1,157 research outputs found
Immune checkpoint inhibitors in ovarian cancer: where do we stand?
Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in advanced OC provided the rationale for investigating the benefit of programmed death-1 (PD1) or PD-L1 inhibition in OC. Unfortunately clinical trials to date evaluating PD1/PD-L1 inhibition in patients with relapsed OC have been disappointing. In this review we will discuss early results from single agent PD1/PD-L1 inhibitors and the strategies to enhance benefit from immune-oncology agents in OC, including proposing anti-PD-L1 in combination with other agents (cytotoxics, anti-angiogenics, poly(ADP-ribose) polymerase. (PARP) inhibitors, targeted therapies or other immunotherapies), as well as evaluating these agents earlier in the disease course, or in biomarker selected patients
Diagonal and Low-Rank Matrix Decompositions, Correlation Matrices, and Ellipsoid Fitting
In this paper we establish links between, and new results for, three problems
that are not usually considered together. The first is a matrix decomposition
problem that arises in areas such as statistical modeling and signal
processing: given a matrix formed as the sum of an unknown diagonal matrix
and an unknown low rank positive semidefinite matrix, decompose into these
constituents. The second problem we consider is to determine the facial
structure of the set of correlation matrices, a convex set also known as the
elliptope. This convex body, and particularly its facial structure, plays a
role in applications from combinatorial optimization to mathematical finance.
The third problem is a basic geometric question: given points
(where ) determine whether there is a centered
ellipsoid passing \emph{exactly} through all of the points.
We show that in a precise sense these three problems are equivalent.
Furthermore we establish a simple sufficient condition on a subspace that
ensures any positive semidefinite matrix with column space can be
recovered from for any diagonal matrix using a convex
optimization-based heuristic known as minimum trace factor analysis. This
result leads to a new understanding of the structure of rank-deficient
correlation matrices and a simple condition on a set of points that ensures
there is a centered ellipsoid passing through them.Comment: 20 page
The kink Casimir energy in a lattice sine-Gordon model
The Casimir energy of quantum fluctuations about the classical kink
configuration is computed numerically for a recently proposed lattice
sine-Gordon model. This energy depends periodically on the kink position and is
found to be approximately sinusoidal.Comment: 10 pages, 4 postscript figure
Kondo effect in a one dimensional d-wave superconductor
We derive a solvable resonant-level type model, to describe an impurity spin
coupled to zero-energy bound states localized at the edge of a one dimensional
d-wave superconductor. This results in a two-channel Kondo effect with a quite
unusual low-temperature thermodynamics. For instance, the local impurity
susceptibility yields a finite maximum at zero temperature (but no
logarithmic-divergence) due to the splitting of the impurity in two Majorana
fermions. Moreover, we make comparisons with the Kondo effect occurring in a
two dimensional d-wave superconductor.Comment: 9 pages, final version; To be published in Europhysics Letter
Fermi surface renormalization in Hubbard ladders
We derive the one-loop renormalization equations for the shift in the
Fermi-wavevectors for one-dimensional interacting models with four Fermi-points
(two left and two right movers) and two Fermi velocities v_1 and v_2. We find
the shift to be proportional to (v_1-v_2)U^2, where U is the Hubbard-U. Our
results apply to the Hubbard ladder and to the t_1-t_2 Hubbard model. The
Fermi-sea with fewer particles tends to empty. The stability of a saddle point
due to shifts of the Fermi-energy and the shift of the Fermi-wavevector at the
Mott-Hubbard transition are discussed.Comment: 5 pages, 4 Postscript figure
Theory of anomalous magnetic interference pattern in mesoscopic SNS Josephson junctions
The magnetic interference pattern in mesoscopic SNS Josephson junctions is
sensitive to the scattering in the normal part of the system. In this paper we
investigate it, generalizing Ishii's formula for current-phase dependence to
the case of normal scattering at NS boundaries in an SNS junction of finite
width. The resulting flattening of the first diffraction peak is consistent
with experimental data for S-2DEG-S mesoscopic junctions.Comment: 6 pages, 5 figures. Phys. Rev. B 68, 144514 (2003
Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy
BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients
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