123 research outputs found

    Application of the Weibull distribution for the optimization of maintenance policies of an electronic railway signaling system

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    ESREL 2017, European Safety and Reliability Conference, PORTOROZ, SLOVÉNIE, 18-/06/2017 - 22/06/2017This paper presents the advantages of using Weibull distribution to describe reliability figures of an electronic railway signaling system, respect to the commonly used exponential distribution. After presenting the context of reliability estimations within the railway domain, this work introduces the approach to use field-return data to build up reliability parameters instead of predictive methodologies, and it is applied to an existing electronic signaling system. A comparison between the two methodologies is also provided, as well as the introduction of further reliability indicators. A model to improve preventive maintenance tasks defining the optimum time interval is then presented and an example is provided. Some suggestions to improve the process of collecting field-return data are presented impacting both the after-sales logbook and the design of the circuit boards

    Low expression of bcl-2 in Brca1-associated breast cancers

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    Little data are available concerning the molecular mechanisms of action of Brca1 and Brca2 in breast oncogenesis. Recent experimental results suggest that Brca1 plays a role in the regulation of apoptosis. In order to determine whether the analysis of human tumours would provide data supporting this hypothesis, we have assessed the expression of the antiapoptotic bcl-2 and of the proapoptotic p53 genes in Brca1- and Brca2-associated breast carcinomas. The levels of expression of these genes were compared to those observed in controls and to the mitotic and the apoptotic indexes. Our series were composed of 16 cases of breast carcinoma in women with a germline Brca1 gene mutation, and of four cases with Brca2 mutation. A group of 39 patients aged under 36 years and for whom the search for Brca1 gene mutations was negative, and a group of 36 cases of sporadic cancers without data on their Brca status were used as controls. Immunohistochemistry was used to detect p53 and bcl-2 gene products. Mitotic and apoptotic indexes were higher in Brca1-associated tumours than in controls. No significant difference in p53 immunostaining was observed between the four groups of patients. In contrast, the rate of bcl-2-positive tumours was lower (31%) in Brca1-carcinomas than in carcinomas without Brca1 mutation (90%) (P< 10–3). A strong Bcl-2 expression was found in the four cases of Brca2-associated carcinomas. No significant correlation was observed between p53 and Bcl-2 immunostainings, either in cases or in controls. The association between Brca1 status and Bcl-2 expression remained significant after adjustment for the oestrogen receptor status. Our study shows that a low expression of bcl-2 characterises most Brca1-associated breast carcinomas, a biological trait which seems not to be shared by Brca2-associated tumours nor to be related to oestrogen receptor and/or p53 status.bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1-associated carcinomas. © 2000 Cancer Research Campaig

    Bcl-2 protein expression is associated with p27 and p53 protein expressions and MIB-1 counts in breast cancer

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    BACKGROUND: Recent experimental studies have shown that Bcl-2, which has been established as a key player in the control of apoptosis, plays a role in regulating the cell cycle and proliferation. The aim of this study was to investigate the relationship between Bcl-2 and p27 protein expression, p53 protein expression and the proliferation activity as defined by the MIB-1 counts. The prognostic implication of Bcl-2 protein expression in relation to p27 and p53 protein expressions and MIB-1 counts for breast cancer was also evaluated. METHODS: The immunohistochemical expression of Bcl-2 protein was evaluated in a series of 249 invasive ductal carcinomas of the breast, in which p27 and p53 protein expressions and MIB-1 counts had been determined previously. RESULTS: The Bcl-2 protein expression was found to be decreased in 105 (42%) cases. A decreased Bcl-2 protein expression was significantly correlated with a nuclear grade of III, a negative estrogen receptor, a decreased p27 protein expression, a positive p53 protein expression, positive MIB-1 counts and a positive HER2 protein expression. The incidence of a nuclear grade of III and positive MIB-1 counts increased as the number of abnormal findings of Bcl-2, p27 and p53 protein expressions increased. A univariate analysis indicated a decreased Bcl-2 protein expression to be significantly (p = 0.0089) associated with a worse disease free survival (DFS), while a multivariate analysis indicated the lymph node status and MIB-1 counts to be independently significant prognostic factors for the DFS. CONCLUSION: The Bcl-2 protein expression has a close correlation with p27 and p53 protein expressions and the proliferation activity determined by MIB-1 counts in invasive ductal carcinoma of the breast. The prognostic value of Bcl-2 as well as p27 and p53 protein expressions was dependent on the proliferation activity in breast cancer

    Multidisciplinary approach of early breast cancer: The biology applied to radiation oncology

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    Early breast cancer treatment is based on a multimodality approach with the application of clinical and histological prognostic factors to determine locoregional and systemic treatments. The entire scientific community is strongly involved in the management of this disease: radiologists for screening and early diagnosis, gynecologists, surgical oncologists and radiation oncologists for locoregional treatment, pathologists and biologists for personalized characterization, genetic counselors for BRCA mutation history and medical oncologists for systemic therapies

    Genome-wide association study identifies multiple susceptibility loci for glioma

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    Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10−9) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10−8), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10−11), 12q21.2 (rs12230172, P=7.53 × 10−11) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10−9). Our findings provide further insights into the genetic basis of the different glioma subtypes

    Mise au point du dosage des IgE anti-a3Gal, responsables de chocs anaphylactiques chez les patients recevant du cétuximab (Erbitux®)

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    Le but de notre travail a été de développer un outil de dosage des IgE anti-a3Gal, afin de dépister en routine les patients les plus à risque de développer un choc anaphylactique au cétuximab (Erbitux®, IgG1 kappa chimérique anti-EGFR). La technique développée repose sur le principe de l'ELISA. Elle est réalisée de façon automatisée sur l'ImmunoCap 100TM (Phadia®) et utilise la technologie des ImmunoCaps streptavidineTM. L'antigène utilisé pour doser les IgE anti-a3Gal est l'oligoside Gala3Galb4GlcNAc, présent sur le N-glycanne du domaine VH du cétuximab. Trois sérums postanaphylaxie au cétuximab ont d'abord permis de déterminer les meilleures conditions pour mesurer les IgE anti-a3Gal. Les sérums de 300 témoins ont ensuite été dosés pour estimer la prévalence des IgE anti-a3Gal dans la population. Dix-huit sérums sont positifs, soit 6,0 % des témoins testés. L'appartenance au sexe masculin est alors apparue comme un facteur associé à un risque plus élevé de présence de ces IgE (p=0,01). Enfin, sur onze sérums pré-traitement (patients atteints de cancers ORL), huit sont négatifs en IgE anti-a3Gal et aucun de ces patients n'a présenté de choc anaphylactique au cétuximab. Trois sérums se sont révélés positifs en IgE anti-a3Gal, mais un seul de ces trois patients a présenté un choc anaphylactique au cétuximab. Il s'agit du patient qui avait la plus forte concentration d'IgE anti-a3Gal dans son sérum avant traitement. Les valeurs trouvées pour les deux autres sont faibles ou très faibles. Une étude sur un plus grand nombre de patients est maintenant nécessaire pour déterminer la concentration d'IgE anti-a3Gal à partir de laquelle un patient est à risque réel de développer un choc anaphylactique au cétuximab.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

    Multiple Acyl-CoA Dehydrogenase Deficiency

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    A Weibull Approach for Enabling Safety-Oriented Decision-Making for Electronic Railway Signaling Systems

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    This paper presents the advantages of using Weibull distributions, within the context of railway signaling systems, for enabling safety-oriented decision-making. Failure rates are used to statistically model the basic event of fault-tree analysis, and their value sizes the maximum allowable latency of failures to fulfill the safety target for which the system has been designed. Relying on field-return failure data, Weibull parameters have been calculated for an existing electronic signaling system and a comparison with existing predictive reliability data, based on exponential distribution, is provided. Results are discussed in order to drive considerations on the respect of quantitative targets and on the impact that a wrong hypothesis might have on the choice of a given architecture. Despite the huge amount of information gathered through the after-sales logbook used to build reliability distribution, several key elements for reliable estimation of failure rate values are still missing. This might affect the uncertainty of reliability parameters and the effort required to collect all the information. We then present how to intervene when operational failure rates present higher values compared to the theoretical approach: increasing the redundancies of the system or performing preventive maintenance tasks. Possible consequences of unjustified adoption of constant failure rate are presented. Some recommendations are also shared in order to build reliability-oriented logbooks and avoid data censoring phenomena by enhancing the functions of the electronic boards composing the system
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