Numerical Integration of Nonlinear Wave Equations for General Relativity

A second-order numerical implementation is given for recently derived nonlinear wave equations for general relativity. The Gowdy T$^3$ cosmology is used as a test bed for studying the accuracy and convergence of simulations of one-dimensional nonlinear waves. The complete freedom in space-time slicing in the present formulation is exploited to compute in the Gowdy line-element. Second-order convergence is found by direct comparison of the results with either analytical solutions for polarized waves, or solutions obtained from Gowdy's reduced wave equations for the more general unpolarized waves. Some directions for extensions are discussed.Comment: 19 pages (LaTex), 3 figures (ps

Scattering Lens Resolves sub-100 nm Structures with Visible Light

The smallest structures that conventional lenses are able to optically resolve are of the order of 200 nm. We introduce a new type of lens that exploits multiple scattering of light to generate a scanning nano-sized optical focus. With an experimental realization of this lens in gallium phosphide we have succeeded to image gold nanoparticles at 97 nm optical resolution. Our work is the first lens that provides a resolution in the nanometer regime at visible wavelengths.Comment: 4 pages, 3 figure

Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up.

Suppression of the secretion of prolactin, growth hormone and insulin-like growth factor 1 (IGF-1) might be important in the growth regulation and treatment of breast cancer. Because oestrogens may counteract the anti-tumour effects of such treatment, the combination of an anti-oestrogen (tamoxifen), a somatostatin analogue (octreotide) and a potent anti-prolactin (CV 205-502) might be attractive. In this respect, we performed a first exploratory long-term study on the feasibility of combined treatment and possible clear differences in endocrine and anti-tumour effects during such combined treatment vs standard treatment with tamoxifen alone. Twenty-two post-menopausal patients with metastatic breast cancer (ER and/or PR positive or unknown) were randomized to receive either 40 mg of tamoxifen per day or the combination of 40 mg of tamoxifen plus 75 microg of CV 205-502 orally plus 3 x 0.2 mg of octreotide s.c. as first-line endocrine therapy. An objective response was found in 36% of the patients treated with tamoxifen alone and in 55% of the patients treated with combination therapy. Median time to progression was 33 weeks for patients treated with tamoxifen and 84 weeks for patients treated with combination therapy, but the numbers are too small for hard conclusions. There was no difference in overall post-relapse survival between the two treatment arms. With respect to the endocrine parameters, there was a significant decrease of plasma IGF-1 levels in both treatment arms, whereas during combined treatment plasma growth hormone tended to decrease and plasma prolactin levels were strongly suppressed; in some patients insulin and transforming growth factor alpha (TGF-alpha) decreased during the triple therapy. Although there was no significant difference in mean decrease of plasma IGF-1 levels between the two treatment arms, combined treatment resulted in a more uniform suppression of IGF-1. Therefore, the addition of a somatostatin analogue and an anti-prolactin may potentially enhance the efficacy of anti-oestrogens in the treatment of breast cancer owing to favourable endocrine and possible direct anti-tumour effects. Large phase III trials using depot formulations (to increase the feasibility) of somatostatin analogues are warranted to demonstrate the potential extra beneficial anti-tumour effects of such combination therapy

Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients

There is controversy regarding the prognostic value of cathepsin-D in primary breast cancer. An increased level of cathepsin-D in tumour extracts has been found to be associated with a poor relapse-free and overall survival. Studies performed with immunohistochemistry or Western blotting have produced diverse results. We have analysed 2810 cytosolic extracts obtained from human primary breast tumours for cathepsin-D expression, and have correlated their levels with prognosis. The median follow-up of the patients still alive was 88 months. Patients with high cathepsin-D levels had a significantly worse relapse-free and overall survival, also in multivariate analysis (P < 0.0001). Adjuvant therapy which was associated with an improved prognosis in node-positive patients in univariate analysis, also significantly added to the multivariate models for relapse-free and overall survival. There were no statistically significant interactions between the levels of cathepsin-D and any of the classical prognostic factors in analysis for relapse-free survival, suggesting that the prognostic value of cathepsin-D is not different in the various subgroups of patients. Indeed, multivariate analyses in subgroups of node-negative and -positive patients, pre- and post-menopausal patients, and their combinations, showed that tumours with high cathepsin-D values had a significantly poor relapse-free survival, with relative hazard rates ranging from 1.3 to 1.5, compared with tumours with low cathepsin-D levels. The results presented here on 2810 patients confirm that high cytosolic cathepsin-D values are associated with poor prognosis in human primary breast cancer. © 1999 Cancer Research Campaig

Electron-Positron Jets from a Critically Magnetized Black Hole

The curved spacetime surrounding a rotating black hole dramatically alters the structure of nearby electromagnetic fields. The Wald field which is an asymptotically uniform magnetic field aligned with the angular momentum of the hole provides a convenient starting point to analyze the effects of radiative corrections on electrodynamics in curved spacetime. Since the curvature of the spacetime is small on the scale of the electron's Compton wavelength, the tools of quantum field theory in flat spacetime are reliable and show that a rotating black hole immersed in a magnetic field approaching the quantum critical value of $B_k=m^2 c^3/(e\hbar) \approx 4.4 \times 10^{13}$~G $\approx 1.3\times10^{-11}$ cm$^{-1}$ is unstable. Specifically, a maximally rotating three-solar-mass black hole immersed in a magnetic field of $2.3 \times 10^{12}$~G would be a copious producer of electron-positron pairs with a luminosity of $3 \times 10^{52}$ erg s$^{-1}$.Comment: 10 pages, 6 figures, submitted to Phys. Rev.

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

Electron-positron outflow from black holes

Gamma-ray bursts (GRBs) appear as the brightest transient phenomena in the Universe. The nature of the central engine in GRBs is a missing link in the theory of fireballs to their stellar mass progenitors. Here it is shown that rotating black holes produce electron-positron outflow when brought into contact with a strong magnetic field. The outflow is produced by a coupling of the spin of the black hole to the orbit of the particles. For a nearly extreme Kerr black hole, particle outflow from an initial state of electrostatic equilibrium has a normalized isotropic emission of $\sim 5\times10^{48}(B/B_c)^2(M/7M_\odot)^2\sin^2\theta$ erg/s, where B is the external magnetic field strength, B_c=4.4 x 10^{13}G, and M is the mass of the black hole. This initial outflow has a half-opening angle $\theta\ge\sqrt{B_c/3B}$. A connection with fireballs in $\gamma$-ray bursts is given.Comment: 10 pages LaTe

On the detectability of gravitational waves background produced by gamma ray bursts

In this paper we discuss a new strategy for the detection of gravitational radiation likely emitted by cosmological gamma ray burst. Robust and conservative estimates lead to the conclusion that the uncorrelated superimposition of bursts of gravitational waves can be detected by interferometric detectors like VIRGO or LIGO. The expected signal is predicted to carry two very distinctive signatures: the cosmological dipole anisotropy and a characteristic time scale in the auto correlation spectrum, which might be exploited, perhaps with ad hoc modifications and/or upgrading of the planned experiments, to confirm the non-instrumental origin of the signal.Comment: 9 pages, 2 figures, LATEX2e, Accepted for pubblications as a Letter to the Editor in Journal of Physics G: Nuclear and Particle Physic