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Viruses, as obligate intracellular parasites, exploit cellular pathways and resources in a variety of fascinating ways. A striking example of this is the remodelling of intracellular membranes into specialized structures that support the replication of positive-sense ssRNA (+RNA) viruses infecting eukaryotes. These distinct forms of virus-induced structures include double-membrane vesicles (DMVs), found during viral infections as diverse and notorious as those of coronaviruses, enteroviruses, noroviruses, or hepatitis C virus. Our understanding of these DMVs has evolved over the past 15 years thanks to advances in imaging techniques and modern molecular biology tools. In this article, we review contemporary understanding of the biogenesis, structure, and function of virus-induced DMVs as well as the open questions posed by these intriguing structures. Positive-sense RNA viruses utilize host membranes to generate viral replication organelles (ROs), inducing either invaginated spherules or double-membrane vesicles (DMVs) to support viral RNA synthesis. DMVs have emerged as a recurrent RO motif among important human pathogenic viruses. These include picornaviruses such as enteroviruses and poliovirus, hepatitis C virus, noroviruses, and coronaviruses such as Middle East respiratory syndrome (MERS)- and severe acute respiratory syndrome (SARS)-coronaviruses. Virus-induced DMVs appear to derive from membranes of the secretory pathway and form via several membrane remodelling steps coordinated by specific viral nonstructural proteins and host factors. Recent evidence demonstrates that DMVs are a central hub for the synthesis of viral RNA (vRNA), making them attractive targets for novel antiviral interventions. [ABSTRACT FROM AUTHOR]

• We study work-related advice networks among competitors in three high-tech clusters. • Specifically, we explore social mechanisms under perceived competitive conditions. • We analyze various network patterns of coopetition by taking a multi-level approach. • Managers actively seek out advice with direct competitors within clusters. • There are tendencies towards reciprocal advice-seeking among competitors. Collaboration with direct competitors is a valuable, yet risky, strategy that might pave the way for competitive advantages. Thus far, we have lacked a detailed understanding of how competitive relations between firms shape collaborative relations between their managers, and consequently the structural interdependencies at both levels. The primary objective of this study is to understand the multi-level structure underlying the ambiguous relationship of coopetition, a state of simultaneous collaboration and competition. Hence, we investigate the influence of perceived inter-firm competition on interpersonal knowledge flows among managers within three high-tech clusters by applying multi-level exponential random graph models to network data. Our results reveal that the interpersonal exchange of advice and information depends strongly on the inter-firm competitive structure and that competitive structures shape these interpersonal exchanges in different ways. Thereby, our research demonstrates that managers utilize asymmetries by means of perceived competitive relations to seek work-related advice and information from their competitors and that stronger forms of competition are significant, but not insuperable, obstacles to the exchange of knowledge. [ABSTRACT FROM AUTHOR]

Background and purpose: The National Cardiovascular Data Registry (NCDR) risk scores for mortality, bleeding and acute kidney injury (AKI) are accurate outcome predictors of coronary catheterization procedures in North American populations. However, their application in German clinical practice remained elusive and we thus aimed to verify their use. Methods: NCDR scores for mortality, bleeding and AKI and corresponding clinical outcomes were retrospectively assessed in patients undergoing catheterization for ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or for elective coronary procedures at a German Heart Center from 2014 to 2017. Risk model performance was assessed using receiver-operating-characteristic curves (discrimination) and graphical analysis/logistic regression (calibration). Results: A total of 1637 patients were included, procedures were performed for STEMI (565 patients, 34.5%), NSTEMI (572 patients, 34.9%) and elective purposes (500 patients, 30.5%); 6% (13% of STEMI and 5% of NSTEMI patients) presented in cardiogenic shock and 3% with resuscitated cardiac arrest. Radial access was used in 38% of procedures and cross-over was necessary in 5%; PCI was performed in 60% of procedures. In-hospital mortality was 6.3% (STEMI 14.5%; NSTEMI 3.7%; elective 0%) and major bleedings occurred in 5.6% (STEMI 10.6%; NSTEMI 5.4%; elective 0.2%); AKI was detected in 18.1% of patients (STEMI 23.7%; NSTEMI 27.3%; elective 1.4%), amounting to KDIGO stage I/II/III in 11.5%/3.5%/3.2%. NCDR risk models discriminated very well for mortality [AUC 0.93 with 95% confidence interval (CI) 0.91–0.95] and well for major bleeding (AUC 0.82, CI 0.78–0.86) and any AKI (AUC 0.83, CI 0.81–0.86). Discrimination in the subgroup of patients with PCI was comparable (mortality: AUC 0.90; major bleeding: AUC 0.78; any AKI: AUC 0.79). However, calibration showed considerable underestimation of mortality and AKI in high-risk patients, while major bleeding was consistently overestimated (Hosmer–Lemeshow p < 0.02 for all outcomes). Conclusions: The NCDR risk models showed excellent performance in discriminating high-risk from low-risk patients in contemporary German interventional cardiology. Model calibration for adverse event probability prediction, however, is limited and demands recalibration, especially in high-risk patients. [ABSTRACT FROM AUTHOR]