Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19

Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19

Navigating the garden of forking paths for data exclusions in fear conditioning research

In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradimgs with a learning element. We illustrate this empirically through case examples from human fear conditioning research where the exclusion of ‘non-learners’ and ‘non-responders’ is common-despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria based on a systematic literature search and highlight potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. Based on this, we propose a consensus on evidence-based rather than idiosyncratic criteria including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element

Higher borides and oxygen-enriched Mg-B-O inclusions as possible pinning centers in nanostructural magnesium diboride and the influence of additives on their formation

The study of high pressure (2 GPa) synthesized MgB2-based materials allows us to conclude that higher borides (with near MgB12 stoichiometry) and oxygen-enriched Mg-B-O inclusions can be pinning centers in nanostructural magnesium diboride matrix (with average grain sizes of 15-37 nm). It has been established that additions of Ti or SiC as well as manufacturing temperature can affect the size, amount and distribution of these inclusions in the material structure and thus, influence critical current density. The superconducting behavior of materials with near MgB12 stoichiometry of matrix is discussed.Comment: 4 pages, 1 figues, presented at VORTEX VI-2009, accepted for Physica

CCPs and network stability in OTC derivatives markets

Among the reforms to OTC derivative markets since the global financial crisis is a commitment to collateralize counterparty exposures and to clear standardized contracts via central counterparties (CCPs). The reforms aim to reduce interconnectedness and improve counterparty risk management in these important markets. At the same time, however, the reforms necessarily concentrate risk in one or a few nodes in the financial network and also increase institutions’ demand for high-quality assets to meet collateral requirements. This paper looks more closely at the implications of increased CCP clearing for both the topology and stability of the financial network. Building on Heath et al. (2013) and Markose (2012), the analysis supports the view that the concentration of risk in CCPs could generate instability if not appropriately managed. Nevertheless, maintaining CCP prefunded financial resources in accordance with international standards and dispersing any unfunded losses widely through the system can limit the potential for a CCP to transmit stress even in very extreme market conditions. The analysis uses the Bank for International Settlements Macroeconomic Assessment Group on Derivatives (MAGD) data set on the derivatives positions of the 41 largest bank participants in global OTC derivative markets in 2012

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Metacognitive modelling competencies in small groups

International audienceMetacognitive modelling competencies are an essential part of modelling competence. When working on a modelling problem in small groups, the metacognitive modelling competencies of an individual may be less important, but in particular those shared in the group are of major importance. In this paper, results of a pilot study are presented which clearly indicate that measuring metacognitive group competencies is challenging. Furthermore, it is shown that the measurement of metacognitive competencies of individuals is not sufficient to get insight in the students' metacognitive behavior