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2.
  • 2019
  • Journal article (peer-reviewed)
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3.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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4.
  • Flannick, Jason, et al. (author)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Journal article (peer-reviewed)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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5.
  • Fuchsberger, Christian, et al. (author)
  • The genetic architecture of type 2 diabetes
  • 2016
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Journal article (peer-reviewed)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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6.
  • Liu, Cong, et al. (author)
  • Ambient Particulate Air Pollution and Daily Mortality in 652 Cities
  • 2019
  • In: New England Journal of Medicine. - Waltham : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 381:8, s. 705-715
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived.RESULTS: On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations.CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).
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7.
  • McKay, James D., et al. (author)
  • A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
  • 2011
  • In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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8.
  • Axfors, Cathrine, et al. (author)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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9.
  • Biermann, Frank, et al. (author)
  • Down to Earth : Contextualizing the Anthropocene
  • 2016
  • In: Global Environmental Change. - : Elsevier BV. - 0959-3780. ; 39, s. 341-350
  • Journal article (peer-reviewed)abstract
    • The ‘Anthropocene’ is now being used as a conceptual frame by different communities and in a variety of contexts to understand the evolving human–environment relationship. However, as we argue in this paper, the notion of an Anthropos, or ‘humanity’, as global, unified ‘geological force’ threatens to mask the diversity and differences in the actual conditions and impacts of humankind, and does not do justice to the diversity of local and regional contexts. For this reason, we interpret in this article the notion of an Anthropocene in a more context-dependent, localized and social understanding. We do this through illustrating examples from four issue domains, selected for their variation in terms of spatial and temporal scale, systems of governance and functional interdependencies: nitrogen cycle distortion (in particular as it relates to food security); ocean acidification; urbanization; and wildfires. Based on this analysis, we systematically address the consequences of the lens of the Anthropocene for the governance of social-ecological systems, focusing on the multi-level, functional and sectoral organization of governance, and possible redefinitions of governance systems and policy domains. We conclude that the notion of the Anthropocene, once seen in light of social inequalities and regional differences, allows for novel analysis of issue-based problems in the context of a global understanding, in both academic and political terms. This makes it a useful concept to help leverage and (re-)focus our efforts in a more innovative and effective way to transition towards sustainability.
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10.
  • Brondizio, Eduardo S., et al. (author)
  • Re-conceptualizing the Anthropocene : A call for collaboration
  • 2016
  • In: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 39, s. 318-327
  • Journal article (peer-reviewed)abstract
    • Since it was first proposed in 2000, the concept of the Anthropocene has evolved in breadth and diversely. The concept encapsulates the new and unprecedented planetary-scale changes resulting from societal transformations and has brought to the fore the social drivers of global change. The concept has revealed tensions between generalized interpretations of humanity's contribution to global change, and interpretations that are historically, politically and culturally situated. It motivates deep ethical questions about the politics and economics of global change, including diverse interpretations of past causes and future possibilities. As such, more than other concepts, the Anthropocene concept has brought front-and center epistemological divides between and within the natural and social sciences, and the humanities. It has also brought new opportunities for collaboration. Here we explore the potential and challenges of the concept to encourage integrative understandings of global change and sustainability. Based on bibliometric analysis and literature review, we discuss the now wide acceptance of the term, its interpretive flexibility, the emerging narratives as well as the debates the concept has inspired. We argue that without truly collaborative and integrative research, many of the critical exchanges around the concept are likely to perpetuate fragmented research agendas and to reinforce disciplinary boundaries. This means appreciating the strengths and limitations of different knowledge domains, approaches and perspectives, with the concept of the Anthropocene serving as a bridge, which we encourage researchers and others to cross. This calls for institutional arrangements that facilitate collaborative research, training, and action, yet also depends on more robust and sustained funding for such activities. To illustrate, we briefly discuss three overarching global change problems where novel types of collaborative research could make a difference: (1) Emergent properties of socioecological systems; (2) Urbanization and resource nexus; and (3) Systemic risks and tipping points. Creative tensions around the Anthropocene concept can help the research community to move toward new conceptual syntheses and integrative action-oriented approaches that are needed to producing useful knowledge commensurable with the challenges of global change and sustainability.
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11.
  • Chen, Kai, et al. (author)
  • Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
  • 2021
  • In: The Lancet Planetary Health. - 2542-5196. ; 5:4, s. e191-e199
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings: Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.
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12.
  • Hartley, Philippa, et al. (author)
  • SKA Science Data Challenge 2: analysis and results
  • 2023
  • In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 1967-1993
  • Journal article (peer-reviewed)abstract
    • The Square Kilometre Array Observatory (SKAO) will explore the radio sky to new depths in order to conduct transformational science. SKAO data products made available to astronomers will be correspondingly large and complex, requiring the application of advanced analysis techniques to extract key science findings. To this end, SKAO is conducting a series of Science Data Challenges, each designed to familiarize the scientific community with SKAO data and to drive the development of new analysis techniques. We present the results from Science Data Challenge 2 (SDC2), which invited participants to find and characterize 233 245 neutral hydrogen (H i) sources in a simulated data product representing a 2000 h SKA-Mid spectral line observation from redshifts 0.25-0.5. Through the generous support of eight international supercomputing facilities, participants were able to undertake the Challenge using dedicated computational resources. Alongside the main challenge, 'reproducibility awards' were made in recognition of those pipelines which demonstrated Open Science best practice. The Challenge saw over 100 participants develop a range of new and existing techniques, with results that highlight the strengths of multidisciplinary and collaborative effort. The winning strategy - which combined predictions from two independent machine learning techniques to yield a 20 per cent improvement in overall performance - underscores one of the main Challenge outcomes: that of method complementarity. It is likely that the combination of methods in a so-called ensemble approach will be key to exploiting very large astronomical data sets.
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13.
  • Masselot, Pierre, et al. (author)
  • Differential mortality risks associated with PM2.5 components : a multi-country, multi-city study
  • 2022
  • In: Epidemiology. - : Wolters Kluwer. - 1044-3983 .- 1531-5487. ; 33:2, s. 167-175
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality.METHODS: We applied a two-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators.RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95%CI: 1.0030-1.0097) to 1.0102 (95%CI:1.0070-1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95%CI: 1.0067-1.0133) to 1.0037 (95%CI: 0.9998- 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk.CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.
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14.
  • Mayes, Maureen D, et al. (author)
  • Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
  • 2014
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
  • Journal article (peer-reviewed)abstract
    • In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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16.
  • Pattaro, Cristian, et al. (author)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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17.
  • Wessel, Jennifer, et al. (author)
  • Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
  • 2015
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Journal article (peer-reviewed)abstract
    • Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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19.
  • Adare, A, et al. (author)
  • Measurement of the relative yields of ψ(2S) to ψ(1S) mesons produced at forward and backward rapidity in p+p, p+Al, p+Au, and He 3 +Au collisions at s NN =200 GeV
  • 2017
  • In: Physical Review C: covering nuclear physics. - 2469-9985. ; 95:3
  • Journal article (peer-reviewed)abstract
    • The PHENIX Collaboration has measured the ratio of the yields of ψ(2S) to ψ(1S) mesons produced in p+p, p+Al, p+Au, and He3+Au collisions at sNN=200 GeV over the forward and backward rapidity intervals 1.2<|y|<2.2. We find that the ratio in p+p collisions is consistent with measurements at other collision energies. In collisions with nuclei, we find that in the forward (p-going or He3-going) direction, the relative yield of ψ(2S) mesons to ψ(1S) mesons is consistent with the value measured in p+p collisions. However, in the backward (nucleus-going) direction, the ψ(2S) meson is preferentially suppressed by a factor of ∼2. This suppression is attributed in some models to the breakup of the weakly bound ψ(2S) meson through final-state interactions with comoving particles, which have a higher density in the nucleus-going direction. These breakup effects may compete with color screening in a deconfined quark-gluon plasma to produce sequential suppression of excited quarkonia states.
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20.
  • Aidala, C., et al. (author)
  • Measurements of B →j /ψ at forward rapidity in p+p collisions at s =510 GeV
  • 2017
  • In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 2470-0010. ; 95:9
  • Journal article (peer-reviewed)abstract
    • We report the first measurement of the fraction of J/ψ mesons coming from B-meson decay (FB→J/ψ) in p+p collisions at s=510 GeV. The measurement is performed using the forward silicon vertex detector and central vertex detector at PHENIX, which provide precise tracking and distance-of-closest-approach determinations, enabling the statistical separation of J/ψ due to B-meson decays from prompt J/ψ. The measured value of FB→J/ψ is 8.1%±2.3%(stat)±1.9%(syst) for J/ψ with transverse momenta 0
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21.
  • Armstrong, Ben, et al. (author)
  • The Role of Humidity in Associations of High Temperature with Mortality : A Multicountry, Multicity Study
  • 2019
  • In: Journal of Environmental Health Perspectives. - : The National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 127:9
  • Journal article (peer-reviewed)abstract
    • Background: There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.Objectives: We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.Methods: In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.Results: Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1–3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.Discussion:The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify.
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22.
  • Boeger, Carsten A., et al. (author)
  • CUBN Is a Gene Locus for Albuminuria
  • 2011
  • In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
  • Journal article (peer-reviewed)abstract
    • Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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23.
  • Botteri, Edoardo, et al. (author)
  • Lifestyle changes in middle age and risk of cancer : evidence from the European Prospective Investigation into Cancer and Nutrition
  • 2024
  • In: European Journal of Epidemiology. - 0393-2990. ; 39:2, s. 147-159
  • Journal article (peer-reviewed)abstract
    • In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.
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24.
  • Cardoso-Moreira, Margarida, et al. (author)
  • Gene expression across mammalian organ development
  • 2019
  • In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 571:7766, s. 505-
  • Journal article (peer-reviewed)abstract
    • The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.
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25.
  • Chen, Gongbo, et al. (author)
  • Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
  • 2021
  • In: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
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26.
  • Chen, Xin, 1980, et al. (author)
  • Improved resource allocation strategy in SU-CoMP network
  • 2011
  • In: The Journal of China Universities of Posts and Telecommunications. - 2210-5123. ; 18:4, s. 7-12
  • Journal article (peer-reviewed)abstract
    • Coordinated Multi-Point transmission and reception (CoMP) for single user, named as SU-CoMP, is considered as an efficient approach tomitigate inter-cell interference in Orthogonal Frequency Division Multiple Access (OFDMA) systems. Two prevalent approaches in SU-CoMP areCoordinated Scheduling (CS) and Joint Processing (JP). Although JP in SU-CoMP has been proved to achieve a great link performanceimprovement for the cell-edge user, efficient Resource Allocation (RA) on the system level is quite needed. However, so far limited work has beendone considering JP, and most existing schemes achieved the improvement of cell-edge performance at cost of the cell-average performancedegradation compared to the single cell RA. In this paper, a two-phase strategy is proposed for SU-CoMP networks. CS and JP are combined toimprove both cell-edge and cell-average performance. Compared to the single cell RA, simulation results demonstrate that, the proposed strategyleads to both higher cell-average and cell-edge throughput.
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27.
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28.
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29.
  • Chen, Yuanying (author)
  • Land-Sea Interactions in the Coastal-Marine System of the Baltic Sea under Hydro-Climatic Variability
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • This thesis investigates a few important component processes for understanding and quantifying eutrophication in the Baltic Sea, that include characterization of nutrient loadings from land, water flow in the sea under changing climate conditions and transport of solutes originating from different locations along the coast. Furthermore, this study aims to improve our understanding on how processes from land (the nutrient loading conditions) and the sea (transport dynamics and water quality) couple to determine the fate of nutrients in the sea and the water quality in a selected localized coastal area, the Himmerfjärden Bay.Comprehensive data are compiled as a basis for numerical simulations. An open source tool for oceanographic studies FVCOM is used to simulate flow and transport processes in the Baltic Sea. Hydrodynamic simulations are verified in terms of temperature, salinity and water level for the year 2005. Results show that most of the investigated Swedish watersheds along the coastline are dominated by subsurface legacy sources, the loads of which are positively and linearly correlated with river discharges. Moreover, subsurface legacy sources are less likely to decrease over time compared with the current surface sources. The Baltic Sea has a stable flow structure considering flux directions between basins, while the flux magnitudes between basins are mainly determined by different wind conditions. The spreading patterns in the sea with solute released from different coastal areas are similar when the released amounts are comparable, even though different cases have different source input and water flow conditions. The overall spreading patterns in the sea are generally dominated by the total mass of released solute. Local transport dynamics and patterns around the coast differ greatly for different cases and are determined by the local flow conditions. Different water quality indicators are influenced by different land-based or sea-based measures for water quality improvement. The dry-cold hydro-climatic condition is the most favorable for improving the water quality and elevating the ecological status in the Himmerfjärden Bay.Based on this investigation, varying hydro-climatic factors impose important influence on the different component processes of nutrient loading from land to the sea. For example, the change of river discharges from land in the future would influence the total load into the sea from subsurface legacy sources, and finally influence the general spreading patterns of nutrients in the sea. The change of wind conditions would affect the flow and transport dynamics at local scale and flow fluxes magnitudes between marine basins at the sea scale. Change towards a dry-cold condition would be beneficial for the water quality and lead to improvement of coastal water quality, while the change towards a wet-warm condition will be generally unfavorable for improving the water quality. Clearly more comprehensive studies are needed based on the component processes considered in this thesis, for mapping water quality and eutrophication long-term trends in the Baltic Sea with confidence that is sufficient for effective mitigation measures and policies. 
  •  
30.
  • Chen, Yuanying, et al. (author)
  • Nutrient source attribution : Quantitative typology distinction of active and legacy source contributions to waterborne loads
  • 2021
  • In: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 35:7
  • Journal article (peer-reviewed)abstract
    • Distinction between active and legacy sources of nutrients is needed for effective reduction of waterborne nutrient loads and associated eutrophication. This study quantifies main typological differences in nutrient load behaviour versus water discharge for active and legacy sources. This quantitative typology is used for source attribution based on monitoring data for water discharge and concentrations of total nitrogen (TN) and total phosphorous (TP) from 37 catchments draining into the Baltic Sea along the coastline of Sweden over the period 2003-2013. Results indicate dominant legacy source contributions to the monitored loads of TN and TP in most (33 of the total 37) study catchments. Dominant active sources are indicated in 1 catchment for TN, and mixed sources are indicated in 3 catchments for TN, and 4 catchments for TP. The TN and TP concentration contributions are quantified to be overall higher from the legacy than the active sources. Legacy concentrations also correlate well with key indicators of human activity in the catchments, agricultural land share for TN (R-2 = 0.65) and population density for TP (R-2 = 0.56). Legacy-dominated nutrient concentrations also change more slowly than in catchments with dominant active or mixed sources. Various data-based results and indications converge in indicating legacy source contributions as largely dominant, mainly anthropogenic, and with near-zero average change trends in the present study of catchments draining into the Baltic Sea along the coastline of Sweden, as in other parts of the world. These convergent indications emphasize needs to identify and map the different types of sources in each catchment, and differentiate strategies and measures to target each source type for possible achievement of shorter- and longer-term goals of water quality improvement.
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31.
  • Dimitrova, Radosveta, et al. (author)
  • Positive Youth Development in Bulgaria, Italy, Norway and Romania : Testing the Factorial Structure and Measurement Invariance of the 5Cs Model
  • 2021
  • In: Handbook of Positive Youth Development. - Cham : Springer Nature. - 9783030702618 - 9783030702649 - 9783030702625 ; , s. 267-281
  • Book chapter (peer-reviewed)abstract
    • This chapter applies the 5Cs model of PYD comprising competence, confidence, character, connection and caring among 1403 youth (M = 18.91 years) in Bulgaria (n = 196), Italy (n = 354), Norway (n = 564) and Romania (n = 289). These countries offer a novel and unique context to apply PYD as related comparative work with youth samples is rare across Eastern (Bulgaria and Romania), Southern (Italy) and Northern Europe (Norway). Further, Bulgaria and Romania are emerging nations following the collapse of the communism in late 1980s in contrast to Italy being a traditionally patriarchal country and social equity driven Norway. The chapter presents an empirical example that evaluates the factorial structure and measurement invariance (i.e., the degree to which the scale measurements conducted across different populations exhibit similar psychometric properties) of the 5Cs model. The results of confirmatory factor analysis (CFA) supported the 5Cs as well as a second-order 5Cs of PYD factors, suggesting that the 5Cs model is a reliable and valid measurement tool in the four European countries investigated. The chapter concludes with an exploration of relevant implications for research, policy, and practice.
  •  
32.
  • Domingo, Nina G.G., et al. (author)
  • Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement
  • 2024
  • In: One Earth. - : Elsevier. - 2590-3330 .- 2590-3322. ; 7:2, s. 325-335
  • Journal article (peer-reviewed)abstract
    • Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.
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33.
  • Gardner, Michael, et al. (author)
  • Gender and telomere length : Systematic review and meta-analysis
  • 2014
  • In: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
  • Research review (peer-reviewed)abstract
    • Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
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34.
  • Gaulton, Kyle J, et al. (author)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Journal article (peer-reviewed)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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35.
  • Gaziano, Liam, et al. (author)
  • Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
  • 2022
  • In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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36.
  • Guo, Yuming, et al. (author)
  • Quantifying excess deaths related to heatwaves under climate change scenarios : A multicountry time series modelling study
  • 2018
  • In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 15:7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited.METHODS AND FINDINGS: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave-mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971-2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031-2080 compared with 1971-2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections.CONCLUSIONS: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change.
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37.
  • Head, Ashley R., et al. (author)
  • In situ characterization of the deposition of anatase TiO2 on rutile TiO2(110)
  • 2018
  • In: Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films. - : American Vacuum Society. - 0734-2101 .- 1520-8559. ; 36:2
  • Journal article (peer-reviewed)abstract
    • Growing additional TiO2 thin films on TiO2 supstrates in ultrahigh vacuum (UHV)-compatible chambers have many applications for sample preparation, such as smoothing surface morphologies, templating, and covering impurities. However, there has been little study into how to control the morphology of TiO2 films deposited onto TiO2 supstrates, especially using atomic layer deposition (ALD) precursors. Here, the authors show the growth of a TiO2 film on a rutile TiO2(110) surface using titanium tetraisopropoxide (TTIP) and water as the precursors at pressures well below those used in common ALD reactors. X-ray absorption spectroscopy suggests that the relatively low sample temperature (175 °C) results in an anatase film despite the rutile template of the supstrate. Using ambient pressure x-ray photoelectron spectroscopy, the adsorption of TTIP was found to be self-limiting, even at room temperature. No molecular water was found to adsorb on the surface. The deposited thickness suggests that an alternate chemical vapor deposition growth mechanism may be dominating the growth process. This study highlights the possibility that metal oxide film deposition from molecular precursors is an option for sample preparations in common UHV-compatible chambers.
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38.
  • Henrysson, Josefin, et al. (author)
  • Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure.
  • 2023
  • In: ESC heart failure. - : Wiley. - 2055-5822. ; 10:1, s. 66-79
  • Journal article (peer-reviewed)abstract
    • To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings.A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6months of up-titration.Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P<0.0001), had lower EF (P=0.022), had higher NTproBNP (P=0.017), had lower eGFR (P=0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P<0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6months of up-titration of GDMT (P<0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P<0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively.Hyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.
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39.
  • Hochgerner, Mathias, et al. (author)
  • BMPR1a Is Required for the Optimal TGFβ1-Dependent CD207+ Langerhans Cell Differentiation and Limits Skin Inflammation through CD11c+ Cells
  • 2022
  • In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X. ; 142:9, s. 3-2454
  • Journal article (peer-reviewed)abstract
    • The cytokine TGFβ1 induces epidermal Langerhans cell (LC) differentiation from human precursors, an effect mediated through BMPR1a/ALK3 signaling, as revealed from ectopic expression and receptor inhibition studies. Whether TGFβ1‒BMPR1a signaling is required for LC differentiation in vivo remained incompletely understood. We found that TGFβ1-deficient mice show defective perinatal expansion and differentiation of LCs. LCs can be identified within the normal healthy human epidermis by anti-BMPR1a immunohistology staining. Deletion of BMPR1a in all (vav+) hematopoietic cells revealed that BMPR1a is required for the efficient TGFβ1-dependent generation of CD207+ LC-like cells from CD11c+ intermediates in vitro. Similarly, BMPR1a was required for the optimal induction of CD207 by preformed major histocompatibility complex II‒positive epidermal resident LC precursors in the steady state. BMPR1a expression is strongly upregulated in epidermal cells in psoriatic lesions, and BMPR1aΔCD11c mice showed a defect in the resolution phase of allergic and psoriatic skin inflammation. Moreover, whereas LCs from these mice expressed CD207, BMPR1a counteracted LC activation and migration from skin explant cultures. Therefore, TGFβ1‒BMPR1a signaling seems to be required for the efficient induction of CD207 during LC differentiation in the steady state, and bone marrow‒derived lesional CD11c+ cells may limit established skin inflammation through enhanced BMPR1a signaling.
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40.
  • Hung, Rayjean J, et al. (author)
  • A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
  • 2008
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
  • Journal article (peer-reviewed)abstract
    • Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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41.
  • Juffermans, Joe F., et al. (author)
  • Multicenter Consistency Assessment of Valvular Flow Quantification With Automated Valve Tracking in 4D Flow CMR
  • 2021
  • In: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1936-878X. ; 14:7, s. 1354-1366
  • Journal article (peer-reviewed)abstract
    • Objectives: This study determined: 1) the interobserver agreement; 2) valvular flow variation; and 3) which variables independently predicted the variation of valvular flow quantification from 4-dimensional (4D) flow cardiac magnetic resonance (CMR) with automated retrospective valve tracking at multiple sites. Background: Automated retrospective valve tracking in 4D flow CMR allows consistent assessment of valvular flow through all intracardiac valves. However, due to the variance of CMR scanners and protocols, it remains uncertain if the published consistency holds for other clinical centers. Methods: Seven sites each retrospectively or prospectively selected 20 subjects who underwent whole heart 4D flow CMR (64 patients and 76 healthy volunteers; aged 32 years [range 24 to 48 years], 47% men, from 2014 to 2020), which was acquired with locally used CMR scanners (scanners from 3 vendors; 2 1.5-T and 5 3-T scanners) and protocols. Automated retrospective valve tracking was locally performed at each site to quantify the valvular flow and repeated by 1 central site. Interobserver agreement was evaluated with intraclass correlation coefficients (ICCs). Net forward volume (NFV) consistency among the valves was evaluated by calculating the intervalvular variation. Multiple regression analysis was performed to assess the predicting effect of local CMR scanners and protocols on the intervalvular inconsistency. Results: The interobserver analysis demonstrated strong-to-excellent agreement for NFV (ICC: 0.85 to 0.96) and moderate-to-excellent agreement for regurgitation fraction (ICC: 0.53 to 0.97) for all sites and valves. In addition, all observers established a low intervalvular variation (≤10.5%) in their analysis. The availability of 2 cine images per valve for valve tracking compared with 1 cine image predicted a decreasing variation in NFV among the 4 valves (beta = −1.3; p = 0.01). Conclusions: Independently of locally used CMR scanners and protocols, valvular flow quantification can be performed consistently with automated retrospective valve tracking in 4D flow CMR.
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42.
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43.
  • Lakshmana, Tilak Rajesh, 1980, et al. (author)
  • Partial joint processing for frequency selective channels
  • 2010
  • In: IEEE Vehicular Technology Conference. - 1550-2252. - 9781424435746
  • Conference paper (peer-reviewed)abstract
    • In this paper, we consider a static cluster of base stations where joint processing is allowed in the downlink. The partial joint processing scheme is a user-centric approach where subclusters or active sets of base stations are dynamically defined for each user in the cluster. In frequency selective channels, the definition of the subclusters or active set thresholding of base stations can be frequency adaptive (per resource block) or non-adaptive (averaged over all the resource blocks). Frequency adaptive thresholding improves the average sum-rate of the cluster, but at the cost of an increased user data interbase information exchange with respect to the non-adaptive frequency thresholding case. On the other hand, the channel state information available at the transmitter side to design the beamforming matrix is very limited and rank deficiency problems arise for low values of active set thresholding and users located close to the base station. To solve this problem, an algorithm is proposed that defines a cooperation area over the cluster where the partial joint processing scheme can be performed, frequency adaptive or non-adaptive, for a given active set threshold value.
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44.
  • Lee, Jae Young, et al. (author)
  • Predicted temperature-increase-induced global health burden and its regional variability
  • 2019
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 131
  • Journal article (peer-reviewed)abstract
    • An increase in the global health burden of temperature was projected for 459 locations in 28 countries worldwide under four representative concentration pathway scenarios until 2099. We determined that the amount of temperature increase for each 100 ppm increase in global CO2 concentrations is nearly constant, regardless of climate scenarios. The overall average temperature increase during 2010-2099 is largest in Canada (1.16 °C/100 ppm) and Finland (1.14 °C/100 ppm), while it is smallest in Ireland (0.62 °C/100 ppm) and Argentina (0.63 °C/100 ppm). In addition, for each 1 °C temperature increase, the amount of excess mortality is increased largely in tropical countries such as Vietnam (10.34%p/°C) and the Philippines (8.18%p/°C), while it is decreased in Ireland (-0.92%p/°C) and Australia (-0.32%p/°C). To understand the regional variability in temperature increase and mortality, we performed a regression-based modeling. We observed that the projected temperature increase is highly correlated with daily temperature range at the location and vulnerability to temperature increase is affected by health expenditure, and proportions of obese and elderly population.
  •  
45.
  • Li, Jingya, 1986, et al. (author)
  • Downlink Radio Resource Allocation for Coordinated Cellular OFDMA Networks
  • 2010
  • In: IEICE Transactions on Communications. - 1745-1345. ; E93B:12, s. 3480-3488
  • Journal article (peer-reviewed)abstract
    • Base station coordination is considered as a promising technique to mitigate inter-cell interference and improve the cell-edge performance in cellular orthogonal frequency division multiple-access (OFDMA) networks. The problem to design an efficient radio resource allocation scheme for coordinated cellular OFDMA networks incorporating base station coordination has been only partially investigated. In this contribution, a novel radio resource allocation algorithm with universal frequency reuse is proposed to support base station coordinated transmission. Firstly, with the assumption of global coordination between all base station sectors in the network, a coordinated subchannel assignment algorithm is proposed. Then, by dividing the entire network into a number of disjoint coordinated clusters of base station sectors, a reduced-feedback algorithm for subchannel assignment is proposed for practical use. The utility function based on the user average throughput is used to balance the efficiency and fairness of wireless resource allocation. System level simulation results demonstrate that the reduced-feedback subchannel assignment algorithm significantly improves the cell-edge average throughput and the fairness index of users in the network, with acceptable degradation of cell-average performance.
  •  
46.
  • Li, Jingya, 1986, et al. (author)
  • Joint Scheduling and Power Control in Coordinated Multi-Point Clusters
  • 2011
  • In: IEEE Vehicular Technology Conference. - 1550-2252. - 9781424483273 ; , s. Art. no. 6092837-
  • Conference paper (peer-reviewed)abstract
    • In this paper, we address the problem of designing a joint scheduling and power control algorithm in a downlink coordinated multi-point (CoMP) cluster supporting CoMP joint transmission. The objective is to maximize the cell-edge throughput under per-point power constraints. By an analytical derivation, binary power control is proved to be the optimal solution for any given selected user group. Utilizing this analytical result, a centralized and a semi-distributed version of joint user selection and power control algorithms are proposed. Compared to algorithms without considering joint transmission and algorithms without considering power control, simulation results show that the proposed algorithms achieve a good trade-off between joint transmission and interference coordination, which helps to improve the cell-edge performance.
  •  
47.
  • Li, Jingya, 1986, et al. (author)
  • Resource allocation for OFDMA systems with multi-cell joint transmission
  • 2012
  • In: 2012 IEEE 13th International Workshop on Signal Processing Advances in Wireless Communications, SPAWC 2012. Cesme, 17-20 June 2012. - 9781467309714 ; , s. 179-183
  • Conference paper (peer-reviewed)abstract
    • This paper considers the downlink resource allocation of a coordinated multi-cell cluster in OFDMA systems with universal frequency reuse. Multi-cell joint transmission is considered via zero-forcing precoding. Furthermore, joint optimization of the user selection and power allocation across multiple subchannels and multiple cells is studied. The objective is to maximize the weighted sum rate under per-base-station power constraints. Based on general duality theory, two iterative resource allocation algorithms are proposed and compared with the optimal solution, which requires an exhaustive search of all possible combinations of users over all subchannels. Simulation results show that the two proposed algorithms achieve a performance very close to the optimal, with much lower computational complexity. In addition, we show that joint user set selection across multiple subchannels significantly improves the system performance in terms of the weighted sum rate.
  •  
48.
  • Liu, Cong, et al. (author)
  • Coarse particulate air pollution and daily mortality : a global study in 205 cities
  • 2022
  • In: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 206:8, s. 999-1007
  • Journal article (peer-reviewed)abstract
    • RATIONALE: The associations between ambient coarse particulate matter (PM2.5-10) and daily mortality is not fully understood at a global scale.OBJECTIVES: To evaluate the short-term associations between PM2.5-10 and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide.METHODS: We collected daily mortality (total, cardiovascular, respiratory) and air pollution data from 205 cities in 20 countries/regions. Concentrations of PM2.5-10 were computed as the difference between inhalable and fine particulate matter. A two-stage time-series analytic approach was applied, with over-dispersed generalized linear models and multilevel meta-analysis. We fitted two-pollutant models to test the independent effect of PM2.5-10 from co-pollutants (fine particulate matter, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide). Exposure-response relationship curves were pooled and regional analyses were conducted.MEASUREMENTS AND MAIN RESULTS: A 10 μg/m3 increase in PM2.5-10 concentration on lag 0-1 day was associated with increments of 0.51% (95% confidence interval [CI]: 0.18%, 0.84%), 0.43% (95%CI: 0.15%, 0.71%) and 0.41% (95%CI: 0.06%, 0.77%) in total, cardiovascular, and respiratory mortality, respectively. The associations varied by country and region. These associations were robust to adjustment by all co-pollutants in two-pollutant models, especially for PM2.5. The exposure-response curves for total, cardiovascular, and respiratory mortality were positive, with steeper slopes at lower exposure ranges and without discernible thresholds.CONCLUSIONS: This study provides novel global evidence on the robust and independent associations between short-term exposure to ambient PM2.5-10 and total, cardiovascular and respiratory mortality, suggesting the need to establish a unique guideline or regulatory limit for daily concentrations of PM2.5-10.
  •  
49.
  • Machuca, Carmen Mas, et al. (author)
  • Cost dependency on protection of optical access networks for dense urban areas
  • 2011
  • In: International Conference on Transparent Optical Networks. - Stockholm. - 9781457708800
  • Conference paper (peer-reviewed)abstract
    • Along with the competition on the telecom market and high reliability requirements of the emerging services operators and service providers are forced to increase connection availability of all users supported by their network. For economical reason most of the investment related to providing protection resources has been so far limited to the core and metro networks. On the other hand, increasing requirement for interrupted access to the network services is moving the focus for protection towards the end user. However, the cost to offer protection in access networks is a limiting factor. In this paper, a protection scenario for passive optical network in dense urban area is proposed. The cost of this protection approach is analysed, and furthermore, the key cost drivers are identified. It is shown that the failure rates of fiber and Optical Network Units (ONUs) and basic salary of technicians are the main cost drivers for the considered dense urban area.
  •  
50.
  • Machuca, Carmen M., et al. (author)
  • Impact of protection to capital and operational expenditures of optical access networks
  • 2011
  • In: Photonische Netze - 12. ITG-Fachtagung. - : VDE Verlag GmbH. ; , s. 72-77
  • Conference paper (peer-reviewed)abstract
    • Reliability is becoming a crucial issue for service providers, operators and users in optical access networks. The increase of network capacity and the importance of reducing service interruption times, force network operators to implement protection mechanisms in optical access networks. However, so far providing backup resources in access networks has been considered too expensive. In order to assess the impact of protection on capital and operational expenditures, the evaluation needs to study the impact to aspects such as the required infrastructure and equipment costs, failure reparation costs, and expected service interruption time. This work deals with the cost and reliability evaluation of time-division-multiplexing (TDM) and wavelength-division-multiplexing (WDM) passive optical networks (PONs). Three strategies to offer protection are evaluated: 1) provide protection in the access network directly from the greenfield, 2) invest initially on an unprotected architecture keeping in mind a future upgrade with protection resources, and 3) roll out an unprotected access network and if needed in the future, invest in deployment of protection resources. The impact of these strategies on the overall cost is studied.
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