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Background and Objectives: Proteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity.
Methods: Patients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded.
Results: Of 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5–8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1–4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3–15.25 vs n = 41, median 4 ng/mL, and IQR 2–7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels.
Discussion: D-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS.
Classification of Evidence: This study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.
The first measurement of the e+e− pair production at low lepton pair transverse momentum (pT,ee) and low invariant mass (mee) in non-central Pb−Pb collisions at sNN−−−√=5.02 TeV at the LHC is presented. The dielectron production is studied with the ALICE detector at midrapidity (|ηe|<0.8) as a function of invariant mass (0.4≤mee<2.7 GeV/c2) in the 50−70% and 70−90% centrality classes for pT,ee<0.1 GeV/c, and as a function of pT,ee in three mee intervals in the most peripheral Pb−Pb collisions. Below a pT,ee of 0.1 GeV/c, a clear excess of e+e− pairs is found compared to the expectations from known hadronic sources and predictions of thermal radiation from the medium. The mee excess spectra are reproduced, within uncertainties, by different predictions of the photon−photon production of dielectrons, where the photons originate from the extremely strong electromagnetic fields generated by the highly Lorentz-contracted Pb nuclei. Lowest-order quantum electrodynamic (QED) calculations, as well as a model that takes into account the impact-parameter dependence of the average transverse momentum of the photons, also provide a good description of the pT,ee spectra. The measured ⟨p2T,ee⟩−−−−−√ of the excess pT,ee spectrum in peripheral Pb−Pb collisions is found to be comparable to the values observed previously at RHIC in a similar phase-space region.
The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its hadronic decay into Ω−π+ at midrapidity (|y|<0.5) in proton-proton (pp) collisions at the centre-of-mass energy s√=13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2<pT<12 GeV/c. The pT dependence of the Ω0c-baryon production relative to the prompt D0-meson and to the prompt Ξ0c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of Ω0c and prompt Λ+c baryons multiplied by the Ω−π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions.
The first measurement of the e+e− pair production at low lepton pair transverse momentum (pT,ee) and low invariant mass (mee) in non-central Pb−Pb collisions at sNN−−−√=5.02 TeV at the LHC is presented. The dielectron production is studied with the ALICE detector at midrapidity (|ηe|<0.8) as a function of invariant mass (0.4≤mee<2.7 GeV/c2) in the 50−70% and 70−90% centrality classes for pT,ee<0.1 GeV/c, and as a function of pT,ee in three mee intervals in the most peripheral Pb−Pb collisions. Below a pT,ee of 0.1 GeV/c, a clear excess of e+e− pairs is found compared to the expectations from known hadronic sources and predictions of thermal radiation from the medium. The mee excess spectra are reproduced, within uncertainties, by different predictions of the photon−photon production of dielectrons, where the photons originate from the extremely strong electromagnetic fields generated by the highly Lorentz-contracted Pb nuclei. Lowest-order quantum electrodynamic (QED) calculations, as well as a model that takes into account the impact-parameter dependence of the average transverse momentum of the photons, also provide a good description of the pT,ee spectra. The measured ⟨p2T,ee⟩−−−−−√ of the excess pT,ee spectrum in peripheral Pb−Pb collisions is found to be comparable to the values observed previously at RHIC in a similar phase-space region.
We report about the properties of the underlying event measured with ALICE at the LHC in pp and p−Pb collisions at sNN−−−√=5.02 TeV. The event activity, quantified by charged-particle number and summed-pT densities, is measured as a function of the leading-particle transverse momentum (ptrigT). These quantities are studied in three azimuthal-angle regions relative to the leading particle in the event: toward, away, and transverse. Results are presented for three different pT thresholds (0.15, 0.5, and 1 GeV/c) at mid-pseudorapidity (|η|<0.8). The event activity in the transverse region, which is the most sensitive to the underlying event, exhibits similar behaviour in both pp and p−Pb collisions, namely, a steep increase with ptrigT for low ptrigT, followed by a saturation at ptrigT≈5 GeV/c. The results from pp collisions are compared with existing measurements at other centre-of-mass energies. The quantities in the toward and away regions are also analyzed after the subtraction of the contribution measured in the transverse region. The remaining jet-like particle densities are consistent in pp and p−Pb collisions for ptrigT>10 GeV/c, whereas for lower ptrigT values the event activity is slightly higher in p−Pb than in pp collisions. The measurements are compared with predictions from the PYTHIA 8 and EPOS LHC Monte Carlo event generators.
