A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Splitting rivers at their seams: bifurcations and avulsion

River bifurcations are critical but poorly understood elements of many geomorphological systems. They are integral elements of alluvial fans, braided rivers, fluvial lowland plains, and deltas and control the partitioning of water and sediment through these systems. Bifurcations are commonly unstable but their lifespan varies greatly. In braided rivers bars and channels migrate, split and merge at annual or shorter timescales, thereby creating and abandoning bifurcations. This behaviour has been studied mainly by geomorphologists and fluid dynamicists. Bifurcations also exist during avulsion, the process of a river changing course on a floodplain or in a delta, which may take 102103 years and has been studied mainly by sedimentologists. This review synthesizes our current understanding of bifurcations and brings together insights from different research communities and different environmental settings. We consider the causes and initiation of bifurcations and avulsion, the physical mechanisms controlling bifurcation and avulsion evolution, mathematical and numerical modelling of these processes, and the possibility of stable bifurcations. We end the review with some open questions. Copyright (c) 2012 John Wiley & Sons, Ltd.

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.

Liver segmentation: Practical tips.

The liver segmentation system, described by Couinaud, is based on the identification of the three hepatic veins and the plane passing by the portal vein bifurcation. Nowadays, Couinaud's description is the most widely used classification since it is better suited for surgery and more accurate for the localisation and monitoring of intra-parenchymal lesions. Knowledge of the anatomy of the portal and venous system is therefore essential, as is knowledge of the variants resulting from changes occurring during the embryological development of the vitelline and umbilical veins. In this paper, the authors propose a straightforward systematisation of the liver in six steps using several additional anatomical points of reference. These points of reference are simple and quickly identifiable in any radiological examination with section imaging, in order to avoid any mistakes in daily practice. In fact, accurate description impacts on many diagnostic and therapeutic applications in interventional radiology and surgery. This description will allow better preparation for biopsy, portal vein embolisation, transjugular intrahepatic portosystemic shunt, tumour resection or partial hepatectomy for transplantation. Such advance planning will reduce intra- and postoperative difficulties and complications.

Early disturbances of gamma band dynamics in mild cognitive impairment.

Recent studies have indicated that gamma band oscillations participate in the temporal binding needed for the synchronization of cortical networks involved in short-term memory and attentional processes. To date, no study has explored the temporal dynamics of gamma band in the early stages of dementia. At baseline, gamma band analysis was performed in 29 cases with mild cognitive impairment (MCI) during the n-back task. Based on phase diagrams, multiple linear regression models were built to explore the relationship between the cognitive status and gamma oscillation changes over time. Individual measures of phase diagram complexity were made using fractal dimension values. After 1 year, all cases were assessed neuropsychologically using the same battery. A total of 16 MCI patients showed progressive cognitive decline (PMCI) and 13 remained stable (SMCI). When adjusted for gamma values at lag -2, and -3 ms, PMCI cases displayed significantly lower average changes in gamma values than SMCI cases both in detection and 2-back tasks. Gamma fractal dimension of PMCI cases displayed significantly higher gamma fractal dimension values compared to SMCI cases. This variable explained 11.8% of the cognitive variability in this series. Our data indicate that the progression of cognitive decline in MCI is associated with early deficits in temporal binding that occur during the activation of selective attention processes.

Expanding molecular modeling and design tools to non-natural sidechains.

Protein-protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein-protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non-natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all structural files (pdb and mol2), as well as parameters and topologies for standard molecular mechanics software (CHARMM and Gromacs). Accurate predictions of rotamer probabilities are provided using a novel combined knowledge and physics based strategy. Non-natural sidechains are useful to increase peptide ligand binding affinity. Our results obtained on non-natural mutants of a BCL9 peptide targeting beta-catenin show very good correlation between predicted and experimental binding free-energies, indicating that such predictions can be used to design new inhibitors. Data generated in this work, as well as PyMOL and UCSF Chimera plug-ins for user-friendly visualization of non-natural sidechains, are all available at http://www.swisssidechain.ch. Our results enable researchers to rapidly and efficiently work with hundreds of non-natural sidechains.

Causal assessment in finite extensive-form games

Two finite extensive-form games are empirically equivalent when theempirical distribution on action profiles generated by every behaviorstrategy in one can also be generated by an appropriately chosen behaviorstrategy in the other. This paper provides a characterization ofempirical equivalence. The central idea is to relate a game's informationstructure to the conditional independencies in the empirical distributionsit generates. We present a new analytical device, the influence opportunitydiagram of a game, describe how such a diagram is constructed for a givenextensive-form game, and demonstrate that it provides a complete summaryof the information needed to test empirical equivalence between two games.

An experimental study of discharge partitioning and flow structure at symmetrical bifurcations

Recent research has examined the factors controlling the geometrical configuration of bifurcations, determined the range of stability conditions for a number of bifurcation types and assessed the impact of perturbations on bifurcation evolution. However, the flow division process and the parameters that influence flow and sediment partitioning are still poorly characterized. To identify and isolate these parameters, three-dimensional velocities were measured at 11 cross-sections in a fixed-walled experimental bifurcation. Water surface gradients were controlled, and systematically varied, using a weir in each distributary. As may be expected, the steepest distributary conveyed the most discharge ( was dominant) while the mildest distributary conveyed the least discharge ( was subordinate). A zone of water surface super-elevation was co-located with the bifurcation in symmetric cases or displaced into the subordinate branch in asymmetric cases. Downstream of a relatively acute-angled bifurcation, primary velocity cores were near to the water surface and against the inner banks, with near-bed zones of lower primary velocity at the outer banks. Downstream of an obtuse-angled bifurcation, velocity cores were initially at the outer banks, with near-bed zones of lower velocities at the inner banks, but patterns soon reverted to match the acute-angled case. A single secondary flow cell was generated in each distributary, with water flowing inwards at the water surface and outwards at the bed. Circulation was relatively enhanced within the subordinate branch, which may help explain why subordinate distributaries remain open, may play a role in determining the size of commonly-observed topographic features, and may thus exert some control on the stability of asymmetric bifurcations. Further, because larger values of circulation result from larger gradient disadvantages, the length of confluence-diffluence units in braided rivers or between diffluences within delta distributary networks may vary depending upon flow structures inherited from upstream and whether, and how, they are fed by dominant or subordinate distributaries. Copyright (C) 2011 John Wiley & Sons, Ltd.

Caste polymorphism of apterous line of the Neotropical termite Nasutitermes corniger (Motschulsky) (Isoptera, Termitidae)

Termite societies are structured by individuals that can be grouped into castes and instars. The development of these instars in most species occurs in irregular patterns and sometimes is distinguished subcastes in physical systems that originate polymorphic soldiers and workers. In this study, we characterized the morphological diversity of castes of apterous in Nasutitermes corniger. We collected four colonies of N. corniger, one every three months between May 2011 and February 2012. Individuals of the nest were separated into groups: larval stages, workers and presoldiers and soldiers. A morphometric analysis was performed on individuals from each group based on head width, metatibia, antenna, and thorax length. The data were submitted to discriminant analysis to confirm different morphological types inside these groups. The apterous line of N. corniger is composed of one first larval instar and two second larval instar. The workers caste has two lines of development with four instars in a larger line and three instars in a lower line. Two morphological types were identified in presoldiers and soldiers. The pattern of castes was similar to other species of the genus, in which bifurcation into two lines of workers, one smaller and one larger occurs after the first molt.

Natural classification of knots

The principal objective of the knot theory is to provide a simple way of classifying and ordering all the knot types. Here, we propose a natural classification of knots based on their intrinsic position in the knot space that is defined by the set of knots to which a given knot can be converted by individual intersegmental passages. In addition, we characterize various knots using a set of simple quantum numbers that can be determined upon inspection of minimal crossing diagram of a knot. These numbers include: crossing number; average three-dimensional writhe; number of topological domains; and the average relaxation value

Cartographier les géomorphosites : objectifs, publics et propositions méthodologiques

Related to the raise of the awareness of the importance of the Earth heritage, geomorphosites receive increasing attention from the scientific community. Assessment methods, classification and conservation strategies have been developed to safeguard the geomorphological heritage for present and future generations. On the other hand, Earth heritage offers opportunities to develop educational and recreational programs as well as tourism projects. Various interpretive supports and local development projects have been engendered in the past few years to promote geoheritage.¦Be it for the assessment, conservation or promotion of geomorphosites, maps are valuable from many standpoints. They can provide fundamental data for detailed geomorphosite description, serve as visual communication tools helping to guide the selection process in defining protection priority or supporting Earth heritage promotion and interpretàtion.¦This study reviews the main achievements and the objectives yet to be accomplished in the field of geomorphosite mapping and proposes a general framework for the mapping of geomorphosites that takes into account the different aims and publics. The main focus is on mapping geomorphosites for non-specialists in the field of Earth heritage promotion (Geotourism). In this context, maps are often employed to show itineraries or points of interest. Like a scheme or a diagram, a map can also be used as a method for visualising geoscientific information. This function is particularly important since some processes, which contributed to the formation of a geomorphosite or a geomorphological landscape are no longer or not always clearly visible in the landscape. In this case, maps become interpretive media that serve popularisation purposes.¦Mapping for non-specialists holds the challenging task to ensure the information transfer between the cartographer and the user. We therefore focus on both the implementation of the map by the cartographer (which information? which visualisation?) and the interpretation of the map by the user (effectiveness of the knowledge transfer). The research is based on empirical studies carried out in the Maderan valley (Canton of Uri) and in classes of the Cantons of Uri and Tessin that aim to gain knowledge about the familiarity and interests of non- specialists for geoheritage as well as about their map reading skills. The final objective is to formulate methodological proposals for geomorphosite mapping for interpretive purpose.

