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  • Agirre, Jon, et al. (author)
  • The CCP4 suite: integrative software for macromolecular crystallography
  • 2023
  • In: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
  • Journal article (peer-reviewed)abstract
    • The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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  • Stephens, Lucas, et al. (author)
  • Archaeological assessment reveals Earth’s early transformation through land use
  • 2019
  • In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
  • Journal article (peer-reviewed)abstract
    • Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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  • Garrard, S. L., et al. (author)
  • Biological impacts of ocean acidification: a postgraduate perspective on research priorities
  • 2013
  • In: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 160:8, s. 1789-1805
  • Journal article (peer-reviewed)abstract
    • Research into the effects of ocean acidification (OA) on marine organisms has greatly increased during the past decade, as realization of the potential dramatic impacts has grown. Studies have revealed the multifarious responses of organisms to OA conditions, indicating a high level of intra- and interspecific variation in species' ability to accommodate these alterations. If we are to provide policy makers with sound, scientific input regarding the expected consequences of OA, we need a broader understanding of these predicted changes. As a group of 20 multi-disciplinary postgraduate students from around the globe, with a study focus on OA, we are a strong representation of 'next generation' scientists in this field. In this unique cumulative paper, we review knowledge gaps in terms of assessing the biological impacts of OA, outlining directions for future research.
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  • Schrey, A W, et al. (author)
  • Broad-scale latitudinal patterns of genetic diversity among native European and introduced house sparrow (Passer domesticus) populations.
  • 2011
  • In: Molecular Ecology. - 0962-1083. ; 20, s. 1133-1143
  • Journal article (peer-reviewed)abstract
    • Introduced species offer unique opportunities to study evolution in new environments, and some provide opportunities for understanding the mechanisms underlying macroecological patterns. We sought to determine how introduction history impacted genetic diversity and differentiation of the house sparrow (Passer domesticus), one of the most broadly distributed bird species. We screened eight microsatellite loci in 316 individuals from 16 locations in the native and introduced ranges. Significant population structure occurred between native than introduced house sparrows. Introduced house sparrows were distinguished into one North American group and a highly differentiated Kenyan group. Genetic differentiation estimates identified a high magnitude of differentiation between Kenya and all other populations, but demonstrated that European and North American samples were differentiated too. Our results support previous claims that introduced North American populations likely had few source populations, and indicate house sparrows established populations after introduction. Genetic diversity also differed among native, introduced North American, and Kenyan populations with Kenyan birds being least diverse. In some cases, house sparrow populations appeared to maintain or recover genetic diversity relatively rapidly after range expansion (<50 years; Mexico and Panama), but in others (Kenya) the effect of introduction persisted over the same period. In both native and introduced populations, genetic diversity exhibited large-scale geographic patterns, increasing towards the equator. Such patterns of genetic diversity are concordant with two previously described models of genetic diversity, the latitudinal model and the species diversity model.
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  • Bellouin, N., et al. (author)
  • Bounding Global Aerosol Radiative Forcing of Climate Change
  • 2020
  • In: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
  • Research review (peer-reviewed)abstract
    • Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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  • Eckel-Passow, Jeanette E., et al. (author)
  • Using germline variants to estimate glioma and subtype risks
  • 2019
  • In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 21:4, s. 451-461
  • Journal article (peer-reviewed)abstract
    • Background: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.Methods: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.Results: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.Conclusions: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.
