Healthy Parent Carers programme: development and feasibility of a novel group-based health-promotion intervention

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background Parent carers of disabled children report poor physical health and mental wellbeing. They experience high levels of stress and barriers to engagement in health-related behaviours and with ‘standard’ preventive programmes (e.g. weight loss programmes). Interventions promoting strategies to improve health and wellbeing of parent carers are needed, tailored to their specific needs and circumstances. Methods We developed a group-based health promotion intervention for parent carers by following six steps of the established Intervention Mapping approach. Parent carers co-created the intervention programme and were involved in all stages of the development and testing. We conducted a study of the intervention with a group of parent carers to examine the feasibility and acceptability. Standardised questionnaires were used to assess health and wellbeing pre and post-intervention and at 2 month follow up. Participants provided feedback after each session and took part in a focus group after the end of the programme. Results The group-based Healthy Parent Carers programme was developed to improve health and wellbeing through engagement with eight achievable behaviours (CLANGERS – Connect, Learn, be Active, take Notice, Give, Eat well, Relax, Sleep), and by promoting empowerment and resilience. The manualised intervention was delivered by two peer facilitators to a group of seven parent carers. Feedback from participants and facilitators was strongly positive. The study was not powered or designed to test effectiveness but changes in measures of participants’ wellbeing and depression were in a positive direction both at the end of the intervention and 2 months later which suggest that there may be a potential to achieve benefit. Conclusions The Healthy Parent Carers programme appears feasible and acceptable. It was valued by, and was perceived to have benefited participants. The results will underpin future refinement of the intervention and plans for evaluation.We acknowledge funding from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care of the South West Peninsula (PenCLAHRC) and the charity Cerebra. The views and opinions expressed in this paper are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care, or Cerebra

What do we really know about the appropriateness of radiation emitting imaging for low back pain in primary and emergency care? A systematic review and meta-analysis of medical record reviews

Background Since 2000, guidelines have been consistent in recommending when diagnostic imaging for low back pain should be obtained to ensure patient safety and reduce unnecessary tests. This systematic review and meta-analysis was conducted to determine the pooled proportion of CT and x-ray imaging of the lumbar spine that were considered appropriate in primary and emergency care. Methods Pubmed, CINAHL, The Cochrane Database of Systematic Reviews and Embase were searched for synonyms of “low back pain”, “guidelines”, and “adherence” that were published after 2000. Titles, abstracts, and full texts were reviewed for inclusion with forward and backward tracking on included studies. Included studies had data extracted and synthesized. Risk of bias was performed on all studies, and GRADE was performed on included studies that provided data on CT and x-ray separately. A random effect, single proportion meta-analysis model was used. Results Six studies were included in the descriptive synthesis, and 5 studies included in the meta-analysis. Five of the 6 studies assessed appropriateness of x-rays; two of the six studies assessed appropriateness of CTs. The pooled estimate for appropriateness of x-rays was 43% (95% CI: 30%, 56%) and the pooled estimate for appropriateness of CTs was 54% (95% CI: 51%, 58%). Studies did not report adequate information to fulfill the RECORD checklist (reporting guidelines for research using observational data). Risk of bias was high in 4 studies, moderate in one, and low in one. GRADE for x-ray appropriateness was low-quality and for CT appropriateness was very-low-quality. Conclusion While this study determined a pooled proportion of appropriateness for both x-ray and CT imaging for low back pain, there is limited confidence in these numbers due to the downgrading of the evidence using GRADE. Further research on this topic is needed to inform our understanding of x-ray and CT appropriateness in order to improve healthcare systems and decrease patient harms

Training teachers in classroom management to improve mental health in primary school children: the STARS cluster RCT

This is the final version. Available from NIHR Journals Library via the DOI in this record.Background Poor mental health in childhood is common, persistent and associated with a range of adverse outcomes that include persistent psychopathology, as well as risk-taking behaviour, criminality and educational failure, all of which may also compromise health. There is a growing policy focus on children’s mental health and the role of schools in particular in addressing this. Objectives To evaluate whether or not the Incredible Years® (IY) Teacher Classroom Management (TCM) training improved children’s mental health, behaviour, educational attainment and enjoyment of school, improved teachers’ mental health and relationship with work, and was cost-effective in relation to potential improvements. Design A two-arm, pragmatic, parallel-group, superiority, cluster randomised controlled trial. Setting A total of 80 UK schools (clusters) were recruited in three distinct cohorts between 2012 and 2014 and randomised to TCM (intervention) or teaching as usual [(TAU) control] with follow-ups at 9, 18 and 30 months. Schools and teachers were not masked to allocation. Participants Eighty schools (n = 2075 children) were randomised: 40 (n = 1037 children) to TCM and 40 (n = 1038 children) to TAU. Interventions TCM was delivered to teachers in six whole-day sessions, spread over 6 months. The explicit goals of TCM are to enhance classroom management skills and improve teacher–student relationships. Main outcome measures The primary planned outcome was the teacher-reported Strengths and Difficulties Questionnaire Total Difficulties (SDQ-TD) score. Random-effects linear regression and marginal logistic regression models using generalized estimating equations were used to analyse outcomes. Results The intervention reduced the SDQ-TD score at 9 months [adjusted mean difference (AMD) –1.0, 95% confidence interval (CI) –1.9 to –0.1; p = 0.03] but there was little evidence of effects at 18 months (AMD –0.1, 95% CI –1.5 to 1.2; p = 0.85) and 30 months (AMD –0.7, 95% CI –1.9 to 0.4; p = 0.23). Planned subgroup analyses suggested that TCM is more effective than TAU for children with poor mental health. Cost-effectiveness analysis using the SDQ-TD suggested that the probability of TCM being cost-effective compared with TAU was associated with some uncertainty (range of 40% to 80% depending on the willingness to pay for a unit improvement in SDQ-TD score). In terms of quality-adjusted life-years (QALYs), there was evidence to suggest that TCM was cost-effective compared with TAU at the National Institute for Health and Care Excellence thresholds of £20,000–30,000 per QALY at 9- and 18-month follow-up, but not at 30-month follow-up. There was evidence of reduced disruptive behaviour (p = 0.04) and reductions in inattention and overactivity (p = 0.02) at the 30-month follow-up. Despite no main effect on educational attainment, subgroup analysis indicated that the intervention’s effect differed between those who did and those who did not have poor mental health for both literacy (interaction p = 0.04) and numeracy (interaction p = 0.03). Independent blind observations and qualitative feedback from teachers suggested that teachers’ behaviour in the classroom changed as a result of attending TCM training. Limitations Teachers were not masked to allocation and attrition was marked for parent-reported data. Conclusions Our findings provide tentative evidence that TCM may be an effective universal child mental health intervention in the short term, particularly for primary school children who are identified as struggling, and it may be a cost-effective intervention in the short term. Future work Further research should explore TCM as a whole-school approach by training all school staff and should evaluate the impact of TCM on academic progress in a more thorough and systematic manner.National Institute for Health Research (NIHR

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Diversification of refugia types needed to secure the future of coral reefs subject to climate change

Identifying locations of refugia from the thermal stresses of climate change for coral reefs and better managing them is one of the key recommendations for climate change adaptation. We review and summarize approximately 30 years of applied research focused on identifying climate refugia to prioritize the conservation actions for coral reefs under rapid climate change. We found that currently proposed climate refugia and the locations predicted to avoid future coral losses are highly reliant on excess heat metrics, such as degree heating weeks. However, many existing alternative environmental, ecological, and life-history variables could be used to identify other types of refugia that lead to the desired diversified portfolio for coral reef conservation. To improve conservation priorities for coral reefs, there is a need to evaluate and validate the predictions of climate refugia with long-term field data on coral abundance, diversity, and functioning. There is also the need to identify and safeguard locations displaying resistance toprolonged exposure to heat waves and the ability to recover quickly after thermal exposure. We recommend using more metrics to identify a portfolio of potential refugia sites for coral reefs that can avoid, resist, and recover from exposure to high ocean temperatures and the consequences of climate change, thereby shifting past efforts focused on avoidance to a diversified risk-spreading portfolio that can be used to improve strategic coral reef conservation in a rapidly warming climate

The obesity-associated gene TMEM18 has a role in the central control of appetite and body weight regulation

