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One of the key challenges for nuclear physics today is to understand from first principles the effective interaction between hadrons with different quark content. First successes have been achieved using techniques that solve the dynamics of quarks and gluons on discrete space-time lattices1,2. Experimentally, the dynamics of the strong interaction have been studied by scattering hadrons off each other. Such scattering experiments are difficult or impossible for unstable hadrons3,4,5,6 and so high-quality measurements exist only for hadrons containing up and down quarks7. Here we demonstrate that measuring correlations in the momentum space between hadron pairs8,9,10,11,12 produced in ultrarelativistic proton–proton collisions at the CERN Large Hadron Collider (LHC) provides a precise method with which to obtain the missing information on the interaction dynamics between any pair of unstable hadrons. Specifically, we discuss the case of the interaction of baryons containing strange quarks (hyperons). We demonstrate how, using precision measurements of proton–omega baryon correlations, the effect of the strong interaction for this hadron–hadron pair can be studied with precision similar to, and compared with, predictions from lattice calculations13,14. The large number of hyperons identified in proton–proton collisions at the LHC, together with accurate modelling15 of the small (approximately one femtometre) inter-particle distance and exact predictions for the correlation functions, enables a detailed determination of the short-range part of the nucleon-hyperon interaction.
Scattering studies with low-energy kaon-proton femtoscopy in proton-proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in
proton–proton collisions at the LHC
(2019)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to several models. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in proton–proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
J/ψ production as a function of charged-particle multiplicity in p–Pb collisions at √sNN = 8.16 TeV
(2020)
Inclusive J/ψ yields and average transverse momenta in p-Pb collisions at a center-of-mass energy per nucleon pair sNN−−−√ = 8.16 TeV are measured as a function of the charged-particle pseudorapidity density with ALICE. The J/ψ mesons are reconstructed at forward (2.03<ycms<3.53) and backward (−4.46<ycms<−2.96) center-of-mass rapidity in their dimuon decay channel while the charged-particle pseudorapidity density is measured around midrapidity. The J/ψ yields at forward and backward rapidity normalized to their respective average values increase with the normalized charged-particle pseudorapidity density, the former showing a weaker increase than the latter. The normalized average transverse momenta at forward and backward rapidity manifest a steady increase from low to high charged-particle pseudorapidity density with a saturation beyond the average value.
J/ψ production as a function of charged-particle multiplicity in p–Pb
collisions at √sNN = 8.16 TeV
(2021)
Inclusive J/ψ yields and average transverse momenta in p-Pb collisions at a center-of-mass energy per nucleon pair sNN−−−√ = 8.16 TeV are measured as a function of the charged-particle pseudorapidity density with ALICE. The J/ψ mesons are reconstructed at forward (2.03<ycms<3.53) and backward (−4.46<ycms<−2.96) center-of-mass rapidity in their dimuon decay channel while the charged-particle pseudorapidity density is measured around midrapidity. The J/ψ yields at forward and backward rapidity normalized to their respective average values increase with the normalized charged-particle pseudorapidity density, the former showing a weaker increase than the latter. The normalized average transverse momenta at forward and backward rapidity manifest a steady increase from low to high charged-particle pseudorapidity density with a saturation beyond the average value.
Coherent photoproduction of ρ⁰ vector mesons in ultra-peripheral Pb-Pb collisions at √sNN = 5.02 TeV
(2020)
Cross sections for the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Pb-Pb collisions at sNN−−−√ = 5.02 TeV are reported. The measurements, which rely on the π+π− decay channel, are presented in three regions of rapidity covering the range |y| < 0.8. For each rapidity interval, cross sections are shown for different nuclear-breakup classes defined according to the presence of neutrons measured in the zero-degree calorimeters. The results are compared with predictions based on different models of nuclear shadowing. Finally, the observation of a coherently produced resonance-like structure with a mass around 1.7 GeV/c2 and a width of about 140 MeV/c2 is reported and compared with similar observations from other experiments.
Measurements of (anti)deuteron and (anti)3He production in the rapidity range |y|< 0.5 as a function of the transverse momentum and event multiplicity in Xe−Xe collisions at a center-of-mass energy per nucleon−nucleon pair of sNN−−−√ = 5.44 TeV are presented. The coalescence parameters B2 and B3 are measured as a function of the transverse momentum per nucleon. The ratios between (anti)deuteron and (anti)3He yields and those of (anti)protons and pions are reported as a function of the mean charged-particle multiplicity density, and compared with two implementations of the statistical hadronization model (SHM) and with coalescence predictions. The elliptic flow of (anti)deuterons is measured for the first time in Xe−Xe collisions and shows features similar to those already observed in Pb−Pb collisions, i.e., the mass ordering at low transverse momentum and the meson−baryon grouping at intermediate transverse momentum. The production of nuclei is particularly sensitive to the chemical freeze-out temperature of the system created in the collision, which is extracted from a grand-canonical-ensemble-based thermal fit, performed for the first time including light nuclei along with light-flavor hadrons in Xe−Xe collisions. The extracted chemical freeze-out temperature Tchem = (154.2 ± 1.1) MeV in Xe−Xe collisions is similar to that observed in Pb−Pb collisions and close to the crossover temperature predicted by lattice QCD calculations.
The intense photon fluxes from relativistic nuclei provide an opportunity to study photonuclear interactions in ultraperipheral collisions. The measurement of coherently photoproduced π+π−π+π− final states in ultraperipheral Pb-Pb collisions at sNN−−−√=5.02 TeV is presented for the first time. The cross section, dσ/dy, times the branching ratio (ρ→π+π+π−π−) is found to be 47.8±2.3 (stat.)±7.7 (syst.) mb in the rapidity interval |y|<0.5. The invariant mass distribution is not well described with a single Breit-Wigner resonance. The production of two interfering resonances, ρ(1450) and ρ(1700), provides a good description of the data. The values of the masses (m) and widths (Γ) of the resonances extracted from the fit are m1=1385±14 (stat.)±3 (syst.) MeV/c2, Γ1=431±36 (stat.)±82 (syst.) MeV/c2, m2=1663±13 (stat.)±22 (syst.) MeV/c2 and Γ2=357±31 (stat.)±49 (syst.) MeV/c2, respectively. The measured cross sections times the branching ratios are compared to recent theoretical predictions.
Measurements of the pT-dependent flow vector fluctuations in Pb-Pb collisions at sNN−−−√=5.02 TeV using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the pT-dependent flow vector fluctuations at sNN−−−√=5.02 TeV with two-particle correlations. Significant pT-dependent fluctuations of the V⃗ 2 flow vector in Pb-Pb collisions are found across different centrality ranges, with the largest fluctuations of up to ∼15% being present in the 5% most central collisions. In parallel, no evidence of significant pT-dependent fluctuations of V⃗ 3 or V⃗ 4 is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than 5σ significance in central collisions. These observations in Pb-Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high pT, which might be biased by pT-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system.
Measurement of beauty-quark production in pp collisions at √s = 13 TeV via non-prompt D mesons
(2024)
The pT-differential production cross sections of non-prompt D0, D+, and D+s mesons originating from beauty-hadron decays are measured in proton−proton collisions at a centre-of-mass energy s√ of 13 TeV. The measurements are performed at midrapidity, |y|<0.5, with the data sample collected by ALICE from 2016 to 2018. The results are in agreement with predictions from several perturbative QCD calculations. The fragmentation fraction of beauty quarks to strange mesons divided by the one to non-strange mesons, fs/(fu+fd), is found to be 0.114±0.016 (stat.)±0.006 (syst.)±0.003 (BR)±0.003 (extrap.). This value is compatible with previous measurements at lower centre-of-mass energies and in different collision systems in agreement with the assumption of universality of fragmentation functions. In addition, the dependence of the non-prompt D meson production on the centre-of-mass energy is investigated by comparing the results obtained at s√=5.02 and 13 TeV, showing a hardening of the non-prompt D-meson pT-differential production cross section at higher s√. Finally, the bb¯¯¯ production cross section per unit of rapidity at midrapidity is calculated from the non-prompt D0, D+, D+s, and Λ+c hadron measurements, obtaining dσ/dy=75.2±3.2 (stat.)±5.2 (syst.)+12.3−3.2 (extrap.) μb.
The two-particle momentum correlation functions between charm mesons (D∗± and D±) and charged light-flavor mesons (π± and K±) in all charge-combinations are measured for the first time by the ALICE Collaboration in high-multiplicity proton–proton collisions at a center-of-mass energy of √s = 13 TeV. For DK and D∗K pairs, the experimental results are in agreement with theoretical predictions of the residual strong interaction based on quantum chromodynamics calculations on the lattice and chiral effective field theory. In the case of Dπ and D∗π pairs, tension between the calculations including strong interactions and the measurement is observed. For all particle pairs, the data can be adequately described by Coulomb interaction only, indicating a shallow interaction between charm and light-flavor mesons. Finally, the scattering lengths governing the residual strong interaction of the Dπ and D∗π systems are determined by fitting the experimental correlation functions with a model that employs a Gaussian potential. The extracted values are small and compatible with zero.
The transverse momentum (pT) differential production cross section of the promptly-produced charm-strange baryon Ξ0c (and its charge conjugate Ξ0c¯¯¯¯¯¯) is measured at midrapidity via its hadronic decay into π+Ξ− in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The Ξ0c nuclear modification factor (RpPb), calculated from the cross sections in pp and p−Pb collisions, is presented and compared with the RpPb of Λ+c baryons. The ratios between the pT-differential production cross section of Ξ0c baryons and those of D0 mesons and Λ+c baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt Ξ0c baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p−Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The pT-integrated cross section of prompt Ξ0c-baryon production at midrapidity extrapolated down to pT = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p−Pb collisions at midrapidity.
Investigating strangeness enhancement with multiplicity in pp collisions using angular correlations
(2024)
A study of strange hadron production associated with hard scattering processes and with the underlying event is conducted to investigate the origin of the enhanced production of strange hadrons in small collision systems characterised by large charged-particle multiplicities. For this purpose, the production of the single-strange meson K0S and the double-strange baryon Ξ± is measured, in each event, in the azimuthal direction of the highest-pT particle (``trigger" particle), related to hard scattering processes, and in the direction transverse to it in azimuth, associated with the underlying event, in pp collisions at s√=5.02 TeV and s√=13 TeV using the ALICE detector at the LHC. The per-trigger yields of K0S and Ξ± are dominated by the transverse-to-leading production (i.e., in the direction transverse to the trigger particle), whose contribution relative to the toward-leading production is observed to increase with the event charged-particle multiplicity. The transverse-to-leading and the toward-leading Ξ±/K0S yield ratios increase with the multiplicity of charged particles, suggesting that strangeness enhancement with multiplicity is associated with both hard scattering processes and the underlying event. The relative production of Ξ± with respect to K0S is higher in transverse-to-leading processes over the whole multiplicity interval covered by the measurement. The K0S and Ξ± per-trigger yields and yield ratios are compared with predictions of three different phenomenological models, namely PYTHIA 8.2 with the Monash tune, PYTHIA 8.2 with ropes and EPOS LHC. The comparison shows that none of them can quantitatively describe either the transverse-to-leading or the toward-leading yields of K0S and Ξ±.
The first measurement of the impact-parameter dependent angular anisotropy in the decay of coherently photoproduced ρ0 mesons is presented. The ρ0 mesons are reconstructed through their decay into a pion pair. The measured anisotropy corresponds to the amplitude of the cos(2ϕ) modulation, where ϕ is the angle between the two vectors formed by the sum and the difference of the transverse momenta of the pions, respectively. The measurement was performed by the ALICE Collaboration at the LHC using data from ultraperipheral Pb−Pb collisions at a center-of-mass energy of sNN−−−√ = 5.02 TeV per nucleon pair. Different impact-parameter regions are selected by classifying the events in nuclear-breakup classes. The amplitude of the cos(2ϕ) modulation is found to increase by about one order of magnitude from large to small impact parameters. Theoretical calculations, which describe the measurement, explain the cos(2ϕ) anisotropy as the result of a quantum interference effect at the femtometer scale that arises from the ambiguity as to which of the nuclei is the source of the photon in the interaction.
The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb−Pb collisions at √sNN=5.02 TeV using the ALICE detector at the CERN Large Hadron Collider. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4−16 GeV/c . Measurements of integrated yields, mean transverse momenta, and particle yield ratios are reported and found to be consistent with previous ALICE measurements for K∗(892)0 within uncertainties. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb−Pb collisions shows a significant suppression at a level of 9.3σ relative to pp collisions. Thermal model calculations result in an overprediction of the particle yield ratio. Although both hadron resonance gas in partial chemical equilibrium (HRG-PCE) and music + smash simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas music + smash simulations tend to overpredict the particle yield ratio. These observations, along with the kinetic freeze-out temperatures extracted from the yields measured for light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which decreases with increasing collision centrality percentile. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are presented and compared with measurements in pp collisions at √s=5.02 TeV. Both pa rticle ratios are found to be suppressed by up to a factor of five at pT<2.0 GeV/c in central Pb−Pb collisions and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor (RAA) shows a smooth evolution with centrality and is found to be below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its semileptonic decay into Ω−e+νe at midrapidity (|y| < 0.8) 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 branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) is measured to be 1.12 ± 0.22 (stat.) ± 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented.
The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its semileptonic decay into Ω−e+νe at midrapidity (|y| < 0.8) 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 branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) is measured to be 1.12 ± 0.22 (stat.) ± 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented.
The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN−−−√=5.02 TeV using the ALICE detector at the LHC. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. The reported measurements of integrated yields, mean transverse momenta, and particle yield ratios are consistent with previous ALICE measurements for K∗(892)0. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb-Pb collisions shows a significant suppression (9.3σ) relative to pp collisions. Thermal model calculations overpredict the particle yield ratio. Although both simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas MUSIC+SMASH tends to overpredict them. These observations, along with the kinetic freeze-out temperatures extracted from the yields of light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which increases towards central collisions. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are suppressed by up to a factor of five at pT<2 GeV/c in central Pb-Pb collisions compared to pp collisions at s√= 5.02 TeV. Both particle ratios and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor shows a smooth evolution with centrality and is below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN−−−√=5.02 TeV using the ALICE detector at the LHC. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. The reported measurements of integrated yields, mean transverse momenta, and particle yield ratios are consistent with previous ALICE measurements for K∗(892)0. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb-Pb collisions shows a significant suppression (9.3σ) relative to pp collisions. Thermal model calculations overpredict the particle yield ratio. Although both simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas MUSIC+SMASH tends to overpredict them. These observations, along with the kinetic freeze-out temperatures extracted from the yields of light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which increases towards central collisions. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are suppressed by up to a factor of five at pT<2 GeV/c in central Pb-Pb collisions compared to pp collisions at s√= 5.02 TeV. Both particle ratios and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor shows a smooth evolution with centrality and is below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
The total charm-quark production cross section per unit of rapidity dσ(cc)/dy, and the fragmentation fractions of charm quarks to different charm-hadron species f(c → hc), are measured for the first time in p–Pb collisions at √sNN = 5.02 TeV at midrapidity (−0.96 < y < 0.04 in the centre-ofmass frame) using data collected by ALICE at the CERN LHC. The results are obtained based on all the available measurements of prompt production of ground-state charm-hadron species: D0, D+,D+s, and J/ψ mesons, and Λ+cand Ξ0cbaryons. The resulting cross section is dσ(cc)/dy = 219.6±6.3 (stat.)+10.5−11.8(syst.)+7.6−2.9(extr.)±5.4 (BR)±4.6 (lumi.)±19.5 (rapidity shape) +15.0 (Ω0c) mb, which is consistent with a binary scaling of pQCD calculations from pp ollisions. The measured fragmentation fractions are compatible with those measured in pp collisions at √s = 5.02 and 13 TeV, showing an increase in the relative production rates of charm baryons with respect to charm mesons in pp and p–Pb collisions compared with e+e − and e−p collisions. The pT-integrated nuclear modification factor of charm quarks, RpPb(cc) = 0.91±0.04 (stat.) +0.08 −0.09 (syst.) +0.04 −0.03 (extr.)±0.03 (lumi.), is found to be consistent with unity and with theoretical predictions including nuclear modifications of the parton distribution functions.
This work aims to differentiate strangeness produced from hard processes (jet-like) and softer processes (underlying event) by measuring the angular correlation between a high-momentum trigger hadron (h) acting as a jet-proxy and a produced strange hadron (φ(1020) meson). Measuring h–φ correlations at midrapidity in p–Pb collisions at √sNN = 5.02 TeV as a function of event multiplicity provides insight into the microscopic origin of strangeness enhancement in small collision systems. The jet-like and the underlying-event-like strangeness production are investigated as a function of event multiplicity. They are also compared between a lower and higher momentum region. The evolution of the per-trigger yields within the near-side (aligned with the trigger hadron) and away-side (in the opposite direction of the trigger hadron) jet is studied separately, allowing for the characterization of two distinct jet-like production regimes. Furthermore, the h–φ correlations within the underlying event give access to a production regime dominated by soft production processes, which can be compared directly to the in-jet production. Comparisons between h–φ and dihadron correlations show that the observed strangeness enhancement is largely driven by the underlying event, where the φ/h ratio is significantly larger than within the jet regions. As multiplicity increases, the fraction of the total φ(1020) yield coming from jets decreases compared to the underlying event production, leading to high-multiplicity events being dominated by the increased strangeness production from the underlying event
The production cross section of inclusive isolated photons has been measured by the ALICE experiment at the CERN LHC in pp collisions at centre-of-momentum energy of s√=13 TeV collected during the LHC Run 2 data-taking period. The measurement is performed by combining the measurements of the electromagnetic calorimeter EMCal and the central tracking detectors ITS and TPC, covering a pseudorapidity range of |ηγ|<0.67 and a transverse momentum range of 7<pγT<200 GeV/c. The result extends to lower pγT and xγT=2pγT/s√ ranges, the lowest xγT of any isolated photon measurements to date, extending significantly those measured by the ATLAS and CMS experiments towards lower pγT at the same collision energy with a small overlap between the measurements. The measurement is compared with next-to-leading order perturbative QCD calculations and the results from the ATLAS and CMS experiments as well as with measurements at other collision energies. The measurement and theory prediction are in agreement with each other within the experimental and theoretical uncertainties.