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  • van der Spek, M., et al. (author)
  • Uncertainty analysis in the techno-economic assessment of CO2 capture and storage technologies. Critical review and guidelines for use
  • 2020
  • In: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 100
  • Journal article (peer-reviewed)abstract
    • Uncertainty analysis is a key element of sound techno-economic analysis (TEA) of CO2 Capture and Storage (CCS) technologies and systems, and in the communication of TEA results. Many CCS technologies are relatively novel, with only few large-scale projects constructed and in operation to date. Therefore, uncertainties in technology performance and costs are often substantial, making it imperative that they be characterized and reported. Although uncertainty analysis itself is not novel, with some methods already frequently used by the CCS TEA community, a document that provides a comprehensive overview of methods and approaches, as well as guidance on their selection and use, is still lacking. Given its importance, we seek to fill this gap by providing a critical review of uncertainty analysis methods along with guidance on the selection and use of these methods for CCS TEAs, highlighting good practice and examples from the CCS literature. The paper starts by identifying the different audiences for CCS TEAs, the different modelling approaches available for CCS technology performance and cost analysis, and the different roles that uncertainty analysis may play. It then continues to discuss established, as well as emerging, uncertainty analysis methods and addresses how and when each method is best used, as well as common pitfalls. We argue that the most commonly used method of one-parameter-at-a-time ‘local’ sensitivity analysis may often be a suboptimal choice, and that other approaches may be more suitable or lead to more insight, especially since uncertainty analysis software is becoming more widespread and easier to use. Finally, the paper discusses the benefits of advanced uses of uncertainty analysis in, for instance, the design of CCS experiments or in the design and planning of CCS infrastructure. Sound uncertainty analysis has an important role to play in TEAs of CCS technologies and systems, and there are many opportunities to bring the use of uncertainty analysis to a higher level than currently practiced. This review of and guidance on available methods is intended to help accelerate continued methods development and their application to more robust and meaningful CCS performance and costing studies. 
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  • Wedding, Lisa M., et al. (author)
  • Advancing the integration of spatial data to map human and natural drivers on coral reefs
  • 2018
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
  • Journal article (peer-reviewed)abstract
    • A major challenge for coral reef conservation and management is understanding how a wide range of interacting human and natural drivers cumulatively impact and shape these ecosystems. Despite the importance of understanding these interactions, a methodological framework to synthesize spatially explicit data of such drivers is lacking. To fill this gap, we established a transferable data synthesis methodology to integrate spatial data on environmental and anthropogenic drivers of coral reefs, and applied this methodology to a case study location-the Main Hawaiian Islands (MHI). Environmental drivers were derived from time series (2002-2013) of climatological ranges and anomalies of remotely sensed sea surface temperature, chlorophyll-a, irradiance, and wave power. Anthropogenic drivers were characterized using empirically derived and modeled datasets of spatial fisheries catch, sedimentation, nutrient input, new development, habitat modification, and invasive species. Within our case study system, resulting driver maps showed high spatial heterogeneity across the MHI, with anthropogenic drivers generally greatest and most widespread on O'ahu, where 70% of the state's population resides, while sedimentation and nutrients were dominant in less populated islands. Together, the spatial integration of environmental and anthropogenic driver data described here provides a first-ever synthetic approach to visualize how the drivers of coral reef state vary in space and demonstrates a methodological framework for implementation of this approach in other regions of the world. By quantifying and synthesizing spatial drivers of change on coral reefs, we provide an avenue for further research to understand how drivers determine reef diversity and resilience, which can ultimately inform policies to protect coral reefs.
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  • McCoy, Brittany M., et al. (author)
  • Mediators of the association between parental severe mental illness and offspring neurodevelopmental problems
  • 2014
  • In: Annals of Epidemiology. - New York, USA : Elsevier. - 1047-2797 .- 1873-2585. ; 24:9, s. 629-634.e1
  • Journal article (peer-reviewed)abstract
    • Purpose: Parental severe mental illness (SMI) is associated with an increased risk of offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We conducted a study to examine the extent to which risk of preterm birth, low birth weight, and small for gestational age mediated this association.Methods: We obtained data on offspring born 1992-2001 in Sweden (n = 870,017) through the linkage of multiple population-based registers. We used logistic and Cox regression to assess the associations between parental SMI, adverse pregnancy outcomes, and offspring ASD and ADHD, as well as tested whether adverse pregnancy outcomes served as mediators.Results: After controlling for measured covariates, maternal and paternal SMI were associated with an increased risk for preterm birth, low birth weight, and gestational age, and for offspring ASD and ADHD. These pregnancy outcomes were also associated with an increased risk of ASD and ADHD. We found that pregnancy outcomes did not mediate the association between parental SMI and offspring ASD and ADHD, as there was no substantial change in magnitude of the risk estimates after controlling for pregnancy outcomes.Conclusions: Parental SMI and adverse pregnancy outcomes appear to be independent risk factors for offspring ASD and ADHD.
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  • McCoy, Daniel T., et al. (author)
  • Aerosol midlatitude cyclone indirect effects in observations and high-resolution simulations
  • 2018
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:8, s. 5821-5846
  • Journal article (peer-reviewed)abstract
    • Aerosol-cloud interactions are a major source of uncertainty in inferring the climate sensitivity from the observational record of temperature. The adjustment of clouds to aerosol is a poorly constrained aspect of these aerosolcloud interactions. Here, we examine the response of midlatitude cyclone cloud properties to a change in cloud droplet number concentration (CDNC). Idealized experiments in high-resolution, convection-permitting global aquaplanet simulations with constant CDNC are compared to 13 years of remote-sensing observations. Observations and idealized aquaplanet simulations agree that increased warm conveyor belt (WCB) moisture flux into cyclones is consistent with higher cyclone liquid water path (CLWP). When CDNC is increased a larger LWP is needed to give the same rain rate. The LWP adjusts to allow the rain rate to be equal to the moisture flux into the cyclone along the WCB. This results in an increased CLWP for higher CDNC at a fixed WCB moisture flux in both observations and simulations. If observed cyclones in the top and bottom tercile of CDNC are contrasted it is found that they have not only higher CLWP but also cloud cover and albedo. The difference in cyclone albedo between the cyclones in the top and bottom third of CDNC is observed by CERES to be between 0.018 and 0.032, which is consistent with a 4.6-8.3Wm(-2) in-cyclone enhancement in upwelling shortwave when scaled by annualmean insolation. Based on a regression model to observed cyclone properties, roughly 60% of the observed variability in CLWP can be explained by CDNC and WCB moisture flux.
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  • McCoy, Isabel L., et al. (author)
  • The hemispheric contrast in cloud microphysical properties constrains aerosol forcing
  • 2020
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:32, s. 18998-19006
  • Journal article (peer-reviewed)abstract
    • The change in planetary albedo due to aerosol-cloud interactions during the industrial era is the leading source of uncertainty in inferring Earth's climate sensitivity to increased greenhouse gases from the historical record. The variable that controls aerosol-cloud interactions in warm clouds is droplet number concentration. Global climate models demonstrate that the present-day hemispheric contrast in cloud droplet number concentration between the pristine Southern Hemisphere and the polluted Northern Hemisphere oceans can be used as a proxy for anthropogenically driven change in cloud droplet number concentration. Remotely sensed estimates constrain this change in droplet number concentration to be between 8 cm(-3) and 24 cm(-3). By extension, the radiative forcing since 1850 from aerosol-cloud interactions is constrained to be -1.2 W.m(-2) to -0.6 W.m(-2). The robustness of this constraint depends upon the assumption that pristine Southern Ocean droplet number concentration is a suitable proxy for preindustrial concentrations. Droplet number concentrations calculated from satellite data over the Southern Ocean are high in austral summer. Near Antarctica, they reach values typical of Northern Hemisphere polluted outflows. These concentrations are found to agree with several in situ datasets. In contrast, climate models show systematic underpredictions of cloud droplet number concentration across the Southern Ocean. Near Antarctica, where precipitation sinks of aerosol are small, the underestimation by climate models is particularly large. This motivates the need for detailed process studies of aerosol production and aerosol-cloud interactions in pristine environments. The hemispheric difference in satellite estimated cloud droplet number concentration implies preindustrial aerosol concentrations were higher than estimated by most models.
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  • McCoy, Isabel L., et al. (author)
  • The Role of Mesoscale Cloud Morphology in the Shortwave Cloud Feedback
  • 2023
  • In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 50:2
  • Journal article (peer-reviewed)abstract
    • A supervised neural network algorithm is used to categorize near-global satellite retrievals into three mesoscale cellular convective (MCC) cloud morphology patterns. At constant cloud amount, morphology patterns differ in brightness associated with the amount of optically thin cloud features. Environmentally driven transitions from closed MCC to other morphology patterns, typically accompanied by more optically thin cloud features, are used as a framework to quantify the morphology contribution to the optical depth component of the shortwave cloud feedback. A marine heat wave is used as an out-of-sample test of closed MCC occurrence predictions. Morphology shifts in optical depth between 65°S and 65°N under projected environmental changes (i.e., from an abrupt quadrupling of CO2) assuming constant cloud cover contributes between 0.04 and 0.07 W m−2 K−1 (aggregate of 0.06) to the global mean cloud feedback.
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  • Ostrom, Quinn T., et al. (author)
  • Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'‐like features associated with younger age
  • 2018
  • In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:10, s. 2359-2366
  • Journal article (peer-reviewed)abstract
    • Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age‐at‐diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age‐at‐diagnosis has been explored, genome‐wide association studies (GWAS) have not previously been stratified by age. Potential age‐specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age‐stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta‐analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54–63 = 1.50x10−9, OR54–63 = 1.28, 95%CI54–63 = 1.18–1.39; p64+ = 2.14x10−11, OR64+ = 1.32, 95%CI64+ = 1.21–1.43] and rs11979158 [p54–63 = 6.13x10−8, OR54–63 = 1.35, 95%CI54–63 = 1.21–1.50; p64+ = 2.18x10−10, OR64+ = 1.42, 95%CI64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p18–53 = 9.30 × 10−11, OR18–53 = 1.76, 95%CI18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’‐like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age‐specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’
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  • Ostrom, Quinn T., et al. (author)
  • Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
  • 2018
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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  • Saunders, Harry D., et al. (author)
  • Energy Efficiency : What Has Research Delivered in the Last 40 Years?
  • 2021
  • In: Annual Review of Environment and Resources. - : Annual Reviews. - 1543-5938 .- 1545-2050. ; 46, s. 135-165
  • Research review (peer-reviewed)abstract
    • This article presents a critical assessment of 40 years of research that may be brought under the umbrella of energy efficiency, spanning different aggregations and domains-from individual producing and consuming agents to economy-wide effects to the role of innovation to the influence of policy. After 40 years of research, energy efficiency initiatives are generally perceived as highly effective. Innovation has contributed to lowering energy technology costs and increasing energy productivity. Energy efficiency programs in many cases have reduced energy use per unit of economic output and have been associated with net improvements in welfare, emission reductions, or both. Rebound effects at the macro level still warrant careful policy attention, as they may be nontrivial. Complexity of energy efficiency dynamics calls for further methodological and empirical advances, multidisciplinary approaches, and granular data at the service level for research in this field to be of greatest societal benefit.
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  • Acharya, Shravan S., et al. (author)
  • Diverse composites of metal-complexes and PEDOT facilitated by metal-free vapour phase polymerization
  • 2017
  • In: Reactive & functional polymers. - : Elsevier. - 1381-5148 .- 1873-166X. ; 116, s. 101-106
  • Journal article (peer-reviewed)abstract
    • Abstract Oxidative polymerization for the manufacture of conducting polymers such as poly(3,4-ethylenedioxy-thiophene) has traditionally employed iron(III) salts. Demonstrated in this study is vapour phase polymerization of 3,4-ethylenedio- xythiophene using a metal-free oxidant, ammonium persulfate, leading to films with an estimated conductivity of 75 S/cm. Additionally, a route for embedding active transition metal complexes into these poly(3,4-ethylenedioxythiophene)/-poly(styrene-4-sulfonate) (PEDOT/PSS) films via vapour assisted complexation is outlined. Here, the vapour pressure of solid ligands around their melting temperatures was exploited to ensure complexation to metal ions added into the oxidant mixture prior to polymerization of PEDOT. Four composite systems are discussed, viz. PEDOT/PSS embedded with tris(8-hydroxyquinolinato)cobalt(III), tris(2,2-bipyridine)cobalt(II), tris(1,10- phenanthroline)cobalt(II) and tris(8-hyd-roxyquinolinato)aluminium(III). Using these composites, electrochemical reduction of nitrite to ammonia with a faradaic efficiency of 61% was reported.
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  • Ahola, Virpi, et al. (author)
  • The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
  • 2014
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
  • Journal article (peer-reviewed)abstract
    • Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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  • Bender, Frida A.-M., et al. (author)
  • Assessment of aerosol-cloud-radiation correlations in satellite observations, climate models and reanalysis
  • 2019
  • In: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 52:7-8, s. 4371-4392
  • Journal article (peer-reviewed)abstract
    • Representing large-scale co-variability between variables related to aerosols, clouds and radiation is one of many aspects of agreement with observations desirable for a climate model. In this study such relations are investigated in terms of temporal correlations on monthly mean scale, to identify points of agreement and disagreement with observations. Ten regions with different meteorological characteristics and aerosol signatures are studied and correlation matrices for the selected regions offer an overview of model ability to represent present day climate variability. Global climate models with different levels of detail and sophistication in their representation of aerosols and clouds are compared with satellite observations and reanalysis assimilating meteorological fields as well as aerosol optical depth from observations. One example of how the correlation comparison can guide model evaluation and development is the often studied relation between cloud droplet number and water content. Reanalysis, with no parameterized aerosol–cloud coupling, shows weaker correlations than observations, indicating that microphysical couplings between cloud droplet number and water content are not negligible for the co-variations emerging on larger scale. These observed correlations are, however, not in agreement with those expected from dominance of the underlying microphysical aerosol–cloud couplings. For instance, negative correlations in subtropical stratocumulus regions show that suppression of precipitation and subsequent increase in water content due to aerosol is not a dominating process on this scale. Only in one of the studied models are cloud dynamics able to overcome the parameterized dependence of rain formation on droplet number concentration, and negative correlations in the stratocumulus regions are reproduced.
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26.
  • Boggs, Dorothy, et al. (author)
  • Rating early child development outcome measurement tools for routine health programme use
  • 2019
  • In: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 104, s. S22-S33
  • Journal article (peer-reviewed)abstract
    • Background Identification of children at risk of developmental delay and/or impairment requires valid measurement of early child development (ECD). We systematically assess ECD measurement tools for accuracy and feasibility for use in routine services in low-income and middle-income countries (LMIC). Methods Building on World Bank and peer-reviewed literature reviews, we identified available ECD measurement tools for children aged 0-3 years used in >= 1 LMIC and matrixed these according to when (child age) and what (ECD domains) they measure at population or individual level. Tools measuring <2 years and covering >= 3 developmental domains, including cognition, were rated for accuracy and feasibility criteria using a rating approach derived from Grading of Recommendations, Assessment, Development and Evaluations. Results 61 tools were initially identified, 8% (n=5) population-level and 92% (n=6) individual-level screening or ability tests. Of these, 27 tools covering >= 3 domains beginning <2 years of age were selected for rating accuracy and feasibility. Recently developed population-level tools (n=2) rated highly overall, particularly in reliability, cultural adaptability, administration time and geographical uptake. Individual-level tool (n=25) ratings were variable, generally highest for reliability and lowest for accessibility, training, clinical relevance and geographical uptake. Conclusions and implications Although multiple measurement tools exist, few are designed for multidomain ECD measurement in young children, especially in LMIC. No available tools rated strongly across all accuracy and feasibility criteria with accessibility, training requirements, clinical relevance and geographical uptake being poor for most tools. Further research is recommended to explore this gap in fit-for-purpose tools to monitor ECD in routine LMIC health services.
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  • Boggs, Dorothy, et al. (author)
  • Rating early child development outcome measurement tools for routine health programme use.
  • 2019
  • In: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 104:Suppl 1, s. S22-S33
  • Research review (peer-reviewed)abstract
    • Identification of children at risk of developmental delay and/or impairment requires valid measurement of early child development (ECD). We systematically assess ECD measurement tools for accuracy and feasibility for use in routine services in low-income and middle-income countries (LMIC).Building on World Bank and peer-reviewed literature reviews, we identified available ECD measurement tools for children aged 0-3 years used in ≥1 LMIC and matrixed these according to when (child age) and what (ECD domains) they measure at population or individual level. Tools measuring <2 years and covering ≥3 developmental domains, including cognition, were rated for accuracy and feasibility criteria using a rating approach derived from Grading of Recommendations, Assessment, Development and Evaluations.61 tools were initially identified, 8% (n=5) population-level and 92% (n=56) individual-level screening or ability tests. Of these, 27 tools covering ≥3 domains beginning <2 years of age were selected for rating accuracy and feasibility. Recently developed population-level tools (n=2) rated highly overall, particularly in reliability, cultural adaptability, administration time and geographical uptake. Individual-level tool (n=25) ratings were variable, generally highest for reliability and lowest for accessibility, training, clinical relevance and geographical uptake.Although multiple measurement tools exist, few are designed for multidomain ECD measurement in young children, especially in LMIC. No available tools rated strongly across all accuracy and feasibility criteria with accessibility, training requirements, clinical relevance and geographical uptake being poor for most tools. Further research is recommended to explore this gap in fit-for-purpose tools to monitor ECD in routine LMIC health services.
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28.
  • Chu, Derek K, et al. (author)
  • Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo.
  • 2014
  • In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 211:8, s. 1657-1672
  • Journal article (peer-reviewed)abstract
    • Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4(+/+) or il4(-/-) eosinophils. Eosinophils controlled CD103(+) dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity.
