195 research outputs found

    The geochemical controls on anaerobic microbial ecology in a phenol-contaminated sandstone aquifer.

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    The Permo-Triassic sandstone aquifer is one of the most important drinking water resources in the UK. Beneath the Four Ashes site, the aquifer is contaminated with toxic levels of phenolic compounds and inorganic species. Although the hydrochemistry of the groundwater has been fully characterised, no research has assessed contaminant plume development with time using full groundwater profiles. Also, studies have investigated the aerobic microbial ecology at the site, but no research has assessed the anaerobic communities. Anaerobes are important for the remediation of the contamination, as the majority of the contaminated groundwater is anoxic. Furthermore, research has demonstrated that the structure of planktonic (free-living) eubacterial communities at 30m below ground level (mbgl) differ significantly from the community attached to quartz sand suspended in the aquifer at the same depth. However, the diverse mineralogical matrices in sandstones may influence microbial attachment, and therefore the communities attached to quartz may not be representative of the true indigenous attached communities. The aim of this thesis was to update the knowledge on the groundwater hydrochemistry, and to investigate the effects of contaminant load and substratum properties on microbial attachment and anaerobic microbial ecology. Groundwater samples were taken from multiple depths using 2 depth-discrete boreholes. Concentrations of phenolic compounds in the groundwater were measured using high performance liquid chromatography, and inorganic species were measured by ion chromatography. Chemical profiles show that the groundwater hydrochemistry at borehole 59 (130m from source) remained stable between 1998 and July 2009. However, the data reveals that the distribution of the contaminants changed in August 2009, due to the onset of the pump and treat remediation strategy implemented at the site. Data from borehole 60 (350m from source) shows that the concentration of total phenolics increased markedly at 42- 45mbgl between 1998 and 2009, due to variations in contaminant spillage on site, potentially resulting in the plume extending further than the deepest sampling point (45mbgl). Denaturing gradient gel electrophoresis (DGGE) of amplified 165 rRNA, napA (nitrate-reductase) and dsrB (dissimilatory sulphate reductase) reveal that the structure of eubacterial and anaerobic communities varied with depth down the groundwater profile, and were therefore influenced by contaminant load. The DGGE profiles of planktonic communities were compared to the communities attached to 3 different geological substrata suspended in the aquifer under the same hydrochemical conditions (i.e. same depth). Profiles reveal that the planktonic communities were highly dissimilar to the attachment communities on all surfaces, and at all samplings. Furthermore, DGGE profiles of the attached communities were compared. Results reveal that the communities attached to 5hap granite and sandstone cluster separately to the community attached to quartz, suggesting that substratum properties are an important control governing microbial attachment. This was investigated by quantifying microbial attachment to 6 different geological coupons (apatite, 5hap granite, hematite, orthoclase, quartz and shale) suspended in the aquifer. Each coupon provided different physiochemical conditions (hydrophobicity, surface charge and nutrient chemistry) to the system. Results indicate that the most extensive attachment was on coupons that contained at least one microbial growth nutrient (Ca, P, K, Na, Fe, Mn); hematite, apatite, orthoclase and particularly 5hap granite, which contains the most nutrients. The least attachment was witnessed on the quartz surface, which contains no microbial nutrients. Quartz has similar surface charge and roughness to orthoclase, and a similar hydrophobicity to the 5hap granite. The only difference between the surfaces is nutrient availability. This confirms that substratum chemistry, in particular nutrient content, is a major control on microbial attachment

    A comparative study of open and closed heat-engines for small-scale CHP applications

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    In this paper the authors compare and contrast open and closed-cycle heat engines. First of all, by way of example and to aid discussion, the performance of proprietary externally heated closed-cycle Stirling engines is compared with that of internally heated open Otto cycle engines. Both types of engine have disadvantages and merits and this suggested that in order to accommodate the best of both engine types an externally-heated open-cycle engine might offer a more satisfactory solution for small-scale combined heat and power (CHP) systems. To investigate this possibility further the paper goes on to compare the performance of externally-heated and recuperated Joule hot-air cycle engines with that of an externally-heated closed Stirling cycle engines. The results show that an externally heated recuperated open Joule cycle engine can exceed that of a closed cycle Stirling engine operating between the same heat source and sink temperatures when a variable temperature heat source is used

    Public attitudes to, and perceived impacts of 20mph (32 km/h) speed limits in Edinburgh:An exploratory study using the Speed Limits Perceptions Survey (SLiPS)

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    The ‘Is 20 plenty for health?’ study is funded by a National Institute for Health Research (NIHR) Public Health Research (PHR) grant 15/82/12.Between 2016 and 2018 a policy was implemented to increase the proportion of 20mph (32km/h) streets in Edinburgh, UK from approximately 50% to 80%, providing the opportunity to evaluate how behaviour and public perceptions change over time. This is important as negative public responses have been reported to limit the implementation of transport policies and may reduce the effectiveness of the policy. The Speed Limits Perception Survey (SLiPS) was developed to assess changes in public perceptions from baseline to 6 and 12 months post-implementation. We collected 3,485 individual responses to the survey, 64.6% (n = 2,253) of which included complete perceptions data. Using exploratory factor analysis, the following perception factors were identified: i) Detraction and resistance, ii) Support, iii) Rule following, iv) Child safety, and v) Walking safety. Following the 20mph implementation at 6–12 months: Support (ii) and Rule following (iii) had increased; Detraction and resistance (i) had decreased; and Child safety (iv) and Walking safety (v) had not changed significantly. These findings indicate that the public in Edinburgh became more positive towards the policy once it was implemented. However, more extensive policy or ongoing communication of the safety benefits of 20mph limits are needed to increase perceptions of safety that might lead to increased walking and cycling. Future research should aim to understand how those implementing speed limit interventions can positively influence public perceptions and how public perceptions about speed limits influence behaviour.Publisher PDFPeer reviewe

    Pediatric high-grade glioma: biologically and clinically in need of new thinking.

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    High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management

    Inducing energetic switching using Klotho improves vascular smooth muscle cell phenotype

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    The cardiovascular disease of atherosclerosis is characterised by aged vascular smooth muscle cells and compromised cell survival. Analysis of human and murine plaques highlights markers of DNA damage such as p53, Ataxia telangiectasia mutated (ATM), and defects in mitochondrial oxidative metabolism as significant observations. The antiageing protein Klotho could prolong VSMC survival in the atherosclerotic plaque and delay the consequences of plaque rupture by improving VSMC phenotype to delay heart attacks and stroke. Comparing wild-type VSMCs from an ApoE model of atherosclerosis with a flox’d Pink1 knockout of inducible mitochondrial dysfunction we show WT Pink1 is essential for normal cell viability, while Klotho mediates energetic switching which may preserve cell survival. Methods: Wild-type ApoE VSMCs were screened to identify potential drug candidates that could improve longevity without inducing cytotoxicity. The central regulator of cell metabolism AMP Kinase was used as a readout of energy homeostasis. Functional energetic switching between oxidative and glycolytic metabolism was assessed using XF24 technology. Live cell imaging was then used as a functional readout for the WT drug response, compared with Pink1 (phosphatase-and-tensin-homolog (PTEN)-induced kinase-1) knockout cells. Results: Candidate drugs were assessed to induce pACC, pAMPK, and pLKB1 before selecting Klotho for its improved ability to perform energetic switching. Klotho mediated an inverse dose-dependent effect and was able to switch between oxidative and glycolytic metabolism. Klotho mediated improved glycolytic energetics in wild-type cells which were not present in Pink1 knockout cells that model mitochondrial dysfunction. Klotho improved WT cell survival and migration, increasing proliferation and decreasing necrosis independent of effects on apoptosis. Conclusions: Klotho plays an important role in VSMC energetics which requires Pink1 to mediate energetic switching between oxidative and glycolytic metabolism. Klotho improved VSMC phenotype and, if targeted to the plaque early in the disease, could be a useful strategy to delay the effects of plaque ageing and improve VSMC survival

    Evaluating the citywide Edinburgh 20mph speed limit intervention effects on traffic speed and volume: A pre-post observational evaluation.

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    OBJECTIVES: Traffic speed is important to public health as it is a major contributory factor to collision risk and casualty severity. 20mph (32km/h) speed limit interventions are an increasingly common approach to address this transport and health challenge, but a more developed evidence base is needed to understand their effects. This study describes the changes in traffic speed and traffic volume in the City of Edinburgh, pre- and 12 months post-implementation of phased city-wide 20mph speed limits from 2016-2018. METHODS: The City of Edinburgh Council collected speed and volume data across one full week (24 hours a day) pre- and post-20mph speed limits for 66 streets. The pre- and post-speed limit intervention data were compared using measures of central tendency, dispersion, and basic t-tests. The changes were assessed at different aggregations and evaluated for statistical significance (alpha = 0.05). A mixed effects model was used to model speed reduction, in the presence of key variables such as baseline traffic speed and time of day. RESULTS: City-wide, a statistically significant reduction in mean speed of 1.34mph (95% CI 0.95 to 1.72) was observed at 12 months post-implementation, representing a 5.7% reduction. Reductions in speed were observed throughout the day and across the week, and larger reductions in speed were observed on roads with higher initial speeds. Mean 7-day volume of traffic was found to be lower by 86 vehicles (95% CI: -112 to 286) representing a reduction of 2.4% across the city of Edinburgh (p = 0.39) but with the direction of effect uncertain. CONCLUSIONS: The implementation of the city-wide 20mph speed limit intervention was associated with meaningful reductions in traffic speeds but not volume. The reduction observed in road traffic speed may act as a mechanism to lessen the frequency and severity of collisions and casualties, increase road safety, and improve liveability

    Use of natural experimental studies to evaluate 20mph speed limits in two major UK cities.

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    INTRODUCTION: Reductions in traffic speed can potentially offer multiple health and public health benefits. In 2016, implementation of 20mph (30kph) speed limit interventions began in Edinburgh (city-wide) and Belfast (city centre). The aims of this paper are to describe 1) the broad theoretical approach and design of two natural experimental studies to evaluate the 20mph speed limits in Edinburgh and Belfast and 2) how these studies allowed us to test and explore theoretical mechanisms of 20mph speed limit interventions. METHODS: The evaluation consisted of several work packages, each with different research foci, including the political decision-making processes that led to the schemes, their implementation processes, outcomes (including traffic speed, perceptions of safety, and casualties) and cost effectiveness. We used a combination of routinely and locally collected quantitative data and primary quantitative and qualitative data. RESULTS: The evaluation identified many contextual factors influencing the likelihood of 20mph speed limits reaching the political agenda. There were substantial differences between the two sites in several aspects related to implementation. Reductions in speed resulted in significant reductions in collisions and casualties, particularly in Edinburgh, which had higher average speed at baseline. The monetary value of collisions and casualties prevented are likely to exceed the costs of the intervention and thus the overall balance of costs and benefits is likely to be favourable. CONCLUSIONS: Innovative study designs, including natural experiments, are important for assessing the impact of 'real world' public health interventions. Using multiple methods, this project enabled a deeper understanding of not only the effects of the intervention but the factors that explain how and why the intervention and the effects did or did not occur. Importantly it has shown that 20mph speed limits can lead to reductions in speed, collisions and casualties, and are therefore an effective public health intervention

    Developing and implementing 20-mph speed limits in Edinburgh and Belfast : mixed-methods study

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    This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme.Background Transport initiatives such as 20-mph (≈30-km/h) speed limits are anticipated to result in fewer road casualties and improve perceptions of safety, leading to increases in active travel. Lower speeds may also lead to more pleasant environments in which to live, work and play. Objectives The main objective was to evaluate and understand the processes and effects of developing and implementing 20-mph speed limits in Edinburgh and Belfast. The focus was on health-related outcomes (casualties and active travel) that may lead to public health improvements. An additional objective was to investigate the political and policy factors (conditions) that led to the decision to introduce the new speed limits. Design This was a mixed-methods study that comprised an outcome, process, policy and economic evaluation of two natural experiments. Setting The study was set in Edinburgh, Scotland, and Belfast, Northern Ireland, from 2000 to 2018. Participants The whole population of each city were participants, as well as stakeholders involved in implementation and decision-making processes. Intervention The intervention was the implementation of 20-mph legislation, signage, enforcement, and education and awareness-raising in Edinburgh (citywide) and Belfast (city centre). Main outcome measures The main outcomes measured were speed; number, type and severity of road collisions; perceptions; and liveability. Data sources The following data sources were used – routinely and locally collected quantitative data for speed, volume of traffic, casualties and collisions, and costs; documents and print media; surveys; interviews and focus groups; and Google Street View (Google Inc., Mountain View, CA, USA). Results Collisions and casualties – the overall percentage reduction in casualty rates was 39% (the overall percentage reduction in collision rates was 40%) in Edinburgh. The percentage reduction for each level of severity was 23% for fatal casualties, 33% for serious casualties and 37% for minor casualties. In Belfast there was a 2% reduction in casualties, reflecting differences in the size, reach and implementation of the two schemes. Perceptions – in Edinburgh there was an increase in two factors (support for 20 mph and rule-following after implementation) supported by the qualitative data. Liveability – for both cities, there was a small statistical increase in liveability. Speed – mean and median speeds reduced by 1.34 mph and 0.47 mph, respectively, at 12 months in Edinburgh, with no statistically significant changes in Belfast. History, political context, local policy goals, local priorities and leadership influenced decision-making and implementation in the two cities. Limitations There was no analysis of active travel outcomes because the available data were not suitable.  Conclusions The pre-implementation period is important. It helps frame public and political attitudes. The scale of implementation and additional activities in the two cities had a bearing on the impacts. The citywide approach adopted by Edinburgh was effective in reducing speeds and positively affected a range of public health outcomes. The city-centre approach in Belfast (where speeds were already low) was less effective. However, the main outcome of these schemes was a reduction in road casualties at all levels of severity.  Future work Future work should develop a statistical approach to public health interventions that incorporates variables from multiple outcomes. In this study, each outcome was analysed independently of each other. Furthermore, population measures of active travel that can be administered simply, inexpensively and at scale should be developed. Study registration This study is registered as ISRCTN10200526. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 9. See the NIHR Journals Library website for further project information.Publisher PDFPeer reviewe
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