27 research outputs found

    A Geologically Based Indoor-Radon Potential Map of Kentucky

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    We combined 71,930 short-term (median duration 4 days) home radon test results with 1:24,000-scale bedrock geologic map coverage of Kentucky to produce a statewide geologically based indoor-radon potential map. The test results were positively skewed with a mean of 266 Bq/m3, median of 122 Bq/m3, and 75th percentile of 289 Bq/m3. We identified 106 formations with ≄10 test results. Analysis of results from 20 predominantly monolithologic formations showed indoor-radon concentrations to be positively skewed on a formation-by-formation basis, with a proportional relationship between sample means and standard deviations. Limestone (median 170 Bq/m3) and dolostone (median 130 Bq/m3) tended to have higher indoor-radon concentrations than siltstones and sandstones (median 67 Bq/m3) or unlithified surficial deposits (median 63 Bq/m3). Individual shales had median values ranging from 67 to 189 Bq/m3; the median value for all shale values was 85 Bq/m3. Percentages of values falling above the U.S. Environmental Protection Agency (EPA) action level of 148 Bq/m3 were sandstone and siltstone: 24%, unlithified clastic: 21%, dolostone: 46%, limestone: 55%, and shale: 34%. Mississippian limestones, Ordovician limestones, and Devonian black shales had the highest indoor-radon potential values in Kentucky. Indoor-radon test mean values for the selected formations were also weakly, but statistically significantly, correlated with mean aeroradiometric uranium concentrations. To produce a map useful to nonspecialists, we classified each of the 106 formations into five radon-geologic classes on the basis of their 75th percentile radon concentrations. The statewide map is freely available through an interactive internet map service

    Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

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    Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation

    Further data on sipuleucel-T immunotherapy

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    Health implications of radon distribution in living rooms and bedrooms in U.K. dwellings – a case study in Northamptonshire

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    Environmental radon exposure of residents of domestic premises in the United Kingdom (UK) and elsewhere in Europe is estimated on the basis of the measured radon concentrations in, and the relative occupancies of, the principal living room and bedroom. While studies on radon concentration variability in the individual units in apartment blocks in various countries have been described, little data has been reported on variability in two-storey single-family dwellings, and the majority of extant studies consolidate living room and bedroom data early in the analysis. To investigate this further, detailed analysis was made of radon concentration data from a set of thirty-four homes situated in areas of Northamptonshire known to exhibit high radon levels. All homes were of typical UK construction of brick/block/stone walls under a pitched tile/slate roof. Approximately 50% of the sample were detached houses, the remainder being semi-detached (duplex) or terraced (row-house). Around 25% of the sample possessed cellars, while 12% were single-storey dwellings (bungalows), reflecting the typical incidence of this type of dwelling in England. In the two-storey homes, all monitored bedrooms were on the upper floor. Distribution of the ratios of bedroom/living room radon concentrations (BR/LR ratio) in individual properties was left-skewed (mean 0.67, median 0.73, range 0.05–1.05) with a tail extending to just above 1.0. The mean is consistent with the outcome of earlier extensive studies in England, while the variability depends principally on the characteristics of the property, and not on seasonal factors. In a small set of homes, the BR/LR ratio was anomalously low, (mean 0.3). BR/LR ratios in single-storey homes clustered around a value of 1.0, indicating that house design, rather than lifestyle, is the dominant factor in determining bedroom radon concentrations. Homes with higher mean annual radon concentrations showed lower BR/LR ratios, supporting our proposal that, in some homes, radon emanation from building materials may comprise a significant component of the overall radon level

    Radon remediation of a two-storey UK dwelling by active sub-slab depressurisation: effects and health implications of radon concentration distributions

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    Radon concentration levels in a two-storey detached single-family dwelling in Northamptonshire, UK, were monitored continuously throughout a 5-week period during which active sub-slab depressurisation remediation measures were installed. Remediation of the property was accomplished successfully, with both the mean radon levels and the diurnal variability greatly reduced both upstairs and downstairs. Following remediation, upstairs and downstairs radon concentrations were 33% and 18% of their pre-remediation values respectively: the mean downstairs radon concentration was lower than that upstairs, with pre- and post-remediation values of the upstairs/downstairs concentration ratio, RU/D, of 0.81 and 1.51 respectively. Cross-correlation between upstairs and downstairs radon concentration time-series indicates a time-lag of the order of 1 h or less, suggesting that diffusion of soil-derived radon from downstairs to upstairs either occurs within that time frame or forms a relatively insignificant contribution to the upstairs radon level. Cross-correlation between radon concentration time-series and the corresponding time-series for local atmospheric parameters demonstrated correlation between radon concentrations and internal/external pressure difference prior to remediation; this correlation disappears following remediation. Overall, these observations provide further evidence that radon concentration levels within a dwelling are not necessarily wholly determined by the effects of soil–gas advection, and further support the suggestion that, depending on the precise content of the building materials, upstairs radon levels, in particular, may be dominated by radon exhalation from the walls of the dwelling, especially in areas of low soil–gas rado

    Lowering the UK domestic radon action level to prevent more lung cancers – is it cost-effective?

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    Case studies have shown that radon gas can accumulate within domestic properties at sufficiently high levels that it can cause lung cancer, and recent studies have suggested that this risk remains significant below the UK domestic Action Level of 200 Bq m−3. Raised radon levels can be reduced by engineering measures, and it has been shown that domestic radon remediation programmes in UK Affected Areas can result in reduced risks to the population and can be cost-effective. We consider here the benefits and costs of the domestic radon remediation programme in Northamptonshire, UK, and consider the implications for that programme of reducing the UK Action Level below its present value. A radon remediation programme based on an Action Level above 200 Bq m−3 will cost less and will target those most at risk, but will be less cost-effective and will lead to higher residual dose and greater risk of cancer in the remaining population. Reducing the Action Level below 200 Bq m−3 will prevent more cancers, but at significantly higher cost. It will also be less cost-effective, because remediation of a significant number of houses with moderate radon levels will provide only a modest health benefit to occupants. Overall, a completed radon remediation programme of the type implemented in Northamptonshire is most cost-effective for an Action Level between 200 and 300 Bq m−3. The implications for future health policy are discusse

    A detailed evaluation of the individual health benefits arising in a domestic property following radon remediation – a case-study in Northamptonshire, U.K.

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    Radon gas occurs naturally in the environment with variable distribution, concentrating sufficiently in the built environment in some areas to pose a public health risk. Radon levels can be successfully reduced in affected buildings, and large-scale remediation programmes have been justified in terms of accrued costs and benefits. We present results from a house where radon levels in the main living-room and master bedroom were monitored on an hourly basis over extended periods before and after radon remediation by sub-slab depressurisation. These results were combined with results from a recent occupancy survey to estimate the health impact on occupants spending varying times in the home. Prior to remediation, mean hourly radon exposure is moderately linearly correlated (R2 = 0.66–0.78) with time spent in the house. Following remediation, correlation is significantly enhanced (R2 = 0.91–0.95), but the exposure reduction of an occupant following remediation is less than that predicted using the NRPB protoco

    Radon mitigation in domestic properties and its health implications - a comparison between during-construction and post-construction radon reduction

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    Although United Kingdom (UK) Building Regulations applicable to houses constructed since 1992 in Radon Affected Areas address the health issues arising from the presence of radon in domestic properties and specify the installation of radon-mitigation measures during construction, no legislative requirement currently exists for monitoring the effectiveness of such remediation once construction is completed and the houses are occupied. To assess the relative effectiveness of During-Construction radon reduction and Post-Construction remediation, radon concentration data from houses constructed before and after 1992 in Northamptonshire, UK, a designated Radon Affected Area, was analysed. Post-Construction remediation of 73 pre-1992 houses using conventional fan-assisted sump technology proved to be extremely effective, with radon concentrations reduced to the Action Level, or below, in all cases. Of 64 houses constructed since 1992 in a well-defined geographical area, and known to have had radon-barrier membranes installed during construction, 11% exhibited radon concentrations in excess of the Action Level. This compares with the estimated average for all houses in the same area of 17%, suggesting that, in some 60% of the houses surveyed, installation of a membrane has not resulted in reduction of mean annual radon concentrations to below the Action Level. Detailed comparison of the two data sets reveals marked differences in the degree of mitigation achieved by remediation. There is therefore an ongoing need for research to resolve definitively the issue of radon mitigation and to define truly effective anti-radon measures, readily installed in domestic properties at the time of construction. It is therefore recommended that mandatory testing be introduced for all new houses in Radon Affected Area
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