The procedure for the energy calibration of the high granularity electromagnetic calorimeter PHOS of the ALICE experiment is presented. The methods used to perform the relative gain calibration, to evaluate the geometrical alignment and the corresponding correction of the absolute energy scale, to obtain the nonlinearity correction coefficients and finally, to calculate the time-dependent calibration corrections, are discussed and illustrated by the PHOS performance in proton-proton (pp) collisions at √s=13 TeV. After applying all corrections, the achieved mass resolutions for π0 and η mesons for pT > 1.7 GeV/c are σmπ0 = 4.56 ± 0.03 MeV/c2 and σmη = 15.3 ± 1.0 MeV/c2, respectively.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer
(2022)
Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell–mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM). Loss of the MHC-I APM is a frequent cause of resistance to cancer immunotherapies, and the pharmacological inhibition of SUMOylation (SUMOi) resulted in reduced activity of the transcriptional repressor scaffold attachment factor B (SAFB) and induction of the MHC-I APM. Consequently, SUMOi enhanced the presentation of antigens and the susceptibility of tumor cells to CD8+ T cell–mediated killing. Importantly, SUMOi also triggered the activation of CD8+ T cells and thereby drove a feed-forward loop amplifying the specific antitumor immune response. In summary, we showed that activated SUMOylation allowed tumor cells to evade antitumor immunosurveillance, and we have expanded the understanding of SUMOi as a rational therapeutic strategy for enhancing the efficacy of cancer immunotherapies.
We present the charged-particle pseudorapidity density in Pb–Pb collisions at √sNN = 5.02 TeV in centrality classes measured by ALICE. The measurement covers a wide pseudorapidity range from −3.5 to 5, which is sufficient for reliable estimates of the total number of charged particles produced in the collisions. For the most central (0–5%) collisions we find 21 400 ± 1 300, while for the most peripheral (80–90%) we find 230 ± 38. This corresponds to an increase of (27 ± 4)% over the results at √sNN = 2.76 TeV previously reported by ALICE. The energy dependence of the total number of charged particles produced in heavy-ion collisions is found to obey a modified power-law like behaviour. The chargedparticle pseudorapidity density of the most central collisions is compared to model calculations — none of which fully describes the measured distribution. We also present an estimate of the rapidity density of charged particles. The width of that distribution is found to exhibit a remarkable proportionality to the beam rapidity, independent of the collision energy from the top SPS to LHC energies.
Two-particle angular correlations were measured in pp collisions at s√=7 TeV for pions, kaons, protons, and lambdas, for all particle/anti-particle combinations in the pair. Data for mesons exhibit an expected peak dominated by effects associated with mini-jets and are well reproduced by general purpose Monte Carlo generators. However, for baryon–baryon and anti-baryon–anti-baryon pairs, where both particles have the same baryon number, a near-side anti-correlation structure is observed instead of a peak. This effect is interpreted in the context of baryon production mechanisms in the fragmentation process. It currently presents a challenge to Monte Carlo models and its origin remains an open question.
Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs.
Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality.
Results: Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival.
Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany.
Trial registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807) on May 1, 2017.
We have identified a mistake in how Fig. 1 is referenced in the text of the article Eur. Phys. J. C 77 (2017) no. 8, 569 which affected three paragraphs of the results section. The corrected three paragraphs as well as the unmodified accompanying figure are reproduced in this document with the correct labeling.
In addition, an editing issue led to a missing acknowledgements section. The missing section is reproduced at the end of this document in the manner in which it should have appeared in the published article.
G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.
We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(α,γ)16O fusion reaction and to reach lower center-ofmass energies than measured so far.
The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-to-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.
Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.
Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy
(2017)
Introduction: Outcome after postoperative radiochemotherapy (RT-CT) for patients with advanced head and neck squamous cell carcinomas (HNSCC) remains unsatisfactory, especially among those with HPV negative tumours. Therefore, new biomarkers are needed to further define subgroups for individualised therapeutic approaches. Preclinical and first clinical observations showed that the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12) play an important role in tumour cell proliferation, survival, cancer progression, metastasis and treatment resistance. However, the data on the prognostic value of SDF-1/CXCR4 expression for HNSCC are conflicting. The aim of our hypothesis-generating study was to retrospectively explore the prognostic potential of SDF-1/CXCR4 in a well-defined cohort of HNSCC patients collected within the multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).
Material and methods: Patients with stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with resection and adjuvant radiotherapy (RT) with ≥60 Gy and concurrent cisplatin-based chemotherapy (CT). Tissue micro-arrays (TMAs) from a total of 221 patients were generated from surgical specimens, 201 evaluated for the SDF-1 and CXCR4 expression by immunofluorescence and correlated with clinico-pathological and outcome data.
Results: In univariate and multivariate analyses intracellular SDF-1 expression was associated with lower loco-regional control (LRC) in the entire patient group as well as in the HPV16 DNA negative subgroup. CXCR4 expression showed a trend for lower LRC in the univariate analysis which was not confirmed in the multivariate analysis. Neither for SDF-1 nor CXCR4 expression associations with distant metastasis free or overall survival were found.
Conclusions: Our exploratory data support the hypothesis that overexpression of intracellular SDF-1 is an independent negative prognostic biomarker for LRC after postoperative RT-CT in high-risk HNSCC. Prospective validation is warranted and further exploration of SDF-1/CXCR4 as a potential therapeutic target to overcome treatment resistance in HNSCC appears promising.
