163 research outputs found

    Influences on Attitudes to a Personal Carbon Trading System

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    There are mixed attitudes to the affect Personal Carbon Trading (PCT) can have on global warming and carbon emissions. The NICHE (Norfolk Island Carbon Health Evaluation) project has been developed to explore attitudes towards PCT. The researchers have designed the project to investigate links between health, obesity and an individual’s carbon footprint. The first stages of the project undertaken in 2012 involve development of point-of-sale applications, personal carbon consumption web site and collection of data to establish a baseline measuring key health indicators and attitudes to climate change and PCT. This paper reports the findings from the correlation analysis of the key variables from the baseline survey. Correlation analysis was used to examine relationships among the variables. The significant relationships identified from the baseline survey will be re-examined in the latter stages of the project during 2014

    Silicon isotopes in Antarctic sponges : an interlaboratory comparison

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    Cycling of deepwater silicon (Si) within the Southern Ocean, and its transport into other ocean basins, may be an important player in the uptake of atmospheric carbon, and global climate. Recent work has shown that the Si isotope (denoted by δ29Si or δ30Si) composition of deep sea sponges reflects the availability of dissolved Si during growth, and is a potential proxy for past deep and intermediate water silicic acid concentrations. As with any geochemical tool, it is essential to ensure analytical precision and accuracy, and consistency between methodologies and laboratories. Analytical bias may exist between laboratories, and sponge material may have matrix effects leading to offsets between samples and standards. Here, we report an interlaboratory evaluation of Si isotopes in Antarctic and sub-Antarctic sponges. We review independent methods for measuring Si isotopes in sponge spicules. Our results show that separate subsamples of non-homogenized sponges measured by three methods yield isotopic values within analytical error for over 80% of specimens. The relationship between δ29Si and δ30Si in sponges is consistent with kinetic fractionation during biomineralization. Sponge Si isotope analyses show potential as palaeoceaongraphic archives, and we suggest Southern Ocean sponge material would form a useful additional reference standard for future spicule analyses

    Ad Hominem Criminalisation and the Rule of Law : The Egalitarian Case Against Knife Crime Prevention Orders

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    This article advances a novel account of ad hominem criminalisation that draws upon a distinct theory of the Rule of Law and its egalitarian foundations. Employing the recent and controversial example of Knife Crime Prevention Orders, as established by the Offensive Weapons Act 2019, it argues that the concept of civic equality is central to understanding the vice of ad hominem criminalisation as an aberrant form of government by law. This vice consists in the manner that such criminalisation individualises, differentiates and instrumentalises the regulatory subject, placing them outwith the bounds of civic equality as established by the Rule of Law

    AD-8 for detection of dementia across a variety of healthcare settings

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    BACKGROUND: Dementia assessment often involves initial screening, using a brief tool, followed by more detailed assessment where required. The AD-8 is a short questionnaire, completed by a suitable 'informant' who knows the person well. AD-8 is designed to assess change in functional performance secondary to cognitive change. OBJECTIVES: To determine the diagnostic accuracy of the informant-based AD-8 questionnaire, in detection of all-cause (undifferentiated) dementia in adults. Where data were available, we described the following: the diagnostic accuracy of the AD-8 at various predefined threshold scores; the diagnostic accuracy of the AD-8 for each healthcare setting and the effects of heterogeneity on the reported diagnostic accuracy of the AD-8. SEARCH METHODS: We searched the following sources on 27 May 2014, with an update to 7 June 2018: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on the AD-8 to try to find additional studies. We developed a sensitive search strategy and used standardised database subject headings as appropriate. Foreign language publications were translated. SELECTION CRITERIA: We selected those studies which included the AD-8 to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. We only included those studies where the AD-8 was used as an informant assessment. We made no exclusions in relation to healthcare setting, language of AD-8 or the AD-8 score used to define a 'test positive' case. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies. We then created summary estimates of sensitivity, specificity and likelihood ratios using the bivariate approach and plotting results in receiver operating characteristic (ROC) space. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool. MAIN RESULTS: From 36 papers describing AD-8 test accuracy, we included 10 papers. We utilised data from nine papers with 4045 individuals, 1107 of whom (27%) had a clinical diagnosis of dementia. Pooled analysis of seven studies, using an AD-8 informant cut-off score of two, indicated that sensitivity was 0.92 (95% confidence interval (CI) 0.86 to 0.96); specificity was 0.64 (95% CI 0.39 to 0.82); the positive likelihood ratio was 2.53 (95% CI 1.38 to 4.64); and the negative likelihood ratio was 0.12 (95% CI 0.07 to 0.21). Pooled analysis of five studies, using an AD-8 informant cut-off score of three, indicated that sensitivity was 0.91 (95% CI 0.80 to 0.96); specificity was 0.76 (95% CI 0.57 to 0.89); the positive likelihood ratio was 3.86 (95% CI 2.03 to 7.34); and the negative likelihood ratio was 0.12 (95% CI 0.06 to 0.24).Four studies were conducted in community settings; four were in secondary care (one in the acute hospital); and one study was in primary care. The AD-8 has a higher relative sensitivity (1.11, 95% CI 1.02 to 1.21), but lower relative specificity (0.51, 95% CI 0.23 to 1.09) in secondary care compared to community care settings.There was heterogeneity across the included studies. Dementia prevalence rate varied from 12% to 90% of included participants. The tool was also used in various different languages. Among all the included studies there was evidence of risk of bias. Issues included the selection of participants, conduct of index test, and flow of assessment procedures. AUTHORS' CONCLUSIONS: The high sensitivity of the AD-8 suggests it can be used to identify adults who may benefit from further specialist assessment and diagnosis, but is not a diagnostic test in itself. This pattern of high sensitivity and lower specificity is often suited to a screening test. Test accuracy varies by setting, however data in primary care and acute hospital settings are limited. This review identified significant heterogeneity and risk of bias, which may affect the validity of its summary findings

