Danube University Krems

About: Danube University Krems is a education organization based out in Krems, Niederösterreich, Austria. It is known for research contribution in the topics: Stroke & Population. The organization has 498 authors who have published 1572 publications receiving 68797 citations.

Characterization of Adsorbents for Cytokine Removal from Blood in an In Vitro Model

Abstract: Introduction. Cytokines are basic targets that have to be removed effectively in order to improve the patient's health status in treating severe inflammation, sepsis, and septic shock. Although there are different adsorbents commercially available, the success of their clinical use is limited. Here, we tested different adsorbents for their effective removal of cytokines from plasma and the resulting effect on endothelial cell activation. Methods. The three polystyrene divinylbenzene (PS-DVB) based adsorbents Amberchrom CG161c and CG300m and a clinically approved haemoperfusion adsorbent (HAC) were studied with regard to cytokine removal in human blood. To induce cytokine release from leucocytes, human blood cells were stimulated with 1 ng/ml LPS for 4 hours. Plasma was separated and adsorption experiments in a dynamic model were performed. The effect of cytokine removal on endothelial cell activation was evaluated using a HUVEC-based cell culture model. The beneficial outcome was assessed by measuring ICAM-1, E-selectin, and secreted cytokines IL-8 and IL-6. Additionally the threshold concentration for HUVEC activation by TNF-α and IL-1β was determined using this cell culture model. Results. CG161c showed promising results in removing the investigated cytokines. Due to its pore size the adsorbent efficiently removed the key factor TNF-α, outperforming the commercially available adsorbents. The CG161c treatment reduced cytokine secretion and expression of cell adhesion molecules by HUVEC which underlines the importance of effective removal of TNF-α in inflammatory diseases. Conclusion. These results confirm the hypothesis that cytokine removal from the blood should approach physiological levels in order to reduce endothelial cell activation.

Past, present and future of hay-making structures in Europe

Abstract: Hay-making structures are part of the agricultural landscape of meadows and pastures. Hay meadows are still used and found all over Europe, but their distribution patterns as well as their characteristics and regional features depend on geographical area, climate, culture, and intensity of agriculture. Intensively used hay meadows are the most dominant, using heavy machinery to store hay mostly as rounded or square bales. Traditional hay-making structures represent structures or constructions, used to quickly dry freshly cut fodder and to protect it from humidity. The ‘ancient’ forms of traditional hay-making structures are becoming a relic, due to mechanisation and the use of new technologies. Both the need for drying hay and the traditional methods for doing so were similar across Europe. Our study of hay-making structures focuses on their current state, their development and history, current use and cultural values in various European countries. Regarding the construction and use of hay-making structures, we have distinguished three different types, which correlate to natural and regional conditions: (1) temporary hay racks of various shapes; (2) hay barracks, a special type of shelters for storing hay and (3) different types of permanent construction and buildings for drying and storing hay. Hay-making structures have been mostly preserved in connection with traditional agricultural landscapes, and particularly in the more remote regions or where associated with strong cultural identity.

Measuring the Cognitive Complexity in the Comprehension of Modular Process Models

Abstract: Modularization in process models is a method to cope with the inherent complexity in such models (e.g., model size reduction). Modularization is capable to increase the quality, the ease of reuse, and the scalability of process models. Prior conducted research studied the effects of modular process models to enhance their comprehension. However, the effects of modularization on cognitive factors during process model comprehension are less understood so far. Therefore, this paper presents the results of two exploratory studies (i.e., a survey research study with N = 95 participants; a follow-up eye tracking study with N = 19 participants), in which three types of modularization (i.e., horizontal, vertical, orthogonal) were applied to process models expressed in terms of the Business Process Model and Notation (BPMN) 2.0. Further, the effects of modularization on the cognitive load, the level of acceptability, and the performance in process model comprehension were investigated. In general, the results revealed that participants were confronted with challenges during the comprehension of modularized process models. Further, performance in the comprehension of modularized process models showed only a few significant differences, however, the results obtained regarding the cognitive load revealed that the complexity and concept of modularization in process models were misjudged initially. The insights unraveled that the attitude towards the application and the behavioral intention to apply modularization in process model is still not clear. In this context, horizontal modularization appeared to be the best comprehensible modularization approach leading to a more fine-grained comprehension of respective process models. The findings indicate that alterations in modular process models (e.g., change in the representation) are important to foster and enable their comprehension. Finally, based on our results, implications for research and practice as well as directions for future work are discussed in this paper.

Pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum‐containing chemotherapy. A Cochrane Rapid Review

Abstract: Background The use of systemic immunotherapy targets is emerging as an important treatment option for metastatic urothelial carcinoma, particularly for patients who cannot tolerate or who fail cisplatin-based chemotherapy. One such target is the inhibition of the checkpoint protein programmed cell death-1 (PD-1) receptor and its ligand (PD-L1) by monoclonal antibodies. Objectives To assess the effects of pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. Search methods We performed a Cochrane Rapid Review, limiting our search to published studies in the English language. We searched databases of the medical literature, including the Cochrane Central Register of Controlled Trials and MEDLINE, as well as trial registries including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Our search extended from January 2000 to June 2018. Selection criteria We included randomised controlled trials except cross-over trials and cluster randomised trials. We excluded all other study designs. Participants included had locally advanced or metastatic urothelial carcinoma of the bladder, with disease progression during or following platinum-containing chemotherapy (synonymous with second-/third-/fourth-line therapy). This review focused on pembrolizumab (synonyms: MK-3475, lambrolizumab, Keytruda). Data collection and analysis Two review authors independently classified and abstracted data from the included study. The certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We identified one randomised controlled trial that included 542 participants, which compared the use of pembrolizumab monotherapy versus chemotherapy for the treatment of advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy. Results were reported after a median follow-up of 14.1 months (range 9.9 to 22.1 months).Primary outcomesPembrolizumab probably reduces the risk of death from any cause (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59 to 0.90; moderate certainty evidence). This corresponds to 115 fewer deaths (191 fewer to 38 fewer) per 1000 participants with pembrolizumab at 12 months. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may slightly improve quality of life (change from baseline to week 15 assessed with the Core Quality of Life Questionnaire; higher value reflects better quality of life; scale 0 to 100) with a mean difference (MD) of 9.05, 95% CI 4.61 to 13.50; low certainty evidence). We downgraded the certainty of evidence two levels for study limitations and imprecision.Secondary outcomesPembrolizumab may have little or no effect on disease progression (HR 0.98, 95% CI 0.81 to 1.19; low certainty evidence). This corresponds to three fewer patients (42 fewer to 24 more) whose disease progressed per 1000 participants at 12 months. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab probably improves treatment response (based on complete or partial radiologic response) with a risk ratio (RR) of 1.85, 95% CI 1.24 to 2.77; moderate certainty evidence). This corresponds to 97 more respondents (27 more to 202 more) per 1000 participants with pembrolizumab. We downgraded the certainty of evidence one level for imprecision.Pembrolizumab may have little or no effect on treatment-related mortality (RR 0.96, 95% CI 0.24 to 3.79; low certainty evidence). This corresponds to one fewer (12 fewer to 44 more) treatment-related deaths per 1000 participants with pembrolizumab. We downgraded the certainty of evidence two levels for study limitations and imprecision.Pembrolizumab may have little or no effect on discontinuations due to adverse events (RR 0.66, 95% CI 0.39 to 1.10). This corresponds to 54 fewer discontinuations per 1000 participants (95% CI 79 fewer to 7 more). We downgraded the certainty of evidence for study limitations and imprecision.Pembrolizumab may reduce serious adverse events (RR 0.83, 95 CI 0.72 to 0.97; low certainty evidence). This corresponds to 107 fewer serious averse events per 1000 participants (95% CI 19 fewer to 176 fewer). We downgraded two levels for study limitations and imprecision. Authors' conclusions The use of pembrolizumab in men with advanced urothelial carcinoma with disease progression during or following platinum-containing chemotherapy probably improves overall survival when compared with chemotherapy alone. At 12 months follow-up about 70% of those in the chemotherapy group had died, compared with 59% of those treated with pembrolizumab. We are very uncertain about the effects of pembolizumab on quality of life. Pembolizumab may also improve treatment response rates, and reduce the risk of serious adverse events, but may make little or no difference to discontinuations of treatment due to adverse events. These conclusions are based on a single trial that was sponsored by the producer of pembrolizumab.