Systemic ventricular function in Fontan patients at rest and after exercise at altitude

ObjectivePhysical activity at high altitude is expected to pose risks for patients with Fontan circulation and to impair systemic ventricular function. This study aims to determine the effect of high-altitude hypoxia on ventricular function in Fontan patients at rest and after exercise. We hypothesize that systemic ventricular function deteriorates under hypoxic conditions in Fontan patients.MethodsIn this prospective study, 21 Fontan patients (NYHA class I-II) and 21 age-, gender- and body mass index-matched healthy controls were enrolled (median age 17.9 and 16.9 years). Transthoracic echocardiography was performed at rest, after peak (PE) and after continuous exercise (CE) in normoxia and hypoxia at simulated altitude (2,500 m above sea level). The effect of hypoxia on echocardiographic parameters was quantified by linear mixed-effects models and the difference between normoxia and hypoxia (Δ= hypoxia-normoxia).ResultsAt rest, cardiac output (CO) estimated by outflow tract velocity time integral × heart rate and annular plane systolic excursion (APSE) were lower in hypoxia compared to normoxia in Fontan patients (CO: Δ = −12.0%, n.s.; APSE: Δ = −9.6%, p < 0.001), an increase was observed in controls (CO: Δ = 8.5%, n.s.; APSE: Δ = 2.5%, n.s.). Other parameters of systolic and diastolic function did not show relevant changes. After exercise under hypoxic conditions, Fontan patients did not show relevant deterioration of systolic function compared to normoxia. Late, active diastolic filling reflected by A-wave velocity remained unchanged in Fontan patients, but increased in controls. Under hypoxic conditions, CO and workload were higher after CE than PE in Fontan patients (CO: PE Δ = 1,530 vs. CE 1630), whereas controls showed higher work load and CO estimates after PE than CE as expected (CO: PE Δ = 2,302 vs. CE 2149).ConclusionFontan patients clinically tolerated short-term altitude exposure up to two hours and exercise and showed no consistent deterioration of systolic systemic ventricular function, but parameters of myocardial contractility, heart rate and cardiac output did not increase as observed in controls. This is likely to be multifactorial and may include intrinsic cardiac dysfunction as well as preload inadequacy and the lack of augmented atrial contraction. CE may be better tolerated than PE

Die Sieben Todsünden

Weshalb faszinieren und inspirieren die Sieben Todsünden bis heute – auch und gerade obwohl theologische Kommentare längst an Verbindlichkeit eingebüßt haben? In exemplarischen Studien widmet sich der Sammelband der Wirkungsgeschichte der Sieben Todsünden in den unterschiedlichen Künsten: Literatur und bildende Kunst, Film und Fernsehen. Der Fokus liegt weniger auf einer Ideengeschichte der Todsünden als auf deren Formelhaftigkeit, die gerade im Verblassen der ursprünglichen Hintergründe ihre Wirkmacht in breiter diskursiver Streuung entfaltet. Dabei reichen die vielfältigen Fortschreibungen und Transformationen weit über das frühe Mittelalter und die klassische Theologie hinaus und zeigen in der Moderne und Postmoderne verstärkt nur noch Allusionen auf die ursprünglich religiöse Ordnungsphantasie. So werden die Todsünden zu einem intermedialen Fundus für ethische und politische Reflexionen, ästhetische Transformationen und künstlerische Experimente. Der Band versammelt Studien, die sich aus literatur-, medien- und kulturwissenschaftlicher Perspektive sowohl den einzelnen Todsünden superbia, invidia, ira, acedia, avaritia, gula, luxuria als auch dem Septenar insgesamt widmen

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

The 2030 Agenda as Agenda Setting Event for Water Governance? Evidence from the Cuautla River Basin in Morelos and Mexico

Policy science has developed various approaches, such as agenda-setting and goal-setting theory, aimed at explaining the emergence of policy shifts and behavioural changes. The 2030 Agenda sets an ambitious vision for human development in times of global environmental change and makes for an interesting subject to study the explanatory power of these approaches. While the Sustainable Development Goals (SDGs) enshrined in the 2030 Agenda resulted from a process of intergovernmental negotiations, they will ultimately have to be implemented by national governments. Using the case of Mexico, we take the governance of water as a starting point to investigate whether the 2030 Agenda has indeed become a focusing event for sustainability transformation. Building on data from 33 expert interviews and findings of a Social Network Analysis of communications between water stakeholders from different sectors in the Cuautla River Basin, we conclude that major paradigm shifts in water governance in Mexico are thus far rather attributable to domestic focusing events and windows of opportunity than to the motivating impact of globally set goals. The Mexican case also illustrates that the implementation of the 2030 Agenda is strongly dependent on political will at the highest level. Ensuring the continuity of its implementation across administrations will, therefore, require mainstreaming and anchoring the SDGs into the sectorial strategies that determine activities at the lower working level of government

"Ein blauer Schleier, wie in Italien gewebt". Kleist-Tage in Venedig

Der Band enthält ein breites Spektrum von Aufsätzen, Essays und Materialien, die sich aus den vielfältigen internationalen und interdisziplinären wissenschaftlichen und künstlerischen Initiativen der Universität Ca' Foscari in Venedig rund um das große Kleist-Jahr 2011 entwickelt haben. Darunter finden sich Beiträge zu Kleists Italienbild und seinen Versuchen einer Selbstverortung, zur Bildungsrhetorik und zur Geldtheorie, zu den Anekdoten, zum Text über das Marionettentheater und dessen Fortschreibungen in der Moderne. Einen weiteren Schwerpunkt bilden Rezeption und Inszenierungspraxis von Kleists Dramen in Italien. Ausführlich dokumentiert sind insbesondere die Arbeiten des italienischen Regisseurs Cesare Lievi und die Theaterfotografien von Maurizio Buscarino

Is There a European Way of War? Role Conceptions, Organizational Frames and the Utility of Force

Europe is the region of the world where the network of security institutions is the densest. Yet, these institutions did not erase differences about conceptions of force employment among European countries and between European countries and the United States. Why have concepts of military power and force employment remained distinct and varied in Europe, and yet, what facilitates their convergence at the European Union level into the ambiguous notion of crisis management? We argue that an important answer to these questions is endogenous to the military: both role conceptions and organizational frames of military institutions are key underlying aspects of the differences at the national level and of the common ground at the European Union level. We examine and compare empirically the role conceptions and organizational frames of the armed forces in France, Germany, Italy and the United Kingdom since the early 1990s

Tracing Cationic Nutrients from Xylem into Stem Tissue of French Bean by Stable Isotope Tracers and Cryo-Secondary Ion Mass Spectrometry[W][OA]

Fluxes of mineral nutrients in the xylem are strongly influenced by interactions with the surrounding stem tissues and are probably regulated by them. Toward a mechanistic understanding of these interactions, we applied stable isotope tracers of magnesium, potassium, and calcium continuously to the transpiration stream of cut bean (Phaseolus vulgaris) shoots to study their radial exchange at the cell and tissue level with stem tissues between pith and phloem. For isotope localization, we combined sample preparation with secondary ion mass spectrometry in a completely cryogenic workflow. After 20 min of application, tracers were readily detectable to various degrees in all tissues. The xylem parenchyma near the vessels exchanged freely with the vessels, its nutrient elements reaching a steady state of strong exchange with elements in the vessels within 20 min, mainly via apoplastic pathways. A slow exchange between vessels and cambium and phloem suggested that they are separated from the xylem, parenchyma, and pith, possibly by an apoplastic barrier to diffusion for nutrients (as for carbohydrates). There was little difference in these distributions when tracers were applied directly to intact xylem via a microcapillary, suggesting that xylem tension had little effect on radial exchange of these nutrients and that their movement was mainly diffusive