Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials

Background Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. Methods A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy

Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>B7 Costimulatory signal is essential to trigger T-cell activation upon the recognition of tumor antigens. This study examined the expression of B7-1 (CD80) and B7-2 (CD86) costimulatory molecules along with HLA-DR and the presence of infiltrating lymphocytes and dendritic cells to assess their significance in patients with nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Expression of CD80, CD86, HLA-DR, S-100 protein and the presence of infiltrating lymphocytes and follicular dendritic reticulum cells were immunohistochemically examined on the paraffin-embedded tissue blocks from newly diagnosed NPC patients (n = 50). The results were correlated with clinical outcome of patients.</p> <p>Results</p> <p>CD80 and CD86 were each expressed in 10 of 50 cases in which they co-expressed in 9 cases. Univariate analysis revealed that patients with CD80/CD86 expression had significantly better overall survival than those without it (P = 0.017), but after adjustment for stage, nodal status, and treatment, the expression of CD80/CD86 did not significantly correlate with overall survival. Expression of HLA-DR and the presence of infiltrating lymphocytes and dendritic cells did not appear to have impact on the survival of patients.</p> <p>Conclusion</p> <p>Expression of CD80 and CD86 costimulatory molecules appears to be a marker of better survival in patient with NPC.</p

Entropy of Molecular Binding at Solvated Mineral Surfaces

We present thermodynamic integration simulations for the binding of mannose and methanoic acid onto the {10.4} calcite surface producing free energy of binding values of −2.89 and −1.64 kJ mol–1, respectively. We extract the entropy of binding from vacuum-based simulations and use these values to determine the entropy of binding for surface water molecules which is ∼6 J mol–1 K–1

The Unreasonable Effectiveness of Texture Transfer for Single Image Super-resolution

While implicit generative models such as GANs have shown impressive results in high quality image reconstruction and manipulation using a combination of various losses, we consider a simpler approach leading to surprisingly strong results. We show that texture loss alone allows the generation of perceptually high quality images. We provide a better understanding of texture constraining mechanism and develop a novel semantically guided texture constraining method for further improvement. Using a recently developed perceptual metric employing "deep features" and termed LPIPS, the method obtains state-of-the-art results. Moreover, we show that a texture representation of those deep features better capture the perceptual quality of an image than the original deep features. Using texture information, off-the-shelf deep classification networks (without training) perform as well as the best performing (tuned and calibrated) LPIPS metrics. The code is publicly available.Comment: 19 pages, 14 figure

Keck spectroscopy and Spitzer Space Telescope analysis of the outer disk of the Triangulum Spiral Galaxy M33

In an earlier study of the spiral galaxy M33, we photometrically identified arcs or outer spiral arms of intermediate age (0.6 Gyr - 2 Gyr) carbon stars precisely at the commencement of the HI-warp. Stars in the arcs were unresolved, but were likely thermally-pulsing asymptotic giant branch carbon stars. Here we present Keck I spectroscopy of seven intrinsically bright and red target stars in the outer, northern arc in M33. The target stars have estimated visual magnitudes as faint as V \sim 25 mag. Absorption bands of CN are seen in all seven spectra reported here, confirming their carbon star status. In addition, we present Keck II spectra of a small area 0.5 degree away from the centre of M33; the target stars there are also identified as carbon stars. We also study the non-stellar PAH dust morphology of M33 secured using IRAC on board the Spitzer Space Telescope. The Spitzer 8 micron image attests to a change of spiral phase at the start of the HI warp. The Keck spectra confirm that carbon stars may safely be identified on the basis of their red J-K_s colours in the outer, low metallicity disk of M33. We propose that the enhanced number of carbon stars in the outer arms are an indicator of recent star formation, fueled by gas accretion from the HI-warp reservoir.Comment: 9 pages, 5 figures, accepted in A&

From presence to consciousness through virtual reality

Immersive virtual environments can break the deep, everyday connection between where our senses tell us we are and where we are actually located and whom we are with. The concept of 'presence' refers to the phenomenon of behaving and feeling as if we are in the virtual world created by computer displays. In this article, we argue that presence is worthy of study by neuroscientists, and that it might aid the study of perception and consciousness

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Electromagnetic Wave Theory and Applications

Contains reports on eleven research projects.Joint Services Electronics Program (Contract DAAG29-83-K-0003)Joint Services Electronics Program (Contract DAAL03-86-K-0002)National Science Foundation (Grant ECS82-03390)National Science Foundation (Grant ECS85-04381)Schlumberger-Doll Research CenterNational Aeronautics and Space Administration (Contract NAG 5-141)National Aeronautics and Space Administration (Contract NAS 5-26861)National Aeronautics and Space Administration (Contract NAG 5-270)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0258)National Aeronautics and Space Administration (Contract NAG 5-725)International Business Machines, Inc.Lincoln Laborator