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We present results of implicit large eddy simulation (LES) and different Reynolds-averaged Navier-Stokes (RANS) models of the MTU 161 low pressure turbine at an exit Reynolds number of 90,000 and exit Mach number of 0.6. The LES results are based on a high order discontinuous Galerkin method and the RANS is computed using a classical finite-volume approach. The paper discusses the steps taken to create realistic inflow boundary conditions in terms of end wall boundary layer thickness and free stream turbulence intensity. This is achieved by tailoring the input distribution of total pressure and temperature, Reynolds stresses and turbulent length scale to a Fourier series based synthetic turbulence generator. With this procedure, excellent agreement with the experiment can be achieved in terms of blade loading at midspan and wake total pressure losses at midspan and over the channel height. Based on the validated setup, we focus on the discussion of secondary flow structures emerging due to the interaction of the incoming boundary layer and the turbine blade and compare the LES to two commonly used RANS models. Since we are able to create consistent setups for both LES and RANS, all discrepancies can be directly attributed to physical modelling problems. We show that both a linear eddy viscosity model and a differential Reynolds stress model coupled with a state-of-the-art correlation-based transition model fail, in this case, to predict the separation induced transition process around midspan. Moreover, their prediction of secondary flow losses leaves room for improvement as shown by a detailed discussion turbulence kinetic energy and anisotropy fields., Comment: invited submission to Flow, Turbulence and Combustion Special Issue: 13th ERCOFTAC Workshop on Direct and Large Eddy Simulation - DLES13

We present first results of an implicit large eddy simulation of the MTU T161 low pressure turbine at a Reynolds number of 90,000 and Mach number of 0.6, both based on isentropic exit conditions, using a high order discontinuous Galerkin method. The aim is to validate the numerical setup with respect to available experimental data. We discuss the steps taken to create realistic inflow boundary conditions in terms of end wall boundary layer thickness and free stream turbulence intensity. This is achieved by tailoring the input distribution of Reynolds stresses and turbulent length scale to a Fourier series based synthetic turbulence generator. Both blade loading and total pressure losses at midspan show excellent agreement with the measurements. Following a short discussion of the secondary flow structures emerging due to the interaction of the incoming boundary layer and the turbine blade, we show that this simulation is also able to reproduce loss distribution behind the blade over the whole channel height., submitted to conference proceedings of DLES13 (Direct and Large Eddy Simulation)

The entire maritime sector, encompassing not only on-shore systems but especially systems onboard vessels, is increasingly endangered by threats from cyberspace. Implementing preventive security like cryptography into existing systems can be costly. Thus, network-based Intrusion Detection Systems (NIDSs) promise to be a retrofittable security solution that alerts suspicious network behavior. Regarding vessels, however, there is still a lack of NIDSs detecting sophisticated cyberattacks manipulating nautical data, e.g., by spoofing a vessel’s course and position. Moreover, the intended users of such NIDSs onboard vessels would be nautical operators rather than cybersecurity experts, although interpreting the alarms of a typical NIDS and understanding their consequences requires expert knowledge in cybersecurity. For this reason, we present a Cyber Incident Monitor (CIM), a security framework combining a specialized maritime NIDS to detect sophisticated attacks in maritime networks with a customized human machine interface (HMI) providing tailored guidance for nautical operators to respond adequately in the event of a cyberattack. Using simulations, we show that CIM detects attacks quickly and through usability tests involving nautical experts, we derive helpful advice for the HMI development. Overall, CIM enables the detection of maritime cyberattacks while providing alerts and recommendations to navigators to take appropriate measures in a timely manner., The work in this paper was partially funded by the German Federal Ministry for Digital and Transport (BMDV) as part of the project SINAV (project 40.0404/2019).

This database documents orchestras digital strategies for remote delivery during the COVID-19 pandemic. It is the first stage of a SSHRC-funded research-creation project between Ryerson University and the National Arts Centre Orchestra, in Canada, to mitigate the impact of post-COVID-19 restrictions on the Canadian classical music sector by innovating audiovisual remote delivery. We used non-probability sampling to select thirty-three orchestras from four continents. From January 13 to March 8, 2021 we collected online data on orchestral activities that had taken place or had been published from March 24, 2020 to March 8, 2021 using the orchestras' websites as our main sources. All data entries were classified in types and categories to enhance searchability. The data was systematically coded on audiovisual correlation.

