Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity

ECIS 2014 E-HEALTH PANEL: CRITICAL CONSIDERATIONS IN THE DESIGN, DEVELOPMENT AND IMPLEMENTATION OF E-HEALTH SOLUTIONS

Healthcare delivery, irrespective of the region in the world, is facing the key challenges of escalating costs, an aging population, an increase in a myriad of diagnostic technologies and the rise of chronic diseases which in turn is leading to a more and more preventative focus. In short, the current state of healthcare delivery is not sustainable (OECD, 2012a;2012b; Porter and Guth, 2012; Porter and Teisberg,2006; Pearce and Haikerwal, 2010; Wickramasinghe and Schaffer, 2010). Most countries are responding with various types of healthcare reform and turning to e-health solutions. But e-health is not a panacea for the maladies faced by healthcare delivery. Moreover, it is important to understand the key macro and micro issues as well as vital people, process and technology aspects if superior and sustainable healthcare delivery is to ensue

The EDGE-CALIFA Survey: Interferometric Observations of 126 Galaxies with CARMA

We present interferometric CO observations, made with the Combined Array for Millimeter-wave Astronomy (CARMA) interferometer, of galaxies from the Extragalactic Database for Galaxy Evolution survey (EDGE). These galaxies are selected from the Calar Alto Legacy Integral Field Area (CALIFA) sample, mapped with optical integral field spectroscopy. EDGE provides good-quality CO data (3σ sensitivity before inclination correction, resolution ∼1.4 kpc) for 126 galaxies, constituting the largest interferometric CO survey of galaxies in the nearby universe. We describe the survey and data characteristics and products, then present initial science results. We find that the exponential scale lengths of the molecular, stellar, and star-forming disks are approximately equal, and galaxies that are more compact in molecular gas than in stars tend to show signs of interaction. We characterize the molecular-to-stellar ratio as a function of Hubble type and stellar mass and present preliminary results on the resolved relations between the molecular gas, stars, and star-formation rate. We then discuss the dependence of the resolved molecular depletion time on stellar surface density, nebular extinction, and gas metallicity. EDGE provides a key data set to address outstanding topics regarding gas and its role in star formation and galaxy evolution, which will be publicly available on completion of the quality assessment.Fil: Bolatto, Alberto. University of Maryland; Estados UnidosFil: Wong, Tony. University of Illinois at Urbana; Estados UnidosFil: Utomo, Dyas. University of California at Berkeley; Estados UnidosFil: Blitz, Leo. University of California at Berkeley; Estados UnidosFil: Vogel, Stuart N.. University of Maryland; Estados UnidosFil: Sánchez, Sebastián F.. Universidad Nacional Autónoma de México; MéxicoFil: Barrera-Ballesteros, Jorge. University Johns Hopkins; Estados UnidosFil: Cao, Yixian. University of Illinois; Estados UnidosFil: Colombo, Dario. Max Planck Institut Fur Radioastronomie; AlemaniaFil: Dannerbauer, Helmut. Universidad de La Laguna; EspañaFil: García-Benito, Rubén. Instituto de Astrofísica de Andalucía; EspañaFil: Herrera-Camus, Rodrigo. Max Planck Institute für Extraterrestrische Physik; AlemaniaFil: Husemann, Bernd. Max-Planck-Institut für Astronomie; AlemaniaFil: Kalinova, Veselina. Max Planck Institut für Radioastronomie; AlemaniaFil: Leroy, Adam K.. Ohio State University; Estados UnidosFil: Leung, Gigi. Max-Planck-Institut für Astronomie; AlemaniaFil: Levy, Rebecca C.. University of Maryland; Estados UnidosFil: Mast, Damian. Observatorio Astronomico de la Universidad Nacional de Cordoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ostriker, Eve. University of Princeton; Estados UnidosFil: Rosolowsky, Erik. University of Alberta; CanadáFil: Sandstrom, Karin M.. University of California at San Diego; Estados UnidosFil: Teuben, Peter. University of Maryland; Estados UnidosFil: Van De Ven, Glenn. Max-Planck-Institut für Astronomie; AlemaniaFil: Walter, Fabian. Max-Planck-Institut für Astronomie; Alemani

Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis

Heritability of obesity is substantial and recent meta-analyses of genome-wide association studies (GWASs) have been successful in detecting several robustly associated genomic regions for obesity using single-nucleotide polymorphisms (SNPs). However, taken together, the SNPs explain only a small proportion of the overall heritability. Copy number variations (CNVs) might contribute to the ‘missing heritability’. We searched genome-wide for association between common CNVs and early-onset extreme obesity. Four hundred and twenty-four case-parents obesity trios and an independent sample of 453 extremely obese children and adolescents and 435 normal-weight and lean adult controls were genotyped by the Affymetrix Genome-Wide Human SNP Array 6.0. We detected 20 common copy number variable regions (CNVRs) which were associated with obesity. The most promising CNVRs were followed-up in an independent sample of 365 obesity trios, confirming the association for two candidate CNVRs. We identified a common CNVR exclusively covering the three olfactory receptor genes OR4P4, OR4S2 and OR4C6 to be associated with obesity (combined P-value = 0.015 in a total of 789 families; odds ratio for the obesity effect allele = 1.19; 95% confidence interval = 1.016–1.394). We also replicated two common deletions (near NEGR1 and at chromosome 10q11.22) that have previously been reported to be associated with body weight. Additionally, we support a rare CNV on chromosome 16 that has recently been reported by two independent groups. However, rare CNVs had not been the focus of our study. We conclude that common CNVs are unlikely to contribute substantially to the genetic basis of early-onset extreme obesity

Indications for liver transplantation in adults

Liver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics