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Sökning: WFRF:(O'Neill T W) > (2005-2009)

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1.
  • Schael, S, et al. (författare)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Forskningsöversikt (refereegranskat)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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  • Ng, M Y M, et al. (författare)
  • Meta-analysis of 32 genome-wide linkage studies of schizophrenia
  • 2009
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
  • Tidskriftsartikel (refereegranskat)abstract
    • A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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  • 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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6.
  • Macfarlane, G. J., et al. (författare)
  • Investigating the determinants of international differences in the prevalence of chronic widespread pain: evidence from the European Male Ageing Study
  • 2009
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:5, s. 690-695
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine whether among middle-aged and elderly men there is evidence of international differences in the prevalence of chronic widespread pain (CWP) and whether any such differences could be explained by psychological, psychosocial factors or differences in physical health status. Methods: The European Male Ageing Study (EMAS) sampled from population registers in cities ( centres) of eight European countries. Each centre recruited an age-stratified sample of men aged 40-79 years. Information on pain was collected by questionnaire and subjects were classified according to whether they satisfied the American College of Rheumatology definition of CWP. Information was collected on social status, mental health, recent life events and co-morbidities. Results: Across all centres 3963 subjects completed a study questionnaire, with participation rates ranging from 24% in Hungary to 72% in Estonia. There were significant differences in prevalence: between 5% and 7% in centres in Italy, England, Belgium and Sweden, 9-15% in centres in Spain, Poland and Hungary and 15% in Estonia. There were strong relationships between poor mental health, adverse recent life events, co-morbidities and CWP. Adjustment for these factors explained between half and all of the excess risk in the eastern European centres: the excess risk in Poland was explained ( odds ratio ( OR) 1.1, 95% CI 0.9 to 1.2) but there remained excess risk in Hungary ( OR 1.6, 95% CI 1.4 to 1.8) and Estonia ( OR 2.6, 95% CI 2.2 to 2.9). Conclusions: This study is the first directly to compare the occurrence of CWP internationally. There is an excess prevalence in countries of eastern Europe and this excess is associated with adverse psychosocial factors as well as poorer psychological and physical health.
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8.
  • Kaptoge, S., et al. (författare)
  • Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study
  • 2006
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 17:9, s. 1369-1381
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. Methods: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. Results: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). Conclusion: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.
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9.
  • Huhtaniemi, Ilpo T, et al. (författare)
  • Increased Estrogen Rather Than Decreased Androgen Action Is Associated with Longer Androgen Receptor CAG Repeats.
  • 2009
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 277-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The individual variability in the waning androgenic-anabolic functions of aging men may be influenced by the CAG repeat polymorphism in exon 1 of the androgen receptor (AR), affecting androgen sensitivity. However, findings on its phenotypic effects are inconclusive. Objective: To investigate the relationships between health status, various reproductive hormones and the AR CAG repeat length. Design: A multi-national prospective cohort observational study - cross-sectional baseline data. Setting: Population survey of community-dwelling men. Participants: Men (40-79-yr-old; n=3,369) randomly recruited from centers in eight European countries; CAG repeat analysis was performed in 2,878 men. Main outcome measures: The correlations of the CAG repeat length with selected endocrine, metabolic and phenotypic parameters related to aging and sex hormone action. Results: Only minor differences were found in CAG repeat lengths between the eight European countries. They showed significant positive association with total, free and bioavailable levels of testosterone (T) and estradiol (E2). FSH but not LH correlated inversely with CAG repeat length. Significant associations were found with bone ultrasound parameters at the calcaneus. Negative correlation was found with triglycerides, but not with other blood lipids, or with anthropometry, blood pressure, hemoglobin, insulin sensitivity, or sexual and prostatic functions. Conclusions: The AR CAG repeat length correlates significantly with serum T and E2 of aging men. Weaker transcriptional activity of the AR with longer CAG-encoded polyglutamine repeats appears to be totally or near-totally compensated for by higher T levels. The residual phenotypic correlations may reflect differences in estrogen levels/actions following aromatization of the higher T levels.
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10.
  • Lee, David M., et al. (författare)
  • Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men
  • 2009
  • Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:7, s. 722-729
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although there is evidence that vitamin D inadequacy may be linked to adverse cognitive outcomes, results from studies on this topic have been inconsistent. The aim of this trial was to examine the association between 25-hydroxyvitamin D (25(OH) D) levels and cognitive performance in middle-aged and older European men. Methods: This population-based cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study. Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). Serum 25(OH) D levels were measured by radioimmunoassay. Additional assessments included measurement of physical activity, functional performance and mood/depression. Associations between cognitive function and 25(OH) D levels were explored using locally weighted and linear regression models. Results: In total, 3,133 men (mean (+/- SD) age 60 +/- 11 years) were included in the analysis. The mean (+/- SD) 25(OH) D concentration was 63 +/- 31 nmol/l. In age-adjusted linear regressions, high levels of 25(OH) D were associated with high scores on the copy component of the ROCF test (beta per 10 nmol/l = 0.096; 95% CI 0.049 to 0.144), the CTRM test (beta per 10 nmol/l= 0.075; 95% CI 0.026 to 0.124) and the DSST (beta per 10 nmol/l = 0.318; 95% CI 0.235 to 0.401). After adjusting for additional confounders, 25(OH) D levels were associated with only score on the DSST (beta per 10 nmol/l = 0.152; 95% CI 0.051 to 0.253). Locally weighted and spline regressions suggested the relationship between 25(OH) D concentration and cognitive function was most pronounced at 25(OH) D concentrations below 35 nmol/l. Conclusion: In this study, lower 25(OH) D levels were associated with poorer performance on the DSST. Further research is warranted to determine whether vitamin D sufficiency might have a role in preserving cognitive function in older adults.
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