The value of pre-transplant coronary angiography findings in kidney transplant candidates at high risk for cardiovascular disease

IntroductionCardiovascular disease is a significant cause of mortality after kidney transplantation. Whether pre-transplant screening for coronary artery disease (CAD) in asymptomatic kidney transplant candidates (KTCs) is beneficial is unclear.MethodsWe conducted a retrospective cohort study evaluating post-transplant cardiovascular events in 192 high-risk KTCs who underwent pre-transplant CAD evaluation. The study aimed to identify risk factors associated with finding severe CAD on pre-transplant angiography, and to assess the relationship between screening strategies and post-transplant cardiovascular events.ResultsAt five years post-transplant, cardiovascular events occurred in 23.9% of subjects. Prior CAD history and left ventricular ejection fraction (LVEF) < 50% were associated with higher odds of finding severe CAD on pre-transplant angiography. Severe CAD on angiography was associated with a higher risk of early cardiovascular events within six months of transplantation. However, coronary intervention in KTCs with severe CAD was not associated with lower rates of post-transplant cardiovascular events.ConclusionPre-transplant coronary angiography to identify severe CAD is of highest yield in KTCs with a history of CAD or an LVEF < 50%. Our findings indicate that the identification of severe CAD in KTCs has prognostic significance for the early post-transplant period. Optimization of medical therapy in these high-risk KTCs may improve post-transplant cardiovascular outcomes

BIOFRAG: A new database for analysing BIOdiversity responses to forest FRAGmentation

Habitat fragmentation studies are producing inconsistent and complex results across which it is nearly impossible to synthesise. Consistent analytical techniques can be applied to primary datasets, if stored in a flexible database that allows simple data retrieval for subsequent analyses. Method: We developed a relational database linking data collected in the field to taxonomic nomenclature, spatial and temporal plot attributes and further environmental variables (e.g. information on biogeographic region. Typical field assessments include measures of biological variables (e.g. presence, abundance, ground cover) of one species or a set of species linked to a set of plots in fragments of a forested landscape. Conclusion: The database currently holds records of 5792 unique species sampled in 52 landscapes in six of eight biogeographic regions: mammals 173, birds 1101, herpetofauna 284, insects 2317, other arthropods: 48, plants 1804, snails 65. Most species are found in one or two landscapes, but some are found in four. Using the huge amount of primary data on biodiversity response to fragmentation becomes increasingly important as anthropogenic pressures from high population growth and land demands are increasing. This database can be queried to extract data for subsequent analyses of the biological response to forest fragmentation with new metrics that can integrate across the components of fragmented landscapes. Meta-analyses of findings based on consistent methods and metrics will be able to generalise over studies allowing inter-comparisons for unified answers. The database can thus help researchers in providing findings for analyses of trade-offs between land use benefits and impacts on biodiversity and to track performance of management for biodiversity conservation in human-modified landscapes.Fil: Pfeifer, Marion. Imperial College London; Reino UnidoFil: Lefebvre, Veronique. Imperial College London; Reino UnidoFil: Gardner, Toby A.. Stockholm Environment Institute; SueciaFil: Arroyo Rodríguez, Víctor. Universidad Nacional Autónoma de México; MéxicoFil: Baeten, Lander. University of Ghent; BélgicaFil: Banks Leite, Cristina. Imperial College London; Reino UnidoFil: Barlow, Jos. Lancaster University; Reino UnidoFil: Betts, Matthew G.. State University of Oregon; Estados UnidosFil: Brunet, Joerg. Swedish University of Agricultural Sciences; SueciaFil: Cerezo Blandón, Alexis Mauricio. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Métodos Cuantitativos y Sistemas de Información; ArgentinaFil: Cisneros, Laura M.. University of Connecticut; Estados UnidosFil: Collard, Stuart. Nature Conservation Society of South Australia; AustraliaFil: D´Cruze, Neil. The World Society for the Protection of Animals; Reino UnidoFil: Da Silva Motta, Catarina. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Duguay, Stephanie. Carleton University; CanadáFil: Eggermont, Hilde. University of Ghent; BélgicaFil: Eigenbrod, Félix. University of Southampton; Reino UnidoFil: Hadley, Adam S.. State University of Oregon; Estados UnidosFil: Hanson, Thor R.. No especifíca;Fil: Hawes, Joseph E.. University of East Anglia; Reino UnidoFil: Heartsill Scalley, Tamara. United State Department of Agriculture. Forestry Service; Puerto RicoFil: Klingbeil, Brian T.. University of Connecticut; Estados UnidosFil: Kolb, Annette. Universitat Bremen; AlemaniaFil: Kormann, Urs. Universität Göttingen; AlemaniaFil: Kumar, Sunil. State University of Colorado - Fort Collins; Estados UnidosFil: Lachat, Thibault. Swiss Federal Institute for Forest; SuizaFil: Lakeman Fraser, Poppy. Imperial College London; Reino UnidoFil: Lantschner, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Laurance, William F.. James Cook University; AustraliaFil: Leal, Inara R.. Universidade Federal de Pernambuco; BrasilFil: Lens, Luc. University of Ghent; BélgicaFil: Marsh, Charles J.. University of Leeds; Reino UnidoFil: Medina Rangel, Guido F.. Universidad Nacional de Colombia; ColombiaFil: Melles, Stephanie. University of Toronto; CanadáFil: Mezger, Dirk. Field Museum of Natural History; Estados UnidosFil: Oldekop, Johan A.. University of Sheffield; Reino UnidoFil: Overal , Williams L.. Museu Paraense Emílio Goeldi. Departamento de Entomologia; BrasilFil: Owen, Charlotte. Imperial College London; Reino UnidoFil: Peres, Carlos A.. University of East Anglia; Reino UnidoFil: Phalan, Ben. University of Southampton; Reino UnidoFil: Pidgeon, Anna Michle. University of Wisconsin; Estados UnidosFil: Pilia, Oriana. Imperial College London; Reino UnidoFil: Possingham, Hugh P.. Imperial College London; Reino Unido. The University Of Queensland; AustraliaFil: Possingham, Max L.. No especifíca;Fil: Raheem, Dinarzarde C.. Royal Belgian Institute of Natural Sciences; Bélgica. Natural History Museum; Reino UnidoFil: Ribeiro, Danilo B.. Universidade Federal do Mato Grosso do Sul; BrasilFil: Ribeiro Neto, Jose D.. Universidade Federal de Pernambuco; BrasilFil: Robinson, Douglas W.. State University of Oregon; Estados UnidosFil: Robinson, Richard. Manjimup Research Centre; AustraliaFil: Rytwinski, Trina. Carleton University; CanadáFil: Scherber, Christoph. Universität Göttingen; AlemaniaFil: Slade, Eleanor M.. University of Oxford; Reino UnidoFil: Somarriba, Eduardo. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Stouffer, Philip C.. State University of Louisiana; Estados UnidosFil: Struebig, Matthew J.. University of Kent; Reino UnidoFil: Tylianakis, Jason M.. University College London; Estados Unidos. Imperial College London; Reino UnidoFil: Teja, Tscharntke. Universität Göttingen; AlemaniaFil: Tyre, Andrew J.. Universidad de Nebraska - Lincoln; Estados UnidosFil: Urbina Cardona, Jose N.. Pontificia Universidad Javeriana; ColombiaFil: Vasconcelos, Heraldo L.. Universidade Federal de Uberlandia; BrasilFil: Wearn, Oliver. Imperial College London; Reino Unido. The Zoological Society of London; Reino UnidoFil: Wells, Konstans. University of Adelaide; AustraliaFil: Willig, Michael R.. University of Connecticut; Estados UnidosFil: Wood, Eric. University of Wisconsin; Estados UnidosFil: Young, Richard P.. Durrell Wildlife Conservation Trust; Reino UnidoFil: Bradley, Andrew V.. Imperial College London; Reino UnidoFil: Ewers, Robert M.. Imperial College London; Reino Unid

