48 research outputs found

    Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

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    Worldwide, millions of people are infected with soil-transmitted helminths, particularly in developing countries. Efforts to control these infections involve periodic mass drug treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring of drug efficacy has become a key issue in order to detect the emergence of resistance. At present, the drop in infection intensity is under examination for monitoring the drug efficacy. However, studies comparing detection techniques based on infection intensities are scarce. Moreover, little attention has been addressed to their feasibility and their ability to estimate drug efficacies. We have compared different techniques for the detection of whipworm (Trichuris) in simian stool samples based on prevalence, infection intensities, feasibility and ability to estimate the ‘true’ drug efficacy. We have found that techniques often fail to detect low infection intensities and that not all techniques are appropriate for estimating infection intensities. The time needed to obtain a test result varied from 3.9 to 17.7 min/sample. Finally, accurate estimates of drug efficacy were only obtained in high pre-drug administration infection intensities. To conclude, along with accurate estimates of infection intensities, feasibility is a considerable criterion for the detection techniques used in drug efficacy monitoring programs

    Loss of DPP6 in neurodegenerative dementia : a genetic player in the dysfunction of neuronal excitability

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    Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked to 7q36. We identified and validated a chromosomal inversion of ca. 4Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identified significantly more rare variants-nonsense, frame-shift, and missense-in early-onset Alzheimer's disease (EOAD, p value = 0.03, OR = 2.21 95% CI 1.05-4.82) and frontotemporal dementia (FTD, p = 0.006, OR = 2.59, 95% CI 1.28-5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel K(v)4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p < 0.001 and p < 0.0001) leading to a loss of protein. Reduced DPP6 and/or K(v)4.2 expression was also detected in brain tissue of missense variant carriers. Loss of DPP6 is known to cause neuronal hyperexcitability and behavioral alterations in Dpp6-KO mice. Taken together, the results of our genomic, genetic, expression and modeling analyses, provided direct evidence supporting the involvement of DPP6 loss in dementia. We propose that loss of function variants have a higher penetrance and disease impact, whereas the missense variants have a variable risk contribution to disease that can vary from high to low penetrance. Our findings of DPP6, as novel gene in dementia, strengthen the involvement of neuronal hyperexcitability and alteration in the homeostasis of neuronal firing as a disease mechanism to further investigate

    ATLAS Run 1 searches for direct pair production of third-generation squarks at the Large Hadron Collider

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    Perspectives managériales et consuméristes du luxe sur Internet: des années 1990 à nos jours

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    Le paradoxe de la distribution des marques de luxe face à l’e-commerce : proposition d’une typologie de consommateurs et de son évolution dans le temps

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    International audienceThe paradox of the distribution of luxury brands regarding e-shopping: evolution of consumers’ attitudes andbehaviorsThe use of e-shopping in the luxury industry represents both an opportunity and a threat and strengthens thedistribution paradox of the luxury brands between diffusion and exclusivity. The objectives of this paper are tobring about a better understanding of the attitudes and behaviors of luxury consumers and to study their evolu-tions. Using a double methodology, qualitative and quantitative (with two data collections in 2010 and 2014), athreefold typology of the luxury consumers according to their profile and luxury levels is developed. Theoreticaland managerial implications are highlighted.A la fois source d’opportunités et de menaces, l’utilisation de l’e-commerce dans le secteur du luxe intensifie leparadoxe de la distribution des marques de luxe entre diffusion et sélectivité. Les objectifs de cet article sont demieux appréhender les attitudes et les comportements des consommateurs de luxe envers l’e-commerce et d’étu-dier leurs évolutions. A l’aide d’une double méthodologie, qualitative et quantitative (avec une double collecte dedonnées en 2010 et 2014), une typologie des consommateurs de luxe en fonction de leur profil et des niveaux deluxe est développée. Des implications théoriques et managériales en sont déduites

    The Internet and communication: how to manage the consistency of luxury brands?

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