The Effects of Airbags and Seatbelts on Occupant Injury in Longitudinal Barrier Crashes

Introduction: Longitudinal barriers, such as guardrails, are designed to prevent a vehicle that leaves the roadway from impacting a more dangerous object while minimizing the risk of injury to the vehicle occupants. Current full-scale test procedures for these devices do not consider the effect of occupant restraints such as seatbelts and airbags. The purpose of this study was to determine the extent to which restraints are used or deployed in longitudinal barrier collisions and their subsequent effect on occupant injury. Methods: Binary logistic regression models were generated to predict occupant injury risk using data from the National Automotive Sampling System / Crashworthiness Data System from 1997 through 2007. Results: In tow-away longitudinal barrier crashes, airbag deployment rates were 70% for airbag-equipped vehicles. Compared with unbelted occupants without an airbag available, seat belt restrained occupants with an airbag available had a dramatically decreased risk of receiving a serious (MAIS 3+) injury (odds-ratio (OR)=0.03; 95% CI: 0.004- 0.24). A similar decrease was observed among those restrained by seat belts, but without an airbag available (OR=0.03; 95% CI: 0.001- 0.79). No significant differences in risk of serious injuries were observed between unbelted occupants with an airbag available compared with unbelted occupants without an airbag available (OR=0.53; 95% CI=0.10-2.68). Impact on Industry: This study refutes the perception in the roadside safety community that airbags rarely deploy in frontal barrier crashes, and suggests that current longitudinal barrier occupant risk criteria may over-estimate injury potential for restrained occupants involved in a longitudinal barrier crash.

Real-World Performance of Longitudinal Barriers Struck by Large Trucks

Outside of relatively limited crash testing with large trucks, very little is known regarding the performance of traffic barriers subjected to real-world large truck impacts. The purpose of this study was to investigate real-world large truck impacts into traffic barriers to determine barrier crash involvement rates, the impact performance of barriers not specifically designed to redirect large trucks, and the real-world performance of large-truck-specific barriers. Data sources included the Fatality Analysis Reporting System (2000-2009), the General Estimates System (2000-2009) and 155 in-depth large truck-to-barrier crashes from the Large Truck Crash Causation Study. Large truck impacts with a longitudinal barrier were found to comprise 3 percent of all police-reported longitudinal barrier impacts and roughly the same proportion of barrier fatalities. Based on a logistic regression model predicting barrier penetration, large truck barrier penetration risk was found to increase by a factor of 6 for impacts with barriers designed primarily for passenger vehicles. Although large-truck-specific barriers were found to perform better than non-heavy vehicle specific barriers, the penetration rate of these barriers were found to be 17 percent. This penetration rate is especially a concern because the higher test level barriers are designed to protect other road users, not the occupants of the large truck. Surprisingly, barriers not specifically designed for large truck impacts were found to prevent large truck penetration approximately half of the time. This suggests that adding costlier higher test level barriers may not always be warranted, especially on roadways with lower truck volumes.

Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells

To gain insights into the molecular mechanisms underlying early host responses to HIV in the CD4(+) T cell target population, we examined gene expression in CD4(+) T cells isolated 24 h after ex vivo HIV infection of lymphocyte aggregate cultures derived from human tonsils. Gene profiling showed a distinct up-regulation of genes related to immune response and response to virus, notably of IFN-stimulated genes (ISGs), irrespective of the coreceptor tropism of the virus. This mostly IFN-alpha-dependent gene signature suggested the involvement of plasmacytoid dendritic cells, a principal component of the antiviral immune response. Indeed, depletion of plasmacytoid dendritic cells before HIV inoculation abrogated transcriptional up-regulation of several ISGs and resulted in increased levels of HIV replication. Treatment with a blocking anti-IFN-alphaR Ab yielded increased HIV replication; conversely, HIV replication was decreased in pDC-depleted cultures treated with IFN-alpha. Among up-regulated ISGs was also TRAIL, indicating a potential role of the IFN signature in apoptosis. However, a blocking anti-TRAIL Ab did not abrogate apoptosis of CD4(+) T cells in CXCR4-tropic HIV-infected cultures, suggesting the involvement of pathways other than TRAIL mediated. We conclude that acute HIV infection of lymphoid tissue results in up-regulation of ISGs in CD4(+) T cells, which induces an anti-HIV state but not apoptosis.

Gain-of-function mutation S422L in the KCNJ8-encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes.

BACKGROUND J-wave syndromes have emerged conceptually to encompass the pleiotropic expression of J-point abnormalities including Brugada syndrome (BrS) and early repolarization syndrome (ERS). KCNJ8, which encodes the cardiac K(ATP) Kir6.1 channel, recently has been implicated in ERS following identification of the functionally uncharacterized missense mutation S422L. OBJECTIVE The purpose of this study was to further explore KCNJ8 as a novel susceptibility gene for J-wave syndromes. METHODS Using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing, comprehensive open reading frame/splice site mutational analysis of KCNJ8 was performed in 101 unrelated patients with J-wave syndromes, including 87 with BrS and 14 with ERS. Six hundred healthy individuals were examined to assess the allelic frequency for all variants detected. KCNJ8 mutation(s) was engineered by site-directed mutagenesis and coexpressed heterologously with SUR2A in COS-1 cells. Ion currents were recorded using whole-cell configuration of the patch-clamp technique. RESULTS One BrS case and one ERS case hosted the identical missense mutation S422L, which was reported previously. KCNJ8-S422L involves a highly conserved residue and was absent in 1,200 reference alleles. Both cases were negative for mutations in all known BrS and ERS susceptibility genes. K(ATP) current of the Kir6.1-S422L mutation was increased significantly over the voltage range from 0 to 40 mV compared to Kir6.1-WT channels (n = 16-21; P <.05). CONCLUSION These findings further implicate KCNJ8 as a novel J-wave syndrome susceptibility gene and a marked gain of function in the cardiac K(ATP) Kir6.1 channel secondary to KCNJ8-S422L as a novel pathogenic mechanism for the phenotypic expression of both BrS and ERS.