Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease

Background: The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Aim: To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients. Methods: A review of data in SpRGD from patients'' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (=1994, cohort A; =1995, cohort B). Results: A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed = 1994 and 53 = 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients'' diagnosed =1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years [cohort A] and 1.6 years [cohort B] (p < 0.001). Conclusions: The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

Measurement of the azimuthal anisotropy of Y(1S) and Y(2S) mesons in PbPb collisions at √S^{S}NN = 5.02 TeV

The second-order Fourier coefficients (υ$_{2}$) characterizing the azimuthal distributions of Υ(1S) and Υ(2S) mesons produced in PbPb collisions at $\sqrt{s_{NN}}$ = 5.02 TeV are studied. The Υmesons are reconstructed in their dimuon decay channel, as measured by the CMS detector. The collected data set corresponds to an integrated luminosity of 1.7 nb$^{-1}$. The scalar product method is used to extract the υ$_{2}$ coefficients of the azimuthal distributions. Results are reported for the rapidity range |y| < 2.4, in the transverse momentum interval 0 < p$_{T}$ < 50 GeV/c, and in three centrality ranges of 10–30%, 30–50% and 50–90%. In contrast to the J/ψ mesons, the measured υ$_{2}$ values for the Υ mesons are found to be consistent with zero

Performance of reconstruction and identification of τ leptons decaying to hadrons and vτ in pp collisions at √s=13 TeV

The algorithm developed by the CMS Collaboration to reconstruct and identify τ leptons produced in proton-proton collisions at √s=7 and 8 TeV, via their decays to hadrons and a neutrino, has been significantly improved. The changes include a revised reconstruction of π⁰ candidates, and improvements in multivariate discriminants to separate τ leptons from jets and electrons. The algorithm is extended to reconstruct τ leptons in highly Lorentz-boosted pair production, and in the high-level trigger. The performance of the algorithm is studied using proton-proton collisions recorded during 2016 at √s=13 TeV, corresponding to an integrated luminosity of 35.9 fb¯¹. The performance is evaluated in terms of the efficiency for a genuine τ lepton to pass the identification criteria and of the probabilities for jets, electrons, and muons to be misidentified as τ leptons. The results are found to be very close to those expected from Monte Carlo simulation

Performance of the CMS Level-1 trigger in proton-proton collisions at √s = 13 TeV

At the start of Run 2 in 2015, the LHC delivered proton-proton collisions at a center-of-mass energy of 13\TeV. During Run 2 (years 2015–2018) the LHC eventually reached a luminosity of 2.1× 10$^{34}$ cm$^{-2}$s$^{-1}$, almost three times that reached during Run 1 (2009–2013) and a factor of two larger than the LHC design value, leading to events with up to a mean of about 50 simultaneous inelastic proton-proton collisions per bunch crossing (pileup). The CMS Level-1 trigger was upgraded prior to 2016 to improve the selection of physics events in the challenging conditions posed by the second run of the LHC. This paper describes the performance of the CMS Level-1 trigger upgrade during the data taking period of 2016–2018. The upgraded trigger implements pattern recognition and boosted decision tree regression techniques for muon reconstruction, includes pileup subtraction for jets and energy sums, and incorporates pileup-dependent isolation requirements for electrons and tau leptons. In addition, the new trigger calculates high-level quantities such as the invariant mass of pairs of reconstructed particles. The upgrade reduces the trigger rate from background processes and improves the trigger efficiency for a wide variety of physics signals

Pileup mitigation at CMS in 13 TeV data

With increasing instantaneous luminosity at the LHC come additional reconstruction challenges. At high luminosity, many collisions occur simultaneously within one proton-proton bunch crossing. The isolation of an interesting collision from the additional "pileup" collisions is needed for effective physics performance. In the CMS Collaboration, several techniques capable of mitigating the impact of these pileup collisions have been developed. Such methods include charged-hadron subtraction, pileup jet identification, isospin-based neutral particle "δβ" correction, and, most recently, pileup per particle identification. This paper surveys the performance of these techniques for jet and missing transverse momentum reconstruction, as well as muon isolation. The analysis makes use of data corresponding to 35.9 fb$^{-1}$ collected with the CMS experiment in 2016 at a center-of-mass energy of 13 TeV. The performance of each algorithm is discussed for up to 70 simultaneous collisions per bunch crossing. Significant improvements are found in the identification of pileup jets, the jet energy, mass, and angular resolution, missing transverse momentum resolution, and muon isolation when using pileup per particle identification

Measurement of the Y(1S) pair production cross section and search for resonances decaying to Y(1S)μ⁺μ⁻ in proton-proton collisions at √s = 13 TeV

The fiducial cross section for Y(1S)pair production in proton-proton collisions at a center-of-mass energy of 13TeVin the region where both Y(1S)mesons have an absolute rapidity below 2.0 is measured to be 79 ± 11 (stat) ±6 (syst) ±3 (B)pbassuming the mesons are produced unpolarized. The last uncertainty corresponds to the uncertainty in the Y(1S)meson dimuon branching fraction. The measurement is performed in the final state with four muons using proton-proton collision data collected in 2016 by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9fb$^{-1}$. This process serves as a standard model reference in a search for narrow resonances decaying to Y(1S)μ$^{+}$μ$^{-}$ in the same final state. Such a resonance could indicate the existence of a tetraquark that is a bound state of two bquarks and two b̅ antiquarks. The tetraquark search is performed for masses in the vicinity of four times the bottom quark mass, between 17.5 and 19.5GeV, while a generic search for other resonances is performed for masses between 16.5 and 27GeV. No significant excess of events compatible with a narrow resonance is observed in the data. Limits on the production cross section times branching fraction to four muons via an intermediate Y(1S)resonance are set as a function of the resonance mass

Identification of heavy, energetic, hadronically decaying particles using machine-learning techniques

Machine-learning (ML) techniques are explored to identify and classify hadronic decays of highly Lorentz-boosted W/Z/Higgs bosons and top quarks. Techniques without ML have also been evaluated and are included for comparison. The identification performances of a variety of algorithms are characterized in simulated events and directly compared with data. The algorithms are validated using proton-proton collision data at √s = 13TeV, corresponding to an integrated luminosity of 35.9 fb−1. Systematic uncertainties are assessed by comparing the results obtained using simulation and collision data. The new techniques studied in this paper provide significant performance improvements over non-ML techniques, reducing the background rate by up to an order of magnitude at the same signal efficiency