Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an "ex vivo" tacrolimus perfusion

Background: Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts. Methods/Design: The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients. Discussion: Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage. Trial register: EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT0156409

Therapeutic anticoagulation complications in the elderly: a case report

Background: The demographic transition leads to a continuously growing number of elderly patients who receive therapeutic anticoagulation by reason of several comorbidities. Though therapeutic anticoagulation may reduce the number of embolic complications in these patients, major complications such as bleeding complications need to be kept in mind when considering such therapy. However, evidence regarding the choice of anticoagulation agents in chronic kidney disease patients of higher age is limited. In this report, a guideline-based anticoagulation treatment which led to a fulminant atraumatic bleeding complication is discussed. Case presentation: We present the case of an 85-year-old female stage V chronic kidney disease patient who suffered from a diffuse arterial, subcutaneous bleeding in her lower left leg due a therapeutic anticoagulation using low molecular weight heparin (LMWH). Anticoagulation was started in accordance with general recommendations for patients with atrial fibrillation, and the dosage was adapted for the patient's renal function. Nevertheless, the above-mentioned complication occurred, and the bleeding led to a hemorrhagic shock and an acute kidney injury on top of a chronic kidney disease. The hematoma required surgical evacuation and local coagulation in the operating room. In the further course, the patient underwent additional four surgical interventions due to a superinfected skin necrosis, including skin grafting. Furthermore, the patient needed continuous renal replacement therapy, as well as intensive care unit treatment, for a total of 47 days followed by 36 days of geriatric rehabilitation. Afterwards, she was discharged from the hospital to her previous nursing home. Discussion and conclusions: Although therapeutic anticoagulation may sufficiently protect patients at cardiovascular risk, major complications such as bleeding complications may occur at any time. Therefore, physicians need to regularly re-evaluate any prior indication for therapeutic anticoagulation. With this case report, we hope to draw attention to the cohort of geriatric patients and the need for more and well differentiated study settings to preferably prevent any potentially avoidable complications

Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage. RESULTS: In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90) on the expression of cytochrome P450 1B1 (CYP1B1) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP) is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 muM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis. CONCLUSION: These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds

Optimal Renewable Energy Systems for Regions

Most sources for renewable energy can be deduced from solar radiation as the main natural income of society. Contrary to conventional fossil and radioactive energy resources that are mined or pumped out from central point sources, solar energy is a de-central resource that requires area for its conversion to useful products and services. This requires a new technological as well as logistical concept for energy systems where regions play a key role as providers of energy and goods. The contribution will provide the conceptual framework for renewable energy system generation on a regional level, taking into account the responsibility of regions to provide goods and services to the larger society and to support urban centres. It will show how optimal resource-technology-demand networks may be constructed, using process network synthesis approaches and how the ecological efficiency of such regional systems can be measured. Application of these methods to real life case studies (in particular the region of Mühlviertel in Austria) will on the one hand prove the versatility of the methods presented and on the other hand will provide insight into the scope of necessary change if society moves towards a low carbon sustainable energy system

A cosmopolitan temptation

For some, the transnationalization of political action and communicative space in the European Union heralds an emergent cosmopolitan order. Need that be so? There are supranational institutions in the EU as well as transnational political and cultural spaces and cross-border communicative flows. However, the Union's member states remain key controllers of citizenship rights and purveyors of collective identities. And for many purposes they still maintain strongly bounded national public spheres. Because the EU's overall character as a polity remains unresolved, this has consequences for the organization of communicative spaces. The EU is a field of tensions and contradictions that is inescapably rooted in institutional realities. Wishful thinking about cosmopolitanism can get in the way of clear analysis

Aerosol Jet Printing of Graphene and Carbon Nanotube Patterns on Realistically Rugged Substrates

Direct-write additive manufacturing of graphene and carbon nanotube (CNT) patterns by aerosol jet printing (AJP) is promising for the creation of thermal and electrical interconnects in (opto)electronics. In realistic application scenarios, this however often requires deposition of graphene and CNT patterns on rugged substrates such as, for example, roughly machined and surface oxidized metal block heat sinks. Most AJP of graphene/CNT patterns has thus far however concentrated on flat wafer-or foil type substrates. Here, we demonstrate AJP of graphene and single walled CNT (SWCNT) patterns on realistically rugged plasma electrolytic-oxidized (PEO) Al blocks, which are promising heat sink materials. We show that AJP on the rugged substrates offers line resolution of down to similar to 40 mu m width for single AJP passes, however, at the cost of noncomplete substrate coverage including noncovered mu m-sized pores in the PEO Al blocks. With multiple AJP passes, full coverage including coverage of the pores is, however, readily achieved. Comparing archetypical aqueous and organic graphene and SWCNT inks, we show that the choice of the ink system drastically influences the nanocarbon AJP parameter window, deposit microstructure including crystalline quality, compactness of deposit, and inter/intrapass layer adhesion for multiple passes. Simple electrical characterization indicates aqueous graphene inks as the most promising choice for AJP-deposited electrical interconnect applications. Our parameter space screening thereby forms a framework for rational process development for graphene and SWCNT AJP on application-relevant, rugged substrates

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

'Open Marxism' against and beyond the 'Great Enclosure'? Reflections on How (Not) to Crack Capitalism

The main purpose of this article is to provide an in-depth discussion of John Holloway’s recent book, Crack Capitalism. To this end, the paper offers a detailed account of the key strengths and weaknesses of Holloway’s version of ‘open Marxism’. The analysis is divided into two parts. The first part focuses on six significant strengths of Crack Capitalism: (1) its insistence upon the importance of autonomous forms of agenda-setting for both individual and collective emancipation; (2) its emphasis on the ordinary constitution of social struggles; (3) its fine-grained interpretation of the socio-ontological conditions underlying human agency; (4) its processual conception of radical social transformation; (5) its recognition of the elastic, adaptable, and integrative power of capitalism; and (6) its proposal for an alternative critical theory, commonly known as ‘open Marxism’ or ‘autonomous Marxism’. The second part of the study examines the principal weaknesses of Crack Capitalism: (1) the counterproductive implications of the preponderance of negativity, owing to a one-sided concern with critique, cracks, and crises; (2) conceptual vagueness; (3) an overuse of poetic and metaphorical language; (4) the absence of a serious engagement with the question of normativity; (5) a lack of substantive evidence; (6) a residual economic reductionism; (7) a simplistic notion of gender; (8) the continuing presence of various problematic ‘isms’; (9) the misleading distinction between ‘doing’ and ‘labour’; (10) a reductive understanding of capitalism; (11) an unrealistic view of society; and (12) socio-ontological idealis