Radioactive isotope analyses of skeletal materials in forensic science: a review of uses and potential uses

A review of information that can be provided from measurements made on natural and anthropogenic radionuclide activities in human skeletal remains has been undertaken to establish what reliable information of forensic anthropological use can be obtained regarding years of birth and death (and hence post-mortem interval (PMI)). Of the anthropogenic radionuclides that have entered the environment, radiocarbon (14C) can currently be used to generate the most useful and reliable information. Measurements on single bones can indicate whether or not the person died during the nuclear era, while recent research suggests that measurements on trabecular bone may, depending on the chronological age of the remains, provide estimates of year of death and hence PMI. Additionally, 14C measurements made on different components of single teeth or on teeth formed at different times can provide estimates of year of birth to within 1–2 years of the true year. Of the other anthropogenic radionuclides, 90Sr shows some promise but there are problems of (1) variations in activities between individuals, (2) relatively large analytical uncertainties and (3) diagenetic contamination. With respect to natural series radionuclides, it is concluded that there is no convincing evidence that 210Pb dating can be used in a rigorous, quantitative fashion to establish a PMI. Similarly, for daughter/parent pairs such as 210Po/210Pb (from the 238U decay series) and 228Th/228Ra (from the 232Th decay series), the combination of analytical uncertainty and uncertainty in activity ratios at the point of death inevitably results in major uncertainty in any estimate of PMI. However, observation of the disequilibrium between these two daughter/parent pairs could potentially be used in a qualitative way to support other forensic evidence

Temporal trend in the transfer of Sellafield-derived 14C into different size fractions of the carbonate component of NE Irish Sea sediment

From 1994 onwards, 14C discharges from the Sellafield nuclear fuel reprocessing plant have been made largely to the Northeast Irish Sea. They represent the largest contributor to UK and European populations of the collective dose commitment derived from the entire nuclear industry discharges. Consequently, it is important to understand the long-term fate of 14C in the marine environment. Research undertaken in 2000 suggested that the carbonate component of Northeast Irish Sea sediments would increase in 14C activity as mollusc shells, which have become enriched in Sellafield-derived 14C, are broken down by physical processes including wave action and incorporated into intertidal and sub-tidal sediments. The current study, undertaken in 2011, tested this hypothesis. The results demonstrate significant increases in 14C enrichments found in whole mussel shells compared to those measured in 2000. Additionally, in 2000, there was an enrichment above ambient background within only the largest size fraction (>500 μm) of the intertidal inorganic sediment at Nethertown and Flimby (north of Sellafield). In comparison, the present study has demonstrated 14C enrichments above ambient background in most size fractions at sites up to 40 km north of Sellafield, confirming the hypothesis set out more than a decade ago

Assessing depleted uranium (DU) contamination of soil, plants and earthworms at UK weapons testing sites

Depleted uranium (DU) weapons testing programmes have been conducted at two locations within the UK. An investigation was therefore carried out to assess the extent of any environmental contamination arising from these test programmes using both alpha spectrometry and mass spectrometry techniques. Uranium isotopic signatures indicative of DU contamination were observed in soil, plant and earthworm samples collected in the immediate vicinity of test firing points and targets, but contamination was found to be localised to these areas. The paper demonstrates the superiority of the 235U:238U ratio over the 234U:238U ratio for identifying and quantifying DU contamination in environmental samples and also describes the respective circumstances under which alpha spectrometry or mass spectrometry may be the more appropriate analytical tool

Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock

The role of drotrecogin alfa (activated) (DAA) in severe sepsis remains controversial and clinicians are unsure whether or not to treat their patients with DAA. In response to a request from the European Medicines Agency, Eli Lilly will sponsor a new placebo-controlled trial and history suggests the results will be subject to great scrutiny. An academic steering committee will oversee the conduct of the study and will write the study manuscripts. The steering committee intends that the study will be conducted with the maximum possible transparency; this includes publication of the study protocol and a memorandum of understanding which delineates the role of the sponsor. The trial has the potential to provide clinicians with valuable data but patients will only benefit if clinicians have confidence in the conduct, analysis and reporting of the trial. This special article describes the process by which the trial was developed, major decisions regarding trial design, and plans for independent analysis, interpretation and reporting of the data

An Observational Cohort Study of the Kynurenine to Tryptophan Ratio in Sepsis: Association with Impaired Immune and Microvascular Function

Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64–235]) compared to controls (36 [28–52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100–286] on day 0 to 89 [65–139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two fundamental processes in sepsis pathophysiology

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700