Charakterisierung der Induktion von CD8 T Zell-Immunität durch sinusoidale Endothelzellen der Leber

Die Leber spielt eine entscheidende Rolle bei der Induktion der peripheren Toleranz. Hierbei sind die sinusoidalen Endothelzellen der Leber (LSEC) von großer Bedeutung, welche mit CD8 T Zellen interagieren und in diesen T Zell-Toleranz induzieren. Bisher war es jedoch unbekannt, ob LSEC als antigen-präsentierende Zellen auch zu der Induktion von Immunität in der Leber beitragen. In dieser Arbeit konnte gezeigt werden, dass LSEC die notwendigen „Pattern-Recognition“-Rezeptoren (PRR) für die Erkennung von Pathogenen funktionell exprimierten, was sich in der Produktion pro-inflammatorischer Zytokine zeigte. Jedoch konnte keine Aktivierung von CD8 T Zellen durch LSEC, welche zuvor mit spezifischen Liganden für PRR stimuliert wurden, beobachtet werden. Diese LSEC induzierten weiterhin einen toleranten Phänotyp in CD8 T Zellen. Es konnte zudem belegt werden, dass LSEC von dem murinen Cytomegalovirus (MCMV) infiziert wurden, wobei es anschließend zu einer Aktivierung von naiven CD8 T Zellen kam, welche in zytotoxische IFN-γ-produzierende Effektorzellen differenzierten. Dies lässt darauf schließen, dass LSEC nach einer viralen Infektion in der Lage sind, funktionell zu reifen und anschließend zu der Induktion von Immunität beitragen. Als möglicher Mechanismus für diese Reifung konnte eine synergetische Aktivierung zweier Signalwege über „Toll-like“ Rezeptoren und cAMP aufgezeigt werden. Die Signale, welche eine T Zell-Aktivierung durch virusinfizierte LSEC induzierten, waren unabhängig von den ko-stimulatorischen Molekülen CD80/86 und IL-12 und weisen darauf hin, dass sich der Mechanismus der LSEC-vermittelten T Zell-Aktivierung von demjenigen durch funktionell mature DC unterscheidet. Des Weiteren konnte durch den Gebrauch von Knochenmarkschimären gezeigt werden, dass LSEC in vivo in der Lage waren, eine zytotoxische CD8 T Zell-Immunantwort nach einer MCMV-Infektion zu induzieren und dass dies auch in vivo unabhängig von CD80/86 erfolgte. Zusammenfassend konnte in dieser Arbeit die Rolle von LSEC bei der Regulation lokaler Immunantworten näher charakterisiert werden

Hospital use of systemic antifungal drugs

BACKGROUND: Sales data indicate a major increase in the prescription of antifungal drugs in the last two decades. Many new agents for systemic use that only recently have become available are likely to be prescribed intensively in acute care hospitals. Sales data do not adequately describe the developments of drug use density. Given the concerns about the potential emergence of antifungal drug resistance, data on drug use density, however, may be valuable and are needed for analyses of the relationship between drug use and antifungal resistance. METHODS: Hospital pharmacy records for the years 2001 to 2003 were evaluated, and the number of prescribed daily doses (PDD, defined according to locally used doses) per 100 patient days were calculated to compare systemic antifungal drug use density in different medical and surgical service areas between five state university hospitals. RESULTS: The 3-year averages in recent antifungal drug use for the five hospitals ranged between 8.6 and 29.3 PDD/100 patient days in the medical services (including subspecialties and intensive care), and between 1.1 and 4.0 PDD/100 patient days in the surgical services, respectively. In all five hospitals, systemic antifungal drug use was higher in the hematology-oncology service areas (mean, 48.4, range, 24 to 101 PDD/100 patient days, data for the year 2003) than in the medical intensive care units (mean, 18.3, range, 10 to 33 PDD/100) or in the surgical intensive care units (mean, 10.7, range, 6 to 18 PDD/100). Fluconazole was the most prescribed antifungal drug in all areas. In 2003, amphotericin B consumption had declined to 3 PDD/100 in the hematology-oncology areas while voriconazole use had increased to 10 PDD/100 in 2003. CONCLUSION: Hematology-oncology services are intense antifungal drug prescribing areas. Fluconazole and other azol antifungal drugs are the most prescribed drugs in all patient care areas while amphotericin B use has considerably decreased. The data may be useful as a benchmark for focused interventions to improve prescribing quality

Energy efficiency and using less – a social sciences and humanities annotated bibliography

