2,107 research outputs found

    The potential impact of BCG vaccine supply shortages on global paediatric tuberculosis mortality.

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    BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is provided to over 100 million neonates annually to protect against childhood tuberculosis (TB). Recent BCG manufacturing interruptions highlight global supply risks. We estimated the potential impact of BCG shortfalls on global paediatric (<15 years) TB mortality. METHODS: A static mathematical model was employed to estimate the number of paediatric TB deaths avoided by usual levels of BCG coverage, and potential additional TB deaths in the first 15 years of life due to 1-year BCG supply shortfalls of 6.3 % (as occurred in 2015) to 27.6 % (as anticipated without mitigating action in 2015) assuming no catch-up campaigns. RESULTS: BCG coverage without shortfalls, estimated at 90 % globally, was estimated to avoid 117,132 (95 % uncertainty range (UR): 5049-306,911) TB deaths globally per birth cohort in the first 15 years of life. An estimated 11,713 (UR: 505-30,691) additional TB deaths would occur in the first 15 years of life per 10 % (26 million dose) annual supply shortfall. A 16.5 million dose (6.3 %) shortfall as reported at the close of 2015, reflecting 84 % global coverage, was estimated as associated with 7433 (95 % UR: 320-19,477) excess TB deaths in the affected cohort in the first 15 years. A possible 24,914 (UR: 1074-65,278) additional deaths were avoided due to prompt shortfall reduction measures in 2015. CONCLUSIONS: BCG shortages could greatly increase paediatric TB mortality. Although rapid action in 2015 minimised BCG shortfalls, avoiding a large number of potential additional deaths, the possible public health impact of even relatively small shortfalls highlights the critical importance of ensuring secure future manufacturing capacity and global BCG supply continuity

    Transient simulations of the last 22,000 years, with a fully dynamic atmosphere in the GENIE earth-system framework

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    This paper presents and discusses an ensemble of transient model simulations from the Last Glacial Maximum to present-day. The model includes a fully dynamic, primitive equation atmosphere (the Reading IGCM), computed vegetation (TRIFFID), and a slab-ocean and seaice. The atmospheric model is more akin to a low-resolution GCM than traditional EMICS, and yet is fast enough for long ensemble simulations to be carried out. The model is tuned in a purely objective manner, using a genetic algorithm, which perturbs 30 tunable paramters in the model to find the best fit to a prescribed pre-industrial climate.The control deglaciation experiment has good agreement with data at the Last glacial Maximum and mid-Holocene. The deglaciation ensembles are over initial conditions, physical processes, and tunable model parameters. The ice-sheets are prescribed, and changes in oceanic heat transport are neglected, and yet the model exhibits rapid transitions in many of the ensemble members. These are attributable to the interaction of the dynamic atmosphere with the sea-ice, and are not observed when the ocean and sea-ice surface temperatures are prescribed. The timing of these transitions is sensitive to the initial conditions, pointing to the chaotic nature of the climate system.The simulations have been carried out making use of GRID technologies, developed as part of the GENIE project

    Anoxic nitrification in marine sediments

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    Nitrate peaks are found in pore-water profiles in marine sediments at depths considerably below the conventional zone of oxic nitrification. These have been interpreted to represent nonsteady- state effects produced by the activity of nitrifying bacteria, and suggest that nitrification occurs throughout the anoxic sediment region. In this study, ΣNO3 peaks and molecular analysis of DNA and RNA extracted from anoxic sediments of Loch Duich, an organic-rich marine fjord, are consistent with nitrification occurring in the anoxic zone. Analysis of ammonia oxidiser 16S rRNA gene fragments amplified from sediment DNA indicated the abundance of autotrophic ammonia-oxidising bacteria throughout the sediment depth sampled (40 cm), while RT-PCR analysis indicated their potential activity throughout this region. A large non-steady-state pore-water ΣNO3 peak at ~21 cm correlated with discontinuities in this ammonia-oxidiser community. In addition, a subsurface nitrate peak at ~8 cm below the oxygen penetration depth, correlated with the depth of a peak in nitrification rate, assessed by transformation of 15N-labelled ammonia. The source of the oxidant required to support nitrification within the anoxic region is uncertain. It is suggested that rapid recycling of N is occurring, based on a coupled reaction involving Mn oxides (or possibly highly labile Fe oxides) buried during small-scale slumping events. However, to fully investigate this coupling, advances in the capability of high-resolution pore-water techniques are required

    Development of a tunable diode laser absorption spectrometer for measurement of the 13C/12C ratio in methane

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    A tunable diode laser absorption spectrometer (TDLAS) for measuring the ratio in methane has been developed. Using a triple path arrangement the spectra of the CH4 sample, a isotope standard and pure 13CH4 are recorded simultaneously and compared to evaluate the ratio of the sample, using a 13CH4---12CH4 absorption line pair near 3007 cm−1. Systematic effects due to variations in temperature, pressure, and optical density were measured for this rotational-vibrational transition pair. Optical interference effects are effectively suppressed by linearly polarizing the laser beam and using Brewster windows for gas cells and detectors. The overall δ13C accuracy vs. the PDB scale is about ± 1 ‰ for a CH4 concentration of 2.5 % (sample size: 5 μmoles = 0.11 STP cm3 CH4) using 36 cm long absorption cells. The future application of a multipass cell should allow measurement concentrations of CH4 down to about 50 ppm. The main advantages of the new method are the short measurement time of 10–15 min for one sample and the direct measurement on the CH4 molecule without the need to chemically convert it to CO2. With the present accuracy the new method should be useful for the measurement of CH4 sources, allowing a greater sample throughput compared to the conventional mass spectrometry technique

    Impact of calibration algorithms on hypoglycaemia detection in newborn infants using continuous glucose monitors

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    invited, 6-pagesNeonatal hypoglycaemia is a common condition that can cause seizures and serious brain injury in infants. It is diagnosed by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) devices can potentially improve hypoglycaemia detection, while reducing the number of BG measurements. Calibration algorithms convert the sensor signal into the CGM output. Thus, these algorithms can have a direct impact on measures used to quantify excursions from normal glycaemic levels. The aim of this study was to quantify the effects of calibration sensor error and non-linear filtering of CGM data on measures of hypoglycaemia (defined as BG < 2.6mmol/L) in neonates. CGM data was recalibrated using an algorithm that explicitly recognised the high accuracy of BG measurements available in this study. Median filtering was also implemented either before or after recalibration. Results for the entire cohort show an increase in the total number of hypoglycaemic events (161 to 193), duration of hypoglycaemia (2.2 to 2.6% of total data), and hypoglycaemic index (4.9 to 7.1µmol/L) after recalibration. With the addition of filtering, the number of hypoglycaemic events was reduced (193 to 131), with little or no change to the other metrics. These results show how reference sensor error and thus calibration algorithms play a significant role in quantifying hypoglycaemia. In particular, metrics such as counting the number of hypoglycaemic events were particularly sensitive to recalibration and filtering effects. While this conclusion might be expected, its potential impact is quantified here, in this case for at-risk neonates for whom hypoglycaemia carries potential long-term negative outcomes

    Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care

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    Background: poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3.Methods: 1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control.Results: the prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to &lt;60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p?&lt;?0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p?&lt;?0.001) for people &gt;80 compared to?&lt;?60).Conclusions: suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects.<br/

    A case of mistaken identity – reappraisal of the species of canid and felid hookworms (Ancylostoma) present in Australia and India

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    This study serves to clarify the current status of canid and felid Ancylostoma species present in Australia. The morphological identification of A. ceylanicum from cats for the first time in Townsville, Australia, appears to be in error, together with the genetic markers provided for the species. Morphological and genetic data presented herein provide strong evidence that the hookworms from cats in Towsville are not A. ceylanicum as previously identified (i.e. the first report of this species in Australia), but are A. braziliense. Therefore the subsequent genetic markers established for A. ceylanicum in subsequent molecular studies based on these Townsville specimens should also be attributed to A. braziliense. Based on this information, a study of canine hookworm species present in northern India is also in error and it is apparent that the hookworms found in this region are those of A. ceylanicum. The distribution of A. braziliense and A. ceylanicum in the Americas and Asia Pacific region is discussed together with the importance of combining parasite morphology with genetic data for parasite diagnosis in epidemiological studies

    A case of mistaken identity – reappraisal of the species of canid and felid hookworms (Ancylostoma) present in Australia and India

    Get PDF
    This study serves to clarify the current status of canid and felid Ancylostoma species present in Australia. The morphological identification of A. ceylanicum from cats for the first time in Townsville, Australia, appears to be in error, together with the genetic markers provided for the species. Morphological and genetic data presented herein provide strong evidence that the hookworms from cats in Towsville are not A. ceylanicum as previously identified (i.e. the first report of this species in Australia), but are A. braziliense. Therefore the subsequent genetic markers established for A. ceylanicum in subsequent molecular studies based on these Townsville specimens should also be attributed to A. braziliense. Based on this information, a study of canine hookworm species present in northern India is also in error and it is apparent that the hookworms found in this region are those of A. ceylanicum. The distribution of A. braziliense and A. ceylanicum in the Americas and Asia Pacific region is discussed together with the importance of combining parasite morphology with genetic data for parasite diagnosis in epidemiological studies
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