UBVRI-CCD photometry of Cepheus OB3 association

Johnson CCD photometry was performed in the two subgroups of the association Cepheus OB3, for selected fields each containing at least one star with previous UBV photoelectric photometry. Photometry for about 1000 stars down to visual magnitude 21 is provided, although the completeness tests show that the sample is complete down to V=19mag. Individual errors were assigned to the magnitude and colours for each star. Colour-colour and colour-magnitude diagrams are shown. Astrometric positions of the stars are also given. Description of the reduction procedure is fully detailed.

An analysis of the currently available calibrations inStromgren photometry by using open clusters

In recent years, several authors have revised the calibrations used to compute physical parameters (tex2html_wrap_inline498, tex2html_wrap_inline500, log g, [Fe/H]) from intrinsic colours in the tex2html_wrap_inline504 photometric system. For reddened stars, these intrinsic colours can be computed through the standard relations among colour indices for each of the regions defined by Strömgren (1966) on the HR diagram. We present a discussion of the coherence of these calibrations for main-sequence stars. Stars from open clusters are used to carry out this analysis. Assuming that individual reddening values and distances should be similar for all the members of a given open cluster, systematic differences among the calibrations used in each of the photometric regions might arise when comparing mean reddening values and distances for the members of each region. To classify the stars into Strömgren's regions we extended the algorithm presented by Figueras et al. (1991) to a wider range of spectral types and luminosity classes. The observational ZAMS are compared with the theoretical ZAMS from stellar evolutionary models, in the range tex2html_wrap_inline506 K. The discrepancies are also discussed.

Period-Luminosity-Colour distribution and classification of Galactic oxygen-rich LPVs I. Luminosity calibrations

The absolute K magnitudes and kinematic parameters of about 350 oxygen-rich Long-Period Variable stars are calibrated, by means of an up-to-date maximum-likelihood method, using HIPPARCOS parallaxes and proper motions together with radial velocities and, as additional data, periods and V-K colour indices. Four groups, differing by their kinematics and mean magnitudes, are found. For each of them, we also obtain the distributions of magnitude, period and de-reddened colour of the base population, as well as de-biased period-luminosity-colour relations and their two-dimensional projections. The SRa semiregulars do not seem to constitute a separate class of LPVs. The SRb appear to belong to two populations of different ages. In a PL diagram, they constitute two evolutionary sequences towards the Mira stage. The Miras of the disk appear to pulsate on a lower-order mode. The slopes of their de-biased PL and PC relations are found to be very different from the ones of the Oxygen Miras of the LMC. This suggests that a significant number of so-called Miras of the LMC are misclassified. This also suggests that the Miras of the LMC do not constitute a homogeneous group, but include a significant proportion of metal-deficient stars, suggesting a relatively smooth star formation history. As a consequence, one may not trivially transpose the LMC period-luminosity relation from one galaxy to the other.

Does gender really matter in cathlab

Purpose: Results of some PCI clinical trials indicated more procedure related complications and worse clinical outcomes in women than men, but due to a lower representation of female patients this question still remains open. We aimed toinvestigate characteristics and early and late clinical outcomes in female patients as compared to male when treated in a real life setting with a new generation DES.Methods: Among 3069 consecutive patients treated with Nobori DES, and enrolled in NOBORI 2 study, 675 were female. The primary endpoint of the study is target lesion failure (TLF), a composite of cardiac death, MI and target lesion revascularization (TLR) at 12 months. Data are entered in an electronic database; all adverse events are adjudicated by an independent clinical event committee and independent corelabs analyse all angiograms.Results: Compared to male patients, female patients were significantly older (68±10 vs ± 63±11 years; p<0.001), had higher incidence of diabetes (37% vs 27%; p<0.001) and hypertension (75% vs 66%; p<0.001), but lower frequency of previous MI, PCI/CABG and smoking history. Lesion characteristics were similar in two genders, except for lesions located at bifurcation which were more frequent inmale patients (22% vs 15% inmale and female patients respectively; p<0.001). Majority of QCA assessed parameters were similar with the exception for RVD, post-procedure MLD in-segment and %DS in-stent which were significantly lower in female patients (p<0.05 for all). In table 1 results at 6 months follow-up are presented and at the time of presentation 1 year results will be available. Table 1. Clinical results at 6 months follow-up Male (n=2394) Female (n=675) P value Cardiac Death 12 (0.5%) 5 (0.7%) 0.5550 MI 5 (2.1%) 4 (1.3%) 0.5089 TLR rate 17 (0.7%) 13 (1.9%) 0.0124 TLF rate 44 (1.8%) 17 (2.5%) 0.2745 Stent Thrombosis 12 (0.5%) 6 (0.9%) 0.2548Conclusions: Results indicate that there are differences in the demographics and risk factors in female and male patient's population. The frequency of adverse events at 6 months is low in both populations, showing trend toward slightly higher rate in female patients, particularly for target lesion revascularization.