The EU's current problems are largely of its own making

European integration used to be a jewel in the liberal crown. Integration was not only seen as a quintessential liberal project, but also as a tool for spreading liberal values in Europe and beyond. How can we explain the dramatic decline in support for the Union? In an extract from his new book, Counter-Revolution, Jan Zielonka (University of Oxford) explores some of the reasons why disillusionment set in

L’Unione europea può essere democratica?

It is well known that Ralf Dahrendorf raised concerns about the functioning of the European Union as a democratic institution. In his opinion, the most authentic and exclusive roots of the democratic experience can be found only within the nation-state. This historical, cultural and institutional aspect cannot be easily reproduced outside the context of the State. In Dahrendorf’s opinion it was essential that the EU Member States be democratic but to give a democratic character to Europe it was not necessary to transform the EU into a sort of Moloch State. This essay addresses the dilemma about European democracy highlighted by Dahrendorf, investigates why and how the EU has tried to build its democratic political system and the causes of the failure of this process. It examines the nature of democracy in a European continent with very wide borders and reflects on the various political crises that threaten its integration. In particular, it highlights the inadequacy of national democracies in managing transnational economies and policies and the possible effects of the populist conjuncture. The participation of citizens and political representation in its various forms of territorial expression remain the basis of a project of innovation in democratic practice that must not leave room for harmful alternatives

Giant hiatal hernias

Dyspnoea is most often caused by disorders of the respiratory and/or cardiovascular systems. Much less often it is brought aboutby the displacement of abdominal organs into the thoracic cage. Hiatal hernias may give rise to diagnostic difficulties, as bothclinical and radiological symptoms suggest different disorders. Computed tomography is the method of choice when makinga diagnosis.We have presented a series of 7 cases of giant hiatal hernias, each with a varying course of the disease, clinical symptoms,radiological features and prognoses.In two of the cases, the hernias were of a post-traumatic nature. Four cases of large diaphragmatic hernias were found in elderlypatients (over 90 years old). An advanced age and numerous coexisting chronic diseases disqualified most of the patients fromsurgical treatment despite the hernias’ large sizes. In only one case was fundoplication performed with a good end result. Twopatients died, and an extensive hernia was the cause of one of the deaths. Upper gastrointestinal symptoms were present onlyin a few of the patients.An early diagnosis of giant hiatal hernia is crucial for the patients to undergo prompt corrective surgeries

Angiogenic Activity of Sera from Pulmonary Tuberculosis Patients in Relation to IL-12p40 and TNFα Serum Levels

The role of angiogenesis in the pathogenesis of tuberculosis (TB) is not clear. The aim of this study was to examine the effect of sera from TB patients on angiogenesis induced by different subsets of normal human mononuclear cells (MNC) in relation to IL-12p40 and TNFα serum levels. Serum samples from 36 pulmonary TB patients and from 22 healthy volunteers were evaluated. To assess angiogenic reaction the leukocytes-induced angiogenesis test according to Sidky and Auerbach was performed. IL-12p40 and TNFα serum levels were evaluated by ELISA. Sera from TB patients significantly stimulated angiogenic activity of MNC compared to sera from healthy donors and PBS (p < 0.001). The number of microvessels formed after injection of lymphocytes preincubated with sera from TB patients was significantly lower compared to the number of microvessels created after injection of MNC preincubated with the same sera (p < 0.016). However, the number of microvessels created after the injection of lymphocytes preincubated with sera from healthy donors or with PBS alone was significantly higher (p < 0.017). The mean levels of IL-12p40 and TNFα were significantly elevated in sera from TB patients compared to healthy donors. We observed a correlation between angiogenic activity of sera from TB patients and IL-12p40 and TNFα serum levels (p < 0.01). Sera from TB patients constitute a source of mediators that participate in angiogenesis and prime monocytes for production of proangiogenic factors. The main proangiogenic effect of TB patients’ sera is mediated by macrophages/monocytes. TNFα and IL-12p40 may indirectly stimulate angiogenesis in TB

Semantic Labelling and Learning for Parity Game Solving in LTL Synthesis

We propose "semantic labelling" as a novel ingredient for solving games in the context of LTL synthesis. It exploits recent advances in the automata-based approach, yielding more information for each state of the generated parity game than the game graph can capture. We utilize this extra information to improve standard approaches as follows. (i) Compared to strategy improvement (SI) with random initial strategy, a more informed initialization often yields a winning strategy directly without any computation. (ii) This initialization makes SI also yield smaller solutions. (iii) While Q-learning on the game graph turns out not too efficient, Q-learning with the semantic information becomes competitive to SI. Since already the simplest heuristics achieve significant improvements the experimental results demonstrate the utility of semantic labelling. This extra information opens the door to more advanced learning approaches both for initialization and improvement of strategies

Antimycobacterial antibody level in pleural, pericardial and cerebrospinal fluid of patients with tuberculosis

The goal of the study was to evaluate IgG, IgA and IgM mediated humoral immune response against 38kDa and 16 kDa or 38kDa and LAM mycobacterial antigens in pleural, pericardial or cerebrospinal fluidfrompatients with tuberculosis (TB) and to compare to non-tuberculous controls (NTB). 30 cerebrospinal fluids(CSF)(16 TB pts and 14 NTB pts),17 pericardial fluids(6 TB and 11 NTB)and 20 pleural fluids(7 TB and 13 NTB) were examined. Commercially available ELISA-based as says (Pathozyme Tb complex plus, Myco G, A and M - Omega Diagnostic) were used. Tests were performed and cut off established according to manufacturer instruction. Mean IgG level against 38 + 16kDa was significantly higher in neurotuberculosis group compared to control (p < 0.05). Sensitivity of the test in detecting neurotuberculosis was of 42% and specificity of 96%. Mean IgG, IgA and IgM against 38kDa + LAM level was higher in TB group compared to NTB in CSF. No difference was observed between TB and NTB group in pleural effusion. Antimycobacterial antibody levels were non-significantly increased in pericardial fluid in TB. The findings of the study indicate that TB is associatedwiththe presence of detectable levels of antibodies in the CSF and pericardial effusion. Anti 38kDa + 16kDa IgG test can be used in combination with other diagnostic methods to increase diagnostic accuracy of neurotuberculosis

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation