Dextran sulfate activates contact system and mediates arterial hypotension via B2 kinin receptors

To define some of the mechanisms underlying dextran sulfate (DXS)-induced hypotension, we investigated the effects of either the plasma kallikrein inhibitor des-Pro2-[Arg15] aprotinin (BAY x 4620) or the specific bradykinin B2-receptor antagonist Hoe-140 on the hypotensive response to DXS. In the first study, anesthetized miniature pigs were given DXS alone, DXS plus BAY x 4620 in various doses, or saline. As expected, DXS alone produced a profound but transient systemic arterial hypotension with a concomitant reduction in kininogen. Circulating kinin levels, complement fragment des-Arg-C3a, and fibrin monomer were all increased. Treatment with BAY x 4620 produced a dose-dependent attenuation of these effects with complete blockade of the hypotension as well as the observed biochemical changes at the highest dose (360 mg). In a second study, two groups of pigs were given either DXS alone or DXS plus Hoe-140. DXS-induced hypotension was completely blocked by Hoe-140 pretreatment; however, kininogen was again depleted. We conclude, therefore, that DXS-induced hypotension is produced by activation of plasma kallikrein that results in the production of bradykinin and that liberation of bradykinin and its action on B2 receptors in the vasculature are both necessary and sufficient to produce the observed effects on circulatory pressure

The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

FAMOUS - Operationelles Konzept

Ziel dieses Dokumentes ist es, die operationellen Abläufe innerhalb eines APOC so detailliert zu beschreiben, dass es als Grundlage für die Erstellung weiterführender Konzepte dienlich ist. Die weiterführenden Konzepte im Projekt FAMOUS sind das technische Konzept, das Simulations- und das Validierungskonzept, welche die Realisierung, das Testen und die Bewertung des im operationellen Konzept beschriebenen APOC als Gegenstand haben. Das FAMOUS-OKD beschränkt sich hierbei hauptsächlich auf die Vorgänge innerhalb des APOC. Wie Entscheidungen außerhalb des APOC gefällt werden, ist sekundär für dieses Dokument

Total Airport Management (Operational Concept and Logical Architectur)

Airports are seen as constraints to growth in the future air transport system. In the context of a doubling of traffic by 2020, increased investment, development and research will be needed to support continuous improvement in airport throughput, efficiency and punctuality with continued safety considerations. Airport processes must be fully integrated within the Air Traffic Management (ATM) system and capable of interacting with other system components in order to be aware of the priorities of aircraft operators and the constraints of the air transport network in order to optimally fulfil the airspace users’ needs when making decisions. As a first step towards this evolution, all essential airport processes from passenger check-in to aircraft turn-round must work collaboratively with the common goal of ensuring that each departure meets its agreed 4D-trajectory. Agreement between air and ground on the 4D-trajectory, based on precise target take-off and target arrival times, not only increases the efficiency of the ATM system but also that of the airport itself. Airports are the nodes of the air transport system. A performance-based airport is needed as a pre-requisite for a future performance-based ATM system. Therefore future concepts aim at an integrated airport management, where all major aircraft operator, airport, aerodrome ATC and ground handling processes are conducted using a single data set. This is embodied in an Airport Operations Centre (APOC) where operators constantly communicate and co-ordinate, develop and maintain dynamically joint plans and execute those in their respective area of responsibility. Different possible APOC-implementations are expected, ranging from a distributed virtual APOC to a high-tech physical APOC, even with new operator roles. The core information basis of Total Airport Management is the Airport Operations Plan (AOP). The AOP is firstly an en-route-to-en-route-conversion of the Network Operations Plan (NOP), enriched by airport specific data. It ranges from agreed airport performance targets, hard and soft constraints of the different stakeholders to a detailed event-resource-usage description enabling the airport to be operated as a time-ordered system. Different implementation options of the AOP exist, ensuring as well the commercial interests of the stakeholders. As the AOP is for sure a result of a dynamic and repetitive layered planning process of several stakeholders, sufficient processes have to be designed to efficiently (and effectively) achieve this joint plan. The APOC facilitates the generation, discussion, commitment to and maintenance of such an AOP. The processes outlined in this document for an APOC are based on some proven principles of distributed complex C4I (command and control) system approaches. The TAM approach integrates existing optimisation support systems. These have been developed in the past to assist the human operators in their individual workflows. E.g. arrival, departure and surface management tools have already demonstrated that they can lead to improved safety and efficiency. But it is only when they evolve from today’s situation where they act as individual support tools and become components of an integrated airport information architecture that they can act as holistic decision-support tools for all airport partners. This document, which is the result of a joint initiative between DLR and EUROCONTROL, is to be seen as the initial definition of the Total Airport Management (TAM) operational concept and the logical architecture of an APOC in the future. Compatibility with previous and ongoing work in DLR and EUROCONTROL is ensured where possible. It is envisaged that the initial concept will be further developed and validated, e.g. by performing human-in-the-loop simulations within SESAR or in related activities