Binary coalescence from case A evolution -- mergers and blue stragglers

We constructed some main-sequence mergers from case A binary evolution and studied their characteristics via Eggleton's stellar evolution code. Both total mass and orbital angular momentum are conservative in our binary evolutions. Some mergers might be on the left of the ZAMS as defined by normal surface composition on a CMD because of enhanced surface helium content. The study also shows that central hydrogen content of the mergers is independent of mass. As a consequence, we fit the formula of magnitude and B-V of the mergers when they return back to thermal equilibrium with maximum error 0.29 and 0.037, respectively. Employing the consequences above, we performed Monte Carlo simulations to examine our models in NGC 2682 and NGC 2660. In NGC 2682, binary mergers from our models cover the region with high luminosity, but its importance is much less than that of AML. Our results are well-matched to the observations of NGC2660 if there is about 0.5Mo of mass loss in the merger process.Comment: 14 pages, 12 figures. accepted by MNRA

A multimarker QPCR-based platform for the detection of circulating tumour cells in patients with early-stage breast cancer

BACKGROUND: The detection of circulating tumour cells (CTCs) has been linked with poor prognosis in advanced breast cancer. Relatively few studies have been undertaken to study the clinical relevance of CTCs in early-stage breast cancer. METHODS: In a prospective study, we evaluated CTCs in the peripheral blood of 82 early-stage breast cancer patients. Control groups consisted of 16 advanced breast cancer patients and 45 healthy volunteers. The CTC detection was performed using ErbB2/EpCAM immunomagnetic tumour cell enrichment followed by multimarker quantitative PCR (QPCR). The CTC status and common clinicopathological factors were correlated to relapse-free, breast cancer-related and overall survival. RESULTS: Circulating tumour cells were detected in 16 of 82 (20%) patients with early-stage breast cancer and in 13 out of 16 (81%) with advanced breast cancer. The specificity was 100%. The median follow-up time was 51 months (range: 17 -60). The CTC positivity in early-stage breast cancer patients resulted in significantly poorer relapse-free survival (log rank test: P ¼ 0.003) and was an independent predictor of relapse-free survival (multivariate hazard ratio ¼ 5.13, P ¼ 0.006, 95% CI: 1.62 -16.31). CONCLUSION: The detection of CTCs in peripheral blood of early-stage breast cancer patients provided prognostic information for relapse-free survival

Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients.

INTRODUCTION: Somatic inactivation of the TP53 gene in breast tumors is a marker for poor outcome, and breast cancer outcome might also be affected by germ-line variation in the TP53 gene or its regulators. We investigated the effects of the germ-line single nucleotide polymorphisms TP53 R72P (215G>C) and MDM2 SNP309 (-410T>G), and p53 protein expression in breast tumors on survival. METHODS: We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models. RESULTS: Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival. CONCLUSIONS: The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Nutri-RecQuest: a web-based search engine on current micronutrient recommendations

Background: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence collated current micronutrient recommendations. A user-friendly tool, Nutri-RecQuest, was developed to allow access to the collated data and to create a database source for use in other nutritional software tools. Methods: Recommendations, that is, intakes of micronutrients sufficient to meet the requirements of the majority of healthy individuals of that population, from 37 European countries/organizations and eight key non-European countries/regions comprising 29 micronutrients were entered into a database. General information on the source of the recommendations, as well scientific background information, was added. Results: A user-friendly web-based interface was developed to provide efficient search, comparison, display, print and export functions. Conclusion: Easy access to existing recommendations through the web-based tool may be valuable for bodies responsible for setting recommendations, as well as for users of recommendations including scientists, policy makers, health professionals and industry. Adding related dietary reference values such as average nutrient requirements and upper limits may extend the utility of the tool. European Journal of Clinical Nutrition (2010) 64, S43-S47; doi:10.1038/ejcn.2010.6

EURRECA's General Framework to make the process of setting up micronutrient recommendations explicit and transparent

EURRECA is a Network of Excellence with the objective of addressing the problem of national variations in micronutrient recommendations and working towards a framework of advice to better inform policy-makers. It became apparent that the network needed a framework that puts the process of recommendation setting in the context of science, policy and society. Although variability in recommendations originates from the scientific evidence-base used and its interpretation (e.g. health outcomes, types and methods of evaluation of evidence, quantification of risk/benefit), the background information provided in the recommendation reports does not easily facilitate the disentangling of the relative contribution of these different aspects because of lack of transparency. The present report portrays the general framework (see Figure) that has been developed by and for EURRECA in order to make the process of setting up micronutrient recommendations explicit and transparent. In explaining the link from science to policy applications, the framework distinguishes four principal components or stages (see Figure). These stages are: a) Defining the nutrient requirements: A judgement about the (best) distribution(s) of the population requirement is necessary for estimating nutrient requirements. Many assumptions need to be made about the attributes of the population group. Furthermore, several factors (consumer behaviour as well as physiology) are to be included to characterize optimal health. b) Setting the nutrient recommendations: All available evidence is needed to formulate recommendations. Incorporating different endpoints provide the basis to formulate an optimal diet in terms of (non-)nutrients and food(group)s. c) Policy options: Policy options should be formulated on how the optimal diet can be achieved. They concern the advice of scientist and/or expert committees to the policy makers. Current policy options are setting up a task force, food based dietary guidelines, general health education, educational programme for specific group(s), voluntary or mandatory fortification, labelling, supplementation (general or for specific groups), inducing voluntary action in industry, legislation on micronutrient composition in food products, fiscal change, monitoring and evaluation of intake (via food consumption surveys) and/or nutritional status. d) Policy applications: Policies and planning, usually done by government, that lead to nutritional interventions or programmes. They usually require consideration of scientific, legal, regulatory, ethical and cultural issues, economic implications, and political and social priorities. This framework illustrates three dimensions of the process of setting (micro)nutrient requirements: 1) The logical sequence of scientific thinking from setting physiological requirements for nutritional health leading to evidence-based derivation of Nutrient Intake Values. 2) In the early stages nutritional and epidemiological science is the dominant source and in the later stages evidence from consumer and social sciences as well as stakeholder influences is used in deriving the options for changing the distribution of nutrient intakes. 3) The wider socio-political context: a feedback loop between health perception, actual health and food intake exists and is directly affected by the food industry and many other stakeholders. Moreover, from the viewpoint of policymakers, there are concerns for health promotion and disease prevention because of population health indices, costs of health care, and economic interests in the agro-food sector. In conclusion: A systematic approach for development and regular review of micronutrient requirements in Europe, transparently based on scientific evidence and best practices, enables national and international authorities/bodies to use the best available information obtained through evidence-based nutrition and accomplish well-considered food policy. Funded by an EU FP6 Network of Excellence (EURRECA, grant no. FP 6–036196-2). G. T. performed part of the work under a short-term contract for WHO Europe

Prognostic gene network modules in breast cancer hold promise

A substantial proportion of lymph node-negative patients who receive adjuvant chemotherapy do not derive any benefit from this aggressive and potentially toxic treatment. However, standard histopathological indices cannot reliably detect patients at low risk of relapse or distant metastasis. In the past few years several prognostic gene expression signatures have been developed and shown to potentially outperform histopathological factors in identifying low-risk patients in specific breast cancer subgroups with predictive values of around 90%, and therefore hold promise for clinical application. We envisage that further improvements and insights may come from integrative expression pathway analyses that dissect prognostic signatures into modules related to cancer hallmarks

Nearest Template Prediction: A Single-Sample-Based Flexible Class Prediction with Confidence Assessment

Gene-expression signature-based disease classification and clinical outcome prediction has not been widely introduced in clinical medicine as initially expected, mainly due to the lack of extensive validation needed for its clinical deployment. Obstacles include variable measurement in microarray assay, inconsistent assay platform, analytical requirement for comparable pair of training and test datasets, etc. Furthermore, as medical device helping clinical decision making, the prediction needs to be made for each single patient with a measure of its reliability. To address these issues, there is a need for flexible prediction method less sensitive to difference in experimental and analytical conditions, applicable to each single patient, and providing measure of prediction confidence. The nearest template prediction (NTP) method provides a convenient way to make class prediction with assessment of prediction confidence computed in each single patient's gene-expression data using only a list of signature genes and a test dataset. We demonstrate that the method can be flexibly applied to cross-platform, cross-species, and multiclass predictions without any optimization of analysis parameters

EURRECA-Evidence-Based Methodology for Deriving Micronutrient Recommendations

The EURopean micronutrient RECommendations Aligned (EURRECA) Network of Excellence explored the process of setting micronutrient recommendations to address the variance in recommendations across Europe. Work centered upon the transparent assessment of nutritional requirements via a series of systematic literature reviews and meta-analyses. In addition, the necessity of assessing nutritional requirements and the policy context of setting micronutrient recommendations was investigated. Findings have been presented in a framework that covers nine activities clustered into four stages: stage one Defining the problem describes Activities 1 and 2: Identifying the nutrition-related health problem and Defining the process; stage two Monitoring and evaluating describes Activities 3 and 7: Establishing appropriate methods, and Nutrient intake and status of population groups; stage three Deriving dietary reference values describes Activities 4, 5, and 6: Collating sources of evidence, Appraisal of the evidence, and Integrating the evidence; stage four Using dietary reference values in policy making describes Activities 8 and 9: Identifying policy options, and Evaluating policy implementation. These activities provide guidance on how to resolve various issues when deriving micronutrient requirements and address the methodological and policy decisions, which may explain the current variation in recommendations across Europe. [Supplementary materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition for the following free supplemental files: Additional text, tables, and figures.]This is the peer-reviewed version of the article: Dhonukshe-Rutten Rosalie, Bouwman Jildau, Brown Kerry A., Cavelaars Adrienne E., Collings Rachel, Grammatikaki Evangelia, de Groot Lisette, Gurinović Mirjana A., Harvey Linda, Hermoso Maria, Hurst Rachel, Kremer Bas, Ngo Joy, Novaković Romana, Raats Monique M., Rollin Fanny, Serra-Majem Lluis, Souverein Olga W., Timotijević Lada, van't Veer Pieter, "EURRECA-Evidence-Based Methodology for Deriving Micronutrient Recommendations" 53, no. 10 (2013):999-1040, [https://doi.org/10.1080/10408398.2012.749209

Incorporating gene co-expression network in identification of cancer prognosis markers

<p>Abstract</p> <p>Background</p> <p>Extensive biomedical studies have shown that clinical and environmental risk factors may not have sufficient predictive power for cancer prognosis. The development of high-throughput profiling technologies makes it possible to survey the whole genome and search for genomic markers with predictive power. Many existing studies assume the interchangeability of gene effects and ignore the coordination among them.</p> <p>Results</p> <p>We adopt the weighted co-expression network to describe the interplay among genes. Although there are several different ways of defining gene networks, the weighted co-expression network may be preferred because of its computational simplicity, satisfactory empirical performance, and because it does not demand additional biological experiments. For cancer prognosis studies with gene expression measurements, we propose a new marker selection method that can properly incorporate the network connectivity of genes. We analyze six prognosis studies on breast cancer and lymphoma. We find that the proposed approach can identify genes that are significantly different from those using alternatives. We search published literature and find that genes identified using the proposed approach are biologically meaningful. In addition, they have better prediction performance and reproducibility than genes identified using alternatives.</p> <p>Conclusions</p> <p>The network contains important information on the functionality of genes. Incorporating the network structure can improve cancer marker identification.</p