26 research outputs found

    An outbreak of cardiovascular syndromes requiring urgent medical treatment and its association with environmental factors: an ecological study

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    <p>Abstract</p> <p>Background</p> <p>In April 2005, syndromic surveillance based on statistical control chart methods in Sydney, Australia, signalled increasing incidence of urgent emergency department visits for cardiovascular and chest pain syndromes compared to the preceding twelve months. This paper aimed to determine whether environmental factors could have been responsible for this 'outbreak'.</p> <p>Methods</p> <p>The outcome studied was daily counts of emergency department visits for cardiovascular or chest pain syndromes that were considered immediately or imminently life threatening on arrival at hospital. The outbreak had a mean daily count of 5.7 visits sustained for eight weeks, compared with 4.0 in the same months in previous years. Poisson regression was used to systematically assess the emergency department visits in relation to available daily weather and pollution variables by first finding the best model that explained short-term variation in the outcome over the period 25 January 2002 to 31 May 2005, and then assessing interactions of all available variables with the 'outbreak' period, April-May 2005. Rate ratios were estimated for an interquartile increase in each variable meaning that the ratio measures the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable. The rate ratios for the outbreak period measure the relative increase (or decrease) in the emergency department visits for an interquartile increase in the weather or pollution variable during the outbreak period only.</p> <p>Results</p> <p>The best fitting model over the whole study period included minimum temperature with a rate ratio (RR) of 0.86 (95% confidence interval (CI), 0.77–0.96), maximum relative humidity of 1.09 (95% CI 1.05–1.14) and minimum daily particulate matter less than 10 microns (PM<sub>10</sub>) of 1.05 (95% CI, 1.01–1.09). During the outbreak period, maximum temperature (RR 1.27, 95% CI 1.03–1.57), solar radiation (RR 1.44, 95% CI, 1.00–2.07) and ozone (RR 1.13, 95% CI 1.01–1.26) were associated with the outcome.</p> <p>Conclusion</p> <p>The increase may have been associated with photochemical pollution. Syndromic surveillance can identify outbreaks of non-communicable diseases associated with environmental factors.</p

    Repair at Single Targeted DNA Double-Strand Breaks in Pluripotent and Differentiated Human Cells

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    Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). For the most part, previous studies of DSB repair in human cells have utilized nonspecific clastogens like ionizing radiation, which are highly nonphysiologic, or assayed repair at randomly integrated reporters. Measuring repair after random integration is potentially confounded by locus-specific effects on the efficiency and precision of repair. We show that the frequency of HR at a single DSB differs up to 20-fold between otherwise isogenic human embryonic stem cells (hESCs) based on the site of the DSB within the genome. To overcome locus-specific effects on DSB repair, we used zinc finger nucleases to efficiently target a DSB repair reporter to a safe-harbor locus in hESCs and a panel of somatic human cell lines. We demonstrate that repair at a targeted DSB is highly precise in hESCs, compared to either the somatic human cells or murine embryonic stem cells. Differentiation of hESCs harboring the targeted reporter into astrocytes reduces both the efficiency and precision of repair. Thus, the phenotype of repair at a single DSB can differ based on either the site of damage within the genome or the stage of cellular differentiation. Our approach to single DSB analysis has broad utility for defining the effects of genetic and environmental modifications on repair precision in pluripotent cells and their differentiated progeny
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