    Membrane insertion of soluble CLIC1 into active chloride channels is triggered by specific divalent cations

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    The CLIC family of proteins display the unique feature of altering their structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, can be found in the cytoplasm or in nuclear, ER and plasma membranes, with membrane overexpression linked to tumour proliferation. The molecular switch promoting CLIC1 membrane insertion has been related to environmental factors, but still remains unclear. Here, we use solution NMR studies to confirm that both the soluble and membrane bound forms are in the same oxidation state. Our data from fluorescence assays and chloride efflux assays indicate that Ca2+ and Zn2+ trigger association to the membrane into active chloride channels. We use fluorescence microscopy to confirm that an increase of the intracellular Ca2+ leads to re-localisation of CLIC1 to both plasma and internal membranes. Finally, we show that soluble CLIC1 adopts an equilibrium of oligomeric species, and Ca2+/Zn2+ mediated membrane insertion promotes the formation of a tetrameric assembly. Thus, our results identify Ca2+ and Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion.SIGNIFICANCE STATEMENT CLIC1, a member of the CLIC family of proteins, is expressed as a soluble protein in cells but can insert in the membrane forming a chloride channel. This chloride channel form is upregulated in different types of cancers including glioblastoma and promote tumour invasiveness and metastasis. The factors promoting CLIC1 membrane insertion nor the mechanism of this process are yet understood. Here, we use a combination of solution NMR, biophysics and fluorescence microscopy to identify Ca2+ and Zn2+ binding as the switch to promote CLIC1 insertion into the membrane to form active chloride channels. We also provide a simple mechanism how such transition to the membrane occurs. Such understanding will enable subsequent studies on the structure of the chloride channel form and its inhibition

    Long-Term Outcomes in IgA Nephropathy

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    BACKGROUND: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope and lifetime risks for kidney failure. METHODS: The IgA nephropathy cohort (2,299 adults, 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy, plus proteinuria >0.5 g/day or eGFR <60 mL/min/1.73m 2 . Incident and prevalent populations were studied as well as a population representative of a typical phase 3 clinical trial cohort. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. RESULTS: Median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. Median (95% CI) kidney survival was 11.4 (10.5, 12.5) years; mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. Based on eGFR and age at diagnosis, almost all patients are at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min/1.73m 2 /year can be maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and "clinical trial" populations. 30% of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the "clinical trial" population each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87-0.92). CONCLUSIONS: Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being "low-risk", with proteinuria <0.88 g/g (<100 mg/mmol), have high rates of kidney failure within 10 years

    The formation of vortex loops (strings) in continuous phase transitions

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    The formation of vortex loops (global cosmic strings) in an O(2) linear sigma model in three spatial dimensions is analyzed numerically. For over-damped Langevin dynamics we find that defect production is suppressed by an interaction between correlated domains that reduces the effective spatial variation of the phase of the order field. The degree of suppression is sensitive to the quench rate. A detailed description of the numerical methods used to analyze the model is also reported.Comment: LaTeX, 17 pages, 6 eps figures 2 references and a footnote adde

    Essential Emergency and Critical Care: a consensus among global clinical experts.

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    BACKGROUND: Globally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19. METHODS: In a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements. RESULTS: The 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19. CONCLUSION: The study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide
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