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Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

We propose an interactive video browsing tool for supporting content management and selection in postproduction. The approach is based on a process model for multimedia content abstraction. A software framework based on this process model and desktop and Web-based client applications are presented. For evaluation, we apply two TRECVID style fact finding approaches (retrieval and question answering tasks) and a user survey to the evaluation of the video browsing tool. We analyze the correlation between the results of the different methods, whether different aspects can be evaluated independently with the survey, and if a learning effect can be measured with the different methods, and we also compare the full-featured desktop and the limited Web-based user interface. The results show that the retrieval task correlates better with the user experience according to the survey. The survey rather measures the general user experience while different aspects of the usability cannot be analyzed independently.

To the extent in which demographic change and selected resulting problems are considered in public, the specialist terms of demography are also losing their isolation. One such term is “carrying capacity”. Problematic are the multiple connotations with which the respective underlying problem is considered, often depending on the respective viewpoint. Like other terms it is moreover used in several disciplines and to top it all in colloquial language. This contribution understands itself as an attempt to explain carrying capacity from the perspective of regional demography, to establish linkages and also to follow a historical line. Remarkable is the variety of aspects of the term that can hardly be reconstructed but also its change in terms of content when it is occupied by political language following strategic objectives.

Funding provided under theAufbau Ost («Rebuilding the East») programme and other forms of financial transfer to theLänder (federal states) of eastern Germany have up to now been at their least effective in the area to the east of the River Elbe. Indeed, many of the instruments of both regional structure policy and economic development policy which have repeatedly proved their worth in the rural areas of the former West Germany have failed in the north-east. This area seems to be something of a bottomless pit. From a regional-demographic perspective, this region has to be clearly distinguished from more “ordinary” rural space, and assigned to a distinct new category to be termed “most rural space”.

Abstract Current approaches to project spatial biodiversity responses to climate change mainly focus on the direct effects of climate on species while regarding land use and land cover as constant or prescribed by global land‐use scenarios. However, local land‐use decisions are often affected by climate change and biodiversity on top of socioeconomic and policy drivers. To realistically understand and predict climate impacts on biodiversity, it is, therefore, necessary to integrate both direct and indirect effects (via climate‐driven land‐use change) of climate change on biodiversity. In this perspective paper, we outline how biodiversity models could be better integrated with regional, climate‐driven land‐use models. We initially provide a short, non‐exhaustive review of empirical and modelling approaches to land‐use and land‐cover change (LU) and biodiversity (BD) change at regional scales, which forms the base for our perspective about improved integration of LU and BD models. We consider a diversity of approaches, with a special emphasis on mechanistic models. We also look at current levels of integration and at model properties, such as scales, inputs and outputs, to further identify integration challenges and opportunities. We find that LU integration in BD models is more frequent than the other way around and has been achieved at different levels: from overlapping predictions to simultaneously coupled simulations (i.e. bidirectional effects). Of the integrated LU‐BD socio‐ecological models, some studies included climate change effects on LU, but the relative contribution of direct vs. indirect effects of climate change on BD remains a key research challenge. Important research avenues include concerted efforts in harmonizing spatial and temporal resolution, disentangling direct and indirect effects of climate change on biodiversity, explicitly accounting for bidirectional feedbacks, and ultimately feeding socio‐ecological systems back into climate predictions. These avenues can be navigated by matching models, plugins for format and resolution conversion, and increasing the land‐use forecast horizon with adequate uncertainty. Recent developments of coupled models show that such integration is achievable and can lead to novel insights into climate–land use–biodiversity relations. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Only a few decades ago, colorful, small‐scale, heterogeneous, and species‐rich hay meadows or extensive pastures were common, but have often been replaced by species‐poor, uniform, large‐scale multicut meadows. Technological advancements and improved efficiency in grassland management have come at the cost of biodiversity. Methods In Germany, 150 grassland plots have been investigated since 2006. Using these extensive data, we propose a new compound index for estimating the site‐specific mowing intensity in order to facilitate assessment of the impact of mowing intensity on biodiversity and ecosystem processes. Our index integrates the various qualitative components of mowing machine type, mowing height and use of a conditioner, with the annual number of cuts. Results The newly proposed index achieves a much finer gradation of mowing intensity compared to the previous quantification based on the number of cuts only. Furthermore, a decrease in plant and arthropod species was observed at higher mowing intensity. Conclusions The proposed mowing intensity index offers enhanced precision in calculations and can easily be integrated into assessments of land‐use intensity in grasslands. Further, it could serve as a basis for providing subsidies to farmers, who adopt low‐impact mowing practices.