Quantitative comparison of reconstruction methods for intra-voxel fiber recovery from diffusion MRI.

Validation is arguably the bottleneck in the diffusion magnetic resonance imaging (MRI) community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the "HARDI reconstruction challenge" organized in the context of the "ISBI 2012" conference. Evaluated methods encompass a mixture of classical techniques well known in the literature such as diffusion tensor, Q-Ball and diffusion spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach. This information can be useful not only for enhancing current algorithms and develop the next generation of reconstruction methods, but also to assist physicians in the choice of the most adequate technique for their studies.

Psychoses a l'adolescence, les neurosciences ameliorent-elles la prediction? [Adolescent psychosis, can neuroscience improve prediction?]

Developments in the field of neuroscience have created a high level of interest in the subject of adolescent psychosis, particularly in relation to prediction and prevention. As the medical practice of adolescent psychosis and its treatment is characterised by a heterogeneity which is both symptomatic and evolutive, the somewhat poor prognosis of chronic development justifies the research performed: apparent indicators of schizophrenic disorders on the one hand and specific endophenotypes on the other are becoming increasingly important. The significant progresses made on the human genome show that the genetic predetermination in current psychiatric pathologies is complex and subject to moderating effects and there is therefore significant potential for nature-nurture interactions (between the environment and the genes). The road to be followed in researching the phenotypic expression of a psychosis gene is long and winding and is susceptible to many external influences at various levels with different effects. Neurobiological, neurophysiological, neuropsychological and neuroanatomical studies help to identify endophenotypes, which allow researchers to create identifying "markers" along this winding road. The endophenotypes could make it possible to redefine the nosological categories and enhance understanding of the physiopathology of schizophrenia. In a predictive approach, large-scale retrospective and prospective studies make it possible to identify risk factors, which are compatible with the neurodevelopmental hypothesis of schizophrenia. However, the predictive value of such markers or risk indicators is not yet sufficiently developed to offer a reliable early-detection method or possible schizophrenia prevention measures. Nonetheless, new developments show promise against the background of a possible future nosographic revolution, based on a paradigm shift. It is perhaps on the basis of homogeneous endophenotypes in particular that we will be able to understand what protects against, or indeed can trigger, psychosis irrespective of the clinical expression or attempts to isolate the common genetic and biological bases according to homogeneous clinical characteristics, which have to date, proved unsuccessful

A model for intra-familial distribution of an infectious disease (Chagas' disease)

A probabilistic model for intra-familial distribution of infectous disease is proposed and applied to the prevalence of positive serology for Trypanosoma cruzi infection in Northeastern Brazilian sample. This double with one tail excess model fits satisfactorily to the data and its interpretation says that around 51% of these 982 families are free of infection risk; among those that are at risk, 3% have a high risk (0.66), probably due to high domestic infestation of the vector bug; while 97% show a small risk (0.11), probably due to accidental, non-domestic transmission.

Adapting dating violence prevention to francophone Switzerland: a story of intra-western cultural differences.

Dating violence prevention programs, which originated in the United States, are beginning to be implemented elsewhere. This article presents the first adaptation of a violence prevention program for a European culture, Francophone Switzerland. A U.S. dating violence prevention program, Safe Dates (Foshee & Langwick, 1994), was reviewed in 19 youth and 4 professional focus groups. The most fundamental program concepts--"dating" and "violence"--are not the same in Switzerland and the United States. Swiss youth were not very focused on establishing monogamous romantic relationships, and there is no ready translation for "dating." Violence has not become the focus of a social movement in Switzerland to the same extent that it has in the United States, and distinctions among terms such as "dating violence" and "domestic violence" are not well known. Psychoeducational approaches are also less common in the Swiss context. As the movement to prevent violence extends worldwide, these issues need greater consideration.

Prediction of the economic cost of individual long-term care in the Spanish population

Pensions together with savings and investments during active life are key elements of retirement planning. Motivation for personal choices about the standard of living, bequest and the replacement ratio of pension with respect to last salary income must be considered. This research contributes to the financial planning by helping to quantify long-term care economic needs. We estimate life expectancy from retirement age onwards. The economic cost of care per unit of service is linked to the expected time of needed care and the intensity of required services. The expected individual cost of long-term care from an onset of dependence is estimated separately for men and women. Assumptions on the mortality of the dependent people compared to the general population are introduced. Parameters defining eligibility for various forms of coverage by the universal public social care of the welfare system are addressed. The impact of the intensity of social services on individual predictions is assessed, and a partial coverage by standard private insurance products is also explored. Data were collected by the Spanish Institute of Statistics in two surveys conducted on the general Spanish population in 1999 and in 2008. Official mortality records and life table trends were used to create realistic scenarios for longevity. We find empirical evidence that the public long-term care system in Spain effectively mitigates the risk of incurring huge lifetime costs. We also find that the most vulnerable categories are citizens with moderate disabilities that do not qualify to obtain public social care support. In the Spanish case, the trends between 1999 and 2008 need to be further explored.

In silico prediction of human carboxylesterase-1 (hCES1) metabolism combining docking analyses and MD simulations.

