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Improved RELAP4 BWR jet pump model
A RELAP4 Boiling Water Reactor (BWR) jet pump model development effort is being conducted to develop a new RELAP4 BWR jet pump model from test data. Results from the Jet Pump Test and Model Development Program conducted at the Idaho National Engineering Laboratory (INEL) are being used. The overall program consisted of three phases, subscale testing, model development, and model evaluation. This paper includes a program description, a model description, and a model evaluation
Biomarker analyses of clinical outcomes in patients with advanced hepatocellular carcinoma treated with Sorafenib with or without Erlotinib in the SEARCH Trial
Purpose: Sorafenib is the current standard therapy for advanced HCC, but validated
biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers
predicting prognosis and/or response to sorafenib, with or without erlotinib, in HCC patients from
the phase 3 SEARCH trial.
Experimental Design: 720 patients were randomized to receive oral sorafenib 400 mg BID plus
erlotinib 150 mg QD or placebo. Fifteen growth factors relevant to the treatment regimen and/or
to HCC were measured in baseline plasma samples.
Results: Baseline plasma biomarkers were measured in 494 (69%) patients (sorafenib plus
erlotinib, n=243; sorafenib plus placebo, n=251). Treatment arm–independent analyses showed
that elevated HGF (HR, 1.687 [high vs low expression]; endpoint multiplicity adjusted [e-adj]
P=0.0001) and elevated plasma VEGF-A (HR, 1.386; e-adj P=0..0377) were significantly
associated with poor OS in multivariate analyses, and low plasma KIT (HR, 0.75 [high vs low];
P=0.0233; e-adj P=0.2793) tended to correlate with poorer OS. High plasma VEGF-C
independently correlated with longer TTP (HR, 0.633; e-adj P=0.0010) and trended toward
associating with improved disease control rate (univariate:OR, 2.047; P=0.030; e-adj P=0.420).
In 67% of evaluable patients (339/494), a multimarker signature of HGF, VEGF-A, KIT, epigen,
and VEGF-C correlated with improved median OS in multivariate analysis (HR, 0.150;
P<0.00001). No biomarker predicted efficacy from erlotinib.
Conclusions: Baseline plasma HGF, VEGF-A, KIT, and VEGF-C correlated with clinical
outcomes in HCC patients treated with sorafenib with or without erlotinib. These biomarkers
plus epigen constituted a multimarker signature for improved OS
Atomic X-ray Spectroscopy of Accreting Black Holes
Current astrophysical research suggests that the most persistently luminous
objects in the Universe are powered by the flow of matter through accretion
disks onto black holes. Accretion disk systems are observed to emit copious
radiation across the electromagnetic spectrum, each energy band providing
access to rather distinct regimes of physical conditions and geometric scale.
X-ray emission probes the innermost regions of the accretion disk, where
relativistic effects prevail. While this has been known for decades, it also
has been acknowledged that inferring physical conditions in the relativistic
regime from the behavior of the X-ray continuum is problematic and not
satisfactorily constraining. With the discovery in the 1990s of iron X-ray
lines bearing signatures of relativistic distortion came the hope that such
emission would more firmly constrain models of disk accretion near black holes,
as well as provide observational criteria by which to test general relativity
in the strong field limit. Here we provide an introduction to this phenomenon.
While the presentation is intended to be primarily tutorial in nature, we aim
also to acquaint the reader with trends in current research. To achieve these
ends, we present the basic applications of general relativity that pertain to
X-ray spectroscopic observations of black hole accretion disk systems, focusing
on the Schwarzschild and Kerr solutions to the Einstein field equations. To
this we add treatments of the fundamental concepts associated with the
theoretical and modeling aspects of accretion disks, as well as relevant topics
from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian
Journal of Physics, in pres
A genome-wide association study in multiple system atrophy
Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy
(MSA), we undertook a genome-wide association study (GWAS).
Methods: We performed a GWAS with .5 million genotyped and imputed single nucleotide polymorphisms
(SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA
cases were collected from North American and European centers, one third of which were neuropathologically
confirmed.
Results: We found no significant loci after stringent multiple testing correction. A number of regions
emerged as potentially interesting for follow-up at p , 1 3 1026, including SNPs in the
genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association
of the genes SNCA and COQ2 with MSA.
Conclusions: We present a GWAS in MSA.We have identified several potentially interesting gene
loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set.
Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the
future, additional samples of well-characterized patients with MSA will need to be collected to
perform a larger MSA GWAS, but this initial study forms the basis for these next steps
Random forest for gene selection and microarray data classification
A random forest method has been selected to perform both gene selection and classification of the microarray data. In this
embedded method, the selection of smallest possible sets of genes with lowest error rates is the key factor in achieving highest
classification accuracy. Hence, improved gene selection method using random forest has been proposed to obtain the smallest
subset of genes as well as biggest subset of genes prior to classification. The option for biggest subset selection is done to assist
researchers who intend to use the informative genes for further research. Enhanced random forest gene selection has performed
better in terms of selecting the smallest subset as well as biggest subset of informative genes with lowest out of bag error rates
through gene selection. Furthermore, the classification performed on the selected subset of genes using random forest has lead to
lower prediction error rates compared to existing method and other similar available methods
Gauge Invariant Effective Lagrangian for Kaluza-Klein Modes
We construct a manifestly gauge invariant Lagrangian in 3+1 dimensions for N
Kaluza-Klein modes of an SU(m) gauge theory in the bulk. For example, if the
bulk is 4+1, the effective theory is \Pi_{i=1}^{N+1} SU(m)_i with N chiral
(\bar{m},m) fields connecting the groups sequentially. This can be viewed as a
Wilson action for a transverse lattice in x^5, and is shown explicitly to match
the continuum 4+1 compactifed Lagrangian truncated in momentum space. Scale
dependence of the gauge couplings is described by the standard renormalization
group technique with threshold matching, leading to effective power law
running. We also discuss the unitarity constraints, and chiral fermions.Comment: 21 pages, 4 figure
Search: A phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma
PURPOSE: To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma (HCC) in a multicenter, multinational, randomized, phase III trial. PATIENTS AND METHODS: Patients with advanced HCC and underlying Child-Pugh class A cirrhosis, who were naive to systemic treatment (N = 720), were randomly assigned to sorafenib plus either erlotinib (n = 362) or placebo (n = 358). The primary end point was overall survival (OS). RESULTS: Median OS was similar in the sorafenib plus erlotinib and sorafenib plus placebo groups (9.5 v 8.5 months, respectively; hazard ratio [HR], 0.929; P = .408), as was median time to progression (3.2 v 4.0 months, respectively; HR, 1.135; P = .18). In the sorafenib/erlotinib arm versus the sorafenib/placebo arm, the overall response rate trended higher (6.6% v 3.9%, respectively; P = .102), whereas the disease control rate was significantly lower (43.9% v 52.5%, respectively; P = .021). The median durations of treatment with sorafenib were 86 days in the sorafenib/erlotinib arm and 123 days in the sorafenib/placebo arm. In the sorafenib/erlotinib and sorafenib/placebo arms, the rates of treatment-emergent serious AEs (58.0% v 54.6%, respectively) and drug-related serious AEs (21.0% v 22.8%, respectively) were similar. AEs matched the known safety profiles of both agents, but rates of rash/desquamation, anorexia, and diarrhea were higher in the sorafenib/erlotinib arm, whereas rates of alopecia and hand-foot skin reaction were higher in the sorafenib/placebo arm. Withdrawal rates for AEs during cycles 1 to 3 were higher in the sorafenib/erlotinib arm. CONCLUSION: Adding erlotinib to sorafenib did not improve survival in patients with advanced HCC
Factors associated with response to growth hormone in pediatric growth disorders: results of a 5-year registry analysis
Context
Growth hormone (GH) therapy can increase linear growth in patients with growth hormone deficiency (GHD), Turner syndrome (TS), Noonan syndrome (NS), and Prader-Willi syndrome (PWS), although outcomes vary by disease state.
Objective
To assess growth and identify factors associated with growth response with long-term GH therapy.
Methods
Data from pediatric patients with GHD, TS, NS, and PWS obtained at GH treatment initiation (baseline) and annually for 5 years in the ANSWER Program and NordiNet® IOS were analyzed retrospectively. Height standard deviation score (HSDS) was assessed over time, and multivariate analyses determined variables with significant positive effects on growth outcomes in each patient cohort.
Results
Data from patients with GHD (n = 12 683), TS (n = 1307), NS (n = 203), and PWS (n = 102) were analyzed. HSDS increased over time during GH treatment in all cohorts. Factors with significant positive effects on ΔHSDS were younger age at GH initiation and lower HSDS at baseline (all cohorts) and higher GH dose (GHD and TS only); sex had no effect in any cohort. The modeling analysis showed that ΔHSDS was greatest in year 1 and attenuated over consecutive years through year 5. Estimated least-squares mean ΔHSDS values at year 5 by cohort were 1.702 (females) and 1.586 (males) in GHD, 1.033 in TS, 1.153 in NS, and 1.392 in PWS.
Conclusion
Long-term GH therapy results in large increases in HSDS in patients with GHD, TS, NS, and PWS. Greater gains in HSDS can be obtained with higher GH doses and earlier initiation of treatment
The Dependence of the Superconducting Transition Temperature of Organic Molecular Crystals on Intrinsically Non-Magnetic Disorder: a Signature of either Unconventional Superconductivity or Novel Local Magnetic Moment Formation
We give a theoretical analysis of published experimental studies of the
effects of impurities and disorder on the superconducting transition
temperature, T_c, of the organic molecular crystals kappa-ET_2X and beta-ET_2X
(where ET is bis(ethylenedithio)tetrathiafulvalene and X is an anion eg I_3).
The Abrikosov-Gorkov (AG) formula describes the suppression of T_c both by
magnetic impurities in singlet superconductors, including s-wave
superconductors and by non-magnetic impurities in a non-s-wave superconductor.
We show that various sources of disorder lead to the suppression of T_c as
described by the AG formula. This is confirmed by the excellent fit to the
data, the fact that these materials are in the clean limit and the excellent
agreement between the value of the interlayer hopping integral, t_perp,
calculated from this fit and the value of t_perp found from angular-dependant
magnetoresistance and quantum oscillation experiments. If the disorder is, as
seems most likely, non-magnetic then the pairing state cannot be s-wave. We
show that the cooling rate dependence of the magnetisation is inconsistent with
paramagnetic impurities. Triplet pairing is ruled out by several experiments.
If the disorder is non-magnetic then this implies that l>=2, in which case
Occam's razor suggests that d-wave pairing is realised. Given the proximity of
these materials to an antiferromagnetic Mott transition, it is possible that
the disorder leads to the formation of local magnetic moments via some novel
mechanism. Thus we conclude that either kappa-ET_2X and beta-ET_2X are d-wave
superconductors or else they display a novel mechanism for the formation of
localised moments. We suggest systematic experiments to differentiate between
these scenarios.Comment: 18 pages, 5 figure
Single Spin Asymmetry in Polarized Proton-Proton Elastic Scattering at GeV
We report a high precision measurement of the transverse single spin
asymmetry at the center of mass energy GeV in elastic
proton-proton scattering by the STAR experiment at RHIC. The was measured
in the four-momentum transfer squared range \GeVcSq, the region of a significant interference between the
electromagnetic and hadronic scattering amplitudes. The measured values of
and its -dependence are consistent with a vanishing hadronic spin-flip
amplitude, thus providing strong constraints on the ratio of the single
spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated
by the Pomeron amplitude at this , we conclude that this measurement
addresses the question about the presence of a hadronic spin flip due to the
Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure
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