian anomaly, Ectopic pregnancy, Twin pregnancy, Ultrasound

Background: The children of parents with severe personality difficulties have greater risk of significant mental health problems. Existing care is poorly co-ordinated, with limited effectiveness. A specialised parenting intervention may improve child and parenting outcomes, reduce family morbidity and lower the service costs. Objectives: To develop a specialised parenting intervention for parents affected by severe personality difficulties who have children with mental health problems and to conduct a feasibility trial. Design: A pragmatic, mixed-methods design to develop and pilot a specialised parenting intervention, Helping Families Programme-Modified, and to conduct a randomised feasibility trial with process evaluation. Initial cost-effectiveness was assessed using UK NHS/Personal Social Services and societal perspectives, generating quality-adjusted life-years. Researchers collecting quantitative data were masked to participant allocation. Setting: Two NHS mental health trusts and concomitant children’s social care services. Participants: Parents who met the following criteria: (1) the primary caregiver of the index child, (2) aged 18–65 years, (3) have severe personality difficulties, (4) proficient in English and (5) capable of providing informed consent. Index children who met the following criteria: (1) aged 3–11 years, (2) living with index parent and (3) have significant emotional/behavioural difficulties. Exclusion criteria were (1) having coexisting psychosis, (2) participating in another parenting intervention, (3) receiving inpatient care, (4) having insufficient language/cognitive abilities, (5) having child developmental disorder, (6) care proceedings and (7) index child not residing with index parent. Intervention: The Helping Families Programme-Modified – a 16-session intervention using structured, goal-orientated strategies and collaborative therapeutic methods to improve parenting, and child and parent functioning. Usual care – standard care augmented by a single psychoeducational session. Main outcome measures: Trial feasibility – rates of recruitment, eligibility, allocation, retention, data completion and experience. Intervention acceptability – rates of acceptance, completion, alliance (Working Alliance Inventory-Short Revised) and experience. Outcomes – child (assessed via Concerns About My Child, Eyberg Child Behaviour Inventory, Child Behaviour Checklist-Internalising Scale), parenting (assessed via the Arnold-O’Leary Parenting Scale, Kansas Parental Satisfaction Scale), parent (assessed via the Symptom Checklist-27), and health economics (assessed via the Client Service Receipt Inventory, EuroQol-5 Dimensions). Results: The findings broadly supported trial feasibility using non-diagnostic screening criteria. Parents were mainly referred from one site (75.0%). Site and participant factors delayed recruitment. An estimate of eligible parents was not obtained. Of the 86 parents referred, 60 (69.7%) completed screening and 48 of these (80.0%) were recruited. Participants experienced significant disadvantage and multiple morbidity. The Helping Families Programme-Modified uptake (87.5%) was higher than usual-care uptake (62.5%). Trial retention (66.7%, 95% confidence interval 51.6% to 79.6%) exceeded the a priori rate. Process findings highlighted the impact of random allocation and the negative effects on retention. The Helping Families Programme-Modified was acceptable, with duration of delivery longer than planned, whereas the usual-care condition was less acceptable. At initial follow-up, effects on child and parenting outcomes were detected across both arms, with a potential outcome advantage for the Helping Families Programme-Modified (effect size range 0.0–1.3). For parental quality-adjusted life-years, the Helping Families Programme-Modified dominated usual care, and child quality-adjusted life-years resulted in higher costs and more quality-adjusted life-years. At second follow-up, the Helping Families Programme-Modified was associated with higher costs and more quality-adjusted life-years than usual care. For child quality-adjusted life-years, when controlled for baseline EuroQol-5 Dimensions, three-level version, usual care dominated the Helping Families Programme-Modified. No serious adverse events were reported. Conclusion: The Helping Families Programme-Modified is an acceptable specialised parenting intervention. Trial methods using non-diagnostic criteria were largely supported. For future work, a definitive efficacy trial should consider site selection, recruitment methods, intervention efficiency and revised comparator condition. Trial registration: Current Controlled Trials ISRCTN14573230. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 14. See the NIHR Journals Library website for further project information.

Success, progression and retention of students are goals of many university strategic directions and policies. For many decades it has been recognised that the greatest focus in any retention strategy should be on first-year students. University of Otago too has goals around student success. The Strategic Plan of the institution also identified that in the context of a fiscally constrained environment, all of our activities and processes need to be assessed for efficiency and effectiveness. To this end, a pilot was undertaken in one area of the university to identify possible indicators of first-year students’ non-engagement in the first semester and their possible impact on the first semester academic performance. The findings suggest that there are indeed some indicators that predict Grade Point Average at the end of the first semester.

The Helping Families Programme is a psychoeducational parenting intervention that aims to improve outcomes and engagement for parents affected by clinically significant personality difficulties. This is achieved by working collaboratively with parents to explore ways in which their emotional and relational difficulties impact on parenting and child functioning, and to identify meaningful and realistic goals for change. The intervention is delivered via one-to-one sessions at weekly intervals over a period of 16 weeks. This protocol describes a two-arm parallel RCT in which consenting parents are randomly allocated in a 1:1 ratio to either the Helping Families Programme plus the usual services that the parent may be receiving from their mental health and/or social care providers, or to standard care (usual services plus a brief parenting advice session). The primary clinical outcome will be child behaviour. Secondary clinical outcomes will be child and parental mental health, parenting satisfaction, parenting behaviour and therapeutic alliance. Health economic measures will be collected on quality of life and service use. Outcome measures will be collected at the initial assessment stage, after the intervention is completed and at 6-month follow-up by research staff blind to group allocation. Trial feasibility will be assessed using rates of trial participation at the three time points and intervention uptake, attendance and retention. A parallel process evaluation will use qualitative interviews to ascertain key-workers’ and parent participants' experiences of intervention delivery and trial participation. The results of this feasibility study will determine the appropriateness of proceeding to a full-scale trial.

Abstract Background Behavioural problems are common in early childhood, and can result in enduring costs to the individual and society, including an increased risk of mental and physical illness, criminality, educational failure and drug and alcohol misuse. Most previous research has examined the impact of interventions targeting older children when difficulties are more established and harder to change, and have rarely included fathers. We are conducting a trial of a psychological intervention delivered to families with very young children, engaging both parents where possible. Methods This study is a two-arm, parallel group, researcher-blind, randomized controlled trial, to test the clinical effectiveness and cost-effectiveness of a parenting intervention, Video Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) for parents of young children (12–36 months) at risk of behavioural difficulties. VIPP-SD is an evidence-based parenting intervention developed at Leiden University in the Netherlands which uses a video-feedback approach to support parents, particularly by enhancing parental sensitivity and sensitive discipline in caring for children. The trial will involve 300 families, who will be randomly allocated into either an intervention group, who will receive the video-feedback intervention (n = 150), or a control group, who will receive treatment as usual (n = 150). The trial will evaluate whether VIPP-SD, compared to treatment as usual, leads to lower levels of behavioural problems in young children who are at high risk of developing these difficulties. Assessments will be conducted at baseline, and 5 and 24 months post-randomization. The primary outcome measure is a modified version of the Preschool Parental Account of Child Symptoms (Pre-PACS), a structured clinical interview of behavioural symptoms. Secondary outcomes include caregiver-reported behavioural difficulties, parenting behaviours, parental sensitivity, parental mood and anxiety and parental relationship adjustment. An economic evaluation will also be carried out to assess the cost-effectiveness of the intervention compared to treatment as usual. Discussion If shown to be effective, the intervention could be delivered widely to parents and caregivers of young children at risk of behavioural problems as part of community based services. Trial registration ISRCTN Registry: ISRCTN58327365 . Registered 19 March 2015.

Abstract Background Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. Methods Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy. In vivo efficacy was tested both as a single agent and in combination therapy in TNBC patient-derived xenografts (PDXs). Results Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively). Conclusions Collectively, these findings strongly suggest that selinexor is a promising therapeutic agent for TNBC as a single agent and in combination with standard chemotherapy.

Abstract Background Bullying and cyberbullying are common phenomena in schools. These negative behaviours can have a significant impact on the health and particularly mental health of those involved in such behaviours, both as victims and as bullies. This UK study aims to investigate student-level and school-level characteristics of those who become involved in bullying and cyberbullying behaviours as victims or perpetrators. Methods We used data from 6667 Year 7 students from the baseline survey of a cluster randomized trial in 40 English schools to investigate the associations between individual-level and school-level variables with bullying victimization, cyberbullying perpetration, and cyberbullying victimization. We ran multilevel models to examine associations of bullying outcomes with individual-level variables and school-level variables. Results In multilevel models, at the school level, school type and school quality measures were associated with bullying risk: students in voluntary-aided schools were less likely to report bullying victimization (0.6 (0.4, 0.9) p = 0.008), and those in community (3.9 (1.5, 10.5) p = 0.007) and foundation (4.0 (1.6, 9.9) p = 0.003) schools were more likely to report being perpetrators of cyberbullying than students in mainstream academies. A school quality rating of “Good” was associated with greater reported bullying victimization (1.3 (1.02, 1.5) p = 0.03) compared to ratings of “Outstanding.” Conclusions Bullying victimization and cyberbullying prevalence vary across school type and school quality, supporting the hypothesis that organisational/management factors within the school may have an impact on students’ behaviour. These findings will inform future longitudinal research investigating which school factors and processes promote or prevent bullying and cyberbullying behaviours. Trial registration Trial ID: ISRCTN10751359 Registered: 11/03/2014 (retrospectively registered).

Background: Bullying, aggression and violence among children and young people are some of the most consequential public mental health problems. Objectives: The INCLUSIVE (initiating change locally in bullying and aggression through the school environment) trial evaluated the Learning Together intervention, which involved students in efforts to modify their school environment using restorative approaches and to develop social and emotional skills. We hypothesised that in schools receiving Learning Together there would be lower rates of self-reported bullying and perpetration of aggression and improved student biopsychosocial health at follow-up than in control schools. Design: INCLUSIVE was a cluster randomised trial with integral economic and process evaluations. Setting: Forty secondary schools in south-east England took part. Schools were randomly assigned to implement the Learning Together intervention over 3 years or to continue standard practice (controls). Participants: A total of 6667 (93.6%) students participated at baseline and 5960 (83.3%) students participated at final follow-up. No schools withdrew from the study. Intervention: Schools were provided with (1) a social and emotional curriculum, (2) all-staff training in restorative approaches, (3) an external facilitator to help convene an action group to revise rules and policies and to oversee intervention delivery and (4) information on local needs to inform decisions. Main outcome measures: Self-reported experience of bullying victimisation (Gatehouse Bullying Scale) and perpetration of aggression (Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale) measured at 36 months. Intention-to-treat analysis using longitudinal mixed-effects models. Results: Primary outcomes – Gatehouse Bullying Scale scores were significantly lower among intervention schools than among control schools at 36 months (adjusted mean difference –0.03, 95% confidence interval –0.06 to 0.00). There was no evidence of a difference in Edinburgh Study of Youth Transitions and Crime scores. Secondary outcomes – students in intervention schools had higher quality of life (adjusted mean difference 1.44, 95% confidence interval 0.07 to 2.17) and psychological well-being scores (adjusted mean difference 0.33, 95% confidence interval 0.00 to 0.66), lower psychological total difficulties (Strengths and Difficulties Questionnaire) score (adjusted mean difference –0.54, 95% confidence interval –0.83 to –0.25), and lower odds of having smoked (odds ratio 0.58, 95% confidence interval 0.43 to 0.80), drunk alcohol (odds ratio 0.72, 95% confidence interval 0.56 to 0.92), been offered or tried illicit drugs (odds ratio 0.51, 95% confidence interval 0.36 to 0.73) and been in contact with police in the previous 12 months (odds ratio 0.74, 95% confidence interval 0.56 to 0.97). The total numbers of reported serious adverse events were similar in each arm. There were no changes for staff outcomes. Process evaluation – fidelity was variable, with a reduction in year 3. Over half of the staff were aware that the school was taking steps to reduce bullying and aggression. Economic evaluation – mean (standard deviation) total education sector-related costs were £116 (£47) per pupil in the control arm compared with £163 (£69) in the intervention arm over the first two facilitated years, and £63 (£33) and £74 (£37) per pupil, respectively, in the final, unfacilitated, year. Overall, the intervention was associated with higher costs, but the mean gain in students’ health-related quality of life was slightly higher in the intervention arm. The incremental cost per quality-adjusted life year was £13,284 (95% confidence interval –£32,175 to £58,743) and £1875 (95% confidence interval –£12,945 to £16,695) at 2 and 3 years, respectively. Limitations: Our trial was carried out in urban and periurban settings in the counties around London. The large number of secondary outcomes investigated necessitated multiple statistical testing. Fidelity of implementation of Learning Together was variable. Conclusions: Learning Together is effective across a very broad range of key public health targets for adolescents. Future work: Further studies are required to assess refined versions of this intervention in other settings. Trial registration: Current Controlled Trials ISRCTN10751359. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 7, No. 18. See the NIHR Journals Library website for further project information. Additional funding was provided by the Educational Endowment Foundation.

Acute asthma or wheeze is a common presentation to emergency services for both adults and children. Although there are phenotypic differences between asthma syndromes, the management of acute symptoms follow similar lines. This article looks at the similarities and differences in approaches for children and adults. Some of these may be age dependent, such as the physiological parameters used to define the severity of the attack or the use of age appropriate inhaler devices. Other differences may reflect the availability of evidence. In other areas there is conflicting evidence between adult and pediatric studies such as a temporary increase in dose of inhaled corticosteroids during an acute attack. Overall there are more similarities than differences.

Abstract Background Systematic reviews suggest that multi-component interventions are effective in reducing bullying victimisation and perpetration. We are undertaking a phase III randomised trial of the INCLUSIVE multi-component intervention. This trial aims to assess the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying victimisation in English secondary schools. This paper updates the original trial protocol published in 2014 (Trials 15:381, 2014) and presents the changes in the process evaluation protocol and the secondary outcome data collection. Methods The methods are summarised as follows. Design: cluster randomised trial. Participants: 40 state secondary schools. Outcomes assessed among the cohort of students at the end of year 7 (n = 6667) at baseline. Intervention: INCLUSIVE is a multi-component school intervention including a social and emotional learning curriculum, changes to school environment (an action group comprising staff and students reviews local data on needs to review rules and policies and determine other local actions) and staff training in restorative practice. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third intervention year involving no external facilitation but all other elements. Comparator: normal practice. Outcomes: Primary: Two primary outcomes at student level assessed at baseline and at 36 months: 1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC) 2. Bullying and victimisation: Gatehouse Bullying Scale (GBS) Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. Sample size: 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level. Randomisation: eligible consenting schools were randomised stratified for single-sex versus mixed-sex schools, school-level deprivation and measures of school attainment. Discussion The trial involves independent research and intervention teams and is supervised by a Trial Steering Committee and a Data Monitoring Committee. Trial registration Current Controlled Trials, ISRCTN10751359 . Registered on 11 March 2014.

Mid- to late-season weeds that escape from the routine early-season weed management threaten agricultural production by creating a large number of seeds for several future growing seasons. Rapid and accurate detection of weed patches in field is the first step of site-specific weed management. In this study, object detection-based convolutional neural network models were trained and evaluated over low-altitude unmanned aerial vehicle (UAV) imagery for mid- to late-season weed detection in soybean fields. The performance of two object detection models, Faster RCNN and the Single Shot Detector (SSD), were evaluated and compared in terms of weed detection performance using mean Intersection over Union (IoU) and inference speed. It was found that the Faster RCNN model with 200 box proposals had similar good weed detection performance to the SSD model in terms of precision, recall, f1 score, and IoU, as well as a similar inference time. The precision, recall, f1 score and IoU were 0.65, 0.68, 0.66 and 0.85 for Faster RCNN with 200 proposals, and 0.66, 0.68, 0.67 and 0.84 for SSD, respectively. However, the optimal confidence threshold of the SSD model was found to be much lower than that of the Faster RCNN model, which indicated that SSD might have lower generalization performance than Faster RCNN for mid- to late-season weed detection in soybean fields using UAV imagery. The performance of the object detection model was also compared with patch-based CNN model. The Faster RCNN model yielded a better weed detection performance than the patch-based CNN with and without overlap. The inference time of Faster RCNN was similar to patch-based CNN without overlap, but significantly less than patch-based CNN with overlap. Hence, Faster RCNN was found to be the best model in terms of weed detection performance and inference time among the different models compared in this study. This work is important in understanding the potential and identifying the algorithms for an on-farm, near real-time weed detection and management.

Background: Child disruptive behavioural problems are a large and costly public health problem. The Incredible Years® (IY) parenting programme has been disseminated across the UK to prevent this problem and shown to be effective in several trials. It is vital for policy to know for which families IY is most effective, to be sure that it helps reduce, rather than widen, socioeconomic inequalities. Individual trials lack power and generalisability to examine differential effects; conventional meta-analysis lacks information about within-trial variability in effects. Objectives: To overcome these limitations by pooling individual-level data from the IY parenting trials in Europe to examine to what extent it benefits socially disadvantaged families. Secondary objectives examine (1) additional moderators of effects on child behaviour, (2) wider health benefits and potential harms and (3) costs, cost-effectiveness and potential long-term savings. Design: Individual participant data meta-analysis of 14 randomised trials of the IY parenting intervention. Settings: UK (eight trials), the Netherlands, Ireland, Norway, Sweden and Portugal. Participants: Data were from 1799 families, with children aged 2–10 years (mean 5.1 years; 63% boys). Interventions: IY Basic parenting programme. Main outcome measures: Primary outcome was disruptive child behaviour, determined by the Eyberg Child Behavior Inventory Intensity scale (ECBI-I). Secondary outcomes included self-reported parenting practices, parenting stress, mental health, children’s attention deficit hyperactivity disorder (ADHD) and emotional symptoms. Results: There were no differential effects of IY on disruptive behaviour in families with different levels of social/socioeconomic disadvantage or differential effects for ethnic minority families, families with different parenting styles, or for children with comorbid ADHD or emotional problems or of different ages. Some moderators were found: intervention effects were strongest in children with more severe baseline disruptive behaviour, in boys, and in children with parents who were more depressed. Wider health benefits included reduced child ADHD symptoms, greater parental use of praise, and reduced harsh and inconsistent discipline. The intervention did not improve parental depression, stress, self-efficacy or children’s emotional problems. Economic data were available for five UK and Ireland trials (maximum n = 608). The average cost per person of the IY intervention was £2414. The probability that the IY intervention is considered cost-effective is 99% at a willingness to pay of £145 per 1-point improvement on the ECBI-I. Estimated longer-term savings over 20 years range from £1000 to £8400 per child, probably offsetting the cost of the intervention. Limitations: Limitations include a focus on one parenting programme; the need to make assumptions in harmonising data; and the fact that data addressed equalities in the effectiveness of, not access to, the intervention. Conclusions: There is no evidence that the benefits of the IY parenting intervention are reduced in disadvantaged or minority families; benefits are greater in the most distressed families, including parents who are depressed. Thus, the intervention is unlikely to widen socioeconomic inequalities in disruptive behaviour and may have effects in narrowing inequalities due to parent depression. It was as likely to be effective for older as for younger children. It has wider benefits for ADHD and parenting and is likely to be considered to be cost-effective. Researchers/funders should encourage data sharing to test equity and other moderator questions for other interventions; further research is needed on enhancing equality of access to interventions. Funding: The National Institute for Health Research Public Health Research programme.

Success in the first year of higher education is important for students’ retention beyond their first year and for completion of their undergraduate degree. Institutions therefore typically front-load resources and interventions in the first year. One such intervention is the Peer Assisted Study Sessions (PASS) program. This program is known in the United States as Supplemental Instruction. It provides first-year students with an opportunity to learn study skills in the context of a particular unit of study (course/module). In this article, we consider the relationship between students’ prior academic achievement and participation in the PASS program, as well as the impact of participation on first-year students’ first-year grade point average, retention, and degree completion. The findings suggest that PASS does not just attract academically high-achieving students and that participation in it contributes to students’ academic achievement in their first year, retention beyond the first year, and completion of an undergraduate degree.

To achieve a clearer picture of injuries within Old Order Anabaptist communities, Purdue University’s Agricultural Safety and Health Program collaborated with the Young Center for Anabaptist and Pietist Studies at Elizabethtown College to conduct a pilot study on this topic. The team developed an injury surveillance system based not on traditional injury data sources and instruments but on data provided in Old Order-produced publications, specifically The Budget, Die Botschaft, and The Diary. While traditional surveillance methods have generally yielded injury data on less than 30 Old Order cases per year, the Old Order Injury Database, developed through the Purdue/Young Center collaboration, yielded data on 1,153 cases for the target year analyzed. While the primary focus of the study was farm-related injuries, it is believed that this type of surveillance system could be used by professionals in a variety of health-related fields to assist in gathering data and developing culturally appropriate interventions for Old Order groups.

Peer learning has long been recognised as an effective way to induct first-year students into the academic skills required to succeed at university. One recognised successful model that has been extensively researched is the Supplemental Instruction (SI) model; it has operated in the US since the mid-1970s. This model is commonly known in Australasia as the Peer Assisted Study Sessions (PASS) program. Although there is a considerable amount of research into SI and PASS, very little has been published about the impact of peer learning on different student groups, for example indigenous and other ethnic groups. This article reports on the results from one New Zealand university of the effectiveness of PASS for Māori and Pasifika students. The questions this article seeks to address are whether attendance of the PASS program results in better final marks for these two groups of students, and whether the number of sessions attended has an impact on the final marks.

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects (N=142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects’ ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects’ mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

BackgroundThe biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear.MethodsWe used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history.ResultsThe CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone.ConclusionsAdolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

The aim of this study was to investigate the effects of elevated donor HbA1c levels (type 2 diabetes, T2D) on the islet yield and functionality postisolation. In this retrospective analysis, donors for islet isolations were classified into two groups: T2D group (HbA1c ≥ 6.5%, n = 18) and normal group (HbA1c < 6.5%, n = 308). Optimum pancreas digestion time (switch time) was significantly higher in the T2D group compared to the normal group (13.7 ± 1.2 vs. 11.7 ± 0.1 min, respectively, p = 0.005). Islet yields were significantly lower in the T2D group compared to the control (T2D vs. control): islet equivalent (IEQ)/g (prepurification 2,318 ± 195 vs. 3,713 ± 114, p = 0.003; postpurification 1,735 ± 175 vs. 2,663 ± 89, p = 0.013) and islet particle number (IPN)/g (prepurification, 2,519 ± 336 vs. 4,433 ± 143, p = 0.001; postpurification, 1,760 ± 229 vs. 2,715 ± 85, p = 0.007). Islets from T2D pancreata had significantly lower viability (T2D vs. control: 91.9 ± 1.6 vs. 94.4 ± 0.3%, p = 0.004) and decreased oxygen consumption rate (DOCR) (T2D vs. control: 0.09 ± 0.01 and 0.21 ± 0.03 nmol O 2 100 islets −1 min −1 , p = 0.049). The islets isolated from T2D donor pancreata reversed diabetes in NOD-SCID mice in 9% (2/22) compared to islets from control donor pancreata, which reversed diabetes in 67% (175/260, p < 0.001). In conclusion, this study demonstrates that elevated HbA1c (≥6.5%) is associated with impairment of islet function and lower islet yield; however, these islets could not be suitable for clinical applications.

Background: Youth bullying and other aggressive behaviours are a major public health concern owing to their impact on adolescent physical and mental health and well-being. Whole-school restorative approaches have been identified as a promising method of addressing aggressive behaviour but there have been no randomised trials undertaken to examine their effects. Aim: To examine the feasibility and acceptability of implementing and trialling the INCLUSIVE (initiating change locally in bullying and aggression through the school environment) intervention in English secondary schools. Design: Cluster randomised controlled pilot trial in eight schools (1 : 1 computer-generated random allocation post baseline by a statistician blind to the identity of clusters) and process evaluation. Setting: Secondary schools in England (purposively sampled to ensure diversity). Participants: Year 8 students (aged 12–13 years), teachers, other school staff and intervention providers. Intervention: Whole-school restorative approach to address bullying and aggression, involving the following standard processes: school action group formation and external facilitation to review needs assessment data, identify priorities, and plan and monitor school-level actions; staff training in restorative practices; and a new social and emotional skills curriculum. Comparison group: Standard practice. Main outcome measures: (1) The primary outcome of interest was the feasibility and acceptability of delivering and trialling the intervention according to prespecified criteria; (2) process data were analysed to explore participants’ experiences of implementing and trialling the intervention and how these varied according to school context; and (3) indicative primary outcomes (aggressive behaviour measures), secondary outcomes, intermediate outcomes and economic evaluation methods were piloted. Data sources: Students (n = 1144 baseline; n = 1114 follow-up) and teachers (n = 387 baseline; n = 336 follow-up) were surveyed at the start and end of the 2011–12 academic year (baseline September 2011; follow-up June–July 2012). A total of 1017 students surveyed at baseline remained in the study at follow-up (89%). Other quantitative data were collected via intervention provider checklists (n = 4) and action group surveys (n = 44); qualitative data were collected via interviews (n = 34), focus groups (n = 20) and observations of action group meetings (n = 16). Results: (1) All prespecified feasibility and acceptability criteria were met. (2) Qualitative data indicated that all intervention components and the trial design were feasible and acceptable to students and staff, including in more disadvantaged school contexts. Qualitative data also suggested that student participation may be a core component in improving relationships and engagement across the school. The later-than-planned project start (July) and the timing of the baseline surveys (September), which needed to be completed pre allocation, caused delays in launching the intervention, staff training and other intervention outputs. (3) Three pilot primary outcomes were examined (completion rate at follow-up range: 91.7–94.2%) and the Gatehouse Bullying Scale and the Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale were acceptable, discriminating and reliable measures of bullying and aggression in this context. Our pilot economic analyses support the use of the Child Health Utility 9D scale with this population and the feasibility of cost–utility analysis, although this should be supplemented with a cost–consequence analysis. There was no evidence of harm. Conclusions: It is feasible and acceptable to implement and trial the INCLUSIVE intervention in English secondary schools, although a longer lead-in time is required to enable timely intervention outputs to occur. A Phase III cluster randomised controlled trial is required to examine the effectiveness and cost-effectiveness over a 3-year period of implementation for reducing aggressive behaviours, promoting mental health and well-being, and reducing health inequalities. Trial registration: Current Controlled Trials ISRCTN88527078. Funding: The National Institute for Health Research Health Technology Assessment programme (research), the Paul Hamlyn Foundation, the Big Lottery Fund and the Coutts Charitable Trust (intervention). The report will be published in full in Health Technology Assessment; Vol. 19, No. 53. See the NIHR Journals Library website for further project information.

Abstract Introduction This objective structured clinical exam (OSCE) involves a 5-minute patient encounter and aims to assess a trainees' ability to function as a first-responder in a non-medical setting. The target audience includes individuals who have received first-responder training, including medical students and emergency medical services professionals. Methods The OSCE encounter begins as the student enters the bedroom of a friend (standardized patient #1), who is found unconscious on the floor with a wound on her antecubital region, blood pooling on the floor, and a rolling chair next to her. The maid (standardized patient #2) joins the student in the room at a specified time. The student is expected to perform several critical actions, including assessing standardized patient #1's responsiveness, airway, breathing, and circulation as well as opening her airway, ensuring neck immobilization, managing her wound and fractured extremity, assessing her for other injuries, obtaining a relevant history, and communicating with emergency medical services personnel. Also included in this submission are three video standards of poor, good, and excellent performance in the OSCE, and completed grading checklists for these videos. Results The OSCE at our institution was run at the Clinical Skills Center in the fall of 2012, with all students in the first-year class participating (N = 42). The OSCE was successful in assessing student performance of the critical actions and highlighting areas that required emphasis and review for our students. Students generally gave positive feedback for the OSCE and requested that they be provided with more similar opportunities to practice their first-responder skills during the course of the year. Discussion We found that students had difficulty in remembering to do a jaw-thrust maneuver to open the patient's airway. The OSCE was meant to be formative for the students and to provide feedback on the course's efficacy to the course directors. The OSCE grade did not contribute to the students' overall medical school grades, although our OSCE checklist can easily be used as a grading tool as well.

Abstract Introduction This objective structured clinical examination (OSCE) involves a 5-minute patient encounter that aims to assess a trainees' basic resuscitation skills in responding to a patient with an un-witnessed collapse in an outpatient clinic setting. The target audience includes preclinical medical students, nursing students, junior resident physicians, and other trainees who have gone through first-responder and basic life support training. Methods The case involved a patient presenting to an outpatient clinic complaining of vague chest pain who collapsed while waiting to see the physician. The encounter began with the student entering the office and a “friend” (a standardized patient) informing him/her of the situation. The patient, “Mona,” was a mannequin on the ground. The student was expected to perform several critical actions, including assessing Mona's responsiveness, checking for a pulse, initiating and continuing chest compressions and mouth-to-mouth ventilation, calling for Emergency Medical Services (EMS) and an automated external defibrillator (AED), and communicating with EMS personnel. Timed cues are incorporated to provide a more structured flow to the case. Results The OSCE at our institution was run at the Clinical Skills Center in the spring of 2012 (n = 43) and 2013 (n = 38), with all first-year students participating. It was successful in assessing student performance of the critical actions, and highlighting areas that required emphasis and review. We found that students had the most difficulty remembering to check for a pulse prior to starting chest compressions (only 51.2% did this), open the airway using a jaw thrust (2.2%) rather than a head-tilt/chin-lift maneuver (74.4%), calling for an AED (37.2%), and the ratio of chest compressions to ventilations. Only 34.9% performed the correct number of chest compressions, while only 27.9% gave at least two breaths per cycle. Discussion The OSCE was meant to be formative for the students and to provide feedback on the course's efficacy for the course directors. The OSCE grade did not contribute to the students' overall medical school grades, although our OSCE checklist can easily be used as a grading tool as well.

Abstract This standardized patient case and its accompanying sequence of activities are intended to build skill among first-year medical students in recognizing patient clues and eliciting contextual information. Additional activities include a large-group introduction prior to the standardized patient encounter, a stimulated review of the standardized patient encounter, and a small-group reflection and discussion. The standardized patient case embeds three contextual themes (beliefs about treatment, stressful environment, and fear of what symptoms mean) that are each assigned a specific behavioral cue or clue. Standardized patients are trained to drop these clues and then to give further information only if the student interviewer follows up on the clue. Each theme is constructed to yield potentially meaningful differences in physician decision-making if the clue is or is not followed up on. Students and standardized patients then review the video independently and mark moments in the video that they feel represented clues and whether or not the clue was followed up on. Once the moments have been marked, the students view the video a second time to compare their own markings with those of the standardized patient. Lastly, the students meet in small groups with a faculty facilitator to share one exemplar moment and discuss with the group. Students indicated that the stimulated recall video review of their standardized patient encounter was the most effective activity for triggering reflection, followed by the small-group discussion and the review of the merged standardized patient bookmarks. Students felt that the activities were effective overall in promoting reflection on the relevance of context in the medical encounter.