Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Pelvic trauma : WSES classification and guidelines

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.Peer reviewe

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Moving Object Recognition and Classification based on Recursive Shape Parameter Estimation

. We present an approach for recognizing and classifying moving vehicles in monocular images sequences of traffic scenes recorded by a stationary camera. A generic vehicle model, represented by a 3D polyhedral model described by 12 length parameters, is used to cover the different shapes of road vehicles. The object recognition process is initialized by formulating a model hypothesis using a reference model and initial values provided by a motion segmentation step from a model-based tracking system described previously. This model hypothesis is verified and the shape as well as the pose and motion parameters of the object are estimated simultaneously. A recursive estimator updates the state description of the shape and motion parameters. In this way all relevant data from the image sequence evaluated so far are accumulated and used for the shape parameter estimation and classification of a moving vehicle. A classification is based on the assumption that differences between class membe..

A Machine Vision Based System for Guiding Lane-change Maneuvers

We propose a new approach for vision based longitudinal and lateral ve-hicle control which makes extensive use of binocular stereopsis. Longitudi-nal control - i.e. maintaining a safe, constant distance from the vehicle infront - is supported by detecting and measuring the distances to leadingvehicles using binocular stereo.A known camera geometry with respect tothe locally planar road is used to map the images of the road plane in thetwo camera views into alignment.Any significant residual image disparitythen indicates an object not lying in the road plane and hence a potentialobstacle. This approach allows us to separate image features into those lyingin the road plane, e.g.lane markers, and those due to other objects. Thefeatures which lie on the road are stationary in the scene and appear to moveonly because of the egomotion of the vehicle. Measurements on these featuresare used for dynamic update of (a) the camera parameters in the presenceof camera vibration and changes in road slope (b) the lateral position of thevehicle with respect to the lane markers.In the absence of this separation,image features due to vehicles which happen to lie in the search zone for lanemarkers would corrupt the estimation of the road boundary contours. Thisproblem has not yet been addressed by any lane marker based vehicle guid-ance approach, but has to be taken very seriously, since usually one has tocope with crowded traffic scenes where lane markers are often obstructed byvehicles. Lane markers are detected and used for lateral control, i.e. followingthe road while maintaining a constant lateral distance to the road boundary.For that purpose we model the road and hence the shape of the lane markersas clothoidal curves, the curvatures of which we estimate recursively along theimage sequence. These curvature estimates also provides desirable look-aheadinformation for a smooth ride in the car