In this paper, we introduce a modified version of linear discriminant analysis, called the "shrunken centroids regularized discriminant analysis" (SCRDA). This method generalizes the idea of the "nearest shrunken centroids" (NSC) (Tibshirani and others, 2003) into the classical discriminant analysis. The SCRDA method is specially designed for classification problems in high dimension low sample size situations, for example, microarray data. Through both simulated data and real life data, it is shown that this method performs very well in multivariate classification problems, often outperforms the PAM method (using the NSC algorithm) and can be as competitive as the support vector machines classifiers. It is also suitable for feature elimination purpose and can be used as gene selection method. The open source R package for this method (named "rda") is available on CRAN (http://www.r-project.org) for download and testing.

Summary Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that driven by commensal fungi, a wave of CD45+CD103+RALDH+ cells migrated to the peripheral lymph nodes after birth. The arrival of these cells introduced a high amounts of retinoic acid, mediated the neonatal to adult addressin switch on endothelial cells, and directed the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH+ cells may serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in Vitamin A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs.

Interferon (IFN)-␣-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-␣ therapy and incubated the cells with or without IFN-␣ for

Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.