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1.
  • Aad, G., et al. (author)
  • 2012
  • swepub:Mat__t (peer-reviewed)
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2.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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3.
  • Aad, G., et al. (author)
  • 2010
  • swepub:Mat__t
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4.
  • Aad, G., et al. (author)
  • Readiness of the ATLAS Tile Calorimeter for LHC collisions
  • 2010
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:4, s. 1193-1236
  • Journal article (peer-reviewed)abstract
    • The Tile hadronic calorimeter of the ATLAS detector has undergone extensive testing in the experimental hall since its installation in late 2005. The readout, control and calibration systems have been fully operational since 2007 and the detector has successfully collected data from the LHC single beams in 2008 and first collisions in 2009. This paper gives an overview of the Tile Calorimeter performance as measured using random triggers, calibration data, data from cosmic ray muons and single beam data. The detector operation status, noise characteristics and performance of the calibration systems are presented, as well as the validation of the timing and energy calibration carried out with minimum ionising cosmic ray muons data. The calibration systems' precision is well below the design value of 1%. The determination of the global energy scale was performed with an uncertainty of 4%.
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5.
  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)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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6.
  • Schael, S., et al. (author)
  • Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
  • 2013
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
  • Research review (peer-reviewed)abstract
    • Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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8.
  • Abat, E., et al. (author)
  • Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
  • 2009
  • In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
  • Journal article (peer-reviewed)abstract
    • A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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9.
  • Abat, E., et al. (author)
  • The ATLAS TRT end-cap detectors
  • 2008
  • In: Journal of Instrumentation. - 1748-0221. ; 3
  • Journal article (peer-reviewed)abstract
    • The ATLAS TRT end-cap is a tracking drift chamber using 245,760 individual tubular drift tubes. It is a part of the TRT tracker which consist of the barrel and two end-caps. The TRT end-caps cover the forward and backward pseudo-rapidity region 1.0 < vertical bar eta vertical bar < 2.0, while the TRT barrel central eta region vertical bar eta vertical bar < 1.0. The TRT system provides a combination of continuous tracking with many measurements in individual drift tubes ( or straws) and of electron identification based on transition radiation from fibers or foils interleaved between the straws themselves. Along with other two sub-systems, namely the Pixel detector and Semi Conductor Tracker (SCT), the TRT constitutes the ATLAS Inner Detector. This paper describes the recently completed and installed TRT end-cap detectors, their design, assembly, integration and the acceptance tests applied during the construction.
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  • Medina-Gomez, C., et al. (author)
  • Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects
  • 2018
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 102:1, s. 88-102
  • Journal article (peer-reviewed)abstract
    • Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course. © 2017 American Society of Human Genetics
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  • Vogel, N, et al. (author)
  • Exposure to Phthalates in European Children, Adolescents and Adults since 2005: A Harmonized Approach Based on Existing HBM Data in the HBM4EU Initiative
  • 2023
  • In: Toxics. - : MDPI AG. - 2305-6304. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Phthalates are mainly used as plasticizers and are associated inter alia with adverse effects on reproductive functions. While more and more national programs in Europe have started monitoring internal exposure to phthalates and its substitute 1,2-Cyclohexanedicarboxylic acid (DINCH), the comparability of results from such existing human biomonitoring (HBM) studies across Europe is challenging. They differ widely in time periods, study samples, degree of geographical coverage, design, analytical methodology, biomarker selection, and analytical quality assurance level. The HBM4EU initiative has gathered existing HBM data of 29 studies from participating countries, covering all European regions and Israel. The data were prepared and aggregated by a harmonized procedure with the aim to describe—as comparably as possible—the EU-wide general population’s internal exposure to phthalates from the years 2005 to 2019. Most data were available from Northern (up to 6 studies and up to 13 time points), Western (11; 19), and Eastern Europe (9; 12), e.g., allowing for the investigation of time patterns. While the bandwidth of exposure was generally similar, we still observed regional differences for Butyl benzyl phthalate (BBzP), Di(2-ethylhexyl) phthalate (DEHP), Di-isononyl phthalate (DiNP), and Di-isobutyl phthalate (DiBP) with pronounced decreases over time in Northern and Western Europe, and to a lesser degree in Eastern Europe. Differences between age groups were visible for Di-n-butyl phthalate (DnBP), where children (3 to 5-year olds and 6 to 11-year olds) had lower urinary concentrations than adolescents (12 to 19-year-olds), who in turn had lower urinary concentrations than adults (20 to 39-year-olds). This study is a step towards making internal exposures to phthalates comparable across countries, although standardized data were not available, targeting European data sets harmonized with respect to data formatting and calculation of aggregated data (such as developed within HBM4EU), and highlights further suggestions for improved harmonization in future studies.
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  • Medina-Gomez, C., et al. (author)
  • Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis
  • 2023
  • In: Communications Biology. - 2399-3642. ; 6:1
  • Journal article (peer-reviewed)abstract
    • Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n similar to 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.
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  • Aad, G., et al. (author)
  • The ATLAS Experiment at the CERN Large Hadron Collider
  • 2008
  • In: Journal of Instrumentation. - 1748-0221. ; 3:S08003
  • Research review (peer-reviewed)abstract
    • The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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  • Falci, S, et al. (author)
  • Obliteration of a posttraumatic spinal cord cyst with solid human embryonic spinal cord grafts : first clinical attempt.
  • 1997
  • In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 14, s. 875-
  • Journal article (peer-reviewed)abstract
    • Cystic lesions of the spinal cord (syringomyelia) may occur after spinal cord injury. Posttraumatic syringomyelia may result in a myelopathy causing symptoms of sensory and motor loss, as well as worsening spasticity, pain, hyperhidrosis, and autonomic dysreflexia. Shunting of the cyst cavity along with untethering of the scarred spinal cord is widely accepted as the treatment of choice. However, the long-term stabilization of the progressive myelopathy caused by a posttraumatic cyst is suboptimal because of arachnoidal rescarring, shunt tube blockage, and cyst reexpansion. A new neurosurgical strategy to overcome the complication of cyst reexpansion was designed. Experimental studies have shown the successful use of embryonic spinal cord grafts, including human grafts, to obliterate induced spinal cord cavities in rats. The authors report the first use of solid human embryonic spinal cord grafts to successfully obliterate 6 cm of a large cyst cavity in a patient becoming myelopathic from a posttraumatic cyst. The grafts are well visualized by MRI to the 7-month postoperative follow-up and cyst obliteration is seen in the region where the grafts were placed.
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  • Akesson, E, et al. (author)
  • A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis
  • 2002
  • In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 3:5, s. 279-285
  • Journal article (peer-reviewed)abstract
    • Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.
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  • Harbo, HF, et al. (author)
  • Two genome-wide linkage disequilibrium screens in Scandinavian multiple sclerosis patients
  • 2003
  • In: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 143:1-2, s. 101-106
  • Journal article (peer-reviewed)abstract
    • We report the first two genome-wide screens for linkage disequilibrium between putative multiple sclerosis (MS) susceptibility genes and genetic markers performed in the genetically homogenous Scandinavian population, using 6000 microsatellite markers and DNA pools of approximately 200 MS cases and 200 controls in each screen. Usable data were achieved from the same 3331 markers in both screens. Nine markers from eight genomic regions (1p33, 3q13, 6p21, 6q14, 7p22, 9p21, 9q21 and Xq22) were identified as potentially associated with MS in both screens. (C) 2003 Elsevier B.V. All rights reserved.
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25.
  • Mingardo, E, et al. (author)
  • A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
  • 2022
  • In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
  • Journal article (peer-reviewed)abstract
    • Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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  • van Meurs, Joyce B, et al. (author)
  • Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis.
  • 2008
  • In: JAMA : the journal of the American Medical Association. - Chicago : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 299:11, s. 1277-90
  • Journal article (peer-reviewed)abstract
    • CONTEXT: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. OBJECTIVE: To generate large-scale evidence on whether 2 common variants of LRP5 (Val667Met, Ala1330Val) and 1 variant of LRP6 (Ile1062Val) are associated with BMD and fracture risk. DESIGN AND SETTING: Prospective, multicenter, collaborative study of individual-level data on 37,534 individuals from 18 participating teams in Europe and North America. Data were collected between September 2004 and January 2007; analysis of the collected data was performed between February and May 2007. Bone mineral density was assessed by dual-energy x-ray absorptiometry. Fractures were identified via questionnaire, medical records, or radiographic documentation; incident fracture data were available for some cohorts, ascertained via routine surveillance methods, including radiographic examination for vertebral fractures. MAIN OUTCOME MEASURES: Bone mineral density of the lumbar spine and femoral neck; prevalence of all fractures and vertebral fractures. RESULTS: The Met667 allele of LRP5 was associated with reduced lumbar spine BMD (n = 25,052 [number of participants with available data]; 20-mg/cm2 lower BMD per Met667 allele copy; P = 3.3 x 10(-8)), as was the Val1330 allele (n = 24,812; 14-mg/cm2 lower BMD per Val1330 copy; P = 2.6 x 10(-9)). Similar effects were observed for femoral neck BMD, with a decrease of 11 mg/cm2 (P = 3.8 x 10(-5)) and 8 mg/cm2 (P = 5.0 x 10(-6)) for the Met667 and Val1330 alleles, respectively (n = 25 193). Findings were consistent across studies for both LRP5 alleles. Both alleles were associated with vertebral fractures (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.08-1.47 for Met667 [2001 fractures among 20 488 individuals] and OR, 1.12; 95% CI, 1.01-1.24 for Val1330 [1988 fractures among 20,096 individuals]). Risk of all fractures was also increased with Met667 (OR, 1.14; 95% CI, 1.05-1.24 per allele [7876 fractures among 31,435 individuals)]) and Val1330 (OR, 1.06; 95% CI, 1.01-1.12 per allele [7802 fractures among 31 199 individuals]). Effects were similar when adjustments were made for age, weight, height, menopausal status, and use of hormone therapy. Fracture risks were partly attenuated by adjustment for BMD. Haplotype analysis indicated that Met667 and Val1330 variants both independently affected BMD. The LRP6 Ile1062Val polymorphism was not associated with any osteoporosis phenotype. All aforementioned associations except that between Val1330 and all fractures and vertebral fractures remained significant after multiple-comparison adjustments. CONCLUSIONS: Common LRP5 variants are consistently associated with BMD and fracture risk across different white populations. The magnitude of the effect is modest. LRP5 may be the first gene to reach a genome-wide significance level (a conservative level of significance [herein, unadjusted P < 10(-7)] that accounts for the many possible comparisons in the human genome) for a phenotype related to osteoporosis.
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  • Bergkvist, C., et al. (author)
  • Dietary exposure to polychlorinated biphenyls is associated with increased risk of stroke in women
  • 2014
  • In: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 276:3, s. 248-259
  • Journal article (peer-reviewed)abstract
    • Objective. The potentially beneficial effects of fish consumption on stroke may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular are proposed to play a role in the aetiology of stroke. The aim of this study was to assess the association between dietary PCB exposure and stroke risk with the intake of long-chain omega-3 fish fatty acids and fish consumption. Design. The prospective population-based Swedish Mammography Cohort was examined. It was comprised of 34 591 women free of cardiovascular diseases and cancer at baseline in 1997 and followed up for 12 years. Validated estimates of dietary PCB exposure were obtained via a food frequency questionnaire at baseline. Incident cases of stroke were ascertained through register linkage. Results. During 12 years of follow-up (397 309 person-years), there were 2015 incident cases of total stroke (1532 ischaemic strokes, 216 intracerebral haemorrhages, 94 subarachnoid haemorrhages and 173 unspecified strokes). Multivariable-adjusted relative risks (RR), controlled for known stroke risk factors and fish consumption, were 1.67 [95% confidence interval (CI), 1.29-2.17] for total stroke, 1.61 (95% CI, 1.19-2.17) for ischaemic stroke and 2.80 (95% CI, 1.42-5.55) for haemorrhagic stroke for women in the highest quartile of dietary PCB exposure (median 288 ng day(-1)) compared with women in the lowest quartile (median 101 ng day(-1)). Conclusion. Dietary exposure to PCBs was associated with an increased stroke risk in women, especially haemorrhagic stroke. The results provide important information regarding the risk-benefit analysis of fish consumption, particularly for cerebrovascular disease prevention.
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  • Datta, P., et al. (author)
  • A follow-up study of Nordic multiple sclerosis candidate gene regions
  • 2007
  • In: MULTIPLE SCLEROSIS. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:5, s. 584-589
  • Journal article (peer-reviewed)abstract
    • In this study, the results from three Nordic linkage disequilibrium screens in multiple sclerosis (MS) were investigated, in a new sample set of 314 Nordic MS trios from Denmark, Norway, Sweden and Iceland. Among 30 non-HLA and two HLA microsatellite markers individually genotyped, eight markers displayed distorted transmission with uncorrected P-value <0.05, ranked in this order: D6S2443 (6p21.32, HLA class II) (P corrected =0.01), D2S2201 (2p24), D19S552 (19q13), D3S3584 (3q21), D17S975 (17q11), D1S2627 (1p22), D6S273 (6p21.33, HLA class III) and D12S1051 (12q23). These non-HLA regions need further investigation as possible MS candidate gene regions in our population. Multiple Sclerosis 2007; 13: 584-589. http://msj.sagepub.com
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  • Donat-Vargas, C., et al. (author)
  • Cardiovascular and cancer mortality in relation to dietary polychlorinated biphenyls and marine polyunsaturated fatty acids : a nutritional-toxicological aspect of fish consumption
  • 2020
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:2, s. 197-209
  • Journal article (peer-reviewed)abstract
    • Background: Co-exposure to environmental contaminants present in fish could mitigate the beneficial effects of fish consumption and possibly explain the lack of association observed for mortality in some geographical regions.Objective: To assess the independent associations of dietary exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fish fatty acids intake with cardiovascular and cancer mortality.Methods: We used the prospective population-based Swedish Mammography Cohort and the Cohort of Swedish Men comprising 32 952 women and 36 545 men, free from cancer, cardiovascular disease and diabetes at baseline in 1998. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] intake were obtained via a food frequency questionnaire at baseline. Information on death was ascertained through register linkage.Results: During a mean follow-up of 15.5 years, we ascertained 16 776 deaths. We observed for cardiovascular mortality, comparing extreme quintiles in multivariable models mutually adjusted for PCBs and EPA-DHA, dose-dependent associations for dietary PCB exposure, hazard ratio (HR) 1.31 (CI 95%: 1.08 to 1.57; P-trend 0.005) and for dietary EPA-DHA intake, HR 0.79 (CI 95%: 0.66 to 0.95; P-trend 0.041). For cancer mortality, no clear associations were discerned.Conclusion: The beneficial effect of fish consumption on the cardiovascular system seems compromised by co-exposure to PCBs - one likely explanation for the inconsistent associations observed between fish consumption and mortality.
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  • Filippini, T, et al. (author)
  • Dietary Acrylamide Exposure and Risk of Site-Specific Cancer: A Systematic Review and Dose-Response Meta-Analysis of Epidemiological Studies
  • 2022
  • In: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 875607-
  • Research review (other academic/artistic)abstract
    • Diet is a main source of acrylamide exposure to humans. Existing observational data on the relationship between dietary exposure to acrylamide and risk of cancer are inconsistent. We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the association between dietary acrylamide exposure and several site-specific cancer. A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases until March 7, 2022. Studies were eligible if they were carried out in non-occupationally exposed adults, assessed dietary acrylamide exposure (μg/day) and reported risk estimates of cancer incidence (all but gynecological cancers). Using a random-effects model, we performed a meta-analysis of site-specific cancer risk comparing the highest vs. lowest category of dietary acrylamide exposure. We also carried out a one-stage dose-response meta-analysis assessing the shape of the association. Out of 1,994 papers screened, 31 were eligible (total of 16 studies), which included 1,151,189 participants in total, out of whom 48,175 developed cancer during the median follow-up period of 14.9 years (range 7.3–33.9). The mean estimated dose of dietary acrylamide across studies was 23 μg/day. Pooled analysis showed no association between the highest vs. lowest dietary acrylamide exposure and each site-specific cancer investigated, with no evidence of thresholds in the dose-response meta-analysis. There were also no associations between dietary acrylamide exposure and the risk of cancers when stratifying by smoking status, except for increased risk of lung cancer in smokers. In conclusion, high dietary acrylamide exposure was not associated with an increased risk of site-specific non-gynecological cancer.
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  • Hsu, Y. H., et al. (author)
  • Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
  • 2019
  • In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 34:7, s. 1284-1296
  • Journal article (peer-reviewed)abstract
    • Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.
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  • Scheja, A, et al. (author)
  • Computer based quantitative analysis of capillary abnormalities in systemic sclerosis and its relation to plasma concentration of von Willebrand factor
  • 1996
  • In: Annals of the Rheumatic Diseases. - 0003-4967. ; 55:1, s. 6-52
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To evaluate an objective and quantitative method for assessment of capillary abnormalities in systemic sclerosis (SSc).METHODS: Nailfold capillaries were investigated by capillary microscopy and photographed in 17 consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc) and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy controls. Investigators having no access to clinical data made drawings from magnified projections of coded photographs and analysed them using a computer program. Capillary density (capillary loops/mm in the distal row) and median capillary loop area were calculated. Presence of functional or organic arterial changes was evaluated by measurement of finger pressure with finger cooling. Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme linked immunosorbent assay (ELISA).RESULTS: In 16 of 17 SSc patients and 13 of 17 controls the technical quality of the photographs was sufficient for computer analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse relation was found between capillary density and median capillary loop area in SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and 409 IE/l in lSSc) compared with controls matched for age and sex (median 276 IE/l). Computer based analysis showed capillary density below the control range and median capillary loop area above the control range in 14 of 16 SSc patients. Measurement of finger pressure with finger cooling showed organic vascular changes in nine of 13 SSc patients.CONCLUSION: Computer based quantitative analysis has low interobserver variability and is a quantitative and sensitive method of assessing capillary abnormalities in SSc.
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  • Schillemans, Tessa, et al. (author)
  • Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis
  • 2022
  • In: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 13
  • Journal article (peer-reviewed)abstract
    • Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.
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