To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
Levels of daily particulates (PM2.5) were monitored at two sites in Karachi, Pakistan. One site (Korangi) is an industrial and residential neighborhood, while the other (Tibet Center) is a commercial and residential area near a major highway. Monitoring was done daily for a period of six weeks during spring, summer, fall and winter. Particulate levels were extraordinarily high, with the great majority of days falling into the “unhealthy for sensitive groups” or “very unhealthy” categories. The mean PM2.5 levels in Karachi exceeded the WHO’s 24 hour air quality guideline almost every day and often by a factor of greater than 5-fold. Daily emergency room (ER) visits and hospital admissions for cardiovascular diseases were obtained by review of medical records at three major tertiary and specialized hospitals. ER and hospitalizations were reported relative to days in which the concentration of PM2.5 was less than 50 µg/m3, and by 50 µg/m3 increments up to 300 µg/m3. There were statistically significant elevations in rates of hospital admissions at each of the PM2.5 categories at the Korangi site, and at concentrations >150 µg/m3 at the Tibet Center site. ER visits were significantly elevated only at PM2.5 concentrations of between 151 and 200 µg/m3 at both sites. These results show that the extremely elevated concentrations of PM2.5 in Karachi, Pakistan are, as expected, associated with significantly elevated rates of hospital admission, and to a lesser extent, ER visits for cardiovascular disease
City-level estimates of ambient ozone concentrations and associated disease burdens are sparsely available, especially for low and middle-income countries. Recently available high-resolution gridded global ozone concentration estimates allow for estimating ozone concentrations and mortality at urban scales and for urban-rural catchment areas worldwide. We applied existing fine resolution global surface ozone estimates, developed by integrating observations (8,834 sites globally) with nine atmospheric chemistry models, in an epidemiologically-derived health impact function to estimate chronic respiratory disease mortality worldwide in 2019. We compared ozone season daily maximum 8 hour mixing ratio concentrations and ozone-attributable mortality for urban areas worldwide (including cities and densely-populated towns), and their surrounding peri-urban, peri-rural, and rural areas. In 2019, population-weighted mean ozone among all urban-rural catchment areas was greatest in peri-urban areas (52 ppb), followed by urban areas (cities and towns; 49 ppb). Of 423,100 estimated global ozone-attributable deaths, 37% (147,100) occurred in urban areas, where 40% of the world’s population resides, and 56% (254,000) occurred in peri-urban areas (<1 hour from an urban area), where 47% of the world’s population resides. Across 12,946 cities (excluding towns), average population-weighted mean ozone was 51 ppb [sd=13 ppb, range=10–78 ppb]. Three quarters of the ozone-attributable deaths worldwide (77%; 112,700) occurred in cities of South and East Asia. City-level ozone-attributable mortality rates varied by a factor of 10 across world regions. Ozone levels and attributable mortality were greatest in Asian and African cities; however, cities of higher-income regions, like high-income Asia Pacific and North America, continue to experience high ozone concentrations and attributable mortality rates, despite successful national air quality measures for reducing ozone precursor emissions. The disproportionate magnitude of ozone mortality compared with population size in peri-urban areas indicates that reducing ozone precursor emissions in places that influence peri-urban concentrations can yield substantial health benefits in these areas.
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