Selection on a eumelanic ornament is stronger in the tropics than in temperate zones in the worldwide-distributed barn owl.

Spatial variation in the pattern of natural selection can promote local adaptation and genetic differentiation between populations. Because heritable melanin-based ornaments can signal resistance to environmentally mediated elevation in glucocorticoids, to oxidative stress and parasites, populations may vary in the mean degree of melanic coloration if selection on these phenotypic aspects varies geographically. Within a population of Swiss barn owls (Tyto alba), the size of eumelanic spots is positively associated with survival, immunity and resistance to stress, but it is yet unknown whether Tyto species that face stressful environments evolved towards a darker eumelanic plumage. Because selection regimes vary along environmental gradients, we examined whether melanin-based traits vary clinally and are expressed to a larger extent in the tropics where parasites are more abundant than in temperate zones. To this end, we considered 39 barn owl species distributed worldwide. Barn owl species living in the tropics displayed larger eumelanic spots than those found in temperate zones. This was, however, verified in the northern hemisphere only. Parasites being particularly abundant in the tropics, they may promote the evolution of darker eumelanic ornaments.

Functional analysis: evaluation of response intensities--tailoring ANOVA for lists of expression subsets.

Background: Microarray data is frequently used to characterize the expression profile of a whole genome and to compare the characteristics of that genome under several conditions. Geneset analysis methods have been described previously to analyze the expression values of several genes related by known biological criteria (metabolic pathway, pathology signature, co-regulation by a common factor, etc.) at the same time and the cost of these methods allows for the use of more values to help discover the underlying biological mechanisms. Results: As several methods assume different null hypotheses, we propose to reformulate the main question that biologists seek to answer. To determine which genesets are associated with expression values that differ between two experiments, we focused on three ad hoc criteria: expression levels, the direction of individual gene expression changes (up or down regulation), and correlations between genes. We introduce the FAERI methodology, tailored from a two-way ANOVA to examine these criteria. The significance of the results was evaluated according to the self-contained null hypothesis, using label sampling or by inferring the null distribution from normally distributed random data. Evaluations performed on simulated data revealed that FAERI outperforms currently available methods for each type of set tested. We then applied the FAERI method to analyze three real-world datasets on hypoxia response. FAERI was able to detect more genesets than other methodologies, and the genesets selected were coherent with current knowledge of cellular response to hypoxia. Moreover, the genesets selected by FAERI were confirmed when the analysis was repeated on two additional related datasets. Conclusions: The expression values of genesets are associated with several biological effects. The underlying mathematical structure of the genesets allows for analysis of data from several genes at the same time. Focusing on expression levels, the direction of the expression changes, and correlations, we showed that two-step data reduction allowed us to significantly improve the performance of geneset analysis using a modified two-way ANOVA procedure, and to detect genesets that current methods fail to detect.

Discriminant validity and test-retest reliability of a self-administered Internet-based questionnaire testing doctors' knowledge in evidence-based medicine.

Aims and objectives  This study aimed to determine the discriminant validity and the test-retest reliability of a questionnaire testing the impact of evidence-based medicine (EBM) training on doctors' knowledge and skills. Methods  Questionnaires were sent electronically to all doctors working as residents and chief residents in two French speaking hospital networks in Switzerland. Participants completed the questionnaire twice, within a 4-week interval. The discriminant validity was examined in comparing doctors' performance according to their reported EBM previous training. Proportion of agreement between both sessions of the questionnaire, Cohen's kappa and 'uniform kappa' determined its test-retest reliability. Results  The participation rate was 9.8%/7.1% to first/second session. Performance increased according to the level of doctors' previous training in EBM. The observed proportion of agreement between both sessions was over 70% for 14/19 questions, and the 'uniform kappa' was superior to 0.60 for 15/19 questions. Conclusion  The discriminant validity and test-retest reliability of the questionnaire were satisfying. The low participation rate did not prevent the study from achieving its aims.

Bridging the Gap: establishing the necessary infrastructure and knowledge for teaching and research in neuroscience in Africa.

Advances in neuroscience research over the last few decades have increased our understanding of how individual neurons acquire their specific properties and assemble into complex circuits, and how these circuits are affected in disease. One of the important motives driving neuroscience research is the development of new scientific techniques and interdisciplinary cooperation. Compared to developed countries, many countries on the African continent are confronted with poor facilities, lack of funding or career development programs for neuroscientists, all of which deter young scientists from taking up neuroscience as a career choice. This article highlights some steps that are being taken to promote neuroscience education and research in Africa.

Improving the implementation of evidence-based knowledge in healthcare

The pace of development of new healthcare technologies and related knowledge is very fast. Implementation of high quality evidence-based knowledge is thus mandatory to warrant an effective healthcare system and patient safety. However, even though only a small fraction of the approximate 2500 scientific publication indexed daily in Medline is actually useful to clinical practice, the amountof the new information is much too large to allow busy healthcare professionals to stay aware of possibly important evidence-based information.

An evaluation of new parsimony-based versus parametric inference methods in biogeography: a case study using the globally distributed plant family Sapindaceae

Aim  Recently developed parametric methods in historical biogeography allow researchers to integrate temporal and palaeogeographical information into the reconstruction of biogeographical scenarios, thus overcoming a known bias of parsimony-based approaches. Here, we compare a parametric method, dispersal-extinction-cladogenesis (DEC), against a parsimony-based method, dispersal-vicariance analysis (DIVA), which does not incorporate branch lengths but accounts for phylogenetic uncertainty through a Bayesian empirical approach (Bayes-DIVA). We analyse the benefits and limitations of each method using the cosmopolitan plant family Sapindaceae as a case study.Location  World-wide.Methods  Phylogenetic relationships were estimated by Bayesian inference on a large dataset representing generic diversity within Sapindaceae. Lineage divergence times were estimated by penalized likelihood over a sample of trees from the posterior distribution of the phylogeny to account for dating uncertainty in biogeographical reconstructions. We compared biogeographical scenarios between Bayes-DIVA and two different DEC models: one with no geological constraints and another that employed a stratified palaeogeographical model in which dispersal rates were scaled according to area connectivity across four time slices, reflecting the changing continental configuration over the last 110 million years.Results  Despite differences in the underlying biogeographical model, Bayes-DIVA and DEC inferred similar biogeographical scenarios. The main differences were: (1) in the timing of dispersal events - which in Bayes-DIVA sometimes conflicts with palaeogeographical information, and (2) in the lower frequency of terminal dispersal events inferred by DEC. Uncertainty in divergence time estimations influenced both the inference of ancestral ranges and the decisiveness with which an area can be assigned to a node.Main conclusions  By considering lineage divergence times, the DEC method gives more accurate reconstructions that are in agreement with palaeogeographical evidence. In contrast, Bayes-DIVA showed the highest decisiveness in unequivocally reconstructing ancestral ranges, probably reflecting its ability to integrate phylogenetic uncertainty. Care should be taken in defining the palaeogeographical model in DEC because of the possibility of overestimating the frequency of extinction events, or of inferring ancestral ranges that are outside the extant species ranges, owing to dispersal constraints enforced by the model. The wide-spanning spatial and temporal model proposed here could prove useful for testing large-scale biogeographical patterns in plants.

VIKI : a semiotic-based system for multilingual knowledge retrieval

Abstract Since its creation, the Internet has permeated our daily life. The web is omnipresent for communication, research and organization. This exploitation has resulted in the rapid development of the Internet. Nowadays, the Internet is the biggest container of resources. Information databases such as Wikipedia, Dmoz and the open data available on the net are a great informational potentiality for mankind. The easy and free web access is one of the major feature characterizing the Internet culture. Ten years earlier, the web was completely dominated by English. Today, the web community is no longer only English speaking but it is becoming a genuinely multilingual community. The availability of content is intertwined with the availability of logical organizations (ontologies) for which multilinguality plays a fundamental role. In this work we introduce a very high-level logical organization fully based on semiotic assumptions. We thus present the theoretical foundations as well as the ontology itself, named Linguistic Meta-Model. The most important feature of Linguistic Meta-Model is its ability to support the representation of different knowledge sources developed according to different underlying semiotic theories. This is possible because mast knowledge representation schemata, either formal or informal, can be put into the context of the so-called semiotic triangle. In order to show the main characteristics of Linguistic Meta-Model from a practical paint of view, we developed VIKI (Virtual Intelligence for Knowledge Induction). VIKI is a work-in-progress system aiming at exploiting the Linguistic Meta-Model structure for knowledge expansion. It is a modular system in which each module accomplishes a natural language processing task, from terminology extraction to knowledge retrieval. VIKI is a supporting system to Linguistic Meta-Model and its main task is to give some empirical evidence regarding the use of Linguistic Meta-Model without claiming to be thorough.

Neue Erkenntnisse zur Pathophysiologie und Therapie der Gicht [New knowledge on the pathophysiology and therapy of gout]

Gout is caused by the deposition of monosodium urate crystals (MSU) in tissue and provokes a local inflammatory reaction. It is the most common form of inflammatory arthritis in the elderly. The formation of MSU crystals is facilitated by hyperuricemia. In the last two decades, both hyperuricemia and gout have increased markedly and similar trends in the epidemiology of the metabolic syndrome have been observed. Recent studies provide new insights into uric acid metabolism in the kidneys as well as possible links between hyperuricemia and hypertension. MSU crystals provoke inflammation by activating leukocytes to produce inflammatory cytokines and other inflammatory mediators. The uptake of MSU crystals by monocytes involves interactions with Toll-like receptors (TLR-2 and TLR-4) and CD14, components of the innate immune system. Intracellularly, MSU crystals activate inflammasomes to activate pro-IL-1 (interleukin 1) processing to yield mature IL-1beta. The inflammatory effects of MSU are IL-1-dependent and can be blocked by IL-1 inhibitors. These advances provide new therapeutic targets to treat hyperuricemia and gout.

Oligopotent stem cells are distributed throughout the mammalian ocular surface.

The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.

Antiepileptika bei Frauen im gebärfähigen Alter und in der Schwangerschaft : Vergleich der Fachinformationen in Deutschland und der Schweiz mit dem aktuellen Wissensstand [Antiepileptics in women of childbearing age and during pregnancy : Comparison of specialized information with the current state of knowledge in Germany and Switzerland].

BACKGROUND: Healthcare professionals regularly read the summary of product characteristics (SmPC) as one of the various sources of information on the risks of drug use in women of childbearing age and during pregnancy. The aim of this article is to present an overview of the teratogenic potential of various antiepileptic drugs and to compare these data with the information provided by the SmPCs. METHODS: A literature search on the teratogenic risks of 19 antiepileptic agents was conducted and the results were compared with the information on the use in women of childbearing age and during pregnancy provided by the SmPCs of 38 commercial products available in Switzerland and Germany. RESULTS: The teratogenic risk is discussed in all available SmPCs. Quantification of the risk for birth defects and the numbers of documented pregnancies are mostly missing. Reproductive safety information in SmPCs showed poor concordance with risk levels reported in the literature. Recommendations concerning the need to monitor plasma levels and possibly perform dose adjustments during pregnancy to prevent treatment failure were missing in five Swiss and two German SmPCs. DISCUSSION: The information regarding use in women of childbearing age and during pregnancy provided by the SmPCs is heterogeneous and poorly reflects the current state of knowledge. Regular updates of SmPCs are warranted in order for these documents to be of reliable use for health care professionals.

Position statement--altitude training for improving team-sport players' performance: current knowledge and unresolved issues.

Despite the limited research on the effects of altitude (or hypoxic) training interventions on team-sport performance, players from all around the world engaged in these sports are now using altitude training more than ever before. In March 2013, an Altitude Training and Team Sports conference was held in Doha, Qatar, to establish a forum of research and practical insights into this rapidly growing field. A round-table meeting in which the panellists engaged in focused discussions concluded this conference. This has resulted in the present position statement, designed to highlight some key issues raised during the debates and to integrate the ideas into a shared conceptual framework. The present signposting document has been developed for use by support teams (coaches, performance scientists, physicians, strength and conditioning staff) and other professionals who have an interest in the practical application of altitude training for team sports. After more than four decades of research, there is still no consensus on the optimal strategies to elicit the best results from altitude training in a team-sport population. However, there are some recommended strategies discussed in this position statement to adopt for improving the acclimatisation process when training/competing at altitude and for potentially enhancing sea-level performance. It is our hope that this information will be intriguing, balanced and, more importantly, stimulating to the point that it promotes constructive discussion and serves as a guide for future research aimed at advancing the bourgeoning body of knowledge in the area of altitude training for team sports.