Von der Subvention zum Leistungsvertrag. Neue Koordinations- und Steuerungsformen zwischen NPOs und dem öffentlichen Sektor und ihre Konsequenzen für NPOs.

In den Beziehungen und in der Zusammenarbeit zwischen Nonprofit Organisationen und öffentlichen Verwaltungen sind in Österreich markante Veränderungen zu beobachten. "Leere Kassen" und Sparprogramme gelten als Argument umfassender finanzpolitischer Restriktionen der öffentlichen Hand. Die Finanzierung der von NPOs erbrachten gesellschaftlichen Leistungen wird prekär. Eine theoretische Legitimation erhält diese Entwicklung durch die Diskussion zur gesellschaftlichen Verantwortung des öffentlichen und des NPO Sektors unter den Stichworten "New Public Management" und "Zivilgesellschaft". Auch supranationale Einflüsse - insbesondere jene der EU - schaffen neue Rahmenbedingungen für die Arbeit der NPOs. Die Konfrontation mit veränderten Spielregeln bedeutet für beide Sektoren eine Herausforderung. Insbesondere der anhaltende Druck in Richtung Sparsamkeit und Effizienz der öffentlichen Mittelverwendung hat erhebliche Auswirkungen auf das Verhältnis zwischen NPOs und öffentlicher Hand. Ein Kernelement dieser Entwicklung ist der Positionswandel vieler NPOs von der Rolle eines in seinen Aktivitäten weitgehend freien Subventionsempfängers, der durch persönliche Vertrauensbeziehungen gestützt wird, hin zum vertraglich gebundenen Dienstleister. Resultat sind widersprüchliche Forderungen, die zu wechselseitigen Fehleinschätzungen führen und den Eindruck einer "falschen Verbindung" entstehen lassen. Einige Beispiele sollen dies verdeutlichen: 1. Zum einen wird eine verstärkte Eigeninitiative von NPOs gefordert, zum anderen unterbinden enge Ausschreibungen jeglichen Spielraum. 2. Einerseits wird im Rahmen einer Zivilgesellschaft die Beteiligung der Ehrenamtlichen hoch gelobt, andererseits machen die Einklagbarkeit von Verträgen und die Vorgabe strikter Kriterien den Einsatz von Ehrenamtlichen zum Risiko. 3. Auf der einen Seite sollen NPOs wie professionelle Unternehmen agieren, auf der anderen Seite will man von der Tradition der Bevormundung und Detailkontrolle nicht lassen. Bislang durchgeführte qualitative Interviews mit Führungskräften des NPO-Sektors und der Geldgeber sprechen u.a. folgenden Forschungsannahmen hohe Plausibilität zu: - NPOs müssen für öffentliche Geldgeber berechenbar sein. Gründete die Berechenbarkeit früher dominant im politisch-werthaften Vertrauen in bestimmte Personen, so stützt sie sich heute zunehmend auf die Professionalität und auf das Wissenspotential der NPO. Die Steuerungsmedien Macht und persönliches Vertrauen werden überlagert durch jene von Geld und Wissen. - Leistungsvertragliche Beziehungen erfordern Entscheidungen und erzwingen Organisation: In Abgrenzung von informellen Handlungsmustern gewinnt formales Handeln in NPOs an Bedeutung. Auch basisnahen NPOs stehen unter Druck, sich vom Ideal und den Fesseln der Basisdemokratie zu verabschieden. - Es gibt eine Tendenz zur Professionalisierung sowohl im einschlägig-fachlichen wie auch im betriebswirtschaftlich-instrumentellen Bereich. Innerbetrieblich führt dies nicht selten zu einer symbolische Polarisierung zwischen Fachexperten einerseits und Betriebswirten andererseits. (Autorenref.)Series: WU-Jahrestagung 200

Distinct Mechanisms of IgM Antibody-Mediated Acquired von Willebrand Syndrome and Successful Treatment with Recombinant von Willebrand Factor in One Patient

Acquired von Willebrand Syndrome (AVWS) is a rare coagulation disorder which can be associated with IgM paraproteinaemia. Recently, recombinant von Willebrand factor (rVWF) has become available for the treatment of bleedings in patients with inherited von Willebrand disease, but experience in patients with AVWS is limited. We report on 2 patients with AVWS with underlying IgM paraproteinaemia with distinct underlying pathomechanisms. In 1 patient, the paraprotein built unspecific complexes with von Willebrand factor (VWF). In the other patient, we were able to detect an IgM antibody against VWF. Bleeding in this patient was successfully treated with rVWF. To our knowledge, this is the first report about the successful use of rVWF in a patient with AVWS with the detection of a VWF-specific antibody

Quantification of bulk lipid species in human platelets and their thrombin-induced release

Lipids play a central role in platelet physiology. Changes in the lipidome have already been described for basal and activated platelets. However, quantitative lipidomic data of platelet activation, including the released complex lipids, are unavailable. Here we describe an easy-to-use protocol based on flow-injection mass spectrometry for the quantitative analysis of bulk lipid species in basal and activated human platelets and their lipid release after thrombin activation. We provide lipid species concentrations of 12 healthy human donors, including cholesteryl ester (CE), ceramide (Cer), free cholesterol (FC), hexosylceramide (HexCer), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin (SM) and triglycerides (TG). The assay exhibited good technical repeatability (CVs < 5% for major lipid species in platelets). Except for CE and TG, the inter-donor variability of the majority of lipid species concentrations in platelets was < 30% CV. Balancing of concentrations revealed the generation of LPC and loss of TG. Changes in lipid species concentrations indicate phospholipase-mediated release of arachidonic acid mainly from PC, PI, and PE but not from PS. Thrombin induced lipid release was mainly composed of FC, PS, PC, LPC, CE, and TG. The similarity of the released lipidome with that of plasma implicates that lipid release may originate from the open-canalicular system (OCS). The repository of lipid species concentrations determined with this standardized platelet release assay contribute to elucidating the physiological role of platelet lipids and provide a basis for investigating the platelet lipidome in patients with hemorrhagic or thrombotic disorders

Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation

Objectives Unfractionated heparin (UFH) is the commonly used anticoagulant to prevent clotting of the ECMO circuit and thrombosis of the cannulated vessels. A side effect of UFH is heparin-induced thrombocytopenia (HIT). Little is known about HIT during ECMO and the impact of changing anticoagulation in ECMO patients with newly diagnosed HIT. The aim of the study was to determine the prevalence, complications, impact of switching anticoagulation to argatroban and outcomes of patients developing heparin-induced thrombocytopenia (HIT) during either veno-venous (VV) or veno-arterial (VA) ECMO. Methods Retrospective observational single centre study of prospectively collected data of consecutive patients receiving VV ECMO therapy for severe respiratory failure and VA ECMO for circulatory failure from January 2006 to December 2016 of the Medical intensive care unit (ICU) of the University Hospital of Regensburg. Treatment of HIT on ECMO was done with argatroban. Results 507 patients requiring ECMO were included. Further HIT-diagnostic was conducted if HIT-4T-score was ≥4. The HIT-confirmed group had positive HIT-enzyme-linked-immunosorbent-assay (ELISA) and positive heparin-induced-platelet-activation (HIPA) test, the HIT-suspicion group a positive HIT-ELISA and missing HIPA but remained on alternative anticoagulation until discharge and the HIT-excluded group a negative or positive HIT-ELISA, however negative HIPA. These were compared to group ECMO-control without any HIT suspicion. The prevalence of HIT-confirmed was 3.2%, of HIT-suspicion 2.0% and HIT-excluded 10.8%. Confirmed HIT was trendwise more frequent in VV than in VA (3.9 vs. 1.7% p = 0.173). Compared to the ECMO control group, patients with confirmed HIT were longer on ECMO (median 13 vs. 8 days, p = 0.002). Different types of complications were higher in the HIT-confirmed than in the ECMO-control group, but in-hospital mortality was not different (31% vs. 41%, p = 0.804). Conclusion HIT is rare on ECMO, should be suspected, if platelets are decreasing, but seems not to increase mortality if treated promptly

Management of Antithrombin Deficiency in Pregnancy

Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. The risk of venous thromboembolism (VTE) is increased in AT-deficient women during pregnancy and the postpartum period and is especially high in women with a prior history of VTE. A thorough assessment of VTE risk is recommended in pregnant AT-deficient women, comprising the degree and type of AT deficiency, genetic mutations, personal and family history, and additional preexisting or pregnancy-specific risk factors. Due to a lack of adequate study data, there is limited guidance on the management of AT deficiency in pregnancy, including the need for prophylactic anticoagulation, the appropriate dose of low-molecular-weight heparin (LMWH), and the role of AT substitution. LMWH is the medication of choice for the pharmacological prophylaxis and treatment of VTE in pregnancy. Patients with a history of VTE should receive full-dose LMWH during pregnancy and the postpartum period. AT concentrates are a treatment option when anticoagulation is withheld in potentially high-risk events such as childbirth, bleeding, or surgery and in cases of acute VTE despite the use of therapeutic dose anticoagulation. Women with AT deficiency should be counseled at specialized centers for coagulation disorders or vascular medicine, and close cooperation between obstetricians and anesthesiologists is warranted before delivery and during the peripartum period

