A Joint Location-Scale Test Improves Power to Detect Associated SNPs,Gene Sets,and Pathways

Gene-based, pathway, and other multivariate association methods are motivated by the possibility of GxG and GxE interactions; however, accounting for such interactions is limited by the challenges associated with adequate modeling information. Here we propose an easy-to-implement joint location-scale (JLS) association testing framework for single-variant and multivariate analysis that accounts for interactions without explicitly modeling them. We apply the JLS method to a gene-set analysis of cystic fibrosis (CF) lung disease, which is influenced by multiple environmental and genetic factors. We identify and replicate an association between the constituents of the apical plasma membrane and CF lung disease (p = 0.0099 and p = 0.0180, respectively) and highlight a role for the SLC9A3-SLC9A3R1/2-EZR complex in contributing to CF lung disease. Many association studies could benefit from re-analysis with the JLS method that leverages complex genetic architecture for SNP, gene, and pathway identification. Analytical verification, simulation, and additional proof-of-principle applications support our approach.     

Paléogéographie des chasseurs de l’Europe du Paléolithique supérieur : répartition et spécialisation des sites

During the Upper Paleolithic, Europe was occupied by human populations mainly living from hunting of big terrestrial mammals. A repartition of fauna and of archeological sites was done with a database: a repartition of Upper Paleolithic sites in central and western Europe. This study shows that the european space was structured following several factors; climate, environment, cynegetic behaviours… We observe a partition of Europe with a mediterranean area with mainly deer, and ibex and an atlantic area with reindeer. Equally, most of the occupations are localized in the “aquitano-cantabric horn” around the Gulf of Gascony. The occupation of Europe undergone a pulsation with a retreat of occupations toward the west and the south during the glacial maximum, then a colonization of North Europe during the Tardiglacial climatic amelioration.     

Temporal Variability and Social Heterogeneity in Disease Transmission: The Case of SARS in Hong Kong

The extent to which self-adopted or intervention-related changes in behaviors affect the course of epidemics remains a key issue for outbreak control. This study attempted to quantify the effect of such changes on the risk of infection in different settings, i.e., the community and hospitals. The 2002–2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong, where 27% of cases were healthcare workers, was used as an example. A stochastic compartmental SEIR (susceptible-exposed-infectious-removed) model was used: the population was split into healthcare workers, hospitalized people and general population. Super spreading events (SSEs) were taken into account in the model. The temporal evolutions of the daily effective contact rates in the community and hospitals were modeled with smooth functions. Data augmentation techniques and Markov chain Monte Carlo (MCMC) methods were applied to estimate SARS epidemiological parameters. In particular, estimates of daily reproduction numbers were provided for each subpopulation. The average duration of the SARS infectious period was estimated to be 9.3 days (±0.3 days). The model was able to disentangle the impact of the two SSEs from background transmission rates. The effective contact rates, which were estimated on a daily basis, decreased with time, reaching zero inside hospitals. This observation suggests that public health measures and possible changes in individual behaviors effectively reduced transmission, especially in hospitals. The temporal patterns of reproduction numbers were similar for healthcare workers and the general population, indicating that on average, an infectious healthcare worker did not infect more people than any other infectious person. We provide a general method to estimate time dependence of parameters in structured epidemic models, which enables investigation of the impact of control measures and behavioral changes in different settings.     

Impact of capsular switch on invasive pneumococcal disease incidence in a vaccinated population

Background

Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity.

Methodology/Principal Findings

Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5×10⁻³/week [4.6×10⁻⁵–4.8×10⁻³/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10⁶ children might occur due to switched pneumococcal strains.

Conclusions

Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines.     

Postsynthetic derivatization of fluorophores with alpha-sulfo-beta-alanine dipeptide linker. Application to the preparation of water-soluble cyanine and rhodamine dyes

A straightforward method to enhance water solubility of fluorescent organic dyes (cyanines and rhodamines) by a postsynthetic chemical derivatization of their carboxylic acid functionality with an original disulfonated heterobifunctional linker is described. Significant water solubility enhancement is achieved without compromising either the photophysical properties (especially large molar extinction coefficients and high quantum yields) or bioconjugation efficiency of the parent non-water-soluble fluorophores. The results both demonstrate the strong potential of these new compounds as fluorescent labels for a broad range of biotechnology and biomedical applications and illustrate the utility of such an easy-to-handle water-solubizing group.     

Integrating ongoing biodiversity monitoring: potential benefits and methods

Halting the loss of biodiversity comes along with the need to quantify biodiversity composition and dynamics at large spatial and temporal scales. Highly standardized, international monitoring networks would be ideal, but they do not exist yet. If we are to assess changes in biodiversity now, combining output available from ongoing monitoring initiatives is the only option. However, integration of biodiversity information across schemes is still very poorly developed. In this paper, we outline practical issues to be considered when planning to combine existing monitoring information. First, we provide an overview of avenues for integration along the four dimensions that characterize a monitoring design: sample size, biological coverage, spatial coverage and temporal coverage. We also emphasize that complementarity in monitoring targets across schemes enables to describe complex processes of biodiversity dynamics, e.g. through relating species traits to the impacts of environmental changes. Second, we review some methods to overcome differences in designs among monitoring schemes, such as site selection, post-stratification and measurement error. Finally, we point out some commonly used statistical methods that are at hand for combining data or parameter estimates. We especially emphasize the possible levels of data integration (raw data, parameter estimates, or effect size estimates), and the largely under-exploited potential of meta-analysis methods and weighted analyses. This contribution aims to bolster the practice and use of integration of ongoing monitoring initiatives for biodiversity assessment.     

Habitat monitoring in Europe: a description of current practices

Monitoring of biodiversity at the level of habitats is becoming increasingly common. Here we describe current practices in habitat monitoring based on 150 schemes in Europe. Most schemes were initiated after 1990 in response to EU nature directives or habitat management/restoration actions, with funding mostly from European or national sources. Schemes usually monitor both the spatial distribution and the quality of the habitats, and they frequently collect data on environmental parameters and potential causes of changes. Many schemes are local or regional rather than national or international in scope, and sampling effort varies greatly across spatial and temporal scales. Experimental design is used in half of the schemes, however, data are rarely analysed by advanced statistics. Most schemes require two months or less per year in manpower and are typically run by professionals rather than by volunteers. Estimated salaries plus equipment costs average 650,000 Euro per year per scheme, and add up to 80 million Euros annually. Costs are particularly high for schemes based on European or international law and for schemes funded by European or national sources. Costs are also high in schemes in which sampling sites are selected subjectively rather than based on sampling theory, and in schemes that do not use field mapping or remote sensing to document spatial variation in habitats. Our survey demonstrates promising developments in European habitat monitoring but also underlines the need for better spatial coverage, documentation of spatial variaton, improved sampling design and advanced data analysis. Such improvements are essential if we are to judge progress towards the 2010 biodiversity targets.