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29.
  • Hervey-Jumper, Shawn L, et al. (author)
  • Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.
  • 2023
  • In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:11, s. 2029-2042
  • Journal article (peer-reviewed)abstract
    • In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible.In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR.Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis.Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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30.
  • Jönsson, Aiden, 1991-, et al. (author)
  • A recipe for simulating the observed interhemispheric albedo symmetry and constraining cloud radiative feedbacks
  • Other publication (other academic/artistic)abstract
    • Earth’s albedo has remained symmetric between the northern and southern hemispheres over the satellite record, a feature that climate models have difficulty capturing. We investigate causes of these biases using a perturbed parameter ensemble of atmospheric simulations to probe the sensitivity of the albedo symmetry to cloud properties and the processes that control them. We find that the most significant parameters to simulated albedo symmetry impact precipitation, turbulent dissipation, and sea salt aerosol emissions. Constraining shortwave cloud feedbacks using the observed albedo symmetry leads to a range of +0.61±0.24 W m-2 K-1 (66% confidence). These are stronger than the model’s control settings due to greater loss of subtropical low clouds and weaker negative cloud phase feedback. Comparing the constrained and control parameter settings shows a preference towards settings that would reduce the control simulation’s biases, indicating that the constraint can select for representations that capture the observed cloud cover.
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31.
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32.
  • McCoy, Annette M., et al. (author)
  • Identification and validation of genetic variants predictive of gait in standardbred horses
  • 2019
  • In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 15:5
  • Journal article (peer-reviewed)abstract
    • Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the gene DMRT3 is permissive for gaitedness across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations. A genome-wide association analysis for the ability to pace was performed in 542 Standardbred horses (n = 176 pacers, n = 366 trotters) with genotype data imputed to similar to 74,000 single nucleotide polymorphisms (SNPs). Nineteen SNPs on nine chromosomes (ECA1, 2, 6, 9, 17, 19, 23, 25, 31) reached genome-wide significance (p < 1.44 x 10(-6)). Variant discovery in regions of interest was carried out via whole-genome sequencing. A set of 303 variants from 22 chromosomes with putative modifying effects on gait was genotyped in 659 Standardbreds (n = 231 pacers, n = 428 trotters) using a high-throughput assay. Random forest classification analysis resulted in an out-of-box error rate of 0.61%. A conditional inference tree algorithm containing seven SNPs predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters). This highly accurate algorithm could be used by owners/trainers to identify Standardbred horses with the potential to race as pacers or as trotters, according to the genotype identified, prior to initiating training and would enable fine-tuning of breeding programs with designed matings. Additional work is needed to determine both the algorithm's utility in other gaited breeds and whether any of the predictive SNPs play a physiologically functional role in the tendency to pace or tag true functional alleles.
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33.
  • McCoy, Christopher Cameron, et al. (author)
  • Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient
  • 2021
  • In: Shock. - : LIPPINCOTT WILLIAMS & WILKINS. - 1073-2322 .- 1540-0514. ; 56:1S
  • Journal article (peer-reviewed)abstract
    • Following advances in blood typing and storage, whole blood transfusion became available for the treatment of casualties during World War I. While substantially utilized during World War II and the Korean War, whole blood transfusion declined during the Vietnam War as civilian centers transitioned to blood component therapies. Little evidence supported this shift, and recent conflicts in Iraq and Afghanistan have renewed interest in military and civilian applications of whole blood transfusion. Within the past two decades, civilian trauma centers have begun to study transfusion protocols based upon cold-stored, low anti-A/B titer type O whole blood for the treatment of severely injured civilian trauma patients. Early data suggests equivalent or improved resuscitation and hemostatic markers with whole blood transfusion when compared to balanced blood component therapy. Additional studies are taking place to define the optimal way to utilize low-titer type O whole blood in both prehospital and trauma center resuscitation of bleeding patients.
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34.
  • McCoy, Daniel T., et al. (author)
  • Predicting decadal trends in cloud droplet number concentration using reanalysis and satellite data
  • 2018
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:3, s. 2035-2047
  • Journal article (peer-reviewed)abstract
    • Cloud droplet number concentration (CDNC) is the key state variable that moderates the relationship between aerosol and the radiative forcing arising from aerosolcloud interactions. Uncertainty related to the effect of anthropogenic aerosol on cloud properties represents the largest uncertainty in total anthropogenic radiative forcing. Here we show that regionally averaged time series of the Moderate-Resolution Imaging Spectroradiometer (MODIS) observed CDNC of low, liquid-topped clouds is well predicted by the MERRA2 reanalysis near-surface sulfate mass concentration over decadal timescales. A multiple linear regression between MERRA2 reanalyses masses of sulfate (SO4), black carbon (BC), organic carbon (OC), sea salt (SS), and dust (DU) shows that CDNC across many different regimes can be reproduced by a simple power-law fit to near-surface SO4, with smaller contributions from BC, OC, SS, and DU. This confirms previous work using a less sophisticated retrieval of CDNC on monthly timescales. The analysis is supported by an examination of remotely sensed sulfur dioxide (SO2) over maritime volcanoes and the east coasts of North America and Asia, revealing that maritime CDNC responds to changes in SO2 as observed by the ozone monitoring instrument (OMI). This investigation of aerosol reanalysis and top-down remote-sensing observations reveals that emission controls in Asia and North America have decreased CDNC in their maritime outflow on a decadal timescale.
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35.
  • Mccoy, D. T., et al. (author)
  • The global aerosol-cloud first indirect effect estimated using MODIS, MERRA, and AeroCom
  • 2017
  • In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 122:3, s. 1779-1796
  • Journal article (peer-reviewed)abstract
    • Aerosol-cloud interactions (ACI) represent a significant source of forcing uncertainty in global climate models (GCMs). Estimates of radiative forcing due to ACI in Fifth Assessment Report range from -0.5 to -2.5 W m(-2). A portion of this uncertainty is related to the first indirect, or Twomey, effect whereby aerosols act as nuclei for cloud droplets to condense upon. At constant liquid water content this increases the number of cloud droplets (Nd) and thus increases the cloud albedo. In this study we use remote-sensing estimates of Nd within stratocumulus regions in combination with state-of-the-art aerosol reanalysis from Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA2) to diagnose how aerosols affect Nd. As in previous studies, Nd is related to sulfate mass through a power law relationship. The slope of the log-log relationship between Nd and SO4 in maritime stratocumulus is found to be 0.31, which is similar to the range of 0.2-0.8 from previous in situ studies and remote-sensing studies in the pristine Southern Ocean. Using preindustrial emissions models, the change in Nd between preindustrial and present day is estimated. Nd is inferred to have more than tripled in some regions. Cloud properties from Moderate Resolution Imaging Spectroradiometer (MODIS) are used to estimate the radiative forcing due to this change in Nd. The Twomey effect operating in isolation is estimated to create a radiative forcing of -0.97 +/- 0.23 W m(-2) relative to the preindustrial era.
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36.
  • McCoy, M., et al. (author)
  • ALMA Observations of the Physical and Chemical Conditions in Centaurus A
  • 2017
  • In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 851:2
  • Journal article (peer-reviewed)abstract
    • Centaurus A, with its gas-rich elliptical host galaxy, NGC 5128, is the nearest radio galaxy at a distance of 3.8 Mpc. Its proximity allows us to study the interaction among an active galactic nucleus, radio jets, and molecular gas in great detail. We present ALMA observations of low-J transitions of three CO isotopologues, HCN, HCO+, HNC, CN, and CCH toward the inner projected 500 pc of NGC 5128. Our observations resolve physical sizes down to 40 pc. By observing multiple chemical probes, we determine the physical and chemical conditions of the nuclear interstellar medium of NGC 5128. This region contains molecular arms associated with the dust lanes and a circumnuclear disk (CND) interior to the molecular arms. The CND is approximately 400 pc by 200 pc and appears to be chemically distinct from the molecular arms. It is dominated by dense gas tracers while the molecular arms are dominated by (CO)-C-12 and its rare isotopologues. The CND has a higher temperature, elevated CN/HCN and HCN/HNC intensity ratios, and much weaker (CO)-C-13 and (CO)-O-18 emission than the molecular arms. This suggests an influence from the AGN on the CND molecular gas. There is also absorption against the AGN with a low velocity complex near the systemic velocity and a high velocity complex shifted by about 60 km s(-1). We find similar chemical properties between the CND in emission and both the low and high velocity absorption complexes, implying that both likely originate from the CND. If the HV complex does originate in the CND, then that gas would correspond to gas falling toward the supermassive black hole.
  •  
37.
  • McCoy, Thomas M, et al. (author)
  • Spontaneous Self-Assembly of Thermoresponsive Vesicles Using a Zwitterionic and an Anionic Surfactant
  • 2020
  • In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:11, s. 4569-4576
  • Journal article (peer-reviewed)abstract
    • Spontaneous formation of vesicles from the self-assembly of two specific surfactants, one zwitterionic (oleyl amidopropyl betaine, OAPB) and the other anionic (Aerosol-OT, AOT), is explored in water using small-angle scattering techniques. Two factors were found to be critical in the formation of vesicles: surfactant ratio, as AOT concentrations less than equimolar with OAPB result in cylindrical micelles or mixtures of micellar structures, and salt concentration, whereby increasing the amount of NaCl promotes vesicle formation by reducing headgroup repulsions. Small-angle neutron scattering measurements reveal that the vesicles are approximately 30-40 nm in diameter, depending on sample composition. Small-angle X-ray scattering measurements suggest preferential partitioning of OAPB molecules on the vesicle inner layer to support vesicular packing. Heating the vesicles to physiological temperature (37 °C) causes them to collapse into smaller ellipsoidal micelles (2-3 nm), with higher salt concentrations (≥10 mM) inhibiting this transition. These aggregates could serve as responsive carriers for loading or unloading of aqueous cargoes such as drugs and pharmaceuticals, with temperature changes serving as a simple release/uptake mechanism.
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38.
  • McNamee, Sara E., et al. (author)
  • Distribution, occurrence and biotoxin composition of the main shellfish toxin producing microalgae within European waters : A comparison of methods of analysis
  • 2016
  • In: Harmful Algae. - : Elsevier BV. - 1568-9883 .- 1878-1470. ; 55, s. 112-120
  • Journal article (peer-reviewed)abstract
    • Harmful algal blooms (HABs) are a natural global phenomena emerging in severity and extent. Incidents have many economic, ecological and human health impacts. Monitoring and providing early warning of toxic HABs are critical for protecting public health. Current monitoring programmes include measuring the number of toxic phytoplankton cells in the water and biotoxin levels in shellfish tissue. As these efforts are demanding and labour intensive, methods which improve the efficiency are essential. This study compares the utilisation of a multitoxin surface plasmon resonance (multitoxin SPR) biosensor with enzyme-linked immunosorbent assay (ELISA) and analytical methods such as high performance liquid chromatography with fluorescence detection (HPLC-FLD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for toxic HAB monitoring efforts in Europe. Seawater samples (n = 256) from European waters, collected 2009-2011, were analysed for biotoxins: saxitoxin and analogues, okadaic acid and dinophysistoxins 1/2 (VDU /DTX2) and domoic acid responsible for paralytic shellfish poisoning (PSP), diarrheic shellfish poisoning (DSP) and amnesic shellfish poisoning (ASP), respectively. Biotoxins were detected mainly in samples from Spain and Ireland. France and Norway appeared to have the lowest number of toxic samples. Both the multitoxin SPR biosensor and the RNA microarray were more sensitive at detecting toxic HABs than standard light microscopy phytoplankton monitoring. Correlations between each of the detection methods were performed with the overall agreement, based on statistical 2 x 2 comparison tables, between each testing platform ranging between 32% and 74% for all three toxin families illustrating that one individual testing method may not be an ideal solution. An efficient early warning monitoring system for the detection of toxic HABs could therefore be achieved by combining both the multitoxin SPR biosensor and RNA microarray. (C) 2016 Elsevier B.V. All rights reserved.
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39.
  • Melin, Beatrice S., et al. (author)
  • Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
  • 2017
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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40.
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41.
  • Tejani, Sanaa, et al. (author)
  • Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank
  • 2022
  • In: Mayo Clinic proceedings. - New York, United States : Elsevier. - 0025-6196 .- 1942-5546. ; 97:2, s. 225-237
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable- adjusted regression and were replicated in the independent UK Biobank.Results: The Dallas Heart Study included 2064 participants (mean SD age, 449 years; 54% female; 47% black). High VATehigh LF and high VATelow LF were associated with prevalent atheroscle- rosis, whereas low VATehigh LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VATehigh LF and high VATelow LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VATehigh LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N1⁄422,354; April 2014-May 2020), only high VATelow LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]).Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual.
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