Metabolic problems lead to numerous failures during clinical trials, and much effort is now devoted in developing in silico models predicting metabolic stability and metabolites. Such models are well known for cytochromes P450 and some transferases, whereas little has been done to predict the hydrolytic activity of human hydrolases. The present study was undertaken to develop a computational approach able to predict the hydrolysis of novel esters by human carboxylesterase hCES1. The study involves both docking analyses of known substrates to develop predictive models, and molecular dynamics (MD) simulations to reveal the in situ behavior of substrates and products, with particular attention being paid to the influence of their ionization state. The results emphasize some crucial properties of the hCES1 catalytic cavity, confirming that as a trend with several exceptions, hCES1 prefers substrates with relatively smaller and somewhat polar alkyl/aryl groups and larger hydrophobic acyl moieties. The docking results underline the usefulness of the hydrophobic interaction score proposed here, which allows a robust prediction of hCES1 catalysis, while the MD simulations show the different behavior of substrates and products in the enzyme cavity, suggesting in particular that basic substrates interact with the enzyme in their unprotonated form.

Intra- and interindividual variation in flank gland secretions of free-ranging shrews Crocidura russula

Individual differences in Rank gland secretions were examined among males of the monogamous shrew Crocidura russula during the breeding and nonbreeding seasons. Gas chromatography was used to measure intra- and interindividual variation of flank gland secretions of free-ranging shrews from different populations. The number of compounds detected by gas chromatographic analyses was correlated with body mass, flank gland size, and the presence of blood parasites in individual shrews. Very few compounds were detected from the Bank gland area of juvenile males. After they reached sexual maturity, however, the number of compounds detected from the Rank gland secretions increased significantly. At the beginning of the reproductive season 48 different compounds were detected from male flank gland secretions. In the middle of the breeding season 70 compounds were detected, while only 11 compounds were detected during the nonbreeding season. Few compounds were common to all males. There were more volatile compounds in the Bank gland secretions of males in the beginning of the breeding season than later in the breeding season. Males from the same population had fewer differences in the elution profile of compounds than males from different populations indicating that individuals from a distinct population have similar elution profiles of compounds and that each population has its own type of elution profile. No correlations were found between the number of compounds detected by gas chromatography for each male and the male's body mass or flank gland size. Blood parasites (trypanosomes, Trypanosoma crocidurae) were found in only three of 30 males investigated.

Insight into cross-talk between intra-amoebal pathogens.

Abstract: Background: Amoebae are phagocytic protists where genetic exchanges might take place between amoeba-resistant bacteria. These amoebal pathogens are able to escape the phagocytic behaviour of their host. They belong to different bacterial phyla and often show a larger genome size than human-infecting pathogens. This characteristic is proposed to be the result of frequent gene exchanges with other bacteria that share a sympatric lifestyle and contrasts with the genome reduction observed among strict human pathogens.Results: We sequenced the genome of a new amoebal pathogen, Legionella drancourtii, and compared its gene content to that of a Chlamydia-related bacterium, Parachlamydia acanthamoebae. Phylogenetic reconstructions identified seven potential horizontal gene transfers (HGTs) between the two amoeba-resistant bacteria, including a complete operon of four genes that encodes an ABC-type transporter. These comparisons pinpointed potential cases of gene exchange between P. acanthamoebae and Legionella pneumophila, as well as gene exchanges between other members of the Legionellales and Chlamydiales orders. Moreover, nine cases represent possible HGTs between representatives from the Legionellales or Chlamydiales and members of the Rickettsiales order.Conclusions: This study identifies numerous gene exchanges between intracellular Legionellales and Chlamydiales bacteria, which could preferentially occur within common inclusions in their amoebal hosts. Therefore it contributes to improve our knowledge on the intra-amoebal gene properties associated to their specific lifestyle.

Intra-articular osteoid osteoma of the knee: clinical and therapeutical particularities

The intra-articular osteoid osteoma (10-13% of the cases) is often difficult to identify. They present frequent atypical clinical signs and radiological images that eventually lead to inadequate treatment. For example, it has been observed that this pathology leads to inappropriate arthroscopies (up to 40%). Meniscal tear and then osteochondritis were initially suspected on a patient with an intra-articular osteoid osteoma at the tibia level. For the treatment, any damage of the cartilage has to be avoided. Thermoablation with radiofrequency is the treatment of choice

Structural prediction of peptides bound to MHC class I.

An ab initio structure prediction approach adapted to the peptide-major histocompatibility complex (MHC) class I system is presented. Based on structure comparisons of a large set of peptide-MHC class I complexes, a molecular dynamics protocol is proposed using simulated annealing (SA) cycles to sample the conformational space of the peptide in its fixed MHC environment. A set of 14 peptide-human leukocyte antigen (HLA) A0201 and 27 peptide-non-HLA A0201 complexes for which X-ray structures are available is used to test the accuracy of the prediction method. For each complex, 1000 peptide conformers are obtained from the SA sampling. A graph theory clustering algorithm based on heavy atom root-mean-square deviation (RMSD) values is applied to the sampled conformers. The clusters are ranked using cluster size, mean effective or conformational free energies, with solvation free energies computed using Generalized Born MV 2 (GB-MV2) and Poisson-Boltzmann (PB) continuum models. The final conformation is chosen as the center of the best-ranked cluster. With conformational free energies, the overall prediction success is 83% using a 1.00 Angstroms crystal RMSD criterion for main-chain atoms, and 76% using a 1.50 Angstroms RMSD criterion for heavy atoms. The prediction success is even higher for the set of 14 peptide-HLA A0201 complexes: 100% of the peptides have main-chain RMSD values < or =1.00 Angstroms and 93% of the peptides have heavy atom RMSD values < or =1.50 Angstroms. This structure prediction method can be applied to complexes of natural or modified antigenic peptides in their MHC environment with the aim to perform rational structure-based optimizations of tumor vaccines.