With the arrival of effective COVID-19 vaccines, the fight against the ongoing global pandemic entered a new stage. The question shifted towards how to vaccinate as many people as quickly as possible. Understanding the reasons people choose to get vaccinated or not is integral in informing immunization campaigns. But who are the unvaccinated? This is determined by using cross-national data from the Survey of Health, Ageing and Retirement in Europe (SHARE). We investigate the interrelation of the (un)willingness to be vaccinated with social and health aspects as well as the economic situation of our sample of adults in Europe, aged 50 and above. We find that respondents’ economic situation as well as diagnosed physical illnesses and education show the strongest relation to vaccination hesitancy. Our results provide a comprehensive picture of influential factors of older adults’ vaccination behaviour that can advance the success of the immunisation campaigns in Europe., easy social sciences (2022): Mixed Starting Point and Frequency: Year: 1989, Issues per Year: 2, easy social sciences

With the arrival of effective COVID-19 vaccines, the fight against the ongoing global pandemic entered a new stage. The question shifted towards how to vaccinate as many people as quickly as possible. Understanding the reasons people choose to get vaccinated or not is integral in informing immunization campaigns. But who are the unvaccinated? This is determined by using cross-national data from the Survey of Health, Ageing and Retirement in Europe (SHARE). We investigate the interrelation of the (un)willingness to be vaccinated with social and health aspects as well as the economic situation of our sample of adults in Europe, aged 50 and above. We find that respondents’ economic situation as well as diagnosed physical illnesses and education show the strongest relation to vaccination hesitancy. Our results provide a comprehensive picture of influential factors of older adults’ vaccination behaviour that can advance the success of the immunisation campaigns in Europe., easy social sciences (2022): Mixed Starting Point and Frequency: Year: 1989, Issues per Year: 2, easy social sciences

Implicit large-eddy simulations of the high-pressure turbine cascade VKI-LS89 under transonic operating conditions using a high-order accurate discontinuous Galerkin spectral element method are presented. The subcell shock capturing method by Hennemann et al. [1] is investigated and compared against simulations with artificial viscosity. Additionally, the effect of laminar and turbulent inflow conditions are validated against numerical and experimental results from literature. This analysis shows that the subcell-shock-capturing method performs well by effectively reducing spurious oscillations across the shock front and acoustic waves while leaving the rest of the solution domain unaffected.

To overcome the challenges that the maritime sector faces, the future must embody more efficient and effective collaboration. This cannot realistically be achieved without further digitalisation. This chapter identifies the principal tensions and opportunities that impact the inevitable and ongoing digitalisation process that is underway in the maritime transportation sector. The chapter also identifies the trends of development at large and those associated with the key stakeholders that are involved in global maritime operations. The digital trends emerging in shipping companies, ports with its actors, authorities and associations, and movements that are being made by diverse digital solution providers, within and outside the maritime domain are also identified. The discussion takes the point of view that shipping is a global phenomenon enabled by ship movements creating a global network of sea transport facilitated by ports. Achieving higher levels of collaboration through digitalisation requires that tools and systems are interoperable by adopting harmonised open standards. It requires the use of standardised formats and standardised interfaces for communication, building upon commonly agreed definitions of phenomena and processes associated with port call operations. The chapter closes with a brief discussion on the emergence of “smart” ports and “smart” ships, which rely heavily of digitalisation, collaboration and the continuous sharing of and access to relevant data.

