Metabolic Syndrome as a Cardiovascular Disease Risk Factor: Patients Evaluated in Primary Care

To estimate the prevalence of metabolic syndrome (MS) in a population receiving attention in primary care centers (PCC) we selected a random cohort of ostensibly normal subjects from the registers of 5 basic-health area (BHA) PCC. Diagnosis of MS was with the WHO, NCEP and IDF criteria. Variables recorded were: socio-demographic data, CVD risk factors including lipids, obesity, diabetes, blood pressure and smoking habit and a glucose tolerance test outcome. Of the 720 individuals selected (age 60.3 ± 11.5 years), 431 were female, 352 hypertensive, 142 diabetic, 233 pre-diabetic, 285 obese, 209 dyslipemic and 106 smokers. CVD risk according to the Framingham and REGICOR calculation was 13.8 ± 10% and 8.8 ± 9.8%, respectively. Using the WHO, NCEP and IDF criteria, MS was diagnosed in 166, 210 and 252 subjects, respectively and the relative risk of CVD complications in MS subjects was 2.56. Logistic regression analysis indicated that the MS components (WHO set), the MS components (IDF set) and the female gender had an increased odds ratio for CVD of 3.48 (95CI%: 2.26–5.37), 2.28 (95%CI: 1.84–4.90) and 2.26 (95%CI: 1.48–3.47), respectively. We conclude that MS and concomitant CVD risk is high in ostensibly normal population attending primary care clinics, and this would necessarily impinge on resource allocation in primary care

Sediment undulations on the Llobregat prodelta: Signs of early slope instability or sedimentary bedforms?

A field of sediment undulations has been mapped by means of high resolution multibeam bathymetry and seismic reflection profiles in the Llobregat River prodelta, off the city of Barcelona, Catalonia, Spain. Similar features had previously been recognized in other prodelta environments and interpreted either as downslope sediment deformation or sedimentary structures induced by bottom currents or hyperpycnal flows. Since the study area is undergoing significant offshore development, proper interpretation of such sediment undulations is needed for a correct risk assessment. The occurrence of the sediment undulations is restricted to the prodelta front on slope gradients between 3 and 0.2º. The undulations have developed at the edge and atop an area of gas bearing sediments within the Late-Holocene high-stand mud wedge. An evaluation is made of the characteristics of the sediment undulations in order to determine the most likely process for the origin of these structures. Amongst these characteristics are the continuity of the reflections and lack of diffractions in between different undulations, their size distribution (large to small) both from shallow to deep and with depth in section, the asymmetry (decreasing from proximal to distal), the crest to trough vertical distance on the landward side of the undulations (up to 0.5 m), and the lack of features that could indicate a progressive movement such as growth structures and drag folds. These characteristics indicate that the sediment undulations on the Llobregat River prodelta do not result from sediment deformation, but rather from the interaction of bottom currents generated by hyperpycnal flows from the Llobregat River with regional sea water circulation. Their identification as sediment waves implies that such features do not pose a major hazard for urther offshore development

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Slit/Robo Signaling Modulates the Proliferation of Central Nervous System Progenitors

Neurogenesis relies on a delicate balance between progenitor maintenance and neuronal production. Progenitors divide symmetrically to increase the pool of dividing cells. Subsequently, they divide asymmetrically to self-renew and produce new neurons or, in some brain regions, intermediate progenitor cells (IPCs). Here we report that central nervous system progenitors express Robo1 and Robo2, receptors for Slit proteins that regulate axon guidance, and that absence of these receptors or their ligands leads to loss of ventricular mitoses. Conversely, production of IPCs is enhanced in Robo1/2 and Slit1/2 mutants, suggesting that Slit/Robo signaling modulates the transition between primary and intermediate progenitors. Unexpectedly, these defects do not lead to transient overproduction of neurons, probably because supernumerary IPCs fail to detach from the ventricular lining and cycle very slowly. At the molecular level, the role of Slit/Robo in progenitor cells involves transcriptional activation of the Notch effector Hes1. These findings demonstrate that Robo signaling modulates progenitor cell dynamics in the developing brain. Video Abstract: Borrell et al. demonstrate that Slit-Robo signaling regulates the progression from radial glia to intermediate progenitor cells in the embryonic mouse cerebral cortex. Robo effects are mediated by regulation of Hes1 transcription independently of, and synergistically to, Notch. © 2012 Elsevier Inc.Supported by grants from Spanish Ministry of Economy and Innovation MINECO (SAF2011-28845 and CONSOLIDER CSD2007-00023) to O.M. R01 NIH(NINDS) to L.M., and MINECO (SAF2009-07367) and the International Human Frontier Science Program Organization to V.B. A.C. and G.C. are recipients of a >Formacion de Personal Investigador> (FPI) fellowship from the MINECO.Peer Reviewe