The role and influence of "Champions" in a community-based lifestyle risk modification programme

This article describes the training and implementation of the Waist Disposal Challenge in service clubs in Western Australia in 2009–2010. Ninety-three Champions from 52 clubs were trained to deliver educational presentations to 1100 peers and facilitate a BMI competition among 764 peers. Champions reported significant improvements in their knowledge and confidence to motivate their peers to make changes to their diet and physical activity with 82% of participants completing the BMI competition and on average 58% experiencing and sustaining a BMI reduction for 12 months. It is evident that the Champions had influenced the uptake and success of the intervention

13.9% efficiency ternary nonfullerene organic solar cells featuring low-structural order

The insufficient phase separation between polymer donors and nonfullerene acceptors (NFAs) featuring low structural order disrupts efficient charge transport and increases charge recombination, consequently limiting the maximum achievable power conversion efficiency (PCE) of organic solar cells (OSCs). Herein, an NFA IT-M has been added as the third component into the PBDB-T:m-INPOIC OSCs and is shown to effectively tune the phase separation between donor and acceptor molecules, although all components in the ternary system exhibit low degrees of structural order. The incorporation of 10 wt % IT-M into a PBDB-T:m-INPOIC binary host blend appreciably increases the length scale of phase separation, creating continuous pathways that increase and balance charge transport. This leads to an enhanced photovoltaic performance from 12.8% in the binary cell to 13.9% for the ternary cell with simultaneously improved open-circuit voltage, short-circuit current, and fill factor. This work highlights the beneficial role of ternary components in controlling the morphology of the active layer for high-performance OSCs

SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects

Congenital heart disease (CHD) is the most common birth defect, and the leading cause of death due to birth defects, yet causative molecular mechanisms remain mostly unknown. We previously implicated a novel CHD candidate gene, SHROOM3, in a patient with CHD. Using a Shroom3 gene trap knockout mouse (Shroom3gt/gt) we demonstrate that SHROOM3 is downstream of the noncanonical Wnt planar cell polarity signaling pathway (PCP) and loss-of-function causes cardiac defects. We demonstrate Shroom3 expression within cardiomyocytes of the ventricles and interventricular septum from E10.5 onward, as well as within cardiac neural crest cells and second heart field cells that populate the cardiac outflow tract. We demonstrate that Shroom3gt/gt mice exhibit variable penetrance of a spectrum of CHDs that include ventricular septal defects, double outlet right ventricle, and thin left ventricular myocardium. This CHD spectrum phenocopies what is observed with disrupted PCP. We show that during cardiac development SHROOM3 interacts physically and genetically with, and is downstream of, key PCP signaling component Dishevelled 2. Within Shroom3gt/gt hearts we demonstrate disrupted terminal PCP components, actomyosin cytoskeleton, cardiomyocyte polarity, organization, proliferation and morphology. Together, these data demonstrate SHROOM3 functions during cardiac development as an actomyosin cytoskeleton effector downstream of PCP signaling, revealing SHROOM3’s novel role in cardiac development and CHD

The Interplay Between Anxiety and Social Functioning in Williams Syndrome

The developmental disorder Williams syndrome (WS) has been associated with an atypical social profile of hyper-sociability and heightened social sensitivity across the developmental spectrum. In addition, previous research suggests that both children and adults with WS have a predisposition towards anxiety. The current research aimed to explore the profiles of social behaviour and anxiety across a broad age range of individuals with the disorder (n = 59, ages 6–36 years). We used insights from parental reports on two frequently used measures, the Spence Children’s Anxiety Scale (SCAS-P) and the Social Responsiveness Scale (SRS). Severity of anxiety was correlated with a greater degree of social dysfunction as measured by the SRS in this group. We split the group according to high or low anxiety as measured by the SCAS-P and explored the profile of social skills for the two groups. Individuals high and low in anxiety differed in their social abilities. The results emphasise the need to address anxiety issues in this disorder and to consider how components of anxiety might relate to other features of the disorder

Physically fit or physically literate? Children with special educational needs understanding of physical education

The role of physical literacy within physical education (PE) has become a widely debated topic in recent years. Its role in educating children about physicality through embodiment, skill acquisition and reading the environment is argued to be of great benefit to children. However, whether children understand the role of PE in the development of these competencies is not clear, and this is even truer for children who have special educational needs (SEN). Drawing on qualitative phenomenological data from 30 children in key stages 2 and three (7 to 14 years of age) who have SEN, this paper explores notions of physical fitness and physical literacy as understood by children in PE lessons. It aims to gain insight into the ways that children understand the purpose of PE, and places these perceptions within a physical literacy framework, using the National Curriculum for PE (NCPE) as a foundation. Findings demonstrate that children with SEN perceive PE as a means for improving physical fitness, whereas concepts surrounding physical literacy appear to be lost. The paper concludes by making recommendations for factoring physical literacy components more forcibly into the PE curriculum, and through initial teacher training and continued professional development

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Anterior impingement syndrome in dancers

Anterior impingement is a common problem in dancers occurring primarily secondary to the repetitive forced ankle dorsiflexion inherent in ballet. Symptoms generally occur progressively and may respond to conservative treatment including addressing biomechanical faults that contribute to the problem. As impingement progresses, movements essential to ballet may become impossible and arthroscopic ankle surgery is often effective for both diagnosis and treatment, allowing athletes to return to dance

An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD)

- Background: Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and wellbeing of the individual and their capacity to interact and learn. - Method: We developed a new methodology to capture the nonsymbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software. - Conclusion: The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate

Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway

During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog

Treatment outcomes of patients with atopic dermatitis (AD) treated with dupilumab through the early access to medicines scheme (EAMS) in the UK

BACKGROUND Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator’s Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16+4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either ‘better’ (19%) or ‘much better’ (65%). CONCLUSIONS Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials