Myocardial perfusion scintigraphy before and after cardioversion for atrial fibrillation: Recovery of quantitative parameters

Cardiovascular Aspects of Radiolog

Genome-wide methylation patterns in Marfan syndrome

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Aortic distensibility in Marfan syndrome:a potential predictor of aortic events?

Contains fulltext : 239962.pdf (Publisher’s version ) (Open Access

Climate geoengineering: issues of path-dependence and socio-technical lock-in

As academic and policy interest in climate geoengineering grows, the potential irreversibility of technological developments in this domain has been raised as a pressing concern. The literature on socio-technical lock-in and path dependence is illuminating in helping to situate current concerns about climate geoengineering and irreversibility in the context of academic understandings of historical socio-technical development and persistence. This literature provides a wealth of material illustrating the pervasiveness of positive feedbacks of various types (from the discursive to the material) leading to complex socio-technical entanglements which may resist change and become inflexible even in the light of evidence of negative impacts. With regard to climate geoengineering, there are concerns that geoengineering technologies might contribute so-called ‘carbon lock-in’, or become irreversibly ‘locked-in’ themselves. In particular, the scale of infrastructures that geoengineering interventions would require, and the issue of the so-called ‘termination effect’ have been discussed in these terms. Despite the emergent and somewhat ill-defined nature of the field, some authors also suggest that the extant framings of geoengineering in academic and policy literatures may already demonstrate features recognizable as forms of cognitive lock-in, likely to have profound implications for future developments in this area. While the concepts of path-dependence and lock-in are the subject of ongoing academic critique, by drawing analytical attention to these pervasive processes of positive feedback and entanglement, this literature is highly relevant to current debates around geoengineering

Long-term clinical outcomes of losartan in patients with Marfan syndrome:follow-up of the multicentre randomized controlled COMPARE trial

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (β-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and β-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and β-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and β-blocker treatment in patients with MFS

Regulation of chloride transport in cultured normal and cystic fibrobis keratinocytes

Abstract Cultured normal (N) and cystic fibrosis (CF) keratinocytes were evaluated for their Cl−-transport properties by patch-clamp-, Ussing chamber- and isotopic efflux-measurements. Special attention was paid to a 32 pS outwardly rectifying Cl− channel which has been reported to be activated upon activation of cAMP-dependent pathways in N, but not in CF cells. This depolarization-induced Cl− channel was found with a similar incidence in N and CF apical keratininocyte membranes. However, activation of this channel in excised patches by protein kinase (PK)-A or PK-C was not successfull in either N or CF keratinocytes. Forskolin was not able to activate Cl− channels in N and CF cell-attached patches. The Ca2+-ionophore A23187 activated in cell-attached patches a linear 17 pS Cl− channel in both N and CF cells. This channel inactivated upon excision. No relationship between the cell-attached 17 pS and the excised 32 pS channel could be demonstrated. Returning to the measurement of Cl− transport at the macroscopic level, we found that a drastic rise in intracellular cAMP induced by forskolin did in N as well as CF cells not result in a change in the short-circuit current (Isc) or the fractional efflux rates of 36Cl− and 125I−. In contrast, addition of A23187 resulted in an increase of the Isc and in the isotopic anion efflux rates in N and CF cells. We conclude that Cl−-transport in cultured human keratinocytes can be activated by Ca2+, but not by cAMP-dependent pathways