Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis

The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion. We utilize a mathematical model to illustrate that electrolyte-free water clearance results in a greater reduction in IF volume compared to blood volume, and that this difference may be mediated by peripheral sequestration of osmotically inactive sodium. By coupling the model with data on plasma and urinary sodium and water in healthy subjects administered either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood volume, while the reduction in IF volume with bumetanide is only 78% of the reduction in blood volume. Heart failure is characterized by excess fluid accumulation, in both the vascular compartment and interstitial space, yet many heart failure patients have arterial underfilling due to low cardiac output, which may be aggravated by conventional diuretic treatment. Thus, we hypothesize that by reducing IF volume to a greater extent than blood volume, SGLT2 inhibitors might provide better control of congestion without reducing arterial filling and perfusion

Precision of a Small Brew House by Determining the Repeatability of Different Brews to Guarantee the Product Stability of the Beer

The most important success factors of a brewery are to brew a high-standard beer and to sell this product successfully on the market. Especially, guaranteeing an objective product quality is a difficult task, in terms of beer quality, for craft brewers. Following these product stability parameters is not only necessary to secure the expiry date but also with regard to the repeatability of the brews (from batch to batch). To evaluate the precision of a small brew house (1 hL), three different beer types, lager beer (Pilsener), pale ale (Kölsch), and wheat beer (Weißbier) were repeatedly produced and analyzed. It was found that small fluctuations in the wort preparation, in terms of time or analysis, have no noticeable difference on the sensory characteristics of the final product. Nevertheless, strict adherence to the brew recipe and raw material monitoring are necessary in order to keep these deviations as minimal as possible. Finally, this study verified that microbrews can be repeated so that the consumers will not detect any differences with their five senses in the end

The Identification of Industrial Clusters – Methodical Aspects in a Multidimensional Framework for Cluster Identification

We use a combination of measures of spatial concentration, qualitative input-output analysis and innovation interaction matrices to identify the horizontal and vertical dimension of industrial clusters in Saxony in 2005. We describe the spatial allocation of the industrial clusters and show possibilities of vertical interaction of clusters based on intermediate goods flows. With the help of region and sector-specific knowledge interaction matrices we are able to show that a sole focus on intermediate goods flows limits the identification of innovative actors in industrial clusters, as knowledge flows and intermediate goods flows do not show any major overlaps.industrial clusters, qualitative input-output-analysis, innovation interaction matrix

Spillover Effects of Spatial Growth Poles - a Reconciliation of Conflicting Policy Targets?

Regional economic policy faces the challenge of two competing policy goals - reducing regional economic disparities vs. promoting economic growth. The allocation of public funds has to weigh these goals particularly under the restriction of scarce financial re- sources. If, however, some region turns out to be a regional growth pole with positive spillovers to its disadvantaged periphery, regional policies could be designed to recon- cile the conflicting targets. In this case, peripheral regions could indirectly participate in the economic development of their growing cores. We start our investigation by defining and identifying such growth poles among German regions on the NUTS 3 administrative level based on spatial and sectoral effects. Using cluster analysis, we determine significant characteristics for the general identification of growth poles. Patterns in the sectoral change are identified by means of the change in the employment. Finally, we analyze whether and to what extent these growth poles ex- ert spatial spillover effects on neighbouring regions and thus mitigate contradictory in- terests in regional public policy. For this purpose, we apply a Spatial-Cross-Regressive- Model (SCR-Model) including the change in the secondary sector which allows to con- sider functional economic relations on the administrative level chosen (NUTS 3).size and spatial distributions of regional economic activity, cross-sectional models, spatial models, treatment effect models, regional analyses, urban analyses, rural analyses

The Identification of Regional Industrial Clusters Using Qualitative Input-Output Analysis

The ‘cluster theory’ has become one of the main concepts promoting regional competitiveness, innovation, and growth. As most studies focus on measures of concentration of one industrial branch in order to identify regional clusters, the appropriate analysis of specific vertical relations within a value-adding chain is developing in this discussion. This paper tries to identify interrelated sectors via national input-output tables with the help of Minimal Flow Analysis by Schnabl (1994). The regionalization of these national industry templates is carried out with the allocation of branch-specific production values on regional employment. As a result, the paper shows concentrations of vertical clusters in only 27 of 439 German NUTS-3 regions.industrial clusters, qualitative input-output analysis, vertical linkages

Mapping Local and Regional Potentials for Inter-sectoral Technology Flows in Industrial Clusters – Empirical Results for Germany

The paper explores the potential for inter-sectoral technology flows in industrial clusters in Germany. With the help of a product-embodied R&D flow matrix, calculated using data on input–output tables and sectoral R&D employment, we construct industrial cluster based networks of technology provider and user relationships and examine the regional embeddedness of different sectors in the technological diffusion network of industrial clusters. As a result, the paper shows that simple graphical representations of relevant product-embodied R&D flows illustrate substantial differences in potentials for technological relations within industrial clusters.

Observation of scalable and deterministic multi-atom Dicke states in an atomic vapor

Dicke state, a coherent state of multiple particles, is fundamentally responsible for various intriguing collective behaviors of many-body systems. Experimental access to Dicke states with a scalable and deterministic number of particles is essential to study how many-body properties depend on the particle number. We report the observation of Dicke states consisting of two, three, four, five, six, and seven atoms in an atomic vapor. Quantum coherences between the ground state and multi-atom states are created and detected by using optical two-dimensional coherent spectroscopy. The signal originated from multi-atom states is manifested as correlation between the multi-quantum coherence and the emission signal, providing direct and unambiguous detection of Dicke states. The manipulation of deterministic atomic Dicke states has possible implications in quantum information processing and fundamental many-body physics.Comment: 16 pages, 6 figure

Konflikt und Konfliktlösung in Guatemala – Die Verwirklichung der Rechte indigener Frauen im rechtspluralistischen Raum

Im 20. Jahrhundert erlebte die Menschheit die Gräueltaten von zwei Weltkriegen und zahllosen Bürgerkriegen, die allesamt unermessliches Leid brachten. Auch Guatemala ist insoweit ein trauriges Beispiel. Der Bürgerkrieg, der dort in der Zeit des Kalten Krieges wütete und erst 1996 endete, hat das Land zutiefst zerrissen. Da vor allem die indigene Bevölkerung verfolgt und vernichtet wurde und die Kriegsstrategie auch grausame, sexuelle Gewalttaten gegenüber indigenen Frauen einschloss, steht die heutige, demokratisch gewählte Regierung vor der Herausforderung, diesen Personen Recht und Würde wiederzugeben. So muss gezeigt werden, dass der Schutz vor Gewalt unabhängig von der ethnischen Zugehörigkeit für jeden Menschen besteht. Grundsätzlich stehen die Chancen hierfür nicht schlecht. Denn im 20. Jahrhundert haben sich auch viel versprechende Rechtssetzungsprozesse zugunsten von Indigenen bzw. Frauen vollzogen, die Standards entstehen ließen und den nationalen Regierungen als Richtschnur dienen können. Obgleich die Herausbildung von Frauenrechten bzw. Rechten von Indigenen zu verschiedenen Momenten einsetzte und sich diese Rechte auch konzeptionell mit unterschiedlicher Dynamik weiter entwickelt haben, so ist diesen Rechten doch gemeinsam, dass die großen Entwicklungsschritte vor allem nach 1945 gesetzt wurden und im übergreifenden Gesamtkonzept der Menschenrechte eingebunden waren, dem eine vorrangig individuelle Ausrichtung innewohnt

Schwierigkeiten der Investitionsförderung – Der Fall CargoLifter AG

This paper shows how the state of Brandenburg has subsidized large investments. The Focus of this papers is the case of the CargoLifter AG. The government intended to prevent in the mid 90's the total break-down of the economy in the state of Brandenburg, which is particularly affected by structural changes. This kind of policy is highly controversial casing lengthy discussions. After raising approximately 220 millions of Euro in the capital market and receiving nearly 50 million Euros from the state of Brandenburg the CargoLifter AG run into financial difficulties. The Government subsidized the CargoLifter AG as part of the "Gemeinschaftsaufgabe zur Verbesserung der regionalen Wirtschaftsstruktur - (GA)". There were arguments to subsidize the CargoLifter AG. This paper analyzes the project management of the company as well as the subsidization with the "Gemeinschaftsaufgabe zur Verbesserung der regionalen Wirtschaftsstruktur - (GA)"of the state of Brandenburg in terms of their contribution to the insolvency of the CargoLifter AG.