Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

The effectiveness of Chance UK's mentoring programme in improving behavioural and emotional outcomes in primary school children with behavioural difficulties: study protocol for a randomised controlled trial

BACKGROUND: There is a need to build the evidence base of early interventions to promote children's health and development in the UK. Chance UK is a voluntary sector organisation based in London that delivers a 12-month mentoring programme for primary school children identified by teachers and parents as having behavioural and emotional difficulties. The aim of the study is to determine the effectiveness of the programme in terms of children's behaviour and emotional well-being; this is the primary outcome of the trial. METHODS/DESIGN: A randomised controlled trial will be conducted in which participants are randomly allocated on a dynamic basis to one of two possible arms: the intervention arm (n = 123) will be offered the mentoring programme, and the control arm (n = 123) will be offered services as usual. Outcome data will be collected at three points: pre-intervention (baseline), mid-way through the mentoring year (c.9 months after randomisation) and post- mentoring programme (c.16 months after randomisation). DISCUSSION: This study will further enhance the evidence for early intervention mentoring programmes for child behaviour and emotional well-being in the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47154925 . Retrospectively registered 9 September 2014

Evaluating Metaphor Reification in Tangible Interfaces

International audienceMetaphors are a powerful conceptual device to reason about human actions. As such, they have been heavily used in designing and describing human computer interaction. Since they can address scripted text, verbal expression, imaging, sound, and gestures, they can also be considered in the design and analysis of multimodal interfaces. In this paper we discuss the description and evaluation of the relations between metaphors and their implementation in human computer interaction with a focus on tangible user interfaces (TUIs), a form of multimodal interface. The objective of this paper is to define how metaphors appear in a tangible context in order to support their evaluation. Relying on matching entities and operations between the domain of interaction and the domain of the digital application, we propose a conceptual framework based on three components: a structured representation of the mappings holding between the metaphor source, the metaphor target, the interface and the digital system; a conceptual model for describing metaphorical TUIs; three relevant properties, coherence, coverage and compliance, which define at what extent the implementation of a metaphorical tangible interface matches the metaphor. The conceptual framework is then validated and applied on a tangible prototype in an educational application

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

A critical role for endocytosis in Wnt signaling

BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of β-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components

The pervasive role of biological cohesion in bedform development

Sediment fluxes in aquatic environments are crucially dependent on bedform dynamics. However, sediment-flux predictions rely almost completely on clean-sand studies, despite most environments being composed of mixtures of non-cohesive sands, physically cohesive muds and biologically cohesive extracellular polymeric substances (EPS) generated by microorganisms. EPS associated with surficial biofilms are known to stabilize sediment and increase erosion thresholds. Here we present experimental data showing that the pervasive distribution of low levels of EPS throughout the sediment, rather than the high surficial levels of EPS in biofilms, is the key control on bedform dynamics. The development time for bedforms increases by up to two orders of magnitude for extremely small quantities of pervasively distributed EPS. This effect is far stronger than for physical cohesion, because EPS inhibit sand grains from moving independently. The results highlight that present bedform predictors are overly simplistic, and the associated sediment transport processes require re-assessment for the influence of EPS