The spectrum effect in tests for risk prediction, screening, and diagnosis.

The spectrum effect describes the variation between settings in performance of tests used to predict, screen for, and diagnose disease. In particular, the predictive use of a test may be different when it is applied in a general population rather than in the study sample in which it was first developed. This article discusses the impact of the spectrum effect on measures of test performance, and its implications for the development, evaluation, application, and implementation of such tests.JUS is supported by a National Institute of Health Research (NIHR) Clinical Lectureship. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. SJS is supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1].This is the final version of the article. It first appeared from the BMJ Group via https://doi.org/10.1136/bmj.i313

Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris)

This work was funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government, and The Wellcome Trust, under the Insect Pollinators Initiative (United Kingdom) Grant BB/ 1000313/1 (to C.N.C.).The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g., clothianidin and imidacloprid) to this decline is controversial, and key to understanding their risk is whether the astonishingly low levels found in the nectar and pollen of plants is sufficient to deliver neuroactive levels to their site of action: the bee brain. Here we show that bumblebees (Bombusterrestris audax) fed field levels [10 nM, 2.1 ppb (w/w)] of neonicotinoid accumulate between 4 and 10 nM in their brains within 3 days. Acute (minutes) exposure of cultured neurons to 10 nM clothianidin, but not imidacloprid, causes a nicotinic acetylcholine receptor-dependent rapid mitochondrial depolarization. However, a chronic (2 days) exposure to 1 nM imidacloprid leads to a receptor-dependent increased sensitivity to a normally innocuous level of acetylcholine, which now also causes rapid mitochondrial depolarization in neurons. Finally, colonies exposed to this level of imidacloprid show deficits in colony growth and nest condition compared with untreated colonies. These findings provide a mechanistic explanation for the poor navigation and foraging observed in neonicotinoid treated bumblebee colonies.Publisher PDFPeer reviewe

A review of published analyses of case-cohort studies and recommendations for future reporting.

The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%). The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.SJS was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1]. IRW was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number U105260558]. MP, SGT and AMW were supported by the British Heart Foundation www.bhf.org.uk [grant number CH/12/2/29428].This is the final published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's website at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.010117

A novel school-based intervention to improve nutrition knowledge in children: cluster randomised controlled trial.

BACKGROUND: Improving nutrition knowledge among children may help them to make healthier food choices. The aim of this study was to assess the effectiveness and acceptability of a novel educational intervention to increase nutrition knowledge among primary school children. METHODS: We developed a card game 'Top Grub' and a 'healthy eating' curriculum for use in primary schools. Thirty-eight state primary schools comprising 2519 children in years 5 and 6 (aged 9-11 years) were recruited in a pragmatic cluster randomised controlled trial. The main outcome measures were change in nutrition knowledge scores, attitudes to healthy eating and acceptability of the intervention by children and teachers. RESULTS: Twelve intervention and 13 control schools (comprising 1133 children) completed the trial. The main reason for non-completion was time pressure of the school curriculum. Mean total nutrition knowledge score increased by 1.1 in intervention (baseline to follow-up: 28.3 to 29.2) and 0.3 in control schools (27.3 to 27.6). Total nutrition knowledge score at follow-up, adjusted for baseline score, deprivation, and school size, was higher in intervention than in control schools (mean difference = 1.1; 95% CI: 0.05 to 2.16; p = 0.042). At follow-up, more children in the intervention schools said they 'are currently eating a healthy diet' (39.6%) or 'would try to eat a healthy diet' (35.7%) than in control schools (34.4% and 31.7% respectively; chi-square test p < 0.001). Most children (75.5%) enjoyed playing the game and teachers considered it a useful resource. CONCLUSIONS: The 'Top Grub' card game facilitated the enjoyable delivery of nutrition education in a sample of UK primary school age children. Further studies should determine whether improvements in nutrition knowledge are sustained and lead to changes in dietary behaviour.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Effect of communicating genetic and phenotypic risk for type 2 diabetes in combination with lifestyle advice on objectively measured physical activity: protocol of a randomised controlled trial.

