Bayesian methods to determine performance differences and to quantify variability among centers in multi-center trials: the IHAST trial

BACKGROUND: To quantify the variability among centers and to identify centers whose performance are potentially outside of normal variability in the primary outcome and to propose a guideline that they are outliers. METHODS: Novel statistical methodology using a Bayesian hierarchical model is used. Bayesian methods for estimation and outlier detection are applied assuming an additive random center effect on the log odds of response: centers are similar but different (exchangeable). The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) is used as an example. Analyses were adjusted for treatment, age, gender, aneurysm location, World Federation of Neurological Surgeons scale, Fisher score and baseline NIH stroke scale scores. Adjustments for differences in center characteristics were also examined. Graphical and numerical summaries of the between-center standard deviation (sd) and variability, as well as the identification of potential outliers are implemented. RESULTS: In the IHAST, the center-to-center variation in the log odds of favorable outcome at each center is consistent with a normal distribution with posterior sd of 0.538 (95% credible interval: 0.397 to 0.726) after adjusting for the effects of important covariates. Outcome differences among centers show no outlying centers. Four potential outlying centers were identified but did not meet the proposed guideline for declaring them as outlying. Center characteristics (number of subjects enrolled from the center, geographical location, learning over time, nitrous oxide, and temporary clipping use) did not predict outcome, but subject and disease characteristics did. CONCLUSIONS: Bayesian hierarchical methods allow for determination of whether outcomes from a specific center differ from others and whether specific clinical practices predict outcome, even when some centers/subgroups have relatively small sample sizes. In the IHAST no outlying centers were found. The estimated variability between centers was moderately large

The Gene Ontology Resource: 20 years and still GOing strong.

The Gene Ontology resource (GO; http://geneontology.org) provides structured, computable knowledge regarding the functions of genes and gene products. Founded in 1998, GO has become widely adopted in the life sciences, and its contents are under continual improvement, both in quantity and in quality. Here, we report the major developments of the GO resource during the past two years. Each monthly release of the GO resource is now packaged and given a unique identifier (DOI), enabling GO-based analyses on a specific release to be reproduced in the future. The molecular function ontology has been refactored to better represent the overall activities of gene products, with a focus on transcription regulator activities. Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations. New evidence codes for high-throughput experiments now enable users to filter out annotations obtained from these sources. GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models. We also provide the ‘GO ribbon’ widget for visualizing GO annotations to a gene; the widget can be easily embedded in any web page.publishedVersionThis is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Non-Linear Integral Equations for complex Affine Toda associated to simply laced Lie algebras

A set of coupled non-linear integral equations is derived for a class of models connected with the quantum group $U_q(\hat g)$ ($g$ simply laced Lie algebra), which are solvable using the Bethe Ansatz; these equations describe arbitrary excited states of a system with finite spatial length $L$. They generalize the Destri-De Vega equation for the Sine-Gordon/massive Thirring model to affine Toda field theory with imaginary coupling constant. As an application, the central charge and all the conformal weights of the UV conformal field theory are extracted in a straightforward manner. The quantum group truncation for $q$ at a root of unity is discussed in detail; in the UV limit we recover through this procedure the RCFTs with extended $W(g)$ conformal symmetry.Comment: 33 pages, TeX with lanlmac (revised: minor misprints corrected, some comments added, appendix slightly expanded revised 05/98: more misprints corrected, important refs added

How to evaluate sexual health in cancer patients:Development of the EORTC sexual health questionnaire for cancer patients

Background: The aim of the study is to describe the development of a comprehensive European Organisation for Research and Treatment of Cancer (EORTC) questionnaire to assess sexual health of female and male cancer patients and for cancer survivors. Methods: According to the EORTC guidelines, the development of an EORTC sexual health questionnaire is typically organised in four phases. The first phases comprise a literature search following interviews with patient and health care professionals (HCPs) (phase 1) and the operationalization into items (phase 2). The translation process is formally conducted according to the EORTC QLG Translation guidelines with a rigorous forward-backward procedure supported by native speakers. Results: Studies on sexuality in oncology patients which were identified by a literature search predominantly focused on issues of activity, experiences of sexual dysfunction, and satisfaction with sexual functioning. The literature review identified themes beyond these aspects. In total 53 potentially relevant issues were presented to 107 patients and 83 HCPs, different evaluations were found. Conclusions: A questionnaire that includes physical, psychological, and social aspects of sexuality of cancer survivors will be needed. Pre-testing and validation of the questionnaire will be done in future (phases 3 and 4). Divergent ratings of patients and professionals should be further investigated. Keywords: Cancer; sexual health; European Organisation for Research and Treatment of Cancer (EORTC) sexual health questionnair

Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union