Molecular Diagnosis of Invasive Aspergillosis and Detection of Azole Resistance by a Newly Commercialized PCR Kit

Item does not contain fulltextAspergillus fumigatus is the main species responsible for aspergillosis in humans. The diagnosis of aspergillosis remains difficult, and the rapid emergence of azole resistance in A. fumigatus is worrisome. The aim of this study was to validate the new MycoGENIE A. fumigatus real-time PCR kit and to evaluate its performance on clinical samples for the detection of A. fumigatus and its azole resistance. This multiplex assay detects DNA from the A. fumigatus species complex by targeting the multicopy 28S rRNA gene and specific TR34 and L98H mutations in the single-copy-number cyp51A gene of A. fumigatus The specificity of cyp51A mutation detection was assessed by testing DNA samples from 25 wild-type or mutated clinical A. fumigatus isolates. Clinical validation was performed on 88 respiratory samples obtained from 62 patients and on 69 serum samples obtained from 16 patients with proven or probable aspergillosis and 13 patients without aspergillosis. The limit of detection was <1 copy for the Aspergillus 28S rRNA gene and 6 copies for the cyp51A gene harboring the TR34 and L98H alterations. No cross-reactivity was detected with various fungi and bacteria. All isolates harboring the TR34 and L98H mutations were accurately detected by quantitative PCR (qPCR) analysis. With respiratory samples, qPCR results showed a sensitivity and specificity of 92.9% and 90.1%, respectively, while with serum samples, the sensitivity and specificity were 100% and 84.6%, respectively. Our study demonstrated that this new real-time PCR kit enables sensitive and rapid detection of A. fumigatus DNA and azole resistance due to TR34 and L98H mutations in clinical samples

Models for Disassembly Lot Sizing Problem with Decisions on Surplus Inventory

International audienceWe consider a single-product Disassembly Lot Sizing Problem with Disposal (DLSPD) which is a problem arising in the context of disassembly systems. This is the problem of determining the quantity and time of the returned products to be disassembled while satisfying the demand of their parts or components over a planning horizon. Disassembly operation generates several components simultaneously. And, the demands are independent and not balanced which can generate unnecessary surplus inventory during planning horizon. Aggregate formulation (AGG) can be used to model this problem by considering disposal decision. Linear-Programming (LP) relaxation of this model doesn’t give very good lower bound, especially for the large size instances. We aim to improve lower bound of the problem. Facility Location-based formulation (FAL) and additional constraints (Valid Inequalities (VIs)) for the LP relaxation of AGG model are proposed. Computational results on generated test instances show that LP relaxation of FAL and AGG with additional constraints can obtain very strong lower bound within a very short computational time which is useful for the varied DLSPD (multi-level, multi-product, …)

Developing strategies for liver fibrosis treatment

Liver fibrosis represents a major worldwide healthcare burden. Current therapy is limited to removing the causal agent. This approach is successful in some diseases; particularly haemochromatosis and chronic viral hepatitis. However, for many patients treatment is not possible, while other patients present to medical attention at an advanced stage of fibrosis. There is therefore a great need for novel therapies for liver fibrosis. The hepatic stellate cell has been recognised to be responsible for most of the excess extracellular matrix observed in chronic liver fibrosis. The detailed understanding of hepatic stellate cell biology has allowed the rational design of novel antifibrotic therapies. This review describes for the general reader the novel emerging therapies for liver fibrosis