Die Entwicklung eines prädiktiven Biomarker-Score für MET im Magenkarzinom

Aims: We aimed to develop a putative predictive biomarker score for future hepatocyte growth factor receptor (MET)-targeted therapy of gastric cancer (GC). Methods and results: MET expression and MET ampli- fication were analysed by immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in 470 GC patients. Immunostaining was documented with the HistoScore. The percentage area of MET- amplified tumour cell clones was assessed by virtual microscopy. The expression of MET was heterogeneous in primary and metastatic GC. Immunostaining inten- sity (MET-IHC 2+/3+) correlated with MET amplifica- tion and a positive MET status was defined by a combination of MET-IHC 2+ or 3+ with MET amplifica- tion, or MET-IHC 3+ without MET amplification. The prognostic significance of the MET status was indepen- dent from the percentage area of positive tumour cells (e.g. <10 versus ≥10%). MET-positive GCs were micro- satellite stable and of KRAS/PIK3CA wild-type. MET- positive GCs had a very poor prognosis, with a median survival of 5.4 months and a hazard ratio of 2.126. Conclusions: A combination of immunohistochemis- try and CISH is suitable to assess MET status. If MET status is used as a predictive biomarker, prospective studies should pay specific attention to adequate tis- sue sampling, should ignore cutoff values for tumour areas, may consider the KRAS and PIK3CA genotype as negative predictive markers and should carry out the analysis expeditiously

An Event History Analysis on the Effects of Academic Integration Factors on Degree Completion of Low-Income Underrepresented Minority Students

Disparities in educational outcomes still exist for low-income and underrepresented students. Community colleges are an important entry point for student groups that have faced the most significant barriers to success. Community colleges account for almost half of all undergraduate enrollments in the United States and also enroll a higher proportion of low-income and minority students (American Association of Community Colleges, 2012; Aud, Hussar, Johnson, Kena, & Roth, 2012). The purpose of this study was to examine the timing of academic integration factors that contribute to degree completion of low income, underrepresented minority community college students over the course of seven years. In order to identify the temporal aspect of academic factors associated with degree completion and withdrawal, this study utilized Event History Analysis (EHA). EHA characterized the probability that a student would graduate or drop out during the study period and modeled the probability as a function of targeted covariates using discrete-time logistic regression. Results indicated that students were most likely to graduate or drop out in year five and six; contrary to most studies that indicate that the first year is the most important retention time period. Variables found to increase chances of graduation included full-time enrollment, successful completion of college level English and Math courses, completion of 20 credit hours, receiving an advanced or basic certificate, maintaining a high ratio of courses attempted to earned, earning a higher GPA, taking online courses, and transferring to a four year institution. Factors that reduced the likelihood of graduation were being male, having a lower family income quartile, failing or withdrawing from multiple courses, and taking remedial Math. Results of this study can be used to promote policies and practices within the community college system that lead to improved degree outcomes for low-income, underrepresented minority students

Evaluation of natural language processing from emergency department computerized medical records for intra-hospital syndromic surveillance

<p>Abstract</p> <p>Background</p> <p>The identification of patients who pose an epidemic hazard when they are admitted to a health facility plays a role in preventing the risk of hospital acquired infection. An automated clinical decision support system to detect suspected cases, based on the principle of syndromic surveillance, is being developed at the University of Lyon's Hôpital de la Croix-Rousse. This tool will analyse structured data and narrative reports from computerized emergency department (ED) medical records. The first step consists of developing an application (UrgIndex) which automatically extracts and encodes information found in narrative reports. The purpose of the present article is to describe and evaluate this natural language processing system.</p> <p>Methods</p> <p>Narrative reports have to be pre-processed before utilizing the French-language medical multi-terminology indexer (ECMT) for standardized encoding. UrgIndex identifies and excludes syntagmas containing a negation and replaces non-standard terms (abbreviations, acronyms, spelling errors...). Then, the phrases are sent to the ECMT through an Internet connection. The indexer's reply, based on Extensible Markup Language, returns codes and literals corresponding to the concepts found in phrases. UrgIndex filters codes corresponding to suspected infections. Recall is defined as the number of relevant processed medical concepts divided by the number of concepts evaluated (coded manually by the medical epidemiologist). Precision is defined as the number of relevant processed concepts divided by the number of concepts proposed by UrgIndex. Recall and precision were assessed for respiratory and cutaneous syndromes.</p> <p>Results</p> <p>Evaluation of 1,674 processed medical concepts contained in 100 ED medical records (50 for respiratory syndromes and 50 for cutaneous syndromes) showed an overall recall of 85.8% (95% CI: 84.1-87.3). Recall varied from 84.5% for respiratory syndromes to 87.0% for cutaneous syndromes. The most frequent cause of lack of processing was non-recognition of the term by UrgIndex (9.7%). Overall precision was 79.1% (95% CI: 77.3-80.8). It varied from 81.4% for respiratory syndromes to 77.0% for cutaneous syndromes.</p> <p>Conclusions</p> <p>This study demonstrates the feasibility of and interest in developing an automated method for extracting and encoding medical concepts from ED narrative reports, the first step required for the detection of potentially infectious patients at epidemic risk.</p

