1. |
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2. |
- Adam, J., et al.
(författare)
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Measurement of jet quenching with semi-inclusive hadron-jet distributions in central Pb-Pb collisions at root s(NN)=2.76 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :9
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Tidskriftsartikel (refereegranskat)abstract
- We report the measurement of a new observable of jet quenching in central Pb-Pb collisions at root s(NN) = 2.76 TeV, based on the semi-inclusive rate of charged jets recoiling from a high transverse momentum (high-p T) charged hadron trigger. Jets are measured using collinear-safe jet reconstruction with infrared cutoff for jet constituents of 0.15 GeV, for jet resolution parameters R = 0.2, 0.4 and 0.5. Underlying event background is corrected at the event-ensemble level, without imposing bias on the jet population. Recoil jet spectra are reported in the range 20 < p(T,jet)(ch) < 100 GeV. Reference distributions for pp collisions at root s = 2.76TeV are calculated using Monte Carlo and NLO pQCD methods, which are validated by comparing with measurements in pp collisions at root s = 7TeV. The recoil jet yield in central Pb-Pb collisions is found to be suppressed relative to that in pp collisions. No significant medium-induced broadening of the intra-jet energy profile is observed within 0.5 radians relative to the recoil jet axis. The angular distribution of the recoil jet yield relative to the trigger axis is found to be similar in central Pb-Pb and pp collisions, with no significant medium-induced acoplanarity observed. Large-angle jet deflection, which may provide a direct probe of the nature of the quasi-particles in hot QCD matter, is explored.
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3. |
- Adam, J., et al.
(författare)
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Centrality dependence of high-p(T) D meson suppression in Pb-Pb collisions at root s(NN)=2.76 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The nuclear modification factor, R-AA, of the prompt charmed mesons D-0, D+ and D*+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy root s(NN) = 2 : 76 TeV in two transverse momentum intervals, 5 < p(T) < 8 GeV/c and 8 < p(T) < 16 GeV/c, and in six collision centrality classes. The R-AA shows a maximum suppression of a factor of 5{6 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the R-AA of non-prompt J/psi from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions.
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4. |
- Adam, J., et al.
(författare)
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Centrality dependence of inclusive J/psi production in p-Pb collisions at root S-NN=5.02TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of inclusive J/psi production in p-Pb collisions at root S-NN = 5.02 TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, p(T), in the backward (-4.46 < y(cms) < -2.96) and forward (2.03 < y(cms) < 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region (-1.37 < y(cms) < 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The p(T)-differential J/psi production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average p(T) and p(T)(2) values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of p(T) for several centrality classes at backward and forward rapidity. At mid-and forward rapidity, the J/psi yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing p(T) of the J/psi. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions.
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5. |
- Adam, J., et al.
(författare)
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One-dimensional pion, kaon, and proton femtoscopy in Pb-Pb collisions at root(NN)-N-S=2.76 TeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- The size of the particle emission region in high-energy collisions can be deduced using the femtoscopic correlations of particle pairs at low relative momentum. Such correlations arise due to quantum statistics and Coulomb and strong final state interactions. In this paper, results are presented from femtoscopic analyses of pi(+/-) pi(+/-), K-+/- K-+/-, K-S(0) K-S(0), pp, and (pp) over bar correlations from Pb-Pb collisions at root s(NN) = 2.76 TeV by the ALICE experiment at the LHC. One-dimensional radii of the system are extracted from correlation functions in terms of the invariant momentum difference of the pair. The comparison of the measured radii with the predictions from a hydrokinetic model is discussed. The pion and kaon source radii display a monotonic decrease with increasing average pair transverse mass m(T) which is consistent with hydrodynamic model predictions for central collisions. The kaon and proton source sizes can be reasonably described by approximate m(T) scaling.
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6. |
- Adam, J., et al.
(författare)
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Coherent psi (2S) photo-production in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76TeV
- 2015
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 751, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- We have performed the first measurement of the coherent psi(2S) photo-production cross section in ultraperipheral Pb-Pb collisions at the LHC. This charmonium excited state is reconstructed via the psi(2S) -> l(+)l(-) and ->(2S) -> J/psi pi(+)pi(-) decays, where the J/psi decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 mu b(-1). The cross section for coherent psi(2S) production in the rapidity interval -0.9 < y < 0.9is d sigma(coh)(psi(2S))/dy = 0.83 +/- 0.19 (stat+syst) mb. The psi(2S) to J/psi coherent cross section ratio is 0.34(-0.07)(+0.08)(stat+syst). The obtained results are compared to predictions from theoretical models. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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7. |
- Adam, J., et al.
(författare)
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Coherent rho(0) photoproduction in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :9
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Tidskriftsartikel (refereegranskat)abstract
- We report the first measurement at the LHC of coherent photoproduction of rho(0) mesons in ultra-peripheral Pb-Pb collisions. The invariant mass and transverse momentum distributions for rho(0) production are studied in the pi(+)pi(-) decay channel at mid-rapidity. The production cross section in the rapidity range vertical bar y vertical bar < 0.5 is found to be d sigma/dy = 425 +/- 10 (stat.) (+42)(-50) (sys.) mb. Coherent rho(0) production is studied with and without requirement of nuclear breakup, and the fractional yields for various breakup scenarios are presented. The results are compared with those from lower energies and with model predictions.
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8. |
- Adam, J., et al.
(författare)
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Inclusive, prompt and non-prompt J/psi production at mid-rapidity in Pb-Pb collisions at root S-NN=2.76 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum (p(T)) dependence of the nuclear modification factor R-AA and the centrality dependence of the average transverse momentum for inclusive J/psi have been measured with ALICE for Pb-Pb collisions at root S-NN = 2.76TeV in the e(+)e(-) decay channel at mid-rapidity (vertical bar y vertical bar < 0.8). The is significantly smaller than the one observed for pp collisions at the same centre-of-mass energy. Consistently, an increase of RAA is observed towards low p(T). These observations might be indicative of a sizable contribution of charm quark coalescence to the J/psi production. Additionally, the fraction of non-prompt J/psi from beauty hadron decays, f(B), has been determined in the region 1.5 < p(T) < 10 GeV/c in three centrality intervals. No significant centrality dependence of fB is observed. Finally, the RAA of non-prompt J/psi is discussed and compared with model predictions. The nuclear modification in the region 4.5 < p(T) < 10 GeV/c is found to be stronger than predicted by most models.
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9. |
- Adam, J., et al.
(författare)
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Centrality dependence of particle production in p-Pb collisions at root s(NN)=5.02 TeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:6
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Tidskriftsartikel (refereegranskat)abstract
- We report measurements of the primary charged-particle pseudorapidity density and transverse momentum distributions in p-Pb collisions at root s(NN) = 5.02 TeV and investigate their correlation with experimental observables sensitive to the centrality of the collision. Centrality classes are defined by using different event-activity estimators, i.e., charged-particle multiplicities measured in three different pseudorapidity regions as well as the energy measured at beam rapidity (zero degree). The procedures to determine the centrality, quantified by the number of participants (N-part) or the number of nucleon-nucleon binary collisions (N-coll) are described. We show that, in contrast to Pb-Pb collisions, in p-Pb collisions large multiplicity fluctuations together with the small range of participants available generate a dynamical bias in centrality classes based on particle multiplicity. We propose to use the zero-degree energy, which we expect not to introduce a dynamical bias, as an alternative event-centrality estimator. Based on zero-degree energy-centrality classes, the N-part dependence of particle production is studied. Under the assumption that the multiplicity measured in the Pb-going rapidity region scales with the number of Pb participants, an approximate independence of the multiplicity per participating nucleon measured at mid-rapidity of the number of participating nucleons is observed. Furthermore, at high-pT the p-Pb spectra are found to be consistent with the pp spectra scaled by N-coll for all centrality classes. Our results represent valuable input for the study of the event-activity dependence of hard probes in p-Pb collisions and, hence, help to establish baselines for the interpretation of the Pb-Pb data.
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10. |
- Adam, J., et al.
(författare)
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Forward-backward multiplicity correlations in pp collisions at root s=0.9, 2.76 and 7 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :5
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Tidskriftsartikel (refereegranskat)abstract
- The strength of forward-backward (FB) multiplicity correlations is measured by the ALICE detector in proton-proton (pp) collisions at = 0.9, 2.76 and 7 TeV. The measurement is performed in the central pseudorapidity region (|eta| < 0.8) for the transverse momentum p (T) > 0.3 GeV/c. Two separate pseudorapidity windows of width (delta eta) ranging from 0.2 to 0.8 are chosen symmetrically around eta = 0. The multiplicity correlation strength (b (corr)) is studied as a function of the pseudorapidity gap (eta (gap)) between the two windows as well as the width of these windows. The correlation strength is found to decrease with increasing eta (gap) and shows a non-linear increase with delta eta. A sizable increase of the correlation strength with the collision energy, which cannot be explained exclusively by the increase of the mean multiplicity inside the windows, is observed. The correlation coefficient is also measured for multiplicities in different configurations of two azimuthal sectors selected within the symmetric FB eta-windows. Two different contributions, the short-range (SR) and the long-range (LR), are observed. The energy dependence of b (corr) is found to be weak for the SR component while it is strong for the LR component. Moreover, the correlation coefficient is studied for particles belonging to various transverse momentum intervals chosen to have the same mean multiplicity. Both SR and LR contributions to b (corr) are found to increase with p (T) in this case. Results are compared to PYTHIA and PHOJET event generators and to a string-based phenomenological model. The observed dependencies of b (corr) add new constraints on phenomenological models.
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11. |
- Adam, J., et al.
(författare)
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Measurement of charged jet production cross sections and nuclear modification in p-Pb collisions at root s(NN)=5.02 TeV
- 2015
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 749, s. 68-81
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Tidskriftsartikel (refereegranskat)abstract
- Charged jet production cross sections in p-Pb collisions at root s(NN) = 5.02 TeV measured with the ALICE detector at the LHC are presented. Using the anti-k(T) algorithm, jets have been reconstructed in the central rapidity region from charged particles with resolution parameters R = 0.2 and R = 0.4. The reconstructed jets have been corrected for detector effects and the underlying event background. To calculate the nuclear modification factor, R-pPb, of charged jets in p-Pb collisions, a pp reference was constructed by scaling previously measured charged jet spectra at root s = 7 TeV. In the transverse momentum range 20 <= p(T, chjet) <= 120 GeV/c, R-pPb is found to be consistent with unity, indicating the absence of strong nuclear matter effects on jet production. Major modifications to the radial jet structure are probed via the ratio of jet production cross sections reconstructed with the two different resolution parameters. This ratio is found to be similar to the measurement in pp collisions at root s = 7 TeV and to the expectations from PYTHIA pp simulations and NLO pQCD calculations at root s(NN) = 5.02 TeV. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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12. |
- Adam, J., et al.
(författare)
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Measurement of charm and beauty production at central rapidity versus charged-particle multiplicity in proton-proton collisions at root s=7 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :9
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Tidskriftsartikel (refereegranskat)abstract
- Prompt D meson and non-prompt J/psi yields are studied as a function of the multiplicity of charged particles produced in inelastic proton-proton collisions at a centre-of-mass energy of root s = 7 TeV. The results are reported as a ratio between yields in a given multiplicity interval normalised to the multiplicity-integrated ones (relative yields). They are shown as a function of the multiplicity of charged particles normalised to the average value for inelastic collisions (relative charged-particle multiplicity). D-0, D+ and D*+ mesons are measured in five p(T) intervals from 1 GeV/c to 20 GeV/c and for |y| < 0.5 via their hadronic decays. The D-meson relative yield is found to increase with increasing charged-particle multiplicity. For events with multiplicity six times higher than the average multiplicity of inelastic collisions, a yield enhancement of a factor about 15 relative to the multiplicity-integrated yield in inelastic collisions is observed. The yield enhancement is independent of transverse momentum within the uncertainties of the measurement. The D-0-meson relative yield is also measured as a function of the relative multiplicity at forward pseudo-rapidity. The non-prompt J/psi, i.e. the B hadron, contribution to the inclusive J/psi production is measured in the di-electron decay channel at central rapidity. It is evaluated for p(T) > 1.3 GeV/c and |y| < 0.9, and extrapolated to p(T) > 0. The fraction of non-prompt J/psi the inclusive J/psi yields shows no dependence on the charged-particle multiplicity at central rapidity. Charm and beauty hadron relative yields exhibit a similar increase with increasing charged-particle multiplicity. The measurements are compared to PYTHIA 8, EPOS 3 and percolation calculations.
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13. |
- Adam, J., et al.
(författare)
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Measurement of dijet k(T) in p-Pb collisions at root s(NN)=5.02 TeV
- 2015
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 746, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- A measurement of dijet correlations in p-Pb collisions at root s(NN) = 5.02 TeV with the ALICE detector is presented. Jets are reconstructed from charged particles measured in the central tracking detectors and neutral energy deposited in the electromagnetic calorimeter. The transverse momentum of the full jet (clustered from charged and neutral constituents) and charged jet (clustered from charged particles only) is corrected event-by-event for the contribution of the underlying event, while corrections for underlying event fluctuations and finite detector resolution are applied on an inclusive basis. A projection of the dijet transverse momentum, k(Ty) = p(T,jet)(ch+ne) sin(Delta phi(dijet)) with Delta phi(dijet) the azimuthal angle between a full and charged jet and p(T,jet)(ch+ne) the transverse momentum of the full jet, is used to study nuclear matter effects in p-Pb collisions. This observable is sensitive to the acoplanarity of dijet production and its potential modificationin p-Pb collisions with respect to pp collisions. Measurements of the dijet k(Ty) as a function of the transverse momentum of the full and recoil charged jet, and the event multiplicity are presented. No significant modification of k(Ty) due to nuclear matter effects in p-Pb collisions with respect to the event multiplicity or a PYTHIA8 reference is observed. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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14. |
- Adam, J., et al.
(författare)
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Measurement of jet suppression in central Pb-Pb collisions at root s(NN)=2.76 TeV
- 2015
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 746, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum(p(T)) spectrum and nuclear modification factor (R-AA) of reconstructed jets in 0-10% and 10-30% central Pb-Pb collisions at root s(NN) = 2.76 TeV were measured. Jets were reconstructed using the anti-k(T) jet algorithm with a resolution parameter of R = 0.2 from charged and neutral particles, utilizing the ALICE tracking detectors and Electromagnetic Calorimeter (EMCal). The jet p(T) spectra are reported in the pseudorapidity interval of \eta(jet)\ < 0.5 for 40 < p(T), jet < 120 GeV/c in 0-10% and for 30 < p(T), jet < 100 GeV/c in 10-30% collisions. Reconstructed jets were required to contain a leading charged particle with p(T) > 5 GeV/c to suppress jets constructed from the combinatorial background in Pb-Pb collisions. The leading charged particle requirement applied to jet spectra both in pp and Pb-Pb collisions had a negligible effect on the R-AA. The nuclear modification factor R-AA was found to be 0.28 +/- 0.04 in 0-10% and 0.35 +/- 0.04 in 10-30% collisions, independent of p(T), jet within the uncertainties of the measurement. The observed suppression is in fair agreement with expectations from two model calculations with different approaches to jet quenching. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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15. |
- Adam, J, et al.
(författare)
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Measurement of pion, kaon and proton production in proton-proton collisions at [Formula: see text] TeV.
- 2015
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of primary [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] production at mid-rapidity ([Formula: see text] 0.5) in proton-proton collisions at [Formula: see text][Formula: see text] 7 TeV performed with a large ion collider experiment at the large hadron collider (LHC) is reported. Particle identification is performed using the specific ionisation energy-loss and time-of-flight information, the ring-imaging Cherenkov technique and the kink-topology identification of weak decays of charged kaons. Transverse momentum spectra are measured from 0.1 up to 3 GeV/[Formula: see text] for pions, from 0.2 up to 6 GeV/[Formula: see text] for kaons and from 0.3 up to 6 GeV/[Formula: see text] for protons. The measured spectra and particle ratios are compared with quantum chromodynamics-inspired models, tuned to reproduce also the earlier measurements performed at the LHC. Furthermore, the integrated particle yields and ratios as well as the average transverse momenta are compared with results at lower collision energies.
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16. |
- Adam, J., et al.
(författare)
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Precision measurement of the mass difference between light nuclei and anti-nuclei
- 2015
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Ingår i: Nature Physics. - 1745-2473. ; 11:10, s. 120-811
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of the mass differences for systems bound by the strong force has reached a very high precision with protons and anti-protons(1,2). The extension of such measurement from (anti-)baryons to (anti-) nuclei allows one to probe any difference in the interactions between nucleons and anti-nucleons encoded in the (anti-) nuclei masses. This force is a remnant of the underlying strong interaction among quarks and gluons and can be described by effective theories(3), but cannot yet be directly derived from quantum chromodynamics. Here we report a measurement of the difference between the ratios of the mass and charge of deuterons (d) and anti-deuterons ((d) over bar), and He-3 and (3)(He) over bar nuclei carried out with the ALICE (A Large Ion Collider Experiment)(4) detector in Pb-Pb collisions at a centre-of-mass energy per nucleon pair of 2.76 TeV. Our direct measurement of the mass-over-charge differences confirms CPT invariance to an unprecedented precision in the sector of light nuclei(5,6). This fundamental symmetry of nature, which exchanges particles with anti-particles, implies that all physics laws are the same under the simultaneous reversal of charge(s) (charge conjugation C), reflection of spatial coordinates (parity transformation P) and time inversion (T).
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17. |
- Adam, J., et al.
(författare)
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Rapidity and transverse-momentum dependence of the inclusive J/psi nuclear modification factor in p-Pb collisions at root s(NN)=5.02 TeV
- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the transverse-momentum (p(T)) dependence of the inclusive J/psi production in p-Pb collisions at root s(NN) = 5.02 TeV, in three center-of-mass rapidity (y(cms)) regions, down to zero p(T). Results in the forward and backward rapidity ranges (2.03 < y(cms) < 3.53 and -4.46 < y(cms) < -2.96) are obtained by studying the J/psi decay to mu(+)mu(-), while the mid-rapidity region (-1.37 < y(cms) < 0.43) is investigated by measuring the e(+)e(-) decay channel. The p(T) dependence of the J/psi production cross section and nuclear modification factor are presented for each of the rapidity intervals, as well as the J/psi mean p(T) values. Forward and mid-rapidity results show a suppression of the J/psi yield, with respect to pp collisions, which decreases with increasing p(T). At backward rapidity no significant J/psi suppression is observed. Theoretical models including a combination of cold nuclear matter effects such as shadowing and partonic energy loss, are in fair agreement with the data, except at forward rapidity and low transverse momentum. The implications of the p-Pb results for the evaluation of cold nuclear matter effects on J/psi production in Pb-Pb collisions are also discussed.
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18. |
- Adam, J., et al.
(författare)
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Search for weakly decaying (Lambda n)over-bar and Lambda Lambda exotic bound states in central Pb-Pb collisions at root S-NN=2.76 TeV
- 2016
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 752, s. 267-277
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Tidskriftsartikel (refereegranskat)abstract
- We present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possible (Lambda n) over bar bound state. The search is performed with the ALICE detector in central (0-10%) Pb-Pb collisions at root S-NN = 2.76 TeV, by invariant mass analysis in the decay modes (Lambda n) over bar (d) over bar pi(+) and H-dibaryon -> Lambda p pi(-). No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.
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19. |
- Adam, J., et al.
(författare)
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Two-pion femtoscopy in p-Pb collisions at root(NN)-N-S=5.02 TeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of the femtoscopic analysis of pairs of identical pions measured in p-Pb collisions at root(NN)-N-S = 5.02 TeV. Femtoscopic radii are determined as a function of event multiplicity and pair momentum in three spatial dimensions. As in the pp collision system, the analysis is complicated by the presence of sizable background correlation structures in addition to the femtoscopic signal. The radii increase with event multiplicity and decrease with pair transverse momentum. When taken at comparable multiplicity, the radii measured in p-Pb collisions, at high multiplicity and low pair transverse momentum, are 10%-20% higher than those observed in pp collisions but below those observed in A-A collisions. The results are compared to hydrodynamic predictions at large event multiplicity as well as discussed in the context of calculations based on gluon saturation.
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20. |
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21. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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22. |
- Wang, Haidong, et al.
(författare)
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Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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23. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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24. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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25. |
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26. |
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27. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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28. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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29. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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30. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)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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31. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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32. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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33. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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34. |
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35. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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36. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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37. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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38. |
- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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39. |
- Chatterjee, Pratishtha, et al.
(författare)
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Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer's disease.
- 2019
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Ingår i: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer's disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation.Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65-90years, with normal global cognition (Mini-Mental State Examination Score≥26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort.A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r=.451, p<.0001). Positive correlations were also observed between NFL and kynurenine (r=.364, p<.0005), kynurenic acid (r=.384, p<.0001), 3-hydroxykynurenine (r=.246, p=.014), anthranilic acid (r=.311, p=.002), and quinolinic acid (r=.296, p=.003). Further, significant associations were observed between plasma Aβ40 and the K/T (r=.375, p<.0005), kynurenine (r=.374, p<.0005), kynurenic acid (r=.352, p<.0005), anthranilic acid (r=.381, p<.0005), and quinolinic acid (r=.352, p<.0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r=.215, p=.034), kynurenic acid (r=.214, p=.035), anthranilic acid (r=.278, p=.006), and quinolinic acid (r=.224, p=.027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent.The current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.
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40. |
- Figueroa, Jonine D., et al.
(författare)
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Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 25:6, s. 1203-1214
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Tidskriftsartikel (refereegranskat)abstract
- Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.
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41. |
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42. |
- Bien, Stephanie A., et al.
(författare)
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Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
- 2019
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Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 138:4, s. 307-326
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n=169) and whole blood (n=922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-4)). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P<0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.
