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1.
  • Amati, L., et al. (author)
  • The THESEUS space mission concept : science case, design and expected performances
  • 2018
  • In: Advances in Space Research. - : ELSEVIER SCI LTD. - 0273-1177 .- 1879-1948. ; 62:1, s. 191-244
  • Journal article (peer-reviewed)abstract
    • THESEUS is a space mission concept aimed at exploiting Gamma-Ray Bursts for investigating the early Universe and at providing a substantial advancement of multi-messenger and time-domain astrophysics. These goals will be achieved through a unique combination of instruments allowing GRB and X-ray transient detection over a broad field of view (more than 1 sr) with 0.5-1 arcmin localization, an energy band extending from several MeV down to 0.3 keV and high sensitivity to transient sources in the soft X-ray domain, as well as on-board prompt (few minutes) follow-up with a 0.7 m class IR telescope with both imaging and spectroscopic capabilities. THESEUS will be perfectly suited for addressing the main open issues in cosmology such as, e.g., star formation rate and metallicity evolution of the inter-stellar and intra-galactic medium up to redshift similar to 10, signatures of Pop III stars, sources and physics of re-ionization, and the faint end of the galaxy luminosity function. In addition, it will provide unprecedented capability to monitor the X-ray variable sky, thus detecting, localizing, and identifying the electromagnetic counterparts to sources of gravitational radiation, which may be routinely detected in the late '20s/early '30s by next generation facilities like aLIGO/ aVirgo, eLISA, KAGRA, and Einstein Telescope. THESEUS will also provide powerful synergies with the next generation of multi-wavelength observatories (e.g., LSST, ELT, SKA, CTA, ATHENA).
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2.
  • Gapstur, S. M., et al. (author)
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies
  • 2015
  • In: The Lancet. - 1474-547X. ; 385:9980, s. 1835-1842
  • Journal article (peer-reviewed)abstract
    • Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1.43, 95% CI 1.31-1.56; p<0.0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p<0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p<0.0001) and endometrioid (1.42, 1.20-1.67; p<0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
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3.
  • Pierre, M., et al. (author)
  • The XXL Survey I. Scientific motivations - XMM-Newton observing plan - Follow-up observations and simulation programme
  • 2016
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
  • Journal article (peer-reviewed)abstract
    • Context. The quest for the cosmological parameters that describe our universe continues to motivate the scientific community to undertake very large survey initiatives across the electromagnetic spectrum. Over the past two decades, the Chandra and XMM-Newton observatories have supported numerous studies of X-ray-selected clusters of galaxies, active galactic nuclei (AGNs), and the X-ray background. The present paper is the first in a series reporting results of the XXL-XMM survey; it comes at a time when the Planck mission results are being finalised. Aims. We present the XXL Survey, the largest XMM programme totaling some 6.9 Ms to date and involving an international consortium of roughly 100 members. The XXL Survey covers two extragalactic areas of 25 deg(2) each at a point-source sensitivity of similar to 5 x 10(-15) erg s(-1) cm(-2) in the [0.5-2] keV band (completeness limit). The survey's main goals are to provide constraints on the dark energy equation of state from the space-time distribution of clusters of galaxies and to serve as a pathfinder for future, wide-area X-ray missions. We review science objectives, including cluster studies, AGN evolution, and large-scale structure, that are being conducted with the support of approximately 30 follow-up programmes. Methods. We describe the 542 XMM observations along with the associated multi-lambda and numerical simulation programmes. We give a detailed account of the X-ray processing steps and describe innovative tools being developed for the cosmological analysis. Results. The paper provides a thorough evaluation of the X-ray data, including quality controls, photon statistics, exposure and background maps, and sky coverage. Source catalogue construction and multi-lambda associations are briefly described. This material will be the basis for the calculation of the cluster and AGN selection functions, critical elements of the cosmological and science analyses. Conclusions. The XXL multi-lambda data set will have a unique lasting legacy value for cosmological and extragalactic studies and will serve as a calibration resource for future dark energy studies with clusters and other X-ray selected sources. With the present article, we release the XMM XXL photon and smoothed images along with the corresponding exposure maps.
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4.
  • Pierre, M., et al. (author)
  • The XXL survey : First results and future
  • 2017
  • In: Astronomical Notes - Astronomische Nachrichten. - : Wiley-VCH Verlagsgesellschaft. - 0004-6337 .- 1521-3994. ; 338:2-3, s. 334-341
  • Journal article (peer-reviewed)abstract
    • The XXL survey currently covers two 25 deg(2) patches with XMM observations of similar to 10 ks. We summarize the scientific results associated with the first release of the XXL dataset, which occurred in mid-2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z < 2) cluster, (z < 4) active galactic nuclei (AGN), and cosmic background survey science will then benefit from an extraordinary data reservoir. This, combined with deep multi-lambda observations, will lead to solid standalone cosmological constraints and provide a wealth of information on the formation and evolution of AGN, clusters, and the X-ray background. In particular, it will offer a unique opportunity to pinpoint the z > 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.
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5.
  • Sampson, Joshua N., et al. (author)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Journal article (peer-reviewed)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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6.
  • Berndt, Sonja I., et al. (author)
  • Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
  • 2016
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Journal article (peer-reviewed)abstract
    • Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
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7.
  • Genkinger, J. M., et al. (author)
  • Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies
  • 2015
  • In: Annals of Oncology. - : OXFORD UNIV PRESS. - 0923-7534 .- 1569-8041. ; 26:11, s. 2257-2266
  • Research review (peer-reviewed)abstract
    • positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity ( e. g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood ( ages 18- 21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later ( n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios ( HRs) and 95% confidence intervals ( CIs) were calculated using Cox proportional hazards regression models. Results: Higher waist-to-hip ratio ( HR = 1.09, 95% CI 1.02- 1.17 per 0.1 increment) and waist circumference ( HR = 1.07, 95% CI 1.00- 1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality ( HR = 1.18, 95% CI 1.11- 1.25 per 5 kg/ m2), with increased risk observed in both overweight and obese individuals ( compared with BMI of 21.0 to < 23 kg/ m(2), HR = 1.36, 95% CI 1.20- 1.55 for BMI 25.0 < 27.5 kg/ m2, HR = 1.48, 95% CI 1.20- 1.84 for BMI 27.5 to < 30 kg/ m2, HR = 1.43, 95% CI 1.11- 1.85 for BMI = 30 kg/ m2). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality ( HR = 1.05, 95% CI 1.01- 1.10 per 5 kg/ m2). Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.
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8.
  • Machiela, Mitchell J., et al. (author)
  • Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
  • 2016
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
  • Journal article (peer-reviewed)abstract
    • Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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9.
  • Bernatsky, Sasha, et al. (author)
  • Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
  • 2017
  • In: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 4:1
  • Journal article (peer-reviewed)abstract
    • Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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10.
  • Din, Lennox, et al. (author)
  • Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes
  • 2019
  • In: Genetic Epidemiology. - : WILEY. - 0741-0395 .- 1098-2272. ; 43:7, s. 844-863
  • Journal article (peer-reviewed)abstract
    • Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p =.0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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11.
  • Vijai, Joseph, et al. (author)
  • A genome-wide association study of marginal zone lymphoma shows association to the HLA region
  • 2015
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Journal article (peer-reviewed)abstract
    • Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P - 3.95 x 10(-15)) and HLA-B (rs2922994, P - 2.43 x 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
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12.
  • Pacaud, F., et al. (author)
  • The XXL Survey II. The bright cluster sample: catalogue and luminosity function
  • 2016
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592
  • Research review (peer-reviewed)abstract
    • Context. The XXL Survey is the largest survey carried out by the XMM-Newton satellite and covers a total area of 50 square degrees distributed over two fields. It primarily aims at investigating the large-scale structures of the Universe using the distribution of galaxy clusters and active galactic nuclei as tracers of the matter distribution. The survey will ultimately uncover several hundreds of galaxy clusters out to a redshift of similar to 2 at a sensitivity of similar to 10 (14) erg s (1) cm (2) in the [0.5-2] keV band. Aims. This article presents the XXL bright cluster sample, a subsample of 100 galaxy clusters selected from the full XXL catalogue by setting a lower limit of 3 x 10(-1)4 erg s(-1) cm(-2) on the source flux within a 1' aperture. Methods. The selection function was estimated using a mixture of Monte Carlo simulations and analytical recipes that closely reproduce the source selection process. An extensive spectroscopic follow-up provided redshifts for 97 of the 100 clusters. We derived accurate X-ray parameters for all the sources. Scaling relations were self-consistently derived from the same sample in other publications of the series. On this basis, we study the number density, luminosity function, and spatial distribution of the sample. Results. The bright cluster sample consists of systems with masses between M-500 = 7 x 10(13) and 3 x 10(14) M-circle dot, mostly located between z = 0.1 and 0.5. The observed sky density of clusters is slightly below the predictions from the WMAP9 model, and significantly below the prediction from the Planck 2015 cosmology. In general, within the current uncertainties of the cluster mass calibration, models with higher values of sigma(8) and/or Omega(M) appear more difficult to accommodate. We provide tight constraints on the cluster differential luminosity function and find no hint of evolution out to z similar to 1. We also find strong evidence for the presence of large-scale structures in the XXL bright cluster sample and identify five new superclusters. ELL GO, 1989, ASTROPHYSICAL JOURNAL SUPPLEMENT SERIES, V70, P1
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13.
  • Patra, B., et al. (author)
  • A genome wide dosage suppressor network reveals genomic robustness
  • 2017
  • In: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 45:1, s. 255-270
  • Journal article (peer-reviewed)abstract
    • Genomic robustness is the extent to which an organism has evolved to withstand the effects of deleterious mutations. We explored the extent of genomic robustness in budding yeast by genome wide dosage suppressor analysis of 53 conditional lethal mutations in cell division cycle and RNA synthesis related genes, revealing 660 suppressor interactions of which 642 are novel. This collection has several distinctive features, including high cooccurrence of mutant-suppressor pairs within protein modules, highly correlated functions between the pairs and higher diversity of functions among the co-suppressors than previously observed. Dosage suppression of essential genes encoding RNA polymerase subunits and chromosome cohesion complex suggests a surprising degree of functional plasticity of macromolecular complexes, and the existence of numerous degenerate pathways for circumventing the effects of potentially lethal mutations. These results imply that organisms and cancer are likely able to exploit the genomic robustness properties, due the persistence of cryptic gene and pathway functions, to generate variation and adapt to selective pressures. © 2016 The Author(s).
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14.
  • Wang, Sophia S., et al. (author)
  • HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
  • 2018
  • In: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:14, s. 4086-4096
  • Journal article (peer-reviewed)abstract
    • A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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15.
  • Adami, C., et al. (author)
  • The XXL Survey: XX. The 365 cluster catalogue
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Journal article (peer-reviewed)abstract
    • Context. In the currently debated context of using clusters of galaxies as cosmological probes, the need for well-defined cluster samples is critical. Aims. The XXL Survey has been specifically designed to provide a well characterised sample of some 500 X-ray detected clusters suitable for cosmological studies. The main goal of present article is to make public and describe the properties of the cluster catalogue in its present state, as well as of associated catalogues of more specific objects such as super-clusters and fossil groups. Methods. Following from the publication of the hundred brightest XXL clusters, we now release a sample containing 365 clusters in total, down to a flux of a few 10-15 erg s-1 cm-2 in the [0.5-2] keV band and in a 1′ aperture. This release contains the complete subset of clusters for which the selection function is well determined plus all X-ray clusters which are, to date, spectroscopically confirmed. In this paper, we give the details of the follow-up observations and explain the procedure adopted to validate the cluster spectroscopic redshifts. Considering the whole XXL cluster sample, we have provided two types of selection, both complete in a particular sense: one based on flux-morphology criteria, and an alternative based on the [0.5-2] keV flux within 1 arcmin of the cluster centre. We have also provided X-ray temperature measurements for 80% of the clusters having a flux larger than 9 × 10-15 erg s-1 cm-2. Results. Our cluster sample extends from z ∼ 0 to z ∼ 1.2, with one cluster at z ∼ 2. Clusters were identified through a mean number of six spectroscopically confirmed cluster members. The largest number of confirmed spectroscopic members in a cluster is 41. Our updated luminosity function and luminosity-temperature relation are compatible with our previous determinations based on the 100 brightest clusters, but show smaller uncertainties. We also present an enlarged list of super-clusters and a sample of 18 possible fossil groups. Conclusions. This intermediate publication is the last before the final release of the complete XXL cluster catalogue when the ongoing C2 cluster spectroscopic follow-up is complete. It provides a unique inventory of medium-mass clusters over a 50 deg2 area out to z ∼ 1.
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16.
  • Fotopoulou, S., et al. (author)
  • The XXL Survey VI. The 1000 brightest X-ray point sources
  • 2016
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592:A5
  • Research review (peer-reviewed)abstract
    • Context. X-ray extragalactic surveys are ideal laboratories for the study of the evolution and clustering of active galactic nuclei (AGN). Usually, a combination of deep and wide surveys is necessary to create a complete picture of the population. Deep X-ray surveys provide the faint population at high redshift, while wide surveys provide the rare bright sources. Nevertheless, very wide area surveys often lack the ancillary information available for modern deep surveys. The XXL survey spans two fields of a combined 50 deg(2) observed for more than 6Ms with XMM-Newton, occupying the parameter space that lies between deep surveys and very wide area surveys; at the same time it benefits from a wealth of ancillary data. Aims. This paper marks the first release of the XXL point source catalogue including four optical photometry bands and redshift estimates. Our sample is selected in the 2-10 keV energy band with the goal of providing a sizable sample useful for AGN studies. The limiting flux is F2-10 keV = 4.8 x 10(14) erg s(-1) cm(-2). Methods. We use both public and proprietary data sets to identify the counterparts of the X-ray point-like sources by means of a likelihood ratio test. We improve upon the photometric redshift determination for AGN by applying a Random Forest classification trained to identify for each object the optimal photometric redshift category (passive, star forming, starburst, AGN, quasi-stellar objects (QSO)). Additionally, we assign a probability to each source that indicates whether it might be a star or an outlier. We apply Bayesian analysis to model the X-ray spectra assuming a power-law model with the presence of an absorbing medium. Results. We find that the average unabsorbed photon index is = 1.85 +/- 0.40 while the average hydrogen column density is log i = 21.07 +/- 1.2 cm(-2). We find no trend of Gamma or N-H with redshift and a fraction of 26% absorbed sources (log N-H > 22) consistent with the literature on bright sources (log L-x > 44). The counterpart identification rate reaches 96.7% for sources in the northern field, 97.7% for the southern field, and 97.2% in total. The photometric redshift accuracy is 0.095 for the full XMM-XXL with 28% catastrophic outliers estimated on a sample of 339 sources. Conclusions. We show that the XXL-1000-AGN sample number counts extended the number counts of the COSMOS survey to higher fluxes and are fully consistent with the Euclidean expectation. We constrain the intrinsic luminosity function of AGN in the 2-10 keV energy band where the unabsorbed X-ray flux is estimated from the X-ray spectral fit up to z = 3. Finally, we demonstrate the presence of a supercluster size structure at redshift 0.14, identified by means of percolation analysis of the XXL-1000-AGN sample. The XXL survey, reaching a medium flux limit and covering a wide area, is a stepping stone between current deep fields and planned wide area surveys.
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17.
  • McMaster, ML, et al. (author)
  • Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
  • 2018
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 4182-
  • Journal article (peer-reviewed)abstract
    • Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
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18.
  • Nichols, Hazel B, et al. (author)
  • Breast Cancer Risk After Recent Childbirth : A Pooled Analysis of 15 Prospective Studies
  • 2019
  • In: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 170:1, s. 22-30
  • Journal article (peer-reviewed)abstract
    • Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.Objective: To characterize breast cancer risk in relation to recent childbirth.Design: Pooled analysis of individual-level data from 15 prospective cohort studies.Setting: The international Premenopausal Breast Cancer Collaborative Group.Participants: Women younger than 55 years.Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.
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19.
  • Nichols, Hazel B., et al. (author)
  • The Premenopausal Breast Cancer Collaboration : A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium
  • 2017
  • In: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 26:9, s. 1360-1369
  • Research review (peer-reviewed)abstract
    • Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individuallevel data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations.
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20.
  • Brisbois, J., et al. (author)
  • Flux penetration in a superconducting film partially capped with a conducting layer
  • 2017
  • In: Physical Review B. - 2469-9969 .- 2469-9950. ; 95:9
  • Journal article (peer-reviewed)abstract
    • The influence of a conducting layer on the magnetic flux penetration in a superconducting Nb film is studied by magneto-optical imaging. The metallic layer partially covering the superconductor provides an additional velocity-dependent damping mechanism for the flux motion that helps to protect the superconducting state when thermomagnetic instabilities develop. If the flux advances with a velocity slower than omega = 2/mu(0)sigma t, where sigma is the cap layer conductivity and t is its thickness, the flux penetration remains unaffected, whereas for incoming flux moving faster than w, the metallic layer becomes an active screening shield. When the metallic layer is replaced by a perfect conductor, it is expected that the flux braking effect will occur for all flux velocities. We investigate this effect by studying Nb samples with a thickness step. Some of the observed features, namely the deflection of the flux trajectories at the border of the thick center, as well as the favored flux penetration at the indentation, are reproduced by time-dependent Ginzburg-Landau simulations.
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21.
  • Guglielmo, V., et al. (author)
  • The XXL Survey: XXII. the XXL-North spectrophotometric sample and galaxy stellar mass function in X-ray detected groups and clusters
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Journal article (peer-reviewed)abstract
    • Context. The fraction of galaxies bound in groups in the nearby Universe is high (50% at z ∼ 0). Systematic studies of galaxy properties in groups are important in order to improve our understanding of the evolution of galaxies and of the physical phenomena occurring within this environment. Aims. We have built a complete spectrophotometric sample of galaxies within X-ray detected, optically spectroscopically confirmed groups and clusters (G&C), covering a wide range of halo masses at z ≤ 0.6. Methods. In the context of the XXL survey, we analyse a sample of 164 G&C in the XXL-North region (XXL-N), at z ≤ 0.6, with a wide range of virial masses (1.24 × 1013 ≤ M500,scal(Mo) ≤ 6.63 × 1014) and X-ray luminosities ((2.27 × 1041 ≤ L500,scalXXL(erg-s-1) ≤ 2.15 × 1044)). The G&C are X-ray selected and spectroscopically confirmed. We describe the membership assignment and the spectroscopic completeness analysis, and compute stellar masses. As a first scientific exploitation of the sample, we study the dependence of the galaxy stellar mass function (GSMF) on global environment. Results. We present a spectrophotometric characterisation of the G&C and their galaxies. The final sample contains 132 G&C, 22 111 field galaxies and 2225 G&C galaxies with r-band magnitude <20. Of the G&C, 95% have at least three spectroscopic members, and 70% at least ten. The shape of the GSMF seems not to depend on environment (field versus G&C) or X-ray luminosity (used as a proxy for the virial mass of the system). These results are confirmed by the study of the correlation between mean stellar mass of G&C members and L500,scalXXL. We release the spectrophotometric catalogue of galaxies with all the quantities computed in this work. Conclusions. As a first homogeneous census of galaxies within X-ray spectroscopically confirmed G&C at these redshifts, this sample will allow environmental studies of the evolution of galaxy properties.
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22.
  • Guglielmo, V., et al. (author)
  • The XXL Survey: XXX. Characterisation of the XLSSsC N01 supercluster and analysis of the galaxy stellar populations
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Journal article (peer-reviewed)abstract
    • Context. Superclusters form from the largest enhancements in the primordial density perturbation field and extend for tens of Mpc, tracing the large-scale structure of the Universe. X-ray detections and systematic characterisations of superclusters and the properties of their galaxies have only been possible in the last few years. Aims. We characterise XLSSsC N01, a rich supercluster at z ∼ 0.3 detected in the XXL Survey, composed of X-ray clusters of different virial masses and X-ray luminosities. As one of the first studies on this topic, we investigate the stellar populations of galaxies in different environments in the supercluster region. Methods. We study a magnitude-limited (r ≤ 20) and a mass-limited sample (log(M ∗ Mo) ≥ 10.8) of galaxies in the virialised region and in the outskirts of 11 XLSSsC N01 clusters, in high-density field regions, and in the low-density field. We compute the stellar population properties of galaxies using spectral energy distribution (SED) and spectral fitting techniques, and study the dependence of star formation rates (SFR), colours, and stellar ages on environment. Results. For r ≤ 20, the fraction of star-forming/blue galaxies, computed either from the specific-SFR (sSFR) or rest-frame colour, shows depletion within the cluster virial radii, where the number of galaxies with log (sSFR/ yr-1) > -12 and with (g - r) restframe < 0.6 is lower than in the field. For log(M ∗ Mo) ≥ 10.8, no trends with environment emerge, as massive galaxies are mostly already passive in all environments. No differences among low- and high-density field members and cluster members emerge in the sSFR-mass relation in the mass-complete regime. Finally, the luminosity-weighted age-mass relation of the passive populations within cluster virial radii show signatures of recent environmental quenching. Conclusions. The study of luminous and massive galaxies in this supercluster shows that while environment has a prominent role in determining the fractions of star-forming/blue galaxies, its effects on the star formation activity in star-forming galaxies are negligible.
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23.
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24.
  • Jackson, Sarah S., et al. (author)
  • Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project
  • 2019
  • In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:15, s. 3973-3982
  • Journal article (peer-reviewed)abstract
    • Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m(2) increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. Significance: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.
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25.
  • McGee, Emma E., et al. (author)
  • Smoking, Alcohol, and Biliary Tract Cancer Risk : A Pooling Project of 26 Prospective Studies
  • 2019
  • In: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 111:12, s. 1263-1278
  • Research review (peer-reviewed)abstract
    • Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided. Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; P-trend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.
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26.
  • Modi, A., et al. (author)
  • Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS)
  • 2017
  • In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:10, s. 2867-2876
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. Introduction The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. Methods MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. Results Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P <= 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. Conclusions The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.
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27.
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28.
  • Modi, A., et al. (author)
  • Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for Osteoporosis in Europe and Canada
  • 2015
  • In: Clinical and Experimental Rheumatology. - 0392-856X. ; 33:4, s. 537-544
  • Journal article (peer-reviewed)abstract
    • Objective The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women >= 50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.
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29.
  • Modi, A., et al. (author)
  • The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study
  • 2018
  • In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:2, s. 329-337
  • Journal article (peer-reviewed)abstract
    • The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score >= 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score >= 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.
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30.
  • Pacaud, F., et al. (author)
  • The XXL Survey: XXV. Cosmological analysis of the C1 cluster number counts
  • 2018
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Research review (peer-reviewed)abstract
    • Context. We present an estimation of cosmological parameters with clusters of galaxies. Aims. We constrain the Ωm, σ8, and w parameters from a stand-alone sample of X-ray clusters detected in the 50 deg2 XMM-XXL survey with a well-defined selection function. Methods. We analyse the redshift distribution of a sample comprising 178 high signal-to-noise ratio clusters out to a redshift of unity. The cluster sample scaling relations are determined in a self-consistent manner. Results. In a lambda cold dark matter (ΛCDM) model, the cosmology favoured by the XXL clusters compares well with results derived from the Planck Sunyaev-Zel'dovich clusters for a totally different sample (mass/redshift range, selection biases, and scaling relations). However, with this preliminary sample and current mass calibration uncertainty, we find no inconsistency with the Planck CMB cosmology. If we relax the w parameter, the Planck CMB uncertainties increase by a factor of ~10 and become comparable with those from XXL clusters. Combining the two probes allows us to put constraints on Ωm = 0.316 ± 0.060, σ8 = 0.814 ± 0.054, and w = -1.02 ± 0.20. Conclusions. This first self-consistent cosmological analysis of a sample of serendipitous XMM clusters already provides interesting insights into the constraining power of the XXL survey. Subsequent analysis will use a larger sample extending to lower confidence detections and include additional observable information, potentially improving posterior uncertainties by roughly a factor of 3.
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31.
  • Petimar, J, et al. (author)
  • Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.
  • 2019
  • In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 26:3, s. 468-475
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality.METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures.RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously.CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.
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32.
  • Schoemaker, Minouk J, et al. (author)
  • Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women.
  • 2018
  • In: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445. ; 4:11
  • Journal article (peer-reviewed)abstract
    • Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation.Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics.Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017.Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years.Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer.Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall.Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.
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33.
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34.
  • Bajunirwe, F, et al. (author)
  • Burden of depressive symptoms and non-alcohol substance abuse; and their association with alcohol use and partner violence: a cross-sectional study in four sub-Saharan Africa countries
  • 2018
  • In: Global mental health (Cambridge, England). - : Cambridge University Press (CUP). - 2054-4251. ; 5, s. e31-
  • Journal article (peer-reviewed)abstract
    • In sub-Saharan Africa, there are limited data on burden of non-alcohol substance abuse (NAS) and depressive symptoms (DS), yet potential risk factors such as alcohol and intimate partner violence (IPV) are common and NAS abuse may be the rise. The aim of this study was to measure the burden of DS and NAS abuse, and determine whether alcohol use and IPV are associated with DS and/or NAS abuse. We conducted a cross-sectional study at five sites in four countries: Nigeria (nurses), South Africa (teachers), Tanzania (teachers) and two sites in Uganda (rural and peri-urban residents). Participants were selected by simple random sampling from a sampling frame at each of the study sites. We used a standardized tool to collect data on demographics, alcohol use and NAS use, IPV and DS and calculated prevalence ratios (PR). We enrolled 1415 respondents and of these 34.6% were male. DS occurred among 383 (32.3%) and NAS use among 52 (4.3%). In the multivariable analysis, being female (PR  =  1.49, p  =  0.008), NAS abuse (PR  =  2.06, p  =  0.02) and IPV (PR  =  2.93, p < 0.001) were significantly associated with DS. Older age [odds ratio (OR) = 0.31, p < 0.001)], female (OR = 0.48, p  =  0.036) were protective of NAS but current smokers (OR = 2.98, p < 0.001) and those reporting IPV (OR  =  2.16, p  =  0.024) were more likely to use NAS. Longitudinal studies should be done to establish temporal relationships with these risk factors to provide basis for interventions.
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35.
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36.
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37.
  • Gaudet, Mia M., et al. (author)
  • Anthropometry and head and neck cancer : a pooled analysis of cohort data
  • 2015
  • In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 44:2, s. 673-681
  • Journal article (peer-reviewed)abstract
    • Background: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. Methods: We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Results: Greater waist circumference (per 5cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m(2): HR = 1.15, 95% CI 1.06-1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m(2): HR = 0.99, 95% CI 0.93-1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m(2): HR = 0.76, 95% CI 0.71-0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Conclusions: Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers.
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38.
  • Gaudet, Mia M, et al. (author)
  • Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.
  • 2017
  • In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 881-893
  • Journal article (peer-reviewed)abstract
    • Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.
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39.
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40.
  • Harris, JR, et al. (author)
  • The Nordic Twin Study on Cancer - NorTwinCan
  • 2019
  • In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:6, s. 817-823
  • Journal article (peer-reviewed)abstract
    • Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
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41.
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42.
  • Kitahara, Cari M., et al. (author)
  • Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype : Pooled Analysis of 22 Prospective Studies
  • 2016
  • In: Thyroid. - : MARY ANN LIEBERT, INC. - 1050-7256 .- 1557-9077. ; 26:2, s. 306-318
  • Journal article (peer-reviewed)abstract
    • Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5cm)=1.07 [1.04-1.10], BMI (per 5kg/m(2))=1.06 [1.02-1.10], waist circumference (per 5cm)=1.03 [1.01-1.05], young-adult BMI (per 5kg/m(2))=1.13 [1.02-1.25], and adulthood BMI gain (per 5kg/m(2))=1.07 [1.00-1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
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43.
  • Mair, Grant, et al. (author)
  • Arterial Obstruction on Computed Tomographic or Magnetic Resonance Angiography and Response to Intravenous Thrombolytics in Ischemic Stroke
  • 2017
  • In: Stroke. - 0039-2499 .- 1524-4628. ; 48:2, s. 353-360
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Computed tomographic angiography and magnetic resonance angiography are used increasingly to assess arterial patency in patients with ischemic stroke. We determined which baseline angiography features predict response to intravenous thrombolytics in ischemic stroke using randomized controlled trial data.METHODS: We analyzed angiograms from the IST-3 (Third International Stroke Trial), an international, multicenter, prospective, randomized controlled trial of intravenous alteplase. Readers, masked to clinical, treatment, and outcome data, assessed prerandomization computed tomographic angiography and magnetic resonance angiography for presence, extent, location, and completeness of obstruction and collaterals. We compared angiography findings to 6-month functional outcome (Oxford Handicap Scale) and tested for interactions with alteplase, using ordinal regression in adjusted analyses. We also meta-analyzed all available angiography data from other randomized controlled trials of intravenous thrombolytics.RESULTS: In IST-3, 300 patients had prerandomization angiography (computed tomographic angiography=271 and magnetic resonance angiography=29). On multivariable analysis, more extensive angiographic obstruction and poor collaterals independently predicted poor outcome (P<0.01). We identified no significant interaction between angiography findings and alteplase effect on Oxford Handicap Scale (P≥0.075) in IST-3. In meta-analysis (5 trials of alteplase or desmoteplase, including IST-3, n=591), there was a significantly increased benefit of thrombolytics on outcome (odds ratio>1 indicates benefit) in patients with (odds ratio, 2.07; 95% confidence interval, 1.18-3.64; P=0.011) versus without (odds ratio, 0.88; 95% confidence interval, 0.58-1.35; P=0.566) arterial obstruction (P for interaction 0.017).CONCLUSIONS: Intravenous thrombolytics provide benefit to stroke patients with computed tomographic angiography or magnetic resonance angiography evidence of arterial obstruction, but the sample was underpowered to demonstrate significant treatment benefit or harm among patients with apparently patent arteries.CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.
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44.
  • Navarrini, A., et al. (author)
  • Design of PHAROS2 Phased Array Feed
  • 2018
  • In: 2018 2nd URSI Atlantic Radio Science Meeting, AT-RASC 2018.
  • Conference paper (peer-reviewed)abstract
    • We describe the design and architecture of PHAROS2, a cryogenically cooled 4-8 GHz Phased Array Feed (PAF) demonstrator with digital beamformer for radio astronomy application. The instrument will be capable of synthesizing four independent single-polarization beams by combining 24 active elements of an array of Vivaldi antennas. PHAROS2, the upgrade of PHAROS (PHased Arrays for Reflector Observing Systems), features: a) commercial cryogenic LNAs with state-of-the-art performance, b) a 'Warm Section' for signal filtering, conditioning and single downconversion to select a≈275 MHz: Intermediate Frequency (IF) bandwidth within the 4-8 GHz Radio Frequency (RF) band, c) an IF signal transportation by analog WDM (Wavelength Division Mutiplexing) fiber-optic link, and d) a FPGA-based Italian Tile Processing Module (iTPM) digital backend. PHAROS2 will be mounted at the primary focus of the 76-m diameter Lovell radio telescope (Jodrell Bank Observatory, UK) for technical and scientific validation.
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45.
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46.
  • Skytthe, A, et al. (author)
  • Cancer Incidence and Mortality in 260,000 Nordic Twins With 30,000 Prospective Cancers
  • 2019
  • In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 22:2, s. 99-107
  • Journal article (peer-reviewed)abstract
    • The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.
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47.
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48.
  • Adami, C., et al. (author)
  • Evolutionary game theory using agent-based methods
  • 2016
  • In: Physics of Life Reviews. - : Elsevier B.V.. - 1571-0645 .- 1873-1457. ; 19, s. 1-26
  • Journal article (peer-reviewed)abstract
    • Evolutionary game theory is a successful mathematical framework geared towards understanding the selective pressures that affect the evolution of the strategies of agents engaged in interactions with potential conflicts. While a mathematical treatment of the costs and benefits of decisions can predict the optimal strategy in simple settings, more realistic settings such as finite populations, non-vanishing mutations rates, stochastic decisions, communication between agents, and spatial interactions, require agent-based methods where each agent is modeled as an individual, carries its own genes that determine its decisions, and where the evolutionary outcome can only be ascertained by evolving the population of agents forward in time. While highlighting standard mathematical results, we compare those to agent-based methods that can go beyond the limitations of equations and simulate the complexity of heterogeneous populations and an ever-changing set of interactors. We conclude that agent-based methods can predict evolutionary outcomes where purely mathematical treatments cannot tread (for example in the weak selection–strong mutation limit), but that mathematics is crucial to validate the computational simulations. © 2016 Elsevier B.V.
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49.
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50.
  • Adami, C., et al. (author)
  • The XXL Survey VIII. MUSE characterisation of intracluster light in a z similar to 0.53 cluster of galaxies
  • 2016
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592:A7
  • Research review (peer-reviewed)abstract
    • Aims. Within a cluster, gravitational effects can lead to the removal of stars from their parent galaxies and their subsequent dispersal into the intracluster medium. Gas hydrodynamical effects can additionally strip gas and dust from galaxies; both gas and stars contribute to intracluster light (ICL). The properties of the ICL can therefore help constrain the physical processes at work in clusters by serving as a fossil record of the interaction history. Methods. The present study is designed to characterise this ICL for the first time in a similar to 10(14) M-circle dot and z similar to 0.53 cluster of galaxies from imaging and spectroscopic points of view. By applying a wavelet-based method to CFHT Megacam and WIRCAM images, we detect significant quantities of diffuse light and are able to constrain their spectral energy distributions. These sources were then spectroscopically characterised with ESO Multi Unit Spectroscopic Explorer (MUSE) spectroscopic data. MUSE data were also used to compute redshifts of 24 cluster galaxies and search for cluster substructures. Results. An atypically large amount of ICL, equivalent in i' to the emission from two brightest cluster galaxies, has been detected in this cluster. Part of the detected diffuse light has a very weak optical stellar component and apparently consists mainly of gas emission, while other diffuse light sources are clearly dominated by old stars. Furthermore, emission lines were detected in several places of diffuse light. Our spectral analysis shows that this emission likely originates from low-excitation parameter gas. Globally, the stellar contribution to the ICL is about 2.3 x 10(9) yr old even though the ICL is not currently forming a large number of stars. On the other hand, the contribution of the gas emission to the ICL in the optical is much greater than the stellar contribution in some regions, but the gas density is likely too low to form stars. These observations favour ram pressure stripping, turbulent viscous stripping, or supernovae winds as the origin of the large amount of intracluster light. Since the cluster appears not to be in a major merging phase, we conclude that ram pressure stripping is the most plausible process that generates the observed ICL sources. Conclusions. This is one of the first times that we are able to spectroscopically study diffuse light in such a distant and massive cluster, and it demonstrates the potential of MUSE observations for such studies.
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