429 research outputs found

    Integrated approach for coastal hazards and risks in Sri Lanka

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    The devastating impact of the tsunami of 26 December 2004 on the shores of the Indian Ocean recalled the importance of knowledge and the taking into account of coastal hazards. Sri Lanka was one of the countries most affected by this tsunami (e.g. 30 000 dead, 1 million people homeless and 70% of the fishing fleet destroyed). Following this tsunami, as part of the French post-tsunami aid, a project to establish a Geographical Information System (GIS) on coastal hazards and risks was funded. This project aims to define, at a pilot site, a methodology for multiple coastal hazards assessment that might be useful for the post-tsunami reconstruction and for development planning. This methodology could be applied to the whole coastline of Sri Lanka. <br><br> The multi-hazard approach deals with very different coastal processes in terms of dynamics as well as in terms of return period. The first elements of this study are presented here. We used a set of tools integrating a GIS, numerical simulations and risk scenario modelling. While this action occurred in response to the crisis caused by the tsunami, it was decided to integrate other coastal hazards into the study. Although less dramatic than the tsunami these remain responsible for loss of life and damage. Furthermore, the establishment of such a system could not ignore the longer-term effects of climate change on coastal hazards in Sri Lanka. <br><br> This GIS integrates the physical and demographic data available in Sri Lanka that is useful for assessing the coastal hazards and risks. In addition, these data have been used in numerical modelling of the waves generated during periods of monsoon as well as for the December 2004 tsunami. Risk scenarios have also been assessed for test areas and validated by field data acquired during the project. The results obtained from the models can be further integrated into the GIS and contribute to its enrichment and to help in better assessment and mitigation of these risks. <br><br> The coastal-hazards-and-risks GIS coupled with modelling thus appears to be a very useful tool that can constitute the skeleton of a coastal zone management system. Decision makers will be able to make informed choices with regards to hazards during reconstruction and urban planning projects

    Conserved Charged Amino Acids within Sendai Virus C Protein Play Multiple Roles in the Evasion of Innate Immune Responses

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    One of the accessory proteins of Sendai virus (SeV), C, translated from an alternate reading frame of P/V mRNA has been shown to function at multiple stages of infection in cell cultures as well as in mice. C protein has been reported to counteract signal transduction by interferon (IFN), inhibit apoptosis induced by the infection, enhance the efficiency of budding of viral particles, and regulate the polarity of viral genome-length RNA synthesis to maximize production of infectious particles. In this study, we have generated a series of SeV recombinants containing substitutions of highly conserved, charged residues within the C protein, and characterized them together with previously-reported C′/C(−), 4C(−), and F170S recombinant viruses in infected cell cultures in terms of viral replication, cytopathogenicity, and antagonizing effects on host innate immunity. Unexpectedly, the amino acid substitutions had no or minimal effect on viral growth and viral RNA synthesis. However, all the substitutions of charged amino acids resulted in the loss of a counteracting effect against the establishment of an IFN-α-mediated anti-viral state. Infection by the virus (Cm2′) containing mutations at K77 and D80 induced significant IFN-β production, severe cytopathic effects, and detectable amounts of viral dsRNA production. In addition to the Cm2′ virus, the virus containing mutations at E114 and E115 did not inhibit the poly(I:C)-triggered translocation of cellular IRF-3 to the nucleus. These results suggest that the C protein play important roles in viral escape from induction of IFN-β and cell death triggered by infection by means of counteracting the pathway leading to activation of IRF-3 as well as of minimizing viral dsRNA production

    Outcome measurement in functional neurological disorder: a systematic review and recommendations.