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43. |
- Huijben, Jilske A., et al.
(författare)
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Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
- 2019
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.
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44. |
- Lee, Crystal Man Ying, et al.
(författare)
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Comparing different definitions of prediabetes with subsequent risk of diabetes: an individual participant data meta-analysis involving 76 513 individuals and 8208 cases of incident diabetes.
- 2019
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Ingår i: BMJ open diabetes research & care. - : BMJ. - 2052-4897. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- There are currently five widely used definition of prediabetes. We compared the ability of these to predict 5-year conversion to diabetes and investigated whether there were other cut-points identifying risk of progression to diabetes that may be more useful.We conducted an individual participant meta-analysis using longitudinal data included in the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox regression models were used to obtain study-specific HRs for incident diabetes associated with each prediabetes definition. Harrell's C-statistics were used to estimate how well each prediabetes definition discriminated 5-year risk of diabetes. Spline and receiver operating characteristic curve (ROC) analyses were used to identify alternative cut-points.Sixteen studies, with 76513 participants and 8208 incident diabetes cases, were available. Compared with normoglycemia, current prediabetes definitions were associated with four to eight times higher diabetes risk (HRs (95% CIs): 3.78 (3.11 to 4.60) to 8.36 (4.88 to 14.33)) and all definitions discriminated 5-year diabetes risk with good accuracy (C-statistics 0.79-0.81). Cut-points identified through spline analysis were fasting plasma glucose (FPG) 5.1mmol/L and glycated hemoglobin (HbA1c) 5.0% (31 mmol/mol) and cut-points identified through ROC analysis were FPG 5.6mmol/L, 2-hour postload glucose 7.0mmol/L and HbA1c 5.6% (38 mmol/mol).In terms of identifying individuals at greatest risk of developing diabetes within 5years, using prediabetes definitions that have lower values produced non-significant gain. Therefore, deciding which definition to use will ultimately depend on the goal for identifying individuals at risk of diabetes.
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45. |
- Lee, Crystal Man Ying, et al.
(författare)
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Comparison of relationships between four common anthropometric measures and incident diabetes
- 2017
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 132, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Aims: First, to conduct a detailed exploration of the prospective relations between four commonly used anthropometric measures with incident diabetes and to examine their consistency across different population subgroups. Second, to compare the ability of each of the measures to predict five-year risk of diabetes. Methods: We conducted a meta- analysis of individual participant data on body mass index (BMI), waist circumference (WC), waist- hip and waist- height ratio (WHtR) from the Obesity, Diabetes and Cardiovascular Disease Collaboration. Cox proportional hazard models were used to estimate the association between a one standard deviation increment in each anthropometric measure and incident diabetes. Harrell's concordance statistic was used to test the predictive accuracy of each measure for diabetes risk at five years. Results: Twenty- one studies with 154,998 participants and 9342 cases of incident diabetes were available. Each of the measures had a positive association with incident diabetes. A one standard deviation increment in each of the measures was associated with 64- 80% higher diabetes risk. WC and WHtR more strongly associated with risk than BMI (ratio of hazard ratios: 0.95 [0.92,0.99] - 0.97 [0.95,0.98]) but there was no appreciable difference between the four measures in the predictive accuracy for diabetes at five years. Conclusions: Despite suggestions that abdominal measures of obesity have stronger associations with incident diabetes and better predictive accuracy than BMI, we found no overall advantage in any one measure at discriminating the risk of developing diabetes. Any of these measures would suffice to assist in primary diabetes prevention efforts.
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46. |
- Nettleton, Jennifer A, et al.
(författare)
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Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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47. |
- Pope, Welkin H, et al.
(författare)
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Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity.
- 2015
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Ingår i: eLIFE. - 2050-084X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery.
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48. |
- Lee, Duk-Hee, et al.
(författare)
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Association between background exposure to organochlorine pesticides and the risk of cognitive impairment : A prospective study that accounts for weight change
- 2016
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 89-90, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- Background: Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change.Methods: Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases.Results: The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and ≥75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (Ptrend=0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and ≥75th percentiles compared to <25th percentile (Ptrend<0.01).Conclusions: This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations.
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49. |
- Lee, Duk-Hee, et al.
(författare)
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Neurotoxic chemicals in adipose tissue : A role in puzzling findings on obesity and dementia
- 2018
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 90:4, s. 176-182
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Tidskriftsartikel (refereegranskat)abstract
- Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.
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50. |
- Zhang, Mingfeng, et al.
(författare)
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Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:41, s. 66328-66343
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
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