Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial

Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3'-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to transdysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important to be able to objectively quantify treatment efficacy at the level of molecular biomarkers. We show how previously described candidate mRNA biomarkers can be used to model an effective reduction in CTG length, using modern high-dimensional statistics (machine learning), and a blood and muscle mRNA microarray dataset. We show how this model could be used to detect treatment effects in the context of a clinical trial

Federal Funds Futures, Risk Premium, and Monetary Policy Actions

This article attempts to determine whether controlling for the time-varying risk premium would improve the ability of the federal funds futures to predict the Federal Open Market Committee\u27s (FOMC) decision regarding the direction and magnitude of changes in the federal funds target rate at different forecast horizons. This is done using an appropriate categorical dependent variable model, which is estimated using real-time monthly data covering the period from January 1994 through September 2008. Following Piazzesi and Swanson (2008), control is made for the risk premium using a number of business-cycle indicators including nonfarm payrolls, the industrial production index, the help wanted index, and a measure of the Treasury yield spread. The results indicate that accounting for the risk premium modestly improves the predictive performance of the futures rate for the longer forecast horizons. Moreover, such a control appears to alleviate the over-prediction of changes in the target rate by the futures rate that has been documented in the literature