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

BIOFRAG - a new database for analyzing BIOdiversity responses to forest FRAGmentation

Peer reviewe

BIOFRAG – a new database for analyzing BIOdiversity responses to forest FRAGmentation

Habitat fragmentation studies have produced complex results that are challenging to synthesize. Inconsistencies among studies may result from variation in the choice of landscape metrics and response variables, which is often compounded by a lack of key statistical or methodological information. Collating primary datasets on biodiversity responses to fragmentation in a consistent and flexible database permits simple data retrieval for subsequent analyses. We present a relational database that links such field data to taxonomic nomenclature, spatial and temporal plot attributes, and environmental characteristics. Field assessments include measurements of the response(s) (e.g., presence, abundance, ground cover) of one or more species linked to plots in fragments within a partially forested landscape. The database currently holds 9830 unique species recorded in plots of 58 unique landscapes in six of eight realms: mammals 315, birds 1286, herptiles 460, insects 4521, spiders 204, other arthropods 85, gastropods 70, annelids 8, platyhelminthes 4, Onychophora 2, vascular plants 2112, nonvascular plants and lichens 320, and fungi 449. Three landscapes were sampled as long-term time series (>10 years). Seven hundred and eleven species are found in two or more landscapes. Consolidating the substantial amount of primary data available on biodiversity responses to fragmentation in the context of land-use change and natural disturbances is an essential part of understanding the effects of increasing anthropogenic pressures on land. The consistent format of this database facilitates testing of generalizations concerning biologic responses to fragmentation across diverse systems and taxa. It also allows the re-examination of existing datasets with alternative landscape metrics and robust statistical methods, for example, helping to address pseudo-replication problems. The database can thus help researchers in producing broad syntheses of the effects of land use. The database is dynamic and inclusive, and contributions from individual and large-scale data-collection efforts are welcome.Keywords: Species turnover, Data sharing, Database, Global change, Landscape metrics, Edge effects, Forest fragmentation, Matrix contrast, Bioinformatic