3,938 research outputs found
Weekly nab-Paclitaxel in Combination With Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Analysis of Safety and Efficacy in Patients With Diabetes
AbstractPurposeTo examine outcomes in a phase 3 trial of nab-paclitaxel plus carboplatin (nab-P/C) versus solvent-based paclitaxel plus carboplatin (sb-P/C) in a subset of patients with advanced non–small-cell lung cancer (NSCLC) and diabetes.Patients and MethodsPatients with stage IIIB/IV NSCLC received nab-P 100 mg/m2 on days 1, 8, and 15 or sb-P 200 mg/m2 on day 1, both with C at an area under the curve of 6 mg·min/mL on day 1 every 3 weeks. Overall response rate (ORR) and progression-free survival (PFS) were determined by blinded, independent, centralized review. P values were based on chi-square test for ORR and log-rank test for overall survival (OS) and PFS.ResultsOf the 1052 randomized patients in the phase 3 trial, 61 had diabetes according to prespecified terms (nab-P/C, 31; sb-P/C, 30). ORR for nab-P/C versus sb-P/C in this subset was 52% versus 27% (relative risk ratio, 1.935; P = .046), median PFS was 10.9 versus 4.9 months (hazard ratio, 0.420; P = .016), and median OS was 17.5 versus 11.1 months (hazard ratio, 0.550; P = .057). Treatment differences in PFS remained significant (P ≤ .036) after adjusting for histology, region, stage, race, and age and also remained significant in OS for histology (P = .039). Patients with diabetes experienced lower rates of grade 3 or higher neutropenia and peripheral neuropathy and higher rates of thrombocytopenia and anemia with nab-P/C versus sb-P/C.Conclusionnab-P/C demonstrated improved efficacy and manageable tolerability in patients with advanced NSCLC and diabetes
Cosmological Implications of a Scale Invariant Standard Model
We generalize the standard model of particle physics such it displays global
scale invariance. The gravitational action is also suitably modified such that
it respects this symmetry. This model is interesting since the cosmological
constant term is absent in the action. We find that the scale symmetry is
broken by the recently introduced cosmological symmetry breaking mechanism.
This simultaneously generates all the dimensionful parameters such as the
Newton's gravitational constant, the particle masses and the vacuum or dark
energy. We find that in its simplest version the model predicts the Higgs mass
to be very small, which is ruled out experimentally. We further generalize the
model such that it displays local scale invariance. In this case the Higgs
particle disappears from the particle spectrum and instead we find a very
massive vector boson. Hence the model gives a consistent description of
particle physics phenomenology as well as fits the cosmological dark energy.Comment: 12 pages, no figure
Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection
BACKGROUND: New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear.
METHODS: We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study.
RESULTS: Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza.
CONCLUSIONS: Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation
Genetic variability of the grey wolf Canis lupus in the Caucasus in comparison with Europe and the Middle East: distinct or intermediary population?
Despite continuous historical distribution of the grey wolf (Canis lupus) throughout Eurasia, the species displays considerable morphological differentiation that resulted in delimitation of a number of subspecies. However, these morphological discontinuities are not always consistent with patterns of genetic differentiation. Here we assess genetic distinctiveness of grey wolves from the Caucasus (a region at the border between Europe and West Asia) that have been classified as a distinct subspecies C. l. cubanensis. We analysed their genetic variability based on mtDNA control region, microsatellite loci and genome-wide SNP genotypes (obtained for a subset of the samples), and found similar or higher levels of genetic diversity at all these types of loci as compared with other Eurasian populations. Although we found no evidence for a recent genetic bottleneck, genome-wide linkage disequilibrium patterns suggest a long-term demographic decline in the Caucasian population – a trend consistent with other Eurasian populations. Caucasian wolves share mtDNA haplotypes with both Eastern European and West Asian wolves, suggesting past or ongoing gene flow. Microsatellite data also suggest gene flow between the Caucasus and Eastern Europe. We found evidence for moderate admixture between the Caucasian wolves and domestic dogs, at a level comparable with other Eurasian populations. Taken together, our results show that Caucasian wolves are not genetically isolated from other Eurasian populations, share with them the same demographic trends, and are affected by similar conservation problems
HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth
The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism
A search for resonant production of pairs in $4.8\ \rm{fb}^{-1}p\bar{p}\sqrt{s}=1.96\ \rm{TeV}$
We search for resonant production of tt pairs in 4.8 fb^{-1} integrated
luminosity of ppbar collision data at sqrt{s}=1.96 TeV in the lepton+jets decay
channel, where one top quark decays leptonically and the other hadronically. A
matrix element reconstruction technique is used; for each event a probability
density function (pdf) of the ttbar candidate invariant mass is sampled. These
pdfs are used to construct a likelihood function, whereby the cross section for
resonant ttbar production is estimated, given a hypothetical resonance mass and
width. The data indicate no evidence of resonant production of ttbar pairs. A
benchmark model of leptophobic Z \rightarrow ttbar is excluded with m_{Z'} <
900 GeV at 95% confidence level.Comment: accepted for publication in Physical Review D Sep 21, 201
Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set
We combine the results of searches for the standard model Higgs boson based
on the full CDF Run II data set obtained from sqrt(s) = 1.96 TeV p-pbar
collisions at the Fermilab Tevatron corresponding to an integrated luminosity
of 9.45/fb. The searches are conducted for Higgs bosons that are produced in
association with a W or Z boson, have masses in the range 90-150 GeV/c^2, and
decay into bb pairs. An excess of data is present that is inconsistent with the
background prediction at the level of 2.5 standard deviations (the most
significant local excess is 2.7 standard deviations).Comment: To be published in Phys. Rev. Lett (v2 contains minor updates based
on comments from PRL
Evidence for t\bar{t}\gamma Production and Measurement of \sigma_t\bar{t}\gamma / \sigma_t\bar{t}
Using data corresponding to 6.0/fb of ppbar collisions at sqrt(s) = 1.96 TeV
collected by the CDF II detector, we present a cross section measurement of
top-quark pair production with an additional radiated photon. The events are
selected by looking for a lepton, a photon, significant transverse momentum
imbalance, large total transverse energy, and three or more jets, with at least
one identified as containing a b quark. The ttbar+photon sample requires the
photon to have 10 GeV or more of transverse energy, and to be in the central
region. Using an event selection optimized for the ttbar+photon candidate
sample we measure the production cross section of, and the ratio of cross
sections of the two samples. Control samples in the dilepton+photon and
lepton+photon+\met, channels are constructed to aid in decay product
identification and background measurements. We observe 30 ttbar+photon
candidate events compared to the standard model expectation of 26.9 +/- 3.4
events. We measure the ttbar+photon cross section to be 0.18+0.08 pb, and the
ratio of the cross section of ttbar+photon to ttbar to be 0.024 +/- 0.009.
Assuming no ttbar+photon production, we observe a probability of 0.0015 of the
background events alone producing 30 events or more, corresponding to 3.0
standard deviations.Comment: 9 pages, 3 figure
Precision Top-Quark Mass Measurements at CDF
We present a precision measurement of the top-quark mass using the full
sample of Tevatron TeV proton-antiproton collisions collected
by the CDF II detector, corresponding to an integrated luminosity of 8.7
. Using a sample of candidate events decaying into the
lepton+jets channel, we obtain distributions of the top-quark masses and the
invariant mass of two jets from the boson decays from data. We then compare
these distributions to templates derived from signal and background samples to
extract the top-quark mass and the energy scale of the calorimeter jets with
{\it in situ} calibration. The likelihood fit of the templates from signal and
background events to the data yields the single most-precise measurement of the
top-quark mass, \mtop = 172.85 \pm\pmComment: submitted to Phys. Rev. Let
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