Summary Background The rate of restoration of intestinal continuity after colonic resection and stoma creation in patients with Crohn’s disease has not been well-documented in the era of biologics. Thus, the incidence of restoration of intestinal continuity since the introduction of biological drugs was assessed. Methods Consecutive patients (n = 43) who underwent colonic resection with ileostomy or colostomy formation for Crohn’s disease at a single tertiary referral center between 2002 and 2014 were identified. Data from individual chart review were analyzed retrospectively. Patients were personally contacted for follow-up. Results Of the 43 patients 8 (18.4%) had a proctectomy leaving 35 patients (81.4%) with the rectum preserved. Of the 30 patients qualifying for final analysis restoration of bowel continuity was finally achieved in 10 patients (33.3%). Permanent stoma rates were comparable in the group of patients with and without biological therapy after surgery (64.3% vs. 60%). The median follow-up period was 7 years (range 3–15 years). Of the patients 20 suffered from perianal disease involvement (66.7%), which was associated with a higher rate of permanent stoma (n = 16/20, 80%) in contrast to patients without perianal disease (n = 4/10, 40%, p = 0.045). Conclusion The overall incidence of stoma formation was low for patients with Crohn’s disease; however, once a stoma is created the chance of ending up with a permanent stoma is high even in the era of biologics. Despite the use of new therapeutic agents perianal disease increases the risk of a permanent stoma.

Purpose: We analyzed the effects of COVID-19 as well as its accompanying epidemiological control measures on health-related outcomes (physical and mental health) and unmet care needs of both caregivers and care recipients across Europe and Israel by taking into account country differences. Methods: We applied comparisons of adjusted predictions, controlling for a large set of relevant respondent characteristics, to investigate changes in the physical and mental health of caregivers and care recipients due to COVID-19. Furthermore, multilevel regression models were used to analyze the effect of individual and contextual indicators on the probability of reporting difficulties in receiving care. For the analyses, we used data from 26 countries with 51,983 respondents over 50 years based on the eighth wave of the Survey of Health, Aging and Retirement in Europe (SHARE), which had to be suspended in March 2020, and the SHARE Corona Survey fielded from June to August 2020. Results: During the first phase of the pandemic in spring/summer 2020, the frequency of providing personal care to parents increased in almost all European countries, while care to children, in turn, decreased. Parental caregivers who increased the frequency of providing personal care reported significantly more mental health strains, that is, feeling sad/depressed and anxious/nervous more often since the outbreak of the pandemic. With respect to receiving care, about one out of five care recipients had difficulty in obtaining adequate care from outside the household during the pandemic. The perception of unmet care needs was significantly associated with country differences regarding the duration of the stay-at-home orders. In contrast, the number of confirmed deaths did not have a significant effect on perceiving difficulties related to receiving care. Conclusions: Our findings show the extent of the burden to which caregivers and care recipients were exposed with respect to the unintended consequences of COVID-19-related epidemiological control measures. There is a great need within this population for interventions, which effectively reduce the burden as well as the symptoms of anxiety or depression for caregivers as well as care recipients. This should be recognized by (health) policymakers and social organizations.

This study provides a synopsis of the current fieldwork monitoring practices of large-scale surveys in Germany. Based on the results of a standardized questionnaire, the study summarizes fieldwork monitoring indicators used and fieldwork measures carried out by 17 large-scale social sciences surveys in Germany. Our descriptive results reveal that a common set of fieldwork indicators and measures exist on which the studied surveys rely. However, it also uncovers the need for additional design-specific indicators. Finally, it underlines the importance of a close cooperation between survey representatives and fieldwork agencies to optimize processes in fieldwork monitoring in the German survey context. The article concludes with implications for fieldwork practice.

This study provides a synopsis of the current fieldwork monitoring practices of large-scale surveys in Germany. Based on the results of a standardized questionnaire, the study summarizes fieldwork monitoring indicators used and fieldwork measures carried out by 17 large-scale social sciences surveys in Germany. Our descriptive results reveal that a common set of fieldwork indicators and measures exist on which the studied surveys rely. However, it also uncovers the need for additional design-specific indicators. Finally, it underlines the importance of a close cooperation between survey representatives and fieldwork agencies to optimize processes in fieldwork monitoring in the German survey-context. The article concludes with implications for fieldwork practice.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein modulating cell-matrix interactions and was found up-regulated in tumor stroma. To explore the effect of high stromal SPARC on colorectal cancer (CRC) cell behavior and clinical outcome, this study determined SPARC expression in patients suffering from stage II and III CRC using a publicly available mRNA data set and immunohistochemistry of tissue microarray sections. Moreover, in vitro co-culture models using CRC cell lines together with colon-associated fibroblasts were established to determine the effect of fibroblast-derived SPARC on cancer cells. In 466 patient samples, high SPARC mRNA was associated with a shorter disease-free survival. In 99 patients of the tissue microarray cohort, high stromal SPARC in the primary tumor was an independent predictor of shorter survival in patients with relapse (27 cases, HR = 4574, p = 0.004). In CRC cell lines, SPARC suppressed phosphorylation of focal adhesion kinase and stimulated cell migration. Colon-associated fibroblasts increased migration velocity by 30% and doubled track-length in SPARC-dependent manner. In a 3D co-culture system, fibroblast-derived SPARC enhanced tumor cell invasion. Taken together, stromal SPARC had a pro-metastatic impact in vitro and was a characteristic of aggressive tumors with poor prognosis in CRC patients.

Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records., What's new? Colorectal cancer exhibits certain characteristic changes in metabolic pathways. To expand upon previous findings, these authors performed a discovery‐replication study using two large independent study populations from different countries, Germany and Austria. They tested metabolic profiles of cancer patients and controls, identifying 691 statistically significant features in the discovery cohort. Testing the second cohort narrowed it to 97. These corresponded to 28 metabolites, of which 15 could be identified. It will be useful to go forward with prospective analysis on these 15 metabolites, to determine whether they have predictive or prognostic value.

T cells in colorectal cancer (CRC) are associated with improved survival. However, checkpoint immunotherapies antagonizing the suppression of these cells are ineffective in the great majority of patients. To better understand the immune cell regulation in CRC, we compared tumor-associated T lymphocytes and macrophages to the immune cell infiltrate of normal mucosa. Human colorectal tumor specimen and tumor-distant normal mucosa tissues of the same patients were collected. Phenotypes and functionality of tissue-derived T cells and macrophages were characterized using immunohistochemistry, RNA in situ hybridization, and multiparameter flow cytometry. CRC contained significantly higher numbers of potentially immunosuppressive CD39 and Helios-expressing regulatory T cells in comparison to normal mucosa. Surprisingly, we found a concomitant increase of pro-inflammatory IFNγ -producing T cells. PD-L1+ stromal cells were decreased in the tumor tissue. Macrophages in the tumor compared to tumor-distant normal tissue appear to have an altered phenotype, identified by HLA-DR, CD14, CX3CR1, and CD64, and tolerogenic CD206+ macrophages are quantitatively reduced. The prognostic effect of these observed differences between distant mucosa and tumor tissue on the overall survival was examined using gene expression data of 298 CRC patients. The combined gene expression of increased FOXP3, IFNγ, CD14, and decreased CD206 correlated with a poor prognosis in CRC patients. These data reveal that the CRC microenvironment promotes the coexistence of seemingly antagonistic suppressive and pro-inflammatory immune responses and might provide an explanation why a blockade of the PD1/PD-L1 axis is ineffective in CRC. This should be taken into account when designing novel treatment strategies.

Scale resolving simulations are indispensable to provide in-depth knowledge of turbulence in order to improve turbulence modelling approaches for turbomachinery design processes. However, the in flow conditions of spatially evolving turbulent flow simulations are of utmost significance for the accurate reproduction of physics especially for Large Eddy Simulations. The present paper compares two approaches to introduce synthetically generated velocity fluctuations for Large Eddy Simulations: an in flow boundary condition and a source term formulation. In case of the boundary condition the velocity fluctuations are added to the mean velocity components at the inlet panel of the computational domain. The source term formulation uses an additional volume term in the momentum equation to add the fluctuating velocity field at an arbitrary location. The functionality of these methods in combination with the synthetic generation of fluctuations is validated in the generic test case of spatially decaying homogeneous isotropic turbulence. Furthermore, the spatial variation and anisotropy of turbulent statistics in a turbulent boundary layer as well as the development length of the different combinations, needed to reach a fully developed flow, are analysed for a turbulent channel flow.

In order to test detector components before their installation in actual experiments, one uses test beams in which one can control particle typ, momentum and size to high degree. For this project the focus of a secondary beam at T10 in the East Area at CERN was analysed using an AZALEA telescope from DESY.

The linear ubiquitin chain assembly complex (LUBAC), consisting of SHANK-associated RH-domain-interacting protein (SHARPIN), heme-oxidized IRP2 ubiquitin ligase-1 (HOIL-1), and HOIL-1-interacting protein (HOIP), is a critical regulator of inflammation and immunity. This is highlighted by the fact that patients with perturbed linear ubiquitination caused by mutations in the Hoip or Hoil-1 genes, resulting in knockouts of these proteins, may simultaneously suffer from immunodeficiency and autoinflammation. TLR3 plays a crucial, albeit controversial, role in viral infection and tissue damage. We identify a pivotal role of LUBAC in TLR3 signaling and discover a functional interaction between LUBAC components and TLR3 as crucial for immunity to influenza A virus infection. On the biochemical level, we identify LUBAC components as interacting with the TLR3-signaling complex (SC), thereby enabling TLR3-mediated gene activation. Absence of LUBAC components increases formation of a previously unrecognized TLR3-induced death-inducing SC, leading to enhanced cell death. Intriguingly, excessive TLR3-mediated cell death, induced by double-stranded RNA present in the skin of SHARPIN-deficient chronic proliferative dermatitis mice (cpdm), is a major contributor to their autoinflammatory skin phenotype, as genetic coablation of Tlr3 substantially ameliorated cpdm dermatitis. Thus, LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation.

In the ever more complex environment navigators need support by integrated systems to ensure Situational Awareness. The concepts of “Ship Domain” and “Ship Arena” are appropriate approaches to evaluate the situational centric risk. Generally, the qualification of SD approach for reliable decision finding requires more research to better define the different factors influencing the ship domain (static/dynamic); and the provision of means to determine and monitor error budgets within integrated systems. In particular, human factors may need an improved quantification of errors & risks; standardized data quality indicators are needed (e.g. see IHO DQWG); DSCC (static/dynamic) needs to be established to ensure the reliable data supply error budget and to indicate the level in during delivery.

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2014/2015 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2014 erarbeitet und im Januar 2015 präsentiert. Das Themenspektrum ist vielfältig und reicht von der Darstellung aktueller Geschäftsmodelle (Siemens, Gagfah, Praktiker, OBI) über die Konkurrenz verschiedener Unternehmen, die bis zu persönlichen Feindschaften führt (Oracle, SAP) oder den Kampf um die Rolle als weltweit größter Autohersteller (VW, Toyota, General Motors) bis zur Schilderung der historischen Entwicklung mit einem Ausblick auf künftige Umstrukturierungen (Bayer) und einer gescheiterten feindlichen Übernahme (Stahl vs. Weidmüller). Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit.

GESIS Papers

Die vorliegende Arbeit stellt ein Security Framework und Traceability-Modell zum Tracking von Sicherheitsanforderungen in System-/ Softwareentwicklungsprojekten vor. Nach der einführenden Darlegung von Aufgabenstellung und Zielen findet eine umfassende Darstellung der verwendeten Ansätze in Form einer Literaturanalyse für die Bereiche Requirements Engineering, insbesondere für Requirements Traceability sowie Security und Secure Software Engineering statt, die im Rahmen eines Vergleiches auf inhaltlicher und struktureller Ebene betrachtet werden. Anschließend wird darauf aufbauend ein Security Framework mit verantwortlichen Rollen für die jeweiligen Aktivitäten entwickelt. Dies ist gemeinsam mit dem Traceability Metamodell und High-End Traceability Model die Basis für die Erstellung eines konzeptionellen Traceability-Modells inkl. Submodellen für Anforderungsmanagement und Design. Die entwickelten Ansätze werden in den Softwareprozess Scrum integriert und anschließend in Form einer Fallstudie evaluiert. Eine Zusammenfassung, Schlussfolgerungen und weiterführende Fragestellungen runden die Arbeit ab., This thesis presents a security framework and traceability model for the tracking of security requirements in system / software development projects. The presentation of tasks and goals is followed by a comprehensive description of currently used approaches in the form of a literature review in the areas of requirements engineering. In particular, detailed survey for requirements traceability and security and secure software engineering is given. These areas are considered in the context of a comparison in terms of content and structural level. On this basis a security framework with responsible roles for each activity was developed. Together with the traceability meta model and high-end traceability model this is the basis for the creation of a conceptual traceability model incl. sub-models for requirements management and design. The developed approaches are then integrated in the software process Scrum and subsequently evaluated in the form of a case study. The thesis finishes with a summary, conclusions and a list of further questions.

