33 research outputs found
Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels
Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case–control studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 × 10−4, per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67–0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P = 4.72 × 10−5, per-allele trend OR = 0.68, 95% CI = 0.57–0.82) and not for advanced cases with Gleason score >8 or stage ≥III (P = 0.31, per-allele trend OR = 1.12, 95% CI = 0.90–1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61 ng/ml, 95% CI = 1.49–1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96–1.28) (P = 9.70 × 10−5). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy
First observation of a doubly charged tetraquark and its neutral partner
A combined amplitude analysis is performed for the decays and , which are
related by isospin symmetry. The analysis is based on data collected by the
LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8
and 13. The full data sample corresponds to an integrated
luminosity of 9. Two new resonant states with masses of
and widths of
are observed, which decay to and
respectively. The former state indicates the first observation of
a doubly charged open-charm tetraquark state with minimal quark content
, and the latter state is a neutral tetraquark composed of
quarks. Both states are found to have spin-parity ,
and their resonant parameters are consistent with each other, which suggests
that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb
public pages
Search for the doubly heavy baryon decaying to
A first search for the
decay is performed by the LHCb experiment with a data sample of proton-proton
collisions, corresponding to an integrated luminosity of
recorded at centre-of-mass energies of 7, 8, and . Two peaking structures are seen with a local (global) significance of
and standard deviations at masses of
and , respectively. Upper limits are set on the baryon
production cross-section times the branching fraction relative to that of the
decay at centre-of-mass energies of 8 and
, in the and in the
rapidity and transverse-momentum ranges from 2.0 to 4.5 and 0 to
, respectively. Upper limits are presented
as a function of the mass and lifetime.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-2022-005.html (LHCb
public pages
Amplitude analysis of and decays
Resonant contributions in and
decays are determined with an amplitude
analysis, which is performed both separately and simultaneously, where in the
latter case isospin symmetry between the decays is assumed. The analysis is
based on data collected by the LHCb detector in proton-proton collisions at
center-of-mass energies of 7, 8 and 13 . The full data sample
corresponds to an integrated luminosity of 9 . A doubly charged
spin-0 open-charm tetraquark candidate together with a neutral partner, both
with masses near , are observed in the decay channel.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-027.html (LHCb
public pages
Searches for rare B-s(0) and B-0 decays into four muons
Searches for rare and decays into four muons are performed
using proton-proton collision data recorded by the LHCb experiment,
corresponding to an integrated luminosity of 9 . Direct decays
and decays via light scalar and 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 and
are set
Next generation sequencing of human enterovirus strains from an outbreak of enterovirus A71 shows applicability to outbreak investigations.
BackgroundThe most recent documented Australian outbreak of enterovirus A71 (EV-A71) occurred in Sydney from 2012 to 2013. Over a four-month period more than 100 children presented to four paediatric hospitals with encephalitic presentations including fever and myoclonic jerks. The heterogeneous presentations included typical encephalomyelitis, and cardiopulmonary complications.ObjectivesTo characterise the genomes of enterovirus strains circulating during the 2013 Sydney EV-A71 outbreak and determine their phylogeny, phylogeography and association between genome and clinical phenotype.Study designWe performed an analysis of enterovirus (EV) positive specimens from children presenting to hospitals in the greater Sydney region of Australia during the 2013 outbreak. We amplified near full-length genomes of EV, and used next generation sequencing technology to sequence the virus. We used phylogenetic/phylogeographic analysis to characterize the outbreak viruses.ResultsWe amplified and sequenced 23/63 (37 %) genomes, and identified the majority (61 %) as EV-A71. The EV-A71 sequences showed high level sequence homology to C4a genogroups of EV-A71 circulating in China and Vietnam during 2012-13. Phylogenetic analysis showed EV-A71 strains associated with more severe symptoms, including encephalitis or cardiopulmonary failure, grouped together more closely than those from patients with hand, foot and mouth disease. Amongst the non-EV-A71 sequences were five other EV subtypes (representing enterovirus subtypes A and B), reflecting the diversity of EV co-circulation within the community.ConclusionsThis is the first Australian study investigating the near full-length genome of EV strains identified during a known outbreak of EV-A71. EV-A71 sequences were very similar to strains circulating in Asia during the same time period. Whole genome sequencing offers additional information over routine diagnostic testing such as characterisation of emerging recombinant strains and inform vaccine design