Radboud University Nijmegen

About: Radboud University Nijmegen is a education organization based out in Nijmegen, Gelderland, Netherlands. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 35417 authors who have published 83035 publications receiving 3285064 citations. The organization is also known as: Catholic University of Nijmegen & Radboud University.

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study

Abstract: Summary Background Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies. Methods In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198. Findings At a median follow-up of 49·2 months (IQR 47·0–51·8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34·7 months [95% CI 32·7–36·8] vs 30·3 months [28·7–33·3]; hazard ratio 0·81 [95% CI 0·70–0·93]; p=0·0033). The most common grade 3–4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [ vs 17 [3%]). Interpretation In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer. Funding Janssen Research & Development.

Robust causal inference using directed acyclic graphs: the R package 'dagitty'.

Abstract: Directed acyclic graphs (DAGs), which offer systematic representations of causal relationships, have become an established framework for the analysis of causal inference in epidemiology, often being used to determine covariate adjustment sets for minimizing confounding bias. DAGitty is a popular web application for drawing and analysing DAGs. Here we introduce the R package 'dagitty', which provides access to all of the capabilities of the DAGitty web application within the R platform for statistical computing, and also offers several new functions. We describe how the R package 'dagitty' can be used to: evaluate whether a DAG is consistent with the dataset it is intended to represent; enumerate 'statistically equivalent' but causally different DAGs; and identify exposure-outcome adjustment sets that are valid for causally different but statistically equivalent DAGs. This functionality enables epidemiologists to detect causal misspecifications in DAGs and make robust inferences that remain valid for a range of different DAGs. The R package 'dagitty' is available through the comprehensive R archive network (CRAN) at [https://cran.r-project.org/web/packages/dagitty/]. The source code is available on github at [https://github.com/jtextor/dagitty]. The web application 'DAGitty' is free software, licensed under the GNU general public licence (GPL) version 2 and is available at [http://dagitty.net/].

X-shooter, the new wide band intermediate resolution spectrograph at the ESO Very Large Telescope

Abstract: X-shooter is the first 2nd generation instrument of the ESO Very Large Telescope(VLT). It is a very efficient, single-target, intermediate-resolution spectrograph that was installed at the Cassegrain focus of UT2 in 2009. The instrument covers, in a single exposure, the spectral range from 300 to 2500 nm. It is designed to maximize the sensitivity in this spectral range through dichroic splitting in three arms with optimized optics, coatings, dispersive elements and detectors. It operates at intermediate spectral resolution (R~4,000 - 17,000, depending on wavelength and slit width) with fixed echelle spectral format (prism cross-dispersers) in the three arms. It includes a 1.8"x4" Integral Field Unit as an alternative to the 11" long slits. A dedicated data reduction package delivers fully calibrated two-dimensional and extracted spectra over the full wavelength range. We describe the main characteristics of the instrument and present its performance as measured during commissioning, science verification and the first months of science operations.

Pulmonary Nodule Detection in CT Images: False Positive Reduction Using Multi-View Convolutional Networks

Abstract: We propose a novel Computer-Aided Detection (CAD) system for pulmonary nodules using multi-view convolutional networks (ConvNets), for which discriminative features are automatically learnt from the training data. The network is fed with nodule candidates obtained by combining three candidate detectors specifically designed for solid, subsolid, and large nodules. For each candidate, a set of 2-D patches from differently oriented planes is extracted. The proposed architecture comprises multiple streams of 2-D ConvNets, for which the outputs are combined using a dedicated fusion method to get the final classification. Data augmentation and dropout are applied to avoid overfitting. On 888 scans of the publicly available LIDC-IDRI dataset, our method reaches high detection sensitivities of 85.4% and 90.1% at 1 and 4 false positives per scan, respectively. An additional evaluation on independent datasets from the ANODE09 challenge and DLCST is performed. We showed that the proposed multi-view ConvNets is highly suited to be used for false positive reduction of a CAD system.

Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.

Abstract: An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years' duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 'disease activity score'. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists' decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms.