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Motor vehicle accidents are the leading cause of death for young adults 18-29 years old worldwide, resulting in nearly 1 million years of life lost annually in the United States. Despite improvements in vehicle safety technologies, young women are at higher risk of dying in car crashes compared with men in matched scenarios. Vehicle crash testing primarily revolves around test dummies representative of the 50th percentile adult male, potentially resulting in these differences in fatality risk for female occupants compared to males. Vehicle occupants involved in fatal car crashes were matched using seating location, vehicle type, airbag deployment, seatbelt usage, and age. The relative risk for fatality (R) between males and females was calculated using a Double Pair Comparison. Young women (20s-40s) are at approximately 20% higher risk of dying in car crashes compared with men of the same age in matched scenarios. In passenger cars, 25-year-old female occupants in passenger car crashes from 1975-2020 exhibit R = 1.201 (95% CI 1.160-1.250) compared to 25-year-old males, and R-1.117 (95% CI 1.040-1.207) for passenger car crashes from 2010-2020. This trend persists across vehicle type, airbag deployment, seatbelt use, and number of vehicles involved in a crash. Known sex-based differences do not explain this large risk differential, suggesting a need for expanded test methodologies and research strategies to address as-yet unexplored sex differences in crash fatalities. These differences should be further investigated to ensure equitable crash protection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abrams, Bass. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Since World War I, helmets have been used to protect the head in warfare, designed primarily for protection against artillery shrapnel. More recently, helmet requirements have included ballistic and blunt trauma protection, but neurotrauma from primary blast has never been a key concern in helmet design. Only in recent years has the threat of direct blast wave impingement on the head-separate from penetrating trauma-been appreciated. This study compares the blast protective effect of historical (World War I) and current combat helmets, against each other and 'no helmet' or bare head, for realistic shock wave impingement on the helmet crown. Helmets included World War I variants from the United Kingdom/United States (Brodie), France (Adrian), Germany (Stahlhelm), and a current United States combat variant (Advanced Combat Helmet). Helmets were mounted on a dummy head and neck and aligned along the crown of the head with a cylindrical shock tube to simulate an overhead blast. Primary blast waves of different magnitudes were generated based on estimated blast conditions from historical shells. Peak reflected overpressure at the open end of the blast tube was compared to peak overpressure measured at several head locations. All helmets provided significant pressure attenuation compared to the no helmet case. The modern variant did not provide more pressure attenuation than the historical helmets, and some historical helmets performed better at certain measurement locations. The study demonstrates that both historical and current helmets have some primary blast protective capabilities, and that simple design features may improve these capabilities for future helmet systems., Competing Interests: The authors have declared that no competing interests exist.

Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.

Polyomaviruses (PyVs) can cause serious disease in immunosuppressed hosts. Several pathogenic PyVs encode microRNAs (miRNAs), small RNAs that regulate gene expression via RNA silencing. Despite recent advances in understanding the activities of PyV miRNAs, the biological functions of PyV miRNAs during in vivo infections are mostly unknown. The studies presented here used murine polyomavirus (MuPyV) as a model to assess the roles of the PyV miRNAs in a natural host. This analysis revealed that a MuPyV mutant that is unable to express miRNAs has enhanced viral DNA loads in select tissues at late times after infection. This is consistent with the PyV miRNAs functioning to reduce viral replication during the persistent phase of infection in a natural host. Additionally, the MuPyV miRNA locus promotes viruria during the acute phase of infection as evidenced by a defect in shedding during infection with the miRNA mutant virus. The viruria defect of the miRNA mutant virus could be rescued by infecting Rag2 -/- mice. These findings implicate the miRNA locus as functioning in both the persistent and acute phases of infection and suggest a role for MuPyV miRNA in evading the adaptive immune response. IMPORTANCE MicroRNAs are expressed by diverse viruses, but for only a few is there any understanding of their in vivo function. PyVs can cause serious disease in immunocompromised hosts. Therefore, increased knowledge of how these viruses interact with the immune response is of clinical relevance. Here we show a novel activity for a viral miRNA locus in promoting virus shedding. This work indicates that in addition to any role for the PyV miRNA locus in long-term persistence, it also has biological activity during the acute phase. As this mutant phenotype is alleviated by infection of mice lacking an adaptive immune response, our work also connects the in vivo activity of the PyV miRNA locus to the immune response. Given that PyV-associated disease is associated with alterations in the immune response, our findings help to better understand how the balance between PyVs and the immune response becomes altered in pathogenic states., (Copyright © 2018 American Society for Microbiology.)

Currently, no scientific consensus exists on the relative safety of catcher mask styles and materials. Due to differences in mass and material properties, the style and material of a catcher mask influences the impact metrics observed during simulated foul ball impacts. The catcher surrogate was a Hybrid III head and neck equipped with a six degree of freedom sensor package to obtain linear accelerations and angular rates. Four mask styles were impacted using an air cannon for six 30 m/s and six 35 m/s impacts to the nasion. To quantify impact severity, the metrics peak linear acceleration, peak angular acceleration, Head Injury Criterion, Head Impact Power, and Gadd Severity Index were used. An Analysis of Covariance and a Tukey's HSD Test were conducted to compare the least squares mean between masks for each head injury metric. For each injury metric a P-Value less than 0.05 was found indicating a significant difference in mask performance. Tukey's HSD test found for each metric, the traditional style titanium mask fell in the lowest performance category while the hockey style mask was in the highest performance category. Limitations of this study prevented a direct correlation from mask testing performance to mild traumatic brain injury., Competing Interests: The authors have declared that no competing interests exist.

The submarine H.L. Hunley was the first submarine to sink an enemy ship during combat; however, the cause of its sinking has been a mystery for over 150 years. The Hunley set off a 61.2 kg (135 lb) black powder torpedo at a distance less than 5 m (16 ft) off its bow. Scaled experiments were performed that measured black powder and shock tube explosions underwater and propagation of blasts through a model ship hull. This propagation data was used in combination with archival experimental data to evaluate the risk to the crew from their own torpedo. The blast produced likely caused flexion of the ship hull to transmit the blast wave; the secondary wave transmitted inside the crew compartment was of sufficient magnitude that the calculated chances of survival were less than 16% for each crew member. The submarine drifted to its resting place after the crew died of air blast trauma within the hull.

Blast-induced traumatic brain injury (bTBI) is a major threat to United States service members in military conflicts worldwide. The effects of primary blast, caused by the supersonic shockwave interacting with the skull and brain, remain unclear. Our group has previously reported that in vitro primary blast exposure can reduce long-term potentiation (LTP), the electrophysiological correlate of learning and memory, in rat organotypic hippocampal slice cultures (OHSCs) without significant changes to cell viability or basal, evoked neuronal function. We investigated the time course of primary blast-induced deficits in LTP and the molecular mechanisms that could underlie these deficits. We found that pure primary blast exposure induced LTP deficits in a delayed manner, requiring longer than 1 hour to develop, and that these deficits spontaneously recovered by 10 days following exposure depending on blast intensity. Additionally, we observed that primary blast exposure reduced total α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor 1 (GluR1) subunit expression and phosphorylation of the GluR1 subunit at the serine-831 site. Blast also reduced the expression of postsynaptic density protein-95 (PSD-95) and phosphorylation of stargazin protein at the serine-239/240 site. Finally, we found that modulation of the cyclic adenosine monophosphate (cAMP) pathway ameliorated electrophysiological and protein-expression changes caused by blast. These findings could inform the development of novel therapies to treat blast-induced loss of neuronal function.

Up to 80% of injuries sustained by U.S. soldiers in Operation Enduring Freedom and Operation Iraqi Freedom were the result of blast exposure from improvised explosive devices. Some soldiers experience multiple blasts while on duty, and it has been suggested that symptoms of repetitive blast are similar to those that follow multiple non-blast concussions, such as sport-related concussion. Despite the interest in the effects of repetitive blast exposure, it remains unknown whether an initial blast renders the brain more vulnerable to subsequent exposure, resulting in a synergistic injury response. To investigate the effect of multiple primary blasts on the brain, organotypic hippocampal slice cultures were exposed to single or repetitive (two or three total) primary blasts of varying intensities. Long-term potentiation was significantly reduced following two Level 2 (92.7 kPa, 1.4 msec, 38.5 kPa·msec) blasts delivered 24 h apart without altering basal evoked response. This deficit persisted when the interval between injuries was increased to 72 h but not when the interval was extended to 144 h. The repeated blast exposure with a 24 h interval increased microglia staining and activation significantly but did not significantly increase cell death or damage axons, dendrites, or principal cell layers. Lack of overt structural damage and change in basal stimulated neuron response suggest that injury from repetitive primary blast exposure may specifically affect long-term potentiation. Our studies suggest repetitive primary blasts can exacerbate injury dependent on the injury severity and interval between exposures.

An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion.

Over the last 13 years, traumatic brain injury (TBI) has affected over 230,000 U.S. service members through the conflicts in Iraq and Afghanistan, mostly as a result of exposure to blast events. Blast-induced TBI (bTBI) is multi-phasic, with the penetrating and inertia-driven phases having been extensively studied. The effects of primary blast injury, caused by the shockwave interacting with the brain, remain unclear. Earlier in vivo studies in mice and rats have reported mixed results for primary blast effects on behavior and memory. Using a previously developed shock tube and in vitro sample receiver, we investigated the effect of isolated primary blast on the electrophysiological function of rat organotypic hippocampal slice cultures (OHSC). We found that pure primary blast exposure inhibited long-term potentiation (LTP), the electrophysiological correlate of memory, with a threshold between 9 and 39 kPa·ms impulse. This deficit occurred well below a previously identified threshold for cell death (184 kPa·ms), supporting our previously published finding that primary blast can cause changes in brain function in the absence of cell death. Other functional measures such as spontaneous activity, network synchronization, stimulus-response curves, and paired-pulse ratios (PPRs) were less affected by primary blast exposure, as compared with LTP. This is the first study to identify a tissue-level tolerance threshold for electrophysiological changes in neuronal function to isolated primary blast.

On the evening of February 17th, 1864, the Confederate submarine H.L. Hunley attacked the Union ship USS Housatonic outside Charleston, South Carolina and became the first submarine in history to successfully sink an enemy ship in combat. One hypothesis for the sinking of the Confederate submarine H.L. Hunley is that the crew, in the enclosed vessel, suffered a lack of oxygen and suffocated. This study estimates the effects of hypoxia and hypercapnia on the crew based on submarine gas volume and crew breathing dynamics. The calculations show the crew of the Hunley had a minimum of 10 min between the onset of uncomfortable hypercapnia symptoms and danger of loss of consciousness from hypoxia. Based on this result and the location of the crew when discovered, hypoxia and hypercapnia do not explain the sinking of the world's first successful combat submarine., (Published by Elsevier Ireland Ltd.)

Underwater blasts propagate further and injure more readily than equivalent air blasts. Development of effective personal protection and countermeasures, however, requires knowledge of the currently unknown human tolerance to underwater blast. Current guidelines for prevention of underwater blast injury are not based on any organized injury risk assessment, human data or experimental data. The goal of this study was to derive injury risk assessments for underwater blast using well-characterized human underwater blast exposures in the open literature. The human injury dataset was compiled using 34 case reports on underwater blast exposure to 475 personnel, dating as early as 1916. Using severity ratings, computational reconstructions of the blasts, and survival information from a final set of 262 human exposures, injury risk models were developed for both injury severity and risk of fatality as functions of blast impulse and blast peak overpressure. Based on these human data, we found that the 50% risk of fatality from underwater blast occurred at 302±16 kPa-ms impulse. Conservatively, there is a 20% risk of pulmonary injury at a kilometer from a 20 kg charge. From a clinical point of view, this new injury risk model emphasizes the large distances possible for potential pulmonary and gut injuries in water compared with air. This risk value is the first impulse-based fatality risk calculated from human data. The large-scale inconsistency between the blast exposures in the case reports and the guidelines available in the literature prior to this study further underscored the need for this new guideline derived from the unique dataset of actual injuries in this study.

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α(+) isoform but not the α(-) isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.

Transcripts possessing a 5'-triphosphate are a hallmark of viral transcription and can trigger the host antiviral response. 5'-triphosphates are also found on common host transcripts transcribed by RNA polymerase III (RNAP III), yet how these transcripts remain non-immunostimulatory is incompletely understood. Most microRNAs (miRNAs) are 5'-monophosphorylated as a result of sequential endonucleolytic processing by Drosha and Dicer from longer RNA polymerase II (RNAP II)-transcribed primary transcripts. In contrast, bovine leukemia virus (BLV) expresses subgenomic RNAP III transcripts that give rise to miRNAs independent of Drosha processing. Here, we demonstrate that each BLV pre-miRNA is directly transcribed by RNAP III from individual, compact RNAP III type II genes. Thus, similar to manmade RNAP III-generated short hairpin RNAs (shRNAs), the BLV pre-miRNAs are initially 5'-triphosphorylated. Nonetheless, the derivative 5p miRNAs and shRNA-generated 5p small RNAs (sRNAs) possess a 5'-monophosphate. Our enzymatic characterization and small RNA sequencing data demonstrate that BLV 5p miRNAs are co-terminal with 5'-triphosphorylated miRNA precursors (pre-miRNAs). Thus, these results identify a 5'-tri-phosphatase activity that is involved in the biogenesis of BLV miRNAs and shRNA-generated sRNAs. This work advances our understanding of retroviral miRNA and shRNA biogenesis and may have implications regarding the immunostimulatory capacity of RNAP III transcripts., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

An increasing number of U.S. soldiers are diagnosed with traumatic brain injury (TBI) subsequent to exposure to blast. In the field, blast injury biomechanics are highly complex and multi-phasic. The pathobiology caused by exposure to some of these phases in isolation, such as penetrating or inertially driven injuries, has been investigated extensively. However, it is unclear whether the primary component of blast, a shock wave, is capable of causing pathology on its own. Previous in vivo studies in the rodent and pig have demonstrated that it is difficult to deliver a primary blast (i.e., shock wave only) without rapid head accelerations and potentially confounding effects of inertially driven TBI. We have previously developed a well-characterized shock tube and custom in vitro receiver for exposing organotypic hippocampal slice cultures to pure primary blast. In this study, isolated primary blast induced minimal hippocampal cell death (on average, below 14% in any region of interest), even for the most severe blasts tested (424 kPa peak pressure, 2.3 ms overpressure duration, and 248 kPa*ms impulse). In contrast, measures of neuronal function were significantly altered at much lower exposures (336 kPa, 0.84 ms, and 86.5 kPa*ms), indicating that functional changes occur at exposures below the threshold for cell death. This is the first study to investigate a tolerance for primary blast-induced brain cell death in response to a range of blast parameters and demonstrate functional deficits at subthreshold exposures for cell death.

Recent studies have demonstrated increased susceptibility to breakdown of the cerebral vasculature associated with repetitive traumatic brain injury. We hypothesized that exposure to two consecutive blast injuries would result in exacerbated damage to an in vitro model of the blood-brain barrier (BBB) compared with exposure to a single blast of the same severity. Contrary to our hypothesis, however, repeated mild or moderate primary blast delivered with a 24 or 72 h interval between injuries did not significantly exacerbate reductions in transendothelial electrical resistance (TEER) across a brain endothelial monolayer compared with sister cultures receiving a single exposure of the same intensity. Permeability of the barrier to a range of different-sized solutes remained unaltered after single and repeated blast, supporting that the effects of repeated blast on BBB integrity were not additive. Single blast exposure significantly reduced immunostaining of ZO-1 and claudin-5 tight junction proteins, but subsequent exposure did not cause additional damage to tight junctions. Although repeated blast did not further reduce TEER, the second exposure delayed TEER recovery in BBB cultures. Similarly, recovery of hydraulic conductivity through the BBB was delayed by a second exposure. Extending the interinjury interval to 72 h, the effects of multiple injuries on the BBB were found to be independent given sufficient recovery time between consecutive exposures. Careful investigation of the effects of repeated blast on the BBB will help identify injury levels and a temporal window of vulnerability associated with BBB dysfunction, ultimately leading to improved strategies for protecting warfighters against repeated blast-induced disruption of the cerebral vasculature.

The incidence of blast-induced traumatic brain injury (bTBI) has increased substantially in recent military conflicts. However, the consequences of bTBI on the blood-brain barrier (BBB), a specialized cerebrovascular structure essential for brain homeostasis, remain unknown. In this study, we utilized a shock tube driven by compressed gas to generate operationally relevant, ideal pressure profiles consistent with improvised explosive devices (IEDs). By multiple measures, the barrier function of an in vitro BBB model was disrupted following exposure to a range of controlled blast loading conditions. Trans-endothelial electrical resistance (TEER) decreased acutely in a dose-dependent manner that was most strongly correlated with impulse, as opposed to peak overpressure or duration. Significantly increased hydraulic conductivity and solute permeability post-injury further confirmed acute alterations in barrier function. Compromised ZO-1 immunostaining identified a structural basis for BBB breakdown. After blast exposure, TEER remained significantly depressed 2 days post-injury, followed by spontaneous recovery to pre-injury control levels at day 3. This study is the first to report immediate disruption of an in vitro BBB model following primary blast exposure, which may be important for the development of novel helmet designs to help mitigate the effects of blast on the BBB.

Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G's and were well correlated with peak incident overpressure (R(2) = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are presented to provide experimental data for computer model validation.

The loading conditions used in some current in vivo and in vitro blast-induced neurotrauma models may not be representative of real-world blast conditions. To address these limitations, we developed a compressed-gas driven shock tube with different driven lengths that can generate Friedlander-type blasts. The shock tube can generate overpressures up to 650 kPa with durations between 0.3 and 1.1 ms using compressed helium driver gas, and peak overpressures up to 450 kPa with durations between 0.6 and 3 ms using compressed nitrogen. This device is used for short-duration blast overpressure loading for small animal in vivo injury models, and contrasts the more frequently used long duration/high impulse blast overpressures in the literature. We also developed a new apparatus that is used with the shock tube to recreate the in vivo intracranial overpressure response for loading in vitro culture preparations. The receiver device surrounds the culture with materials of similar impedance to facilitate the propagation of a single overpressure pulse through the tissue. This method prevents pressure waves reflecting off the tissue that can cause unrealistic deformation and injury. The receiver performance was characterized using the longest helium-driven shock tube, and produced in-fluid overpressures up to 1500 kPa at the location where a culture would be placed. This response was well correlated with the overpressure conditions from the shock tube (R(2) = 0.97). Finite element models of the shock tube and receiver were developed and validated to better elucidate the mechanics of this methodology. A demonstration exposing a culture to the loading conditions created by this system suggest tissue strains less than 5% for all pressure levels simulated, which was well below functional deficit thresholds for strain rates less than 50 s(-1). This novel system is not limited to a specific type of culture model and can be modified to reproduce more complex pressure pulses.

