Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

First available in BioRxiv doi: http://dx.doi.org/10.1101/063438International audienceBackground. The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.Methods. Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.Results. We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.Conclusions. The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.Trial registration. Clinical-Trial.gov NCT02212522. Registered August 6, 2014.

Further development and validation of CO2FOAM for the atmospheric dispersion of accidental releases from carbon dioxide pipelines

This paper reports on the further development and validation of CO2FOAM, a dedicated computational fluid dynamics solver for the atmospheric dispersion of Carbon Dioxide (CO2) from accidental pipeline releases. The code has been developed within the framework of the open source CFD code OpenFOAM® (OpenCFD, 2014). Its earlier version used the homogeneous equilibrium method for fully compressible two-phase flow. Validation of the code against CO2 releases through vertical vent pipes and horizontal shock tubes was previously reported by Wen et al. (2013). In the present study, the homogeneous relaxation model has been implemented as it is more suited to account for the presence of solid CO2 within the releases. For validation, the enhanced CO2FOAM has been used to predict CO2 dispersion in a range of full scale tests within the dense phase CO2 PipeLine TRANSportation (COOLTRANS) research programme (Cooper, 2012) funded by National Grid. The test case used in the present study involved a puncture in a buried pipe. The experimental measurements were supplied to the authors after the predictions were completed and submitted to National Grid. Hence, the validation reported here is indeed ‘blind’. The validated model has also been used to study the effect of a commercial building located downstream from the release location

SR120819A, an orally-active and selective neuropeptide Y Y1 receptor antagonist

AbstractAn orally-active antagonist of neuropeptide Y (NPY) Y1 receptors, SR 120819A, has been characterized. This compound displays highly selective and competitive affinity for rat, guinea-pig and human (Ki = 15 nM) NPY Y1 receptors. In vitro, SR 120819A blocks the inhibitory effect of NPY on adenylyl cyclase activity in human SK-N-MC cells and that of the selective Y1 agonist, [Leu31,Pro34]NPY, on rabbit vas deferens contraction (pA2 = 7.20 ± 0.07). In vivo, by intravenous route, this compound acts as an antagonist in anesthetized guinea-pigs and, notably, after oral administration, SR 120819A counteracts the pressor response of [Leu31,Pro34]NPY (5 μg/kg i.v.) with a long duration of action (>4 h at 5 mg/kg p.o.). Thus, SR 120819A is the first orally-effective NPY Y1 receptor antagonist yet descrobed. It could be a useful tool for exploring the role of NPY and the therapeutic relevance of an antagonist at NPY Y1 receptors

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201

Association of the CpG Methylation Pattern of the Proximal Insulin Gene Promoter with Type 1 Diabetes

The insulin (INS) region is the second most important locus associated with Type 1 Diabetes (T1D). The study of the DNA methylation pattern of the 7 CpGs proximal to the TSS in the INS gene promoter revealed that T1D patients have a lower level of methylation of CpG -19, -135 and -234 (p = 2.10−16) and a higher methylation of CpG -180 than controls, while methylation was comparable for CpG -69, -102, -206. The magnitude of the hypomethylation relative to a control population was 8–15% of the corresponding levels in controls and was correlated in CpGs -19 and -135 (r = 0.77) and CpG -135 and -234 (r = 0.65). 70/485 (14%) of T1D patients had a simultaneous decrease in methylation of CpG -19, -135, -234 versus none in 317 controls. CpG methylation did not correlate with glycated hemoglobin or with T1D duration. The methylation of CpG -69, -102, -180, -206, but not CpG -19, -135, -234 was strongly influenced by the cis-genotype at rs689, a SNP known to show a strong association with T1D. We hypothesize that part of this genetic association could in fact be mediated at the statistical and functional level by the underlying changes in neighboring CpG methylation. Our observation of a CpG-specific, locus-specific methylation pattern, although it can provide an epigenetic biomarker of a multifactorial disease, does not indicate whether the reported epigenetic pattern preexists or follows the establishment of T1D. To explore the effect of chronic hyperglycemia on CpG methylation, we studied non obese patients with type 2 diabetes (T2D) who were found to have decreased CpG-19 methylation versus age-matched controls, similar to T1D (p = 2.10−6) but increased CpG-234 methylation (p = 5.10−8), the opposite of T1D. The causality and natural history of the different epigenetic changes associated with T1D or T2D remain to be determined

Approche éco-épidémiologique de la Tremblante du mouton (étude du rôle de l'environnement dans le Pays Basque français)

PARIS-Museum-Bib zoologie mam. (751052312) / SudocNANTES-Ecole Nat.Vétérinaire (441092302) / SudocSudocFranceF

Etude de variants génétiques associés a la variabilité individuelle de l'insulinorésistance et de l'insulinosécrétion

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Improving performance of water and sanitation public services

International audienceImproving the performance of water and sanitation services is an objective shared by all, professionals and citizens. It will only be possible with well-designed policies and tools. An international working group bringing together all stakeholders involved in performance improvement recently gathered best practices