The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy.

Two major pathways contribute to Ras-proximate-1-mediated integrin activation in stimulated platelets. Calcium and diacyglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI, RasGRP2) mediates the rapid but reversible activation of integrin αIIbβ3, while the adenosine diphosphate receptor P2Y12, the target for antiplatelet drugs like clopidogrel, facilitates delayed but sustained integrin activation. To establish CalDAG-GEFI as a target for antiplatelet therapy, we compared how each pathway contributes to thrombosis and hemostasis in mice. Ex vivo, thrombus formation at arterial or venous shear rates was markedly reduced in CalDAG-GEFI(-/-) blood, even in the presence of exogenous adenosine diphosphate and thromboxane A(2). In vivo, thrombosis was virtually abolished in arterioles and arteries of CalDAG-GEFI(-/-) mice, while small, hemostatically active thrombi formed in venules. Specific deletion of the C1-like domain of CalDAG-GEFI in circulating platelets also led to protection from thrombus formation at arterial flow conditions, while it only marginally increased blood loss in mice. In comparison, thrombi in the micro- and macrovasculature of clopidogrel-treated wild-type mice grew rapidly and frequently embolized but were hemostatically inactive. Together, these data suggest that inhibition of the catalytic or the C1 regulatory domain in CalDAG-GEFI will provide strong protection from athero-thrombotic complications while maintaining a better safety profile than P2Y12 inhibitors like clopidogrel.

Conspicuous redemption? Reflections on the promises and perils of the 'celebritization' of climate change

With rising public awareness of climate change, celebrities have become an increasingly important community of non nation-state ‘actors’ influencing discourse and action, thereby comprising an emergent climate science–policy–celebrity complex. Some feel that these amplified and prominent voices contribute to greater public understanding of climate change science, as well as potentially catalyze climate policy cooperation. However, critics posit that increased involvement from the entertainment industry has not served to influence substantive long-term advancements in these arenas; rather, it has instead reduced the politics of climate change to the domain of fashion and fad, devoid of political and public saliency. Through tracking media coverage in Australia, Canada, the United States, and United Kingdom, we map out the terrain of a ‘Politicized Celebrity System’ in attempts to cut through dualistic characterizations of celebrity involvement in politics. We develop a classification system of the various types of climate change celebrity activities, and situate movements in contemporary consumer- and spectacle-driven carbon-based society. Through these analyses, we place dynamic and contested interactions in a spatially and temporally-sensitive ‘Cultural Circuits of Climate Change Celebrities’ model. In so doing, first we explore how these newly ‘authorized’ speakers and ‘experts’ might open up spaces in the public sphere and the science/policy nexus through ‘celebritization’ effects. Second, we examine how the celebrity as the ‘heroic individual’ seeking ‘conspicuous redemption’ may focus climate change actions through individualist frames. Overall, this paper explores potential promises, pitfalls and contradictions of this increasingly entrenched set of ‘agents’ in the cultural politics of climate change. Thus, as a form of climate change action, we consider whether it is more effective to ‘plant’ celebrities instead of trees.

On the reprocessing and reanalysis of observations for climate

The long observational record is critical to our understanding of the Earth’s climate, but most observing systems were not developed with a climate objective in mind. As a result, tremendous efforts have gone into assessing and reprocessing the data records to improve their usefulness in climate studies. The purpose of this paper is to both review recent progress in reprocessing and reanalyzing observations, and summarize the challenges that must be overcome in order to improve our understanding of climate and variability. Reprocessing improves data quality through more scrutiny and improved retrieval techniques for individual observing systems, while reanalysis merges many disparate observations with models through data assimilation, yet both aim to provide a climatology of Earth processes. Many challenges remain, such as tracking the improvement of processing algorithms and limited spatial coverage. Reanalyses have fostered significant research, yet reliable global trends in many physical fields are not yet attainable, despite significant advances in data assimilation and numerical modeling. Oceanic reanalyses have made significant advances in recent years, but will only be discussed here in terms of progress toward integrated Earth system analyses. Climate data sets are generally adequate for process studies and large-scale climate variability. Communication of the strengths, limitations and uncertainties of reprocessed observations and reanalysis data, not only among the community of developers, but also with the extended research community, including the new generations of researchers and the decision makers is crucial for further advancement of the observational data records. It must be emphasized that careful investigation of the data and processing methods are required to use the observations appropriately.

The interpretation and use of biases in decadal climate predictions

Decadal climate predictions exhibit large biases, which are often subtracted and forgotten. However, understanding the causes of bias is essential to guide efforts to improve prediction systems, and may offer additional benefits. Here the origins of biases in decadal predictions are investigated, including whether analysis of these biases might provide useful information. The focus is especially on the lead-time-dependent bias tendency. A “toy” model of a prediction system is initially developed and used to show that there are several distinct contributions to bias tendency. Contributions from sampling of internal variability and a start-time-dependent forcing bias can be estimated and removed to obtain a much improved estimate of the true bias tendency, which can provide information about errors in the underlying model and/or errors in the specification of forcings. It is argued that the true bias tendency, not the total bias tendency, should be used to adjust decadal forecasts. The methods developed are applied to decadal hindcasts of global mean temperature made using the Hadley Centre Coupled Model, version 3 (HadCM3), climate model, and it is found that this model exhibits a small positive bias tendency in the ensemble mean. When considering different model versions, it is shown that the true bias tendency is very highly correlated with both the transient climate response (TCR) and non–greenhouse gas forcing trends, and can therefore be used to obtain observationally constrained estimates of these relevant physical quantities.

The supply and movement of Denarii in Roman Britain

Hoards of denarii are common in Britain and the number which have been recorded in detail means that it is now possible to suggest reasonably accurately what a ‘normal’ hoard of a particular date should look like. That being the case, we can then look for variation around that norm and both investigate and speculate what that variation means. A methodology is developed which suggests periods of faster and less rapid coin circulation which has implications for consideration of monetisation. The model also enables us to view where denarii entered circulation; unsurprisingly the army looms large in this picture. The methodology is directly transferable to other provinces and other periods where there are longlived, relatively stable monetary systems.

Impacts of plant-based foods in ancestral hominin diets on the metabolism and function of gut microbiota in vitro

Ancestral human populations had diets containing more indigestible plant material than present-day diets in industrialized countries. One hypothesis for the rise in prevalence of obesity is that physiological mechanisms for controlling appetite evolved to match a diet with plant fiber content higher than that of present-day diets. We investigated how diet affects gut microbiota and colon cells by comparing human microbial communities with those from a primate that has an extreme plant-based diet, namely, the gelada baboon, which is a grazer. The effects of potato (high starch) versus grass (high lignin and cellulose) diets on human-derived versus gelada-derived fecal communities were compared in vitro. We especially focused on the production of short-chain fatty acids, which are hypothesized to be key metabolites influencing appetite regulation pathways. The results confirmed that diet has a major effect on bacterial numbers, short-chain fatty acid production, and the release of hormones involved in appetite suppression. The potato diet yielded greater production of short-chain fatty acids and hormone release than the grass diet, even in the gelada cultures, which we had expected should be better adapted to the grass diet. The strong effects of diet on hormone release could not be explained, however, solely by short-chain fatty acid concentrations. Nuclear magnetic resonance spectroscopy found changes in additional metabolites, including betaine and isoleucine, that might play key roles in inhibiting and stimulating appetite suppression pathways. Our study results indicate that a broader array of metabolites might be involved in triggering gut hormone release in humans than previously thought. IMPORTANCE: One theory for rising levels of obesity in western populations is that the body's mechanisms for controlling appetite evolved to match ancestral diets with more low-energy plant foods. We investigated this idea by comparing the effects of diet on appetite suppression pathways via the use of gut bacterial communities from humans and gelada baboons, which are modern-day primates with an extreme diet of low-energy plant food, namely, grass. We found that diet does play a major role in affecting gut bacteria and the production of a hormone that suppresses appetite but not in the direction predicted by the ancestral diet hypothesis. Also, bacterial products were correlated with hormone release that were different from those normally thought to play this role. By comparing microbiota and diets outside the natural range for modern humans, we found a relationship between diet and appetite pathways that was more complex than previously hypothesized on the basis of more-controlled studies of the effects of single compounds.

On the structure and dynamics of Indian monsoon depressions

ERA-Interim reanalysis data from the past 35 years have been used with a newly-developed feature tracking algorithm to identify Indian monsoon depressions originating in or near the Bay of Bengal. These were then rotated, centralised and combined to give a fully three-dimensional 106-depression composite structure – a considerably larger sample than any previous detailed study on monsoon depressions and their structure. Many known features of depression structure are confirmed, particularly the existence of a maximum to the southwest of the centre in rainfall and other fields, and a westward axial tilt in others. Additionally, the depressions are found to have significant asymmetry due to the presence of the Himalayas; a bimodal mid-tropospheric potential vorticity core; a separation into thermally cold- (~–1.5K) and neutral- (~0K) cores near the surface with distinct properties; and that the centre has very large CAPE and very small CIN. Variability as a function of background state has also been explored, with land/coast/sea, diurnal, ENSO, active/break and Indian Ocean Dipole contrasts considered. Depressions are found to be markedly stronger during the active phase of the monsoon, as well as during La Niña. Depressions on land are shown to be more intense and more tightly constrained to the central axis. A detailed schematic diagram of a vertical cross-section through a composite depression is also presented, showing its inherent asymmetric structure.

