Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 mu g) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol

Magnetic field generation through angular momentum exchange between circularly polarized radiation and charged particles

The interaction between circularly polarized (CP) radiation and charged particles can lead to generation of magnetic field through an inverse Faraday effect. The spin of the circularly polarized electromagnetic wave can be converted into the angular momentum of the charged particles so long as there is dissipation. We demonstrate this by considering two mechanisms of angular momentum absorption relevant for laser-plasma interactions: electron-ion collisions and ionization. The precise dissipative mechanism, however, plays a role in determining the efficiency of the magnetic field generation

Stochastic excitation of acoustic modes in stars

For more than ten years, solar-like oscillations have been detected and frequencies measured for a growing number of stars with various characteristics (e.g. different evolutionary stages, effective temperatures, gravities, metal abundances ...). Excitation of such oscillations is attributed to turbulent convection and takes place in the uppermost part of the convective envelope. Since the pioneering work of Goldreich & Keely (1977), more sophisticated theoretical models of stochastic excitation were developed, which differ from each other both by the way turbulent convection is modeled and by the assumed sources of excitation. We review here these different models and their underlying approximations and assumptions. We emphasize how the computed mode excitation rates crucially depend on the way turbulent convection is described but also on the stratification and the metal abundance of the upper layers of the star. In turn we will show how the seismic measurements collected so far allow us to infer properties of turbulent convection in stars.Comment: Notes associated with a lecture given during the fall school organized by the CNRS and held in St-Flour (France) 20-24 October 2008 ; 39 pages ; 11 figure

A Survey of Finite Algebraic Geometrical Structures Underlying Mutually Unbiased Quantum Measurements

The basic methods of constructing the sets of mutually unbiased bases in the Hilbert space of an arbitrary finite dimension are discussed and an emerging link between them is outlined. It is shown that these methods employ a wide range of important mathematical concepts like, e.g., Fourier transforms, Galois fields and rings, finite and related projective geometries, and entanglement, to mention a few. Some applications of the theory to quantum information tasks are also mentioned.Comment: 20 pages, 1 figure to appear in Foundations of Physics, Nov. 2006 two more references adde

Quantum Attractor Flows

Motivated by the interpretation of the Ooguri-Strominger-Vafa conjecture as a holographic correspondence in the mini-superspace approximation, we study the radial quantization of stationary, spherically symmetric black holes in four dimensions. A key ingredient is the classical equivalence between the radial evolution equation and geodesic motion of a fiducial particle on the moduli space M^*_3 of the three-dimensional theory after reduction along the time direction. In the case of N=2 supergravity, M^*_3 is a para-quaternionic-Kahler manifold; in this case, we show that BPS black holes correspond to a particular class of geodesics which lift holomorphically to the twistor space Z of M^*_3, and identify Z as the BPS phase space. We give a natural quantization of the BPS phase space in terms of the sheaf cohomology of Z, and compute the exact wave function of a BPS black hole with fixed electric and magnetic charges in this framework. We comment on the relation to the topological string amplitude, extensions to N>2 supergravity theories, and applications to automorphic black hole partition functions.Comment: 43 pages, 6 figures; v2: typos and references added; v3: published version, minor change

Prospects for asteroseismology

The observational basis for asteroseismology is being dramatically strengthened, through more than two years of data from the CoRoT satellite, the flood of data coming from the Kepler mission and, in the slightly longer term, from dedicated ground-based facilities. Our ability to utilize these data depends on further development of techniques for basic data analysis, as well as on an improved understanding of the relation between the observed frequencies and the underlying properties of the stars. Also, stellar modelling must be further developed, to match the increasing diagnostic potential of the data. Here we discuss some aspects of data interpretation and modelling, focussing on the important case of stars with solar-like oscillations.Comment: Proc. HELAS Workshop on 'Synergies between solar and stellar modelling', eds M. Marconi, D. Cardini & M. P. Di Mauro, Astrophys. Space Sci., in the press Revision: correcting abscissa labels on Figs 1 and

Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling

Although conventional therapies for acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) are effective in inducing remission, many patients relapse upon treatment. Hence, there is an urgent need for novel therapies. PIM kinases are often overexpressed in AML and DLBCL and are therefore an attractive therapeutic target. However, in vitro experiments have demonstrated that intrinsic resistance to PIM inhibition is common. It is therefore likely that only a minority of patients will benefit from single agent PIM inhibitor treatment. In this study, we performed an shRNA-based genetic screen to identify kinases whose suppression is synergistic with PIM inhibition. Here, we report that suppression of p38α (MAPK14) is synthetic lethal with the PIM kinase inhibitor AZD1208. PIM inhibition elevates reactive oxygen species (ROS) levels, which subsequently activates p38α and downstream AKT/mTOR signaling. We found that p38α inhibitors sensitize hematological tumor cell lines to AZD1208 treatment in vitro and in vivo. These results were validated in ex vivo patient-derived AML cells. Our findings provide mechanistic and translational evidence supporting the rationale to test a combination of p38α and PIM inhibitors in clinical trials for AML and DLBCL

Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution

Increased angiogenesis is associated with a higher metastasis- and mortality rate in uveal melanoma (UM). Recently, it was demonstrated that genetic events, such as 8q-gain and BAP1-loss, influence the level of immune infiltrate. We aimed to determine whether genetic events, and specific cytokines, relate to angiogenesis in UM. Data from UM patients who underwent enucleation between 1999 and 2008 were analysed. Microvascular density (MVD) and the presence of infiltrating immune cells were determined with immunohistochemistry (IHC) and immunofluorescence in 43 cases. Chromosome status, BAP1 IHC and mRNA expression of angiogenesis-related genes were known in 54 cases. Tumours with monosomy 3/BAP1-loss showed a higher MVD compared to tumours with disomy 3/normal BAP1 expression (p = 0.008 and p = 0.004, respectively). Within BAP1-positive lesions (n = 20), 8q-gain did not relate to MVD (p = 0.51). A high MVD was associated with an increased expression of angiopoietin 2 (ANGPT2) (p = 0.041), Von Willebrand Factor (VWF) (p = 0.010), a decreased expression of vascular endothelial growth factor B (VEGF-B) (p = 0.024), and increased numbers of tumour-infiltrating macrophages (CD68+, p = 0.017; CD68+CD163+, p = 0.031) and lymphocytes (CD4+, p = 0.027). Concluding, vascular density of UM relates to its genetic profile: Monosomy 3 and BAP1-loss are associated with an increased MVD, while an early event (gain of 8q) is not independently related to MVD, but may initiate a preparation phase towards development of vessels. Interestingly, VEGF-B expression is decreased in UM with a high MVD

Positrons and antiprotons from inert doublet model dark matter

In the framework of the Inert Doublet Model, a very simple extension of the Standard Model, we study the production and propagation of antimatter in cosmic rays coming from annihilation of a scalar dark matter particle. We consider three benchmark candidates, all consistent with the WMAP cosmic abundance and existing direct detection experiments, and confront the predictions of the model with the recent PAMELA, ATIC and HESS data. For a light candidate, M_{DM} = 10 GeV, we argue that the positron and anti-proton fluxes may be large, but still consistent with expected backgrounds, unless there is an enhancement (boost factor) in the local density of dark matter. There is also a substantial anti-deuteron flux which might be observable by future experiments. For a candidate with M_{DM} = 70 GeV, the contribution to positron and anti-proton fluxes is much smaller than the expected backgrounds. Even if a boost factor is invoked to enhance the signals, the candidate is unable to explain the observed positron and anti-proton excesses. Finally, for a heavy candidate, M_{DM} = 10 TeV, it is possible to fit the PAMELA excess (but, unfortunately, not the ATIC one) provided there is a large enhancement, either in the local density of dark matter or through the Sommerfeld effect.Comment: 17 pages ; v2: matches JCAP published versio