Optimising seat design for all-terrain vehicle injury prevention: wide variability illustrates need for evidence-based standardisation.

BACKGROUND: All-terrain vehicle (ATV)-related deaths and injuries are a growing public health concern, particularly in rural and suburban communities. More engineering approaches that address vehicle safety and promote injury prevention are critically needed. OBJECTIVES: Our study was designed to determine the variability in seat characteristics among 2012 model-year, adult-size ATVs. METHODS: Measurements of 67 models were performed using an image-based method. Seat characteristics were compared by manufacturer and by ATV type (sport vs utility). RESULTS: There were significant differences in seat length and seat placement among manufacturers and between sport and utility ATVs. Seat lengths ranged from 19.8 to 37.0 inches, with sport models significantly longer than utility models. Longer seats resulted from the back of the seat extending further beyond the rear axle and/or the seat front extending closer to the handle grips. Seat front to handle grip distances ranged from 3.25 to 16.5 inches. Combined data showed a strong inverse correlation between seat length and the distance from the seat front to the handle grips, but no significant correlation with wheelbase or engine size. CONCLUSIONS: We found wide variability in seat length and placement for adult-size ATVs. However, existing seat specifications were identified that may be a good starting point for improved seat design. Optimal design would allow for safe operation while reducing the likelihood of multiple riders and use by underaged operators, both major risk factors for ATV-related deaths and injuries. Ultimately, regulations may be needed to ensure standardised seat design is incorporated throughout the ATV industry.

An image-based method to measure all-terrain vehicle dimensions for engineering safety purposes.

BACKGROUND: All-terrain vehicle (ATV) crashes are a serious public health and safety concern. Engineering approaches that address ATV injury prevention are critically needed. Avenues to pursue include evidence-based seat design that decreases risky behaviours, such as carrying passengers and operation of adult-size vehicles by children. OBJECTIVES: The goal of this study was to create and validate an image-based method to measure ATV seat length and placement. METHODS: Publicly available ATV images were downloaded. Adobe Photoshop was then used to generate a vertical grid through the centre of the vehicle, to define the grid scale using the manufacturer's reported wheelbase, and to determine seat length and placement relative to the front and rear axles using this scale. Images that yielded a difference greater than 5% between the calculated and the manufacturer's reported ATV lengths were excluded from further analysis. RESULTS: For the 77 images that met inclusion criteria, the mean±SD for the difference in calculated versus reported vehicle length was 1.8%±1.2%. The Pearson correlation coefficient for comparing image-based seat lengths determined by two independent measurers (20 models) and image-based lengths versus lengths measured at dealerships (12 models) were 0.95 and 0.96, respectively. CONCLUSIONS: The image-based method provides accurate and reproducible results for determining ATV measurements, including seat length and placement. This method greatly expands the number of ATV models that can be studied, and may be generalisable to other motor vehicle types. These measurements can be used to guide engineering approaches that improve ATV safety design.

Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α.

Metabolic reprogramming toward glycolysis is a hallmark of cancer malignancy. The molecular mechanisms by which the tumor glycolysis pathway promotes immune evasion remain to be elucidated. Here, by performing genome-wide CRISPR screens in murine tumor cells co-cultured with cytotoxic T cells (CTLs), we identified that deficiency of two important glycolysis enzymes, Glut1 (glucose transporter 1) and Gpi1 (glucose-6-phosphate isomerase 1), resulted in enhanced killing of tumor cells by CTLs. Mechanistically, Glut1 inactivation causes metabolic rewiring toward oxidative phosphorylation, which generates an excessive amount of reactive oxygen species (ROS). Accumulated ROS potentiate tumor cell death mediated by tumor necrosis factor alpha (TNF-α) in a caspase-8- and Fadd-dependent manner. Genetic and pharmacological inactivation of Glut1 sensitizes tumors to anti-tumor immunity and synergizes with anti-PD-1 therapy through the TNF-α pathway. The mechanistic interplay between tumor-intrinsic glycolysis and TNF-α-induced killing provides new therapeutic strategies to enhance anti-tumor immunity.

Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects.

F-652 is a recombinant fusion protein consisting of two human interleukin-22 (IL-22) molecules linked to an immunoglobulin constant region (IgG2-Fc). IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection. The safety, pharmacokinetics (PK), tolerability, and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized, double-blind, placebo-controlled study. Following single-dose subcutaneous (SC) injection of F-652 at 2.0 µg/kg into healthy subjects, six out of six subjects experienced delayed injection site reactions, which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing. F-652 was then administered to the healthy subjects via an intravenous (IV) infusion at 2.0, 10, 30, and 45 µg/kg. No severe adverse event (SAE) was observed during the study. Among the IV-dosed cohorts, eye and skin treatment emergent adverse events (TEAEs) were observed in the 30 and 45 µg/kg cohorts. F-652 IV dosing resulted in linear increases in Cmax and AUC(0-t), and the T1/2 ranged from 39.4 to 206 h in the cohorts. An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A, C-reactive protein, and FIB, and decreased serum triglycerides. The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45 µg/kg. In conclusion, IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties. These results warrant further clinical development of F-652 to treat inflammatory diseases.