A longitudinal study of the distance that young people walk to school.

Walking or cycling to school has been associated with important health benefits. Distance between home and school is the main correlate of active commuting to school, but how far children walk to school and how this changes as children age is unknown. Mode of commuting and objectively-assessed distance to school were measured at 3 time points: aged 9/10 years, 10/11 years and 13/14 years. Data were analysed using ROC-curve analyses. With age, children walked further to school; the threshold distance that best discriminated walkers from passive commuters was 1421 m in 10-year-olds, 1627 m in 11-year-olds and 3046 m in 14-year-olds. Future interventions should consider the distance that young people actually walk.The SPEEDY study is funded by the National Prevention Research Initiative (http://www.npri.org.uk), consisting of the following Funding Partners: British Heart Foundation; Cancer Research UK; Department of Health; Diabetes UK; Economic and Social Research Council; Medical Research Council; Health and Social Care Research and Development Office for the Northern Ireland; Chief Scientist Office, Scottish Government Health Directorates; Welsh Assembly Government and World Cancer Research Fund. This work was also supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/7; MC_UU_12015/4] and the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research: Centre of Excellence. 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. Jenna Panter is funded through a post-doctoral fellowship funded by the National Institute of Health Research. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the NIHR PHR programme or the Department of Health.This is the final version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S135382921400159

Unveiling relationships between crime and property in England and Wales via density scale-adjusted metrics and network tools

Scale-adjusted metrics (SAMs) are a significant achievement of the urban scaling hypothesis. SAMs remove the inherent biases of per capita measures computed in the absence of isometric allometries. However, this approach is limited to urban areas, while a large portion of the world’s population still lives outside cities and rural areas dominate land use worldwide. Here, we extend the concept of SAMs to population density scale-adjusted metrics (DSAMs) to reveal relationships among different types of crime and property metrics. Our approach allows all human environments to be considered, avoids problems in the definition of urban areas, and accounts for the heterogeneity of population distributions within urban regions. By combining DSAMs, cross-correlation, and complex network analysis, we find that crime and property types have intricate and hierarchically organized relationships leading to some striking conclusions. Drugs and burglary had uncorrelated DSAMs and, to the extent property transaction values are indicators of affluence, twelve out of fourteen crime metrics showed no evidence of specifically targeting affluence. Burglary and robbery were the most connected in our network analysis and the modular structures suggest an alternative to "zero-tolerance" policies by unveiling the crime and/or property types most likely to affect each other

Level of Arterial Ligation in Rectal Cancer Surgery: Low Tie Preferred over High Tie. A Review

Consensus does not exist on the level of arterial ligation in rectal cancer surgery. From oncologic considerations, many surgeons apply high tie arterial ligation (level of inferior mesenteric artery). Other strategies include ligation at the level of the superior rectal artery, just caudally to the origin of the left colic artery (low tie), and ligation at a level without any intraoperative definition of the inferior mesenteric or superior rectal arteries

Bmp7 Functions via a Polarity Mechanism to Promote Cloacal Septation

During normal development in human and other placental mammals, the embryonic cloacal cavity separates along the axial longitudinal plane to give rise to the urethral system, ventrally, and the rectum, dorsally. Defects in cloacal development are very common and present clinically as a rectourethral fistula in about 1 in 5,000 live human births. Yet, the cellular mechanisms of cloacal septation remain poorly understood.We previously detected Bone morphogenetic protein 7 (Bmp7) expression in the urorectal mesenchyme (URM), and have shown that loss of Bmp7 function results in the arrest of cloacal septation. Here, we present evidence that cloacal partitioning is driven by Bmp7 signaling in the cloacal endoderm. We performed TUNEL and immunofluorescent analysis on cloacal sections from Bmp7 null and control littermate embryos. We found that loss of Bmp7 results in a dramatic decrease in the endoderm survival and a delay in differentiation. We used immunological methods to show that Bmp7 functions by activating the c-Jun N-terminal kinase (JNK) pathway. We carried out confocal and 3D imaging analysis of mitotic chromosome bundles to show that during normal septation cells in the cloacal endoderm divide predominantly in the apical-basal direction. Loss of Bmp7/JNK signaling results in randomization of mitotic angles in the cloacal endoderm. We also conducted immunohistochemical analysis of human fetal sections to show that BMP/phospho-SMAD and JNK pathways function in the human cloacal region similar as in the mouse.Our results strongly indicate that Bmp7/JNK signaling regulates remodeling of the cloacal endoderm resulting in a topological separation of the urinary and digestive systems. Our study points to the importance of Bmp and JNK signaling in cloacal development and rectourethral malformations

Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Mediates Neuronal Aβ42 Uptake and Lysosomal Trafficking

Alzheimer's disease (AD) is characterized by the presence of early intraneuronal deposits of amyloid-beta 42 (Abeta42) that precede extracellular amyloid deposition in vulnerable brain regions. It has been hypothesized that endosomal/lysosomal dysfunction might be associated with the pathological accumulation of intracellular Abeta42 in the brain. Our previous findings suggest that the LDL receptor-related protein 1 (LRP1), a major receptor for apolipoprotein E, facilitates intraneuronal Abeta42 accumulation in mouse brain. However, direct evidence of neuronal endocytosis of Abeta42 through LRP1 is lacking.Here we show that LRP1 endocytic function is required for neuronal Abeta42 uptake. Overexpression of a functional LRP1 minireceptor, mLRP4, increases Abeta42 uptake and accumulation in neuronal lysosomes. Conversely, knockdown of LRP1 expression significantly decreases neuronal Abeta42 uptake. Disruptions of LRP1 endocytic function by either clathrin knockdown or by removal of its cytoplasmic tail decreased both uptake and accumulation of Abeta42 in neurons. Finally, we show that LRP1-mediated neuronal accumulation of Abeta42 is associated with increased cellular toxicity.These results demonstrate that LRP1 endocytic function plays an important role in the uptake and accumulation of Abeta42 in neuronal lysosomes. These findings emphasize the central function of LRP1 in neuronal Abeta metabolism

Prevalence of physical activity through the practice of sports among adolescents from Portuguese speaking countries

This study evaluated the prevalence of physical activity through the practice of sports in adolescents from schools in two Brazilian cities and a Portuguese school, and its association with independent variables, such as gender and age. A cross-sectional study was conducted of schoolchildren from two cities in Brazil and one in Portugal. The total study sample was 3694 subjects (1622 males and 1872 females). Physical activity levels were assessed using Baecke's questionnaire. Body weight was measured on electronic scales and stature was measured with a portable wooden stadiometer. Numerical variables were expressed as mean, categorical variables were expressed as percentages and the chi-square test analyzed associations. The prevalence of no sport was high (39.7%), being higher in the Portuguese school than in the Brazilian schools (p < 0.001). Irrespective of being an adolescent in a Brazilian or Portuguese school, boys showed higher engagement in sports practice than girls (p < 0.001). In both, differences were identified between adolescents aged 13 to 15 (P = 0.001) and 16 to 17 (P = 0.001). The prevalence of physical inactivity among schoolchildren from two cities in Brazil and a school in Portugal was high, with the girls practicing less sport than the boys and with this imbalance likely to be higher in adolescents

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention