104 research outputs found
Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome
Introduction: Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. Results: A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (n = 77) or placebo (n = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m2, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was -4.9 mL/min/1.73 m2 despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. Discussion/Conclusion: CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry
Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya
Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Saethre-Chotzen syndrome : cranofacial anomalies caused by genetic changes in the TWIST gene
In this thesis, one of the most frequently occurring and most variable craniosynostosis
syndromes was investigated; Saethre-Chotzen syndrome. Craniosynostosis is the premature
obliteration of cranial sutures in the developing embryo. It can also occur in the first few
months of life. Saethre-Chotzen syndrome is, besides craniosynostosis, characterized by
specific facial and limb abnormalities, of which the most frequently reported are ptosis,
prominent crus helicis, cutaneous syndactyly of digit 2 and 3 on both hands and feet, and
broad halluces. Saethre-Chotzen syndrome has been linked to the TWIST gene on
chromosome 7p21.1. Mutations in and variably sized deletions of this gene can be found in
patients with clinical features of Saethre-Chotzen syndrome. The latter, TWIST deletions,
often also include part of the surrounding chromosome 7p and are reported to be associated
with mental retardation. In Saethre-Chotzen patients, in whom neither a mutation nor a
deletion of TWIST had been found, the FGFR3 P250R mutation was in some cases detected.
This mutation has specifically been linked to Muenke syndrome that is characterized by unior
bicoronal synostosis and slight facial dysmorphology. However, a Saethre-Chotzen like
phenotype can also result from this mutation.
Because of the possible overlap of Saethre-Chotzen with Muenke syndrome, these syndromes
were studied in order to provide clinical criteria that discriminate between the two (chapter 4).
Many phenotypic features occur in both syndromes. In addition, although unicoronal
synostosis occurs slightly more frequently in Muenke syndrome, unicoronal and bicoronal
synostosis are seen in both syndromes. The discrimination between Saethre-Chotzen and
Muenke is often not made easily and the associated genes, TWIST and FGFR3, respectively,
are simultaneously tested for pathogenic m
Measurement of the Bs Lifetime in Fully and Partially Reconstructed Bs -> Ds- (phi pi-)X Decays in pbar-p Collisions at sqrt(s) = 1.96 TeV
We present a measurement of the Bs lifetime in fully and partially
reconstructed Bs -> Ds(phi pi)X decays in 1.3 fb-1 of pbar-p collisions at
sqrt(s) = 1.96 TeV collected by the CDF II detector at the Fermilab Tevatron.
We measure tau(Bs) = 1.518 +/- 0.041 (stat.) +/- 0.027 (syst.) ps. The ratio of
this result and the world average B0 lifetime yields tau(Bs)/tau(B0) = 0.99
+/-0.03, which is in agreement with recent theoretical predictions.Comment: submitted to Phys. Rev. Let
W boson polarization measurement in the ttbar dilepton channel using the CDF II Detector
We present a measurement of boson polarization in top-quark decays in
events with decays to dilepton final states using of integrated luminosity in collisions collected by the
CDF II detector at the Tevatron. A simultaneous measurement of the fractions of
longitudinal () and right-handed () bosons yields the results
and . Combining this measurement
with our previous result based on single lepton final states, we obtain and . The results are consistent with standard
model expectation.Comment: Published in Phys. Lett.
Observation of the structure in the Mass Spectrum in cays
The observation of the structure in decays produced in collisions at \sqrt{s}=1.96~\TeV is
reported with a statistical significance greater than 5 standard deviations. A
fit to the mass spectrum is performed assuming the presence of a
Breit-Wigner resonance. The fit yields a signal of resonance
events, and resonance mass and width of
4143.4^{+2.9}_{-3.0}(\mathrm{stat})\pm0.6(\mathrm{syst})~\MeVcc and
15.3^{+10.4}_{-6.1}(\mathrm{stat})\pm2.5(\mathrm{syst})~\MeVcc respectively.
The parameters of this resonance-like structure are consistent with values
reported from an earlier CDF analysis.Comment: 7 pages, 2 figures, submited to Phys. Rev. Let
Complete remission in the nephrotic syndrome study network
Background and objectives This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). Design, setting, participants, & measurements We enrolled adults and children with proteinuria âĽ0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC)<0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. Results We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m2 (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. Conclusions In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission
Studies of jet quenching using isolated-photon + jet correlations in PbPb and pp collisions at sqrt(s[NN]) = 2.76 TeV
Results from the first study of isolated-photon + jet correlations in
relativistic heavy ion collisions are reported. The analysis uses data from
PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair
corresponding to an integrated luminosity of 150 inverse microbarns recorded by
the CMS experiment at the LHC. For events containing an isolated photon with
transverse momentum pt(gamma) > 60 GeV and an associated jet with pt(Jet) > 30
GeV, the photon + jet pt imbalance is studied as a function of collision
centrality and compared to pp data and PYTHIA calculations at the same
collision energy. Using the pt(gamma) of the isolated photon as an estimate of
the momentum of the associated parton at production, this measurement allows an
unbiased characterisation of the in-medium parton energy loss. For more central
PbPb collisions, a significant decrease in the ratio pt(Jet)/pt(gamma) relative
to that in the PYTHIA reference is observed. Furthermore, significantly more
pt(gamma) > 60 GeV photons in PbPb are observed not to have an associated
pt(Jet) > 30 GeV jet, compared to the reference. However, no significant
broadening of the photon + jet azimuthal correlation is observed.Comment: Submitted to Physics Letters
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