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Background
Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries.Objective
In this study we aimed to measure the association between out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke.Methods
We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site.Results
There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 μm (PM2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 μg/m3) or ≤ 10 μm (PM10) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 μg/m3) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventy-four “fire-hours” (i.e., hours in which Melbourne’s air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations in PM2.5 during these fire-hours.Conclusions
This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.Citation
Dennekamp M, Straney LD, Erbas B, Abramson MJ, Keywood M, Smith K, Sim MR, Glass DC, Del Monaco A, Haikerwal A, Tonkin AM. 2015. Forest fire smoke exposures and out-of-hospital cardiac arrests in Melbourne, Australia: a case-crossover study. Environ Health Perspect 123:959–964; http://dx.doi.org/10.1289/ehp.1408436 相似文献Endosialin/tumor endothelial marker-1 (TEM1) is an attractive theranostic target expressed by the microenvironment of a wide range of tumors, as well as by sarcoma and neuroblastoma cells. We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1.
ProceduresThe scFv78-Fc was conjugated with the chelator p-SCN-Bn-CHX-A”-DTPA, followed by labeling with indium-111. The number of chelators per molecule was estimated by mass spectrometry. A conventional saturation assay, extrapolated to infinite antigen concentration, was used to determine the immunoreactive fraction of the radioimmunoconjugate. The radiopharmaceutical biodistribution was assessed in immunodeficient mice grafted with Ewing’s sarcoma RD-ES and neuroblastoma SK-N-AS human TEM1-positive tumors. The full biodistribution studies were preceded by a dose-escalation experiment based on the simultaneous administration of the radiopharmaceutical with increasing amounts of unlabeled scFv78-Fc. Radiation dosimetry extrapolations to human adults were obtained from mouse biodistribution data according to established methodologies and additional assumptions concerning the impact of the tumor antigenic sink in the cross-species translation.
Results[111In]CHX-DTPA-scFv78-Fc was obtained with a radiochemical purity >?98 % after 1 h incubation at 42 °C and ultrafiltration. It showed good stability in human serum and >?70 % immunoreactive fraction. Biodistribution data acquired in tumor-bearing mice confirmed fast blood clearance and specific tumor targeting in both xenograft models. The radiopharmaceutical off-target uptake was predominantly abdominal. After a theoretical injection of [111In]CHX-DTPA-scFv78-Fc to the reference person, the organs receiving the highest absorbed dose would be the spleen (0.876 mGy/MBq), the liver (0.570 mGy/MBq) and the kidneys (0.298 mGy/MBq). The total body dose and the effective dose would be 0.058 mGy/MBq and 0.116 mSv/MBq, respectively.
Conclusions[111In]CHX-DTPA-scFv78-Fc binds specifically to endosialin/TEM1 in vitro and in vivo. Dosimetry estimates are in the range of other monoclonal antibodies radiolabeled with indium-111. [111In]CHX-DTPA-scFv78-Fc could be potentially translated into clinic.
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