Human long intrinsically disordered protein regions are frequent targets of positive selection

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher-order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here we address this question by investigating the evolutionary pattern of more than 6,600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a-priori knowledge of disordered protein regions and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs 4-fold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts

Joint system quantum descriptions arising from local quantumness

Bipartite correlations generated by non-signalling physical systems that admit a finite-dimensional local quantum description cannot exceed the quantum limits, i.e., they can always be interpreted as distant measurements of a bipartite quantum state. Here we consider the effect of dropping the assumption of finite dimensionality. Remarkably, we find that the same result holds provided that we relax the tensor structure of space-like separated measurements to mere commutativity. We argue why an extension of this result to tensor representations seems unlikely

Consensus guidelines for digital scholarship in academic promotion

Copyright: © 2020 Husain et al. This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) License. See: http://creativecommons.org/licenses/by/4.0/ Introduction: As scholarship moves into the digital sphere, applicant and promotion and tenure (P&T) committee members lack formal guidance on evaluating the impact of digital scholarly work. The P&T process requires the appraisal of individual scholarly impact in comparison to scholars across institutions and disciplines. As dissemination methods evolve in the digital era, we must adapt traditional P&T processes to include emerging forms of digital scholarship. Methods: We conducted a blended, expert consensus procedure using a nominal group process to create a consensus document at the Council of Emergency Medicine Residency Directors Academic Assembly on April 1, 2019. Results: We discussed consensus guidelines for evaluation and promotion of digital scholarship with the intent to develop specific, evidence-supported recommendations to P&T committees and applicants. These recommendations included the following: demonstrate scholarship criteria; provide external evidence of impact; and include digital peer-review roles. As traditional scholarship continues to evolve within the digital realm, academic medicine should adapt how that scholarship is evaluated. P&T committees in academic medicine are at the epicenter for supporting this changing paradigm in scholarship. Conclusion: P&T committees can critically appraise the quality and impact of digital scholarship using specific, validated tools. Applicants for appointment and promotion should highlight and prepare their digital scholarship to specifically address quality, impact, breadth, and relevance. It is our goal to provide specific, timely guidance for both stakeholders to recognize the value of digital scholarship in advancing our field. [West J Emerg Med. 2020;21(4)882-890.]

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell\u27s C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Funding: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

What are the mechanisms that support healthcare professionals to adopt assisted decision-making practice? A rapid realist review

Background The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) establishes a right to legal capacity for all people, including those with support needs. People with disabilities have a legal right to be given the appropriate supports to make informed decisions in all aspects of their lives, including health. In Ireland, the Assisted Decision-Making (Capacity) Act (2015) ratifies the Convention and has established a legal framework for Assisted Decision Making (ADM). The main provisions of the Act are not yet implemented. Codes of Practice to guide health and social care professionals are currently being developed. Internationally, concerns are expressed that ADM implementation is poorly understood. Using realist synthesis, this study aims to identify Programme Theory (PT) that will inform ADM implementation in healthcare. Methods A Rapid Realist Review using collaborative methods was chosen to appraise relevant literature and engage knowledge users from Irish health and social care. The review was led by an expert panel of relevant stakeholders that developed the research question which asks, ‘what mechanisms enable healthcare professionals to adopt ADM into practice?’ To ensure the PT was inclusive of local contextual influences, five reference panels were conducted with healthcare professionals, family carers and people with dementia. PT was refined and tested iteratively through knowledge synthesis informed by forty-seven primary studies, reference panel discussions and expert panel refinement and consensus. Results The review has developed an explanatory PT on ADM implementation in healthcare practice. The review identified four implementation domains as significant. These are Personalisation of Health & ADM Service Provision, Culture & Leadership, Environmental & Social Re-structuring and Education, Training & Enablement. Each domain is presented as an explanatory PT statement using realist convention that identifies context, mechanism and outcome configurations. Conclusions This realist review makes a unique contribution to this field. The PT can be applied by policymakers to inform intervention development and implementation strategy. It informs the imminent policy and practice developments in Ireland and has relevance for other worldwide healthcare systems dealing with similar legislative changes in line with UNCRPD

Climate vulnerability assessment for Pacific salmon and steelhead in the California Current Large Marine Ecosystem.

Major ecological realignments are already occurring in response to climate change. To be successful, conservation strategies now need to account for geographical patterns in traits sensitive to climate change, as well as climate threats to species-level diversity. As part of an effort to provide such information, we conducted a climate vulnerability assessment that included all anadromous Pacific salmon and steelhead (Oncorhynchus spp.) population units listed under the U.S. Endangered Species Act. Using an expert-based scoring system, we ranked 20 attributes for the 28 listed units and 5 additional units. Attributes captured biological sensitivity, or the strength of linkages between each listing unit and the present climate; climate exposure, or the magnitude of projected change in local environmental conditions; and adaptive capacity, or the ability to modify phenotypes to cope with new climatic conditions. Each listing unit was then assigned one of four vulnerability categories. Units ranked most vulnerable overall were Chinook (O. tshawytscha) in the California Central Valley, coho (O. kisutch) in California and southern Oregon, sockeye (O. nerka) in the Snake River Basin, and spring-run Chinook in the interior Columbia and Willamette River Basins. We identified units with similar vulnerability profiles using a hierarchical cluster analysis. Life history characteristics, especially freshwater and estuary residence times, interplayed with gradations in exposure from south to north and from coastal to interior regions to generate landscape-level patterns within each species. Nearly all listing units faced high exposures to projected increases in stream temperature, sea surface temperature, and ocean acidification, but other aspects of exposure peaked in particular regions. Anthropogenic factors, especially migration barriers, habitat degradation, and hatchery influence, have reduced the adaptive capacity of most steelhead and salmon populations. Enhancing adaptive capacity is essential to mitigate for the increasing threat of climate change. Collectively, these results provide a framework to support recovery planning that considers climate impacts on the majority of West Coast anadromous salmonids

A second Arid shower outburst in 2021

The predicted Arid meteor shower outburst on October 6-7, 2021, caused by Earth encountering the debris ejected by comet 15P/Finlay during its activity outbursts in 2014 and 2015, did materialize. The 2014 outburst dust was documented by CAMS low-light video networks in Chile. The observed activity was higher than that during the 1995-dust trail crossing, especially at small particle sizes, suggesting that the cometary activity had an influence on the density of the 2014 dust trail

Two approaches to testing general relativity in the strong-field regime

Observations of compact objects in the electromagnetic spectrum and the detection of gravitational waves from them can lead to quantitative tests of the theory of general relativity in the strong-field regime following two very different approaches. In the first approach, the general relativistic field equations are modified at a fundamental level and the magnitudes of the potential deviations are constrained by comparison with observations. In the second approach, the exterior spacetimes of compact objects are parametrized in a phenomenological way, the various parameters are measured observationally, and the results are finally compared against the general relativistic predictions. In this article, I discuss the current status of both approaches, focusing on the lessons learned from a large number of recent investigations.Comment: To appear in the proceedings of the conference New Developments in Gravit

A physical approach to Tsirelson's problem

Tsirelson's problem deals with how to model separate measurements in quantum mechanics. In addition to its theoretical importance, the resolution of Tsirelson's problem could have great consequences for device independent quantum key distribution and certified randomness. Unfortunately, understanding present literature on the subject requires a heavy mathematical background. In this paper, we introduce quansality, a new theoretical concept that allows to reinterpret Tsirelson's problem from a foundational point of view. Using quansality as a guide, we recover all known results on Tsirelson's problem in a clear and intuitive way.Comment: 11 pages, 2 figure