Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S-transferase in chronic alcoholic pancreatitis

Chronic alcohol consumption is a major risk factor for the development of chronic pancreatitis. However, chronic pancreatitis occurs only in a minority of heavy drinkers. This variability may be due to yet unidentified genetic factors. Several enzymes involved in the degradation of reactive oxidants and xenobiotics, such as glutathione-S-transferase P1 (GSTP1) and manganese-superoxide dismutase (MnSOD) reveal functional polymorphisms that affect the antioxidative capacity and may therefore modulate the development of chronic pancreatitis and long-term complications like endocrine and exocrine pancreatic insufficiency. Two functional polymorphisms of the MnSOD and the GSTP1 gene were assessed by polymerase chain reaction and restriction fragment length polymorphism in 165 patients with chronic alcoholic pancreatitis, 140 alcoholics without evidence of pancreatic disease and 160 healthy control subjects. The distribution of GSTP1 and MnSOD genotypes were in Hardy-Weinberg equilibrium in the total cohort. Genotype and allele frequencies for both genes were not statistically different between the three groups. Although genotype MnSOD Ala/Val was seemingly associated with the presence of exocrine pancreatic insufficiency, this subgroup was too small and the association statistically underpowered. None of the tested genotypes affected the development of endocrine pancreatic insufficiency. Polymorphisms of MnSOD and GSTP1 are not associated with chronic alcoholic pancreatitis. The present data emphasize the need for stringently designed candidate gene association studies with well-characterized cases and controls and sufficient statistical power to exclude chance observation

DNS of vertical plane channel flow with finite-size particles: Voronoi analysis, acceleration statistics and particle-conditioned averaging

We have performed a direct numerical simulation of dilute turbulent particulate flow in a vertical plane channel, fully resolving the phase interfaces. The flow conditions are the same as those in the main case of "Uhlmann, M., Phys. Fluids, vol. 20, 2008, 053305", with the exception of the computational domain length which has been doubled in the present study. The statistics of flow and particle motion are not significantly altered by the elongation of the domain. The large-scale columnar-like structures which had previously been identified do persist and they are still only marginally decorrelated in the prolonged domain. Voronoi analysis of the spatial particle distribution shows that the state of the dispersed phase can be characterized as slightly more ordered than random tending towards a homogeneous spatial distribution. It is also found that the p.d.f.'s of Lagrangian particle accelerations for wall-normal and spanwise directions follow a lognormal distribution as observed in previous experiments of homogeneous flows. The streamwise component deviates from this law presenting significant skewness. Finally, a statistical analysis of the flow in the near field around the particles reveals that particle wakes present two regions, a near wake where the velocity deficit decays as 1/x and a far wake with a decay of approximately 1/(x*x).Comment: accepted for publication in Int. J. Multiphase Flo

Responsibility and Economics

Empirically, responsibility is a concept increasingly made use of in order to address societal issues. At the same time, it is a concept mainstream economics has, so far, hardly touched on. The paper shows that the application of economic reasoning to the responsibility concept can instruct a twofold learning process: First, the very tradition of economics allows to better understand and elaborate the semantics of responsibility. Here, the paper develops the concept of ordo-responsibility that differentiates between the initial basic game and the related meta-games. The focus thus shifts to the rule- setting processes and rule-finding discourses for which the actors can accept governance responsibility and discourse responsibility, respectively. Second, the rational-choice analysis of the responsibility concept also produces important insights for mainstream economic theory. Building on a simple model that delineates the responsibility aptitude of an actor, the paper explains why standard economics tends to attribute the rule-setting function exclusively to state actors. Yet, as the underlying nation-state paradigm depends on social determinants that are not universally given, such economic theory shows a double blind spot. Against this backdrop, the paper sketches out how to broaden the conventional perspective and identifies policy recommendations for state actors and business corporations

The Economic Ethics of Social Dilemmas

Economic ethics is a research program that employs instruments of economic analysis in order to reflect upon problems of morality, e.g. the legitimization of market and state in shaping individual conduct. From the perspective of economic ethics, this paper examines the concept of social dilemmas and its significance for understanding – and improving – the institutional structures of modern society. A social dilemma is a situation, in which all actors behave according to their individual interests but the outcome is Pareto-inferior. The archetype of a social dilemma is the prisoners' dilemma that has become famous as a centerpiece of game theory. However, while game theory looks at optimal strategies for individual players in the interaction with others, economic ethics analyzes the institutional conditions of the interaction from a social perspective. It employs the concept of social dilemmas as a heuristics to identify changes in the rules of the game that improve the overall outcome. In light of this approach, economic ethics is concerned with transforming the outcome of strategy combinations rather than trying to modify individual strategies. This can either imply establishing a social dilemma or overcoming it, depending on the effect of cooperation on a third party. This approach involves changing the payoffs for actors by introducing rewards or penalties through either external authority or through actors' selfcommitment. The optimal choice of method depends on the type of situation, the existence of an effective authority and the available incentives. Thus, understanding the economic logic of social dilemmas is vital for assessing the legitimacy of institutional arrangements

Radiochemotherapy with or without cetuximab for unresectable esophageal cancer: final results of a randomized phase 2 trial (LEOPARD-2)

Abstract Purpose To investigate the efficacy and toxicity of cetuximab when added to radiochemotherapy for unresectable esophageal cancer. Methods This randomized phase 2 trial (clinicaltrials.gov, identifier NCT01787006) compared radiochemotherapy plus cetuximab (arm A) to radiochemotherapy (arm B) for unresectable esophageal cancer. Primary objective was 2‑year overall survival (OS). Arm A was considered insufficiently active if 2‑year OS was ≤40% (null hypothesis = H0), and promising if the lower limit of the 95% confidence interval was >45%. If that lower limit was >40%, H0 was rejected. Secondary objectives included progression-free survival (PFS), locoregional control (LC), metastases-free survival (MFS), response, and toxicity. The study was terminated early after 74 patients; 68 patients were evaluable. Results Two-year OS was 71% in arm A (95% CI: 55–87%) vs. 53% in arm B (95% CI: 36–71%); H0 was rejected. Median OS was 49.1 vs. 24.1 months (p = 0.147). Hazard ratio (HR) for death was 0.60 (95% CI: 0.30–1.21). At 2 years, PFS was 56% vs. 44%, LC 84% vs. 72%, and MFS 74% vs. 54%. HRs were 0.51 (0.25–1.04) for progression, 0.43 (0.13–1.40) for locoregional failure, and 0.43 (0.17–1.05) for distant metastasis. Overall response was 81% vs. 69% (p = 0.262). Twenty-six and 27 patients, respectively, experienced at least one toxicity grade ≥3 (p = 0.573). A significant difference was found for grade ≥3 allergic reactions (12.5% vs. 0%, p = 0.044). Conclusion Given the limitations of this trial, radiochemotherapy plus cetuximab was feasible. There was a trend towards improved PFS and MFS. Larger studies are required to better define the role of cetuximab for unresectable esophageal cancer