35 research outputs found
Обеспечение безопасности ядерных материалов на гипотетическом объекте
Предметом исследования являются инсайдерские угрозы, угрозы со стороны, инсайдер в сговоре с угрозами со стороны, уязвимость атомных электростанций, анализ угроз, беспилотные летательные аппараты (беспилотные летательные аппараты), АЭС ВВЭР, категоризация и анализ наиболее уязвимых районов этого объекта , учет и контроль ядерных материалов, проектирование и функции ППС.The subject of the study are insider threats, outsider threats, insider in collusion with outsider threats, nuclear power plant vulnerabilities, analysis of threats that unmanned aerial vehicles (drones) impose on nuclear power plant, design of hypothetical nuclear facility for VVER NPP, categorization
Natural Scrapie and BSE in genetically resistant sheep
International audienceBecause ARR/ARR genotype sheep were considered to be totally resistant to TSE oralcontamination, they are massively selected in order to protect human food chain from smallruminant BSE risk.A controversial natural scrapie ARR/ARR case was reported in 1994, but genotype of that animalwas never confirmed. Recent identification of (i) atypical abnormal PrP accumulation inasymptomatic animals and (ii) successful transmission of BSE after intracerebral challenge bothraised new concerns about the resistance of ARR/ARR genotype sheep towards natural Priondiseases.However since neither PrPSc nor infectivity was reported in peripheral tissue from the orally orintracerebrally BSE challenged ARR/ARR animals (Bellworthy et al., 2005; Jeffrey et al., 2001).The ‘breeding for resistance’ policy aiming at protecting human food chain was not affected.In a first study, TSE free ARR/ARR and ARQ/ARQ lambs were orally challenged with 5g ofBSE infected sheep brain material. Strikingly, in one challenged ARR/ARR animal, PrPSc wasobserved in spleen at 10 months post challenge. ELISA and WB allowed estimating the totalPrPSc amount in ARR/ARR spleen to be 5 to 10 fold lower than in ARQ/ARQ.In a second study TSE free ARQ/ARQ and ARR/ARR sheep were IC challenged with BSE. Insymptomatic animals from both genotypes, PrPSc was detected in samples from a large panel ofskeletal muscle.Finally the retrospective study of a large scrapie tissue bank allowed us to identify a classicalscrapie case in an ARR/ARR field flock animal.Taken together all those data suggest that ARR/ARR sheep could be lowly susceptible to naturalTSE. It also raises new questions about (i) the pathogenesis and contagiousness of Prion diseasein animals bearing that genotype and (ii) the potential consequence for human food chain
Clinically Relevant Oxygraphic Assay to Assess Mitochondrial Energy Metabolism in Acute Myeloid Leukemia Patients
Resistant acute myeloid leukemia (AML) exhibits mitochondrial energy metabolism changes compared to newly diagnosed AML. This phenotype is often observed by evaluating the mitochondrial oxygen consumption of blasts, but most of the oximetry protocols were established from leukemia cell lines without validation on primary leukemia cells. Moreover, the cultures and storage conditions of blasts freshly extracted from patient blood or bone marrow cause stress, which must be evaluated before determining oxidative phosphorylation (OXPHOS). Herein, we evaluated different conditions to measure the oxygen consumption of blasts using extracellular flow analyzers. We first determined the minimum number of blasts required to measure OXPHOS. Next, we compared the OXPHOS of blasts cultured for 3 h and 18 h after collection and found that to maintain metabolic organization for 18 h, cytokine supplementation is necessary. Cytokines are also needed when measuring OXPHOS in cryopreserved, thawed and recultured blasts. Next, the concentrations of respiratory chain inhibitors and uncoupler FCCP were established. We found that the FCCP concentration required to reach the maximal respiration of blasts varied depending on the patient sample analyzed. These protocols provided can be used in future clinical studies to evaluate OXPHOS as a biomarker and assess the efficacy of treatments targeting mitochondria
Chemotherapy Treatment Doesn't Beneficiate to a Group of Elderly AML Patients with Absence of Complex Karyotype and Circulating Blasts
60th Annual Meeting of the American-Society-of-Hematology (ASH), San Diego, CA, DEC 01-04, 2018International audienceIntroductionAlthough the median age at diagnosis of acute myeloid leukemia (AML) is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options are available for the elderly. There is no standard of care for older patients with AML unfit for intensive chemotherapy. In this case, despite specific treatment such as low-dose cytarabine (LDA) and 5 azacytidine (5AZA), outcome remains extremely poor, without cure (Thomas X, Current Treat Options Oncol 2017, 18(1):2). The goal of our study is to establish a prognostic model of survival in order to identify whether the absence of specific treatment may not be harmful in a subset of patients.Patients and MethodsThe French Hauts-de-France AML observatory is a population-based database reporting AML cases diagnosed and supported in 9 Hospital Centers from the French region Haut-de-France. From January 2008 to December 2016, 572 patients older than 75 years were included in the observatory. Among them 324 patients received best supportive care (BSC) alone, 142 hypomethylating agents, 82 low doses aracytine, and 24 other treatments. As a general consensus accepted in all participating centers, BSC was proposed in unfit patients, after performance status and comprehensive geriatric assessment according to results of a preliminary fast geriatric assessment oncodage G8 (Bellera CA, Ann Oncol 2012, 23(8):2166-72). Clinical data were collected in each center. The study was conducted according to the Declaration of Helsinki and was approved by the Human Research Committee of Lille and the internal review board of the Lille University Hospital Tumor Bank (certification NF 96900-2014/65453-1).ResultsIn the BSC group, median age at diagnosis was 82 years (interquartile range [IQR] 78-86). Median WBC count was 7.3 x10^3/mL (IQR 2.18-42.5) with a median peripheral blood blasts percentage of 21% (IQR 6-59.5). Median bone marrow blasts was 51% (IQR 30-75). Karyotype was available for 181 patients. Two patients were in the favorable, 111 patients (61%) were in the intermediate, 68 patients (38%) were in the unfavorable cytogenetics group and 58 patients (32%) had a complex karyotype.For the BSC group, median survival was 3.2 months (IC 2.3- 4) with a 18% 12-months survival estimate.In univariate Cox models, WBC count (p 75 years), 18% are alive at 12 months without any chemotherapy. Our results indicate that the absence of chemotherapy may not be detrimental in a small subset of unfit patients identified by the absence of both complex karyotype and circulating blasts. However further studies are mandatory for characterizing most of patients alive at 12 months with BSC
De Novo and Secondary Acute Myeloid Leukemia, Real World Data on Outcomes from the French Nord-Pas-De-Calais Picardie Acute Myeloid Leukemia Observatory
Comprehensive molecular landscape in patients older than 80 years old diagnosed with acute myeloid leukemia: A study of the French Hauts-de-France AML observatory
International audienceNo abstract availabl
Transgenic rabbits expressing ovine PrP are susceptible to scrapie
Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6-8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background
Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group
International audiencePurpose This study assessed the prognostic impact of postinduction NPM1-mutated (NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P < .001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P < .001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a, 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and, 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a, 4-log reduction in PB-MRD. This benefit was not observed in those with a. 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response (P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1mPB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication. (C) 2016 by American Society of Clinical Oncolog