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Sökning: WFRF:(Gardiner Stephen)

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1.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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2.
  • Lundgren, Markus, et al. (författare)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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3.
  • Zheng, Hou-Feng, et al. (författare)
  • Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
  • Tidskriftsartikel (refereegranskat)abstract
    • The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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4.
  • Brandstedt, Eric, et al. (författare)
  • The Just Savings Principle
  • 2021
  • Ingår i: The Oxford Handbook of Intergenerational Ethics. - : Oxford University Press.
  • Bokkapitel (refereegranskat)abstract
    • This chapter situates John Rawls’ just savings principle in a discussion about how much a nation-state should save. The main question addressed is whether this principle is a viable alternative to the dominant utilitarian theory of optimal growth. Rawls certainly gives savings a different aim (i.e., to create and maintain just institutions) and introduces additional permissibility conditions on reaching this goal (i.e., the necessary burdens should be fairly shared between generations). He thereby gives rise to the field of research now known as intergenerational justice. To assess the relative merits of the just savings principle, however, more details are needed; and this chapter aims to supply some of them. First, the principle of just savings is given a more determinate form whereby it is understood as a two-stage combination of a priority principle at the stage of institutional development and a difference principle at the maintenance stage. Second, some of its practical bearings are explored (i.e., its implications for real-life savings decisions). Among other things, the idea that the principle leads to a steady-state economy is problematized, and its relevance to concrete problems, such as climate change and the design of pension schemes, is assessed.
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5.
  • Gardiner, Stephen J., et al. (författare)
  • A characterization of annular domains by quadrature identities
  • 2019
  • Ingår i: Bulletin of the London Mathematical Society. - : WILEY. - 0024-6093 .- 1469-2120. ; 51:3, s. 436-442
  • Tidskriftsartikel (refereegranskat)abstract
    • This note verifies a conjecture of Armitage and Goldstein that annular domains may be characterized as quadrature domains for harmonic functions with respect to a uniformly distributed measure on a sphere.
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6.
  • Gardiner, Stephen J., et al. (författare)
  • Analytic content and the isoperimetric inequality in higher dimensions
  • 2018
  • Ingår i: Journal of Functional Analysis. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0022-1236 .- 1096-0783. ; 275:9, s. 2284-2298
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper establishes a conjecture of Gustafsson and Khavinson, which relates the analytic content of a smoothly bounded domain in R-N to the classical isoperimetric inequality. The proof is based on a novel combination of partial balayage with optimal transport theory. (C) 2018 Elsevier Inc. All rights reserved.
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7.
  • Gardiner, Stephen J., et al. (författare)
  • Boundary points of angular type form a set of zero harmonic measure
  • 2022
  • Ingår i: Annales Fennici Mathematici. - : SUOMALAINEN TIEDEAKATEMIA. - 2737-0690 .- 2737-114X. ; 47:2, s. 641-644
  • Tidskriftsartikel (refereegranskat)abstract
    • This note addresses a problem of Dvoretzky concerning the harmonic measure of the set of boundary points of a domain in Euclidean space that are of angular type.
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8.
  • Gardiner, Stephen J., et al. (författare)
  • Isoperimetric Inequalities for Bergman Analytic Content
  • 2020
  • Ingår i: Indiana University Mathematics Journal. - : INDIANA UNIV MATH JOURNAL. - 0022-2518 .- 1943-5258. ; 69:4, s. 1231-1249
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bergman p-analytic content (1 <= p < infinity) of a planar domain Omega measures the L-p (Omega)-distance between (z) over bar and the Bergman space A(p) (Omega) of holomorphic functions. It has a natural analogue in all dimensions which is formulated in terms of harmonic vector fields. This paper investigates isoperimetric inequalities for Bergman p-analytic content in terms of the St. Venant functional for torsional rigidity, and addresses the cases of equality with the upper and lower bounds.
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9.
  • Gardiner, Stephen J., et al. (författare)
  • On a conjecture of Gustafsson and Lin concerning Laplacian growth
  • 2022
  • Ingår i: Analysis and Mathematical Physics. - : Springer Basel AG. - 1664-2368 .- 1664-235X. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gustafsson and Lin recently published a significant result concerning Laplacian growth problems that start from a simply connected planar domain. However, the validity of their result depends on the verification of a particular conjecture. This paper provides the missing proof.
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10.
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