11 research outputs found

    Relationship between ozone and temperature during the 2003 heat wave in France: consequences for health data analysis

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    BACKGROUND: PAPRICA is a research program designed to estimate the impact on the health of patients with chronic respiratory insufficiency of a prevention strategy based on notification of ozone pollution. The first year of this study was conducted during the 2003 heat wave, and high temperatures were therefore considered as a confounding factor in the data analysis. The aim of the present study was to assess the relationship between ozone and temperature in order to propose a methodology to distinguish between the effects of ozone and temperature on the impact of a prevention strategy with regard to ozone pollution. METHODS: Multivariate analyses were used to identify associated climate and ozone pollution profiles. This descriptive method is of great value to highlight the complexity of interactions between these parameters. RESULTS: Ozone concentration and temperature were strongly correlated, but the health impact of ozone pollution alone will be evaluated by focusing on situations characterized by ozone concentrations above 110 μg/m(3)/8h (air quality guidelines to protect human health defined by the French legislation) and temperatures lower than 26°C, below the discomfort threshold. CONCLUSION: The precise relationship between ambient ozone concentration and temperature identified during the PAPRICA 2003 study period will be used in analysing the PAPRICA health data

    Bioclimatic Architecture and Urban Morphology. Studies on Intermediate Urban Open Spaces

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    This paper deals with the interactions between biophysical and microclimatic factors on the one hand with, on the other, the urban morphology of intermediate urban open spaces, the relationship between environmental and bioclimatic thermal comfort, and the implementation of innovative materials and the use of greenery, aimed at the users’ well-being. In particular, the thermal comfort of the open spaces of the consolidated fabrics of the city of Rome is studied, by carrying out simulations of cooling strategies relating to two scenarios applied to Piazza Bainsizza. The first scenario involves the use of cool materials for roofs, cladding surfaces, and pavement, while the second scenario, in addition to the cool materials employed in the first scenario, also includes the use of greenery and permeable green surfaces. The research was performed using summer and winter microclimatic simulations of the CFD (ENVI-met v. 3.1) type, in order to determine the dierent influences of the materials with cold colors, trees, and vegetated surfaces on the thermal comfort of the urban morphology itself. Meanwhile, the comfort assessment was determined through the physiological equivalent temperature (PET) calculated with the RayMan program. The first scenario, with the use of cool materials, improves summer conditions and reduces the urban heat island eect but does not eliminate thermal discomfort due to the lack of shaded surfaces and vegetation. The second scenario, where material renovations is matched with vegetation improvements, has a slightly bad eect on winter conditions but drastically ameliorates the summer situation, both for direct users and, thanks to the strong reduction of the urban heat island eect, to urban inhabitants as a whole

    A predictive model relating daily fluctuations in summer temperatures and mortality rates

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    <p>Abstract</p> <p>Background</p> <p>In the context of climate change, an efficient alert system to prevent the risk associated with summer heat is necessary. The authors' objective was to describe the temperature-mortality relationship in France over a 29-year period and to define and validate a combination of temperature factors enabling optimum prediction of the daily fluctuations in summer mortality.</p> <p>Methods</p> <p>The study addressed the daily mortality rates of subjects aged over 55 years, in France as a whole, from 1975 to 2003. The daily minimum and maximum temperatures consisted in the average values recorded by 97 meteorological stations. For each day, a cumulative variable for the maximum temperature over the preceding 10 days was defined.</p> <p>The mortality rate was modelled using a Poisson regression with over-dispersion and a first-order autoregressive structure and with control for long-term and within-summer seasonal trends. The lag effects of temperature were accounted for by including the preceding 5 days. A "backward" method was used to select the most significant climatic variables. The predictive performance of the model was assessed by comparing the observed and predicted daily mortality rates on a validation period (summer 2003), which was distinct from the calibration period (1975–2002) used to estimate the model.</p> <p>Results</p> <p>The temperature indicators explained 76% of the total over-dispersion. The greater part of the daily fluctuations in mortality was explained by the interaction between minimum and maximum temperatures, for a day <it>t </it>and the day preceding it. The prediction of mortality during extreme events was greatly improved by including the cumulative variables for maximum temperature, in interaction with the maximum temperatures. The correlation between the observed and estimated mortality ratios was 0.88 in the final model.</p> <p>Conclusion</p> <p>Although France is a large country with geographic heterogeneity in both mortality and temperatures, a strong correlation between the daily fluctuations in mortality and the temperatures in summer on a national scale was observed. The model provided a satisfactory quantitative prediction of the daily mortality both for the days with usual temperatures and for the days during intense heat episodes. The results may contribute to enhancing the alert system for intense heat waves.</p

    MERTK Inhibition Induces Polyploidy and Promotes Cell Death and Cellular Senescence in Glioblastoma Multiforme

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    MER receptor tyrosine kinase (MERTK) is expressed in a variety of malignancies, including glioblastoma multiforme (GBM). Our previous work demonstrated that inhibition of MERTK using RNA interference induced cell death and chemosensitivity in GBM cells, implicating MERTK as a potential therapeutic target. Here we investigate whether a novel MERTK-selective small molecule tyrosine kinase inhibitor, UNC2025, has similar anti-tumor effects in GBM cell lines.Correlations between expression of GAS6, a MERTK ligand, and prognosis were determined using data from the TCGA database. GBM cell lines (A172, SF188, U251) were treated in vitro with increasing doses of UNC2025 (50-400nM). Cell count and viability were determined by trypan blue exclusion. Cell cycle profiles and induction of apoptosis were assessed by flow cytometric analysis after BrdU or Po-Pro-1/propidium iodide staining, respectively. Polyploidy was detected by propidium iodide staining and metaphase spread. Cellular senescence was determined by β-galactosidase staining and senescence-associated secretory cytokine analysis.Decreased overall survival significantly correlated with high levels of GAS6 expression in GBM, highlighting the importance of TAM kinase signaling in GBM tumorigenesis and/or therapy resistance and providing strong rationale for targeting these pathways in the clinic. All three GBM cell lines exhibited dose dependent reductions in cell number and colony formation (>90% at 200nM) after treatment with UNC2025. Cell cycle analysis demonstrated accumulation of cells in the G2/M phase and development of polyploidy. After extended exposure, 60-80% of cells underwent apoptosis. The majority of surviving cells (65-95%) were senescent and did not recover after drug removal. Thus, UNC2025 mediates anti-tumor activity in GBM by multiple mechanisms.The findings described here provide further evidence of oncogenic roles for MERTK in GBM, demonstrate the importance of kinase activity for MERTK tumorigenicity and validate UNC2025, a novel MERTK inhibitor, as a potential therapeutic agent for treatment of GBM
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