Active Galactic Nuclei at the Crossroads of Astrophysics

Over the last five decades, AGN studies have produced a number of spectacular examples of synergies and multifaceted approaches in astrophysics. The field of AGN research now spans the entire spectral range and covers more than twelve orders of magnitude in the spatial and temporal domains. The next generation of astrophysical facilities will open up new possibilities for AGN studies, especially in the areas of high-resolution and high-fidelity imaging and spectroscopy of nuclear regions in the X-ray, optical, and radio bands. These studies will address in detail a number of critical issues in AGN research such as processes in the immediate vicinity of supermassive black holes, physical conditions of broad-line and narrow-line regions, formation and evolution of accretion disks and relativistic outflows, and the connection between nuclear activity and galaxy evolution.Comment: 16 pages, 5 figures; review contribution; "Exploring the Cosmic Frontier: Astrophysical Instruments for the 21st Century", ESO Astrophysical Symposia Serie

Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk

Background: Estrogen plus progestin therapy increases both mammographic density and breast cancer incidence. Whether mammographic density change associated with estrogen plus progestin initiation predicts breast cancer risk is unknown. Methods: We conducted an ancillary nested case-control study within the Women's Health Initiative trial that randomly assigned postmenopausal women to daily conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg or placebo. Mammographic density was assessed from mammograms taken prior to and one year after random assignment for 174 women who later developed breast cancer (cases) and 733 healthy women (controls). Logistic regression analyses included adjustment for confounders and baseline mammographic density when appropriate. Results: Among women in the estrogen plus progestin arm (97 cases/378 controls), each 1% positive change in percent mammographic density increased breast cancer risk 3% (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01 to 1.06). For women in the highest quintile of mammographic density change (>19.3% increase), breast cancer risk increased 3.6-fold (95% CI = 1.52 to 8.56). The effect of estrogen plus progestin use on breast cancer risk (OR = 1.28, 95% CI = 0.90 to 1.82) was eliminated in this study, after adjusting for change in mammographic density (OR = 1.00, 95% CI = 0.66 to 1.51). Conclusions: We found the one-year change in mammographic density after estrogen plus progestin initiation predicted subsequent increase in breast cancer risk. All of the increased risk from estrogen plus progestin use was mediated through mammographic density change. Doctors should evaluate changes in mammographic density with women who initiate estrogen plus progestin therapy and discuss the breast cancer risk implications

A roadmap for Antarctic and Southern Ocean science for the next two decades and beyond

Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i)Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access toAntarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.Tinker Foundation, Antarctica New Zealand, The New Zealand Antarctic Research Institute, the Scientific Committee on Antarctic Research (SCAR), the Council of Managers of National Antarctic Programs (COMNAP), the Alfred Wegner Institut, Helmholtz Zentrum für Polar und Meeresforschung (Germany), and the British Antarctic Survey (UK).http://journals.cambridge.org/action/displayJournal?jid=ANShb201

Comparison of dose-finding designs for narrow-therapeutic-index drugs: Concentration-controlled vs. dose-controlled trials

This study compared the performances of randomized dose-controlled trials (DCTs) with those of concentration-controlled trials (CCTs) in dose finding for drugs with narrow therapeutic indexes. A simulation-based study was performed for a hypothetical immunosuppressant agent with two clinical end points. Different scenarios were simulated and analyzed, and three designs were compared: one DCT and two CCTs (a target-equivalent CCT and a variability-equivalent CCT). The DCT was consistently superior to the CCTs in the following aspects: (i) precision and bias reduction in parameter estimates, (ii) precision and bias reduction in the estimate of optimal exposure, (iii) bias reduction in prediction of the estimated therapeutic benefit at estimated optimal exposure, and (iv) bias reduction in prediction of the estimated benefit of therapeutic drug monitoring as compared with fixed dosing. DCT designs are more informative when describing the exposure-response relationship for drugs with narrow therapeutic indexes and provide a better basis for decision making with regard to dosing strategy

Ocean acidification and seasonal temperature extremes combine to impair the thermal physiology of a sub-Antarctic fish

To predict the potential impacts of climate change on marine organisms, it is critical to understand how multiple stressors constrain the physiology and distribution of species. We evaluated the effects of seasonal changes in seawater temperature and near-future ocean acidification (OA) on organismal and sub-organismal traits associated with the thermal performance of Eleginops maclovinus, a sub-Antarctic notothenioid species with economic importance to sport and artisanal fisheries in southern South America. Juveniles were exposed to mean winter and summer sea surface temperatures (4 and 10 °C) at present-day and near-future pCO2 levels (~500 and 1800 μatm). After a month, the Critical Thermal maximum and minimum (CTmax, CTmin) of fish were measured using the Critical Thermal Methodology and the aerobic scope of fish was measured based on the difference between their maximal and standard rates determined from intermittent flow respirometry. Lipid peroxidation and the antioxidant capacity were also quantified to estimate the oxidative damage potentially caused to gill and liver tissue. Although CTmax and CTmin were higher in individuals acclimated to summer versus winter temperatures, the increase in CTmax was minimal in juveniles exposed to the near-future compared to present-day pCO2 levels (there was a significant interaction between temperature and pCO2 on CTmax). The reduction in the thermal tolerance range under summer temperatures and near-future OA conditions was associated with a reduction in the aerobic scope observed at the elevated pCO2 level. Moreover, an oxidative stress condition was detected in the gill and liver tissues. Thus, chronic exposure to OA and the current summer temperatures pose limits to the thermal performance of juvenile E. maclovinus at the organismal and sub-organismal levels, making this species vulnerable to projected climate-driven warming.</p