Bone symptoms can be an early manifestation of Gaucher disease implications for diagnosis

Gaucher disease (GD) is caused by mutations in the gene GBA1, which encodes for the synthesis of the enzyme lysosomal glucocerebrosidase (GCase). Lack or deficiency of GCase activity causes accumulation of glucosylceramide in the lysosomes of the monocyte-macrophage system in the bone marrow, spleen, and liver, and less frequently in the lungs and the central nervous system; this accumulation results in cell damage and organ dysfunction.Currently available diagnostic algorithms are based on the well-recognized hematological manifestations (cytopenia and splenomegaly), which are the manifestations most commonly associated with GD. However, 25 to 32% of patients have been found to present with bone signs and/or symptoms as the only or main presenting sign of the disease.A number of physicians may be unaware of this clinical presentation of GD, and may therefore delay in establishing diagnosis and initiating treatment, when necessary.We developed an educational program for early detection and diagnosis of GD, which includes a diagnostic algorithm based on GD-related bone manifestations.We herein report the case of a girl with bone symptoms as the only first manifestation of GD that were mistaken for stress fracture and osteomyelitis, and who was seen by 5 different specialists over a 4-year period before she was accurately diagnosed with GD.The case presented here shows the usefulness of the educational program for early detection and diagnosis of GD based on bone symptoms.Fil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delgado González, Diana Catherine. Mautalen Salud e Investigación; ArgentinaFil: Ferrari, Emma. Hospital SAMCO Villa Ocampo; Argentin

Mujeres que inspiran…Grandes historias de guerreras

Recopilación de historias propias o contadas por terceros de mujeres que han superado retos, dificultades, competencias y cómo han conseguido lograr hazañas inspiradoras.Collection of own or told stories by third parties of women who have overcome challenges, difficulties, competencies and how they have managed to achieve inspiring feats.Yamel Rodríguez -- Iber James Quiñones -- Diana Yamileth Velasquez Maldonado -- Nidia Karina Mora Londoño -- Aura María Rosero -- Catherine Caicedo -- David Alejandro Mera Benavides -- Elizabeth Cárdenas Berrío -- Jhon Jairo Leal F. -- Miguel Ángel Solís -- Milton Cesar Mera Osorio -- Elizabeth González Londoño -- Lorena Villegas -- Ana María Cortés Rosero -- Jhonathan Paul Obando Vera -- María Elena Realpe Delgado -- Carolina Medina Alcalde -- Yaneth Ariasna34 página

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Measurement of B-c(2S)(+) and B-c*(2S)(+) cross section ratios in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe

Reconstruction of signal amplitudes in the CMS electromagnetic calorimeter in the presence of overlapping proton-proton interactions

A template fitting technique for reconstructing the amplitude of signals produced by the lead tungstate crystals of the CMS electromagnetic calorimeter is described. This novel approach is designed to suppress the contribution to the signal of the increased number of out-of-time interactions per beam crossing following the reduction of the accelerator bunch spacing from 50 to 25 ns at the start of Run 2 of the LHC. Execution of the algorithm is sufficiently fast for it to be employed in the CMS high-level trigger. It is also used in the offline event reconstruction. Results obtained from simulations and from Run 2 collision data (2015-2018) demonstrate a substantial improvement in the energy resolution of the calorimeter over a range of energies extending from a few GeV to several tens of GeV.Peer reviewe

Observation of the Production of Three Massive Gauge Bosons at root s=13 TeV

The first observation is reported of the combined production of three massive gauge bosons (VVV with V = W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV. The analysis is based on a data sample recorded by the CMS experiment at the CERN LHC corresponding to an integrated luminosity of 137 fb(-1). The searches for individualWWW, WWZ, WZZ, and ZZZ production are performed in final states with three, four, five, and six leptons (electrons or muons), or with two same-sign leptons plus one or two jets. The observed (expected) significance of the combinedVVV production signal is 5.7 (5.9) standard deviations and the corresponding measured cross section relative to the standard model prediction is 1.02(-0.23)(+0.26). The significances of the individual WWW and WWZ production are 3.3 and 3.4 standard deviations, respectively. Measured production cross sections for the individual triboson processes are also reported

Performance of the CMS muon trigger system in proton-proton collisions at √s = 13 TeV

The muon trigger system of the CMS experiment uses a combination of hardware and software to identify events containing a muon. During Run 2 (covering 2015-2018) the LHC achieved instantaneous luminosities as high as 2 × 10 cm s while delivering proton-proton collisions at √s = 13 TeV. The challenge for the trigger system of the CMS experiment is to reduce the registered event rate from about 40 MHz to about 1 kHz. Significant improvements important for the success of the CMS physics program have been made to the muon trigger system via improved muon reconstruction and identification algorithms since the end of Run 1 and throughout the Run 2 data-taking period. The new algorithms maintain the acceptance of the muon triggers at the same or even lower rate throughout the data-taking period despite the increasing number of additional proton-proton interactions in each LHC bunch crossing. In this paper, the algorithms used in 2015 and 2016 and their improvements throughout 2017 and 2018 are described. Measurements of the CMS muon trigger performance for this data-taking period are presented, including efficiencies, transverse momentum resolution, trigger rates, and the purity of the selected muon sample. This paper focuses on the single- and double-muon triggers with the lowest sustainable transverse momentum thresholds used by CMS. The efficiency is measured in a transverse momentum range from 8 to several hundred GeV

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV