Qualitative findings from an exploratory trial of the Healthy Lifestyles Programme (HeLP) and their implications for the process evaluation in the definitive trial.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Approximately one third of 10-11 year olds in England are now overweight or obese suggesting that population approaches are urgently required. However, despite the increasing number of school-based interventions to prevent obesity, results continue to be inconsistent and it is still unclear what the necessary conditions are that lead to the sustained behaviour change required to affect weight status. The Healthy Lifestyles Programme is a theoretically informed four phase multi-component intervention which seeks to create supportive school and home environments for healthy behaviours.National Institute for Health Research (NIHR) Research for Patient Benefit ProgrammeCollaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsul

Working with parents to support children's learning

This is the final version. freely available from the Education Endowment Foundation via the link in this recordThis guidance report aims to help schools considering how they can work with parents and carers to improve children’s learning.* Schools work with parents and families in many ways and with a range of aims, for example, to involve parents in school decisionmaking, to be proactive about safeguarding, and to engender relationships of trust and respect between school and home. In this report, we focus mostly on activities that aim to improve children’s learning directly. So, when we refer to ‘parental engagement’ we mean ‘schools working with parents to improve children’s academic outcomes’. This guidance report draws on a recent review of the evidence about parental engagement in children’s learning funded by the Education Endowment Foundation (EEF). It is not a new study in itself, but rather is intended as an accessible overview of existing research with clear, actionable guidance. The guidance also draws on a wider body of evidence and expert input. Relative to other areas in which the EEF has produced guidance to date, for example related to literacy, there is, as yet, less rigorous evidence for what constitutes effective parental engagement in children’s learning, so an over-arching message for schools is to plan and monitor their work in this area carefully. In addition to the evidence review, the EEF commissioned a survey of what schools in England are currently doing to engage parents in children’s learning. This information is used to provide context for the recommendations, and to identify where there are gaps between current practice and the evidence. More information about the review and how it was produced is provided at the end of this guidance report. Some key references are included for those wishing to explore the subject in more depth. The full evidence review and research on current practices that underpin this guidance will be published separately, and will contain a more comprehensive reference section.Education Endowment Fun

Infant cortex responds to other humans from shortly after birth

A significant feature of the adult human brain is its ability to selectively process information about conspecifics. Much debate has centred on whether this specialization is primarily a result of phylogenetic adaptation, or whether the brain acquires expertise in processing social stimuli as a result of its being born into an intensely social environment. Here we study the haemodynamic response in cortical areas of newborns (1–5 days old) while they passively viewed dynamic human or mechanical action videos. We observed activation selective to a dynamic face stimulus over bilateral posterior temporal cortex, but no activation in response to a moving human arm. This selective activation to the social stimulus correlated with age in hours over the first few days post partum. Thus, even very limited experience of face-to-face interaction with other humans may be sufficient to elicit social stimulus activation of relevant cortical regions

Impact of CTLA-4 checkpoint antibodies on ligand binding and Transendocytosis

Anti-CTLA-4 antibodies have pioneered the field of tumour immunotherapy. However, despite impressive clinical response data, the mechanism by which anti-CTLA-4 antibodies work is still controversial. Two major checkpoint antibodies (ipilimumab and tremelimumab) have been trialled clinically. Both have high affinity binding to CTLA-4 and occupy the ligand binding site, however recently it has been suggested that in some settings such antibodies may not block ligand-CTLA-4 interactions. Here we evaluated blocking capabilities of these antibodies in a variety of settings using both soluble and cell bound target proteins. We found that when ligands (CD80 or CD86) were expressed on cells, soluble CTLA-4-Ig bound in line with affinity expectations and that this interaction was effectively disrupted by both ipilimumab and tremelimumab antibodies. Similarly, cellular CTLA-4 binding to soluble ligands was comparably prevented. We further tested the ability of these antibodies to block transendocytosis, whereby CTLA-4 captures ligands from target cells during a cognate cell-cell interaction. Once again ipilimumab and tremelimumab were similar in preventing removal of ligand by transendocytosis. Furthermore, even once transendocytosis was ongoing and cell contact was fully established, the addition of these antibodies could prevent further ligand transfer. Together these data indicate that the above checkpoint inhibitors performed in-line with predictions based on affinity and binding site data and are capable of blocking CTLA-4-ligand interactions in a wide range of settings tested

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Prevention of cardiovascular disease in patients with familial hypercholesterolaemia: the role of PCSK9 inhibitors

Familial hypercholesterolaemia is an autosomal dominant inherited disorder characterised by elevated low-density lipoprotein cholesterol levels and consequently an increased risk of atherosclerotic cardiovascular disease (ASCVD). Familial hypercholesterolaemia is relatively common, but is often underdiagnosed and undertreated. Cardiologists are likely to encounter many individuals with familial hypercholesterolaemia; however, patients presenting with premature ASCVD are rarely screened for familial hypercholesterolaemia and fasting lipid levels are infrequently documented. Given that individuals with familial hypercholesterolaemia and ASCVD are at a particularly high risk of subsequent cardiac events, this is a missed opportunity for preventive therapy. Furthermore, because there is a 50% chance that first-degree relatives of individuals with familial hypercholesterolaemia will also be affected by the disorder, the underdiagnosis of familial hypercholesterolaemia among patients with ASCVD is a barrier to cascade screening and the prevention of ASCVD in affected relatives. Targeted screening of patients with ASCVD is an effective strategy to identify new familial hypercholesterolaemia index cases. Statins are the standard treatment for individuals with familial hypercholesterolaemia; however, low-density lipoprotein cholesterol targets are not achieved in a large proportion of patients despite treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to reduce low-density lipoprotein cholesterol levels considerably in individuals with familial hypercholesterolaemia who are concurrently receiving the maximal tolerated statin dose. The clinical benefit of PCSK9 inhibitors must, however, also be considered in terms of their cost-effectiveness. Increased awareness of familial hypercholesterolaemia is required among healthcare professionals, particularly cardiologists and primary care physicians, in order to start early preventive measures and to reduce the mortality and morbidity associated with familial hypercholesterolaemia and ASCVD

Quantum enhanced positioning and clock synchronization

A wide variety of positioning and ranging procedures are based on repeatedly sending electromagnetic pulses through space and measuring their time of arrival. This paper shows that quantum entanglement and squeezing can be employed to overcome the classical power/bandwidth limits on these procedures, enhancing their accuracy. Frequency entangled pulses could be used to construct quantum positioning systems (QPS), to perform clock synchronization, or to do ranging (quantum radar): all of these techniques exhibit a similar enhancement compared with analogous protocols that use classical light. Quantum entanglement and squeezing have been exploited in the context of interferometry, frequency measurements, lithography, and algorithms. Here, the problem of positioning a party (say Alice) with respect to a fixed array of reference points will be analyzed.Comment: 4 pages, 2 figures. Accepted for publication by Natur

Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa

Cortical mapping of cognitive function during infancy is poorly understood in low-income countries due to the lack of transportable neuroimaging methods. We have successfully piloted functional near infrared spectroscopy (fNIRS) as a neuroimaging tool in rural Gambia. Four-to-eight month old infants watched videos of Gambian adults perform social movements, while haemodynamic responses were recorded using fNIRS. We found distinct regions of the posterior superior temporal and inferior frontal cortex that evidenced either visual-social activation or vocally selective activation (vocal > non-vocal). The patterns of selective cortical activation in Gambian infants replicated those observed within similar aged infants in the UK. These are the first reported data on the measurement of localized functional brain activity in young infants in Africa and demonstrate the potential that fNIRS offers for field-based neuroimaging research of cognitive function in resource-poor rural communities

Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9–10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial. Methods Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, 1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months. Results At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0–13) energy dense snacks (EDS) and 3.23 (0–9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than ‘light’ intensity activity. Less than 5% of children achieved the Departments of Health’s recommendation of 60 min of MVPA every day. Conclusion We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. Intervention materials and delivery was funded by the Peninsula College of Medicine and Dentistry. PenCLAHRC provided methodological support during the transition from the exploratory trial to the definitive evaluation

Unusual but consistent latitudinal patterns in macroalgal habitats and their invertebrate communities across two countries

Aim: The physical characteristics of biogenic habitats and environmental conditions are important determinants of biodiversity, yet their relative importance can change across spatial scales. We aimed to understand how relationships between the physical characteristics of macroalgal habitats and their invertebrate communities varied across spatial scales and whether general ecological patterns occurred across two countries. Location: Eighteen sites across the temperate east coasts of Australia (over 1,300 km) and New Zealand (over 1,000 km), with the latitudinal gradient in the two countries overlapping by 6.73 decimal degrees. Time period: January to early April 2012. Major taxa studied: Three intertidal macroalgal habitats in each country and the invertebrate communities within them. Methods: We measured variation in patch- and individual-level characteristics of macroalgal habitats and their invertebrate communities. Patterns in macroalgal characteristics and communities were compared across latitude, and at smaller spatial scales, and correlated with 26 abiotic environmental variables using multiple multivariate analyses. Results: Separately, macroalgal habitat characteristics and communities showed unusual but consistent nonlinear latitudinal patterns, with greater similarity among sites at the edges of the sampled distribution (i.e., north and south) than at centrally located sites. Macroalgal characteristics did not correlate with a particular set of environmental variables; however, communities were structured by sea surface temperature at the country scale and by macroalgal habitat type and biomass within countries. Anthropogenic variables were also important and may have contributed to the unusual nonlinear patterns observed between macroalgal characteristics and communities across latitude. Main conclusions: Our results support other studies showing that large-scale patterns can emerge from systems where there is high local-scale variability. The results show that communities within macroalgal habitats respond to both the physical characteristics of the habitat and external environmental conditions (e.g., temperature), suggesting that local-scale environmental factors, including anthropogenic stressors, may modulate environmental gradients over larger scales