BACKGROUND: Type 2 diabetes (T2D) is associated with increased risk of morbidity and premature mortality. Among those at high risk, incidence can be halved through healthy changes in behaviour. Information about genetic and phenotypic risk of T2D is now widely available. Whether such information motivates behaviour change is unknown. We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours, anxiety, and other cognitive and emotional theory-based antecedents of behaviour change. METHODS: In a parallel group, open randomised controlled trial, approximately 580 adults born between 1950 and 1975 will be recruited from the on-going population-based, observational Fenland Study (Cambridgeshire, UK). Eligible participants will have undergone clinical, anthropometric, and psychosocial measurements, been genotyped for 23 single-nucleotide polymorphisms associated with T2D, and worn a combined heart rate monitor and accelerometer (Actiheart(®)) continuously for six days and nights to assess physical activity. Participants are randomised to receive either standard lifestyle advice alone (control group), or in combination with a genetic or a phenotypic risk estimate for T2D (intervention groups). The primary outcome is objectively measured physical activity. Secondary outcomes include self-reported diet, self-reported weight, intention to be physically active and to engage in a healthy diet, anxiety, diabetes-related worry, self-rated health, and other cognitive and emotional outcomes. Follow-up occurs eight weeks post-intervention. Values at follow-up, adjusted for baseline, will be compared between randomised groups. DISCUSSION: This study will provide much needed evidence on the effects of providing information about the genetic and phenotypic risk of T2D. Importantly, it will be among the first to examine the impact of genetic risk information using a randomised controlled trial design, a population-based sample, and an objectively measured behavioural outcome. Results of this trial, along with recent evidence syntheses of similar studies, should inform policy concerning the availability and use of genetic risk information.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Seasonal Variation in Children's Physical Activity and Sedentary Time.

PURPOSE: Understanding seasonal variation in physical activity is important for informing public health surveillance and intervention design. The aim of the current study was to describe seasonal variation in children's objectively measured physical activity and sedentary time. METHODS: Data are from the UK Millennium Cohort Study. Participants were invited to wear an accelerometer for 7 d on five occasions between November 2008 and January 2010. Outcome variables were sedentary time (2241 counts per minute, min·d(-1)). The season was characterized using a categorical variable (spring, summer, autumn, or winter) and a continuous function of day of the year. Cross-classified linear regression models were used to estimate the association of each of these constructs with the outcome variables. Modification of the seasonal variation by sex, weight status, urban/rural location, parental income, and day of the week (weekday/weekend) was examined using interaction terms in regression models. RESULTS: At least one wave of valid accelerometer data was obtained from 704 participants (47% male; baseline age, 7.6 (0.3) yr). MVPA was lower in autumn and winter relative to spring, with the magnitude of this difference varying by weekday/weekend, sex, weight status, urban/rural location, and family income (P for interaction <0.05 in all cases). Total sedentary time was greater in autumn and winter compared with spring; the seasonal effect was stronger during the weekend than during the weekday (P for interaction <0.01). CONCLUSIONS: Lower levels of MVPA and elevated sedentary time support the implementation of intervention programs during autumn and winter. Evidence of greater seasonal variation in weekend behavior and among certain sociodemographic subgroups highlights targets for tailored intervention programs.The co-operation of the participating families is gratefully acknowledged. The fourth sweep of the Millennium Cohort Study was funded by grants to Professor Health Joshi, former director of the study, from the Economic and Social Research Council and a consortium of government funders. The current director is Professor Lucinda Platt. The authors acknowledge: the Centre for Longitudinal Studies, Institute of Education for the use of these data; the UK Data Service for making them available; the MRC Centre of Epidemiology for Child Health (Grant reference G0400546), Institute of Child Health, University College London for creating the accelerometer data resource which was funded by the Wellcome Trust (grant reference 084686/Z/08/A). The institutions and funders acknowledged bear no responsibility for the analysis or interpretation of these data. The work of Andrew J Atkin, Flo Harrison, and Esther M F van Sluijs was supported, wholly or in part, by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Soren Brage, Stephen Sharp and Esther MF van Sluijs was supported by the Medical Research Council (MC_UU_12015/7, MC_UU_12015/3, MC_UU_12015/1).This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.1249/MSS.000000000000078

Prevalence and correlates of screen time in youth: an international perspective.

BACKGROUND: Screen time (including TV viewing/computer use) may be adversely associated with metabolic and mental health in children. PURPOSE: To describe the prevalence and sociodemographic correlates of screen time in an international sample of children aged 4-17 years. METHODS: Data from the International Children's Accelerometry Database were collected between 1997-2009 and analyzed in 2013. Participants were 11,434 children (48.9% boys; mean [SD] age at first assessment, 11.7 [3.2] years). Exposures were sex, age, weight status, maternal education, and ethnicity. The outcome was self- or proxy-reported screen time 2 hours/day. Analyses were conducted initially at study level and then combined using random-effects meta-analysis. RESULTS: Within each contributing study, at least two thirds of participants exceeded 2 hours/day of screen time. In meta-analytic models, overweight or obese children were more likely to exceed 2 hours/day of screen time than those who were non-overweight (OR=1.58, 95% CI=1.33,1.88). Girls (vs boys: 0.65; 0.54, 0.78) and participants with more highly educated mothers (vs <university level: 0.53; 0.42, 0.68) were less likely to exceed 2 hours/day of screen time. Associations of age and ethnicity with screen time were inconsistent at study level and non-significant in pooled analyses. CONCLUSIONS: Screen time in excess of public health guidelines was highly prevalent, particularly among boys, those who were overweight or obese, and those with mothers of lower educational attainment. The population-attributable risk associated with this exposure is potentially high; further efforts to understand the determinants of within- and between-country variation in these behaviors and inform the development of effective behavior change intervention programs is warranted.The work of Andrew J Atkin was supported by the UKCRC Centre for Diet and Activity Research (CEDAR), a UK Clinical Research Collaboration Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Esther M F van Sluijs and Kirsten Corder was supported by the Medical Research Council (MC_UU_12015/7).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.amepre.2014.07.04

An investigation of patterns of children's sedentary and vigorous physical activity throughout the week.

BACKGROUND: Participation in higher intensity activity (i.e. vigorous physical activity [VPA]) appears more consistently associated with lower adiposity, unfortunately little is known about the nature and patterns of VPA participation in children. OBJECTIVE: To examine the volume and patterns of vigorous and sedentary activity during different segments of the week (weekend, school-based and out-of-school). We also investigated differences by sex, socioeconomic status (SES) and weight status. DESIGN: A cross-sectional study including 1568 UK children aged 9-10 years. OUTCOME MEASURES: Sedentary activity (mins), total activity (counts/min) and VPA (mins) were measured by accelerometry. Using a series of 2 level mixed effects linear regression models we tested differences across the segmented week (school time [0900-1500] vs. out-of-school time [0700-0900 & 1500-2100]; and weekday vs. weekend); all models were adjusted for sex, weight status (gender- and age-specific body mass index [BMI] cut points), SES, age and accelerometer registered wear time. RESULTS: Boys and girls accumulated higher VPA out-of-school compared to during school (boys mean ± SD 16.9 ± 9.6 vs 12.6 ± 5.8; girls, 13.1 ± 7.7 vs 8.2 ± 4.0, both p 0.05). Less time was spent sedentary on weekdays compared to weekends (p < 0.001). Although boys were more physically active and girls accumulated more sedentary time, the overall pattern in which their physical activity intensity varied across the various day segments was similar when stratified by weight status and SES; and large volumes of sedentary time were observed each hour across the day. CONCLUSIONS: The promotion of VPA during the weekend may hold the greatest promise for increasing VPA. Interventions aimed at increasing physical activity in 9-10 year old children should aim to target all children independent of sex, SES or weight status.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis.

BACKGROUND: The prevalence of autism spectrum conditions (ASC) is 1% in developed countries, but little data are available from mainland China, Hong Kong and Taiwan. This study synthesizes evidence relating to the prevalence of ASC in these areas and assesses the effects of research methodology on prevalence estimates. METHODS: Systematic literature searches were conducted in PubMed, Web of Knowledge, China Web of Knowledge and Weipu databases, as well as relevant papers published from 1987 to 2011, reporting prevalence estimates of ASC or childhood autism in mainland China, Hong Kong and Taiwan. Summary estimates of prevalence were calculated with a random effects model. The effects of research methodology on the prevalence estimates were assessed using a meta-regression model. RESULTS: There were 25 studies eligible for review, 18 of which were suitable for inclusion in a meta-analysis. Pooled prevalence of childhood autism was 11.8 per 10,000 individuals (95% confidence interval (CI): 8.2, 15.3) in mainland China. Pooled prevalence of ASC was 26.6 per 10,000 (95% CI: 18.5, 34.6) in three areas. Substantial heterogeneity was identified between studies (I2>75%). The prevalence estimate of childhood autism was most strongly associated with the choice of screening instrument. After adjustment for age group, the odds ratio for prevalence estimates when using the Autism Behavior Checklist (ABC) as the screening instrument compared with those using the Clancy Autism Behavior Scale (CABS) was 0.29 (95% CI: 0.12, 0.69), and 1.79 (95% CI: 0.70, 4.55; P= 0.20) when using the Checklist for Autism in Toddlers (CHAT) compared to the CABS. CONCLUSIONS: The available studies investigating the prevalence of ASC in China, Hong Kong and Taiwan have focused mainly on childhood autism rather than the whole spectrum. The prevalence estimates are lower than estimates from developed countries. Studies using more recently developed screening instruments reported higher prevalence than older ones. However, available studies have methodological weaknesses and therefore these results lack comparability with those from developed countries. Our findings indicate a potential under-diagnosis and under-detection of ASC in mainland China, Hong Kong and Taiwan, and a need to adopt more advanced methods for research of ASC in these areas.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The pathway to diagnosis of type 1 diabetes in children: a questionnaire study.

OBJECTIVE: To explore the pathway to diagnosis of type 1 diabetes (T1D) in children. DESIGN: Questionnaire completed by parents. PARTICIPANTS: Parents of children aged 1 month to 16 years diagnosed with T1D within the previous 3 months. SETTING: Children and parents from 11 hospitals within the East of England. RESULTS: 88/164 (54%) invited families returned the questionnaire. Children had mean±SD age of 9.41±4.5 years. 35 (39.8%) presented with diabetic ketoacidosis at diagnosis. The most common symptoms were polydipsia (97.7%), polyuria (83.9%), tiredness (75.9%), nocturia (73.6%) and weight loss (64.4%) and all children presented with at least one of those symptoms. The time from symptom onset to diagnosis ranged from 2 to 315 days (median 25 days). Most of this was the appraisal interval from symptom onset until perceiving the need to seek medical advice. Access to healthcare was good but one in five children presenting to primary care were not diagnosed at first encounter, most commonly due to waiting for fasting blood tests or alternative diagnoses. Children diagnosed at first consultation had a shorter duration of symptoms (p=0.022) and children whose parents suspected the diagnosis were 1.3 times more likely (relative risk (RR) 1.3, 95% CI 1.02 to 1.67) to be diagnosed at first consultation. CONCLUSIONS: Children present with the known symptoms of T1D but there is considerable scope to improve the diagnostic pathway. Future interventions targeted at parents need to address the tendency of parents to find alternative explanations for symptoms and the perceived barriers to access, in addition to symptom awareness.The study was funded by the Royal College of General Practitioners Scientific Foundation Board (SFB-2011-15). JUS was supported by a National Institute of Health Research (NIHR) Academic Clinical Fellowship and subsequently Clinical Lectureship, and FMW by an NIHR Clinician Scientist award. SJS was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1]. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.This is the final version of the article. It was first published by BMJ Group at http://bmjopen.bmj.com/content/5/3/e006470.ful