We report about the properties of the underlying event measured with ALICE at the LHC in pp and p−Pb collisions at sNN−−−√=5.02 TeV. The event activity, quantified by charged-particle number and summed-pT densities, is measured as a function of the leading-particle transverse momentum (ptrigT). These quantities are studied in three azimuthal-angle regions relative to the leading particle in the event: toward, away, and transverse. Results are presented for three different pT thresholds (0.15, 0.5, and 1 GeV/c) at mid-pseudorapidity (|η|<0.8). The event activity in the transverse region, which is the most sensitive to the underlying event, exhibits similar behaviour in both pp and p−Pb collisions, namely, a steep increase with ptrigT for low ptrigT, followed by a saturation at ptrigT≈5 GeV/c. The results from pp collisions are compared with existing measurements at other centre-of-mass energies. The quantities in the toward and away regions are also analyzed after the subtraction of the contribution measured in the transverse region. The remaining jet-like particle densities are consistent in pp and p−Pb collisions for ptrigT>10 GeV/c, whereas for lower ptrigT values the event activity is slightly higher in p−Pb than in pp collisions. The measurements are compared with predictions from the PYTHIA 8 and EPOS LHC Monte Carlo event generators.
The production of K∗(892)0 and ϕ(1020) resonances has been measured in p-Pb collisions at sNN−−−√ = 8.16 TeV using the ALICE detector. Resonances are reconstructed via their hadronic decay channels in the rapidity interval −0.5 < y < 0 and the transverse momentum spectra are measured for various multiplicity classes up to pT = 20 GeV/c for K∗(892)0 and pT = 16 GeV/c for ϕ(1020). The pT -integrated yields and mean transverse momenta are reported and compared with previous results in pp, p-Pb and Pb-Pb collisions. The xT scaling for K∗(892)0 and ϕ(1020) resonance production is newly tested in p-Pb collisions and found to hold in the high-pT region at Large Hadron Collider energies. The nuclear modification factors (RpPb) as a function of pT for K∗0 and ϕ at sNN−−−−√ = 8.16 TeV are presented along with the new RpPb measurements of K∗0, ϕ , Ξ, and Ω at sNN−−−√ = 5.02 TeV. At intermediate pT (2-8 GeV/c), RpPb of Ξ, Ω show a Cronin-like enhancement, while K∗0 and ϕ show no or little nuclear modification. At high pT (> 8 GeV/c), the RpPb values of all hadrons are consistent with unity within uncertainties. The RpPb of K∗(892)0 and ϕ(1020) at sNN−−−√ = 8.16 and 5.02 TeV show no significant energy dependence.
The production of K∗(892)0 and ϕ(1020) resonances has been measured in p-Pb collisions at sNN−−−√ = 8.16 TeV using the ALICE detector. Resonances are reconstructed via their hadronic decay channels in the rapidity interval −0.5 < y < 0 and the transverse momentum spectra are measured for various multiplicity classes up to pT = 20 GeV/c for K∗(892)0 and pT = 16 GeV/c for ϕ(1020). The pT -integrated yields and mean transverse momenta are reported and compared with previous results in pp, p-Pb and Pb-Pb collisions. The xT scaling for K∗(892)0 and ϕ(1020) resonance production is newly tested in p-Pb collisions and found to hold in the high-pT region at Large Hadron Collider energies. The nuclear modification factors (RpPb) as a function of pT for K∗0 and ϕ at sNN−−−−√ = 8.16 TeV are presented along with the new RpPb measurements of K∗0, ϕ , Ξ, and Ω at sNN−−−√ = 5.02 TeV. At intermediate pT (2-8 GeV/c), RpPb of Ξ, Ω show a Cronin-like enhancement, while K∗0 and ϕ show no or little nuclear modification. At high pT (> 8 GeV/c), the RpPb values of all hadrons are consistent with unity within uncertainties. The RpPb of K∗(892)0 and ϕ(1020) at sNN−−−√ = 8.16 and 5.02 TeV show no significant energy dependence.
This article reports on the inclusive production cross section of several quarkonium states, J/ψ, ψ(2S), Υ(1S), Υ(2S), and Υ(3S), measured with the ALICE detector at the LHC, in pp collisions at s√=5.02 TeV. The analysis is performed in the dimuon decay channel at forward rapidity (2.5<y<4). The integrated cross sections and transverse-momentum (pT) and rapidity (y) differential cross sections for J/ψ, ψ(2S), Υ(1S), and the ψ(2S)-to-J/ψ cross section ratios are presented. The integrated cross sections, assuming unpolarized quarkonia, are: σJ/ψ(pT<20 GeV/c) = 5.88 ± 0.03 ± 0.34 μb, σψ(2S)(pT<12 GeV/c) = 0.87 ± 0.06 ± 0.10 μb, σΥ(1S)(pT<15 GeV/c) = 45.5 ± 3.9 ± 3.5 nb, σΥ(2S)(pT<15 GeV/c) = 22.4 ± 3.2 ± 2.7 nb, and σΥ(3S)(pT<15 GeV/c) = 4.9 ± 2.2 ± 1.0 nb, where the first (second) uncertainty is the statistical (systematic) one. For the first time, the cross sections of the three Υ states, as well as the ψ(2S) one as a function of pT and y, are measured at s√=5.02 TeV at forward rapidity. These measurements also significantly extend the J/ψ pT reach and supersede previously published results. A comparison with ALICE measurements in pp collisions at s√=2.76, 7, 8, and 13 TeV is presented and the energy dependence of quarkonium production cross sections is discussed. Finally, the results are compared with the predictions from several production models.
This article reports on the inclusive production cross section of several quarkonium states, J/ψ, ψ(2S), Υ(1S), Υ(2S), and Υ(3S), measured with the ALICE detector at the LHC, in pp collisions at s√=5.02 TeV. The analysis is performed in the dimuon decay channel at forward rapidity (2.5<y<4). The integrated cross sections and transverse-momentum (pT) and rapidity (y) differential cross sections for J/ψ, ψ(2S), Υ(1S), and the ψ(2S)-to-J/ψ cross section ratios are presented. The integrated cross sections, assuming unpolarized quarkonia, are: σJ/ψ(pT<20 GeV/c) = 5.88 ± 0.03 ± 0.34 μb, σψ(2S)(pT<12 GeV/c) = 0.87 ± 0.06 ± 0.10 μb, σΥ(1S)(pT<15 GeV/c) = 45.5 ± 3.9 ± 3.5 nb, σΥ(2S)(pT<15 GeV/c) = 22.4 ± 3.2 ± 2.7 nb, and σΥ(3S)(pT<15 GeV/c) = 4.9 ± 2.2 ± 1.0 nb, where the first (second) uncertainty is the statistical (systematic) one. For the first time, the cross sections of the three Υ states, as well as the ψ(2S) one as a function of pT and y, are measured at s√=5.02 TeV at forward rapidity. These measurements also significantly extend the J/ψ pT reach and supersede previously published results. A comparison with ALICE measurements in pp collisions at s√=2.76, 7, 8, and 13 TeV is presented and the energy dependence of quarkonium production cross sections is discussed. Finally, the results are compared with the predictions from several production models.