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Prehistoric rock art : polemics and progress
\"Prehistoric rock art is the markings - paintings, engravings, or pecked images - left on rocks or cave walls by ancient peoples. In this book, Paul G. Bahn provides a richly illustrated overview of prehistoric rock art and cave art from around the world. Summarizing the recent advances in our understanding of this extraordinary visual record, he discusses new discoveries, new approaches to recording and interpretation, and current problems in conservation. Bahn focuses in particular on current issues in the interpretation of rock art, notably the \"shamanic\" interpretation that has been influential in recent years and that he refutes. This book is based on the Rhind Lectures that the author delivered for the Society of Antiquaries of Scotland in 2006\"-- Provided by publisher.
Book
Metformin Inhibits Growth of Human Glioblastoma Cells and Enhances Therapeutic Response
High-grade gliomas, glioblastomas (GB), are refractory to conventional treatment combining surgery, chemotherapy, mainly temozolomide, and radiotherapy. This highlights an urgent need to develop novel therapies and increase the efficacy of radio/chemotherapy for these very aggressive and malignant brain tumors. Recently, tumor metabolism became an interesting potential therapeutic target in various cancers. Accordingly, combining drugs targeting cell metabolism with appropriate chemotherapeutic agents or radiotherapy has become attractive. In light of these perspectives, we were particularly interested in the anti-cancer properties of a biguanide molecule used for type 2 diabetes treatment, metformin. In our present work, we demonstrate that metformin decreases mitochondrial-dependent ATP production and oxygen consumption and increases lactate and glycolytic ATP production. We show that metformin induces decreased proliferation, cell cycle arrest, autophagy, apoptosis and cell death in vitro with a concomitant activation of AMPK, Redd1 and inhibition of the mTOR pathway. Cell sensitivity to metformin also depends on the genetic and mutational backgrounds of the different GB cells used in this study, particularly their PTEN status. Interestingly, knockdown of AMPK and Redd1 with siRNA partially, but incompletely, abrogates the induction of apoptosis by metformin suggesting both AMPK/Redd1-dependent and -independent effects. However, the primary determinant of the effect of metformin on cell growth is the genetic and mutational backgrounds of the glioma cells. We further demonstrate that metformin treatment in combination with temozolomide and/or irradiation induces a synergistic anti-tumoral response in glioma cell lines. Xenografts performed in nude mice demonstrate in vivo that metformin delays tumor growth. As current treatments for GB commonly fail to cure, the need for more effective therapeutic options is overwhelming. Based on these results, metformin could represent a potential enhancer of the cytotoxic effects of temozolomide and/or radiotherapy.
Journal Article
The Galloway Hoard : Viking-age treasure
Buried at the beginning of the 10th century in Dumfries and Galloway, the Galloway Hoard lay undisturbed for a thousand years before being unearthed by a metal detectorist in September 2014. This incredible discovery comprises more than 100 objects, including a rich Viking Age hoard of silver jewellery and ingots. It also contains an unparalleled range of precious metal and jewelled items, including a rare gold ingot, a unique gold bird-shaped pin and a decorated silver-gilt vessel, the only complete lidded vessel of its type ever discovered in Britain and Ireland.
Book
Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial
Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment.
From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607.
Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015–0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI –1·99 to –0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events.
Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment.
Medical Research Council.
Journal Article
Edinburgh : mapping the city
Maps can tell much about the story of a place that traditional histories fail to communicate. This is particularly true of Edinburgh, one of the most visually stunning cities in the world and a place rich in historical and cultural associations. This lavishly illustrated book features 71 maps of Edinburgh which have been selected for the particular stories they reveal about the political, commercial and social life of Scotland and her capital. Many are reproduced in book form for the first time. Together, they present a fascinating insight into how Edinburgh has changed and developed over the last 500 years, and will appeal to all those with an interest in Edinburgh and Scottish history, as well as anyone interested in urban history, architectural history, town planning or the history of cartography.
Book
Uncertainty in Divergence Time Estimation
Understanding and representing uncertainty is crucial in academic research because it enables studies to build on the conclusions of previous studies, leading to robust advances in a particular field. Here, we evaluate the nature of uncertainty and the manner by which it is represented in divergence time estimation, a field that is fundamental to many aspects of macroevolutionary research, and where there is evidence that uncertainty has been seriously underestimated. We address this issue in the context of methods used in divergence time estimation, and with respect to the manner by which time-calibrated phylogenies are interpreted. With respect to methods, we discuss how the assumptions underlying different methods may not adequately reflect uncertainty about molecular evolution, the fossil record, or diversification rates. Therefore, divergence time estimates may not adequately reflect uncertainty and may be directly contradicted by subsequent findings. For the interpretation of time-calibrated phylogenies, we discuss how the use of time-calibrated phylogenies for reconstructing general evolutionary timescales leads to inferences about macroevolution that are highly sensitive to methodological limitations in how uncertainty is accounted for. By contrast, we discuss how the use of time-calibrated phylogenies to test specific hypotheses leads to inferences about macroevolution that are less sensitive to methodological limitations. Given that many biologists wish to use time-calibrated phylogenies to reconstruct general evolutionary timescales, we conclude that the development of methods of divergence time estimation that adequately account for uncertainty is necessary.
Journal Article
The Implications of Interrelated Assumptions on Estimates of Divergence Times and Rates of Diversification
Phylogenies are increasingly being used as a basis to provide insight into macroevolutionary history. Here, we use simulation experiments and empirical analyses to evaluate methods that use phylogenies as a basis to make estimates of divergence times and rates of diversification. This is the first study to present a comprehensive assessment of the key variables that underpin analyses in this field—including substitution rates, speciation rates, and extinction, plus character sampling and taxon sampling. We show that in unrealistically simplistic cases (where substitution rates and speciation rates are constant, and where there is no extinction), increased character and taxon sampling lead to more accurate and precise parameter estimates. By contrast, in more complex but realistic cases (where substitution rates, speciation rates, and extinction rates vary), gains in accuracy and precision from increased character and taxon sampling are far more limited. The lack of accuracy and precision even occurs when using methods that are designed to account for more complex cases, such as relaxed clocks, fossil calibrations, and models that allow speciation rates and extinction rates to vary. The problem also persists when analyzing genomic scale data sets. These results suggest two interrelated problems that occur when the processes that generated the data are more complex. First, methodological assumptions are more likely to be violated. Second, limitations in the information content of the data become more important.
Journal Article
Insights from Empirical Analyses and Simulations on Using Multiple Fossil Calibrations with Relaxed Clocks to Estimate Divergence Times
Relaxed clock methods account for among-branch-rate-variation when estimating divergence times by inferring different rates for individual branches. In order to infer different rates for individual branches, important assumptions are required. This is because molecular sequence data do not provide direct information about rates but instead provide direct information about the total number of substitutions along any branch, which is a product of the rate and time for that branch. Often, the assumptions required for estimating rates for individual branches depend heavily on the implementation of multiple fossil calibrations in a single phylogeny. Here, we show that the basis of these assumptions is often critically undermined. First, we highlight that the temporal distribution of the fossil record often violates key assumptions of methods that use multiple fossil calibrations with relaxed clocks. With respect to “node calibration” methods, this conclusion is based on our inference that different fossil calibrations are unlikely to reflect the relative ages of different clades. With respect to the fossilized birth–death process, this conclusion is based on our inference that the fossil recovery rate is often highly heterogeneous. We then demonstrate that methods of divergence time estimation that use multiple fossil calibrations are highly sensitive to assumptions about the fossil record and among-branch-rate-variation. Given the problems associated with these assumptions, our results highlight that using multiple fossil calibrations with relaxed clocks often does little to improve the accuracy of divergence time estimates.
Journal Article