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    OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

    La longue séquence de Marchésieux: reconstitution de paléoenvironnements marins durant le premier cycle glaciaire de l'hémisphère nord

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    International audienceA l'échelle des cinq derniers millions d'années, les enregistrements paléoclimatiques restitués par les sédiments océaniques illustrent le contrôle des paramètres orbitaux (précession, obliquité et excentricité) sur le climat global. La tendance au refroidissement qui accompagne la fin du Néogène est ainsi marquée, vers -2,4 Ma, par le développement rapide des calottes de glace de l'hémisphère nord (Shackleton et al., 1984). Alors que l'histoire du climat global restituée par les enregistrements océaniques est sans cesse précisée, les données concernant l'évolution des environnements continentaux et côtiers au cours de ces changements restent essentiellement fragmentaires. Le forage effectué à Marchésieux (Manche; Normandie) a permis de réaliser une étude pluridisciplinaire de la signature de ce premier cycle glaciaire de l'hémisphère nord (Prétiglien). Les premiers résultats stratigraphiques, paléoenvironnementaux (eustatisme, température, paléobathymétrie) sont présentés

    The metabolic syndrome is not associated with homocysteinemia: The Persian Gulf Healthy Heart Study

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    Background: It is uncertain whether homocysteine and the metabolic syndrome or its components are related in the general population, as studies investigating the association between homocysteine levels and insulin resistance have shown conflicting results. Methods: In an ancillary study to the Persian Gulf Healthy Heart Study, a cohort study of Iranian men and women aged ≥25 yr, a random sample of 1754 subjects were evaluated for the association of plasma homocysteine levels and the metabolic syndrome using National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria. Total homocysteine levels and high sensitivity C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assays. Results: Subjects with lower HDL-cholesterol and higher blood pressure showed significantly higher homocysteine levels (p=0.001 and p<0.0001; respectively). There was no significant difference in serum levels of homocysteine between subjects with and without the metabolic syndrome. In multiple logistic regression analysis, the metabolic syndrome did not show a significant association with serum homocysteine levels after adjusting for sex, age, smoking, fruit and vegetable intake pattern, body mass index, and physical inactivity. Concurrent elevated CRP levels and the metabolic syndrome also did not show a significant association with serum homocysteine levels after adjusting for sex, age, and lifestyle cardiovascular risk factors. Conclusions: There was no association between the metabolic syndrome using NCEP-ATPIII criteria and homocysteinemia in this study. These data refute the hypothesis that homocysteine levels are influenced by the metabolic syndrome, at least in general healthy population

    The Nonstructural Proteins of Nipah Virus Play a Key Role in Pathogenicity in Experimentally Infected Animals

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    Nipah virus (NiV) P gene encodes P protein and three accessory proteins (V, C and W). It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V−), rNiV(C−), and rNiV(W−), respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V−) and rNiV(C−) were lower than the other recombinants. The rNiV(V−), rNiV(C−) and rNiV(W−) suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V−) and rNiV(C−) but not the rNiV(W−) virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo

    A Bayesian Approach to Sparse Model Selection in Statistical Shape Models

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    Groupwise registration of point sets is the fundamental step in creating statistical shape models (SSMs). When the number of points on the sets varies across the population, each point set is often regarded as a spatially transformed Gaussian mixture model (GMM) sample, and the registration problem is formulated as the estimation of the underlying GMM from the training samples. Thus, each Gaussian in the mixture specifies a landmark (or model point), which is probabilistically corresponded to a training point. The Gaussian components, transformations, and probabilistic matches are often computed by an expectation-maximization (EM) algorithm. To avoid over- and under-fitting errors, the SSM should be optimized by tuning the required number of components. In this paper, rather than manually setting the number of components before training, we start from a maximal model and prune out the negligible points during the registration by a sparsity criterion. We show that by searching over the continuous space for optimal sparsity level, we can reduce the fitting errors (generalization and specificities), and thereby help the search process for a discrete number of model points. We propose an EM framework, adopting a symmetric Dirichlet distribution as a prior, to enforce sparsity on the mixture weights of Gaussians. The negligible model points are pruned by a quadratic programming technique during EM iterations. The proposed EM framework also iteratively updates the estimates of the rigid registration parameters of the point sets to the mean model. Next, we apply the principal component analysis to the registered and equal-length training point sets and construct the SSMs. This method is evaluated by learning of sparse SSMs from 15 manually segmented caudate nuclei, 24 hippocampal, and 20 prostate data sets. The generalization, specificity, and compactness of the proposed model favorably compare to a traditional EM based model
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