Due to the prominent role of improvised explosive devices (IEDs) in wounding patterns of U.S. war-fighters in Iraq and Afghanistan, blast injury has risen to a new level of importance and is recognized to be a major cause of injuries to the brain. However, an injury risk-function for microscopic, macroscopic, behavioral, and neurological deficits has yet to be defined. While operational blast injuries can be very complex and thus difficult to analyze, a simplified blast injury model would facilitate studies correlating biological outcomes with blast biomechanics to define tolerance criteria. Blast-induced traumatic brain injury (bTBI) results from the translation of a shock wave in-air, such as that produced by an IED, into a pressure wave within the skull-brain complex. Our blast injury methodology recapitulates this phenomenon in vitro, allowing for control of the injury biomechanics via a compressed-gas shock tube used in conjunction with a custom-designed, fluid-filled receiver that contains the living culture. The receiver converts the air shock wave into a fast-rising pressure transient with minimal reflections, mimicking the intracranial pressure history in blast. We have developed an organotypic hippocampal slice culture model that exhibits cell death when exposed to a 530 ± 17.7-kPa peak overpressure with a 1.026 ± 0.017-ms duration and 190 ± 10.7 kPa-ms impulse in-air. We have also injured a simplified in vitro model of the blood-brain barrier, which exhibits disrupted integrity immediately following exposure to 581 ± 10.0 kPa peak overpressure with a 1.067 ± 0.006-ms duration and 222 ± 6.9 kPa-ms impulse in-air. To better prevent and treat bTBI, both the initiating biomechanics and the ensuing pathobiology must be understood in greater detail. A well-characterized, in vitro model of bTBI, in conjunction with animal models, will be a powerful tool for developing strategies to mitigate the risks of bTBI.

Radiologic imaging is crucial in the diagnosis of skull fracture, but there is some doubt as to whether different imaging modalities can accurately identify fractures present on a human skull. While studies have been performed to evaluate the efficacy of radiologic imaging at other anatomical locations, there have been no systematic studies comparing various CT techniques, including high resolution imaging with and without 3D reconstructions to conventional radiologic imaging in children, we investigated which imaging modalities: high-resolution CT scan with 3D projections, clinical-resolution CT scans or X-rays, best showed fracture occurrence in a pediatric human cadaver skull by having an expert pediatric radiologist examine radiologic images from fractured skulls. The skulls used were taken from pediatric cadavers ranging in age from 5 months to 16 years. We evaluated the sensitivity and specificity for the imaging modalities using dissection findings as the gold standard. We found that high-resolution CT scans with 3D projections and conventional CT provided the most accurate fracture diagnosis (single-fracture sensitivity of 71%) followed by X-rays (single-fracture sensitivity of 63%). Linear fractures outsider the region of the sutures were more identifiable than diastatic fractures, though the incidence of false positives was greater for linear fractures. In the two cases where multiple fractures were present on the same anatomical skull location, the radiologist was less likely to identify the presence of additional fractures than a single fracture. Overall, the high-resolution and clinical-resolution CT scans had the similar accuracy for detecting skull fractures while the use of the X-ray was both less accurate and had a lower specificity., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Many soldiers returning from the current conflicts in Iraq and Afghanistan have had at least one exposure to an explosive event and a significant number have symptoms consistent with traumatic brain injury. Although blast injury risk functions have been determined and validated for pulmonary injury, there is little information on the blast levels necessary to cause blast brain injury. Anesthetized male New Zealand White rabbits were exposed to varying levels of shock tube blast exposure focused on the head, while their thoraces were protected. The specimens were euthanized and evaluated when the blast resulted in respiratory arrest that was non-responsive to resuscitation or at 4?h post-exposure. Injury was evaluated by gross examination and histological evaluation. The fatality data from brain injury were then analyzed using Fisher's exact test to determine a brain fatality risk function. Greater blast intensity was associated with post-blast apnea and the need for mechanical ventilation. Gross examination revealed multifocal subdural hemorrhages, most often near the brainstem, at more intense levels of exposure. Histological evaluation revealed subdural and subarachnoid hemorrhages in the non-responsive respiratory-arrested specimens. A fatality risk function from blast exposure to the head was determined for the rabbit specimens with an LD(50) at a peak overpressure of 750?kPa. Scaling techniques were used to predict injury risk at other blast overpressure/duration combinations. The fatality risk function showed that the blast level needed to cause fatality from an overpressure wave exposure to the head was greater than the peak overpressure needed to cause fatality from pulmonary injury. This risk function can be used to guide future research for blast brain injury by providing a realistic fatality risk to guide the design of protection or to evaluate injury.

The mechanical response of ligaments under fast strain-rate deformations is a necessary input into computational models that are used for injury assessment. However, this information frequently is not available for the ligaments that are routinely injured in fast-rate loading scenarios. In the current study, experiments were conducted at fast strain rates for the cervical spinal ligaments: the anterior longitudinal ligament, the posterior longitudinal ligament and the ligamentum flavum. Bone-ligament-bone complexes at three spine levels were harvested for mechanical testing. Displacement-controlled sub-failure uniaxial tensile tests were performed in both load-relaxation and sinusoidal conditions. A nonlinear (separable) viscoelastic model was used to examine the experimental data. An unexpected result of the modeling was that the instantaneous elastic functions could be approximated as linear for these strain rates. A five-parameter model was sufficient to characterize the ligament viscoelastic responses and had good predictive capacity under different applied loading conditions.

Intranasal pressures were measured in adults during nose blowing, sneezing, and coughing and were used for fluid dynamic modeling. Sinus CT scans were performed after instillation of radiopaque contrast medium into the nasopharynx followed by nose blowing, sneezing, and coughing. The mean (+/-SD) maximal intranasal pressure was 66 (+/-14) mm Hg during 35 nose blows, 4.6 (+/-3.8) mm Hg during 13 sneezes, and 6.6 (+/-3.8) mm Hg during 18 coughing bouts. A single nose blow can propel up to 1 mL of viscous fluid in the middle meatus into the maxillary sinus. Sneezing and coughing do not generate sufficient pressure to propel viscous fluid into the sinus. Contrast medium from the nasopharynx appeared in >/=1 sinuses in 4 of 4 subjects after a nose blow but not after sneezing or coughing.

This paper presents the dynamic injury tolerances for the female humerus and forearm derived from dynamic 3-point bending tests using 22 female cadaver upper extremities. Twelve female humeri were tested at an average strain rate of 3.7+/-1.3%/s. The strain rates were chosen to be representative of those observed during upper extremity interaction with frontal and side airbags. The average moment to failure when mass scaled for the 5th centile female was 128+/-19 Nm. Using data from the in situ strain gauges during the drop tests and geometric properties obtained from pretest CT scans, an average dynamic elastic modulus for the female humerus was found to be 24.4+/-3.9 GPa. The injury tolerance for the forearm was determined from 10 female forearms tested at an average strain rate of 3.94+/-2.0%/s. Using 3 matched forearm pairs, it was determined that the forearm is 21% stronger in the supinated position (92+/-5 Nm) versus the pronated position (75+/-7 Nm). Two distinct fracture patterns were seen for the pronated and supinated groups. In the supinated position the average difference in fracture time between the radius and ulna was a negligible 0.4+/-0.3 ms. However, the pronated tests yielded an average difference in fracture time of 3.6+/-1.2 ms, with the ulna breaking before the radius in every test. This trend implies that in the pronated position, the ulna and radius are loaded independently, while in the supinated position the ulna and radius are loaded together as a combined structure. To produce a conservative injury criterion, a total of 7 female forearms were tested in the pronated position, which resulted in the forearm injury criterion of 58+/-12 Nm when scaled for the 5th centile female. It is anticipated that these data will provide injury reference values for the female forearm during driver air bag loading, and the female humerus during side air bag loading.