Democratic Control in the Member States of the European Council and the Euro zone summits

This report on the "Democratic Control in the Member States of the European Council and the Euro zone summits" analyses the democratic control of the European Council in all 27 Member States, identifies seven different models of control and formulates twelve policy recommendations. It was written by a team of researchers at Notre Europe - Jacques Delors Institute and TEPSA at the request of the Directorate General for Internal Policies, Policy Department C: Citizens’ Rights and Constitutional Affairs of the European Parliament. Olivier Rozenberg, Associate Research Professor at Sciences Po Paris co-directed the report on behalf of Notre Europe - Jacques Delors Institute together with Wolfgang Wessels, Jean Monet Professor at the University of Cologne and Chairperson of TEPSA. Valentin Kreilinger, Research Fellow Politics and Institutions, is a co-author of the report, alongside Claudia Hefftler, Mirte Van Den Berge, Laura Ventura and the co-directors of the project. The European Council is increasingly central to the governance of the European Union. Even if national parliaments have originally focused their involvement in EU affairs on the ordinary legislative process, most of the chambers have started to develop specific activities, before or after European summits. From ex-ante influence to ex-post accountability, seven different models of control of parliamentary control have been identified across the 27 Member States. Beyond their differences rooted in national democratic systems, the authors of the report formulate twelve policy recommendations. One of the proposals is of special interest due to the ongoing debate on the parliamentary control over the coordination of budgetary and economic policies in the Eurozone and among the Contracting Parties of the Treaty on Stability, Coordination and Governance in the Economic and Monetary Union. On the basis of Article 13 TSCG, this report proposes to create an Inter-Parliamentary Conference for budgetary and economic issues and to model it according to the Inter-Parliamentary Conference for CFSP and CSDP

Determinants of quality of life in acute heart failure patients with and without comorbidities:a prospective, observational study

AIMS: The relation between non-cardiac comorbidities and health-related quality of life (HRQoL) in patients with heart failure (HF) has been studied to a limited extent. To investigate the HRQoL and their determinants among HF patients with and without comorbidities. METHODS AND RESULTS: TRIUMPH (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure) is a Dutch prospective, multicentre study enrolling 496 acute HF patients between 2009 and 2014. We included 334 patients who had completed the HRQoL questionnaires at baseline. The HRQoL was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) en EuroQuality-of-life five Dimensions (EQ-5D). Comorbidity was defined as having a history of at least one of the following comorbidities: chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and/or cerebrovascular accident. Patients with comorbidity (n = 205, 61%) had lower scores on the physical limitation scale and clinical summary score of the KCCQ (P = 0.03 and P = 0.01, respectively). Female sex, COPD, previous HF, increasing body mass index (BMI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), high systolic blood pressure, and the presence of anxiety and/or depression negatively influenced the HRQoL among HF patients with comorbidity. Besides anxiety and depression, we hardly found any other determinant of HRQoL in patients without comorbidity. CONCLUSION: Heart failure patients without comorbidity had better HRQoL than patients with comorbidity. Sex, previous HF, BMI, COPD, systolic blood pressure, NT-proBNP levels, and also anxiety and depression were determinants of HRQoL in patients with comorbidity. In those without comorbidity, apart from anxiety and depression, no further determinants of HRQoL were found

Risk factors for corticosteroid- and antibiotic only-treated asthma attacks in the NOVELTY cohort

Research funding source: This study was supported by AstraZeneca.Peer reviewedPostprin

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Asthma is a heterogeneous disease characterized by chronic inflammation and structural changes in the airways. The airway smooth muscle (ASM) is responsible for airway narrowing and an important source of inflammatory mediators. We and others have previously shown that WNT5A mRNA and protein expression is higher in the ASM of asthmatics compared to healthy controls. Here, we aimed to characterize the functional role of (smooth muscle-derived) WNT5A in asthma. We generated a tet-ON smooth-muscle-specific WNT5A transgenic mouse model, enabling in vivo characterization of smooth-muscle-derived WNT5A in response to ovalbumin. Smooth muscle specific WNT5A overexpression showed a clear trend towards enhanced actin (α-SMA) expression in the ASM in ovalbumin challenged animals, but had no effect on collagen content. WNT5A overexpression in ASM also significantly enhanced the production of the Th2-cytokines IL4 and IL5 in lung tissue after ovalbumin exposure. In line with this, WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. In addition, CD4+ T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. WNT5A promoted expression of 234 genes in human CD4+ T cells, among which the Th2 cytokine IL31 was among the top 5 upregulated genes. IL31 was also upregulated in response to smooth muscle-specific WNT5A overexpression in the mouse. In conclusion, smooth-muscle derived WNT5A augments Th2 type inflammation and remodelling. Our findings imply a pro-inflammatory role for smooth muscle-derived WNT5A in asthma, resulting in increased airway wall inflammation and remodelling

