How funding structures for HIV/AIDS research shape outputs and utilization: a Swiss case study

Background: Research policy in the field of HIV has changed substantially in recent decades in Switzerland. Until 2004, social science research on HIV/AIDS was funded by specialized funding agencies. After 2004, funding of such research was “normalized” and integrated into the Swiss National Science Foundation as the main funding agency for scientific research in Switzerland. This paper offers a longitudinal analysis of the relationship between the changing nature of funding structures on the one hand and the production and communication of policy-relevant scientific knowledge in the field of HIV on the other hand. Methods: The analysis relies on an inventory of all social sciences research projects on HIV in Switzerland that were funded between 1987 and 2010, including topics covered and disciplines involved, as well as financial data. In addition, in-depth interviews were conducted with 18 stakeholders. Results: The analysis highlights that the pre-2004 funding policy ensured good coverage of important social science research themes. Specific incentives and explicit promotion of social science research related to HIV gave rise to a multidisciplinary, integrative and health-oriented approach. The abolition of a specific funding policy in 2004 was paralleled by a drastic reduction in the number of social science research projects submitted for funding, and a decline of public money dedicated to such research. Although the public administration in charge of HIV policy still acknowledges the relevance of findings from social sciences for the development of prevention, treatment and care, HIV-related social science research does not flourish under current funding conditions. Conclusions: The Swiss experience sheds light on the difficulties of sustaining social science research and multidisciplinary approaches related to HIV without specialized funding agencies. Future funding policy might not necessarily require specialized agencies, but should better take into account research dynamics and motivations in the field of social sciences

Effekt der Remifentanilkonzentration auf die postoperative Schmerzintensität und das subjektive Wohlbefinden : Ein Beitrag zur Versorgungsforschung im Bereich der ambulanten Anästhesie

Einleitung: Ziel dieser Studie war die Optimierung bestehender Anästhesieverfahren im ambu-lanten Bereich unter dem Aspekt der Patientenzufriedenheit während des Aufenthalts im Aufwachraum und der ersten zwei postoperativen Tage.Methode: 50 Patienten wurden in zwei Gruppen mit jeweils unterschiedlichem Anästhesie-verfahren (TIVA mit Remifentanil und Propofol nach BIS titriert (BIS 30-55)) randomisiert. Gruppe 1 (n=26) erhielt eine Remifentanil Zielkonzentration von 2 ng/ml, Gruppe 2 (n=24) entsprechend 4 ng/ml. Patientenzufriedenheit, Schmerzintensität, Analgetikabedarf, unerwünschte Nebenwirkungen und Propofolverbrauch wurden durch ein standardisiertes Studienprotokoll erfasst. Die Daten wurden als Verteilung oder Mittelwerte mit Standardabweichung dargestellt, die Prüfung der Nullhypothese der Gruppengleichheit erfolgte mittels χ2- oder t-Teste für unverbundenen Stichproben bei einer Irrtumswahrscheinlichkeit von p Ergebnis: Der Propofolgesamtverbrauch unterschied sich, bei vergleichbarer Narkosetiefe, nicht signifikant. Gruppe 1 verbrauchte im Mittel 9,73 ± 6,04 mg/kgKG/h, Gruppe 2 durchschnittlich 7,85 ± 2,64 mg/kgKG/h. Die Patientenzufriedenheit im Aufwachraum zeigte keinen signifikanten Unterschied (Gruppe 1: 15,48±1,61; Gruppe 2: 15,05±2,57; p=0,49. Maximalpunktzahl: 18). Die Schmerzintensität im Aufwachraum zeigte einen leicht höheren Score in Gruppe 2 (Gruppe 1: 1,62±1,47; Gruppe 2 1,91±1,11; ANOVA: pSchlussfolgerung: Es zeigten sich geringe Unterschiede hinsichtlich der Schmerzintensität und des Analgetikaverbrauchs im Aufwachraum. Hinsichtlich der Wirksamkeit des Anästhesie-verfahrens, der Patientenzufriedenheit und der Häufigkeit von Nebenwirkungen gab es keine Unterschiede. Eine TCI-Zielkonzentration von 2 ng/ml Remifentanil kann als Therapiestandard gesehen werden, der optimale Wirksamkeit mit maximaler Patientenzufriedenheit verbindet

Decoding Functional High-Density Lipoprotein Particle Surfaceome Interactions

High-density lipoprotein (HDL) is a mixture of complex particles mediating reverse cholesterol transport (RCT) and several cytoprotective activities. Despite its relevance for human health, many aspects of HDL-mediated lipid trafficking and cellular signaling remain elusive at the molecular level. During HDL's journey throughout the body, its functions are mediated through interactions with cell surface receptors on different cell types. To characterize and better understand the functional interplay between HDL particles and tissue, we analyzed the surfaceome-residing receptor neighborhoods with which HDL potentially interacts. We applied a combination of chemoproteomic technologies including automated cell surface capturing (auto-CSC) and HATRIC-based ligand-receptor capturing (HATRIC-LRC) on four different cellular model systems mimicking tissues relevant for RCT. The surfaceome analysis of EA.hy926, HEPG2, foam cells, and human aortic endothelial cells (HAECs) revealed the main currently known HDL receptor scavenger receptor B1 (SCRB1), as well as 155 shared cell surface receptors representing potential HDL interaction candidates. Since vascular endothelial growth factor A (VEGF-A) was recently found as a regulatory factor of transendothelial transport of HDL, we next analyzed the VEGF-modulated surfaceome of HAEC using the auto-CSC technology. VEGF-A treatment led to the remodeling of the surfaceome of HAEC cells, including the previously reported higher surfaceome abundance of SCRB1. In total, 165 additional receptors were found on HAEC upon VEGF-A treatment representing SCRB1 co-regulated receptors potentially involved in HDL function. Using the HATRIC-LRC technology on human endothelial cells, we specifically aimed for the identification of other bona fide (co-)receptors of HDL beyond SCRB1. HATRIC-LRC enabled, next to SCRB1, the identification of the receptor tyrosine-protein kinase Mer (MERTK). Through RNA interference, we revealed its contribution to endothelial HDL binding and uptake. Furthermore, subsequent proximity ligation assays (PLAs) demonstrated the spatial vicinity of MERTK and SCRB1 on the endothelial cell surface. The data shown provide direct evidence for a complex and dynamic HDL receptome and that receptor nanoscale organization may influence binding and uptake of HDL

Domain analysis of lipoprotein LppQ in Mycoplasma mycoides subsp. mycoides SC

The lipoprotein LppQ is the most prominent antigen of Mycoplasma mycoides subsp. mycoides small colony type (SC) during infection of cattle. This pathogen causes contagious bovine pleuropneumonia (CBPP), a devastating disease of considerable socio-economic importance in many countries worldwide. The dominant antigenicity and high specificity for M. mycoides subsp. mycoides SC of lipoprotein LppQ have been exploited for serological diagnosis and for epidemiological investigations of CBPP. Scanning electron microscopy and immunogold labelling were used to provide ultrastructural evidence that LppQ is located to the cell membrane at the outer surface of M. mycoides subsp. mycoides SC. The selectivity and specificity of this method were demonstrated through discriminating localization of extracellular (i.e., in the zone of contact with host cells) vs. integral membrane domains of LppQ. Thus, our findings support the suggestion that the accessible N-terminal domain of LppQ is surface exposed and such surface localization may be implicated in the pathogenesis of CBP