Application of the heart failure meta-score to predict prognosis in patients with cardiac resynchronization defibrillators

Background: The Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality. Methods: Data from 648 consecutive patients from two centers were used for the evaluation of the performance of the HF Meta-score. The primary endpoint was mortality and the secondary endpoint was time to first appropriate implantable cardioverter-defibrillator (ICD) shock or death without prior appropriate ICD shock. Fine-Gray model was used for competing risk regression analysis. Results: In the entire cohort, 237 patients died over a median follow-up of 5.2 years. Five-year cumulative incidence of mortality ranged from 12% to 53%, for quintiles 1 through 5 of the HF Meta-score, respectively (log-rank P < 0.001). Compared with the lowest quintile, mortality risk was higher in the highest quintile (HR 6.9; 95%CI 3.7–12.8). The HF Meta-score had excellent calibration, accuracy, and good discrimination in predicting mortality (C-statistic 0.76 at 1-year and 0.71 at 5-year). The risk of death without appropriate ICD shock was higher in risk quintile 5 compared to quintile 1 (sub HR 5.8; 95%CI 3.1–11.0, P < 0.001). Conclusions: Our study demonstrated a good ability of the HF Meta-score to predict survival in HF patients treated with CRT-D as primary prevention. The HF Meta-score proved to be useful in identifying a subgroup with a significantly poor prognosis despite a CRT-D

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Two-particle transverse momentum correlations in pp and p-Pb collisions at LHC energies

Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at LHC energies, provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb--Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at $\sqrt{s} = 7$ TeV and $\sqrt{s_{\rm NN}} = 5.02$ TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.Two-particle transverse momentum differential correlators, recently measured in Pb--Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at $\sqrt{s} = 7$ TeV and $\sqrt{s_{\rm NN}} = 5.02$ TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p--Pb to Pb--Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behavior. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at s=7TeV and sNN=5.02TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed

Towards the understanding of the genuine three-body interaction for p−-p−-p and p−-p−Λ-\Lambda

Three-body nuclear forces play an important role in the structure of nuclei and hypernuclei and are also incorporated in models to describe the dynamics of dense baryonic matter, such as in neutron stars. So far, only indirect measurements anchored to the binding energies of nuclei can be used to constrain the three-nucleon force, and if hyperons are considered, the scarce data on hypernuclei impose only weak constraints on the three-body forces. In this work, we present the first direct measurement of the p–p–p and p–p–$\Lambda$ systems in terms of three-particle correlation functions carried out for pp collisions at $\sqrt{s} = 13$ TeV. Three-particle cumulants are extracted from the correlation functions by applying the Kubo formalism, where the three-particle interaction contribution to these correlations can be isolated after subtracting the known two-body interaction terms. A negative cumulant is found for the p–p–p system, hinting to the presence of a residual three-body effect while for p–p–$\Lambda$ the cumulant is consistent with zero. This measurement demonstrates the accessibility of three-baryon correlations at the LHC.Three-body nuclear forces play an important role in the structure of nuclei and hypernuclei and are also incorporated in models to describe the dynamics of dense baryonic matter, such as in neutron stars. So far, only indirect measurements anchored to the binding energies of nuclei can be used to constrain the three-nucleon force, and if hyperons are considered, the scarce data on hypernuclei impose only weak constraints on the three-body forces. In this work, we present the first direct measurement of the p$-$p$-$p and p$-$p$-\Lambda$ systems in terms of three-particle correlation functions carried out for pp collisions at $\sqrt{s} = 13$ TeV. Three-particle cumulants are extracted from the correlation functions by applying the Kubo formalism, where the three-particle interaction contribution to these correlations can be isolated after subtracting the known two-body interaction terms. A negative cumulant is found for the p$-$p$-$p system, hinting to the presence of a residual three-body effect while for p$-$p$-\Lambda$ the cumulant is consistent with zero. This measurement demonstrates the accessibility of three-baryon correlations at the LHC

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at <math display="inline"><mrow><msqrt><mrow><mi>s</mi></mrow></msqrt><mo>=</mo><mn>5.02</mn></mrow></math> and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum ($p_{\rm T}$) thresholds of 0.15, 0.5, 1, and 2 GeV$/c$ was measured in pp collisions at centre-of-mass energies of $\sqrt{s}=$ 5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity ($\eta$) within $\pm0.8$ and $p_{\rm T}$ larger than the corresponding threshold. The measurements were also performed for inelastic and non-single-diffractive events as well as for inelastic events with at least one charged particle having $|\eta|2 {\rm\ GeV}/c$), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments.The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2  GeV/c is measured in pp collisions at the center of mass energies of s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within ±0.8 and pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|&lt;1 in pp collisions at s=5.02  TeV for the first time at the LHC. These measurements are compared to the pythia 6, pythia 8, and epos-lhc models. In general, the models describe the η dependence of particle production well. However, discrepancies are observed for the highest transverse momentum threshold (pT&gt;2  GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at s=13  TeV.The pseudorapidity density of charged particles with minimum transverse momentum ($p_{\rm T}$) thresholds of 0.15, 0.5, 1, and 2 GeV$/c$ is measured in pp collisions at the centre of mass energies of $\sqrt{s} =$ 5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity ($\eta$) within $\pm0.8$ and $p_{\rm T}$ larger than the corresponding threshold. In addition, measurements without $p_{\rm T}$-thresholds are performed for inelastic and non-single-diffractive events as well as for inelastic events with at least one charged particle having $|\eta|2 {\rm\ GeV}/c$), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at $\sqrt{s} = 13$ TeV