Gene expression analyses in breast cancer epidemiology: the Norwegian Women and Cancer postgenome cohort study

Introduction The introduction of high-throughput technologies, also called -omics technologies, into epidemiology has raised the need for high-quality observational studies to reduce several sources of error and bias. Methods The Norwegian Women and Cancer (NOWAC) postgenome cohort study consists of approximately 50,000 women born between 1943 and 1957 who gave blood samples between 2003 and 2006 and filled out a two-page questionnaire. Blood was collected in such a way that RNA is preserved and can be used for gene expression analyses. The women are part of the NOWAC study consisting of 172,471 women 30 to 70 years of age at recruitment from 1991 to 2006 who answered one to three questionnaires on diet, medication use, and lifestyle. In collaboration with the Norwegian Breast Cancer Group, every NOWAC participant born between 1943 and 1957 who is admitted to a collaborating hospital for a diagnostic biopsy or for surgery of breast cancer will be asked to donate a tumor biopsy and two blood samples. In parallel, at least three controls are approached for each breast cancer case in order to obtain blood samples from at least two controls per case. The controls are drawn at random from NOWAC matched by time of follow-up and age. In addition, 400 normal breast tissues as well as blood samples will be collected among healthy women participating at the Norwegian Mammography Screening program at the Breast Imaging Center at the University Hospital of North-Norway, Tromsø. Results The NOWAC postgenome cohort offers a unique opportunity (a) to study blood-derived gene expression profiles as a diagnostic test for breast cancer in a nested case-control design with adjustment for confounding factors related to different exposures, (b) to improve the reliability and accuracy of this approach by adjusting for an individual's genotype (for example, variants in genes coding for hormone and drug-metabolizing and detoxifying enzymes), (c) to study gene expression profiles from peripheral blood as surrogate tissue to biomonitor defined exposure (for example, hormone) and its association with disease risk (that is, breast cancer), and (d) to study gene variants (single nucleotide polymorphisms and copy number variations) and environmental exposure (endogenous and exogenous hormones) and their influence on the incidence of different molecular subtypes of breast cancer. Conclusion The NOWAC postgenome cohort combining a valid epidemiological approach with richness of biological samples should make an important contribution to the study of the etiology and system biology of breast cancer

Making Informed Choices about Microarray Data Analysis

This article describes the typical stages in the analysis of microarray data for non-specialist researchers in systems biology and medicine. Particular attention is paid to significant data analysis issues that are commonly encountered among practitioners, some of which need wider airing. The issues addressed include experimental design, quality assessment, normalization, and summarization of multiple-probe data. This article is based on the ISMB 2008 tutorial on microarray data analysis. An expanded version of the material in this article and the slides from the tutorial can be found at http://www.people.vcu.edu/~mreimers/OGMDA/index.html

Multi-criteria ranking of corporate distress prediction models: empirical evaluation and methodological contributions

YesAlthough many modelling and prediction frameworks for corporate bankruptcy and distress have been proposed, the relative performance evaluation of prediction models is criticised due to the assessment exercise using a single measure of one criterion at a time, which leads to reporting conflicting results. Mousavi et al. (Int Rev Financ Anal 42:64–75, 2015) proposed an orientation-free super-efficiency DEA-based framework to overcome this methodological issue. However, within a super-efficiency DEA framework, the reference benchmark changes from one prediction model evaluation to another, which in some contexts might be viewed as “unfair” benchmarking. In this paper, we overcome this issue by proposing a slacks-based context-dependent DEA (SBM-CDEA) framework to evaluate competing distress prediction models. In addition, we propose a hybrid crossbenchmarking- cross-efficiency framework as an alternative methodology for ranking DMUs that are heterogeneous. Furthermore, using data on UK firms listed on London Stock Exchange, we perform a comprehensive comparative analysis of the most popular corporate distress prediction models; namely, statistical models, under both mono criterion and multiple criteria frameworks considering several performance measures. Also, we propose new statistical models using macroeconomic indicators as drivers of distress

Efeitos local e sistêmico do laser de baixa potência no limiar de dor por pressão em indivíduos saudáveis

O laser de baixa potência é utilizado como recurso terapêutico para controle da dor. Porém, ainda é questionado o real efeito como também a dosimetria mais eficaz para esse efeito analgésico. Assim, este estudo teve como objetivo avaliar os efeitos local e sistêmico do laser de baixa potência no limiar de dor por pressão, em indivíduos saudáveis. Cento e cinquenta indivíduos foram distribuídos aleatoriamente em cinco grupos: Controle, Laser Placebo, 3 J, 6 J e 12 J. Para avaliar o limiar de dor, utilizou-se um algômetro de pressão em cinco tempos distintos. Na região da mão dominante do indivíduo, foi realizado o laser e a algometria para verificar o efeito local. Já naquela da perna dominante, realizou-se somente a algometria para verificar efeito sistêmico do laser de baixa potência. Houve redução local do limiar de dor por pressão no Grupo 3 J em comparação com os grupos Controle (p=0,0016) e Placebo (p=0,004), e não houve alteração sistêmica do limiar de dor por pressão. O laser de baixa potência, quando utilizado com energia de 3 J, reduziu o limiar de dor por pressão local em indivíduos saudáveis, porém não houve alteração sistêmica