Serum RNA biomarkers for predicting survival in non-human primates following thoracic radiation.

In a mass radiation exposure, the healthcare system may rely on differential expression of miRNA to determine exposure and effectively allocate resources. To this end, miRNome analysis was performed on non-human primate serum after whole thorax photon beam irradiation of 9.8 or 10.7 Gy with dose rate 600 cGy/min. Serum was collected up to 270 days after irradiation and sequenced to determine immediate and delayed effects on miRNA expression. Elastic net based GLM methods were used to develop models that predicted the dose vs. controls at 81% accuracy at Day 15. A three-group model at Day 9 achieved 71% accuracy in determining if an animal would die in less than 90 days, between 90 and 269 days, or survive the length of the study. At Day 21, we achieved 100% accuracy in determining whether an animal would later develop pleural effusion. These results demonstrate the potential ability of miRNAs to determine thorax partial-body irradiation dose and forecast survival or complications early following whole thorax irradiation in large animal models. Future experiments incorporating additional doses and independent animal cohorts are warranted to validate these results. Development of a serum miRNA assay will facilitate the administration of medical countermeasures to increase survival and limit normal tissue damage following a mass exposure.

A Rayleigh Scatter-Based Ocular Flare Analysis Meter for Flare Photometry of the Anterior Chamber.

PURPOSE: Existing flare photometers are based on the Tyndall effect, which requires sophisticated laser photometry. The ocular flare analysis meter (OFAM) is a nonlaser photometer that uses quantitative Rayleigh scatter and absorption from visible light to compute a flare value. This study is designed to correlate OFAM measurements with qualitative measurements of flare in vitro and in vivo. METHODS: Following validation of the device on artificial anterior chambers containing known protein concentrations, flare readings were obtained from 90 subjects (46 with and 44 without uveitis) in one eye. Subjects were graded by the Standardization of Uveitis Nomenclature (SUN) working group flare scoring system and received the OFAM flare measurements. RESULTS: The OFAM showed linear response in vitro to protein concentrations ranging from 0 to 0.5 mg/ml. In clinical use in subjects ranging from SUN flare scores of 0+ to 2+, OFAM showed statistically significant measurement accuracy (P = 0.0008 of flare 0 versus flare 2; P = 0.031 of flare 0 versus flare 1). Distinction of SUN scores 1 and 2 was borderline significant (P = 0.057). CONCLUSION: The OFAM photometry correlates with the standard SUN scoring system. This method may provide an objective method to diagnosis and monitor uveitis. Further longitudinal studies are warranted. TRANSLATIONAL RELEVANCE: Currently, ocular flare is assessed qualitatively in most clinical settings. The existing methodology uses only Tyndall effect to measure flare. The OFAM uses an alternate, nonlaser means for measurement of anterior chamber flare by measure of Raleigh scatter. This pilot clinical study suggests that the OFAM device may be useful in measurement of uveitis activity.