46 research outputs found

    Spalling tests on embedded cores and slabs: A comparative study

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    A comparative analysis of the spalling of (a) cores made of 3 concrete mixes embedded into 3 slabs made of the 3 same concrete mixes; and (b) 3 reference slabs made again of the same 3 concrete mixes has been made. Samples have been exposed to the French Increased HydroCarbon temperature curve. Results confirm that concrete spalling phenomena is not only related to the material properties. Concrete spalling is also very much influenced by the geometry of the samples

    Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

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    Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29–14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni

    Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

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    Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general

    Year in review in Intensive Care Medicine, 2008: II. Experimental, acute respiratory failure and ARDS, mechanical ventilation and endotracheal intubation

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    SCOPUS: re.jinfo:eu-repo/semantics/publishe

    Renal replacement therapy in acute kidney injury: controversy and consensus

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    Renal replacement therapies (RRTs) represent a cornerstone in the management of severe acute kidney injury. This area of intensive care and nephrology has undergone significant improvement and evolution in recent years. Continuous RRTs have been a major focus of new technological and treatment strategies. RRT is being used increasingly in the intensive care unit, not only for renal indications but also for other organ-supportive strategies. Several aspects related to RRT are now well established, but others remain controversial. In this review, we review the available RRT modalities, covering technical and clinical aspects. We discuss several controversial issues, provide some practical recommendations, and where possible suggest a research agenda for the future

    Spalling tests on embedded cores and slabs: A comparative study

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    A comparative analysis of the spalling of (a) cores made of 3 concrete mixes embedded into 3 slabs made of the 3 same concrete mixes; and (b) 3 reference slabs made again of the same 3 concrete mixes has been made. Samples have been exposed to the French Increased HydroCarbon temperature curve. Results confirm that concrete spalling phenomena is not only related to the material properties. Concrete spalling is also very much influenced by the geometry of the samples

    Distinct Cortical Areas for Names of Numbers and Body Parts Independent Of Language and Input Modality

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    INTRODUCTION The goal of the present work is to examine whether the semantic representations of numbers and body parts are associated with partially distinct cortical territories. Clinical and cognitive neuropsychology studies associate semantic deficits in both domains to lesions coarsely localized to the left parietal lobe (McCarthy and Warrington, 1990). Furthermore, patients with left inferior parietal lesions often exhibit simultaneous deficits for numbers and body parts (Benton, 1992; Gerstmann, 1940). Such an association of neuropsychological deficits is however notoriously ambiguous, and has been the subject of much debate. It might suggest that there is a shared substrate for numbers and body parts in the left parietal region, perhaps based on a common functional system for spatial representation and manipulation (Gerstmann, 1940) or on the crucial role that finger counting plays in numerical development (Butterworth, 1999). However, it might also reflect the existence of di

    Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

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    Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni.Copyright: © 2019 Chevalier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article
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