Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

Chapter 13 The Nature of the Entrepreneurial Process: Causation, Effectuation, and Pragmatism

This chapter is an appreciation of and a critical reflection on Sarasvathy's work on the causation and effectuation models of entrepreneurship. While Sarasvathy has made significant contributions to the field, it is suggested that more fruitful results can be achieved if two modifications are made. First, it is argued that the six dimensions on which the two models differ are independent and therefore it is more fruitful to focus on the dimensions rather than on the two models. Second, it is argued that a pragmatic view of entrepreneurship is most fruitful when it is not applied at the level of the entrepreneurial process, but at the level of underlying human actions

Structure and management of European R&D projects: A view from industrial liaison organizations

Collaboration between economic agents, especially in technological areas, is characterized by ambiguity in terminology, multiple analytical approaches, a diversity of objectives and multiple organizational forms, among which the network constitutes the most important example of ?common organization? in international collaboration. This paper describes the main factors in the structure of a network that develops an R&D project and the predominant aspects of its management. The authors then discuss an empirical study based on technological projects developed within the framework of European RTD programmes. The sample comprises 350 industrial liaison organizations (ILOs) which often take an active part in the European Commission's Framework Programmes. The results show, from a structural point of view, how a network is shaped for technological product development. From the management perspective, the discussion highlights the role of the promoter and partners in achieving a project's objectives in terms of organization, decision and control