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1.
  • Adam, J., et al. (author)
  • Centrality dependence of inclusive J/psi production in p-Pb collisions at root S-NN=5.02TeV
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)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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2.
  • Adam, J., et al. (author)
  • Centrality dependence of high-p(T) D meson suppression in Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)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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3.
  • Adam, J., et al. (author)
  • Coherent psi (2S) photo-production in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76TeV
  • 2015
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 751, s. 358-370
  • Journal article (peer-reviewed)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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4.
  • Adam, J., et al. (author)
  • Coherent rho(0) photoproduction in ultra-peripheral Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479. ; :9
  • Journal article (peer-reviewed)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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5.
  • Adam, J., et al. (author)
  • Inclusive, prompt and non-prompt J/psi production at mid-rapidity in Pb-Pb collisions at root S-NN=2.76 TeV
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)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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6.
  • Adam, J., et al. (author)
  • Measurement of charged jet production cross sections and nuclear modification in p-Pb collisions at root s(NN)=5.02 TeV
  • 2015
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 749, s. 68-81
  • Journal article (peer-reviewed)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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7.
  • Adam, J., et al. (author)
  • Measurement of dijet k(T) in p-Pb collisions at root s(NN)=5.02 TeV
  • 2015
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 746, s. 385-395
  • Journal article (peer-reviewed)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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8.
  • Adam, J., et al. (author)
  • Measurement of jet quenching with semi-inclusive hadron-jet distributions in central Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2015
  • In: Journal of High Energy Physics. - 1029-8479. ; :9
  • Journal article (peer-reviewed)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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9.
  • Adam, J., et al. (author)
  • One-dimensional pion, kaon, and proton femtoscopy in Pb-Pb collisions at root(NN)-N-S=2.76 TeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:5
  • Journal article (peer-reviewed)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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10.
  • Adam, J., et al. (author)
  • 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
  • In: Journal of High Energy Physics. - 1029-8479. ; :6
  • Journal article (peer-reviewed)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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11.
  • Adam, J., et al. (author)
  • Measurement of jet suppression in central Pb-Pb collisions at root s(NN)=2.76 TeV
  • 2015
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 746, s. 1-14
  • Journal article (peer-reviewed)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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12.
  • Adam, J, et al. (author)
  • Measurement of pion, kaon and proton production in proton-proton collisions at [Formula: see text] TeV.
  • 2015
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Journal article (peer-reviewed)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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13.
  • Adam, J., et al. (author)
  • Precision measurement of the mass difference between light nuclei and anti-nuclei
  • 2015
  • In: Nature Physics. - 1745-2473. ; 11:10, s. 120-811
  • Journal article (peer-reviewed)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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14.
  • Adam, J., et al. (author)
  • 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
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 752, s. 267-277
  • Journal article (peer-reviewed)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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15.
  • Adam, J., et al. (author)
  • Two-pion femtoscopy in p-Pb collisions at root(NN)-N-S=5.02 TeV
  • 2015
  • In: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
  • Journal article (peer-reviewed)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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18.
  • Forstner, A. J., et al. (author)
  • Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
  • 2021
  • In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 4179-4190
  • Journal article (peer-reviewed)abstract
    • Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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19.
  • Schwarz, E, et al. (author)
  • Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
  • 2019
  • In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
  • Journal article (peer-reviewed)abstract
    • Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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22.
  • Kaufmann, Tobias, et al. (author)
  • Common brain disorders are associated with heritable patterns of apparent aging of the brain
  • 2019
  • In: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
  • Journal article (peer-reviewed)abstract
    • Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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23.
  • Malmqvist, Anna, et al. (author)
  • Increased peripheral levels of TARC/CCL17 in first episode psychosis patients
  • 2019
  • In: Schizophrenia Research. - : ELSEVIER. - 0920-9964 .- 1573-2509. ; 210, s. 221-227
  • Journal article (peer-reviewed)abstract
    • Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
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25.
  • Elvsashagen, T, et al. (author)
  • The genetic architecture of human brainstem structures and their involvement in common brain disorders
  • 2020
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
  • Journal article (peer-reviewed)abstract
    • Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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26.
  • Gracias, J., et al. (author)
  • Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
  • 2022
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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27.
  • Orhan, F, et al. (author)
  • CSF GABA is reduced in first-episode psychosis and associates to symptom severity
  • 2018
  • In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 23:5, s. 1244-1250
  • Journal article (peer-reviewed)abstract
    • Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.
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28.
  • Orhan, F., et al. (author)
  • Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis
  • 2018
  • In: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 138:5, s. 432-440
  • Journal article (peer-reviewed)abstract
    • ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
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29.
  • Orhan, F., et al. (author)
  • Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
  • 2016
  • In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 84:5, s. 262-271
  • Journal article (peer-reviewed)abstract
    • Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.
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39.
  • Erhardt, A., et al. (author)
  • Replication and meta-analysis of TMEM132D gene variants in panic disorder
  • 2012
  • In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 2:e156
  • Journal article (peer-reviewed)abstract
    • A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n = 1670 cases and n 2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n 1038 cases and n 2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P = 1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations. Translational Psychiatry (2012) 2, e156; doi:10.1038/tp.2012.85; published online 4 September 2012
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40.
  • Erhardt, Leif RW, et al. (author)
  • A global survey of physicians' perceptions on cholesterol management: the From The Heart study
  • 2007
  • In: International Journal of Clinical Practice. - : Hindawi Limited. - 1742-1241 .- 1368-5031. ; 61:7, s. 1078-1085
  • Journal article (peer-reviewed)abstract
    • Aims: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. Methods: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. Results: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. Conclusion: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.
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41.
  • Erhardt, Leif RW, et al. (author)
  • Cardiologists' awareness and perceptions of guidelines for chronic heart failure. The ADDress your Heart survey.
  • 2008
  • In: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 10, s. 1020-1025
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Several surveys show that patients with chronic heart failure (CHF) are sub-optimally managed and treatment guidelines are not implemented in clinical practice. AIMS: To investigate awareness and perceptions of the 2005 European Society of Cardiology (ESC) guidelines for CHF. METHODS: 467 cardiologists from seven European countries completed an on-line interview using a validated, semi-structured questionnaire including questions about awareness and relevance of CHF guidelines. To assess agreement with ESC guidelines, three fictitious patient cases were presented and respondents' management choices compared with those of an expert panel based on the guidelines. RESULTS: Awareness of CHF guidelines was high, with 98% aware of any guideline and 65% aware of ESC guidelines. ESC guidelines were considered relevant (51%) or very relevant (38%) for guiding treatment decisions. Up to 92% of respondents perceived that they adhered to the ESC guidelines. For the patient cases,
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42.
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43.
  • Erhardt, Leif RW, et al. (author)
  • Lipid management in cardiovascular disease prevention guidelines: Strategies and tactics for implementation.
  • 2008
  • In: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 196:2, s. 532-541
  • Research review (peer-reviewed)abstract
    • Despite the widespread dissemination of clinical practice guidelines on the prevention and treatment of cardiovascular disease (CVD), CVD causes one third of deaths worldwide and almost half of all deaths in the developed world. It is therefore likely that, although some aspects of CVD management have improved, there is still a significant shortfall between what is known about CVD prevention and what is put into action. Twenty-one experts in the field of CVD from around the world attended a focus panel meeting in Marlow-on-Thames, UK (see acknowledgements for a list of meeting participants). These experts were invited to discuss practical strategies and tactics for overcoming barriers to the implementation of guidelines on CVD prevention, and lipid management in particular. This article reviews and updates the key topics presented during the course of the meeting, captures the essence of the group discussions, and summarizes the meeting outcomes. The participants concluded that initial efforts to implement CVD prevention guidelines more effectively are best directed at high-risk patients who have already been identified. Once current patients achieve their targets, more attention can be paid to finding untreated patients at risk. Recommendations from the expert panel included: Harmonize guidelines; focus on common areas of consensus rather than state-of-the-art science Remove the boundary between primary and secondary prevention and focus on level of overall risk. Help policy makers understand the different components of CVD. Include professional societies from different specialties in guideline development and implementation, to increase ownership and decrease fragmentation of guideline committees. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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44.
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45.
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46.
  • Erhardt, Tobias, et al. (author)
  • High-resolution aerosol concentration data from the Greenland NorthGRIP and NEEM deep ice cores
  • 2022
  • In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:3, s. 1215-1231
  • Journal article (peer-reviewed)abstract
    • Records of chemical impurities from ice cores enable us to reconstruct the past deposition of aerosols onto polar ice sheets and alpine glaciers. Through this they allow us to gain insight into changes of the source, transport and deposition processes that ultimately determine the deposition flux at the coring location. However, the low concentrations of the aerosol species in the ice and the resulting high risk of contamination pose a formidable analytical challenge, especially if long, continuous and highly resolved records are needed. Continuous flow analysis, CFA, the continuous melting, decontamination and analysis of ice-core samples has mostly overcome this issue and has quickly become the de facto standard to obtain high-resolution aerosol records from ice cores after its inception at the University of Bern in the mid-1990s.Here, we present continuous records of calcium (Ca2+), sodium (Na+), ammonium (NH+4), nitrate (NO-3) and electrolytic conductivity at 1 mm depth resolution from the NGRIP (North Greenland Ice Core Project) and NEEM (North Greenland Eemian Ice Drilling) ice cores produced by the Bern Continuous Flow Analysis group in the years 2000 to 2011 (Erhardt et al., 2021). Both of the records were previously used in a number of studies but were never published in full 1 mm resolution. Alongside the 1 mm datasets we provide decadal averages, a detailed description of the methods, relevant references, an assessment of the quality of the data and its usable resolution. Along the way we will also give some historical context on the development of the Bern CFA system.
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48.
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49.
  • Hobbs, F D Richard, et al. (author)
  • The From The Heart study: a global survey of patient understanding of cholesterol management and cardiovascular risk, and physician-patient communication
  • 2008
  • In: Current Medical Research and Opinion. - 1473-4877. ; 24:5, s. 1267-1278
  • Journal article (peer-reviewed)abstract
    • Objectives: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. A high level of low-density lipoprotein cholesterol (LDL-C) is a major CVD risk factor. Guidelines recommend effective cholesterol management and set LDL-C goals, yet deficiencies exist in physician implementation of these recommendations and in patient uptake of the advice. However, little is known of patient perceptions about CVD risk. Methods: Patients and physicians were randomly selected from ten countries to complete a confidential, semi-structured questionnaire. Results: Response rates were 27% (n = 750) for physicians and 83% (n = 1547) for patients, Patients believed cancer (43%) to be a greater cause of mortality than heart attack or stroke (34%). Despite 77% of patients claiming to be satisfied with information on high cholesterol, only 26% were aware that heart attack was a possible consequence, and only 35% of patients thought they had achieved their cholesterol goals. Virtually all physicians (99%) claimed to inform patients of their cholesterol level, while 18% of patients reported that they were not informed. Although patients and physicians were selected at random, limitations of this survey relate typically to the reliability of physician and patient responses and the possibility that the survey population may not represent the overall population. A broad range of patients' backgrounds and a high response rate (83%) suggest these effects would be minimal in the patient population. Conclusions: The From The Heart study has shown surprisingly poor knowledge of CVD risk amongst patients with elevated cholesterol. This may contribute to poor concordance with recommendations and treatment.
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50.
  • Hutchinson, Louise A., et al. (author)
  • Using ecological and field survey data to establish a national list of the wild bee pollinators of crops
  • 2021
  • In: Agriculture, Ecosystems and Environment. - : Elsevier BV. - 0167-8809 .- 1873-2305. ; 315
  • Journal article (peer-reviewed)abstract
    • The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.
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