Genetic regulation of gene expression of MIF family members in lung tissue

Macrophage migration inhibitory factor (MIF) is a cytokine found to be associated with chronic obstructive pulmonary disease (COPD). However, there is no consensus on how MIF levels differ in COPD compared to control conditions and there are no reports on MIF expression in lung tissue. Here we studied gene expression of members of the MIF family MIF, D-Dopachrome Tautomerase (DDT) and DDT-like (DDTL) in a lung tissue dataset with 1087 subjects and identified single nucleotide polymorphisms (SNPs) regulating their gene expression. We found higher MIF and DDT expression in COPD patients compared to non-COPD subjects and found 71 SNPs significantly influencing gene expression of MIF and DDTL. Furthermore, the platform used to measure MIF (microarray or RNAseq) was found to influence the splice variants detected and subsequently the direction of the SNP effects on MIF expression. Among the SNPs found to regulate MIF expression, the major LD block identified was linked to rs5844572, a SNP previously found to be associated with lower diffusion capacity in COPD. This suggests that MIF may be contributing to the pathogenesis of COPD, as SNPs that influence MIF expression are also associated with symptoms of COPD. Our study shows that MIF levels are affected not only by disease but also by genetic diversity (i.e. SNPs). Since none of our significant eSNPs for MIF or DDTL have been described in GWAS for COPD or lung function, MIF expression in COPD patients is more likely a consequence of disease-related factors rather than a cause of the disease

Smooth-muscle-derived WNT5A augments allergen-induced airway remodelling and Th2 type inflammation

Asthma is a heterogeneous disease characterized by chronic inflammation and structural changes in the airways. The airway smooth muscle (ASM) is responsible for airway narrowing and an important source of inflammatory mediators. We and others have previously shown that WNT5A mRNA and protein expression is higher in the ASM of asthmatics compared to healthy controls. Here, we aimed to characterize the functional role of (smooth muscle-derived) WNT5A in asthma. We generated a tet-ON smooth-muscle-specific WNT5A transgenic mouse model, enabling in vivo characterization of smooth-muscle-derived WNT5A in response to ovalbumin. Smooth muscle specific WNT5A overexpression showed a clear trend towards enhanced actin (α-SMA) expression in the ASM in ovalbumin challenged animals, but had no effect on collagen content. WNT5A overexpression in ASM also significantly enhanced the production of the Th2-cytokines IL4 and IL5 in lung tissue after ovalbumin exposure. In line with this, WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. In addition, CD4+ T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. WNT5A promoted expression of 234 genes in human CD4+ T cells, among which the Th2 cytokine IL31 was among the top 5 upregulated genes. IL31 was also upregulated in response to smooth muscle-specific WNT5A overexpression in the mouse. In conclusion, smooth-muscle derived WNT5A augments Th2 type inflammation and remodelling. Our findings imply a pro-inflammatory role for smooth muscle-derived WNT5A in asthma, resulting in increased airway wall inflammation and remodelling

Gene signatures from scRNA-seq accurately quantify mast cells in biopsies in asthma

Respiratory disease, characterized by changes in the cells of the lung, can affect molecular phenotype of cells and the intercellular interactions, resulting in a disbalance in the relative proportions of individual cell types. Understanding these changes is essential to understand the pathophysiology of lung disease. Conventional 'bulk' RNA-sequencing (RNA-seq), analyzing the entire transcriptome of the tissue sample, provides information about average expression levels of each gene in the mixed cell population; whereas it does not consider the cellular heterogeneity in samples composed of more than one cell type 1 . Single-cell RNA-seq (scRNA-seq) assesses the transcriptome of a complex biological sample with single-cell resolution, allowing identification of the relative frequency of discrete cell-types and analysis of their transcriptomes 1 . Nevertheless, analyzing the transcriptomic signature in large numbers of patients by scRNA-Seq is currently limited by its high costs. Mast cells are key regulatory cells driving the inflammatory process in asthma2 . Since they can be quantified by immunohistochemical staining for validation purposes, we used mast cells as an example of a rare cell population to assess the validity of our deconvolution approach. Recently, a number of bulk RNA-seq deconvolution methods have become available 3 , for instance of two deconvolution methods, namely support vector regression (SVR) 4 , the machine-learning method implemented in CYBERSORT, and Non-Negative Least Square (NNLS) 5 , using a matrix of cell-type selective genes identified with AutoGeneSc 6 . Both approaches are designed to estimate relative proportion of the main, common cell types present in the sample. When we used these methods to estimate the number of mast cells, we found a poor correlation with the number of mast cells stained by immunohistochemistry in the biopsies, suggesting the CIBERSORT and NNLS are less reliable in the case of rare cell types. We explored the possibility to use scRNA-Seq data from small numbers of subjects to specifically interrogate the relative cell type frequency of a rare cell population in a bulk RNA-Seq dataset obtained from a large asthma cohort

Long-term effects of best management practices on crop yield and nitrogen surplus

Inherent in the concept of good agricultural practice (BMP) is that it improves resource use efficiency, mitigates environmental impact or increases farm profitability. However, it is usually impossible to achieve all the objectives, and trade-offs need to be accepted, such as a reduction in productivity together with a reduction in costs or an increase of soil organic matter. A European FP7 project, Catch-C (http://www.catch-c.eu) analyses the effects that different management practices have on productivity, mitigation of climate change and chemical, physical and biological soil fertility, based on simple indicators. Such indicators were collected from international literature, national scientific or technical journals, or grey literature that dealt with long-term field trials in Europe. We collected and analysed data from more than 350 experiments. This paper presents the overall results of the effects of a series of BMP have on crop productivity, soil nitrogen (N) uptake, N use efficiency end N balance. Important interactions with soil and climate types, crop and duration of the experiment were noticed for most BMPs. Rotations, also including double cropping, were among practices with more positive effects of productivity and N indicators. A slight reduction of yield counteracted benefits to soil quality and to climate change mitigation of minimum and no tillage, and of organic fertilisers