Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Variability of energy use for domestic space heating

The level of reported variability of domestic space heating energy use is extremely high, the coefficient of variation being 20% even for groups of similar houses. In consequence, there is a need for heating systems to work effectively and economically over a wide range of energy use levels and there is also a need for large sample sizes in evaluating field results if the effects of individual factors contributing to the overall variability are to be assessed. For dissimilar houses, samples of 25 or more are necessary for the detection of individual factors and hundreds may be required for their accurate estimation. The effect on energy use of night temperature set-back is shown theoretically to be equivalent to a 2% energy saving per degree Kelvin temperature depression. The effects of more intermittent heating system operation are provisionally estimated, a 50% energy saving being estimated for a 6-h period of daily use at the required temperature. Effects of choice of internal temperature and ventilation rate on energy use are assessed. The energy savings made by such personal control strategies can be nullified by equipment deficiencies. The magnitudes of the effects of three such deficiencies (pipe or duct losses, unresponsive emitter control and upstairs overheating in mild weather) are estimated as each adding around 20% to the heating energy use of a typical house. The combined effects of energy saving strategies and equipment deficiencies make possible annual energy use figures from half to one-and-a-half times the designed level. The implications of this variability for heating system design are discussed.

Guide du transport frigorifique

This guide provides all the basic information necessary on the transport of perishable foodstuffs, regardless of the mode of transport : sea, land (road or rail), air. It deals in particular with containers and multimodal transport. It is abundantly illustrated with graphics and tables. / L'objectif de cet ouvrage est de fournir l'ensemble des informations essentielles sur le transport des denrées périssables quel que soit le mode de transport : terrestre (route, rail), maritime ou aérien. Il traite notamment du transfert multimodal et des conteneurs. Il est abondamment doté de chiffres, de tableaux et d'illustrations