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In early October 2017, the International Atomic Energy Agency (IAEA) was informed by Member States that low concentrations of Ru-106 were measured inhigh-volume air samples in Europe from routine monitoring networks. However,no information was given that an accidental release of Ru-106 had taken place.Such events signify the need for prompt and accurate responses from nationalradiation protection authorities in such cases. This requires that methodologies,suited for operational use, are developed for spatial and temporal localization ofthe source of contamination based on available monitoring data.For operational use, nuclear decision-support systems (DSSs) should be extended with modules handling such monitoring data automatically, e.g. by employing the European Radiological Data Exchange Platform (EURDEP), andconveying selected data to the national meteorological centre accompanied by arequest to run an atmospheric dispersion model in inverse mode. The aim wouldbe to determine a geographical area in which to find the potential release pointas well as the release period.In the first year of SLIM (2019), the following results are obtained:• Two case studies are identified and selected, viz. the European Tracer Experiment (ETEX-1) and the October 2017 case of Ru-106 in Europe.• Methods for temporal and spatial source localization are developed, implemented and described.• Deterministic numerical weather prediction (NWP) model data are derivedfrom the European Centre for Medium-Range Weather Forecasts (ECMWF)corresponding to the selected cases.• Quality-controlled measurement data of ground-level concentration are obtained from filter stations.• The inverse methods for source localization are applied by using the DERMA,MATCH and SNAP atmospheric dispersion models to both cases.

Additional file 2: Figure S2. Correlations between heat-shock protein 90 (HSP90), age of the patients and calcification of the valves. A) HSP90 correlated with the age of the patients (y). Additionally, B) calcium area of the total valve area (%) correlated with the relative expression of HSP90 C) The age of the patients correlated with calcium area of the total valve area.

with substantial contributions from Iñaki Aldasoro, Silvia Gabrieli, Henrik Hansen,Alex Hodbod, Heinrich Kick, Falk Mazelis and Guillaume Vuillemey An epidemiologist calculating the risk of a localised epidemic becoming a global pandemic would investigate every possible channel of contagion from the infected region to the rest of the world. Focusing on, say, the incidence of close human contact would underestimate the pandemic risk if the disease could also spread through the air. Likewise, calculating the quantity of financial system risk requires practitioners to understand all of the channels through which small and local shocks can become big and global. Much of the empirical finance literature has focused only on “direct” contagion arising from firms’ contractual obligations. Direct contagion occurs if one firm’s default on its contractual obligations triggers distress (such as illiquidity or insolvency) at a counterparty firm. But contractual obligations are not the only means by which financial distress can spread, just as close human contact is not the only way that many infectious diseases are transmitted. Focusing only on direct contagion underestimates the risk of financial crisis given that other important channels exist. This paper represents an attempt to move systemic risk analysis closer to the holism of epidemiology. In doing so, we begin by identifying the fundamental channels of indirect contagion, which manifest even in the absence of direct contractual links. The first is the market price channel, in which scarce funding liquidity and low market liquidity reinforce each other, generating a vicious spiral. The second is information spillovers, in which bad news can adversely affect a broad range of financial firms and markets. Indirect contagion spreads market failure through these two channels. In the case of illiquidity spirals, firms do not internalise the negative externality of holding low levels of funding liquidity or of fire-selling assets into a thin market. Lack of information and information asymmetries can cause markets to unravel, even following a relatively small piece of bad news. In both cases, market players act in ways that are privately optimal but socially harmful. The spreading of market failure by indirect contagion motivates policy intervention. Substantial progress has been made in legislating for policies that will improve systemic resilience to indirect contagion. But more tools might be needed to achieve a fully effective and efficient macroprudential policy framework. This paper aims to frame a high-level policy discussion on three policy tools that could be effective and efficient in ensuring systemic resilience to indirect contagion – namely macroprudential liquidity regulation; restrictions on margins and haircuts; and information disclosure. The ADEMU Working Paper Series is being supported by the European Commission Horizon 2020 European Union funding for Research & Innovation, grant agreement No 649396.

Calcific aortic valve disease (CAVD) represents a spectrum of disease spanning from milder degrees of calcification of valve leaflets, i.e., aortic sclerosis, to severe calcification i.e., aortic stenosis (AS) with hemodynamic instability. The prevalence of CAVD is increasing rapidly due to the aging of the population, being up to 2.8% among patients over 75 years of age. Even without significant aortic valve stenosis, aortic sclerosis is associated with a 50% increased risk of myocardial infarction and death from cardiovascular causes. To date, there is no pharmacological treatment available to reverse or hinder the progression of CAVD. So far, the cholesterol-lowering therapies (statins) and renin-angiotensin system (RAS) blocking drugs have been the major pharmacological agents investigated for treatment of CAVD. Especially angiotensin receptor blockers (ARB)s and angiotensin convertase enzyme inhibitors (ACEI)s, have been under active investigation in clinical trials, but have proven to be unsuccessful in slowing the progression of CAVD. Several studies have suggested that other vasoactive hormones, including endothelin and apelin systems are also associated with development of AS. In the present review, we discuss the role of vasoactive factors in the pathogenesis of CAVD as novel pharmacological targets for the treatment of aortic valve calcification.

Failing to account for joint dynamics of credit and asset prices can be hazardous for countercyclical macroprudential policy. We show that composite financial cycles, emphasising expansions and contractions common to credit and asset prices, powerfully predict systemic banking crises. Further, the joint consideration yields a more robust view on financial cycle characteristics, reconciling an empirical puzzle concerning cycle properties when using two popular alternative methodologies: frequency decompositions and standard turning point analysis. Using a novel spectral approach, we establish the following facts for G-7 countries (1970Q1-2013Q4): Relative to business cycles, financial cycles differ in amplitude and persistence - albeit with heterogeneity across countries. Average financial cycle length is around 15 years, compared with 9 years (6.7 excluding Japan) for business cycles. Still, country-level business and financial cycles relate occasionally. Across countries, financial cycle synchronisation is strong for most countries; but not for all. In contrast, business cycles relate homogeneously.

This paper analyses whether the post-crisis regulatory reforms developed by globalstandard-setting bodies have created appropriate incentives for different types of market participants to centrally clear Over-The-Counter (OTC) derivative contracts. Beyond documenting the observed facts, we analyse four main drivers for the decision to clear: 1) the liquidity and riskiness of the reference entity; 2) the credit risk of the counterparty; 3) the clearing member's portfolio net exposure with the Central Counterparty Clearing House (CCP) and 4) post trade transparency. We use confidential European trade repository data on single-name Sovereign Credit Derivative Swap (CDS) transactions, and show that for all the transactions reported in 2016 on Italian, German and French Sovereign CDS 48% were centrally cleared, 42% were not cleared despite being eligible for central clearing, while 9% of the contracts were not clearable because they did not satisfy certain CCP clearing criteria. However, there is a large difference between CCP clearing members that clear about 53% of their transactions and non-clearing members, even those that are subject to counterparty risk capital requirements, that almost never clear their trades. Moreover, we find that diverse factors explain clearing members' decision to clear different CDS contracts: for Italian CDS, counterparty credit risk exposures matter most for the decision to clear, while for French and German CDS, margin costs are the most important factor for the decision. Moreover, clearing members use clearing to reduce their exposures to the CCP and largely clear contracts when at least one of the traders has a high counterparty credit risk.