The climate and environment of Byzantine Anatolia: integrating science, history, and archaeology

The integration of high-resolution archaeological, textual, and environmental data with longer-term, low-resolution data affords greater precision in identifying some of the causal relationships underlying societal change. Regional and microregional case studies about the Byzantine world—in particular, Anatolia, which for several centuries was the heart of that world—reveal many of the difficulties that researchers face when attempting to assess the influence of environmental factors on human society. The Anatolian case challenges a number of assumptions about the impact of climatic factors on socio-political organization and medium-term historical evolution, highlighting the importance of further collaboration between historians, archaeologists, and climate scientists.

The lives and deaths of young medieval women: the osteological evidence

Written sources from the medieval period focus mainly on the activities of adults, particularly males and often those from the wealthier sections of society. Recent scholarship has attempted to redress this balance by giving attention to medieval women and children, but we are still limited by what we can learn about the daily lives of all members of medieval English society. Osteology, the study of human skeletal remains, suffers from no such bias and can provide substantial and detailed information on growth, health and daily life of the general population. This paper presents the results of a new analysis of the skeletal remains of over 300 medieval girls and young women aged at between 14 and 25 years from a number of English cemetery sites. We incorporate data from the published archaeological literature as well as documentary evidence to provide new insights into the lives and deaths of young medieval women.

On the detection and attribution of gravity waves generated by the 20 March 2015 solar eclipse

Internal gravity waves are generated as adjustment radiation whenever a sudden change in forcing causes the atmosphere to depart from its large-scale balanced state. Such a forcing anomaly occurs during a solar eclipse, when the Moon’s shadow cools part of the Earth’s surface. The resulting atmospheric gravity waves are associated with pressure and temperature perturbations, which in principle are detectable both at the surface and aloft. In this study, surface pressure and temperature data from two UK sites at Reading and Lerwick are analysed for eclipse-driven gravity-wave perturbations during the 20 March 2015 solar eclipse over north-west Europe. Radiosonde wind data from the same two sites are also analysed using a moving parcel analysis method, to determine the periodicities of the waves aloft. On this occasion, the perturbations both at the surface and aloft are found not to be confidently attributable to eclipse-driven gravity waves. We conclude that the complex synoptic weather conditions over the UK at the time of this particular eclipse helped to mask any eclipse-driven gravity waves.

A new regime of carbon counting: the practices and politics of accounting for everyday carbon through C02e

Inspired by the commercial desires of global brands and retailers to access the lucrative green consumer market, carbon is increasingly being counted and made knowable at the mundane sites of everyday production and consumption, from the carbon footprint of a plastic kitchen fork to that of an online bank account. Despite the challenges of counting and making commensurable the global warming impact of a myriad of biophysical and societal activities, this desire to communicate a product or service's carbon footprint has sparked complicated carbon calculative practices and enrolled actors at literally every node of multi-scaled and vastly complex global supply chains. Against this landscape, this paper critically analyzes the counting practices that create the ‘e’ in ‘CO2e’. It is shown that, central to these practices are a series of tools, models and databases which, in building upon previous work (Eden, 2012 and Star and Griesemer, 1989) we conceptualize here as ‘boundary objects’. By enrolling everyday actors from farmers to consumers, these objects abstract and stabilize greenhouse gas emissions from their messy material and social contexts into units of CO2e which can then be translated along a product's supply chain, thereby establishing a new currency of ‘everyday supply chain carbon’. However, in making all greenhouse gas-related practices commensurable and in enrolling and stabilizing the transfer of information between multiple actors these objects oversee a process of simplification reliant upon, and subject to, a multiplicity of approximations, assumptions, errors, discrepancies and/or omissions. Further the outcomes of these tools are subject to the politicized and commercial agendas of the worlds they attempt to link, with each boundary actor inscribing different meanings to a product's carbon footprint in accordance with their specific subjectivities, commercial desires and epistemic framings. It is therefore shown that how a boundary object transforms greenhouse gas emissions into units of CO2e, is the outcome of distinct ideologies regarding ‘what’ a product's carbon footprint is and how it should be made legible. These politicized decisions, in turn, inform specific reduction activities and ultimately advance distinct, specific and increasingly durable transition pathways to a low carbon society.

A new method for the characterisation and verification of local spatial predictability for convective scale ensembles

The use of kilometre-scale ensembles in operational forecasting provides new challenges for forecast interpretation and evaluation to account for uncertainty on the convective scale. A new neighbourhood based method is presented for evaluating and characterising the local predictability variations from convective scale ensembles. Spatial scales over which ensemble forecasts agree (agreement scales, S^A) are calculated at each grid point ij, providing a map of the spatial agreement between forecasts. By comparing the average agreement scale obtained from ensemble member pairs (S^A(mm)_ij), with that between members and radar observations (S^A(mo)_ij), this approach allows the location-dependent spatial spread-skill relationship of the ensemble to be assessed. The properties of the agreement scales are demonstrated using an idealised experiment. To demonstrate the methods in an operational context the S^A(mm)_ij and S^A(mo)_ij are calculated for six convective cases run with the Met Office UK Ensemble Prediction System. The S^A(mm)_ij highlight predictability differences between cases, which can be linked to physical processes. Maps of S^A(mm)_ij are found to summarise the spatial predictability in a compact and physically meaningful manner that is useful for forecasting and for model interpretation. Comparison of S^A(mm)_ij and S^A(mo)_ij demonstrates the case-by-case and temporal variability of the spatial spread-skill, which can again be linked to physical processes.

Maternal health care professionals perspective on the provision and use of antenatal and delivery care : a qualitative descriptive study in rural Vietnam

Background. High quality maternal health care is an important tool to reduce maternal and neonatal mortality. Services offered should be evidence based and adapted to the local setting. This qualitative descriptive study explored the perspectives and experiences of midwives, assistant physicians and medical doctors on the content and quality of maternal health care in rural Vietnam. Method. The study was performed in a rural district in northern Vietnam. Four focus group discussions with health care professionals at primary health care level were conducted. The data was analysed using qualitative manifest and latent content analysis. Result. Two main themes emerged: "Contextual conditions for maternal health care" and "Balancing between possibilities and constraints". Contextual conditions influenced both pregnant women's use of maternal health care and health care professionals' performance. The study participants stated that women's uses of maternal health care were influenced by economical constraints and cultural norms that impeded their autonomy in relation to childbearing. Structural constraints within the health care system included inadequate financing of the primary health care, resulting in lack of human resources, professional re-training and adequate equipment. Conclusion. Contextual conditions strongly influenced the performance and interaction between pregnant women and health care professionals within antenatal care and delivery care in a rural district of Vietnam. Although Vietnam is performing comparatively well in terms of low maternal and child mortality figures, this study revealed midwives' and other health care professionals' perceived difficulties in their daily work. It seemed maternal health care was under-resourced in terms of staff, equipment and continuing education activities. The cultural setting in Vietnam constituting a strong patriarchal society and prevailing Confucian norms limits women's autonomy and reduce their possibility to make independent decisions about their own reproductive health. This issue should be further addressed by policy-makers. Strategies to reduce inequities in maternal health care for pregnant women are needed. The quality of client-provider interaction and management of pregnancy may be strengthened by education, human resources, re-training and provision of essential equipment.

Influence of a Brazilian sewage outfall on the toxicity and contamination of adjacent sediments

The submarine sewage outfall of Santos (SSOS) is situated in the Santos Bay (São Paulo, Brazil) and is potentially a significant source of contaminants to the adjacent marine ecosystem. The present study aimed to assess the influence of SSOS on the sediment toxicity and contamination at Santos Bay. At the disposal site, sediments tended to be finer, organically richer and exhibited higher levels of surfactants and metals, sometimes exceeding the Threshold Effect Level values. The SSOS influence was more evident toward the East, where the sediments exhibited higher levels of TOC, total S and metals during the summer 2000 sampling campaign. Sediment toxicity to amphipods was consistently detected in four of the five stations studied. Amphipod survival tended to correlate negatively to Hg, total N and % mud. This work provides evidence that the SSOS discharge affects the quality of sediments from Santos Bay, and that control procedures are warranted. (c) 2005 Elsevier Ltd. All rights reserved.

Ephemeroptera, Plecoptera and Trichoptera assemblages from riffles in mountain streams of Central Brazil: environmental factors influencing the distribution and abundance of immatures

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)