Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK-Biobank. The Lifelines, and The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK-Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans

A call for standardised age-disaggregated health data.

The 2030 Sustainable Development Goals agenda calls for health data to be disaggregated by age. However, age groupings used to record and report health data vary greatly, hindering the harmonisation, comparability, and usefulness of these data, within and across countries. This variability has become especially evident during the COVID-19 pandemic, when there was an urgent need for rapid cross-country analyses of epidemiological patterns by age to direct public health action, but such analyses were limited by the lack of standard age categories. In this Personal View, we propose a recommended set of age groupings to address this issue. These groupings are informed by age-specific patterns of morbidity, mortality, and health risks, and by opportunities for prevention and disease intervention. We recommend age groupings of 5 years for all health data, except for those younger than 5 years, during which time there are rapid biological and physiological changes that justify a finer disaggregation. Although the focus of this Personal View is on the standardisation of the analysis and display of age groups, we also outline the challenges faced in collecting data on exact age, especially for health facilities and surveillance data. The proposed age disaggregation should facilitate targeted, age-specific policies and actions for health care and disease management

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

Measurement of prompt D0^{0}, D+^{+}, D∗+^{*+}, and DS+ {\mathrm{D}}_{\mathrm{S}}^{+} production in p–Pb collisions at sNN \sqrt{{\mathrm{s}}_{\mathrm{NN}}} = 5.02 TeV

International audienceThe measurement of the production of prompt D$^{0}$, D$^{+}$, D$^{*+}$, and ${\mathrm{D}}_{\mathrm{S}}^{+}$ mesons in proton–lead (p–Pb) collisions at the centre-of-mass energy per nucleon pair of $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV, with an integrated luminosity of 292 ± 11 μb$^{−1}$, are reported. Differential production cross sections are measured at mid-rapidity (−0.96 < y$_{cms}$< 0.04) as a function of transverse momentum (p$_{T}$) in the intervals 0 < p$_{T}$< 36 GeV/c for D$^{0}$, 1 < p$_{T}$< 36 GeV/c for D$^{+}$ and D$^{*+}$, and 2 < p$_{T}$< 24 GeV/c for D$^{+}$ mesons. For each species, the nuclear modification factor R$_{pPb}$ is calculated as a function of p$_{T}$ using a proton-proton (pp) ref- erence measured at the same collision energy. The results are compatible with unity in the whole p$_{T}$ range. The average of the non-strange D mesons R$_{pPb}$ is compared with theoretical model predictions that include initial-state effects and parton transport model predictions. The p$_{T}$ dependence of the D$^{0}$, D$^{+}$, and D$^{*+}$ nuclear modification factors is also reported in the interval 1 < p$_{T}$< 36 GeV/c as a function of the collision centrality, and the central-to-peripheral ratios are computed from the D-meson yields measured in different centrality classes. The results are further compared with charged-particle measurements and a similar trend is observed in all the centrality classes. The ratios of the p$_{T}$-differential cross sections of D$^{0}$, D$^{+}$, D$^{*+}$, and ${\mathrm{D}}_{\mathrm{S}}^{+}$ mesons are also reported. The ${\mathrm{D}}_{\mathrm{S}}^{+}$ and D$^{+}$ yields are compared as a function of the charged-particle multiplicity for several p$_{T}$ intervals. No modification in the relative abundances of the four species is observed with respect to pp collisions within the statistical and systematic uncertainties

Λc+\Lambda_\mathrm{c}^+ production in Pb-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}} = 5.02 TeVUC

A measurement of the production of prompt $\Lambda_\mathrm{c}^+$ baryons in Pb–Pb collisions at $\sqrt{s_{\rm NN}}$ = 5.02 TeV with the ALICE detector at the LHC is reported. The $\Lambda_\mathrm{c}^+$ and $\bar{\Lambda_\mathrm{c}}^-$ were reconstructed at midrapidity (|y|<0.5) via the hadronic decay channel $\Lambda_\mathrm{c}^+$→pK$_{\rm S}^0$ (and charge conjugate) in the transverse momentum and centrality intervals 6 < $p_{\rm T}$ < 12 GeV/ c and 0–80%. The $\Lambda_\mathrm{c}^+$/D$^0$ ratio, which is sensitive to the charm quark hadronisation mechanisms in the medium, is measured and found to be larger than the ratio measured in minimum-bias pp collisions at $\sqrt{s}$ = 7 TeV and in p–Pb collisions at $\sqrt{s_{\rm NN}}$ = 5.02 TeV. In particular, the values in p–Pb and Pb–Pb collisions differ by about two standard deviations of the combined statistical and systematic uncertainties in the common $p_{\rm T}$ interval covered by the measurements in the two collision systems. The $\Lambda_\mathrm{c}^+$/D$^0$ ratio is also compared with model calculations including different implementations of charm quark hadronisation. The measured ratio is reproduced by models implementing a pure coalescence scenario, while adding a fragmentation contribution leads to an underestimation. The $\Lambda_\mathrm{c}^+$ nuclear modification factor, $R_{\rm AA}$, is also presented. The measured values of the $R_{\rm AA}$ of $\Lambda_\mathrm{c}^+$, D$_{\rm s}^+$ and non-strange D mesons are compatible within the combined statistical and systematic uncertainties. They show, however, a hint of a hierarchy ($R_{\rm AA}^{D^0}$ < $R_{\rm AA}^{D_\mathrm{s}^+}$ < $R_{\rm AA}^{\Lambda_\mathrm{c}^+}$) , conceivable with a contribution from coalescence mechanisms to charm hadron formation in the medium