The challenge: * Technological progress and changes in energy supply are not sufficient for a transition to a low-carbon energy system; demand also needs to be considered. Energy efficiency and reducing total consumption - the topics of this bibliography - are typical elements of a demand side approach. * The uptake of energy efficient technologies, and understanding how we might use less energy, represent big challenges for researchers, policymakers, practitioners and end-users themselves. The aim: * European energy policy has so far mainly relied on research from Science, Technology, Engineering and Mathematics (STEM) disciplines. Energy-related Social Sciences and Humanities (SSH) have been significantly underrepresented. This bibliography aims to discuss different disciplinary perspectives on energy efficiency and using less and to demonstrate their relevance for energy policy. Coverage: * A major focus of this bibliography is on behaviour and behavioural change. The bibliography highlights the diversity of end-users and their needs, the impacts they experience, abilities, as well as the range of sites where energy is consumed. * It also looks at how SSH research addresses more structural elements of demand - such as markets, institutions, and policy - and how these interact. Key findings: * There is no such thing as a one size fits all approach; different disciplines frame the problems of energy efficiency and using less differently, and do not always agree. Economics is very highly represented in research about energy efficiency, closely followed by Sociology. Other disciplines such as Urban Studies and Industrial Design are slowly becoming part of the work. * Most disciplines focus mainly on mainstream types of users and use. Fewer studies focus on the exceptions - deviants, others, non-users or energy poor, excessive users - or low-energy practices such as sleep, music making or sports. * Electricity is the main focus of most social science research on energy use and efficiency, possibly due to a focus on monitoring savings which is more difficult for gas and energy for hot water use. * There is an overrepresentation of work on feedback devices and smart meters, in contrast to more everyday technologies such as water heaters or washing machines. Several studies urge for more study of this everyday material culture because it strongly shapes how users can engage in using less or using more efficiently; some technologies are simply built to have high energy use. * Less research is done on the responsibility of stakeholders (other than the end-user) for the energy transition, especially the market. It is argued that markets are not neutral or depoliticised, but bear responsibility for the energy transition too. * Dominant areas of research include: a focus on the gap between awareness and actual energy behaviour action; and rebound effects, which may arise when increased energy efficiency leads to lower costs for energy which in turn may lead to increased energy consumption. * New areas of research include new demand side initiatives, services/business models and markets such as peer-to-peer, DIY, and community approaches to engagement. * Most demand side approaches in the policy domain focus on cost reduction, education and communication. Insights from Social Sciences such as Sociology, Anthropology, Urban studies, Ethics, and Science and Technology Studies see less uptake in the policy domain

Brake response time before and after total knee arthroplasty: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although the numbers of total knee arthroplasty (TKA) are increasing, there is only a small number of studies investigating driving safety after TKA. The parameter 'Brake Response Time (BRT)' is one of the most important criteria for driving safety and was therefore chosen for investigation.</p> <p>The present study was conducted to test the hypotheses that patients with right- or left-sided TKA show a significant increase in BRT from pre-operative (pre-op, 1 day before surgery) to post-operative (post-op, 2 weeks post surgery), and a significant decrease in BRT from post-op to the follow-up investigation (FU, 8 weeks post surgery). Additionally, it was hypothesized that the BRT of patients after TKA is significantly higher than that of healthy controls.</p> <p>Methods</p> <p>31 of 70 consecutive patients (mean age 65.7 +/- 10.2 years) receiving TKA were tested for their BRT pre-op, post-op and at FU. BRT was assessed using a custom-made driving simulator. We used normative BRT data from 31 healthy controls for comparison.</p> <p>Results</p> <p>There were no significant increases between pre-op and post-op BRT values for patients who had undergone left- or right-sided TKA. Even the proportion of patients above a BRT threshold of 700 ms was not significantly increased postop. Controls had a BRT which was significantly better than the BRT of patients with right- or left-sided TKA at all three time points.</p> <p>Conclusion</p> <p>The present study showed a small and insignificant postoperative increase in the BRT of patients who had undergone right- or left-sided TKA. Therefore, we believe it is not justified to impair the patient's quality of social and occupational life post-surgery by imposing restrictions on driving motor vehicles beyond an interval of two weeks after surgery.</p

Students benefit from developing their own emergency medicine OSCE stations: a comparative study using the matched-pair method

Background: Students can improve the learning process by developing their own multiple choice questions. If a similar effect occurred when creating OSCE (objective structured clinical examination) stations by themselves it could be beneficial to involve them in the development of OSCE stations. This study investigates the effect of students developing emergency medicine OSCE stations on their test performance. Method: In the 2011/12 winter semester, an emergency medicine OSCE was held for the first time at the Faculty of Medicine at the University of Leipzig. When preparing for the OSCE, 13 students (the intervention group) developed and tested emergency medicine examination stations as a learning experience. Their subsequent OSCE performance was compared to that of 13 other students (the control group), who were parallelized in terms of age, gender, semester and level of previous knowledge using the matched-pair method. In addition, both groups were compared to 20 students who tested the OSCE prior to regular emergency medicine training (test OSCE group). Results: There were no differences between the three groups regarding age (24.3 +/- 2.6; 24.2 +/- 3.4 and 24 +/- 2.3 years) or previous knowledge (29.3 +/- 3.4; 29.3 +/- 3.2 and 28.9 +/- 4.7 points in the multiple choice {[} MC] exam in emergency medicine). Merely the gender distribution differed (8 female and 5 male students in the intervention and control group vs. 3 males and 17 females in the test OSCE group). In the exam OSCE, participants in the intervention group scored 233.4 +/- 6.3 points (mean +/- SD) compared to 223.8 +/- 9.2 points (p &lt; 0.01) in the control group. Cohen's effect size was d = 1.24. The students of the test OSCE group scored 223.2 +/- 13.4 points. Conclusions: Students who actively develop OSCE stations when preparing for an emergency medicine OSCE achieve better exam results

Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi