Human Validation of Genes Associated With a Murine Atherosclerotic Phenotype

ObjectiveThe genetically modified mouse is the most commonly used animal model for studying the pathogenesis of atherosclerotic disease. We aimed to assess if mice atherosclerosis-related genes could be validated in human disease through examination of results from genome-wide association studies. Approach and ResultsWe performed a systematic review to identify atherosclerosis-causing genes in mice and carried out gene-based association tests of their human orthologs for an association with human coronary artery disease and human large artery ischemic stroke. Moreover, we investigated the association of these genes with human atherosclerotic plaque characteristics. In addition, we assessed the presence of tissue-specific cis-acting expression quantitative trait loci for these genes in humans. Finally, using pathway analyses we show that the putative atherosclerosis-causing genes revealed few associations with human coronary artery disease, large artery ischemic stroke, or atherosclerotic plaque characteristics, despite the fact that the majority of these genes have cis-acting expression quantitative trait loci. ConclusionsA role for genes that has been observed in mice for atherosclerotic lesion development could scarcely be confirmed by studying associations of disease development with common human genetic variants. The value of murine atherosclerotic models for selection of therapeutic targets in human disease remains unclear

Differences in identification of patients' deterioration may hamper the success of clinical escalation protocols

\u3cp\u3eBACKGROUND: Timely and consistent recognition of a 'clinical crisis', a life threatening condition that demands immediate intervention, is essential to reduce 'failure to rescue' rates in general wards. AIM: To determine how different clinical caregivers define a 'clinical crisis' and how they respond to it. DESIGN: An international survey. METHODS: Clinicians working on general wards, intensive care units or emergency departments in the Netherlands, the United Kingdom and Denmark were asked to review ten scenarios based on common real-life cases. Then they were asked to grade the urgency and severity of the scenario, their degree of concern, their estimate for the risk for death and indicate their preferred action for escalation. The primary outcome was the scenarios with a National Early Warning Score (NEWS) ≥7 considered to be a 'clinical crisis'. Secondary outcomes included how often a rapid response system (RRS) was activated, and if this was influenced by the participant's professional role or experience. The data from all participants in all three countries was pooled for analysis. RESULTS: A total of 150 clinicians participated in the survey. The highest percentage of clinicians that considered one of the three scenarios with a NEWS ≥7 as a 'clinical crisis' was 52%, while a RRS was activated by <50% of participants. Professional roles and job experience only had a minor influence on the recognition of a 'clinical crisis' and how it should be responded to. CONCLUSION: This international survey indicates that clinicians differ on what they consider to be a 'clinical crisis' and on how it should be managed. Even in cases with a markedly abnormal physiology (i.e. NEWS ≥7) many clinicians do not consider immediate activation of a RRS is required.\u3c/p\u3

A Human(e) Factor in Clinical Decision Support Systems

The overwhelming amount, production speed, multidimensionality, and potential value of data currently available-often simplified and referred to as big data -exceed the limits of understanding of the human brain. At the same time, developments in data analytics and computational power provide the opportunity to obtain new insights and transfer data-provided added value to clinical practice in real time. What is the role of the health care professional in collaboration with the data scientist in the changing landscape of modern care? We discuss how health care professionals should provide expert knowledge in each of the stages of clinical decision support design: data level, algorithm level, and decision support level. Including various ethical considerations, we advocate for health care professionals to responsibly initiate and guide interprofessional teams, including patients, and embrace novel analytic technologies to translate big data into patient benefit driven by human(e) values

A Human(e) Factor in Clinical Decision Support Systems

The overwhelming amount, production speed, multidimensionality, and potential value of data currently available-often simplified and referred to as big data -exceed the limits of understanding of the human brain. At the same time, developments in data analytics and computational power provide the opportunity to obtain new insights and transfer data-provided added value to clinical practice in real time. What is the role of the health care professional in collaboration with the data scientist in the changing landscape of modern care? We discuss how health care professionals should provide expert knowledge in each of the stages of clinical decision support design: data level, algorithm level, and decision support level. Including various ethical considerations, we advocate for health care professionals to responsibly initiate and guide interprofessional teams, including patients, and embrace novel analytic technologies to translate big data into patient benefit driven by human(e) values

Climate change and invasion by intracontinental range-expanding exotic plants: the role of biotic interactions

In this Botanical Briefing we describe how the interactions between plants and their biotic environment can change during range-expansion within a continent and how this may influence plant invasiveness. We address how mechanisms explaining intercontinental plant invasions by exotics (such as release from enemies) may also apply to climate-warming-induced range-expanding exotics within the same continent. We focus on above-ground and below-ground interactions of plants, enemies and symbionts, on plant defences, and on nutrient cycling. Range-expansion by plants may result in above-ground and below-ground enemy release. This enemy release can be due to the higher dispersal capacity of plants than of natural enemies. Moreover, lower-latitudinal plants can have higher defence levels than plants from temperate regions, making them better defended against herbivory. In a world that contains fewer enemies, exotic plants will experience less selection pressure to maintain high levels of defensive secondary metabolites. Range-expanders potentially affect ecosystem processes, such as nutrient cycling. These features are quite comparable with what is known of intercontinental invasive exotic plants. However, intracontinental range-expanding plants will have ongoing gene-flow between the newly established populations and the populations in the native range. This is a major difference from intercontinental invasive exotic plants, which become more severely disconnected from their source populations