Active School Transport among Children from Canada, Colombia, Finland, South Africa, and the United States: A Tale of Two Journeys

Walking and biking to school represent a source of regular daily physical activity (PA). The objectives of this paper are to determine the associations of distance to school, crime safety, and socioeconomic variables with active school transport (AST) among children from five culturally and socioeconomically different country sites and to describe the main policies related to AST in those country sites. The analytical sample included 2845 children aged 9–11 years from the International Study of Childhood Obesity, Lifestyle and the Environment. Multilevel generalized linear mixed models were used to estimate the associations between distance, safety and socioeconomic variables, and the odds of engaging in AST. Greater distance to school and vehicle ownership were associated with a lower likelihood of engaging in AST in sites in upper-middle- and high-income countries. Crime perception was negatively associated to AST only in sites in high-income countries. Our results suggest that distance to school is a consistent correlate of AST in different contexts. Our findings regarding crime perception support a need vs. choice framework, indicating that AST may be the only commuting choice for many children from the study sites in upper-middle-income countries, despite the high perception of crime

Perceived and objective neighborhood support for outside of school physical activity in South African children.

The neighborhood environment has the potential to influence children's participation in physical activity. However, children's outdoor play is controlled by parents to a great extent. This study aimed to investigate whether parents' perceptions of the neighborhood environment and the objectively measured neighborhood environment were associated with children's moderate-to-vigorous intensity physical activity (MVPA) outside of school hours; and to determine if these perceptions and objective measures of the neighborhood environment differ between high and low socio-economic status (SES) groups.In total, 258 parents of 9-11 year-old children, recruited from the South African sample of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), completed a questionnaire concerning the family and neighborhood environment. Objective measures of the environment were also obtained using Geographic Information Systems (GIS). Children wore an Actigraph (GT3X+) accelerometer for 7 days to measure levels of MVPA. Multilevel regression models were used to determine the association between the neighborhood environment and MVPA out of school hours.Parents' perceptions of the neighborhood physical activity facilities were positively associated with children's MVPA before school (β = 1.50 ± 0.51, p = 0.003). Objective measures of neighborhood safety and traffic risk were associated with children's after-school MVPA (β = -2.72 ± 1.35, p = 0.044 and β = -2.63 ± 1.26, p = 0.038, respectively). These associations were significant in the low SES group (β = -3.38 ± 1.65, p = 0.040 and β = -3.76 ± 1.61, p = 0.020, respectively), but unrelated to MVPA in the high SES group.This study found that several of the objective measures of the neighborhood environment were significantly associated with children's outside-of-school MVPA, while most of the parents' perceptions of the neighborhood environment were unrelated

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity

Extremely High Tp53 Mutation Load in Esophageal Squamous Cell Carcinoma in Golestan Province, Iran

Background: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. Methodology/Principal Findings: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40 at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. Conclusion/Significance: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis

Meta-Analysis for Genome-Wide Association Study Identifies Multiple Variants at the BIN1 Locus Associated with Late-Onset Alzheimer's Disease

Recent GWAS studies focused on uncovering novel genetic loci related to AD have revealed associations with variants near CLU, CR1, PICALM and BIN1. In this study, we conducted a genome-wide association study in an independent set of 1034 cases and 1186 controls using the Illumina genotyping platforms. By coupling our data with available GWAS datasets from the ADNI and GenADA, we replicated the original associations in both PICALM (rs3851179) and CR1 (rs3818361). The PICALM variant seems to be non-significant after we adjusted for APOE e4 status. We further tested our top markers in 751 independent cases and 751 matched controls. Besides the markers close to the APOE locus, a marker (rs12989701) upstream of BIN1 locus was replicated and the combined analysis reached genome-wide significance level (p = 5E-08). We combined our data with the published Harold et al. study and meta-analysis with all available 6521 cases and 10360 controls at the BIN1 locus revealed two significant variants (rs12989701, p = 1.32E-10 and rs744373, p = 3.16E-10) in limited linkage disequilibrium (r2 = 0.05) with each other. The independent contribution of both SNPs was supported by haplotype conditional analysis. We also conducted multivariate analysis in canonical pathways and identified a consistent signal in the downstream pathways targeted by Gleevec (P = 0.004 in Pfizer; P = 0.028 in ADNI and P = 0.04 in GenADA). We further tested variants in CLU, PICALM, BIN1 and CR1 for association with disease progression in 597 AD patients where longitudinal cognitive measures are sufficient. Both the PICALM and CLU variants showed nominal significant association with cognitive decline as measured by change in Clinical Dementia Rating-sum of boxes (CDR-SB) score from the baseline but did not pass multiple-test correction. Future experiments will help us better understand potential roles of these genetic loci in AD pathology

Association of temporal factors and suicides in the United States, 2000–2004

The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects

The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) : design and methods

Background: The primary aim of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was to determine the relationships between lifestyle behaviours and obesity in a multi-national study of children, and to investigate the influence of higher-order characteristics such as behavioural settings, and the physical, social and policy environments, on the observed relationships within and between countries. Methods/design: The targeted sample included 6000 10-year old children from 12 countries in five major geographic regions of the world (Europe, Africa, the Americas, South-East Asia, and the Western Pacific). The protocol included procedures to collect data at the individual level (lifestyle, diet and physical activity questionnaires, accelerometry), family and neighborhood level (parental questionnaires), and the school environment (school administrator questionnaire and school audit tool). A standard study protocol was developed for implementation in all regions of the world. A rigorous system of training and certification of study personnel was developed and implemented, including web-based training modules and regional in-person training meetings. Discussion: The results of this study will provide a robust examination of the correlates of adiposity and obesity in children, focusing on both sides of the energy balance equation. The results will also provide important new information that will inform the development of lifestyle, environmental, and policy interventions to address and prevent childhood obesity that may be culturally adapted for implementation around the world. ISCOLE represents a multi-national collaboration among all world regions, and represents a global effort to increase research understanding, capacity and infrastructure in childhood obesity.Peer reviewe

Are the correlates of active school transport context-specific?

OBJECTIVES: Previous research consistently indicates that children who engage in active school transport (AST) are more active than their peers who use motorized modes (car or bus). However, studies of the correlates of AST have been conducted predominantly in high-income countries and have yielded mixed findings. Using data from a heterogeneous sample of 12 country sites across the world, we investigated the correlates of AST in 9–11-year olds. METHODS: The analytical sample comprised 6555 children (53.8% girls), who reported their main travel mode to school and the duration of their school trip. Potential individual and neighborhood correlates of AST were assessed with a parent questionnaire adapted from previously validated instruments. Multilevel generalized linear mixed models (GLMM) were used to examine the associations between individual and neighborhood variables and the odds of engaging in AST while controlling for the child's school. Site moderated the relationship of seven of these variables with AST; therefore we present analyses stratified by site. RESULTS: The prevalence of AST varied from 5.2 to 79.4% across sites and the school-level intra-class correlation ranged from 0.00 to 0.56. For each site, the final GLMM included a different set of correlates of AST. Longer trip duration (that is, ⩾16 min versus ⩽15 min) was associated with lower odds of AST in eight sites. Other individual and neighborhood factors were associated with AST in three sites or less. CONCLUSIONS: Our results indicate wide variability in the prevalence and correlates of AST in a large sample of children from twelve geographically, economically and culturally diverse country sites. This suggests that AST interventions should not adopt a ‘one size fits all' approach. Future research should also explore the association between psychosocial factors and AST in different countries