669 research outputs found
Ixabepilone as Monotherapy or in Combination with Capecitabine for the Treatment of Advanced Breast Cancer
Breast Cancer is the most prevalent cancer in the world with 4.4 million survivors up to 5 years following the diagnosis.1 In the US alone approximately forty thousand women die annually of metastatic breast cancer (MBC). Despite many effective systemic treatment options approximately 50% of women with MBC succumb to the disease within 24 months of the diagnosis.2 Ixabepilone is a novel, first in class member of the epothilone class of antineoplastic agents. Ixabepilone is indicated as monotherapy for the treatment of metastatic or locally advanced breast cancer in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and Capecitabine. Ixabepilone is also indicated in combination with Capecitabine for the treatment of patients with metastatic or locally advanced breast cancer resistant to treatment with an anthracycline and a taxane, or whose cancer is taxane resistant and for whom further anthracycline therapy is contraindicated. Ixabepilone was extensively studied as a single agent in patients with MBC and was found to be effective and well tolerated with a predictable and manageable safety profile. Not surprisingly prior exposure to anthracyclines and taxanes affects significantly the potential for response to therapy with single agent Ixabepilone in metastatic setting. MBC patients with taxane resistant MBC have objective response rate (RR) of 12%, patients with prior low exposure to taxanes and/or resistance RR = 22%, Ixabepilone treatment after adjuvant anthracycline therapy exposure renders RR = 42% and in Taxane naïve patients RR = 57%. In two large phase III studies of Ixabepilone + Capecitabine versus Capecitabine alone, progression free survival (PFS) and overall response rates (RR) were higher in the combination treatment arms, but no survival advantage was seen overall. Treatment with Ixabepilone + Capecitabine in a phase II study resulted in an overall response rate (ORR) of 23% in ER/PR/HER2 negative, triple-negative breast cancer patients (TNBC) while ORR of 31% was seen in a preplanned pooled analysis of TNBC in the phase III trials of Ixabepilone + Capecitabine. Significantly prolonged median PFS was seen for TNBC treated with the combination of Ixabepilone + Capecitabine compared to Capecitabine alone 4.2 vs. 1.7 months respectively. Ixabepilone as single agent appears to show excellent antitumor activity in patients with TNBC MBC. Addition of Ixabepilone to Capecitabine results in approximately doubling in median PFS for TNBC versus Capecitabine alone. Single agent Ixabepilone is generally well tolerated, and its toxicity profile does not overlap with that of Capecitabine and therefore depending on prior exposure to chemotherapy both single agent Ixabepilone or in combination with Capecitabine can be used safely and effectively for treatment of advanced breast cancer
Defect Conformal Field Theory and Locally Localized Gravity
Gravity may be "locally localized" over a wide range of length scales on a
d-dimensional anti-de Sitter (AdS) brane living inside AdS_{d+1}. In this paper
we examine this phenomenon from the point of view of the holographic dual
"defect conformal field theory". The mode expansion of bulk fields on the
gravity side is shown to be precisely dual to the "boundary operator product
expansion" of operators as they approach the defect. From the field theory
point of view, the condition for localization is that a "reduced operator"
appearing in this expansion acquires negative anomalous dimension. In
particular, a very light localized graviton exists when a mode arising from the
reduction of the ambient stress-energy tensor to the defect has conformal
dimension Delta ~ d-1. The part of the stress tensor containing the defect
dynamics has dimension Delta = d-1 in the free theory, but we argue that it
acquires an anomalous dimension in the interacting theory, and hence does not
participate in localization in the regime of small backreaction of the brane.
We demonstrate that such an anomalous dimension is consistent with the
conservation of the full stress-energy tensor. Finally, we analyze how to
compute the anomalous dimensions of reduced operators from gravity at leading
order in the interactions with the brane.Comment: 38 pages, LaTeX, 5 figures. v2: typos fixe
Dynamical stability of infinite homogeneous self-gravitating systems: application of the Nyquist method
We complete classical investigations concerning the dynamical stability of an
infinite homogeneous gaseous medium described by the Euler-Poisson system or an
infinite homogeneous stellar system described by the Vlasov-Poisson system
(Jeans problem). To determine the stability of an infinite homogeneous stellar
system with respect to a perturbation of wavenumber k, we apply the Nyquist
method. We first consider the case of single-humped distributions and show
that, for infinite homogeneous systems, the onset of instability is the same in
a stellar system and in the corresponding barotropic gas, contrary to the case
of inhomogeneous systems. We show that this result is true for any symmetric
single-humped velocity distribution, not only for the Maxwellian. If we
specialize on isothermal and polytropic distributions, analytical expressions
for the growth rate, damping rate and pulsation period of the perturbation can
be given. Then, we consider the Vlasov stability of symmetric and asymmetric
double-humped distributions (two-stream stellar systems) and determine the
stability diagrams depending on the degree of asymmetry. We compare these
results with the Euler stability of two self-gravitating gaseous streams.