An intergenic region of human chromosome 2 (2p25.3) harbors genetic variants which are among those most strongly and reproducibly associated with obesity. The gene closest to these variants is TMEM18, although the molecular mechanisms mediating these effects remain entirely unknown. Tmem18 expression in the murine hypothalamic paraventricular nucleus (PVN) was altered by changes in nutritional state. Germline loss of Tmem18 in mice resulted in increased body weight, which was exacerbated by high fat diet and driven by increased food intake. Selective overexpression of Tmem18 in the PVN of wild-type mice reduced food intake and also increased energy expenditure. We provide evidence that TMEM18 has four, not three, transmembrane domains and that it physically interacts with key components of the nuclear pore complex. Our data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity.RL, YCLT, DR, GSHY, SOR and APC are funded by the Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1) and animal work was carried out with the assistance of MRC Disease Model Core of the Wellcome Trust MRC Institute of Metabolic Sciences (MRC_MC_UU_12012/5 and Wellcome Trust Strategic Award (100574/Z/12/Z). F. Bosch is the recipient of an award from the ICREA Academia, Generalitat de Catalunya, Spain. Vector generation and production were funded by Ministerio de Economía y Competitividad (SAF 2014-54866-R), Spain. CD and DWL were supported by the Wellcome Trust (WT098051) and CD was supported by the Wellcome Trust PhD Programme for Clinicians (100679/Z/12/Z)

High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

Assessing stimulus–stimulus (semantic) conflict in the Stroop task using saccadic two-to-one color response mapping and preresponse pupillary measures

© 2015, The Psychonomic Society, Inc. Conflict in the Stroop task is thought to come from various stages of processing, including semantics. Two-to-one response mappings, in which two response-set colors share a common response location, have been used to isolate stimulus–stimulus (semantic) from stimulus–response conflict in the Stroop task. However, the use of congruent trials as a baseline means that the measured effects could be exaggerated by facilitation, and recent research using neutral, non-color-word trials as a baseline has supported this notion. In the present study, we sought to provide evidence for stimulus–stimulus conflict using an oculomotor Stroop task and an early, preresponse pupillometric measure of effort. The results provided strong (Bayesian) evidence for no statistical difference between two-to-one response-mapping trials and neutral trials in both saccadic response latencies and preresponse pupillometric measures, supporting the notion that the difference between same-response and congruent trials indexes facilitation in congruent trials, and not stimulus–stimulus conflict, thus providing evidence against the presence of semantic conflict in the Stroop task. We also demonstrated the utility of preresponse pupillometry in measuring Stroop interference, supporting the idea that pupillary effects are not simply a residue of making a response

A Glucose Fuel Cell for Implantable Brain–Machine Interfaces

We have developed an implantable fuel cell that generates power through glucose oxidation, producing steady-state power and up to peak power. The fuel cell is manufactured using a novel approach, employing semiconductor fabrication techniques, and is therefore well suited for manufacture together with integrated circuits on a single silicon wafer. Thus, it can help enable implantable microelectronic systems with long-lifetime power sources that harvest energy from their surrounds. The fuel reactions are mediated by robust, solid state catalysts. Glucose is oxidized at the nanostructured surface of an activated platinum anode. Oxygen is reduced to water at the surface of a self-assembled network of single-walled carbon nanotubes, embedded in a Nafion film that forms the cathode and is exposed to the biological environment. The catalytic electrodes are separated by a Nafion membrane. The availability of fuel cell reactants, oxygen and glucose, only as a mixture in the physiologic environment, has traditionally posed a design challenge: Net current production requires oxidation and reduction to occur separately and selectively at the anode and cathode, respectively, to prevent electrochemical short circuits. Our fuel cell is configured in a half-open geometry that shields the anode while exposing the cathode, resulting in an oxygen gradient that strongly favors oxygen reduction at the cathode. Glucose reaches the shielded anode by diffusing through the nanotube mesh, which does not catalyze glucose oxidation, and the Nafion layers, which are permeable to small neutral and cationic species. We demonstrate computationally that the natural recirculation of cerebrospinal fluid around the human brain theoretically permits glucose energy harvesting at a rate on the order of at least 1 mW with no adverse physiologic effects. Low-power brain–machine interfaces can thus potentially benefit from having their implanted units powered or recharged by glucose fuel cells