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Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion. Therefore, more accurate diagnostic markers are needed for sport-related concussion.This was a multicenter, prospective, case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment, Research, and Education Consortium conducted between 2015 and 2019. The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints. Athletes with concussion were divided into 6 h post-injury (0-6 h post-injury) and after 6 h post-injury (7-48 hours post-injury) groups. We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305 proteins in plasma samples from athletes with and without sport-related concussion.A total of 140 athletes with concussion (79.3% male; aged 18.71 ± 1.10 years, mean ± SD) and 21 non-concussed athletes (76.2% male; 19.14 ± 1.10 years) were included in this study. We identified 338 plasma proteins that significantly differed in abundance (319 upregulated and 19 downregulated) in concussed athletes compared to non-concussed athletes. The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve of 0.954 (95% confidence interval: 0.922‒0.986). Specifically, after 6 h of injury, the individual area under the curve of plasma erythrocyte membrane protein band 4.1 (EPB41) and alpha-synuclein were 0.956 and 0.875, respectively. The combination of EPB41 and alpha-synuclein provided the best area under the curve (1.000), which suggests this combination of candidate plasma biomarkers is best for diagnosing concussion in athletes after 6 h of injury.Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and alpha-synuclein is the most predictive biomarker of concussion after 6 h of injury.

Contact sport athletes are exposed to a unique environment where they sustain repeated head impacts throughout the season and can sustain hundreds of head impacts over a few months. Accordingly, recent studies outlined the role that head impact exposure (HIE) has in concussion biomechanics and in the development of cognitive and brain-based changes. Those studies focused on time-bound effects by quantifying exposure leading up to the concussion, or cognitive changes after a season in which athletes had high HIE. However, HIE may have a more prolonged effect. This study identified associations between HIE and concussion incidence during different periods of the college football fall season.This study included 1120 athlete seasons from six National Collegiate Athletic Association Division I football programs across 5 yr. Athletes were instrumented with the Head Impact Telemetry System to record daily HIE. The analysis quantified associations of preseason/regular season/total season concussion incidence with HIE during those periods.Strong associations were identified between HIE and concussion incidence during different periods of the season. Preseason HIE was associated with preseason and total season concussion incidence, and total season HIE was associated with total season concussion incidence.These findings demonstrate a prolonged effect of HIE on concussion risk, wherein elevated preseason HIE was associated with higher concussion risk both during the preseason and throughout the entire fall season. This investigation is the first to provide evidence supporting the hypothesis of a relationship between elevated HIE during the college football preseason and a sustained decreased tolerance for concussion throughout that season.

Sport-related concussions can result from a single high magnitude impact that generates concussive symptoms, repeated subconcussive head impacts aggregating to generate concussive symptoms, or a combined effect from the two mechanisms. The array of symptoms produced by these mechanisms may be clinically interpreted as a sport-related concussion. It was hypothesized that head impact exposure resulting in concussion is influenced by severity, total number, and frequency of subconcussive head impacts. The influence of total number and magnitude of impacts was previously explored, but frequency was investigated to a lesser degree. In this analysis, head impact frequency was investigated over a new metric called 'time delta', the time difference from the first recorded head impact of the day until the concussive impact. Four exposure metrics were analyzed over the time delta to determine whether frequency of head impact exposure was greater for athletes on their concussion date relative to other dates of contact participation. Those metrics included head impact frequency, head impact accrual rate, risk weighted exposure (RWE), and RWE accrual rate. Athletes experienced an elevated median number of impacts, RWE, and RWE accrual rate over the time delta on their concussion date compared to non-injury sessions. This finding suggests elevated frequency of head impact exposure on the concussion date compared to other dates that may precipitate the onset of concussion. National Institute of Neurological Disorders and Stroke of the National Institutes of Health [1R01NS126449]; Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium - National Collegiate Athletic Association (NCAA); Department of Defense (DOD); Office of the Assistant Secretary of Defense for Health Affairs [W81XWH-14-2-0151]; Veterans Affairs Medical Research Published version Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number 1R01NS126449. This publication was also made possible with support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium, funded in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DOD). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Psychological Health and Traumatic Brain Injury Program under Award NO W81XWH-14-2-0151. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense (DHP funds). This study was also supported by Veterans Affairs Medical Research. The authors would also like to thank Jody Harland, MS, Janetta Matesan, BA, Michael Menser, Larry Riggen, MS (Indiana University School of Medicine); Ashley Rettmann, BS, Nicole L'Heureux, MBA (University of Michigan); Melissa Koschnitzke, MA (Medical College of Wisconsin); Michael Jarrett, MBA, Vibeke Brinck, MS and Bianca Byrne, BA (Quesgen); Melissa Baker, BS (Datalys Center for Sports Injury Research and Prevention); and the research and medical staff at each of the CARE participation sites. The team would also like to acknowledge the HIT System operators that participated in this study: Julia Ford (UNC), Philippe Gagnon-Joseph (UNC), Miranda Kruse (UNC), Gus Hendricks (UCLA), Quinn Lukens (UW), Brett Griesemer (VT), Alex Black (VT), Lewis Young (VT), Dom Calhoun (USAFA), Mike Aderman (USMA), Sean Roach (USMA), and Jeremy Ross (USMA).

Identifying the associations between head impact biomechanics and clinical recovery may inform better head impact monitoring procedures and identify athletes who may benefit from early treatments aimed to enhance recovery. The purpose of this study was to test whether head injury biomechanics are associated with clinical recovery of symptom severity, balance, and mental status, as well as symptom resolution time (SRT) and return-to-participation (RTP) time. We studied 45 college American football players (n = 51 concussions) who sustained an incident concussion while participating in a multi-site study. Player race/ethnicity, prior concussion, medical history, position, body mass index, event type, and impact location were covariates in our multivariable analyses. Multivariable negative binomial regression models analyzed associations between our study outcomes and (1) injury-causing linear and rotational head impact severity, (2) season repetitive head impact exposure (RHIE), and (3) injury day RHIE. Median SRT was 6.1 days (IQR 5.8 days, n = 45) and median RTP time was 12.3 days (IQR 7.8 days, n = 36) across our study sample. RTP time was 86% (Ratio 1.86, 95% CI [1.05, 3.28]) longer in athletes with a concussion history. Offensive players had SRTs 49% shorter than defensive players (Ratio 0.51, 95% CI [0.29, 0.92]). Per-unit increases in season RHIE were associated with 22% longer SRT (Ratio 1.22, 95% CI [1.09, 1.36]) but 28% shorter RTP time (Ratio 0.72, 95% CI [0.56, 0.93]). No other head injury biomechanics predicted injury recovery.

Understanding the biomechanics of head injuries is essential for the development of preventive strategies and protective equipment design. However, there are many challenges associated with determining the forces that cause injury. Acceleration of the skull is often measured because it is relatively easy to quantify and relates to severity of impact, but it is difficult to relate those measurements to the type and extent of injury that occurs. Experimental work in the laboratory has used either human cadavers or volunteers. Cadavers can be instrumented with high-grade sensors that are tightly coupled to the skull for accurate measurements, but they cannot exhibit a functional response to determine a threshold for brain injury. Volunteers can also be instrumented with high-grade sensors in controlled laboratory experiments, but any head accelerations they experience must be well below an injurious level. Athletes participating in contact sports present a unique opportunity to collect biomechanical data from populations that have increased exposure to head impacts and a higher risk of head injury than the general population. Recent advances in sensor technology have allowed for more accurate measurements from instrumented athletes during play, but it is challenging to tightly couple the instrumentation to the skull to provide meaningful measurements. Because of the challenges associated with on-field measurements, it is important to consider the type of sensor used and its accuracy in the field when evaluating head impact data from athletes.

Optical choppers are applied in a large range of systems, from radiometers and telescopes to spectral and biomedical apparatuses. While classical choppers are built as rotational disks with windows with linear margins (or with oscillatory elements, but also with linear margins to progressively obscure light beams), we have introduced two different types of such devices; (i) eclipse choppers , with disks windows with non-linear margins, oriented outward or inward; (ii) choppers with rotational shafts of different shapes (with slits of various profiles). The former are capable to produce laser impulses with other shapes than classical choppers, while the latter have the potential to achieve much higher chop frequencies than disk choppers in a more compact construct. We have considered in previous studies the typical case of laser beams with circular sections for these choppers. The present study explores a different case, of laser lines being chopped. Geometrical aspects of the obscuration of laser lines considered in different positions – and for different chopper configurations – are discussed. Experiments are carried out to determine the transmission functions for some of the above devices.

This study examines the pattern of facial fractures in automotive collisions using the National Automotive Sampling System – Crashworthiness Data System. The database was examined for trends within collision and occupant descriptors among occupants sustaining facial fractures. Drivers and right front passengers were included in an analysis of frontal collisions. Side impacts were assessed separately by identifying occupants exposed to near and far side collisions. The distribution of facial bone fractures and injury sources were demonstrated for each impact configuration. Risk ratios were used to demonstrate the effects of restraint use and airbag deployment. Seatbelts were found to reduce the risk of sustaining a facial fracture by 74% in frontal impacts. Facial fractures are associated with severe impacts with a risk of 5% at a Delta-V of 40 km/h and 65 km/h for unbelted and belted occupants respectively.

This study describes a method for utilizing Acoustic Emission (AE) in facial fracture detection and demonstrates the association between fracture and acoustic emission magnitude. AE sensors were mounted to the frontal bone and mandible of cadaver skulls (n=14) exposed to impacts to the frontal bone, nasal bone, maxilla and mandible. The presence of AE during fracture and non-fracture tests necessitated the development of a threshold to distinguish AE associated with fracture. Based on the obtained data, a threshold of 9 volts was established. The association between above-threshold AE and fracture was demonstrated by performing low-severity impacts on pre-fractured frontal bones. These tests demonstrated that above threshold AE is produced as a result of high-severity impacts, resulting in fracture as well as low-severity impacts on prefracture bone. The results of these tests indicate that above threshold AE was associated with the fracture process and not a function of the force applied to the facial bones.

Placental abruption accounts for 50% to 70% of fetal losses in motor vehicle crashes. Since automobile crashes are the leading cause of traumatic fetal injury mortality in the United States, research of this injury mechanism is important. Before research can adequately evaluate current and future restraint designs, a detailed model of the pregnant uterine tissues is necessary. The purpose of this study is to develop a methodology for testing the pregnant uterus in biaxial tension at a rate normally seen in a motor vehicle crash. Since the majority of previous biaxial work has established methods for quasi-static testing, this paper combines previous research and new methods to develop a custom designed system to strain the tissue at a dynamic rate. Load cells and optical markers are used for calculating stress strain curves of the perpendicular loading axes. Results for this methodology show images of a tissue specimen loaded and a finite verification of the optical strain measurement. The biaxial test system dynamically pulls the tissue to failure with synchronous motion of four tissue grips that are rigidly coupled to the tissue specimen. The test device models in situ loading conditions of the pregnant uterus and overcomes previous limitations of biaxial testing. A non-contact method of measuring strains combined with data reduction to resolve the stresses in two directions provides the information necessary to develop a three dimensional constitutive model of the material. Moreover, future research can apply this method to other soft tissues with similar in situ loading conditions.

Computational models are used to investigate placental abruption in motor vehicle crashes, which is the leading cause of traumatic fetal injury mortality in the United States. Material parameters for computational modeling of pregnant occupant kinematics come from early research on placenta tissue at quasi-static loading rates. The purpose of this research is to develop a methodology for using cryogenic grips to test placenta specimens in uniaxial tension at a rate normally seen in a motor vehicle crash. For dynamic testing of placental tissue, implementing and adapting a cryogenic grip mechanism provides the ability to grip the tissue throughout the thickness and eliminates potential slipping of the tissue in the grip during the dynamic test. The validation for using the cryogenic grips is presented with video images of a typical test event showing the tissue failing in the active area. Additionally, local and global strain measures are compared to confirm the tissue strain is similar throughout the specimen. The cryogenic grips provide a low-cost and effective method of gripping and pulling a thick soft tissue in uniaxial tension. As a result, these methods can be used to acquire the material properties of placenta tissue loaded at a dynamic rate to apply in a computational pregnant model.

Facial bone fractures in the military can result from direct loading of night vision goggles on the orbital region. Facial fracture research has shown that increasing the area over which the load is applied increases the load tolerance. The purpose of this study is to apply this concept to reducing the risk of facial bone fracture from night vision goggle impacts. The effectiveness of countermeasures in prevention of orbital fracture was evaluated using a vertical drop tower with two impact velocities of 2.6 m/s and 3.6 m/s. The countermeasure used was a rigid plastic custom face shield made from a plaster impression of each head. In addition to two human cadaver subjects, one male and one female, tests were completed on a Hybrid III 50th percentile dummy head. Three impacts to the dummy headform included no countermeasure, safety glasses, and a custom face shield. These tests yielded peak loads of 8700 N, 7500 N, and 5640 N respectively. Using the female subject, impacts were preformed successively until injury occurred. These two impacts to the subject wearing a custom face shield resulted in peak loads of 4025 N and 5158 N. The highest load corresponds to an impact velocity of 3.6 m/s and a nasal bone fracture. Two impacts to the male subject with a custom face shield resulted in peak loads of 4554 N and 5101 N with no injury. The final impact to the male subject had a peak load of 2010 N with complete orbital fracture due to the absence of a countermeasure. From these tests it is shown that facial fracture risk from night vision goggle impact can be reduced using a contoured rigid face shield.

The purpose of this study was to investigate the relationship between bone mineral density and the biomechanical response. This study presents results from 117 human rib cortical bone coupon tests from six cadavers, three male and three female, ranging in age from 18 to 67 years old. First, the material properties of human rib cortical bone were determined using dynamic tension coupon testing. The rib sections were taken from the anterior, lateral, and posterior regions on ribs 1 through 12 of each cadaver's rib cage. The cortical bone was isolated from each rib section with a low speed diamond saw, and milled into dog bone shaped tension coupons using a small computer numerical control machine. A high-rate servohydraulic Material Testing System equipped with a custom slack adaptor, to provide constant strain rates, was used to apply tension loads to failure at an average rate of 0.5 strains/sec. The elastic modulus, yield stress, yield strain, ultimate stress, ultimate strain, and strain energy density were determined from the resulting stress versus strain curves. Second, two measures of bone mineral density (BMD) were determined: the global BMD of each cadaver through standard radiographic scaling, and the percent mineralization of each coupon through ash analysis. Overall, the global BMD was correlated with the biomechanical properties, but the local apparent density was not. The global BMD is actually a surrogate for the volume of bone present and it is highly correlated with subject age. In contrast, the apparent density is the true local BMD and it was not correlated with subject age. This is consistent with previous research and illustrates that the overall structural biomechanics of bone are related to the volume of bone, or global BMD, while they are much less related to the apparent density, or local BMD, which varies much less with age.

Sports-related concussions constitute 20 percent of brain injuries each year in the United States. Concussion research has included a variety of instrumentation and techniques to measure head accelerations. Most recently, the Head Impact Telemetry (HIT) System (Simbex, Lebanon, NH), a wireless system that provides real-time data from impacts, is used to measure in-situ head accelerations in collegiate football. The purpose of this study is to compare helmet shell acceleration to head center of gravity acceleration using two measures of linear head acceleration. A study of 50 helmet to helmet impact tests using a pendulum provided a range of head accelerations from 5 g to 50 g. The primary measure of head acceleration is accelerometers mounted at the center of gravity of the Hybrid III head. A secondary measure is the in-helmet HIT System. The series of 50 pendulum impacts included three impact velocities of 2.0 m/s, 3.5 m/s and 5.0 m/s at four different impact locations. The impact locations were on the side, back, top and just above the facemask on the front. By comparing these two measured head accelerations and the helmet acceleration during a pendulum impact, it is shown that the response of the head and the helmet vary greatly and the in-helmet system matches the head and not helmet acceleration. Specifically, head acceleration is less than 10 percent of helmet acceleration in football impacts; moreover, the HIT System is able to accurately measure the head acceleration.

The purpose of this study was to determine the biomechanical response of human clavicles when subjected to dynamic three-point bending. A total of 10 human cadaver clavicles were tested at an anatomical impact of 0 degrees relative to the transverse plane. Each clavicle was instrumented with a strain gage located under the impactor. Two load cells were used to capture the impactor and reaction loads. The average failure load was 732 +/- 175 N and the average failure moment was 28.3 +/- 7.8 m. The average failure strain was 19738 +/- 2927 microstrain. Using the cross-sectional geometry properties of each bone obtained from CT scans and the strain gage data, the average elastic modulus was 20.8 +/- 5.7 GPa for the linear region of the loading phase. The data presented in this paper is useful to understand clavicle fractures as well as to develop advanced human computational models.

The purpose of this paper is to present a method to determine the exact timing of all rib fractures during dynamic belt loading tests on the thorax of human cadavers. In order to generate non-censored rib fracture data, a total of 47 strain gages were placed throughout the thorax of two human cadavers (1 male, 1 female). In order to simulate thoracic loading from a severe car crash, a table-top belt loading device was developed that utilizes a servo-hydraulic test machine to apply a dynamic input. The belt load pulse was configured to result in 40% chest compression through a 150 ms load and unload cycle. Potentiometers and accelerometers measured the chest compression and acceleration at three locations, load cells in line with the belt provided belt loads, and load cells on the posterior side of the thorax measured the reaction loads. The time histories of each strain gage were analyzed to determine the time of fracture which could then be compared directly to the reaction loads and chest displacements at that exact time, thereby creating a non-censored data set. In both cadavers, all fractures (20 for female and 12 for male) occurred within the first 35% compression of the thorax. By utilizing this technique, the exact timing of an injury level can be characterized relative to the mechanical parameters.

In this study, we successfully performed local thrombolysis in 6 patients with peripheral arterial occlusions by using a novel high-molecular-weight urokinase. Mean duration of recanalization was 12.8 hours, mean fibrinogen consumption was relatively low (42%), reptilase time was relatively long (mean increase by 47%). These findings would suggest that the substance is highly effective, though systemic adverse reactions are mild.