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

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

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

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

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

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

Wide metastatic spreading in infiltrating lobular carcinoma of the breast

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin...) (

Increased cell size and Akt activation in HER-2/neu-overexpressing invasive ductal carcinoma of the breast

Aims: To determine whether cell size is related to HER-2/neu status and/or to Akt activation in breast carcinomas. HER-2/neu overexpression is observed in 20-30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/neu activation. Akt has been found to be involved in the HER-2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models