Ruimtelijke en stedelijke ontwikkelingen na 1984 : de nieuwe welvaart van de Randstad en haar prijs. De ruimtelijke toekomst van Nederland.

Includes bibliographies.De nieuwe welvaart van de Randstad en haar prijs / A. Verbaan, H. Puylaert, J. van Staalduine.De ruimtelijke toekomst van Nederland / H.J. van Hunnik

Occurrence and determinants of selective reporting of clinical drug trials : Design of an inception cohort study

Introduction: Responsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort. Methods and analysis: In 2007, Dutch IRBs reviewed 622 clinical drug trials. For each trial, we assessed the stages of progress. We discriminated five intermediate stages and five definite stages. Intermediate stages of progress are: approved by an IRB; started inclusion; completed as planned; terminated early; published as article. The definite stages of progress are: rejected by an IRB; never started inclusion; not published as article; completely reported; selectively reported. We will use univariate and multivariate Cox regression models to identify trial characteristics associated with non-publication. We will identify seven trial-specific discrepancy items, including the objectives, inclusion and exclusion criteria, end points, sample size, additional analyses, type of population analysis and sponsor acknowledgement. The percentage of trials with discrepancies between the protocol and the publication will be scored. We will investigate the association between trial characteristics and the occurrence of discrepancies. Ethics and dissemination: No IRB-approval is required for this study. Access to confidential research protocols was provided by the Central Committee on Research Involving Human Subjects. We plan to finish data collection in June 2015, and expect to complete data cleaning, analysis and manuscript preparation within the next 3 months. Hence, a first draft of an article containing the results is expected before the end of October 2015

Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation

Aims Atrial fibrillation (AF) produces a hypercoagulable state. Stimulation of protease-activated receptors by coagulation factors provokes pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues. We studied the effects of thrombin on atrial fibroblasts and tested the hypothesis that hypercoagulability contributes to the development of a substrate for AF. Methods and results In isolated rat atrial fibroblasts, thrombin enhanced the phosphorylation of the pro-fibrotic signalling molecules Akt and Erk and increased the expression of transforming growth factor beta 1 (2.7-fold) and the pro-inflammatory factor monocyte chemoattractant protein-1 (6.1-fold). Thrombin also increased the incorporation of H-3-proline, suggesting enhanced collagen synthesis by fibroblasts (2.5-fold). All effects could be attenuated by the thrombin inhibitor dabigatran. In transgenic mice with a pro-coagulant phenotype (TMpro/pro), the inducibility of AF episodes lasting >1 s was higher (7 out of 12 vs. 1 out of 10 in wild type) and duration of AF episodes was longer compared with wild type mice (maximum episode duration 42.8 +/- 68.4 vs. 0.23 +/- 0.39 s). In six goats with persistent AF treated with nadroparin, targeting Factor Xa-mediated thrombin generation, the complexity of the AF substrate was less pronounced than in control animals (LA maximal activation time differences 23.3 +/- 3.1 ms in control vs. 15.7 +/- 2.1 ms in nadroparin, P <0.05). In the treated animals, AF-induced a-smooth muscle actin expression was lower and endomysial fibrosis was less pronounced. Conclusion The hypercoagulable state during AF causes pro-fibrotic and pro-inflammatory responses in adult atrial fibroblasts. Hypercoagulability promotes the development of a substrate for AF in transgenic mice and in goats with persistent AF. In AF goats, nadroparin attenuates atrial fibrosis and the complexity of the AF substrate. Inhibition of coagulation may not only prevent strokes but also inhibit the development of a substrate for AF

Electrochemical corrosion behavior of X52 and X60 steels in carbon dioxide containing saltwater solution

X52 and X60 high strength low alloy (HSLA) steels are widely used in the construction of petroleum pipelines. This paper discusses the corrosion resistance of X52 and X60 steels in CO2 containing saltwater at pH 4.4 and 50 ºC. A circulating flow loop system inside an autoclave was used for conducting the experimental work. The rotating impeller speed was 2000 rpm. The corrosion rate was monitored using in situ electrochemical methods such as potentiodynamic sweep, linear polarization resistance, and electrochemical impedance spectroscopy (EIS) methods. Results indicated that the corrosion rate of X60 steel is relatively higher than that of X52 steel