155 research outputs found

    Consensus statement on the use of high sensitivity cardiac troponins

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    The increased sensitivity of high sensitivity cardiac troponin assays comes at a cost of decreased specificity, and “false positive” diagnosis of acute coronary syndromes has made clinicians wary of their use, fearing unnecessary hospitalisations, angiography and revascularisation. The Ethics and Guidelines Standing Committee of SA Heart Association convened a meeting of cardiologists, chemical pathologists, emergency medicine specialists and industry representatives to discuss the role of high sensitivity troponin (hsTn) testing. An international expert provided guidance, and this Consensus Statement is the product of that meeting. It is recommended that hsTn assays be widely adopted as the preferred biomarker for diagnosis of myocardial infarction. Pathology laboratories will standardise the units of measurement and the reporting of results. Rules for interpretation of results and algorithms for their application are provided. Separate algorithms apply to troponin T and troponin I, and the several troponin I assays on the market each have different numerical values. Use of high sensitivity troponin assays will result in earlier diagnosis of myocardial infarction, more reliable ruling out of myocardial infarction, and shortening of chest pain triage (to 4 hours), compared to former assays

    An experimental investigation into the behaviour of de-structured chalk under cyclic loading

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    Low-to-medium density chalk can be de-structured to soft putty by high-pressure compression, dynamic impact or large-strain repetitive shearing. These process all occur during pile driving and affect subsequent static and cyclic load-carrying capacities. This paper reports undrained triaxial experiments on de-structured chalk, which shows distinctly time-dependent behaviour as well as highly non-linear stiffness, well-defined phase transformation (PT) and stable ultimate critical states under monotonic loading. Its response to high-level undrained cyclic loading invokes both contractive and dilative phases that lead to pore pressure build-up, leftward effective stress path drift, permanent strain accumulation, cyclic stiffness losses and increasing damping ratios that resemble those of silts. These outcomes are relatively insensitive to consolidation pressures and are distinctly different to those of the parent intact chalk. The maximum number of cycles that can be sustained under given combinations of mean and cyclic stresses are expressed in an interactive stress diagram which also identifies conditions under which cycling has no deleterious effect. Empirical correlations are proposed to predict the number of cycles to failure and mean effective stress drift trends under the most critical cyclic conditions. Specimens that survive long-term cycling present higher post-cyclic stiffnesses and shear strengths than equivalent ‘virgin’ specimens

    Advanced in-situ and laboratory characterisation of the ALPACA chalk research site

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    Low-to-medium density chalk at St Nicholas at Wade, UK, is characterised by intensive testing to inform the interpretation of axial and lateral tests on driven piles. The chalk de-structures when taken to large strains, especially under dynamic loading, leading to remarkably high pore pressures beneath penetrating CPT and driven pile tips, weak putty annuli around their shafts and degraded responses in full-displacement pressuremeter tests. Laboratory tests on carefully formed specimens explore the chalk's unstable structure and markedly time and rate-dependent mechanical behaviour. A clear hierarchy is found between profiles of peak strength with depth of Brazilian tension (BT), drained and undrained triaxial and direct simple shear (DSS) tests conducted from in-situ stress conditions. Highly instrumented triaxial tests reveal the chalk's unusual effective stress paths, markedly brittle failure behaviour from small strains and the effects of consolidating to higher than in-situ stresses. The chalk's mainly sub-vertical jointing and micro-fissuring leads to properties depending on specimen scale, with in-situ mass stiffnesses falling significantly below high-quality laboratory measurements and vertical Young's moduli exceeding horizontal stiffnesses. While compressive strength and stiffness appear relatively insensitive to effective stress levels, consolidation to higher pressures closes micro-fissures, increases stiffness and reduces anisotropy

    A characteristics framework for Semantic Information Systems Standards

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    Semantic Information Systems (IS) Standards play a critical role in the development of the networked economy. While their importance is undoubted by all stakeholders—such as businesses, policy makers, researchers, developers—the current state of research leaves a number of questions unaddressed. Terminological confusion exists around the notions of “business semantics”, “business-to-business interoperability”, and “interoperability standards” amongst others. And, moreover, a comprehensive understanding about the characteristics of Semantic IS Standards is missing. The paper addresses this gap in literature by developing a characteristics framework for Semantic IS Standards. Two case studies are used to check the applicability of the framework in a “real-life” context. The framework lays the foundation for future research in an important field of the IS discipline and supports practitioners in their efforts to analyze, compare, and evaluate Semantic IS Standard

    Application of Nitrogen and Carbon Stable Isotopes (δ15Ν and δ13C) to Quantify Food Chain Length and Trophic Structure

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    Increasingly, stable isotope ratios of nitrogen (delta N-15) and carbon (delta C-13) are used to quantify trophic structure, though relatively few studies have tested accuracy of isotopic structural measures. For laboratory-raised and wild-collected plant-invertebrate food chains spanning four trophic levels we estimated nitrogen range (NR) using delta N-15, and carbon range (CR) using delta C-13, which are used to quantify food chain length and breadth of trophic resources respectively. Across a range of known food chain lengths we examined how NR and CR changed within and between food chains. Our isotopic estimates of structure are robust because they were calculated using resampling procedures that propagate variance in sample means through to quantified uncertainty in final estimates. To identify origins of uncertainty in estimates of NR and CR, we additionally examined variation in discrimination (which is change in delta N-15 ordelta C-13 from source to consumer) between trophic levels and among food chains. delta N-15 discrimination showed significant enrichment, while variation in enrichment was species and system specific, ranged broadly (1.4‰ to 3.3‰), and importantly, propagated variation to subsequent estimates of NR. However, NR proved robust to such variation and distinguished food chain length well, though some overlap between longer food chains infers a need for awareness of such limitations. delta C-13 discrimination was inconsistent; generally no change or small significant enrichment was observed. Consequently, estimates of CR changed little with increasing food chain length, showing the potential utility of delta C-13 as a tracer of energy pathways. This study serves as a robust test of isotopic quantification of food chain structure, and given global estimates of aquatic food chains approximate four trophic levels while many food chains include invertebrates, our use of four trophic level plant-invertebrate food chains makes our findings relevant for a majority of ecological systems

    A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

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    Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10−6) and GPC6 showed suggestive evidence for interaction with age (p≈10−7). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism

    A whole genome association study of neuroticism using DNA pooling.

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    We describe a multistage approach to identify single nucleotide polymorphisms (SNPs) associated with neuroticism, a personality trait that shares genetic determinants with major depression and anxiety disorders. Whole genome association with 452 574 SNPs was performed on DNA pools from approximately 2000 individuals selected on extremes of neuroticism scores from a cohort of 88 142 people from southwest England. The most significant SNPs were then genotyped on independent samples to replicate findings. We were able to replicate association of one SNP within the PDE4D gene in a second sample collected by our laboratory and in a family-based test in an independent sample; however, the SNP was not significantly associated with neuroticism in two other independent samples. We also observed an enrichment of low P-values in known regions of copy number variations. Simulation indicates that our study had approximately 80% power to identify neuroticism loci in the genome with odds ratio (OR)&gt;2, and approximately 50% power to identify small effects (OR=1.5). Since we failed to find any loci accounting for more than 1% of the variance, the heritability of neuroticism probably arises from many loci each explaining much less than 1%. Our findings argue the need for much larger samples than anticipated in genetic association studies and that the biological basis of emotional disorders is extremely complex

    High Viral Fitness during Acute HIV-1 Infection

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    Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection

    A framework for integrated environmental health impact assessment of systemic risks

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    Traditional methods of risk assessment have provided good service in support of policy, mainly in relation to standard setting and regulation of hazardous chemicals or practices. In recent years, however, it has become apparent that many of the risks facing society are systemic in nature – complex risks, set within wider social, economic and environmental contexts. Reflecting this, policy-making too has become more wide-ranging in scope, more collaborative and more precautionary in approach. In order to inform such policies, more integrated methods of assessment are needed. Based on work undertaken in two large EU-funded projects (INTARESE and HEIMTSA), this paper reviews the range of approaches to assessment now in used, proposes a framework for integrated environmental health impact assessment (both as a basis for bringing together and choosing between different methods of assessment, and extending these to more complex problems), and discusses some of the challenges involved in conducting integrated assessments to support policy
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