Optimised investigation of radioactively contaminated land

Measurements of the radioactive content of environmental samples are potentially very costly, especially when these are made ex situ in a laboratory. A less expensive alternative is to acquire in situ measurements in the field. Both measurement types are subject to uncertainties, some of which arise from different sources depending on the measurement method used. Surveys on radioactively contaminated land found that in situ measurements produced results that were as useful in satisfying the typical objectives of such surveys as ex situ measurements. The random component of analytical uncertainty estimated from duplicated in situ measurements was 2-4 times higher than would have been expected from Poisson statistics, however the sampling uncertainty (0-10 %) was found to be much lower than that for ex situ measurements (44-73 %). This resulted from the combined effects of high heterogeneity of the target radionuclide (137Cs) in the ground, and the comparatively large primary sample mass associated with in situ measurements of gamma-emitting radionuclides. A large sampling mass also means that in situ measurements have an advantage in finding small hotspots of activity, although they may not provide sufficient resolution for spatially mapping lateral distributions of contaminants for remediation purposes. The degree of resolution can be readily changed in the field, however, by the simple expedient of changing the detector height. Experiments with an in situ detector close to the ground surface enabled the position of a small hotspot to be determined to within a few centimetres. To evaluate activity concentrations in the soil, assumptions need to be made about the dimensions of the measured sample, and the distributions of activity within it. This requires some information that might be best obtained from ex situ measurements of excavated samples. However, well planned in situ surveys have the potential to significantly reduce the requirement for these expensive laboratory measurements. A new method of optimising the design of in situ surveys has been developed, based on a generic model for predicting the detector response to small particles of activity at different positions relative to the detector. The new mathematical model used by this method compares well with field measurements, and also with predictions made using a commercially available calibration program

Confidence intervals for robust estimates of measurement uncertainty

Uncertainties arising at different stages of a measurement process can be estimated using Analysis of Variance (ANOVA) on duplicated measurements. In some cases it is also desirable to calculate confidence intervals for these uncertainties. This can be achieved using probability models that assume the measurement data are normally distributed. However, it is often the case in practice that a set of otherwise normally distributed measurement values is contaminated by a small number of outlying values, which may have a disproportionate effect on the variances calculated using the ‘classical’ form of ANOVA. In this case, robust ANOVA methods are able to provide variance estimates that are much closer to the parameters of the underlying normal distributions. A method using bootstrapping to calculate confidence intervals from robust estimates of variances is proposed and evaluated, and is shown to work well when the number of outlying values is small. The method has been implemented in a Visual Basic program

Interactions of short-term and chronic treadmill training with aging of the left ventricle of the heart

With aging, there is a decline in cardiac function accompanying increasing risk of arrhythmias. These effects are likely to be mechanistically associated with age-associated changes in calcium regulation within cardiac myocytes. Previous studies suggest that lifelong exercise can potentially reduce age-associated changes in the heart. Although exercise itself is associated with changes in cardiac function, little is known about the interactions of aging and exercise with respect to myocyte calcium regulation. To investigate this, adult (12 months) and old (24 months) C57/Bl6 mice were trained using moderate-intensity treadmill running. In response to 10 weeks’ training, comparable cardiac hypertrophic responses were observed, although aging independently associated with additional cardiac hypertrophy. Old animals also showed increased L- and T-type calcium channels, the sodium–calcium exchange, sarcoendoplasmic reticulum calcium ATPase, and collagen (by 50%, 92%, 66%, 88%, and 113% respectively). Short-term exercise training increased D-type and T-type calcium channels in old animals only, whereas an increase in sodium–calcium exchange was seen only in adult animals. Long-term (12 months) training generally opposed the effects of aging. Significant hypertrophy remained in long-term trained old animals, but levels of sarcoendoplasmic reticulum calcium ATPase, sodium–calcium exchange, and collagen were not significantly different from those found in the adult trained animals

Optimising in situ gamma measurements to identify the presence of radioactive particles in land areas

High-coverage in situ surveys with gamma detectors are the best means of identifying small hotspots of activity, such as radioactive particles, in land areas. Scanning surveys can produce rapid results, but the probabilities of obtaining false positive or false negative errors are often unknown, and they may not satisfy other criteria such as estimation of mass activity concentrations. An alternative is to use portable gamma-detectors that are set up at a series of locations in a systematic sampling pattern, where any positive measurements are subsequently followed up in order to determine the exact location, extent and nature of the target source. The preliminary survey is typically designed using settings of detector height, measurement spacing and counting time that are based on convenience, rather than using settings that have been calculated to meet requirements. This paper introduces the basis of a repeatable method of setting these parameters at the outset of a survey, for pre-defined probabilities of false positive and false negative errors in locating spatially small radioactive particles in land areas. It is shown that an un-collimated detector is more effective than a collimated detector that might typically be used in the field

Increasing precipitation variability on daily-to-multiyear timescales in a warmer world

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper, supplementary materials, and/or linked repositories. The GPCP precipitation data is acquired from https://climatedataguide.ucar.edu/climate-data/gpcp-daily-global precipitation-climatology-project. The IMERG precipitation data is acquired from https://gpm.nasa.gov/data/directory. For the HadGEM3-GC3.05 PPE simulations, two-dimensional fields can be accessed from https://catalogue.ceda.ac.uk/uuid/f1a2fc3c120f400396a92f5de84d596a, and post-processed three dimensional fields can be accessed from https://doi.org/10.7910/DVN/GHWGG0.The hydrological cycle intensifies under global warming with precipitation increases. How the increased precipitation varies temporally at a given location has vital implications for regional climates and ecosystem services. Based on ensemble climate model projections under a high emission scenario, here we show that approximately two-thirds of land on Earth will face a “wetter and more variable” hydroclimate on daily to multiyear timescales. This means wider swings between wet and dry extremes. Such an amplification of precipitation variability is particularly prominent over climatologically wet regions, with percentage increases in variability more than twice those in mean precipitation. Thermodynamic effects, linked to increased moisture availability, increase precipitation variability uniformly everywhere. It is the dynamic effects (negative) linked to weakened circulation variability that make precipitation variability changes strongly region dependent. The increase in precipitation variability poses a new challenge to the climate resilience of infrastructures and human society.National Natural Science Foundation of ChinaChina Postdoctoral Science FoundationInternational Partnership Program of Chinese Academy of SciencesUK–China Research Innovation Partnership Fun

Light smoking at base-line predicts a higher mortality risk to women than to men; evidence from a cohort with long follow-up

BACKGROUND: There is conflicting evidence as to whether smoking is more harmful to women than to men. The UK Cotton Workers’ Cohort was recruited in the 1960s and contained a high proportion of men and women smokers who were well matched in terms of age, job and length of time in job. The cohort has been followed up for 42 years. METHODS: Mortality in the cohort was analysed using an individual relative survival method and Cox regression. Whether smoking, ascertained at baseline in the 1960s, was more hazardous to women than to men was examined by estimating the relative risk ratio women to men, smokers to never smoked, for light (1–14), medium (15–24), heavy (25+ cigarettes per day) and former smoking. RESULTS: For all-cause mortality relative risk ratios were 1.35 for light smoking at baseline (95% CI 1.07-1.70), 1.15 for medium smoking (95% CI 0.89-1.49) and 1.00 for heavy smoking (95% CI 0.63-1.61). Relative risk ratios for light smoking at baseline for circulatory system disease was 1.42 (95% CI 1.01 to 1.98) and for respiratory disease was 1.89 (95% CI 0.99 to 3.63). Heights of participants provided no explanation for the gender difference. CONCLUSIONS: Light smoking at baseline was shown to be significantly more hazardous to women than to men but the effect decreased as consumption increased indicating a dose response relationship. Heavy smoking was equally hazardous to both genders. This result may help explain the conflicting evidence seen elsewhere. However gender differences in smoking cessation may provide an alternative explanation

Robust observational constraint of uncertain aerosol processes and emissions in a climate model and the effect on aerosol radiative forcing

The effect of observational constraint on the ranges of uncertain physical and chemical process parameters was explored in a global aerosol–climate model. The study uses 1 million variants of the Hadley Centre General Environment Model version 3 (HadGEM3) that sample 26 sources of uncertainty, together with over 9000 monthly aggregated grid-box measurements of aerosol optical depth, PM2.5, particle number concentrations, sulfate and organic mass concentrations. Despite many compensating effects in the model, the procedure constrains the probability distributions of parameters related to secondary organic aerosol, anthropogenic SO2 emissions, residential emissions, sea spray emissions, dry deposition rates of SO2 and aerosols, new particle formation, cloud droplet pH and the diameter of primary combustion particles. Observational constraint rules out nearly 98 % of the model variants. On constraint, the ±1σ (standard deviation) range of global annual mean direct radiative forcing (RFari) is reduced by 33 % to −0.14 to −0.26 W m−2, and the 95 % credible interval (CI) is reduced by 34 % to −0.1 to −0.32 W m−2. For the global annual mean aerosol–cloud radiative forcing, RFaci, the ±1σ range is reduced by 7 % to −1.66 to −2.48 W m−2, and the 95 % CI by 6 % to −1.28 to −2.88 W m−2. The tightness of the constraint is limited by parameter cancellation effects (model equifinality) as well as the large and poorly defined “representativeness error” associated with comparing point measurements with a global model. The constraint could also be narrowed if model structural errors that prevent simultaneous agreement with different measurement types in multiple locations and seasons could be improved. For example, constraints using either sulfate or PM2.5 measurements individually result in RFari±1σ ranges that only just overlap, which shows that emergent constraints based on one measurement type may be overconfident

Randomised controlled trial of GM-CSF in critically ill patients with impaired neutrophil phagocytosis

Background. Critically ill patients with impaired neutrophil phagocytosis have significantly increased risk of nosocomial infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) improves phagocytosis by neutrophils ex vivo. This study tested the hypothesis that GM-CSF improves neutrophil phagocytosis in critically ill patients in whom phagocytosis is known to be impaired Methods. This was a multi-centre, phase 2a randomised, placebo-controlled clinical trial Using a personalised medicine approach, only critically ill patients with impaired neutrophil phagocytosis were included. Patients were randomised 1:1 to subcutaneous GM-CSF (3 microgrammws/kg/day) or placebo, once daily for 4 days. The primary outcome measure was neutrophil phagocytosis 2 days after initiation of GM-CSF. Secondary outcomes included neutrophil phagocytosis over time, neutrophil functions other than phagocytosis, monocyte HLA-DR expression, and safety. Results. Thirty-eight patients were recruited from 5 intensive care units (17 randomised to GM-CSF). Mean neutrophil phagocytosis at day 2 was 57.2% (SD 13.2%) in the GM-CSF group and 49.8% (13.4%) in the placebo group, p=0.73. The proportion of patients with neutrophil phagocytosis >50% at day 2, and monocyte HLA-DR, appeared significantly higher in the GM-CSF group. Neutrophil functions other than phagocytosis did not appear significantly different between the groups. The most common adverse event associated with GM-CSF was pyrexia. Conclusions. GM-CSF did not improve mean neutrophil phagocytosis at day 2, but was safe and appeared to increase the proportion of patients with adequate phagocytosis. The study suggests proof of principle for a pharmacological effect on neutrophil function in a subset of critically ill patients.This work was funded by a grant from the Medical Research Council (G1100233), with additional support from the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre. It was sponsored by Newcastle Universit

Nile red fluorescence screening facilitating neutral lipid phenotype determination in budding yeast, Saccharomyces cerevisiae, and the fission yeast Schizosaccharomyces pombe.

Investigation of yeast neutral lipid accumulation is important for biotechnology and also for modelling aberrant lipid metabolism in human disease. The Nile red (NR) method has been extensively utilised to determine lipid phenotypes of yeast cells via microscopic means. NR assays have been used to differentiate lipid accumulation and relative amounts of lipid in oleaginous species but have not been thoroughly validated for phenotype determination arising from genetic modification. A modified NR assay, first described by Sitepu et al. (J Microbiol Methods 91:321-328, 2012), was able to detect neutral lipid changes in Saccharomyces cerevisiae deletion mutants with sensitivity similar to more advanced methodology. We have also be able to, for the first time, successfully apply the NR assay to the well characterised fission yeast Schizosaccharomyces pombe, an increasingly important organism in biotechnology. The described NR fluorescence assay is suitable for increased throughput and rapid screening of genetically modified strains in both the biotechnology industry and for modelling ectopic lipid production for a variety of human diseases. This ultimately negates the need for labour intensive and time consuming lipid analyses of samples that may not yield a desirable lipid phenotype, whilst genetic modifications impacting significantly on the cellular lipid phenotype can be further promoted for more in depth analyses

Management and treatment of children, young people and adults with systemic lupus erythematosus: British Society for Rheumatology guideline scope

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.The objective of this guideline is to provide up-to-date, evidence-based recommendations for the management of SLE that builds upon the existing treatment guideline for adults living with SLE published in 2017. This will incorporate advances in the assessment, diagnosis, monitoring, non-pharmacological and pharmacological management of SLE. General approaches to management as well as organ-specific treatment, including lupus nephritis and cutaneous lupus, will be covered. This will be the first guideline in SLE using a whole life course approach from childhood through adolescence and adulthood. The guideline will be developed with people with SLE as an important target audience in addition to healthcare professionals. It will include guidance related to emerging approved therapies and account for National Institute for Health and Care Excellence Technology Appraisals, National Health Service England clinical commissioning policies and national guidance relevant to SLE. The guideline will be developed using the methods and rigorous processes outlined in ‘Creating Clinical Guidelines: Our Protocol’ by the British Society for Rheumatology