372 research outputs found
Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial
This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection.
Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks.
Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance.
Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants
from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red
Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e
Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)
X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients
Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern
Observation of excited Lambda_b0 baryons
Using pp collision data corresponding to 1.0 fb-1 integrated luminosity
collected by the LHCb detector, two narrow states are observed in the
Lambda_b0pi+pi- spectrum with masses 5911.97 +- 0.12(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2 and 5919.77 +- 0.08(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2. The significances of the observations are 5.2 and
10.2 standard deviations, respectively. These states are interpreted as the
orbitally-excited Lambda_b0 baryons, Lambda_b*0(5912) and Lambda_b*0(5920).Comment: Replaced by version published in Phys. Rev. Lett, modified fit with
better mass resolution treatmen
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
+ →J/ψK
+, B0 →J/ψK
∗0 and B0 →D
∗−
μ
+
νμ decay
modes with 0.37 fb−1 of data collected in pp collisions
at
√
s = 7 TeV during the 2011 physics run. The oppositeside
tagging power is determined in the B
+ → J/ψK
+
channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty
is statistical and the second is systematic
Measurements of the branching fractions of B+→ppK+ decays
The branching fractions of the decay B+ → pp̄K+ for different intermediate states are measured using data, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb experiment. The total branching fraction, its charmless component Mpp̄ < 2.85 GeV/c2 and the branching fractions via the resonant cc̄ states η c(1S) and ψ(2S) relative to the decay via a J/ψ intermediate state are [Equation not available: see fulltext.] Upper limits on the B + branching fractions into the η c(2S) meson and into the charmonium-like states X(3872) and X(3915) are also obtained
Strong constraints on the rare decays Bs -> mu+ mu- and B0 -> mu+ mu-
A search for Bs -> mu+ mu- and B0 -> mu+ mu- decays is performed using 1.0
fb^-1 of pp collision data collected at \sqrt{s}=7 TeV with the LHCb experiment
at the Large Hadron Collider. For both decays the number of observed events is
consistent with expectation from background and Standard Model signal
predictions. Upper limits on the branching fractions are determined to be BR(Bs
-> mu+ mu-) mu+ mu-) < 1.0 (0.81) x 10^-9 at
95% (90%) confidence level.Comment: 2+6 pages; 4 figures; Accepted for publication in Physical Review
Letter
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
Measurement of charged particle multiplicities in collisions at TeV in the forward region
The charged particle production in proton-proton collisions is studied with
the LHCb detector at a centre-of-mass energy of TeV in different
intervals of pseudorapidity . The charged particles are reconstructed
close to the interaction region in the vertex detector, which provides high
reconstruction efficiency in the ranges and
. The data were taken with a minimum bias trigger, only requiring
one or more reconstructed tracks in the vertex detector. By selecting an event
sample with at least one track with a transverse momentum greater than 1 GeV/c
a hard QCD subsample is investigated. Several event generators are compared
with the data; none are able to describe fully the multiplicity distributions
or the charged particle density distribution as a function of . In
general, the models underestimate the charged particle production
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
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