Pulmonary arterial hypertension (PAH) is a rare disease characterized by obstructive lesions of the small pulmonary vessels, leading to increased pulmonary artery pressure (PAP), right-sided heart failure, and death within several years. 1,2 Despite the advent of improved therapies, outcome remains poor. 3,4 Prognosis correlates with severity of right ventricular (RV) structure and function. 2,5 More recently, male sex was identifi ed as an independent predictor of mortality. [6][7][8][9][10] Men treated with endothelin receptor antagonists had less 6-min walk distance (6MWD) improvement. 11 The cause of these sex differences is unknown; however, a distinct vascular and/or RV response to medical therapies is one possibility. Considering the need for improved treatments and "personalized therapy," Background: Male sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This fi nding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH. Methods: This was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15 heritable, four anorexigen associated) who were diagnosed at VU University Medical Centre between February 1999 and January 2011 and underwent right-sided heart catheterization and cardiac MRI to assess RV function. Change in pulmonary vascular resistance (PVR) was taken as a measure of treatment response in the pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to assess RV response to therapy. Results: PVR and RVEF were comparable between men and women at baseline; however, male patients had a worse transplant-free survival compared with female patients ( P 5 .002). Although male and female patients showed a similar reduction in PVR after 1 year, RVEF improved in female patients, whereas it deteriorated in male patients. In a mediator analysis, after correcting for confounders, 39.0% of the difference in transplant-free survival between men and women was mediated through changes in RVEF after initiating PAH medical therapies. Conclusions: This study suggests that differences in RVEF response with initiation of medical therapy in idiopathic PAH explain a signifi cant portion of the worse survival seen in men.

A theory of institutional change: Illustrated by Dutch city-provinces and Dutch land policy Since the early nineties, planning theory has focused on the issue of institutional change. Not only does institutional change have clear bearings on processes of spatial planning, it is also, increasingly, seen as an object of planning. A core concept in the literature is the juxtaposition of 'institutional design' and 'institutional evolution'. Yet, in understanding processes and the role of institutional change, this dichotomy does not appear to be very helpful. We therefore propose a more encompassing perspective that includes both 'design' and 'evolution' dimensions, invoking various components from theories of policy change, inspired by the work of Kingdon. Our perspective tries to unravel, in particular, why, under seemingly comparable conditions, some cases show substantive institutional transformations while others do not. The paper briefly discusses two cases from the Netherlands to illustrate this point, namely the thwarted process of establishing city regions within the scalar fabric of territorial governance, and some instrumental changes in land policy in the Netherlands.

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Within research on world cities, much attention has been paid to advanced producer services (APS) and their role within both global urban hierarchies and network formation between cities. What is largely ignored is that these APS provide services to firms operating in a range of different sectors. Does sector-specific specialisation of advanced producer services influence the economic geography of corporate networks between cities? If so, what factors might explain this geographical pattern? This paper investigates these theoretical questions by empirically focusing on those advanced producer services related to the port and maritime sector. The empirical results show that the location of AMPS is correlated with maritime localisation economies, expressed in the presence of shipowners and port-related industry as well as APS in general, but not by throughput flows of ports. Based upon the findings, policy recommendations are addressed. Taylor, 2004;Derudder et al., 2010). The various advanced producer services (APS), finance, insurance, consultancy and so on, are treated as a distinctive sector that serves global production functions and that tends to agglomerate within 'world cities' or 'global

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