An Economic Approach to Article 82

This report argues in favour of an economics-based approach to Article 82, in a way similar to the reform of Article 81 and merger control. In particular, we support an effects-based rather than a form-based approach to competition policy. Such an approach focuses on the presence of anti-competitive effects that harm consumers, and is based on the examination of each specific case, based on sound economics and grounded on facts

An Economic Approach to Article 82

This report argues in favour of an economics-based approach to Article 82, in a way similar to the reform of Article 81 and merger control. In particular, we support an effects-based rather than a form-based approach to competition policy. Such an approach focuses on the presence of anti-competitive effects that harm consumers, and is based on the examination of each specific case, based on sound economics and grounded on facts.competition policy; abuse of market power

Large spread in the representation of compound long-duration dry and hot spells over Europe in CMIP5

Long-duration, sub-seasonal dry spells in combination with high temperature extremes during summer have led to extreme impacts on society and ecosystems in the past. Such events are expected to become more frequent due to increasing temperatures as a result of anthropogenic climate change. However, there is little information on how long-duration dry and hot spells are represented in global climate models (GCMs). In this study, we evaluate 33 CMIP5 (coupled model intercomparison project 5) GCMs in their representation of long-duration dry spells and temperatures during dry spells. We define a dry spell as a consecutive number of days with a daily precipitation of less than 1 mm. CMIP5 models tend to underestimate the persistence of dry spells in northern Europe, while a large variability exists between model estimates in central and southern Europe, where models have contrasting biases. Throughout Europe, we also find a large spread between models in their representation of temperature extremes during dry spells. In central and southern Europe this spread in temperature extremes between models is related to the representation of dry spells, where models that produce longer dry spells also produce higher temperatures, and vice versa. Our results indicate that this variability in model estimates is due to model differences and not internal variability. At latitudes between 50–60∘ N, the differences in the representation of persistent dry spells are strongly related to the representation of persistent anticyclonic systems, such as atmospheric blocking and subtropical ridges. Furthermore, models simulating a higher frequency of anticyclonic systems than ERA5 also simulate temperatures in dry spells that are between 1.4, and 2.8 K warmer than models with a lower frequency in these areas. Overall, there is a large spread between CMIP5 models in their representation of long-duration dry and hot events that is due to errors in the representation of large-scale anticyclonic systems in certain parts of Europe. This information is important to consider when interpreting the plausibility of future projections from climate models and highlights the potential value that improvements in the representation of anticyclonic systems may have for the simulation of impactful hazards.</p

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

Distribution and Characteristics of Colonic Diverticula in a United States Screening Population

Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population

A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents

Kupffer Cells and Blood Monocytes Orchestrate the Clearance of Iron-Carbohydrate Nanoparticles from Serum.

Intravenous (IV) iron nanoparticle preparations are widely used to treat iron deficiency. The mechanism of mononuclear phagocyte system-mediated clearance of IV iron nanoparticles is unknown. The early uptake and homeostasis of iron after injection of ferric carboxymaltose (FCM) in mice was studied. An increase in serum iron was observed at 2.5 h followed by a return to baseline by 24 h. An increase in circulating monocytes was observed, particularly Ly6Chi and Ly6Clow. FCM was also associated with a time-dependent decrease in liver Kupffer cells (KCs) and increase in liver monocytes. The increase in liver monocytes suggests an influx of iron-rich blood monocytes, while some KCs underwent apoptosis. Adoptive transfer experiments demonstrated that following liver infiltration, blood monocytes differentiated to KCs. KCs were also critical for IV iron uptake and biodegradation. Indeed, anti-Colony Stimulating Factor 1 Receptor (CSF1R)-mediated depletion of KCs resulted in elevated serum iron levels and impaired iron uptake by the liver. Gene expression profiling indicated that C-C chemokine receptor type 5 (CCR5) might be involved in monocyte recruitment to the liver, confirmed by pharmaceutical inhibition of CCR5. Liver KCs play a pivotal role in the clearance and storage of IV iron and KCs appear to be supported by the expanded blood monocyte population