Real-time data processing in the ALICE High Level Trigger at the LHC

International audienceAt the Large Hadron Collider at CERN in Geneva, Switzerland, atomic nuclei are collided at ultra-relativistic energies. Many final-state particles are produced in each collision and their properties are measured by the ALICE detector. The detector signals induced by the produced particles are digitized leading to data rates that are in excess of 48 GB/s. The ALICE High Level Trigger (HLT) system pioneered the use of FPGA- and GPU-based algorithms to reconstruct charged-particle trajectories and reduce the data size in real time. The results of the reconstruction of the collision events, available online, are used for high level data quality and detector-performance monitoring and real-time time-dependent detector calibration. The online data compression techniques developed and used in the ALICE HLT have more than quadrupled the amount of data that can be stored for offline event processing

Λ3H^3_\Lambda\mathrm{H} and Λˉ3H‾^3_{\bar{\Lambda}}\mathrm{\overline{H}} lifetime measurement in Pb-Pb collisions at sNN=\sqrt{s_{\mathrm{NN}}} = 5.02 TeV via two-body decay

International audienceAn improved value for the lifetime of the (anti-)hypertriton has been obtained using the data sample of Pb–Pb collisions at sNN=5.02 TeV collected by the ALICE experiment at the LHC. The (anti-)hypertriton has been reconstructed via its charged two-body mesonic decay channel and the lifetime has been determined from an exponential fit to the d N /d( ct ) spectrum. The measured value, τ=242−38+34 (stat.) ± 17 (syst.) ps, is compatible with representative theoretical predictions, thus contributing to the solution of the longstanding hypertriton lifetime puzzle

Exploration of jet substructure using iterative declustering in pp and Pb–Pb collisions at LHC energies

The ALICE collaboration at the CERN LHC reports novel measurements of jet substructure in pp collisions at $\sqrt{s}$= 7 TeV and central Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 2.76 TeV. Jet substructure of track-based jets is explored via iterative declustering and grooming techniques. We present the measurement of the momentum sharing of two-prong substructure exposed via grooming, the $z_{\rm{g}}$, and its dependence on the opening angle, in both pp and Pb-Pb collisions. We also present the first measurement of the distribution of the number of branches obtained in the iterative declustering of the jet, which is interpreted as the number of its hard splittings. In Pb-Pb collisions, we observe a suppression of symmetric splittings at large opening angles and an enhancement of splittings at small opening angles relative to pp collisions, with no significant modification of the number of splittings. The results are compared to predictions from various Monte Carlo event generators to test the role of important concepts in the evolution of the jet in the medium such as color coherence

Measurement of charged jet cross section in pp collisions at √s = 5.02 TeV

The cross section of jets reconstructed from charged particles is measured in the transverse momentum range of 5<pT<100 GeV/c in pp collisions at the center-of-mass energy of s√=5.02 TeV with the ALICE detector. The jets are reconstructed using the anti-kT algorithm with resolution parameters R=0.2, 0.3, 0.4, and 0.6 in the pseudorapidity range |η|<0.9−R. The charged jet cross sections are compared with the leading order (LO) and to next-to-leading order (NLO) perturbative Quantum ChromoDynamics (pQCD) calculations. It was found that the NLO calculations agree better with the measurements. The cross section ratios for different resolution parameters were also measured. These ratios increase from low pT to high pT and saturate at high pT, indicating that jet collimation is larger at high pT than at low pT. These results provide a precision test of pQCD predictions and serve as a baseline for the measurement in Pb−Pb collisions at the same energy to quantify the effects of the hot and dense medium created in heavy-ion collisions at the LHC