Lipid profiling of lipoprotein X: Implications for dyslipidemia in cholestasis

Lipoprotein X (Lp-X) is an abnormal lipoprotein that may typically be formed in intra- and extrahepatic cholestasis and potentially interfere with lipid analysis in the routine lab. To gain insight into lipid class and species composition, Lp-X, LDL and HDL from cholestatic and control serum samples were subjected to mass spectrometric analysis including phospholipids (PL), sphingolipids, free cholesterol (FC), cholesteryl esters (CE) and bile acids. Our analysis of Lp-X revealed a content of 46% FC, 49% PL with 34% phosphatidylcholine (PC) as main PL component. The lipid species pattern of Lp-X showed remarkable high fractions of mono-unsaturated species including PC 32:1 and PC 34:1 and phosphatidylethanolamine (PE) 32:1 and 34:1. LDL and HDL lipid composition in the same specimens strongly reflected the lipid composition of Lp-X with increased PC 32:1, PC 34:1, PE 32:1, PE 34:1 and FC accompanied by decreased CE compared to controls. Comparison of Lp-X and biliary lipid composition clearly indicates that Lp-X does not originate from a sole release of bile lipids. Moreover, these data present evidence for increased hepatic fatty add and PL synthesis which may represent a reaction to high hepatic FC level observed during cholestasis. (C) 2016 Elsevier B.V. All rights reserved

How Do We Treat Pregnancy-Related Venous Thromboembolism?

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy and the postpartum period. Due to a lack of adequate study data, therapeutic strategies for pregnancy-related VTE are deduced from observational studies and extrapolated from recommendations for nonpregnant patients. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low-molecular-weight heparins (LMWHs) are the anticoagulant treatment of choice in cases of VTE during pregnancy. Once- and twice-daily dosing regimens are suitable. There is no evidence that measurement of factor Xa activities and consecutive LMWH dose adjustments improve clinical outcomes. There is no support for the routine use of vitamin K antagonists, direct oral thrombin or factor Xa inhibitors, fondaparinux, or danaparoid in uncomplicated pregnancy-related VTE. Management of delivery deserves special attention, and treatment strategies depend on the time interval between the diagnosis of acute VTE and the expected delivery date. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months

Expression of tumor necrosis factor alpha and its receptors during cellular differentiation

Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine also involved in cellular differentiation processes. TNFalpha and both of its receptors (TNFR1 and TNFR2) can be co-expressed on the same cell, allowing for local signaling. This study has examined the expression of all components necessary for autocrine cytokine regulation during human hematopoietic, epithelial, and mesenchymal models of cellular differentiation. Macrophage and dendritic differentiation of human peripheral blood monocytes decreased their TNFalpha and TNFR2 expression while increasing the TNFR1 mRNA. In colon epithelial cell lines (HT-29 and Caco-2) TNFalpha-, TNFR1-, and TNFR2-expression was decreased upon differentiation. No changes, however, were seen during human skin keratinocyte differentiation. TNFR1 expression was unchanged in all three mesenchymal lineages (adipogenesis, chondrogenesis, osteogenesis) tested. Differentiation decreases the TNFalpha message in adipocytes and the TNFR2 mRNA in adipocytes and osteocytes. Our results demonstrate that there is no general principle for TNFalpha signaling during conversion of cells from progenitor to a more differentiated phenotype. Paracrine signaling by TNFalpha to orchestrate different cell types during tissue development and remodeling, therefore, probably overrides the autocrine regulation of differentiation by TNFalpha. Non-signaling TNF-receptors may protect chondrocytes and osteocytes from the anti-differentiation effects of local TNFalpha production

Contextual Factors of Resilient Tourism Destinations in a Pandemic Situation: Selected Cases from North and South Tyrol during the SARS-CoV-2 Pandemic

This study examines critical factors for tourism destination resilience in the first year of the SARS-CoV-2 pandemic in North Tyrol (AT) and South Tyrol (IT). Based on a mixed-method approach, the summer seasons of 2019 and 2020 are compared regarding change in overnight stays in 26 municipalities. The results highlight the importance of the classical 4Ps of marketing and specific contextual factors. These and their implications for research and practice are discussed. Marketing mix aspects most relevant for resilience in a highly tourism-dependent region are outlined