A novel blood-sparing agent in cardiac surgery? First in-patient experience with the synthetic serine protease inhibitor MDCO-2010: a phase II, randomized, double-blind, placebo-controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

BACKGROUND Antifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients. METHODS In this phase II, double-blind, placebo-controlled study, 32 patients undergoing isolated primary coronary artery bypass grafting with cardiopulmonary bypass were randomly assigned to 1 of 5 increasing dosage groups of MDCO-2010. The primary aim was to evaluate pharmacokinetics (PK) with assessment of plasmatic concentrations of the drug, short-term safety, and tolerance of MDCO-2010. Secondary end points were influence on coagulation, chest tube drainage, and transfusion requirements. RESULTS PK analysis showed linear dosage-proportional correlation between MDCO-2010 infusion rate and PK parameters. Blood loss was significantly reduced in the 3 highest dosage groups compared with control (P = 0.002, 0.004 and 0.011, respectively). The incidence of allogeneic blood product transfusions was lower with MDCO-2010 4/24 (17%) vs 4/8 (50%) in the control group. MDCO-2010 exhibited dosage-dependent antifibrinolytic effects through suppression of D-dimer generation and inhibition of tissue plasminogen activator-induced lysis in ROTEM analysis as well as anticoagulant effects demonstrated by prolongation of activated clotting time and activated partial thromboplastin time. No systematic differences in markers of end organ function were observed among treatment groups. Three patients in the MDCO-2010 groups experienced serious adverse events. One patient experienced intraoperative thrombosis of venous grafts considered possibly related to the study drug. No reexploration for mediastinal bleeding was required, and there were no deaths. CONCLUSIONS This first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.

Climate change in Switzerland: a review of physical, institutional, and political aspects

Climate change is clearly discernible in observed climate records in Switzerland. It impacts on natural systems, ecosystems, and economic sectors such as agriculture, tourism, and energy, and it affects Swiss livelihood in various ways. The observed and projected changes call for a response from the political system, which in Switzerland is characterized by federalism and direct democratic instruments. Swiss climate science embraces natural and social sciences and builds on institutionalized links between researchers, public, and private stakeholders. In this article, we review the physical, institutional, and political aspects of climate change in Switzerland. We show how the current state of Swiss climate science and policy developed over the past 20 years in the context of international developments and national responses. Specific to Switzerland is its topographic setting with mountain regions and lowlands on both sides of the Alpine ridge, which makes climate change clearly apparent and for some aspects (tourist sector, hydropower, and extreme events) highly relevant and better perceivable (e.g., retreating glaciers). Not surprisingly the Alpine region is of central interest in Swiss climate change studies.

How involved are they really? A comparative network analysis of the institutional drivers of local actor inclusion

Different socio-economic and environmental drivers lead local communities in mountain regions to adapt land use practices and engage in protection policies. The political system also has to develop new approaches to adapt to those drivers. Local actors are the target group of those policy approaches, and the question arises of if and how much those actors are consulted or even integrated into the design of local land use and protection policies. This article addresses this question by comparing seven different case studies in Swiss mountain regions. Through a formal social network analysis, the inclusion of local actors in collaborative policy networks is investigated and compared to the involvement of other stakeholders representing the next higher sub-national or national decisional levels. Results show that there is a significant difference (1) in how local actors are embedded compared to other stakeholders; and (2) between top-down versus bottom-up designed policy processes.

IMRT credentialing for prospective trials using institutional virtual phantoms: results of a joint European Organization for the Research and Treatment of Cancer and Radiological Physics Center project.

BACKGROUND AND PURPOSE Intensity-modulated radiotherapy (IMRT) credentialing for a EORTC study was performed using an anthropomorphic head phantom from the Radiological Physics Center (RPC; RPC(PH)). Institutions were retrospectively requested to irradiate their institutional phantom (INST(PH)) using the same treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT credentialing. MATERIALS AND METHODS CT data set of the institutional phantom and measured 2D dose matrices were requested from centers and sent to a dedicated secure EORTC uploader. Data from the RPC(PH) and INST(PH) were thereafter centrally analyzed and inter-compared by the QA team using commercially available software (RIT; ver.5.2; Colorado Springs, USA). RESULTS Eighteen institutions participated to the VPP. The measurements of 6 (33%) institutions could not be analyzed centrally. All other centers passed both the VPP and the RPC ±7%/4 mm credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing), 11(92%) as compared to 12 (100%) centers pass the credentialing process with RPC(PH) and INST(PH) (p = 0.29), respectively. The corresponding pass rate for the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p = 0.01), respectively. CONCLUSIONS IMRT dosimetry gamma evaluations in a single plane for a H&N prospective trial using the INST(PH) measurements showed agreement at the gamma index criteria of ±5%/5 mm (90% of pixels passing) for a small number of VPP measurements. Using more stringent, criteria, the RPC(PH) and INST(PH) comparison showed disagreement. More data is warranted and urgently required within the framework of prospective studies.

Economic analysis of soil conservation: Case studies from the highlands of Amhara Region, Ethiopia

Soil degradation is widespread in the Ethiopian Highlands. Its negative impacts on soil productivity contribute to the extreme poverty of the rural population. Soil conservation is propagated as a means of reducing soil erosion, however, it is a costly investment for small-scale farming households. The present study is an attempt to show whether or not selected mechanical Soil and Water Conservation (SWC) technologies are profitable from a farmer’s point of view. A financial Cost-Benefit Analysis (CBA) is carried out to assess whether or not the considered SWC technologies are profitable from a farmer’s point of view. The CBA is supplemented by an evaluation of aspects from the economic and institutional environment. Whether or not soil conservation is profitable from a farmer’s point of view depends on a broad range of factors from the ecological, economic, political, institutional and socio-cultural sphere and also depends on the technology and the prevailing farming system. Because these factors are closely interlinked, it is often not sufficient to change or influence one to make SWC profitable. Several recommendations are formulated with regard to improving the profitability of SWC investments from a farmer’s point of view. Because the reasons for unsustainable resource use are manifold and highly interlinked, only a multi-stakeholder, multi-level and multi-objective approach is likely to offer solutions that address the underlying problems adequately.

Diagnosing institutional barriers and opportunities for adaptation to climate change

Institutions are one of the decisive factors which enable, constrain and shape adaptation to the impacts of climate change, variability and extreme events. However, current understanding of institutions in adaptation situations is fragmented across the scientific community, evidence diverges, and cumulative learning beyond single studies is limited. This study adopts a diagnostic approach to elaborate a nuanced understanding of institutional barriers and opportunities in climate adaptation by means of a model-centred meta-analysis of 52 case studies of public climate adaptation in Europe. The first result is a novel taxonomy of institutional attributes in adaptation situations. It conceptually organises and decomposes the many details of institutions that empirical research has shown to shape climate adaptation. In the second step, the paper identifies archetypical patterns of institutional traps and trade-offs which hamper adaptation. Thirdly, corresponding opportunities are identified that enable actors to alleviate, prevent or overcome specific institutional traps or trade-offs. These results cast doubt on the validity of general institutional design principles for successful adaptation. In contrast to generic principles, the identified opportunities provide leverage to match institutions to specific governance problems that are encountered in specific contexts. Taken together, the results may contribute to more coherence and integration of adaptation research that we need if we are to foster learning about the role of institutions in adaptation situations in a cumulative fashion.