AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Search for time-dependent CP violation in D-0 -> K+K- and D-0 -> pi(+)pi(-) decays

A search for time-dependent violation of the charge-parity symmetry in $D^0 \to K^+ K^-$ and $D^0 \to \pi^+ \pi^-$ decays is performed at the LHCb experiment using proton-proton collision data recorded from 2015 to 2018 at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. The $D^0$ meson is required to originate from a $D^*(2010)^+ \to D^0 \pi^+$ decay, such that its flavour at production is identified by the charge of the accompanying pion. The slope of the time-dependent asymmetry of the decay rates of $D^0$ and $\bar{D}^0$ mesons into the final states under consideration is measured to be $\Delta Y_{K^+ K^-} = (-2.3 \pm 1.5 \pm 0.3) \times 10^{-4}$, $\Delta Y_{\pi^+ \pi^-} = (-4.0 \pm 2.8 \pm 0.4)\times 10^{-4}$, where the first uncertainties are statistical and the second are systematic. These results are compatible with the conservation of the charge-parity symmetry at the level of 2 standard deviations and improve the precision by nearly a factor of two.Comment: Updated to match published version; all figures and tables, along with supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2020-045.htm

Evidence of a J/psi Lambda structure and observation of excited Xi(-) states in the Xi(-)(b) -> J/psi Lambda K- decay

First evidence of a structure in the $J/\psi \varLambda$ invariant mass distribution is obtained from an amplitude analysis of $\varXi_b^- \to J/\psi \varLambda K^-$ decays. The observed structure is consistent with being due to a charmonium pentaquark with strangeness. Its mass and width are determined to be 4458.8\pm2.9\,^{+4.7}_{-1.1}MeV and 17.3\pm6.5\,^{+8.0}_{-5.7}MeV, where the quoted uncertainties are statistical and systematic, respectively. The structure is also consistent with being due to two resonances. In addition, the narrow excited $\varXi^-$ states, $\varXi(1690)^-$ and $\varXi(1820)^-$, are seen for the first time in a $\varXi_b^-$ decay, and their masses and widths are measured with improved precision. The analysis is performed using $pp$ collision data corresponding to a total integrated luminosity of 9fb$^{-1}$, collected with the LHCb experiment at centre-of-mass energies of $7$, $8$ and $13$TeV.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2020-039.html (LHCb public pages

Searches for rare B-s(0) and B-0 decays into four muons

Searches for rare $B_s^0$ and $B^0$ decays into four muons are performed using proton-proton collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 9 $\text{fb}^{-1}$. Direct decays and decays via light scalar and $J/\psi$ resonances are considered. No evidence for the six decays searched for is found and upper limits at the 95% confidence level on their branching fractions ranging between $1.8\times10^{-10}$ and $2.6\times10^{-9}$ are set

Search for the doubly charmed baryon Ξ cc + in the Ξ c + π − π + final state

Abstract: A search for the doubly charmed baryon Ξcc+ is performed in the Ξc+π−π+ invariant-mass spectrum, where the Ξc+ baryon is reconstructed in the pK−π+ final state. The study uses proton-proton collision data collected with the LHCb detector at a centre- of-mass energy of 13 TeV, corresponding to a total integrated luminosity of 5.4 fb−1. No significant signal is observed in the invariant-mass range of 3.4–3.8 GeV/c2. Upper limits are set on the ratio of branching fractions multiplied by the production cross-section with respect to the Ξcc++→ (Ξc+→ pK−π+)π+ decay for different Ξcc+ mass and lifetime hypotheses in the rapidity range from 2.0 to 4.5 and the transverse momentum range from 2.5 to 25 GeV/c. The results from this search are combined with a previously published search for the Ξcc+→Λc+K−π+ decay mode, yielding a maximum local significance of 4.0 standard deviations around the mass of 3620 MeV/c2, including systematic uncertainties. Taking into account the look-elsewhere effect in the 3.5–3.7 GeV/c2 mass window, the combined global significance is 2.9 standard deviations including systematic uncertainties

Test of lepton universality in beauty-quark decays

The standard model of particle physics currently provides our best description of fundamental particles and their interactions. The theory predicts that the different charged leptons, the electron, muon and tau, have identical electroweak interaction strengths. Previous measurements have shown that a wide range of particle decays are consistent with this principle of lepton universality. This article presents evidence for the breaking of lepton universality in beauty-quark decays, with a significance of 3.1 standard deviations, based on proton–proton collision data collected with the LHCb detector at CERN’s Large Hadron Collider. The measurements are of processes in which a beauty meson transforms into a strange meson with the emission of either an electron and a positron, or a muon and an antimuon. If confirmed by future measurements, this violation of lepton universality would imply physics beyond the standard model, such as a new fundamental interaction between quarks and leptons

Measurement of forward W and Z boson production in pppp collisions at s=8 \sqrt{s}=8 TeV

Measurements are presented of electroweak boson production using data from $pp$ collisions at a centre-of-mass energy of $\sqrt{s} = 8\mathrm{\,Te\kern -0.1em V}$. The analysis is based on an integrated luminosity of $2.0\mathrm{\,fb}^{-1}$ recorded with the LHCb detector. The bosons are identified in the $W\rightarrow\mu\nu$ and $Z\rightarrow\mu^{+}\mu^{-}$ decay channels. The cross-sections are measured for muons in the pseudorapidity range $2.0 20{\mathrm{\,Ge\kern -0.1em V\!/}c}$ and, in the case of the $Z$ boson, a dimuon mass within $60 < M_{\mu^{+}\mu^{-}} < 120{\mathrm{\,Ge\kern -0.1em V\!/}c^{2}}$. The results are \begin{align*} \sigma_{W^{+}\rightarrow\mu^{+}\nu} &= 1093.6 \pm 2.1 \pm 7.2 \pm 10.9 \pm 12.7{\rm \,pb} \, , \sigma_{W^{-}\rightarrow\mu^{-}\bar{\nu}} &= \phantom{0}818.4 \pm 1.9 \pm 5.0 \pm \phantom{0}7.0 \pm \phantom{0}9.5{\rm \,pb} \, , \sigma_{Z\rightarrow\mu^{+}\mu^{-}} &= \phantom{00}95.0 \pm 0.3 \pm 0.7 \pm \phantom{0}1.1 \pm \phantom{0}1.1{\rm \,pb} \, , \end{align*} where the first uncertainties are statistical, the second are systematic, the third are due to the knowledge of the LHC beam energy and the fourth are due to the luminosity determination. The evolution of the $W$ and $Z$ boson cross-sections with centre-of-mass energy is studied using previously reported measurements with $1.0\mathrm{\,fb}^{-1}$ of data at $7\mathrm{\,Te\kern -0.1em V}$. Differential distributions are also presented. Results are in good agreement with theoretical predictions at next-to-next-to-leading order in perturbative quantum chromodynamics.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-049.htm

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified