A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Assembling the Dead, Gathering the Living: Radiocarbon Dating and Bayesian Modelling for Copper Age Valencina de la Concepción (Seville, Spain)

The great site of Valencina de la Concepción, near Seville in the lower Guadalquivir valley of southwest Spain, is presented in the context of debate about the nature of Copper Age society in southern Iberia as a whole. Many aspects of the layout, use, character and development of Valencina remain unclear, just as there are major unresolved questions about the kind of society represented there and in southern Iberia, from the late fourth to the late third millennium cal BC. This paper discusses 178 radiocarbon dates, from 17 excavated sectors within the c. 450 ha site, making it the best dated in later Iberian prehistory as a whole. Dates are modelled in a Bayesian statistical framework. The resulting formal date estimates provide the basis for both a new epistemological approach to the site and a much more detailed narrative of its development than previously available. Beginning in the 32nd century cal BC, a long-lasting tradition of simple, mainly collective and often successive burial was established at the site. Mud-vaulted tholoi appear to belong to the 29th or 28th centuries cal BC; large stone-vaulted tholoi such as La Pastora appear to date later in the sequence. There is plenty of evidence for a wide range of other activity, but no clear sign of permanent, large-scale residence or public buildings or spaces. Results in general support a model of increasingly competitive but ultimately unstable social relations, through various phases of emergence, social competition, display and hierarchisation, and eventual decline, over a period of c. 900 years