The global energy system is undergoing a major transition, and in energy planning and decision-making across governments, industry and academia, models play a crucial role. Because of their policy relevance and contested nature, the transparency and open availability of energy models and data are of particular importance. Here we provide a practical how-to guide based on the collective experience of members of the Open Energy Modelling Initiative (Openmod). We discuss key steps to consider when opening code and data, including determining intellectual property ownership, choosing a licence and appropriate modelling languages, distributing code and data, and providing support and building communities. After illustrating these decisions with examples and lessons learned from the community, we conclude that even though individual researchers' choices are important, institutional changes are still also necessary for more openness and transparency in energy research.
Background: The exponential growth of image-based diagnostic and minimally invasive interventions requires a detailed three-dimensional anatomical knowledge and increases the demand towards the undergraduate anatomical curriculum. This randomized controlled trial investigates whether musculoskeletal ultrasound (MSUS) or arthroscopic methods can increase the anatomical knowledge uptake.
Methods: Second-year medical students were randomly allocated to three groups. In addition to the compulsory dissection course, the ultrasound group (MSUS) was taught by eight, didactically and professionally trained, experienced student-teachers and the arthroscopy group (ASK) was taught by eight experienced physicians. The control group (CON) acquired the anatomical knowledge only via the dissection course. Exposure (MSUS and ASK) took place in two separate lessons (75 minutes each, shoulder and knee joint) and introduced standard scan planes using a 10-MHz ultrasound system as well as arthroscopy tutorials at a simulator combined with video tutorials. The theoretical anatomic learning outcomes were tested using a multiple-choice questionnaire (MCQ), and after cross-over an objective structured clinical examination (OSCE). Differences in student's perceptions were evaluated using Likert scale-based items.
Results: The ASK-group (n = 70, age 23.4 (20--36) yrs.) performed moderately better in the anatomical MC exam in comparison to the MSUS-group (n = 84, age 24.2 (20--53) yrs.) and the CON-group (n = 88, 22.8 (20--33) yrs.; p = 0.019). After an additional arthroscopy teaching 1 % of students failed the MC exam, in contrast to 10 % in the MSUS- or CON-group, respectively. The benefit of the ASK module was limited to the shoulder area (p < 0.001). The final examination (OSCE) showed no significant differences between any of the groups with good overall performances. In the evaluation, the students certified the arthroscopic tutorial a greater advantage concerning anatomical skills with higher spatial imagination in comparison to the ultrasound tutorial (p = 0.002; p < 0.001).
Conclusions: The additional implementation of arthroscopy tutorials to the dissection course during the undergraduate anatomy training is profitable and attractive to students with respect to complex joint anatomy. Simultaneous teaching of basic-skills in musculoskeletal ultrasound should be performed by medical experts, but seems to be inferior to the arthroscopic 2D-3D-transformation, and is regarded by students as more difficult to learn. Although arthroscopy and ultrasound teaching do not have a major effect on learning joint anatomy, they have the potency to raise the interest in surgery.
Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma
(2016)
Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.
This assessment concept paper provides a methodological approach for the formative assessment and summative assessment of GIZ’s International Water Stewardship Programme (IWaSP) and its component partnerships. IWaSP promotes partnerships between the private sector (corporations and SMEs), the public sector and the society to tackle shared water risks and to manage water equitably to meet competing demands. This evaluative assessment concept describes the generic approach of the assessment, the cycle for the assessment of partnerships, the country coordination and the programme.
The overall goal of the assessment is to provide evidence for taxpayers in the donor countries and for citizens in the partnership countries. It also aims to examine the relevance of the programme’s approach, its underlying assumptions, and the heterogeneity of stakeholders and their specific interests. Since the assessment is also formative feedback to GIZ and IWaSP stakeholders, it aims to guide the future implementation of the partnerships and the programme.
The assessment is guided by several generic principles: assessing for learning (formative assessment); assessment of learning (summative assessment); iteration; structuring complex problems; unblocking results; and conformity with other assessment criteria set out by the OECD the Development Assistance Committee (DAC) and GIZ’s Capacity Works success factors (GTZ 2010).
These generic criteria are adapted to the three levels of the IWaSP structure. First, the assessment cycle for partnerships includes the validation of stakeholders (mapping), the analysis of secondary literature, face-to-face interviews and a process for feeding back the findings. Generic tools are provided to guide the assessment, such as a list of key documents and an interview guide. Partnerships will undergo a baseline, interim assessment and final assessment. As progress varies across individual IWaSP partnerships, the steps taken by each partnership to assess shared water risks, prioritise and agree interventions, are expected to differ slightly. In response to these differences the sequencing and content of the assessment may need to be adapted for the different partnerships.
Second, the country-level assessment considers issues such as the coordination of partnerships within a country, scoping strategies, and interaction between partnership and the programme. Information gathered during the partnership assessment feeds into the country-level assessment.
Third, the assessment cycle for the programme involves a document and monitoring plan analysis, reflection on the different perspectives of the programme staff, country staff and external stakeholders.
The final section is concerned with reporting. Several annexes are provided relating to the organisation and preparation of the assessment, including question guidelines and analysis procedures.
Background: Dual-source dual-energy computed tomography (DECT) offers the potential for opportunistic osteoporosis screening by enabling phantomless bone mineral density (BMD) quantification. This study sought to assess the accuracy and precision of volumetric BMD measurement using dual-source DECT in comparison to quantitative CT (QCT). Methods: A validated spine phantom consisting of three lumbar vertebra equivalents with 50 (L1), 100 (L2), and 200 mg/cm3 (L3) calcium hydroxyapatite (HA) concentrations was scanned employing third-generation dual-source DECT and QCT. While BMD assessment based on QCT required an additional standardised bone density calibration phantom, the DECT technique operated by using a dedicated postprocessing software based on material decomposition without requiring calibration phantoms. Accuracy and precision of both modalities were compared by calculating measurement errors. In addition, correlation and agreement analyses were performed using Pearson correlation, linear regression, and Bland-Altman plots. Results: DECT-derived BMD values differed significantly from those obtained by QCT (p < 0.001) and were found to be closer to true HA concentrations. Relative measurement errors were significantly smaller for DECT in comparison to QCT (L1, 0.94% versus 9.68%; L2, 0.28% versus 5.74%; L3, 0.24% versus 3.67%, respectively). DECT demonstrated better BMD measurement repeatability compared to QCT (coefficient of variance < 4.29% for DECT, < 6.74% for QCT). Both methods correlated well to each other (r = 0.9993; 95% confidence interval 0.9984–0.9997; p < 0.001) and revealed substantial agreement in Bland-Altman plots. Conclusions: Phantomless dual-source DECT-based BMD assessment of lumbar vertebra equivalents using material decomposition showed higher diagnostic accuracy compared to QCT.
Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode the cis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affecting RON exon 11 skipping, which corresponds to the pathological isoform RON∆165. Importantly, the effects correlate with RON alternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.
Background: Inflammation, angiogenesis and oxidative stress have been implicated in the pathogenesis of various vascular diseases. Recent evidence suggests that dimethylfumarate (DMF), an antiposriatic and anti-multiple sclerosis agent, possesses anti-inflammatory, anti-oxidative and anti-angiogenic properties. Here, we analyze the influence of DMF on TNF-α-induced expression of the important pro-inflammatory and pro-atherogenic chemokine MCP-1 and investigate the underlying mechanisms of this expression.
Findings: We analyzed constitutive and TNF-α-induced expression of MCP-1 in human umbilical vascular endothelial cells (HUVEC) +/− DMF treatment via enzyme-linkes immunosorbent assay (ELISA). DMF significantly inhibited the protein expression levels in a time- and concentration-dependent manner. Furthermore, MCP-1 mRNA expression was also reduced in response to DMF, as demonstrated by RT-PCR. Thus, the regulation occurs at the transcriptional level. Interestingly, DMF prolonged the TNF-α-induced p38 and JNK phosphorylation in HUVEC, as demonstrated by Western blot analysis; however, the p38 and JNK inhibitor SB203580 did not affect the DMF-conveyed suppression of TNF-α-induced MCP-1 expression. DMF suppressed the TNF-α-induced nuclear translocation and phosphorylation (Serine 536) of p65 in these cells. These results were additionally approved by p65 luciferase promoter assays. Furthermore, we found that DMF slightly inhibited the early degradation of IκBα. In addition, we verified our results using other important inflammatory cytokines such as CCL-5, PDGF-BB, GM-CSF and IL-6.
Conclusion: DMF suppresses various TNF-α-induced pro-inflammatory and pro-atherogenic cytokines/chemokines in human endothelial cells. This action is regulated by reduced p65 activity and nuclear translocation, which can be explained in part by the reduced early degradation of IκBα and more important the reduced phosphorylation of p65 at Serine 536. These effects were independent of the p38, PI3K and p42/44 signaling pathways. As a result, DMF might be suitable for treating patients with vascular diseases.
Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, and are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely sensed biomass products and are undersampled by in situ monitoring. Current global change threats emphasize the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we developed and deployed a new protocol for photogrammetric height using unoccupied aerial vehicle (UAV) images to test its capability for delivering standardized measurements of biomass across a globally distributed field experiment. We assessed whether canopy height inferred from UAV photogrammetry allows the prediction of aboveground biomass (AGB) across low-stature plant species by conducting 38 photogrammetric surveys over 741 harvested plots to sample 50 species. We found mean canopy height was strongly predictive of AGB across species, with a median adjusted R2 of 0.87 (ranging from 0.46 to 0.99) and median prediction error from leave-one-out cross-validation of 3.9%. Biomass per-unit-of-height was similar within but different among, plant functional types. We found that photogrammetric reconstructions of canopy height were sensitive to wind speed but not sun elevation during surveys. We demonstrated that our photogrammetric approach produced generalizable measurements across growth forms and environmental settings and yielded accuracies as good as those obtained from in situ approaches. We demonstrate that using a standardized approach for UAV photogrammetry can deliver accurate AGB estimates across a wide range of dynamic and heterogeneous ecosystems. Many academic and land management institutions have the technical capacity to deploy these approaches over extents of 1–10 ha−1. Photogrammetric approaches could provide much-needed information required to calibrate and validate the vegetation models and satellite-derived biomass products that are essential to understand vulnerable and understudied non-forested ecosystems around the globe.
CD4+ T cell lymphopenia predicts mortality from Pneumocystis pneumonia in kidney transplant patients
(2020)
Background: Pneumocystis jirovecii pneumonia (PcP) remains a life-threatening opportunistic infection after solid organ transplantation, even in the era of Pneumocystis prophylaxis. The association between risk of developing PcP and low CD4+ T cell counts has been well established. However, it is unknown whether lymphopenia in the context of post-renal transplant PcP increases the risk of mortality. Methods: We carried out a retrospective analysis of a cohort of kidney transplant patients with PcP (n = 49) to determine the risk factors for mortality associated with PcP. We correlated clinical and demographic data with the outcome of the disease. For CD4+ T cell counts, we used the Wilcoxon rank sum test for in-hospital mortality and a Cox proportional-hazards regression model for 60-day mortality. Results: In univariate analyses, high CRP, high neutrophils, CD4+ T cell lymphopenia, mechanical ventilation, and high acute kidney injury network stage were associated with in-hospital mortality following presentation with PcP. In a receiver-operator characteristic (ROC) analysis, an optimum cutoff of ≤200 CD4+ T cells/µL predicted in-hospital mortality, CD4+ T cell lymphopenia remained a risk factor in a Cox regression model. Conclusions: Low CD4+ T cell count in kidney transplant recipients is a biomarker for disease severity and a risk factor for in-hospital mortality following presentation with PcP.
Relationship between regional white matter hyperintensities and alpha oscillations in older adults
(2021)
Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7–13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60–80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources.
Utility of the new cobas HCV test for viral load monitoring during direct-acting antiviral therapy
(2019)
Background: The COBAS AmpliPrep/COBAS TaqMan assay HCV (CAP/CTM) is widely used in clinical routine for HCV testing. Recently, the new cobas HCV test was established for high throughput testing with minimal operator intervention. As different assays may yield different quantitative/qualitative results that possibly impact treatment decisions, the aim of this study was to externally evaluate the cobas HCV test performance in comparison to CAP/CTM in a clinically relevant setting.
Methods: Serum samples were obtained from 270 patients who received direct acting antiviral therapy with different treatment regimens at two study sites (Hannover and Frankfurt) in 2016. Overall, 1545 samples (baseline, on-treatment and follow-up) were tested in parallel by both assays.
Results: The mean difference between cobas HCV and CAP/CTM for the quantification of HCV RNA was 0.008 log10 IU/ml HCV RNA (95% limits of agreement: -0.02–0.036) showing excellent agreement of both assays. With respect to clinical cut offs (HCV RNA detectable vs. target not detected and HCV RNA above the lower limit of quantification (LLOQ) vs. <LLOQ), discordant results were obtained in 9.5% and 4.6%, respectively; the greatest differences were observed during early stages of antiviral therapy (week 1, week 2 and week 4), but none were statistically significant. Overall percent agreement for SVR between cobas HCV and CAP/CTM at the 15 IU/ml cutoff was 99.2% (95%CI 92.7%-100%).
Conclusion: The performance of the new cobas HCV test was comparable to CAP/CTM in a clinical setting representing a large patient population with HCV GT 1 and 3 treated with DAAs.
The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future due to global climate change. Dynamic global vegetation models (DGVMs) are very useful for understanding vegetation dynamics under the present climate, and for predicting its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna, and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modeling. The outcomes of the models, which include different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. By drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need improved representation in the examined DGVMs. The first mechanism includes water limitation to tree growth, and tree–grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass–fire feedback, which maintains both forest and savanna presence in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant forest trees, and fire-resistant and shade-intolerant savanna trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.
The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future, due to global climate change. Dynamic Global Vegetation Models (DGVMs) are very useful to understand vegetation dynamics under present climate, and to predict its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modelling. Model outcomes, obtained including different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. Through these comparisons, and by drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need an improved representation in the DGVMs. The first mechanism includes water limitation to tree growth, and tree-grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass-fire feedback, which maintains both forest and savanna occurrences in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant savanna trees, and fire-resistant and shade-intolerant forest trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.