2,792 research outputs found
Targeted next-generation sequencing on hirschsprung disease: A pilot study exploits DNA pooling
To adopt an efficient approach of identifying rare variants possibly related to Hirschsprung disease (HSCR), a pilot study was set up to evaluate the performance of a newly designed protocol for next generation targeted resquencing. In total, 20 Chinese HSCR patients and 20 Chinese sex-matched individuals with no HSCR were included, for which coding sequences (CDS) of 62 genes known to be in signaling pathways relevant to enteric nervous system development were selected for capture and sequencing. Blood DNAs from eight pools of five cases or controls were enriched by PCR-based RainDance technology (RDT) and then sequenced on a 454 FLX platform. As technical validation, five patients from case Pool-3 were also independently enriched by RDT, indexed with barcode and sequenced with sufficient coverage. Assessment for CDS single nucleotide variants showed DNA pooling performed well (specificity/sensitivity at 98.4%/83.7%) at the common variant level; but relatively worse (specificity/sensitivity at 65.5%/61.3%) at the rare variant level. Further Sanger sequencing only validated five out of 12 rare damaging variants likely involved in HSCR. Hence more improvement at variant detection and sequencing technology is needed to realize the potential of DNA pooling for large-scale resequencing projects. © 2014 John Wiley & Sons Ltd/University College London.postprin
Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation
BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of ÂŁ20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of ÂŁ9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of ÂŁ28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (ÂŁ30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a ÂŁ20,000 threshold (ICER: ÂŁ19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of ÂŁ822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme
Differential branching fraction and angular analysis of the decay B0âKâ0ÎŒ+ÎŒâ
The angular distribution and differential branching fraction of the decay B 0â K â0 ÎŒ + ÎŒ â are studied using a data sample, collected by the LHCb experiment in pp collisions at sâ=7 TeV, corresponding to an integrated luminosity of 1.0 fbâ1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions
Opposite-side flavour tagging of B mesons at the LHCb experiment
The calibration and performance of the oppositeside
flavour tagging algorithms used for the measurements
of time-dependent asymmetries at the LHCb experiment
are described. The algorithms have been developed using
simulated events and optimized and calibrated with
B
+ âJ/ÏK
+, B0 âJ/ÏK
â0 and B0 âD
ââ
Ό
+
ΜΌ decay
modes with 0.37 fbâ1 of data collected in pp collisions
at
â
s = 7 TeV during the 2011 physics run. The oppositeside
tagging power is determined in the B
+ â J/ÏK
+
channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty
is statistical and the second is systematic
Search for CP violation in D+âÏÏ+ and D+sâK0SÏ+ decays
A search for CP violation in D + â ÏÏ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fbâ1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (â0.04 ± 0.14 ± 0.14)% for candidates with K â K + mass within 20 MeV/c 2 of the Ï meson mass. A search for a CP -violating asymmetry that varies across the Ï mass region of the D + â K â K + Ï + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+sâK0SÏ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Observation of two new baryon resonances
Two structures are observed close to the kinematic threshold in the mass spectrum in a sample of proton-proton collision data, corresponding
to an integrated luminosity of 3.0 fb recorded by the LHCb experiment.
In the quark model, two baryonic resonances with quark content are
expected in this mass region: the spin-parity and
states, denoted and .
Interpreting the structures as these resonances, we measure the mass
differences and the width of the heavier state to be
MeV,
MeV,
MeV, where the first and second
uncertainties are statistical and systematic, respectively. The width of the
lighter state is consistent with zero, and we place an upper limit of
MeV at 95% confidence level. Relative
production rates of these states are also reported.Comment: 17 pages, 2 figure
Model-independent search for CP violation in D0âKâK+ÏâÏ+ and D0âÏâÏ+Ï+Ïâ decays
A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states KâK+ÏâÏ+ and ÏâÏ+Ï+Ïâ is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fbâ1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the KâK+ÏâÏ+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the ÏâÏ+Ï+Ïâ final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Measurement of the CP-violating phase phi_s in the decay Bs->J/psi phi
We present a measurement of the time-dependent CP-violating asymmetry in B_s
-> J/psi phi decays, using data collected with the LHCb detector at the LHC.
The decay time distribution of B_s -> J/psi phi is characterized by the decay
widths Gamma_H and Gamma_L of the heavy and light mass eigenstates of the
B_s-B_s-bar system and by a CP-violating phase phi_s. In a sample of about 8500
B_s -> J/psi phi events isolated from 0.37 fb^-1 of pp collisions at sqrt(s)=7
TeV we measure phi_s = 0.15 +/- 0.18 (stat) +/- 0.06 (syst) rad. We also find
an average B_s decay width Gamma_s == (Gamma_L + Gamma_H)/2 = 0.657 +/- 0.009
(stat) +/- 0.008 (syst) ps^-1 and a decay width difference Delta Gamma_s ==
Gamma_L - Gamma_H} = 0.123 +/- 0.029 (stat) +/- 0.011 (syst) ps^-1. Our
measurement is insensitive to the transformation (phi_s,DeltaGamma_s --> pi -
phi_s, - Delta Gamma_s.Comment: 9 pages, 3 figure
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