Finally, we determine the corresponding stability diagrams in the case of
plasmas and compare the results with self-gravitating systems
Measurement of a small atmospheric ratio
From an exposure of 25.5~kiloton-years of the Super-Kamiokande detector, 900
muon-like and 983 electron-like single-ring atmospheric neutrino interactions
were detected with momentum MeV/, MeV/, and
with visible energy less than 1.33 GeV. Using a detailed Monte Carlo
simulation, the ratio was measured to be , consistent with previous results from the
Kamiokande, IMB and Soudan-2 experiments, and smaller than expected from
theoretical models of atmospheric neutrino production.Comment: 14 pages with 5 figure
Calibration of Super-Kamiokande Using an Electron Linac
In order to calibrate the Super-Kamiokande experiment for solar neutrino
measurements, a linear accelerator (LINAC) for electrons was installed at the
detector. LINAC data were taken at various positions in the detector volume,
tracking the detector response in the variables relevant to solar neutrino
analysis. In particular, the absolute energy scale is now known with less than
1 percent uncertainty.Comment: 24 pages, 16 figures, Submitted to NIM
Measurement of radon concentrations at Super-Kamiokande
Radioactivity from radon is a major background for observing solar neutrinos
at Super-Kamiokande. In this paper, we describe the measurement of radon
concentrations at Super-Kamiokande, the method of radon reduction, and the
radon monitoring system. The measurement shows that the current low-energy
event rate between 5.0 MeV and 6.5 MeV implies a radon concentration in the
Super-Kamiokande water of less than 1.4 mBq/m.Comment: 11 pages, 4 figure
How Coupling Determines the Entrainment of Circadian Clocks
Autonomous circadian clocks drive daily rhythms in physiology and behaviour.
A network of coupled neurons, the suprachiasmatic nucleus (SCN), serves as a
robust self-sustained circadian pacemaker. Synchronization of this timer to the
environmental light-dark cycle is crucial for an organism's fitness. In a
recent theoretical and experimental study it was shown that coupling governs
the entrainment range of circadian clocks. We apply the theory of coupled
oscillators to analyse how diffusive and mean-field coupling affects the
entrainment range of interacting cells. Mean-field coupling leads to amplitude
expansion of weak oscillators and, as a result, reduces the entrainment range.
We also show that coupling determines the rigidity of the synchronized SCN
network, i.e. the relaxation rates upon perturbation. %(Floquet exponents). Our
simulations and analytical calculations using generic oscillator models help to
elucidate how coupling determines the entrainment of the SCN. Our theoretical
framework helps to interpret experimental data
Dilepton mass spectra in p+p collisions at sqrt(s)= 200 GeV and the contribution from open charm
The PHENIX experiement has measured the electron-positron pair mass spectrum
from 0 to 8 GeV/c^2 in p+p collisions at sqrt(s)=200 GeV. The contributions
from light meson decays to e^+e^- pairs have been determined based on
measurements of hadron production cross sections by PHENIX. They account for
nearly all e^+e^- pairs in the mass region below 1 GeV/c^2. The e^+e^- pair
yield remaining after subtracting these contributions is dominated by
semileptonic decays of charmed hadrons correlated through flavor conservation.
Using the spectral shape predicted by PYTHIA, we estimate the charm production
cross section to be 544 +/- 39(stat) +/- 142(syst) +/- 200(model) \mu b, which
is consistent with QCD calculations and measurements of single leptons by
PHENIX.Comment: 375 authors from 57 institutions, 18 pages, 4 figures, 2 tables.
Submitted to Physics Letters B. v2 fixes technical errors in matching authors
to institutions. Plain text data tables for the points plotted in figures for
this and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Inclusive cross section and double helicity asymmetry for \pi^0 production in p+p collisions at sqrt(s)=200 GeV: Implications for the polarized gluon distribution in the proton
The PHENIX experiment presents results from the RHIC 2005 run with polarized
proton collisions at sqrt(s)=200 GeV, for inclusive \pi^0 production at
mid-rapidity. Unpolarized cross section results are given for transverse
momenta p_T=0.5 to 20 GeV/c, extending the range of published data to both
lower and higher p_T. The cross section is described well for p_T < 1 GeV/c by
an exponential in p_T, and, for p_T > 2 GeV/c, by perturbative QCD. Double
helicity asymmetries A_LL are presented based on a factor of five improvement
in uncertainties as compared to previously published results, due to both an
improved beam polarization of 50%, and to higher integrated luminosity. These
measurements are sensitive to the gluon polarization in the proton, and exclude
maximal values for the gluon polarization.Comment: 375 authors, 7 pages, 3 figures. Submitted to Phys. Rev. D, Rapid
Communications. Plain text data tables for the points plotted in figures for
this and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV
We present azimuthal angle correlations of intermediate transverse momentum
(1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) =
62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is
broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and
semi-central collisions in all the systems. The broadening and peak location
are found to depend upon the number of participants in the collision, but not
on the collision energy or beam nuclei. These results are consistent with sound
or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables.
Submitted to Physical Review Letters. Plain text data tables for the points
plotted in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
- …