| 1. |
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| 2. |
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| 3. |
- Adare, A., et al.
(författare)
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Medium Modification of Jet Fragmentation in Au plus Au Collisions at root S-NN=200 GeV Measured in Direct Photon-Hadron Correlations
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:3
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Tidskriftsartikel (refereegranskat)abstract
- The jet fragmentation function is measured with direct photon-hadron correlations in p + p and Au + Au collisions at root S-NN = 200 GeV. The P-T of the photon is an excellent approximation to the initial P-T of the jet and the ratio Z(T) = P-T(h)/P-T(gamma) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au + Au collisions while a photon isolation cut is applied in p + p. I-AA, the ratio of hadron yield opposite the photon in Au + Au to that in p + p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high Z(T). The associated hadron yield at low Z(T) is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.
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| 4. |
- Adare, A., et al.
(författare)
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Production of omega mesons in p plus p, d plus Au, Cu plus Cu, and Au plus Au collisions at root s(NN)=200 GeV
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:4
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured omega meson production via leptonic and hadronic decay channels in p + p, d + Au, Cu+ Cu, and Au + Au collisions at root s(NN) = 200 GeV. The invariant transverse momentum spectra measured in different decay modes give consistent results. Measurements in the hadronic decay channel in Cu Cu and Au + Au collisions show that. production has a suppression pattern at high transverse momentum, similar to that of pi(0) and eta in central collisions, but no suppression is observed in peripheral collisions. The nuclear modification factors, R-AA, are consistent in Cu + Cu and Au + Au collisions at similar numbers of participant nucleons.
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| 5. |
- Adare, A., et al.
(författare)
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Measurement of higher cumulants of net-charge multiplicity distributions in Au plus Au collisions at root s(NN)=7.7-200 GeV
- 2016
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 93:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the measurement of cumulants (C-n,n = 1, ..., 4) of the net-charge distributions measured within pseudorapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(NN) = 7.7-200 GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g., C-1/C-2, C-3/C-1) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of C-1/C-2 and C-3/C-1 can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy. The extracted baryon chemical potentials are in excellent agreement with a thermal-statistical analysis model.
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| 6. |
- Adare, A., et al.
(författare)
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Centrality dependence of low-momentum direct-photon production in Au plus Au collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:6
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at RHIC has measured the centrality dependence of the direct photon yield from Au + Au collisions at root s(NN) = 200 GeV down to pT = 0.4 GeV/c. Photons are detected via photon conversions to e(+)e(-) pairs and an improved technique is applied that minimizes the systematic uncertainties that usually limit direct photon measurements, in particular at low pT. We find an excess of direct photons above the N-coll-scaled yield measured in p + p collisions. This excess yield is well described by an exponential distribution with an inverse slope of about 240 MeV/c in the pT range 0.6-2.0 GeV/c. While the shape of the pT distribution is independent of centrality within the experimental uncertainties, the yield increases rapidly with increasing centrality, scaling approximately with N-part(alpha), where alpha = 1.38 +/- 0.03(stat) +/- 0.07(syst).
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| 7. |
- Adare, A., et al.
(författare)
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Systematic study of charged-pion and kaon femtoscopy in Au plus Au collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
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Tidskriftsartikel (refereegranskat)abstract
- We present a systematic study of charged-pion and kaon interferometry in Au + Au collisions at root s(NN) = 200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.
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| 8. |
- Adare, A., et al.
(författare)
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Azimuthal correlations of electrons from heavy-flavor decay with hadrons in p plus p and Au plus Au collisions at root s(NN)=200 GeV
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 83:4
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of electrons from the decay of open-heavy-flavor mesons have shown that the yields are suppressed in Au+Au collisions compared to expectations from binary-scaled p+p collisions. These measurements indicate that charm and bottom quarks interact with the hot dense matter produced in heavy-ion collisions much more than expected. Here we extend these studies to two-particle correlations where one particle is an electron from the decay of a heavy-flavor meson and the other is a charged hadron from either the decay of the heavy meson or from jet fragmentation. These measurements provide more detailed information about the interactions between heavy quarks and the matter, such as whether the modification of the away-side-jet shape seen in hadron-hadron correlations is present when the trigger particle is from heavy-meson decay and whether the overall level of away-side-jet suppression is consistent. We statistically subtract correlations of electrons arising from background sources from the inclusive electron-hadron correlations and obtain two-particle azimuthal correlations at root s(NN) = 200 GeV between electrons from heavy-flavor decay with charged hadrons in p+p and also first results in Au+Au collisions. We find the away-side-jet shape and yield to be modified in Au+Au collisions compared to p+p collisions.
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| 9. |
- Adare, A., et al.
(författare)
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Suppression of away-side jet fragments with respect to the reaction plane in Au plus Au collisions at root s(NN)=200 GeV
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:2
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Tidskriftsartikel (refereegranskat)abstract
- Pair correlations between large transverse momentum neutral pion triggers (p(T) = 4-7 GeV/c) and charged hadron partners (p(T) = 3-7 GeV/c) in central (0%-20%) and midcentral (20%-60%) Au + Au collisions at root s(NN) = 200 GeV are presented as a function of trigger orientation with respect to the reaction plane. The particles are at larger momentum than where jet shape modifications have been observed, and the correlations are sensitive to the energy loss of partons traveling through hot densematter. An out-of-plane trigger particle produces only 26 +/- 20% of the away-side pairs that are observed opposite of an in-plane trigger particle for midcentral (20%-60%) collisions. In contrast, near-side jet fragments are consistent with no suppression or dependence on trigger orientation with respect to the reaction plane. These observations are qualitatively consistent with a picture of little near-side parton energy loss either due to surface bias or fluctuations and increased away-side parton energy loss due to a long path through the medium. The away-side suppression as a function of reaction-plane angle is shown to be sensitive to both the energy loss mechanism and the space-time evolution of heavy-ion collisions.
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| 10. |
- Adare, A., et al.
(författare)
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Transition in Yield and Azimuthal Shape Modification in Dihadron Correlations in Relativistic Heavy Ion Collisions
- 2010
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Ingår i: Physical Review Letters. - 1079-7114. ; 104:25
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Tidskriftsartikel (refereegranskat)abstract
- Hard-scattered parton probes produced in collisions of large nuclei indicate large partonic energy loss, possibly with collective produced-medium response to the lost energy. We present measurements of pi(0) trigger particles at transverse momenta p(T)(t) = 4-12 GeV/c and associated charged hadrons (p(T)(a) = 0.5-7 GeV/c) vs relative azimuthal angle Delta phi in Au + Au and p + p collisions at root s(NN) = 200 GeV. The Au + Au distribution at low p(T)(a), whose shape has been interpreted as a medium effect, is modified for p(T)(t) < 7 GeV/c. At higher p(T)(t), the data are consistent with unmodified or very weakly modified shapes, even for the lowest measured p(T)(a), which quantitatively challenges some medium response models. The associated yield of hadrons opposing the trigger particle in Au + Au relative to p + p (I-AA) is suppressed at high p(T) (I-AA approximate to 0.35-0.5), but less than for inclusive suppression (R-AA approximate to 0.2).
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| 11. |
- Adare, A., et al.
(författare)
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Transverse momentum dependence of eta meson suppression in Au plus Au collisions at root s(NN)=200 GeV
- 2010
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 82:1
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Tidskriftsartikel (refereegranskat)abstract
- New measurements by the PHENIX experiment at the Relativistic Heavy Ion Collider for. production at midrapidity as a function of transverse momentum ((PT)) and collision centrality in root s(NN) = 200 GeV Au + Au and p + p collisions are presented. They indicate nuclear modification factors (R-AA) which are similar in both magnitude and trend to those found in earlier pi(0) measurements. Linear fits to R-AA as a function of (PT) in 5-20 GeV/c show that the slope is consistent with zero within two standard deviations at all centralities, although a slow rise cannot be excluded. Having different statistical and systematic uncertainties, the pi(0) and eta measurements are complementary at high (PT); thus, along with the extended (PT) range of these data they can provide additional constraints for theoretical modeling and the extraction of transport properties.
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| 12. |
- Adare, A., et al.
(författare)
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Spectra and ratios of identified particles in Au plus Au and d plus Au collisions at root s(NN)=200 GeV
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:2
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Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum (p(T)) spectra and ratios of identified charged hadrons (pi(+/-), K-+/-, p, (p) over bar) produced in root s(NN) = 200 GeV Au + Au and d + Au collisions are reported in five different centrality classes for each collision species. The measurements of pions and protons are reported up to p(T) = 6 GeV/c (5 GeV/c), and the measurements of kaons are reported up to p(T) = 4 GeV/c (3.5 GeV/c) in Au + Au (d + Au) collisions. In the intermediate p(T) region, between 2 and 5 GeV/c, a significant enhancement of baryon-to-meson ratios compared to those measured in p + p collisions is observed. This enhancement is present in both Au + Au and d + Au collisions and increases as the collisions become more central. We compare a class of peripheral Au + Au collisions with a class of central d + Au collisions which have a comparable number of participating nucleons and binary nucleon-nucleon collisions. The p(T)-dependent particle ratios for these classes display a remarkable similarity, which is then discussed.
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| 13. |
- Adare, A., et al.
(författare)
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Azimuthal anisotropy of pi(0) and eta mesons in Au plus Au collisions at root s(NN)=200 GeV
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:6
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Tidskriftsartikel (refereegranskat)abstract
- The azimuthal anisotropy coefficients v2 and v4 of p 0 and. mesons are measured in Au + Au collisions at root s(NN) = 200 GeV as a function of transverse momentum p(T) (1-14 GeV/c) and centrality. The extracted v(2) coefficients are found to be consistent between the two meson species over the measured p(T) range. The ratio of v(4)/v(2)(2) for pi(0) mesons is found to be independent of p(T) for 1- 9 GeV/c, implying a lack of sensitivity of the ratio to the change of underlying physics with p(T). Furthermore, the ratio of v(4)/v(2)(2) is systematically larger in central collisions, which may reflect the combined effects of fluctuations in the initial collision geometry and finite viscosity in the evolving medium.
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| 14. |
- Adare, A., et al.
(författare)
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Azimuthal Anisotropy of pi(0) Production in Au plus Au Collisions at root s(NN)=200 GeV: Path-Length Dependence of Jet Quenching and the Role of Initial Geometry
- 2010
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Ingår i: Physical Review Letters. - 1079-7114. ; 105:14
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Tidskriftsartikel (refereegranskat)abstract
- We have measured the azimuthal anisotropy of pi(0) production for 1 < p(T) < 18 GeV/c for Au + Au collisions at root s(NN) = 200 GeV. The observed anisotropy shows a gradual decrease for 3 less than or similar to p(T) less than or similar to 7-10 GeV/c, but remains positive beyond 10 GeV/c. The magnitude of this anisotropy is underpredicted, up to at least similar to 10 GeV/c, by current perturbative QCD (PQCD) energy-loss model calculations. An estimate of the increase in anisotropy expected from initial-geometry modification due to gluon saturation effects and fluctuations is insufficient to account for this discrepancy. Calculations that implement a path-length dependence steeper than what is implied by current PQCD energy-loss models show reasonable agreement with the data.
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| 15. |
- Adare, A., et al.
(författare)
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Deviation from quark number scaling of the anisotropy parameter v(2) of pions, kaons, and protons in Au+Au collisions at root s(NN)=200 GeV
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:6
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the anisotropy parameter v(2) of identified hadrons (pions, kaons, and protons) as a function of centrality, transverse momentum p(T), and transverse kinetic energy KET at midrapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(N N) = 200 GeV are presented. Pions and protons are identified up to p(T) = 6 GeV/c, and kaons up to p(T) = 4 GeV/c, by combining information from time-of-flight and aerogel Cerenkov detectors in the PHENIX Experiment. The scaling of v(2) with the number of valence quarks (n(q)) has been studied in different centrality bins as a function of transverse momentum and transverse kinetic energy. A deviation from previously observed quark-number scaling is observed at large values of KET/n(q) in noncentral Au + Au collisions (20-60%), but this scaling remains valid in central collisions (0-10%).
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| 16. |
- Adare, A., et al.
(författare)
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Elliptic and Hexadecapole Flow of Charged Hadrons in Au plus Au Collisions at root s(NN)=200 GeV
- 2010
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Ingår i: Physical Review Letters. - 1079-7114. ; 105:6
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Tidskriftsartikel (refereegranskat)abstract
- Differential measurements of the elliptic (upsilon(2)) and hexadecapole (upsilon(4)) Fourier flow coefficients are reported for charged hadrons as a function of transverse momentum (p(T)) and collision centrality or number of participant nucleons (N-part) for Au + Au collisions at root s(NN) = 200 GeV/ The upsilon(2,4) measurements at pseudorapidity vertical bar eta vertical bar <= 0.35, obtained with four separate reaction-plane detectors positioned in the range 1.0 < vertical bar eta vertical bar < 3.9, show good agreement, indicating the absence of significant Delta eta-dependent nonflow correlations. Sizable values for upsilon(4)(p(T)) are observed with a ratio upsilon(4)(p(T), N-part)/upsilon(2)(2)(p(T), N-part) approximate to 0.8 for 50 less than or similar to N-part less than or similar to 200, which is compatible with the combined effects of a finite viscosity and initial eccentricity fluctuations. For N-part greater than or similar to 200 this ratio increases up to 1.7 in the most central collisions.
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| 17. |
- Adare, A., et al.
(författare)
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J/psi suppression at forward rapidity in Au plus Au collisions at root s(NN)=200 GeV
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:5
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Tidskriftsartikel (refereegranskat)abstract
- Heavy quarkonia are observed to be suppressed in relativistic heavy-ion collisions relative to their production in p + p collisions scaled by the number of binary collisions. In order to determine if this suppression is related to color screening of these states in the produced medium, one needs to account for other nuclear modifications including those in cold nuclear matter. In this paper, we present new measurements from the PHENIX 2007 data set of J/psi yields at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in Au + Au collisions at root s(NN) = 200 GeV. The data confirm the earlier finding that the suppression of J/. at forward rapidity is stronger than at midrapidity, while also extending the measurement to finer bins in collision centrality and higher transverse momentum (p(T)). We compare the experimental data to the most recent theoretical calculations that incorporate a variety of physics mechanisms including gluon saturation, gluon shadowing, initial-state parton energy loss, cold nuclear matter breakup, color screening, and charm recombination. We find J/psi suppression beyond cold-nuclear-matter effects. However, the current level of disagreement between models and d + Au data precludes using these models to quantify the hot-nuclear-matter suppression.
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| 18. |
- Adare, A., et al.
(författare)
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Measurements of Higher Order Flow Harmonics in Au plus Au Collisions at root s(NN)=200 GeV
- 2011
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Ingår i: Physical Review Letters. - 1079-7114. ; 107:25
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Tidskriftsartikel (refereegranskat)abstract
- Flow coefficients nu(n) for n = 2, 3, 4, characterizing the anisotropic collective flow in Au + Au collisions at root s(NN) = 200 GeV, are measured relative to event planes Psi(n), determined at large rapidity. We report nu(n) as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The nu(n) are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio eta/s.
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| 19. |
- Adare, A., et al.
(författare)
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Neutral pion production with respect to centrality and reaction plane in Au plus Au collisions at root S-NN=200 GeV
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:3
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment has measured the production of pi(0)s in Au + Au collisions at root S-NN = 200 GeV. The new data offer a fourfold increase in recorded luminosity, providing higher precision and a larger reach in transverse momentum, p(T), to 20 GeV/c. The production ratio of eta/pi(0) is 0.46 +/- 0.01(stat) +/- 0.05(syst), constant with p(T) and collision centrality. The observed ratio is consistent with earlier measurements, as well as with the p + p and d + Au values. pi(0) are suppressed by a factor of 5, as in earlier findings. However, with the improved statistical precision a small but significant rise of the nuclear modification factor R-AA vs p(T), with a slope of 0.0106 +/-(0.0034)(0.0029) (Gev/c)(-1), is discernible in central collisions. A phenomenological extraction of the average fractional parton energy loss shows a decrease with increasing p(T). To study the path-length dependence of suppression, the pi(0) yield is measured at different angles with respect to the event plane; a strong azimuthal dependence of the pi(0) R-AA is observed. The data are compared to theoretical models of parton energy loss as a function of the path length L in the medium. Models based on perturbative quantum chromodynamics are insufficient to describe the data, while a hybrid model utilizing pQCD for the hard interactions and anti-de-Sitter space/conformal field theory (AdS/CFT) for the soft interactions is consistent with the data. DOI: 10.1103/PhysRevC.87.034911
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| 20. |
- Adare, A., et al.
(författare)
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Observation of Direct-Photon Collective Flow in Au plus Au Collisions at root s(NN)=200 GeV
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 109:12
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Tidskriftsartikel (refereegranskat)abstract
- The second Fourier component v(2) of the azimuthal anisotropy with respect to the reaction plane is measured for direct photons at midrapidity and transverse momentum (p(T)) of 1-12 GeV/c in Au + Au collisions at root s(NN) = 200 GeV. Previous measurements of this quantity for hadrons with p(T) < 6 GeV/c indicate that the medium behaves like a nearly perfect fluid, while for p(T) > 6 GeV/c a reduced anisotropy is interpreted in terms of a path-length dependence for parton energy loss. In this measurement with the PHENIX detector at the Relativistic Heavy Ion Collider we find that for p(T) > 4 GeV/c the anisotropy for direct photons is consistent with zero, which is as expected if the dominant source of direct photons is initial hard scattering. However, in the p(T) < 4 GeV/c region dominated by thermal photons, we find a substantial direct-photon v(2) comparable to that of hadrons, whereas model calculations for thermal photons in this kinematic region underpredict the observed v(2).
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| 21. |
- Adare, A, et al.
(författare)
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Azimuthal-Angle Dependence of Charged-Pion-Interferometry Measurements with Respect to Second- and Third-Order Event Planes in Au+Au Collisions at sqrt[s_{NN}]=200 GeV.
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 112:22
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Tidskriftsartikel (refereegranskat)abstract
- Charged-pion-interferometry measurements were made with respect to the second- and third-order event plane for Au+Au collisions at sqrt[s_{NN}]=200 GeV. A strong azimuthal-angle dependence of the extracted Gaussian-source radii was observed with respect to both the second- and third-order event planes. The results for the second-order dependence indicate that the initial eccentricity is reduced during the medium evolution, which is consistent with previous results. In contrast, the results for the third-order dependence indicate that the initial triangular shape is significantly reduced and potentially reversed by the end of the medium evolution, and that the third-order oscillations are largely dominated by the dynamical effects from triangular flow.
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| 22. |
- 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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| 23. |
- Dunn, R. J. H., et al.
(författare)
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GLOBAL CLIMATE : State of the Climate in 2020
- 2021
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Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 102:8
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Tidskriftsartikel (refereegranskat)
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| 24. |
- Izadi, Z., et al.
(författare)
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Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19
- 2021
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. OBJECTIVE To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. DESIGN, SETTING, AND PARTICIPANTS This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age >= 18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. EXPOSURES Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. MAIN OUTCOMES AND MEASURES The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. RESULTS A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. CONCLUSIONS AND RELEVANCE In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.
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| 25. |
- Pulit, SL, et al.
(författare)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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| 26. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Sparks, JA, et al.
(författare)
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Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry
- 2021
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:9, s. 1137-1146
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Tidskriftsartikel (refereegranskat)abstract
- To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.
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| 32. |
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| 33. |
- Winick-Ng, W, et al.
(författare)
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Cell-type specialization is encoded by specific chromatin topologies
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 599:7886, s. 684-
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.
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| 34. |
- Jans, A., et al.
(författare)
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Impact of dietary fat quantity and quality on skeletal muscle fatty acid metabolism in subjects with the metabolic syndrome
- 2012
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:11, s. 1554-1565
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is characterized by disturbances in lipid metabolism in skeletal muscle. Our aim was to investigate whether gene expression and fatty acid (FA) profile of skeletal muscle lipids are affected by diets differing in fat quantity and quality in subjects with the metabolic syndrome (MetS) and varying degrees of insulin sensitivity. 84 subjects (age 57.3 ± 0.9 y, BMI 30.9 ± 0.4 kg/m 2, 42 M/42 F) were randomly assigned to one of four iso-energetic diets: high-SFA (HSFA); high-MUFA (HMUFA) or two low-fat, high-complex carbohydrate diets, supplemented with 1.24 g/day of long-chain n-3 PUFA (LFHCCn-3) or control oil (LFHCC) for 12 weeks. In a subgroup of men (n = 26), muscle TAG, DAG, FFA and phospholipid contents were determined including their fractional synthetic rate (FSR) and FA composition at fasting and 4 h after consumption of a high-fat mixed-meal, both pre- and post-intervention. Genes involved in lipogenesis were downregulated after HMUFA (mean fold change - 1.3) and after LFHCCn-3 (fold change - 1.7) in insulin resistant subjects (< median of (S I)), whereas in insulin sensitive subjects (> median of insulin sensitivity) the opposite effect was shown (fold change + 1.6 for both diets). HMUFA diet tended to decrease FSR in TAG (P =.055) and DAG (P =.066), whereas the LFHCCn-3 diet reduced TAG content (P =.032). In conclusion, HMUFA and LFHCCn-3 diets reduced the expression of the lipogenic genes in skeletal muscle of insulin resistant subjects, whilst HMUFA reduced the fractional synthesis rate of DAG and TAG and LFHCC n-3 the TAG content. Our data indicate that these diets may reduce muscle fat accumulation by affecting the balance between FA synthesis, storage and oxidation.
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| 35. |
- Sattui, Sebastian E., et al.
(författare)
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Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry : a retrospective cohort study
- 2021
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 3:12, s. E855-E864
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. Methods In this retrospective cohort study, adult patients (aged >= 18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behcet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. Findings Of 1202 eligible patients identified in the registry, 733 (61.0%) were women arid 469 (39.0%) were men, and their mean age was 63.8 years (SD 17.1). A total of 374 (31.1%) patients had polymyalgia rheumatica, 353 (29.4%) had ANCA-associated vasculitis, 183 (15.2%) had giant cell arteritis, 112 (9.3%) had Behcet's syndrome, and 180 (15.0%) had other vasculitis. Of 1020 (84. 9%) patients with outcome data, 512 (S0.2%) were not hospitalised, 114 (11.2%) were hospitalised and did not receive supplemental oxygen, 239 (23 - 4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15.2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1.44 [95% CI 1. 31-1- 571), were male compared with female (1.38 [1.05-1.801), had more comorbidities (per each additional comorbidity 1.39 [1- 23-1- 581), were taking 10 mg/day or more of prednisolone compared with none (2.14 [1.50-3.04J), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2.12 [1.49-3.021). Risk factors varied among different disease subtypes. Interpretation Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to info rm mitigation strategies for patients with these diseases.
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| 36. |
- Wu, J., et al.
(författare)
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Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
- 2012
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 150:2, s. 366-376
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Tidskriftsartikel (refereegranskat)abstract
- Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential.
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| 37. |
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| 38. |
- Jatuworapruk, Kanon, et al.
(författare)
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Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19 : Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry
- 2022
-
Ingår i: ACR Open Rheumatology. - : John Wiley & Sons. - 2578-5745. ; 4:11, s. 948-953
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes.MethodsData on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death.ResultsOne hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities.ConclusionThis cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.
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| 39. |
- Ng, Bobby G, et al.
(författare)
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ALG1-CDG: Clinical and Molecular Characterization of 39 Unreported Patients.
- 2016
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794.
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Tidskriftsartikel (refereegranskat)abstract
- Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over one hundred genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate (DLO) required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date thirteen mutations in eighteen patients from fourteen families have been described with varying degrees of clinical severity. We identified and characterized thirty-nine previously unreported cases of ALG1-CDG from thirty-two families and add twenty-six new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all twenty-seven patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder. This article is protected by copyright. All rights reserved.
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| 40. |
- Sparks, Justin L, et al.
(författare)
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RNase H2-Initiated Ribonucleotide Excision Repair
- 2012
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 47:6, s. 980-986
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotides are incorporated into DNA by the replicative DNA polymerases at frequencies of about 2 per kb, which makes them by far the most abundant form of potential DNA damage in the cell. Their removal is essential for restoring a stable intact chromosome. Here, we present a complete biochemical reconstitution of the ribonucleotide excision repair (RER) pathway with enzymes purified from Saccharomyces cerevisiae. RER is most efficient when the ribonucleotide is incised by RNase H2, and further excised by the flap endonuclease FEN1 with strand displacement synthesis carried out by DNA polymerase δ, the PCNA clamp, its loader RFC, and completed by DNA ligase I. We observed partial redundancy for several of the enzymes in this pathway. Exo1 substitutes for FEN1 and Pol ε for Pol δ with reasonable efficiency. However, RNase H1 fails to substitute for RNase H2 in the incision step of RER.
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| 41. |
- Izadi, Zara, et al.
(författare)
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Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease : an observational study
- 2022
-
Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 4:9, s. e603-e613
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally.Methods: In this observational study, we derived individual-level data on adults (aged 18–99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death.Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01–1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10–1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02–1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00–1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88–1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44–0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74–0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69–0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1–9·5]; p=0·14).Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities.
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| 42. |
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| 43. |
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| 44. |
- Strangfeld, Anja, et al.
(författare)
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Factors associated with COVID-19-related death in people with rheumatic diseases : results from the COVID-19 Global Rheumatology Alliance physician-reported registry
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:7, s. 930-942
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases.Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.
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| 45. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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