Potential impacts of Washington State's wildfire worker protection rule on construction workers.

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.

Factors Affecting Material-Cart Handling in the Roofing Industry: Evidence for Administrative Controls.

Material-cart handling can be strenuous and lead to overexertion injuries. The aim of this study is to produce a thorough understanding of how the cart condition, tire type, physical environment-related factors, and load interact to influence the ergonomics and productivity of cart handling. Eighteen roofing carts with different conditions, tires, and loads were tested by one subject on three laboratory tracks: one L-shaped, one with ramps within constrained spaces, and one with obstacles within constrained spaces. A multiple linear regression analysis was performed to quantify the main and interaction effects of the factors of interest on the cart operations. The research findings confirm that using aged carts increases the injury risk by as much as 30.5% and decreases productivity by 35.4%. Our study also highlights the necessity of keeping an open space for cart operation; the travel distance from a cart to a ramp/obstacle should be greater than 61 cm. Finally, the results suggest the at-risk thresholds for different ramp slopes and obstacle heights, and the safe load capacities for the various working circumstances that are common on construction sites. The evidence created in this study can be translated into administrative controls for cart handling to reduce overexertion injuries and enhance performance.

Understanding the Social Contagion Effect of Safety Violations within a Construction Crew: A Hybrid Approach Using System Dynamics and Agent-Based Modeling.

Previous research has recognized the importance of eliminating safety violations in the context of a social group. However, the social contagion effect of safety violations within a construction crew has not been sufficiently understood. To address this deficiency, this research aims to develop a hybrid simulation approach to look into the cognitive, social, and organizational aspects that can determine the social contagion effect of safety violations within a construction crew. The hybrid approach integrates System Dynamics (SD) and Agent-based Modeling (ABM) to better represent the real world. Our findings show that different interventions should be employed for different work environments. Specifically, social interactions play a critical role at the modest hazard levels because workers in this situation may encounter more ambiguity or uncertainty. Interventions related to decreasing the contagion probability and the safety⁻productivity tradeoff should be given priority. For the low hazard situation, highly intensive management strategies are required before the occurrence of injuries or accidents. In contrast, for the high hazard situation, highly intensive proactive safety strategies should be supplemented by other interventions (e.g., a high safety goal) to further control safety violations. Therefore, this research provides a practical framework to examine how specific accident prevention measures, which interact with workers or environmental characteristics (i.e., the hazard level), can influence the social contagion effect of safety violations.

The Impact of Coworkers' Safety Violations on an Individual Worker: A Social Contagion Effect within the Construction Crew.

This research developed and tested a model of the social contagion effect of coworkers’ safety violations on individual workers within construction crews. Both situational and routine safety violations were considered in this model. Empirical data were collected from 345 construction workers in China using a detailed questionnaire. The results showed that both types of safety violations made by coworkers were significantly related to individuals’ perceived social support and production pressure. Individuals’ attitudinal ambivalence toward safety compliance mediated the relationships between perceived social support and production pressure and both types of individuals’ safety violations. However, safety motivation only mediated the effects of perceived social support and production pressure on individuals’ situational safety violations. Further, this research supported the differences between situational and routine safety violations. Specifically, we found that individuals were more likely to imitate coworkers’ routine safety violations than their situational safety violations. Coworkers’ situational safety violations had an indirect effect on individuals’ situational safety violations mainly through perceived social support and safety motivation. By contrast, coworkers’ routine safety violations had an indirect effect on individuals’ routine safety violations mainly through perceived production pressure and attitudinal ambivalence. Finally, the theoretical and practical implications, research limitations, and future directions were discussed.

An evaluation of wearable sensors and their placements for analyzing construction worker's trunk posture in laboratory conditions.

This study investigates the effect of sensor placement on the analysis of trunk posture for construction activities using two off-the-shelf systems. Experiments were performed using a single-parameter monitoring wearable sensor (SPMWS), the ActiGraph GT9X Link, which was worn at six locations on the body, and a multi-parameter monitoring wearable sensor (MPMWS), the Zephyr BioHarness™3, which was worn at two body positions. One healthy male was recruited and conducted 10 experiment sessions to repeat measurements of trunk posture within our study. Measurements of upper-body thoracic bending posture during the lifting and lowering of raised deck materials in a laboratory setting were compared against video-captured observations of posture. The measurements from the two sensors were found to be in agreement during slow-motion symmetric bending activities with a target bending of ≤45°. However, for asymmetric bending tasks, when the SPMWS was placed on the chest, its readings were substantially different from those of the MPMWS worn on the chest or under the armpit.

Tissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGF(c) chimeric protein targeting tissue factor.

We evaluated the expression of tissue factor (TF) in ovarian cancer (EOC) and the potential of hI-con1, an antibody-like molecule targeting TF, as a novel form of therapy against chemotherapy-resistant ovarian disease. We studied the expression of TF in 88 EOC by immunohistochemistry (IHC) and real-time-PCR (qRT-PCR) and the levels of membrane-bound-complement-regulatory-proteins CD46, CD55 and CD59 in primary EOC cell lines by flow-cytometry. Sensitivity to hI-con1-dependent-cell-mediated-cytotoxicity (IDCC), complement-dependent-cell-cytotoxicity and inhibition of IDCC by γ-immunoglobulin were evaluated in 5-h (51)chromium-release-assays. Cytoplasmic and/or membrane TF expression was observed in 24 out of 25 (96%) of the EOC samples tested by IHC, but not in normal ovarian-tissue. EOC with clear cell histology significantly overexpress TF when compared to serous, endometrioid, or undifferentiated tumors by qRT-PCR. With a single exception, all primary EOC that overexpressed TF demonstrated high levels of CD46, CD55 and CD59 and regardless of their histology or resistance to chemotherapy, were highly sensitive to IDCC. The effect of complement and physiologic doses of γ-immunoglobulin on IDCC in ovarian cancer cell lines overexpressing TF was tumor specific and related to the overexpression of CD59 on tumor cells. Small-interfering-RNA-mediated knockdown of CD59 expression in ovarian tumors significantly increased hI-con1-mediated cytotoxic activity in vitro. Finally, low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (P < 0.01). hI-con1 molecule induces strong cytotoxicity against primary chemotherapy-resistant ovarian cancer cell lines overexpressing TF and may represent a novel therapeutic agent for the treatment of ovarian tumors refractory to standard treatment modalities.

Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion.

Immune escape is an important reason why the immune system cannot control tumor growth, but how escape variants emerge during immunotherapy remains poorly understood. Here, we identify a new mechanism of tumor immune escape using an in vivo selection strategy. We generated a highly immune-resistant cancer cell line (P3) by subjecting a susceptible cancer cell line (P0/TC-1) to multiple rounds of in vivo immune selection. Microarray analysis of P0 and P3 revealed that vascular cell adhesion molecule-1 (VCAM-1) is up-regulated in the P3-resistant variant. Retroviral transfer of VCAM-1 into P0 significantly increased its resistance against a vaccine-induced immune response. Analysis of tumors showed a dramatic decrease in the number of tumor-infiltrating cluster of differentiation 8(+) (CD8(+)) T cells in the tumors expressing VCAM-1. In vitro transwell migration assays showed that VCAM-1 can promote the migration of CD8(+) T cells through its interaction with the alpha(4)beta(1) integrin. Site-directed mutagenesis of VCAM-1 at amino acid residues required for interaction with alpha(4)beta(1) integrin completely abolished the immune resistance conferred by VCAM-1 in vivo. Surface staining showed that most renal cell carcinomas (RCC) express VCAM-1, whereas an RCC that responded to vaccination was VCAM-1 negative. These data provide evidence that tumor expression of VCAM-1 represents a new mechanism of immune evasion and has important implications for the development of immunotherapy for human RCC.

Human papillomavirus type-16 virus-like particles activate complementary defense responses in key dendritic cell subpopulations.

Human papillomavirus type-16 (HPV16) L1 virus-like particles (VLPs) activate dendritic cells (DCs) and induce protective immunity. In this study, we demonstrate, using global gene expression analysis, that HPV16 VLPs produce quite distinct innate responses in murine splenic DC subpopulations. While HPV16 VLPs increase transcription of IFN-gamma and numerous Th1-related cytokines and chemokines in CD8alpha(+)CD11c(+) DCs, CD4(+)CD11c(+) DCs up-regulate only type I IFN and a different set of Th2-associated cytokines and chemokines. Type I IFN, but not IFN-gamma, potentiates humoral immunity, notably production of VLP-specific IgG2a. However, HPV16 VLP-stimulated IL-12 production by CD8alpha(+)CD11c(+) DCs is augmented by autocrine IFN-gamma signaling. Thus, before adaptive immunity, HPV16 VLPs signal complementary defense responses in key DC subpopulations, indicating specialized DC lineages with predetermined polarization.

Boosting with recombinant vaccinia increases HPV-16 E7-Specific T cell precursor frequencies and antitumor effects of HPV-16 E7-expressing Sindbis virus replicon particles.

Immunotherapy using the heterologous prime-boost regimen has emerged as an attractive approach for generating antigen-specific T-cell-mediated immune responses against tumors and infectious diseases. We have previously linked the Mycobacterium tuberculosis heat-shock protein 70 (HSP70) to the HPV-16 E7 antigen creating a chimera, E7/HSP70. We found that nucleic acid vaccines encoding E7/HSP70 can generate strong antitumor immunity. Recently, replication-defective Sindbis virus replicon particle vaccines have been considered as an important vector system for vaccine development. In this study, we assessed whether the combination of E7/HSP70 Sindbis virus replicon particles (SINrep5-E7/HSP70) and E7/HSP70 vaccinia (Vac-E7/HSP70) can further enhance E7-specific immune responses using sequential vaccination. We found that priming with SINrep5-E7/HSP70 and boosting with Vac-E7/HSP70 generated the highest number of E7-specific CD8(+) T cells and best antitumor effect compared to other combinations. Moreover, our data showed that at the dosage and route of immunization used in this study, mice treated with the Sindbis virus replicon particle prime-vaccinia boost regimen generated stronger antitumor responses compared to mice treated with the DNA prime-vaccinia boost vaccine regimen. Our results encourage the use of the Sindbis virus replicon particle prime-vaccinia boost regimen in future clinical trials.

Cell surface-binding motifs of L2 that facilitate papillomavirus infection.

Human papillomavirus type 16 (HPV16) is the primary etiologic agent of cervical carcinoma, whereas bovine papillomavirus type 1 (BPV1) causes benign fibropapillomas. However, the capsid proteins, L1 and L2, of these divergent papillomaviruses exhibit functional conservation. A peptide comprising residues 1 to 88 of BPV1 L2 binds to a variety of cell lines, but not to the monocyte-derived cell line D32, and blocks BPV1 infection of mouse C127 cells. Residues 13 to 31 of HPV16 L2 and BPV1 L2 residues 1 to 88 compete for binding to the cell surface, and their binding, unlike that of HPV16 L1/L2 virus-like particles, is unaffected by heparinase or trypsin pretreatment of HeLa cells. A fusion of HPV16 L2 peptide 13-31 and GFP binds (K(d), approximately 1 nM) to approximately 45,000 receptors per HeLa cell. Furthermore, mutation of L2 residues 18 and 19 or 21 and 22 significantly reduces both the ability of the HPV16 L2 13-31-GFP fusion protein to bind to SiHa cells and the infectivity of HPV16 pseudovirions. Antibody to BPV1 L2 peptides comprising residues 115 to 135 binds to intact BPV1 virions, but fails to neutralize at a 1:10 dilution. However, deletion of residues 91 to 129 from L2 abolishes the infectivity of BPV1, but not their binding to the cell surface. In summary, L2 residues 91 to 129 contain epitopes displayed on the virion surface and are required for infection, but not virion binding to the cell surface. Upon the binding of papillomavirus to the cell surface, residues 13 to 31 of L2 interact with a widely expressed, trypsin- and heparinase-resistant cell surface molecule and facilitate infection.