Driven by climate change, wildfires are increasing in frequency, duration, and intensity across the Western United States. Outdoor workers are being exposed to increasing wildfire-related particulate matter and smoke. Recognizing this emerging risk, Washington adopted an emergency rule and is presently engaged in creating a permanent rule to protect outdoor workers from wildfire smoke exposure. While there are growing bodies of literature on the exposure to and health effects of wildfire smoke in the general public and wildland firefighters, there is a gap in knowledge about wildfire smoke exposure among outdoor workers generally and construction workers specifically—a large category of outdoor workers in Washington totaling 200,000 people. Several data sources were linked in this study—including state-collected employment data and national ambient air quality data—to gain insight into the risk of PM2.5 exposure among construction workers and evaluate the impacts of different air quality thresholds that would have triggered a new Washington emergency wildfire smoke rule aimed at protecting workers from high PM2.5 exposure. Results indicate the number of poor air quality days has increased in August and September in recent years. Over the last decade, these months with the greatest potential for particulate matter exposure coincided with an annual peak in construction employment that was typically 9.4–42.7% larger across Washington counties (one county was 75.8%). Lastly, the ‘encouraged’ threshold of the Washington emergency rule (20.5 μg m−3) would have resulted in 5.5 times more days subject to the wildfire rule on average across all Washington counties compared to its ‘required’ threshold (55.5 μg m−3), and in 2020, the rule could have created demand for 1.35 million N-95 filtering facepiece respirators among construction workers. These results have important implications for both employers and policy makers as rules are developed. The potential policy implications of wildfire smoke exposure, exposure control strategies, and data gaps that would improve understanding of construction worker exposure to wildfire smoke are also discussed.

e16542 Background: TRC253 is a high-affinity, orally active small molecule antagonist of the androgen receptor (AR) and specific mutated variants of AR that does not possess agonist activity towards either wild type or mutated AR. TRC253 inhibits AR nuclear translocation as well as AR binding to DNA and is a transcription antagonist. TRC253 treatment is efficacious in an LNCaP xenograft model driven by F877L mutant AR. Methods: In P1 dose escalation, pts with mCRPC previously treated with an AR inhibitor were assigned to increasing TRC253 doses of 40-320 mg daily. Dose escalation followed single-pt dose escalation design for the 40, 80 mg cohorts and expanded to 3+3 design in the 160, 240, 280, and 320 mg cohorts to assess safety, determine the recommended phase 2 dose (RP2D), and evaluate prostate-specific antigen response at week 12. Toxicity and efficacy assessments used NCI-CTCAE v4.03 and PCWG3 criteria, respectively. Pts were centrally screened by circulating tumor DNA using the BEAMing digital PCR assay. Results: Twenty-two pts were enrolled in phase 1 at TRC253 doses of 40 (n = 1), 80 (n = 1), 160 (n = 2), 240 (n = 6), 280 (n = 4), and 320 mg (n = 8) daily in 28-day cycles. One DLT of G3 QTcF prolongation occurred at 320 mg. No drug-related SAEs were reported. Drug-related AEs ≥ G2 included QTcF prolongation (2 G2, 2 G3), elevated lipase (1 G3), fatigue (4 G2), arthralgia (1 G2), diarrhea (1 G2), and platelet count decrease (1 G2). One pt on study had AR F877L at baseline and remained on treatment for 49 wks with PR by RECIST. The remaining 21 pts did not have AR F877L at baseline and of these, 48% (10) remained on study > 6 cycles and one pts had a > 50% decrease in PSA. Target PK exposures were achieved consistently at 280 mg. 280 mg was selected as the RP2D based on safety and PK data. Conclusions: TRC253 daily at 280 mg was well-tolerated and selected as the RP2D. P2 dose expansion is currently enrolling 2 cohorts: 15 pts with AR F877L and 30 pts without AR F877L. The objectives of P2 include collection of additional data for safety, PK, PET and efficacy of TRC253 in mCRPC pts with specific AR mutations. Clinical trial information: NCT02987829.

Abstract-This study explored the limitations of contemporary distance video teaching, including unsynchronized audio/video, lack of interaction, and broadband occupancy. The theoretical basis and supporting technology for developing an audio-triggered courseware teaching system were discussed and the corresponding system was designed and developed. The author applied this system to teach a course on Guzheng specialty at the Department of Music and designed a control experiment to verify the effects of this system. Results show that the effect of audio-triggered courseware teaching is significantly superior to that of a traditional distance video teaching system. When students cannot attend classes, using the audio-triggered courseware teaching system may be a preferable option.

TPS403 Background: Resistance to AR-targeted therapy is a challenge in the treatment of mCRPC. Single amino acid mutations of the AR ligand binding domain may mediate resistance to second generation AR inhibitors, including enzalutamide (Rathkopf, Annals of Oncology 2017). Development of potent antagonists of wild-type (WT) AR as well as mutated AR is a priority. TRC253 is an orally available, high-affinity, small molecule antagonist of AR with inhibitory activity against WT AR as well as mutated variants. TRC253 blocks AR nuclear translocation and AR binding to DNA and antagonizes transcription. TRC253 does not have agonist activity toward WT or mutated ARs. Methods: This phase 1/2a study of TRC253 in patients with mCRPC will be conducted in two parts: dose-escalation (part 1) and dose-expansion (part 2). Objectives include assessment of safety, selection of a phase 2 dose, and to evaluate PSA response at week 12. Secondary objectives include the evaluation of the extent of receptor occupancy (FDHT PET) and anti-tumor effects of TRC253. Toxicity and efficacy assessments will be determined using NCI-CTCAE and PCWG3 criteria. Dose escalation will begin with single-patient cohorts. Cohorts will be expanded to 3 patients when pre-defined grades of drug-related toxicity occur. TRC253 doses in part 1 are 40 mg, 80 mg, 160 mg, 240 mg, 320 mg, and 400 mg. The DLT evaluation period will be the first 28 days of continuous daily dosing. Six patients have been enrolled to Part 1 to date. Part 2 will consist of two cohorts of up to 30 patients each. Cohort 1 (AR F876L mutation positive) and cohort 2 (AR F876L mutation negative) will receive TRC253 at the RP2D. Circulating tumor DNA will be analyzed in plasma samples to test for AR mutations. In Part 1 patients must have received ≥ 2 prior therapies. Part 2 patients must have demonstrated acquired resistance to enzalutamide or apalutamide. Descriptive statistics will be used to summarize patient characteristics, safety, efficacy, PK, and immunologic biomarkers. Clinical trial information: NCT02987829.

Envelope correlation coefficient (ECC) of the maximal ratio combining (MRC) output in correlated Rican fading channels is discussed in this paper in a close form, which is similar to that of single path conditions in stationary environment. Besides, with minor approximation we get the analytical formula outage probability. On this base, a simple relationship between ECC and the outage probability is derived, which indicates that ECC can be used to make predictions of outage probability.