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1.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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2.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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3.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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4.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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5.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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6.
  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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7.
  • Nicolas, Aude, et al. (författare)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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8.
  • Patterson, Nick, et al. (författare)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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9.
  • Sise, Andrew, et al. (författare)
  • Health and well-being needs of Indigenous adolescents : a protocol for a scoping review of qualitative studies
  • 2024
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.Methods and analysis: This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10-24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.Ethics and dissemination: Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.
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10.
  • Wang, Haidong, et al. (författare)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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11.
  • Aad, G., et al. (författare)
  • 2012
  • swepub:Mat__t (refereegranskat)
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12.
  • Ahmad, Amais, et al. (författare)
  • IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 4 : Prediction accuracy and software comparisons with improved data and modelling strategies
  • 2020
  • Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 156, s. 50-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption is much needed. Current status of predictive performance, within the confinement of commonly available in vitro data on drugs and formulations alongside systems information, were tested using 3 PBPK software packages (GI-Sim (ver.4.1), Simcyp® Simulator (ver.15.0.86.0), and GastroPlusTM (ver.9.0.00xx)). This was part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project.Fifty eight active pharmaceutical ingredients (APIs) were qualified from the OrBiTo database to be part of the investigation based on a priori set criteria on availability of minimum necessary information to allow modelling exercise. The set entailed over 200 human clinical studies with over 700 study arms. These were simulated using input parameters which had been harmonised by a panel of experts across different software packages prior to conduct of any simulation. Overall prediction performance and software packages comparison were evaluated based on performance indicators (Fold error (FE), Average fold error (AFE) and absolute average fold error (AAFE)) of pharmacokinetic (PK) parameters.On average, PK parameters (Area Under the Concentration-time curve (AUC0-tlast), Maximal concentration (Cmax), half-life (t1/2)) were predicted with AFE values between 1.11 and 1.97. Variability in FEs of these PK parameters was relatively high with AAFE values ranging from 2.08 to 2.74. Around half of the simulations were within the 2-fold error for AUC0-tlast and around 90% of the simulations were within 10-fold error for AUC0-tlast. Oral bioavailability (Foral) predictions, which were limited to 19 APIs having intravenous (i.v.) human data, showed AFE and AAFE of values 1.37 and 1.75 respectively. Across different APIs, AFE of AUC0-tlast predictions were between 0.22 and 22.76 with 70% of the APIs showing an AFE > 1. When compared across different formulations and routes of administration, AUC0-tlast for oral controlled release and i.v. administration were better predicted than that for oral immediate release formulations. Average predictive performance did not clearly differ between software packages but some APIs showed a high level of variability in predictive performance across different software packages. This variability could be related to several factors such as compound specific properties, the quality and availability of information, and errors in scaling from in vitro and preclinical in vivo data to human in vivo behaviour which will be explored further. Results were compared with previous similar exercise when the input data selection was carried by the modeller rather than a panel of experts on each in vitro test. Overall, average predictive performance was increased as reflected in smaller AAFE value of 2.8 as compared to AAFE value of 3.8 in case of previous exercise.
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13.
  • An, Junghwa, et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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14.
  • Balabanski, Anna H., et al. (författare)
  • Incidence of stroke in indigenous populations of countries with a very high human development index : a systematic review
  • 2024
  • Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 102:5
  • Forskningsöversikt (refereegranskat)abstract
    • Background and objectives: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health.Methods: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study.Results: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations.Discussion: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building.
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15.
  • Balabanski, Anna H., et al. (författare)
  • The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index : A Systematic Review Protocol
  • 2021
  • Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
  • Forskningsöversikt (refereegranskat)abstract
    • Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations.Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research.Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this.Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.
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16.
  • Bernal, Ximena E., et al. (författare)
  • Empowering Latina scientists
  • 2019
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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17.
  • Billing, Matilda, et al. (författare)
  • A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic progenitor cells.
  • 2016
  • Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 44:5, s. 399-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell (HSC) function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFβ response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFβ signaling effector molecule p57 was found to be upregulated as a secondary response to TGFβ. We observed Gata2 binding upstream of the p57 genomic locus, and importantly loss of Gata2 abolished TGFβ-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in HSC self-renewal and reveal a functionally relevant network regulating proliferation of primitive hematopoietic cells.
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18.
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19.
  • Boltz, Frederick, et al. (författare)
  • Water is a master variable : Solving for resilience in the modern era
  • 2019
  • Ingår i: Water Security. - : Elsevier BV. - 2468-3124. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Resilience is increasingly recognized as an imperative for any prospect of sustainable development, as it relates to our ability to sustain human well-being and progress under the planetary and societal changes that we face now and into the future. Yet, we are ill-prepared to meet this challenge. We neither fully understand nor manage consistently for resilience of the human and natural systems that we must steward through extraordinary change. A unifying approach and common currency would help us to understand and manage for resilience under uncertain futures. Water is an essential, defining element in human and natural systems. Human civilization and water systems have co-evolved as a coupled system, with the majority of natural freshwater systems transformed to meet our demands. Shifting patters of water availability in space and time will define key pathways and tipping points for our resilience, and thus requirements for water system resilience must guide the trajectories and boundaries of human development. Here, we consider the thesis that water offers a key to unlocking the complex challenge of designing and managing for the resilience of coupled human-natural systems. We examine what constitutes a resilient system, what drives freshwater resilience, and how pathways to human resilience may be charted and navigated through the medium of water. Our theoretical treatise frames a portfolio of research that tests this thesis, including modeling and applications to water and water-dependent systems. 
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20.
  • Brehm, Nicolas, et al. (författare)
  • Tree-rings reveal two strong solar proton events in 7176 and 5259 BCE
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sun sporadically produces eruptive events leading to intense fluxes of solar energetic particles (SEPs) that dramatically disrupt the near-Earth radiation environment. Such events have been directly studied for the last decades but little is known about the occurrence and magnitude of rare, extreme SEP events. Presently, a few events that produced measurable signals in cosmogenic radionuclides such as 14C, 10Be and 36Cl have been found. Analyzing annual 14C concentrations in tree-rings from Switzerland, Germany, Ireland, Russia, and the USA we discovered two spikes in atmospheric 14C occurring in 7176 and 5259 BCE. The ~2% increases of atmospheric 14C recorded for both events exceed all previously known 14C peaks but after correction for the geomagnetic field, they are comparable to the largest event of this type discovered so far at 775 CE. These strong events serve as accurate time markers for the synchronization with floating tree-ring and ice core records and provide critical information on the previous occurrence of extreme solar events which may threaten modern infrastructure.
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21.
  • Brown, Alex D., et al. (författare)
  • The environmental context of a prehistoric rock carving on the Bjare Peninsula, Scania, southern Sweden
  • 2011
  • Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 1095-9238 .- 0305-4403. ; 38:3, s. 746-752
  • Tidskriftsartikel (refereegranskat)abstract
    • Palaeoecological analysis of peat deposits from a small bog at Lingarden, southern Sweden, have been used to examine the nature and timing of vegetation changes and anthropogenic activity associated with a nearby rock carving located close to the edge of the wetland. This study is the first of its type to investigate the environmental context of rock carvings in southern Sweden. Debate has tended to focus on chronology and iconography, with little consideration of the environmental relationships of rock carvings and how vegetation may help construct a site within its surrounding landscape. The pollen evidence from Lingarden demonstrates that the rock carving was located in an isolated semi-wooded setting during the late Bronze Age. This is in stark contrast to several other pollen studies from the Bjare Peninsula that record widespread woodland clearance and agricultural activity from the late Neolithic Bronze Age transition. The results of this study support hypotheses that suggest complex rock carvings, such as Lingarden, were separated from settled areas. This sense of separation and isolation is reinforced by the vegetation surrounding the rock carving. This paper also discusses the relationship between charcoal in the pollen sequence and evidence that the decorated outcrop had been burnt. (c) 2010 Elsevier Ltd. All rights reserved.
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22.
  • Brown, Dylan R., et al. (författare)
  • Hypersaline tidal flats as important "blue carbon" systems : a case study from three ecosystems
  • 2021
  • Ingår i: Biogeosciences. - : COPERNICUS GESELLSCHAFT MBH. - 1726-4170 .- 1726-4189. ; 18:8, s. 2527-2538
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypersaline tidal flats (HTFs) are coastal ecosystems with freshwater deficits often occurring in arid or semiarid regions near mangrove supratidal zones with no major fluvial contributions. Here, we estimate that organic carbon (OC), total nitrogen (TN) and total phosphorus (TP) were buried at rates averaging 21 (+/- 6), 1.7 (+/- 0.3) and 1.4 (+/- 0.3) gm(-2) yr(-1), respectively, during the previous century in three contrasting HTF systems, one in Brazil (eutrophic) and two in Australia (oligotrophic). Although these rates are lower than those from nearby mangrove, saltmarsh and seagrass systems, the importance of HTFs as sinks for OC, TN and TP may be significant given their extensive coverage. Despite the measured short-term variability between net air-saltpan CO2 influx and emission estimates found during the dry and wet season in the Brazilian HTF, the only site with seasonal CO2 flux measurements, the OC sedimentary profiles over several decades suggest efficient OC burial at all sites. Indeed, the stable isotopes of OC and TN (delta C-13 and delta N-1(5)) along with C : N ratios show that microphytobenthos are the major source of the buried OC in these HTFs. Our findings highlight a previously unquantified carbon as well as a nutrient sink and suggest that coastal HTF ecosystems could be included in the emerging blue carbon framework.
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23.
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24.
  • Chuang, Yi-De, et al. (författare)
  • Modular soft x-ray spectrometer for applications in energy sciences and quantum materials
  • 2017
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 1089-7623 .- 0034-6748. ; 88:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past decade, the advances in grating-based soft X-ray spectrometers have revolutionizedthe soft X-ray spectroscopies in materials research. However, these novel spectrometers are mostlydedicated designs, which cannot be easily adopted for applications with diverging demands. Here wepresent a versatile spectrometer design concept based on the Hettrick-Underwood optical scheme thatuses modular mechanical components. The spectrometer’s optics chamber can be used with gratingsoperated in either inside or outside orders, and the detector assembly can be reconfigured accordingly.The spectrometer can be designed to have high spectral resolution, exceeding 10 000 resolvingpower when using small source (∼1 µm) and detector pixels (∼5 µm) with high line density gratings(∼3000 lines/mm), or high throughput at moderate resolution. We report two such spectrometers withslightly different design goals and optical parameters in this paper. We show that the spectrometer withhigh throughput and large energy window is particularly useful for studying the sustainable energymaterials. We demonstrate that the extensive resonant inelastic X-ray scattering (RIXS) map of batterycathode material LiNi1/3Co1/3Mn1/3O2 can be produced in few hours using such a spectrometer.Unlike analyzing only a handful of RIXS spectra taken at selected excitation photon energies across theelemental absorption edges to determine various spectral features like the localized dd excitations andnon-resonant fluorescence emissions, these features can be easily identified in the RIXS maps. Studyingsuch RIXS maps could reveal novel transition metal redox in battery compounds that are sometimeshard to be unambiguously identified in X-ray absorption and emission spectra. We propose that thismodular spectrometer design can serve as the platform for further customization to meet specificscientific demands.
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25.
  • Chuang, Yi De, et al. (författare)
  • Momentum-resolved resonant inelastic soft X-ray scattering (qRIXS) endstation at the ALS
  • 2022
  • Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048. ; 257
  • Tidskriftsartikel (refereegranskat)abstract
    • A momentum resolved resonant inelastic X-ray scattering (qRIXS) experimental station with continuously rotatable spectrometers and parallel detection is designed to operate at different beamlines at synchrotron and free electron laser (FEL) facilities. This endstation, currently located at the Advanced Light Source (ALS), has five emission ports on the experimental chamber for mounting the high-throughput modular soft X-ray spectrometers (MXS) [24]. Coupled to the rotation from the supporting hexapod, the scattered X-rays from 27.5° (forward scattering) to 152.5° (backward scattering) relative to the incident photon beam can be recorded, enabling the momentum-resolved RIXS spectroscopy. The components of this endstation are described in details, and the preliminary RIXS measurements on highly oriented pyrolytic graphite (HOPG) reveal the low energy vibronic excitations from the strong electron-phonon coupling at C K edge around σ* band. The grating upgrade option to enhance the performance at low photon energies is presented and the potential of this spectroscopy is discussed in summary.
  •  
26.
  • Crüwell, Sophia, et al. (författare)
  • What’s in a Badge? : A Computational Reproducibility Investigation of the Open Data Badge Policy in One Issue of Psychological Science
  • 2023
  • Ingår i: Psychological Science. - : Sage Publications. - 0956-7976 .- 1467-9280. ; 34:4, s. 512-522
  • Tidskriftsartikel (refereegranskat)abstract
    • In April 2019, Psychological Science published its first issue in which all Research Articles received the Open Data badge.We used that issue to investigate the effectiveness of this badge, focusing on the adherence to its aim at Psychological Science: sharing both data and code to ensure reproducibility of results. Twelve researchers of varying experience levels attempted to reproduce the results of the empirical articles in the target issue (at least three researchers per article). We found that all 14 articles provided at least some data and six provided analysis code, but only one article was rated to be exactly reproducible, and three were rated as essentially reproducible with minor deviations. We suggest that researchers should be encouraged to adhere to the higher standard in force at Psychological Science. Moreover, a check of reproducibility during peer review may be preferable to the disclosure method of awarding badges.
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27.
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28.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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29.
  • Elsik, Christine G., et al. (författare)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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30.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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31.
  • Figtree, Gemma A., et al. (författare)
  • Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
  • 2023
  • Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 82:13, s. 1343-1359
  • Forskningsöversikt (refereegranskat)abstract
    • Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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32.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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33.
  • Grüning, Björn, et al. (författare)
  • Bioconda: A sustainable and comprehensive software distribution for the life sciences
  • 2017
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
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34.
  • Jenniskens, Peter, et al. (författare)
  • The impact and recovery of asteroid 2018 LA
  • 2021
  • Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 56:4, s. 844-893
  • Tidskriftsartikel (refereegranskat)abstract
    • The June 2, 2018 impact of asteroid 2018 LA over Botswana is only the second asteroid detected in space prior to impacting over land. Here, we report on the successful recovery of meteorites. Additional astrometric data refine the approach orbit and define the spin period and shape of the asteroid. Video observations of the fireball constrain the asteroid's position in its orbit and were used to triangulate the location of the fireball's main flare over the Central Kalahari Game Reserve. Twenty‐three meteorites were recovered. A consortium study of eight of these classifies Motopi Pan as an HED polymict breccia derived from howardite, cumulate and basaltic eucrite, and diogenite lithologies. Before impact, 2018 LA was a solid rock of ~156 cm diameter with high bulk density ~2.85 g cm−3, a relatively low albedo pV ~ 0.25, no significant opposition effect on the asteroid brightness, and an impact kinetic energy of ~0.2 kt. The orbit of 2018 LA is consistent with an origin at Vesta (or its Vestoids) and delivery into an Earth‐impacting orbit via the ν6 resonance. The impact that ejected 2018 LA in an orbit toward Earth occurred 22.8 ± 3.8 Ma ago. Zircons record a concordant U‐Pb age of 4563 ± 11 Ma and a consistent 207Pb/206Pb age of 4563 ± 6 Ma. A much younger Pb‐Pb phosphate resetting age of 4234 ± 41 Ma was found. From this impact chronology, we discuss what is the possible source crater of Motopi Pan and the age of Vesta's Veneneia impact basin.
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35.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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36.
  • Kyu, Hmwe H, et al. (författare)
  • Global and National Burden of Diseases and Injuries Among Children and Adolescents Between 1990 and 2013 : Findings From the Global Burden of Disease 2013 Study.
  • 2016
  • Ingår i: JAMA pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:3, s. 267-287
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810 304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
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37.
  • Lauvset, Siv K., et al. (författare)
  • The annual update GLODAPv2.2023: the global interior ocean biogeochemical data product
  • 2024
  • Ingår i: Earth System Science Data. - 1866-3591. ; 16, s. 2047-2072
  • Tidskriftsartikel (refereegranskat)abstract
    • The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface to bottom ocean biogeochemical bottle data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of seawater samples. GLODAPv2.2023 is an update of the previous version, GLODAPv2.2022 (Lauvset et al., 2022). The major changes are as follows: data from 23 new cruises were added. In addition, a number of changes were made to the data included in GLODAPv2.2022. GLODAPv2.2023 includes measurements from more than 1.4 million water samples from the global oceans collected on 1108 cruises. The data for the now 13 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, chlorofluorocarbon-11 (CFC-11), CFC-12, CFC-113, CCl4, and SF6) have undergone extensive quality control with a focus on the systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but converted to World Ocean Circulation Experiment (WOCE) exchange format and (ii) as a merged data product with adjustments applied to minimize bias. For the present annual update, adjustments for the 23 new cruises were derived by comparing those data with the data from the 1085 quality-controlled cruises in the GLODAPv2.2022 data product using crossover analysis. SF6 data from all cruises were evaluated by comparison with CFC-12 data measured on the same cruises. For nutrients and ocean carbon dioxide (CO2), chemistry comparisons to estimates based on empirical algorithms provided additional context for adjustment decisions. The adjustments that we applied are intended to remove potential biases from errors related to measurement, calibration, and data-handling practices without removing known or likely time trends or variations in the variables evaluated. The compiled and adjusted data product is believed to be consistent to better than 0.005 in salinity, 1% in oxygen, 2% in nitrate, 2% in silicate, 2% in phosphate, 4µmolkg−1 in dissolved inorganic carbon, 4µmolkg−1 in total alkalinity, 0.01–0.02 in pH (depending on region), and 5% in the halogenated transient tracers. The other variables included in the compilation, such as isotopic tracers and discrete CO2 fugacity (fCO2), were not subjected to bias comparison or adjustments. The original data, their documentation, and DOI codes are available at the Ocean Carbon and Acidification Data System of NOAA National Centers for Environmental Information (NCEI), which also provides access to the merged data product. This is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/zyrq-ht66 (Lauvset et al., 2023). These bias-adjusted product files also include significant ancillary and approximated data, which were obtained by interpolation of, or calculation from, measured data. This living data update documents the GLODAPv2.2023 methods and provides a broad overview of the secondary quality control procedures and results.
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38.
  • Loos, Ruth J. F., et al. (författare)
  • Common variants near MC4R are associated with fat mass, weight and risk of obesity
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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39.
  • MacKenzie, Alison, et al. (författare)
  • Dissolving the Dichotomies Between Online and Campus-Based Teaching : a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)
  • 2022
  • Ingår i: Postdigital Science and Education. - : Springer. - 2524-4868 .- 2524-485X. ; , s. 271-329
  • Tidskriftsartikel (refereegranskat)abstract
    • This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching.
  •  
40.
  • MacKenzie, Alison, et al. (författare)
  • Dissolving the Dichotomies Between Online and Campus-Based Teaching : a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)
  • 2022
  • Ingår i: Postdigital Science and Education. - : Springer. - 2524-4868 .- 2524-485X. ; 4, s. 271-329
  • Tidskriftsartikel (refereegranskat)abstract
    • This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching.
  •  
41.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
  •  
42.
  • May, Gillian, et al. (författare)
  • Dynamic Analysis of Gene Expression and Genome-wide Transcription Factor Binding during Lineage Specification of Multipotent Progenitors
  • 2013
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 13:6, s. 754-768
  • Tidskriftsartikel (refereegranskat)abstract
    • We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIP-seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (1) differential complexity of sequence motifs bound by GATA1, GATA2, and PU.1; (2) the scope and interplay of GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (3) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression; and (4) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry. This rubric exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.
  •  
43.
  • McKee, David, et al. (författare)
  • Role of measurement uncertainties in observed variability in the spectral backscattering ratio : a case study in mineral-rich coastal waters
  • 2009
  • Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 48:24, s. 4663-4675
  • Tidskriftsartikel (refereegranskat)abstract
    • The particulate backscattering ratio (b(bp)/b(p)) is a useful indicator of the angular scattering characteristics of natural waters. Recent studies have shown evidence both for and against significant spectral variability in b(bp)/b(p) in the visible domain, but most show significant variability in its magnitude. We present results from a case study in which both backscattering and scattering coefficients were measured at nine wavelengths in a region of UK coastal waters where optical scattering is strongly influenced by inorganic particles and where a wide range of turbidities is found in a small geographic area. Using a new approach based on regression analysis of in situ signals, it is shown that, for this study site, most of the apparent variability in the magnitude of the backscattering ratio can be attributed to measurement uncertainties. Regression analysis suggests that b(bp)/b(p) is wavelength dependent for these mineral-rich waters. This conclusion can only be avoided by positing the existence of undocumented, systematic, wavelength-dependent errors in backscattering measurements made by two independently calibrated sensors. These results are important for radiative transfer simulations in mineral-dominated waters where the backscattering ratio has often been assumed to be spectrally flat. Furthermore, spectral dependence also has profound implications for our understanding of the relationship between b(bp)/b(p) and particle size distributions in coastal waters since the commonly assumed power-law distribution is associated with a spectrally flat particulate backscattering ratio for nonabsorbing particles.
  •  
44.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
  •  
45.
  • Panzer, Matthew B., et al. (författare)
  • NUMERICAL CROWDSOURCING OF NFL FOOTBALL HELMETS
  • 2018
  • Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:16, s. A148-A148
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
46.
  • Pecunia, Vincenzo, et al. (författare)
  • Roadmap on energy harvesting materials
  • 2023
  • Ingår i: Journal of Physics. - : IOP Publishing. - 2515-7639. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
  •  
47.
  • Pfeffer, W. Tad, et al. (författare)
  • The Randolph Glacier Inventory : a globally complete inventory of glaciers
  • 2014
  • Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 60:221, s. 537-552
  • Tidskriftsartikel (refereegranskat)abstract
    • The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the similar to 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 +/- 34 000 km(2). The uncertainty, about +/- 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
  •  
48.
  • Pina, Cristina, et al. (författare)
  • Inferring rules of lineage commitment in haematopoiesis
  • 2012
  • Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 14:3, s. 287-287
  • Tidskriftsartikel (refereegranskat)abstract
    • How the molecular programs of differentiated cells develop as cells transit from multipotency through lineage commitment remains unexplored. This reflects the inability to access cells undergoing commitment or located in the immediate vicinity of commitment boundaries. It remains unclear whether commitment constitutes a gradual process, or else represents a discrete transition. Analyses of in vitro self-renewing multipotent systems have revealed cellular heterogeneity with individual cells transiently exhibiting distinct biases for lineage commitment(1-6). Such systems can be used to molecularly interrogate early stages of lineage affiliation and infer rules of lineage commitment. In haematopoiesis, population-based studies have indicated that lineage choice is governed by global transcriptional noise, with self-renewing multipotent cells reversibly activating transcriptome-wide lineage-affiliated programs(7). We examine this hypothesis through functional and molecular analysis of individual blood cells captured from self-renewal cultures, during cytokine-driven differentiation and from primary stem and progenitor bone marrow compartments. We show dissociation between self-renewal potential and transcriptome-wide activation of lineage programs, and instead suggest that multipotent cells experience independent activation of individual regulators resulting in a low probability of transition to the committed state.
  •  
49.
  • Qiu, Ting, et al. (författare)
  • Structural white matter properties and cognitive resilience to tau pathology
  • Ingår i: Alzheimer's and Dementia. - 1552-5260.
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. METHODS: We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-β/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties. RESULTS: Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks. DISCUSSION: White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties. Highlights: Aβ and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.
  •  
50.
  • Rajangam, Alex S., et al. (författare)
  • MAP20, a Microtubule-Associated Protein in the Secondary Cell Walls of Hybrid Aspen, Is a Target of the Cellulose Synthesis Inhibitor 2,6-Dichlorobenzonitrile
  • 2008
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 148:3, s. 1283-1294
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified a gene, denoted PttMAP20, which is strongly up-regulated during secondary cell wall synthesis and tightly coregulated with the secondary wall-associated CESA genes in hybrid aspen (Populus tremula x tremuloides). Immunolocalization studies with affinity-purified antibodies specific for PttMAP20 revealed that the protein is found in all cell types in developing xylem and that it is most abundant in cells forming secondary cell walls. This PttMAP20 protein sequence contains a highly conserved TPX2 domain first identified in a microtubule-associated protein (MAP) in Xenopus laevis. Overexpression of PttMAP20 in Arabidopsis (Arabidopsis thaliana) leads to helical twisting of epidermal cells, frequently associated with MAPs. In addition, a PttMAP20-yellow fluorescent protein fusion protein expressed in tobacco (Nicotiana tabacum) leaves localizes to microtubules in leaf epidermal pavement cells. Recombinant PttMAP20 expressed in Escherichia coli also binds specifically to in vitro-assembled, taxol-stabilized bovine microtubules. Finally, the herbicide 2,6-dichlorobenzonitrile, which inhibits cellulose synthesis in plants, was found to bind specifically to PttMAP20. Together with the known function of cortical microtubules in orienting cellulose microfibrils, these observations suggest that PttMAP20 has a role in cellulose biosynthesis.
  •  
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