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2014/2015 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2014 erarbeitet und im Januar 2015 präsentiert. Das Themenspektrum ist vielfältig und reicht von der Darstellung aktueller Geschäftsmodelle (Siemens, Gagfah, Praktiker, OBI) über die Konkurrenz verschiedener Unternehmen, die bis zu persönlichen Feindschaften führt (Oracle, SAP) oder den Kampf um die Rolle als weltweit größter Autohersteller (VW, Toyota, General Motors) bis zur Schilderung der historischen Entwicklung mit einem Ausblick auf künftige Umstrukturierungen (Bayer) und einer gescheiterten feindlichen Übernahme (Stahl vs. Weidmüller). Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit.

GESIS Papers

This study examined the effects of the CYP3A/P-glycoprotein inducer, rifampicin, on the pharmacokinetics of dabigatran following oral administration of the prodrug, dabigatran etexilate.This was an open-label, fixed-sequence, four-period study in healthy volunteers. Subjects received a single dose of dabigatran etexilate 150 mg on day 1, rifampicin 600 mg once daily on days 2-8, and single doses of dabigatran etexilate on days 9, 16 and 23.Twenty-four subjects were treated, of whom 22 received all treatments. Relative to the reference (single dose of dabigatran etexilate alone; treatment A), administration of dabigatran etexilate following 7 days of rifampicin (treatment B) decreased the geometric mean (gMean) area under the concentration-time curve (AUC(0-∞)) and maximal plasma concentration (C(max)) of total dabigatran by 67 and 65.5%, respectively. The time to peak and the terminal half-life were not affected. The gMean ratio for the primary comparison (treatment B vs. treatment A) was 33.0% (90% confidence interval 26.5, 41.2%) for AUC(0-∞) and 34.5% (90% confidence interval 26.9, 44.1%) for C(max), indicating a significant effect on total dabigatran exposure (total pharmacologically active dabigatran represents the sum of nonconjugated dabigatran and dabigatran glucuronide). After a 7 day (treatment C) or 14 day washout (treatment D), the AUC(0-∞) and C(max) of dabigatran were reduced by 18 and 20%, and by 15 and 20%, respectively, compared with treatment A, which was considered not clinically relevant. The overall safety profile of all treatments was good.Administration of rifampicin for 7 days resulted in a significant reduction in the bioavailability of dabigatran, which returned almost to baseline after 7 days washout.

Diese Arbeit befasst sich mit der Phase I des Projekts des IASB einen allgemein gültigen Rechnungslegungsstandard für Versicherungsverträge zu gestalten. Ziel war es herauszuarbeiten, wie der Standard aufgrund des Entwurfes (Exposure Draft) gestaltet werden sollte und welche Fragen der IASB in diesem Zusammenhang aufgeworfen hat. Da es insgesamt 133 Stellungnahmen von diversen Institutionen, Versicherungen, Verbänden, Standardsettern, usw. zum Entwurf gab, wurden diese unter Mithilfe von Univ.-Prof. Dr. Otto A. Altenburger und Mag. Magdalena Kuntner in Kategorien eingeteilt und gesondert bearbeitet, wobei sich die vorliegende Arbeit mit den Kommentaren der Standardsetter befasst. Der Hauptteil der Arbeit gliedert sich in 13 Fragen, die der IASB zur Stellungnahme ausgeschrieben hat und bearbeitet dadurch den Standardentwurf. Ergänzend wurden zu jeder dieser Fragen die größten Kritikpunkte, aber auch zustimmenden Kommentare und gewünschte Ergänzungen der Standardsetter angeführt, wobei versucht wurde, eine grundlegende Tendenz zu den einzelnen Punkten aufzuzeigen. Schließlich galt es zu untersuchen, welche Änderungen in den derzeit gültigen Standard IFRS 4 übernommen worden sind und eine Aussicht zu geben, wie sich die noch aktuell laufende Phase II weiterentwickelt.