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors

There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile

Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon

BACKGROUND: Malaria transmission in most of Latin America can be considered as controlled. In such a scenario, parameters of baseline immunity to malaria antigens are of specific interest with respect to future malaria eradication efforts. METHODS: A cross-sectional study was carried out in two indigenous population groups in Amazonas/Venezuela. Data from the regional malaria documentation system were extracted and participants from the ethnic groups of the Guahibo (n = 180) and Piaroa (n = 295) were investigated for the presence of Plasmodium parasites and naturally acquired antibodies to Plasmodium falciparum antigens in serum. The GMZ2 vaccine candidate proteins MSP3 and GLURP were chosen as serological markers. RESULTS: The incidence of P. falciparum in both communities was found to be less than 2%, and none of the participants harboured P. falciparum at the time of the cross-sectional. Nearly a quarter of the participants (111/475; 23,4%) had positive antibody titres to at least one of the antigens. 53/475 participants (11.2%) were positive for MSP3, and 93/475 participants (19.6%) were positive for GLURP. High positive responses were detected in 36/475 participants (7.6%) and 61/475 participants (12.8%) for MSP3 and GLURP, respectively. Guahibo participants had significantly higher antibody titres than Piaroa participants. CONCLUSIONS: Considering the low incidence of P. falciparum, submicroscopical infections may explain the comparatively high anti-P. falciparum antibody concentrations

Numérique : impact sur le cycle de vie du document (Le)

Actes du colloque "Le numérique : impact sur le cycle de vie du document" organisé à l\u27université de Montréal par l\u27EBSI et l\u27ENSSIB du 13 au 15 octobre 2004. Son objectif était de traiter de façon interdisciplinaire la problématique suivante : « La numérisation, la diffusion des formats numériques originaux, les nouvelles méthodes d\u27indexation et d\u27analyse du document ainsi que le fonctionnement en réseau changent les données de base de la vie du document qui devient une sorte de phénix incessamment renaissant » (programme du colloque)

Does Kin Recognition and Sib-Mating Avoidance Limit the Risk of Genetic Incompatibility in a Parasitic Wasp?

Background: When some combinations of maternal and paternal alleles have a detrimental effect on offspring fitness, females should be able to choose mates on the basis of their genetic compatibility. In numerous Hymenoptera, the sex of an individual depends of the allelic combination at a specific locus (single-locus Complementary Sex Determination), and in most of these species individuals that are homozygous at this sexual locus develop into diploid males with zero fitness. Methods and Findings: In this paper, we tested the hypothesis of genetic incompatibility avoidance by investigating sibmating avoidance in the solitary wasp parasitoid, Venturia canescens. In the context of mate choice we show, for the first time in a non-social hymenopteran species, that females can avoid mating with their brothers through kin recognition. In ‘‘no-choice’ ’ tests, the probability a female will mate with an unrelated male is twice as high as the chance of her mating with her brothers. In contrast, in choice tests in small test arenas, no kin discrimination effect was observed. Further experiments with male extracts demonstrate that chemical cues emanating from related males influence the acceptance rate of unrelated males. Conclusions: Our results are compatible with the genetic incompatibility hypothesis. They suggest that the female wasps recognize sibs on the basis of a chemical signature carried or emitted by males possibly using a ‘‘self-referent phenotyp