Genetic overlap in kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia.

Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain.

A multidimensional segmentation evaluation for medical image data.

Evaluation of segmentation methods is a crucial aspect in image processing, especially in the medical imaging field, where small differences between segmented regions in the anatomy can be of paramount importance. Usually, segmentation evaluation is based on a measure that depends on the number of segmented voxels inside and outside of some reference regions that are called gold standards. Although some other measures have been also used, in this work we propose a set of new similarity measures, based on different features, such as the location and intensity values of the misclassified voxels, and the connectivity and the boundaries of the segmented data. Using the multidimensional information provided by these measures, we propose a new evaluation method whose results are visualized applying a Principal Component Analysis of the data, obtaining a simplified graphical method to compare different segmentation results. We have carried out an intensive study using several classic segmentation methods applied to a set of MRI simulated data of the brain with several noise and RF inhomogeneity levels, and also to real data, showing that the new measures proposed here and the results that we have obtained from the multidimensional evaluation, improve the robustness of the evaluation and provides better understanding about the difference between segmentation methods.

Substantial deletion overlap among divergent Arabidopsis genomes revealed by intersection of short reads and tiling arrays.

ABSTRACT: Identification of small polymorphisms from next generation sequencing short read data is relatively easy, but detection of larger deletions is less straightforward. Here, we analyzed four divergent Arabidopsis accessions and found that intersection of absent short read coverage with weak tiling array hybridization signal reliably flags deletions. Interestingly, individual deletions were frequently observed in two or more of the accessions examined, suggesting that variation in gene content partly reflects a common history of deletion events.

Use of a multidimensional assessment tool in a psychiatric adolescent care unit.

AIMS: Adolescent mental health problems require treatment and care that are adapted to their needs. To evaluate this issue, it was decided to implement a multidimensional instrument focused on a global approach to adolescent social and behavioural functioning, combined with the ICD-10 classification. METHODS: The combination of an assessment interview and a classification tool enabled the method to integrate the measurement of several domains of patient-based outcome rather than focus on the measurement of symptoms. A group of 68 adolescents from an inpatient unit were compared with 67 adolescents from the general population. RESULTS: Results suggest that adolescents from the care unit adopt significantly riskier behaviour compared with adolescents from the control group. As expected, the main problems identified refer to the psychological and familial areas. A cluster analysis was performed and provided three different profiles: a group with externalizing disorders and two groups with internalizing disorders. On the basis of a structured interview it was possible to obtain information in a systematic way about the adolescents' trajectory (delinquency, physical and sexual abuse, psychoactive substance use). CONCLUSION: It was shown that treatment and care should not focus exclusively on mental health symptoms, but also upon physical, psychological and social aspects of the adolescent. A global approach helps in the consideration of the multitude of factors which must be taken into account when working with people with serious mental health problems and may help to turn the care unit's activity more specifically towards the needs of these adolescents.

Measuring ecological niche overlap from occurrence and spatial environmental data

1. Aim - Concerns over how global change will influence species distributions, in conjunction with increased emphasis on understanding niche dynamics in evolutionary and community contexts, highlight the growing need for robust methods to quantify niche differences between or within taxa. We propose a statistical framework to describe and compare environmental niches from occurrence and spatial environmental data.¦2. Location - Europe, North America, South America¦3. Methods - The framework applies kernel smoothers to densities of species occurrence in gridded environmental space to calculate metrics of niche overlap and test hypotheses regarding niche conservatism. We use this framework and simulated species with predefined distributions and amounts of niche overlap to evaluate several ordination and species distribution modeling techniques for quantifying niche overlap. We illustrate the approach with data on two well-studied invasive species.¦4. Results - We show that niche overlap can be accurately detected with the framework when variables driving the distributions are known. The method is robust to known and previously undocumented biases related to the dependence of species occurrences on the frequency of environmental conditions that occur across geographic space. The use of a kernel smoother makes the process of moving from geographical space to multivariate environmental space independent of both sampling effort and arbitrary choice of resolution in environmental space. However, the use of ordination and species distribution model techniques for selecting, combining and weighting variables on which niche overlap is calculated provide contrasting results.¦5. Main conclusions - The framework meets the increasing need for robust methods to quantify niche differences. It is appropriate to study niche differences between species, subspecies or intraspecific lineages that differ in their geographical distributions. Alternatively, it can be used to measure the degree to which the environmental niche of a species or intraspecific lineage has changed over time.

Ecological niche overlap in sister species: how do oil-collecting bees Macropis europaea and M. fulvipes (Hymenoptera: Melittidae) avoid competition and hybridization?

Oil-collecting bees are found worldwide and always in association with particular oil-producing flowers. In the Western Palearctic, three oil-collecting bee species within the genus Macropis (Hymenoptera, Melittidae) interact in a tight pollination mutualism with species of the only European oil-producing plant genus Lysimachia L. (Myrsinaceae). Two of these oil-collecting bees (Macropis europaea and Macropis fulvipes) show overlapping geographic distributions, comparable morphologies, and similar ecological characteristics (e.g., habitat type, floral preferences). In view of these similarities, we presume that hybridization should occur between the two species unless potential variation among the species' ecological niches prevents it, simultaneously decreasing competition for resources. Using modern genetic analyses and ecological niche modeling on a large bee sampling throughout Europe, we discuss new perspectives on the ecology and evolutionary history of this mutualism.

Efficacy of in-hospital multidimensional interventions of secondary prevention after acute coronary syndrome: a systematic review and meta-analysis

BACKGROUND: Secondary prevention programs for patients experiencing an acute coronary syndrome have been shown to be effective in the outpatient setting. The efficacy of in-hospital prevention interventions administered soon after acute cardiac events is unclear. We performed a systematic review and meta-analysis to determine whether in-hospital, patient-level interventions targeting multiple cardiovascular risk factors reduce all-cause mortality after an acute coronary syndrome. METHODS AND RESULTS: Using a prespecified search strategy, we included controlled clinical trials and before-after studies of secondary prevention interventions with at least a patient-level component (ie, education, counseling, or patient-specific order sets) initiated in hospital with outcomes of mortality, readmission, or reinfarction rates in acute coronary syndrome patients. We classified the interventions as patient-level interventions with or without associated healthcare provider-level interventions and/or system-level interventions. Twenty-six studies met our inclusion criteria. The summary estimate of 14 studies revealed a relative risk of all-cause mortality of 0.79 (95% CI, 0.69 to 0.92; n=37,585) at 1 year. However, the apparent benefit depended on study design and level of intervention. The before-after studies suggested reduced mortality (relative risk [RR], 0.77; 95% CI, 0.66 to 0.90; n=3680 deaths), whereas the RR was 0.96 (95% CI, 0.64 to 1.44; n=99 deaths) among the controlled clinical trials. Only interventions including a provider- or system-level intervention suggested reduced mortality compared with patient-level-only interventions. CONCLUSIONS: The evidence for in-hospital, patient-level interventions for secondary prevention is promising but not definitive because only before-after studies suggest a significant reduction in mortality. Future research should formally test which components of interventions provide the greatest benefit.

The handaxe and the microscope: individual and social learning in a multidimensional model of adaptation

When individuals learn by trial-and-error, they perform randomly chosen actions and then reinforce those actions that led to a high payoff. However, individuals do not always have to physically perform an action in order to evaluate its consequences. Rather, they may be able to mentally simulate actions and their consequences without actually performing them. Such fictitious learners can select actions with high payoffs without making long chains of trial-and-error learning. Here, we analyze the evolution of an n-dimensional cultural trait (or artifact) by learning, in a payoff landscape with a single optimum. We derive the stochastic learning dynamics of the distance to the optimum in trait space when choice between alternative artifacts follows the standard logit choice rule. We show that for both trial-and-error and fictitious learners, the learning dynamics stabilize at an approximate distance of root n/(2 lambda(e)) away from the optimum, where lambda(e) is an effective learning performance parameter depending on the learning rule under scrutiny. Individual learners are thus unlikely to reach the optimum when traits are complex (n large), and so face a barrier to further improvement of the artifact. We show, however, that this barrier can be significantly reduced in a large population of learners performing payoff-biased social learning, in which case lambda(e) becomes proportional to population size. Overall, our results illustrate the effects of errors in learning, levels of cognition, and population size for the evolution of complex cultural traits. (C) 2013 Elsevier Inc. All rights reserved.