Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery

Introduction: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors’ subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia.Methods and analysis: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1?year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30?days after surgery, and the secondary outcome is all-cause death within 1?year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration.Ethics and dissemination: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.<br/

recount3: summaries and queries for large-scale RNA-seq expression and splicing

We present recount3, a resource consisting of over 750,000 publicly available human and mouse RNA sequencing (RNA-seq) samples uniformly processed by our new Monorail analysis pipeline. To facilitate access to the data, we provide the recount3 and snapcount R/Bioconductor packages as well as complementary web resources. Using these tools, data can be downloaded as study-level summaries or queried for specific exon-exon junctions, genes, samples, or other features. Monorail can be used to process local and/or private data, allowing results to be directly compared to any study in recount3. Taken together, our tools help biologists maximize the utility of publicly available RNA-seq data, especially to improve their understanding of newly collected data. recount3 is available from http://rna.recount.bio

Transit Photometry as an Exoplanet Discovery Method

Photometry with the transit method has arguably been the most successful exoplanet discovery method to date. A short overview about the rise of that method to its present status is given. The method's strength is the rich set of parameters that can be obtained from transiting planets, in particular in combination with radial velocity observations; the basic principles of these parameters are given. The method has however also drawbacks, which are the low probability that transits appear in randomly oriented planet systems, and the presence of astrophysical phenomena that may mimic transits and give rise to false detection positives. In the second part we outline the main factors that determine the design of transit surveys, such as the size of the survey sample, the temporal coverage, the detection precision, the sample brightness and the methods to extract transit events from observed light curves. Lastly, an overview over past, current and future transit surveys is given. For these surveys we indicate their basic instrument configuration and their planet catch, including the ranges of planet sizes and stellar magnitudes that were encountered. Current and future transit detection experiments concentrate primarily on bright or special targets, and we expect that the transit method remains a principal driver of exoplanet science, through new discoveries to be made and through the development of new generations of instruments.Comment: Review chapte

Optimising the prescribing of drugs that may cause dependency: An evidence and gap map of systematic reviews.

This is the final version. Available from SAGE Publications via the DOI in this record. OBJECTIVES: We set out to map the quantitative and qualitative systematic review evidence available to inform the optimal prescribing of drugs that can cause dependency (benzodiazepines, opioids, non-benzodiazepine hypnotics, gabapentinoids and antidepressants). We also consider how this evidence can be used to inform decision-making in the patient care pathway for each type of medication. METHODS: Eight bibliographic databases were searched for the period 2010 to 2020. All included reviews were initially appraised using four items from the Collaboration for Environmental Evidence Synthesis Assessment Tool, with reviews that scored well on all items proceeding to full quality appraisal. Key characteristics of the reviews were tabulated, and each review was incorporated into an evidence and gap map based on a patient care pathway. The care pathway was based upon an amalgamation of existing NICE guidelines and feedback from clinical and patient stakeholders. RESULTS: We identified 80 relevant reviews and displayed them in an evidence and gap map. The evidence included in these reviews was predominantly of low overall quality. Areas where systematic reviews have been conducted include barriers and facilitators to the deprescribing of drugs that may cause dependency, although we identified little evidence exploring the experiences or evaluations of specific interventions to promote deprescribing. All medications of interest, apart from gabapentinoids, were included in at least one review. CONCLUSIONS: The evidence and gap map provides an interactive resource to support (i) policy developers and service commissioners to use evidence in the development and delivery of services for people receiving a prescription of drugs that may cause dependency, where withdrawal of medication may be appropriate, (ii) the clinical decision-making of prescribers and (iii) the commissioning of further research. The map can also be used to inform the commissioning of further systematic reviews. To address the concerns regarding the quality of the existing evidence based raised in this report, future reviews should be conducted according to best-practice guidelines. Systematic reviews focusing on evaluating interventions to promote deprescribing would be particularly beneficial, as would reviews focusing on addressing the paucity of evidence regarding the deprescription of gabapentinoids.National Institute for Health Research (NIHR

Consideration of health inequity in systematic reviews and primary studies on risk factors for hearing loss

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.Background: Health inequities are systematic, avoidable, and unfair differences in health between populations or population subgroups. There is increased recognition of the need for systematic reviews (SRs) to address health inequities, including drawing out findings relevant to low‐ and middle‐income countries (LMICs). The aim of this study was to determine the extent to which SRs on risk factors for hearing loss reported findings associated with health inequities, and the extent to which this data was captured in the primary studies included within these SRs. Methods: We identified SRs on risk factors for hearing loss from a report on this topic which included a systematic search for relevant SRs. SRs thus identified were inspected for data related to health inequity with reference to PROGRESS‐Plus. We compared how data were reported in SRs versus within primary studies included in the SRs, and the extent to which primary studies from LMICs were represented. Results: We included 17 SRs which reported findings on a variety of physiological, behavioral, demographic, and environmental risk factors for hearing loss. There were 296 unique primary studies included in the SRs, of which 251 (81.49%) were successfully retrieved. Data relating to health inequities was reported relatively infrequently in the SRs and mainly focused on gender and age. Data related to health inequities was more frequently reported in primary studies. However, several PROGRESS‐Plus criteria were only reported in a minority of primary studies. Approximately one‐third of primary studies were from LMICs. Conclusions: There is scope to improve the reporting of data relating to health inequities in primary studies on risk factors for hearing loss. However, SR authors could do more to report health inequities than is currently undertaken, including drawing out findings relevant to LMICs where data are available.National Institute for Health Research (NIHR

The Incremental Cooperative Design of Preventive Healthcare Networks

This document is the Accepted Manuscript version of the following article: Soheil Davari, 'The incremental cooperative design of preventive healthcare networks', Annals of Operations Research, first published online 27 June 2017. Under embargo. Embargo end date: 27 June 2018. The final publication is available at Springer via http://dx.doi.org/10.1007/s10479-017-2569-1.In the Preventive Healthcare Network Design Problem (PHNDP), one seeks to locate facilities in a way that the uptake of services is maximised given certain constraints such as congestion considerations. We introduce the incremental and cooperative version of the problem, IC-PHNDP for short, in which facilities are added incrementally to the network (one at a time), contributing to the service levels. We first develop a general non-linear model of this problem and then present a method to make it linear. As the problem is of a combinatorial nature, an efficient Variable Neighbourhood Search (VNS) algorithm is proposed to solve it. In order to gain insight into the problem, the computational studies were performed with randomly generated instances of different settings. Results clearly show that VNS performs well in solving IC-PHNDP with errors not more than 1.54%.Peer reviewe

Modelling terrigenous DOC across the north west European Shelf: Fate of riverine input and impact on air-sea CO2 fluxes

Terrigenous carbon in aquatic systems is increasingly recognised as an important part of the global carbon cycle. Despite this, the fate and distribution of terrigenous dissolved organic carbon (tDOC) in coastal and oceanic systems is poorly understood. We have implemented a theoretical framework for the degradation of tDOC across the land to ocean continuum in a 3D hydrodynamical-biogeochemical model on the North West European Shelf. A key feature of this model is that both photochemical and bacterial tDOC degradation rates are age dependant constituting an advance in our ability to describe carbon cycling in the marine environment. Over the time period 1986-2015, 182±17 Gmol yr− 1 of riverine tDOC is input to the shelf. Results indicate that bacterial degradation is by far the most important process in removing tDOC on the shelf, contributing to 73±6 % (132±11 Gmol yr− 1 ) of the total removal flux, while 21±3 % (39±6 Gmol yr− 1 ) of riverine tDOC was advected away from the shelf and photochemical degradation removing 5±0.5 % of the riverine flux. Explicitly including tDOC in the model decreased the air-sea carbon dioxide (CO2) flux by 112±8 Gmol yr− 1 (4±0.4 %), an amount approximately equivalent to the CO2 released by the UK chemical industry in 2020. The reduction is equivalent to 62 % of the riverine tDOC input to the shelf while approximately 17 % of riverine input is incorporated into the foodweb. This work can improve the assumptions of the fate of tDOC by Earth System Models and demonstrates that the inclusion of tDOC in models can impact ecosystem dynamics and change predicted global carbon budgets for the ocean

Engineering supported membranes for cell biology

Cell membranes exhibit multiple layers of complexity, ranging from their specific molecular content to their emergent mechanical properties and dynamic spatial organization. Both compositional and geometrical organizations of membrane components are known to play important roles in life processes, including signal transduction. Supported membranes, comprised of a bilayer assembly of phospholipids on the solid substrate, have been productively served as model systems to study wide range problems in cell biology. Because lateral mobility of membrane components is readily preserved, supported lipid membranes with signaling molecules can be utilized to effectively trigger various intercellular reactions. The spatial organization and mechanical deformation of supported membranes can also be manipulated by patterning underlying substrates with modern micro- and nano-fabrication techniques. This article focuses on various applications and methods to spatially patterned biomembranes by means of curvature modulations and spatial reorganizations, and utilizing them to interface with live cells. The integration of biological components into synthetic devices provides a unique approach to investigate molecular mechanisms in cell biology

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie