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Two experiments were designed to investigate possible abnormal face processing strategies in children with autistic spectrum disorders. A group of 11 children with autism was compared to two groups of normally developing children matched on verbal mental age and on chronological age. In the first experiment, participants had to recognize faces on the basis of identity, emotion, gaze direction, gender, and lip reading. All aspects of face processing, except for identity matching, were deficient in the autistic population compared with controls. In the second study, children had to match faces on either high-(i.e., local facial features) or low-spatial frequency information (i.e., global configuration of faces). Contrary to the control subjects, children with autism showed better performance when using high rather than low spatial frequency, confirming face-processing peculiarities in this population. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to examine the relationship between lap belt tension and force measured at the iliac wing and the effects of model type and torso posture on this relationship. From this analysis, preliminary transfer functions were developed to predict loads applied to the iliac wing as a function of lap belt tension at magnitudes typically measured in sled and vehicle crash tests., Methods: A DOE study was conducted to provide a robust assessment of the lap belt-pelvis load relationship under various conditions. The GHBMC, THUMS, and THOR FE models were positioned in upright and reclined postures with several other intrinsic and extrinsic parameters varied for a total of 360 simulations. For the HBMs, instrumentation was developed to measure ASIS load at each iliac wing. Simulations that resulted in submarining were identified and removed from the subsequent development of lap belt-ASIS force transfer functions., Results: The GHBMC exhibited submarining more frequently than the THUMS and THOR models. In addition to submarining, there were several cases in which the lap belt remained below the ASIS instrumentation or roped during the model's forward excursion. These phenomena, particularly prevalent in the THUMS model, also influenced how the lap belt engaged the ASIS instrumentation and were thus eliminated from the transfer function development. Transfer functions relating peak lap belt tension and corresponding ASIS force magnitudes were developed for the GHBMC and THOR models in upright and reclined postures. In the upright posture, the THOR showed a higher level of ASIS load measured for a given level of lap belt tension than the GHBMC; however, in recline the lap belt-pelvis load relationship was similar between the two models., Conclusions: The lap belt-pelvis load relationship was found to be affected by model type, posture, the area in which the ASIS instrumentation was defined, and occupant kinematics. This study showed it was possible to minimize the ASIS force by having the lap belt engage low on the pelvis and upper thighs, though further study is needed to determine if this loading mechanism is truly protective from an injury standpoint or an artifact of bypassing the ASIS instrumentation. The transfer function that showed the highest ASIS force measured for a given level of lap belt tension is recommended for future use.

Disparities in injury tolerance and kinematic response remain understudied despite field data highlighting sex-based differences in injury risk. Furthermore, the automotive industry anticipates occupants will prefer reclined seating in highly automated vehicles. This study aimed to compare thoracolumbar spine kinematics and injuries between mid-size female and male post-mortem human subjects (PMHS) in reclined frontal impacts. Seven adult PMHS (three female, four male) were tested in reclined (50°) 50 km/h frontal impacts. The PMHS were seated on a semi-rigid seat and restrained by a prototype three-point seat belt system designed to mitigate submarining. The 3-D motions of five vertebrae and the pelvis were measured by an optical motion tracking system. Pressure transducers were inserted into intervertebral discs at three locations along the lumbar spine to track timing of lumbar vertebra fractures. Due to variations in the geometry of the pelvis and soft tissue surrounding the pelvis compared to the male subjects, the female subjects could not be positioned in the seat the same as the males, and, as a result, the females and their belt anchors needed to be translated forward in the seat to maintain similar belt geometry relative to the males. The females exhibited similar pre-test spinal curvatures and kinematics to the males. An L1 fracture was observed in one of three female subjects and two of four male subjects, and timing of these fractures were both similar (61 ∼ 65 ms) and close to the time of peak downward seat force. Generally, the female and male subjects exhibited similar kinematic and injury responses in this reclined frontal impact sled test condition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The interaction of the three-point seat belt with the occupant, particularly the lap belt with the pelvis, is affected by a multitude of intrinsic and extrinsic factors, including the torso recline angle, lap belt angle, and occupant body mass index (BMI). While field data analyses have shown the strong safety benefit for seat belt use regardless of occupant size or crash direction, the term "submarining" historically has been used to describe a scenario in which the lap belt loads the abdominal soft tissue and organs, superior and posterior to the pelvic bone. While contemporary restraint systems work to effectively address the risk of submarining in occupants properly seated and properly belted, scenarios in which the lap belt may not properly engage the load-bearing pelvis remain. These scenarios, including a reclined torso angle or shallow lap belt angle, require further study. In this research study, eight non-injurious seated belt pull tests were conducted on two constrained whole-body cadavers of above-normal BMI (≥ 25 kg/m 2 ) with controlled variation of torso and lap belt-pelvis angles. Test factors affecting belt engagement with the pelvis were identified for each subject. Belt engagement was largely affected by the initial placement of the lap belt. The initial belt placement was affected by the torso angle which influenced the distribution of the abdominal soft tissue. The belt disengagement thresholds differed between subjects due to the inter-subject differences in soft tissue distribution, which affected the lap belt kinematics relative to the pelvis. In addition to improving the understanding of this particular submarining mechanism, this study provides a dataset for future validation of human body model soft tissue deformation response from lap belt loading., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Iliac wing fractures due to lap belt loading have been identified in laboratory tests for almost 50 years and an analysis of recent data suggests these injuries are also occurring in the field. With the introduction of highly autonomous vehicles on the horizon, vehicle manufacturers are exploring open cabin concepts that permit reclined postures and separation of the occupant from the knee bolster and instrument panel. This will result in greater reliance on the lap belt and lap belt/pelvis loading to restrain occupants. No injury criteria exist for iliac wing fractures resulting from lap belt loading like that seen in frontal crash conditions. This study tested the tolerance of isolated iliac wings in a controlled lap belt-like loading environment while incorporating the effect of loading angle after analyzing lap belt loading experiments from a previous study. Twenty-two iliac wings were tested; nineteen of them sustained fracture (exact), but the loading input was insufficient to cause fracture in the other three (right censored). The fracture tolerance of the tested specimens ranged widely (1463-8895 N) and averaged 4091 N (SD 2381 N). Injury risk functions were created by fitting Weibull survival models to data that integrated censored and exact failure observations., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Objective: The goal of this study was to evaluate the effect of axial compression, employed with a follower-load mechanism, on the response of the lumbar spine in flexion and extension bending. Additional goals include measurement of both the kinetic (stiffness) and kinematic (deformation distribution) responses, evaluating how the responses vary across specimens, and to develop response corridors that can be used to evaluate human body models (HBMs) and anthropomorphic test devices (ATDs)., Methods: Seven mid-sized male adult lumbar spines (T12-S1) from postmortem human surrogates were tested in subinjurious flexion and extension bending with 0, 900, and 1800 N of superimposed axial compression. Tests were performed in load-control with a 6-DOF robotic test system that applied pure flexion and extension moments to the specimens, and axial compression was directed along the spine's curvature via a follower load mechanism powered by force-controlled linear actuators. Load-deformation response data were captured and used to characterize the kinetic response of the lumbar spine in flexion/extension, and how it varies with axial compression. Individual vertebral kinematics were captured using 3D motion capture and the data was used to illustrate the distribution of bending deformation across each intervertebral joint of the spine, as well has how that distribution changes with axial compression. These response data were used to develop elliptical path-length parameterized response corridors for surrogate biofidelity evaluation., Results: The lumbar spine was found to be generally stiffer in extension than in flexion, but this difference decreased with increasing axial compression. The lumbar spine exhibited a nonlinear kinetic (moment vs. angle) response in flexion that became more linear and stiffer with the addition of axial compression. In flexion without axial load, the majority of the bending deformation occurred at the L5-S1 joint, whereas in extension, deformation was more evenly distributed across the different intervertebral levels, but the locus of deformation was located in the mid-proximal lumbar at L2-L3., Conclusions: The superposition of axial compression in the lumbar spine affects the kinetic and kinematic response of the lumbar spine in flexion and extension. The response data and approach detailed in this study permit better assessment of ATD and HBM biofidelity.

Objective: Automobile booster seats are intended to improve belt fit for children that are too large for a harness-style child restraint, but not yet big enough to fit properly in an adult seat belt. Our objective was to prospectively study the relationship between booster seat design and interaction with the seat belt (specifically, submarining risk) for a child occupant using computer simulation of automobile crash events., Methods: Frontal-impact simulations were performed with a 6-year-old child human body model. Simplified models of booster seats were developed using an automated process designed to capture key characteristics of booster geometry, stiffness, belt guide construction, and attachment to the vehicle seat. The child model was positioned in a range of postures from upright to slouched. Our main interest was submarining, where the child's pelvis slips under the lap belt and the belt loads into the abdomen (defined based on the motion of the lower lap belt edge relative to the ASIS)., Results: Among the parameters studied, the factors that had the greatest effect on submarining risk were the booster's stiffness and the child's posture. Booster models of a low-stiffness construction (similar to an inflatable booster) nearly always resulted in submarining, regardless of the other design characteristics of the booster. A slouched posture also substantially increased the likelihood of submarining (even for high-stiffness boosters)., Conclusions: These results suggest that booster seats of a stiffer construction, and booster seats that promote an upright posture may provide a protective benefit compared to softer boosters and boosters that are more likely to result in slouching of the child.

The world often goes too fast for children with autism spectrum disorder (ASD) to process. We tested the therapeutic effectiveness of input slowing in children with ASD. Over 12 months, 12 children with ASD had weekly speech therapy sessions where stimuli were slowly played on a PC, while 11 age- and level-matched children with ASD had speech therapy using real-time stimuli. At the beginning and end of the study, all participants were assessed on communication, imitation, facial emotion recognition, behavior, and face exploration. Whereas communication and facial emotion recognition improved in both groups, imitation increased, inappropriate behaviors decreased, and time spent fixating mouth and eyes increased solely in the group using slowness. Slowness therapy seems very promising for ASD children., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Facial movements of others during verbal and social interaction are often too rapid to be faced and/or processed in time by numerous children and adults with autism spectrum disorder (ASD), which could contribute to their face-to-face interaction peculiarities. We wish here to measure the effect of reducing the speed of one's facial dynamics on the visual exploration of the face by children with ASD. Twenty-three children with ASD and 29 typically-developing control children matched for chronological age passively viewed a video of a speaker telling a story at various velocities, i.e., a real-time speed and two slowed-down speeds. The visual scene was divided into four areas of interest (AOI): face, mouth, eyes, and outside the face. With an eye-tracking system, we measured the percentage of total fixation duration per AOI and the number and mean duration of the visual fixations made on each AOI. In children with ASD, the mean duration of visual fixations on the mouth region, which correlated with their verbal level, increased at slowed-down velocity compared with the real-time one, a finding which parallels a result also found in the control children. These findings strengthen the therapeutic potential of slowness for enhancing verbal and language abilities in children with ASD.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with a very large number of risk loci detected in the genome. However, at best, each of them explains rare cases, the majority being idiopathic. Genomic data on ASD derive mostly from post-mortem brain analyses or cell lines derived from blood or patient-specific induced pluripotent stem cells (iPSCS). Therefore, the transcriptional and regulatory architecture of the nervous system, particularly during early developmental periods, remains highly incomplete. To access the critical disturbances that may have occurred during pregnancy or early childhood, we recently isolated stem cells from the nasal cavity of anesthetized patients diagnosed for ASD and compared them to stem cells from gender-matched control individuals without neuropsychiatric disorders. This allowed us to discover MOCOS, a non-mutated molybdenum cofactor sulfurase-coding gene that was under-expressed in the stem cells of most ASD patients of our cohort, disturbing redox homeostasis and synaptogenesis. We now report that a divergent transcription upstream of MOCOS generates an antisense long noncoding RNA, to which we coined the name COSMOC. Surprisingly, COSMOC is strongly under-expressed in all ASD patients of our cohort with the exception of a patient affected by Asperger syndrome. Knockdown studies indicate that loss of COSMOC reduces MOCOS expression, destabilizes lipid and energy metabolisms of stem cells, but also affects neuronal maturation and splicing of synaptic genes. Impaired expression of the COSMOC/MOCOS bidirectional unit might shed new lights on the origins of ASD that could be of importance for future translational studies.

The objective of this study was to leverage and compare multiple machine learning techniques for predicting the human body model response in restraint design simulations. Parametric simulations with 16 independent variables were performed. Ordinary least-squares (OLS), least absolute shrinkage and selection operator (LASSO), neural network (NN), support vector regression (SVR), regression forest (RF), and an ensemble method were used to develop response surface models of the simulations. The hyperparameters of the machine learning techniques were optimized through grid search and cross-validation to avoid under-fitting and over-fitting. The ensemble method outperformed other techniques, followed by LASSO, SVR, NN, RF, and OLS. Findings indicated that optimizing the metamodel hyper-parameters are essential to predict the optimum set of restraint design parameters.

Objective: To optimize the components of restraint systems for protecting obese (BMI = 35 kg/m 2 ) and normal BMI (BMI = 25) human body models (HBMs) in frontal crash simulations, and to compare the two optimized designs., Methods: The Life Years Lost metric, which incorporates the risk of injury and long-term disability to different body regions, was used as the optimization objective function. Parametric simulations, sampled from a 15-parameter design space using the Latin Hypercube technique, were performed and metamodels of the HBM responses were developed. A genetic algorithm was applied to the metamodels to identify the optimized designs., Results: While most of the restraint parameters between the optimized design for obese and normal BMI HBMs were similar, the main difference was that the restraint for the obese HBM included an under-the-seat airbag, which mitigated its lower extremity excursion, improved its torso kinematics, and decreased its lower extremity and lumbar spine injury risks. The optimized designs for both HBMs included an inflatable seat belt, which reduced the risk of thoracic injury., Conclusions: The design recommendations from this study should be considered to improve safety of occupants with obesity.

Objective: Self-driving technology will bring novelty in vehicle interior design and allow for a wide variety of occupant seating choices. Previous studies have shown that the increased risk of submarining exhibited by reclined occupants cannot be fully mitigated by changes in the seat configuration alone. This study aims to investigate the effects of three restraint countermeasures on cases with marginal submarining events and estimate their effect on submarining risk and injury prediction metrics., Methods: Vehicle environment frontal crash Finite Element (FE) simulations were performed with the two simplified Global Human Body Model Consortium (GHBMC) occupant models: small female and midsize male. The baseline occupant restraints consisted of a frontal airbag, a seatback-integrated 3-point belt with a lap belt anchor pre-tensioner, and a retractor-mounted pre-tensioner and load limiter. Based on submarining thresholds identified in previous studies, three baseline configurations were identified for each occupant size. For each baseline case three restraint system modifications were evaluated. The modifications consisted of the introduction of a pelvis restraint cushion airbag (PRC), the use of a knee airbag (KAB) and the modification of the of the passenger airbag location (PAB). Simulations were performed using the USNCAP 56 km/h frontal crash pulse. Occupant kinematic data was extracted from each simulation to investigate how changes in the restraint system configuration affects submarining., Results: Overall, in only one of the investigated cases did the proposed restraint modification prevent submarining occurrence, however each of the restraint modifications reduced the pelvis excursion over the baseline scenario. The presence of the PRC airbag showed the highest reduction in pelvis forward excursion for the female model. The presence of the KAB and the modified location of the PAB also contributed to reductions in excursion to a smaller degree. For the male surrogate, the KAB showed the highest reduction in pelvis forward excursion. The presence of the PRC led to a reduction in the lumbar spine shear force., Conclusions: Submarining may be a major challenge to overcome for reclined occupants in autonomous driving systems. This suggests that there may not be a single generalizable currently-existing countermeasure able to effectively prevent marginal submarining cases in reclined positions.

Frontal impacts with reclined occupants are rare but severe, and they are anticipated to become more common with the introduction of vehicles with automated driving capabilities. Computational and physical human surrogates are needed to design and evaluate injury countermeasures for reclined occupants, but the validity of such surrogates in a reclined posture is unknown. Experiments with post-mortem human subjects (PMHS) in a recline posture are needed both to define biofidelity targets for other surrogates and to describe the biomechanical response of reclined occupants in restrained frontal impacts. The goal of this study was to evaluate the kinematic and injury response of reclined PMHS in 30 g, 50 km/h frontal sled tests. Five midsize adult male PMHS were tested. A simplified semi-rigid seat with an anti-submarining pan and a non-production threepoint seatbelt (pre-tensioned, force-limited, seat-integrated) were used. Global motions and local accelerations of the head, pelvis, and multiple vertebrae were measured. Seat and seatbelt forces were also measured. Injuries were assessed via post-test dissection. The initial reclined posture aligned body regions (pelvis, lumbar spine, and ribcage) in a way that reduced the likelihood of effective restraint by the seat and seatbelt: the occupant's pelvis was initially rotated posteriorly, priming the occupant for submarining, and the lumbar spine was loaded in combined compression and bending due to the inertia of the upper torso during forward excursion. Coupled with the high restraining forces of the seat and seatbelt, the unfavorable kinematics resulted in injuries of the sacrum/coccyx (four of five PMHS injured), iliac wing (two of five PMHS injured), lumbar spine (three of five PMHS injured), and ribcage (all five PMHS suffered sternal fractures, and three of five PMHS suffered seven or more rib fractures). The kinematic and injury outcomes strongly motivate the development of injury criteria for the lumbar spine and pelvis, the inclusion of intrinsic variability (e.g., abdomen depth and pelvis shape) in computational simulations of frontal impacts with reclined occupants, and the adaptation of comprehensive restraint paradigms to predicted variability of occupant posture.

Objective: Self-driving technology will bring novelty in vehicle interior design and allow for a wide variety of occupant seating choices. Thus, vehicle safety systems may be challenged to protect occupants over a wider range of potential postures. This study aims to investigate the effects of the seat cushion angle on submarining risk, lumbar spine loads and pelvis excursion for reclined occupants in frontal crashes., Methods: Frontal crash finite element simulations were performed with two of the simplified Global Human Body Model Consortium (GHBMC) occupant models: the small female and the midsize male. Occupant restraints consisted of a frontal airbag, a seatback-integrated 3-point belt with a lap belt anchor pre-tensioner, and a retractor pre-tensioner with a force limiter. For each simulation, parameters including seat cushion angle (3°, 8°, 13°), seatback recline angle (0°, 10°, 20°, 30°), and knee bolster (KB) position relative to the occupant (baseline and no KB) were varied. A full-factorial simulation matrix was performed using the USNCAP 56 km/h frontal crash pulse. Occupant kinematics data were extracted from each simulation to investigate how changes in seat cushion angle, anthropometry, seatback angle, and KB position would affect submarining across all simulated cases., Results: Overall, the F05-OS female model was more likely to submarine when compared to the male occupant model. The threshold for submarining was also affected by the seat cushion angle, seatback angle and KB distance. For the F05-OS model, increasing the seat cushion angle to 13° prevented submarining in the 10° seatback angle case, regardless of the KB position. Similarly, the 13° cushion angle prevented submarining for the M50-OS in the 30° seatback angle configuration but only in the presence of a KB. The results further show an increased lumbar flexion load with increased seat recline angle, as well as occupant-to-KB distance, although an opposite trend with the increased seat cushion angle., Conclusions: Submarining may be a major challenge to overcome for reclined occupants in autonomous driving systems. This study shows that seat cushion angle plays a role in restraining occupants in recline scenarios, but it is not sufficient to prevent submarining without additional countermeasures.

Objective: Highly automated vehicles may permit alternative seating postures, which could alter occupant kinematics and challenge current restraint designs. One predicted posture is a reclined seated position. While the spine of upright occupants is subjected to flexion during frontal crashes, the orientation of reclined occupants tends to subject the spine to high compressive loads followed by high flexion loads. This study aims to investigate kinematics and mechanisms of loading in the thoracolumbar spine for a reclined seated posture through the use of postmortem human subjects (PMHS)., Methods: Frontal impact sled tests (50 kph delta-v) were conducted on five adult midsize male PMHS seated with the torso reclined to 50 degrees with respect to the vertical. The PMHS were seated on a semi-rigid seat and restrained by a seat-integrated three-point belt with dual lap-belt pretensioners and a shoulder-belt pretensioner with a 3 kN load-limiter. 3-D kinematic trajectories of five chosen vertebrae, and the pelvis were measured relative to the vehicle buck. Intervertebral pressure transducers were installed at three locations in the lumbar column to detect load timing., Results: Three PMHS suffered fractures at L1. Combined compression and flexion of the thoracolumbar spine occurred in all tests, but the magnitude of peak flexion varied across the PMHS. During the PMHS' forward excursion, the pelvis rotated anteriorly in two tests and posteriorly in two tests (lap-belt submarining occurred in one). In one test, the pelvis mount interacted with the seat, but did not affect kinematics., Conclusions: Anterior rotation of the pelvis caused increased extension of the lumbar spine, which exacerbated lumbar compression in two of the PMHS; the one subject whose pelvis kinematic tracking was lost exhibited similar compression kinematics. Posterior rotation of the pelvis enabled lumbar flexion, which decreased lumbar compression, but lead to lap-belt submarining in one case. Lumbar kinematics for these reclined frontal impacts were sensitive to changes in initial posture of the spine (magnitude of lordosis or kyphosis) and pelvis (pitch angle). To our knowledge, this study is the first to analyze thoracolumbar kinematics and resulting injuries of a reclined seating posture using PMHS.

Background: Previous studies have shown that occupants with obesity are at a greater risk of fatality and serious injury than other occupants in motor vehicle crashes., Objective: To provide a more complete description of the most frequent injuries and the most frequently injured body regions for occupants with obesity., Methods: Sampled cases (n = 13,470) representing ~4.7 million adult occupants involved in frontal crashes (between 2000 and 2015) were selected from the U.S. National Automotive Sampling System-Crashworthiness Data System database. A retrospective cohort study was performed to study the effect of BMI on the risk of injury to different body regions and to identify the most frequent injuries to occupants with different BMIs. Lastly, in-depth crash analysis cases from the U.S. Crash Injury Research and Engineering Network (CIREN) database were studied to elucidate the source of the most common injuries to occupants with obesity., Results: Occupants with obesity experienced a higher risk of upper extremity (4.79 vs 2.92%), lower extremity (8.37 vs 3.23%), and spine (1.53 vs 1.09%) injuries than other occupants. After adjusting for other variables, the risks of spinal, thoracic, and extremities injuries were found to be affected by the BMI class. Seven out of the ten most common injuries sustained by occupants with obesity were lower extremity injuries, and talus fractures were the most common overall. Direct loading through the plantar surface of the foot by the vehicle toe pan was found to be a likely cause of many of those injuries based on CIREN cases., Conclusions: The injuries of occupants with obesity are different than other occupants which can be attributed to their different interaction with the seat belt and vehicle interior. The findings of this study should be considered for designing restraint systems to protect occupants with obesity in car crashes.

Objective: Self-driving technology will bring novelty in occupant seating choices and vehicle interior design. Thus, vehicle safety systems may be challenged to protect occupants over a wider range of potential postures and seating choices. This study aims to investigate the effects of occupant size, seat recline, and knee bolster position on submarining risk and injury prediction metrics for reclined occupants in frontal crashes. Methods: Frontal crash finite element (FE) simulations were performed with the 3 simplified Global Human Body Model Consortium (GHBMC) occupant models: small female, midsize male, and large male. Additionally, a detailed GHBMC midsize male model was used to compare with selected simplified cases. For each simulation, parameters including seatback recline angle (0.9°, 10.9°, 20.9°, 30.9°) and knee bolster position relative to the occupant (baseline, close, far, and no knee bolster) were varied. Impacts were simulated with the U.S. New Car Assessment Program 56 km/h frontal crash pulse. Occupant kinematics data were extracted from each simulation in a full-factorial sensitivity study to investigate how changes in anthropometry, seating position, and knee bolster position would affect submarining across all simulated cases. Results: Overall, increasing the occupant-to-knee bolster distance resulted in more submarining cases. The threshold for submarining was also affected by the seat recline angle. The lowest threshold observed occurred with 10.9° of recline with the small female model. Submarining was observed at recline angles at and above 20.9° for the midsize male model and 30° for the large male model. The initial lap belt position, pelvis orientation, and their relationship were good predictors of submarining. Increased lumbar flexion moment was observed with increased seat recline angle as well as occupant-to-knee bolster distance. The detailed GHBMC model was more prone to submarining than the simplified model. Conclusions: Submarining may be a major challenge to overcome for reclined occupants, which may become more prevalent with autonomous driving systems. This study shows that the angle of recline, anthropometric variation, and position of the knee bolster affect the risk of submarining. To our knowledge, this is the first study to computationally evaluate the occupant protection implications of seatback recline for multiple body sizes, postures, and positions relative to the vehicle interior.

Objective: Recreational off-highway vehicle (ROHV) crashes are of concern because sales of these vehicles have been growing rapidly and because newer vehicles tend to have significantly greater performance than older models. We evaluated the available data to understand trends in ROHV crashes and the factors that contributed to serious injury., Methods: We combined information from (1) the Fatality Analysis Reporting System (FARS), (2) a database compiled by the Consumer Product Safety Commission, and (3) a vehicle sales database. These aggregated data were used to describe trends, demographics, and frequent causes of serious injuries and fatalities., Results: On-road fatal crashes grew from 0 in the year 2000 to 37 in 2015; at the same time, sales grew from approximately 100,000 to 400,000 vehicles annually. Much of the increase in ROHV sales was in 2 new, higher performance classes of vehicles. Further, seat belt and helmet use in this cohort was rare (at least 46% unbelted, only 2% confirmed to be helmeted) and drinking and driving was common (57% of crashes in FARS). These vehicles appear to have increased potential for rollover, which often led unbelted occupants to be ejected, putting them at risk of being injured as the vehicle rolled on top of them., Conclusions: Serious ROHV crashes have grown with sales. Resulting injuries appear to be strongly influenced by inconsistent seat belt use, frequent drunk driving, and increased propensity for the vehicles to roll over.

Objective: To meet increasing customer demand, many vehicle manufacturers are now offering a panoramic sunroof option in their vehicle lineup. Currently, there is no regulatory or consumer test aimed at assessing the potential for ejection mitigation of roof glazing, which leaves manufacturers to develop internal performance standards to guide designs. The goal of this study was to characterize the variety of occupant-to-roof impacts involving unbelted occupants in rollover crashes to determine the ranges of possible effective masses and impact velocities. This information can be used to define occupant retention requirements and performance criteria for roof glazing in occupant ejection protection., Methods: This study combined computational (MADYMO and LS-Dyna) simulations of occupant kinematics in rollover crashes with laboratory rollover crash tests using the dynamic rollover test system (DRoTS) and linked them through controlled anthropomorphic test device (ATD)-to-roof ("drop") impact tests. The DRoTS and the ATD drop tests were performed to explore impact scenarios and estimate dummy-to-roof impact impulses. Next, 13 sets of vehicle kinematics and deformation data were extracted from a combination of vehicle dynamics and finite element model simulations that reconstructed variations of rollover crash cases from the field data. Then occupant kinematics data were extracted from a full-factorial sensitivity study that used MADYMO simulations to investigate how changes in anthropometry and seating position would affect occupant-roof impacts across all 13 cases. Finite element (FE) simulations of ATD and Global Human Body Models Consortium (GHBMC) human body model (HBM) roof impacts were performed to investigate the most severe cases from the MADYMO simulations to generate a distribution of head-to-roof impact energies., Results: From the multiparameter design of experiment and experimental study, kinematics and energy output were extracted and analyzed. Based on dummy-to-roof impact force and dummy-to-roof impact velocity, the most severe rollover scenarios were identified. In the DRoTS experiments followed by the drop tests, the range of identified impact velocities was between 2 and 5.8 m/s. However, computational simulations of the rollover crashes showed higher impact velocities and similar effective masses. The largest dummy-to-roof impact velocity was 11 m/s., Conclusions: This study combined computational and experimental analyses to determine a range of possible unbelted occupant-to-roof impact energies. These results can be used to determine design parameters for an impactor for the assessment of the risk of roof glazing ejection for unbelted occupants in rollover crashes.

According to the temporal theory of autism spectrum disorders (ASDs), audiovisual changes in environment, particularly those linked to facial and verbal language, are often too fast to be faced, perceived, and/or interpreted online by many children with ASD, which could help explain their facial, verbal, and/or socioemotional interaction impairments. Our goal here was to test for the first time the impact of slowed-down audiovisual information on verbal cognition and behavior in 2 boys with ASD and verbal delay. Using 15 experimental sessions during 4 months, both boys were presented with various stimuli (eg, pictures, words, sentences, cartoons) and were then asked questions or given instructions regarding stimuli. The audiovisual stimuli and instructions/questions were presented on a computer's screen and were always displayed twice: at real-time speed (RTS) and at slowed-down speed (SDS) using the software Logiral. We scored the boys' verbal cognition performance (ie, ability to understand questions/instructions and answer them verbally/nonverbally) and their behavioral reactions (ie, attention, verbal/nonverbal communication, social reciprocity), and analyzed the effects of speed and order of the stimuli presentation on these factors. According to the results, both participants exhibited significant improvements in verbal cognition performance with SDS presentation compared with RTS presentation, and they scored better with RTS presentation when having SDS presentation before rather than after RTS presentation. Behavioral reactions were also improved in SDS conditions compared with RTS conditions. This initial evidence of a positive impact of slowed-down audiovisual information on verbal cognition should be tested in a large cohort of children with ASD and associated speech/language impairments., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Objective: Face and gaze avoidance are among the most characteristic and salient symptoms of autism spectrum disorders (ASD). Studies using eye tracking highlighted early and lifelong ASD-specific abnormalities in attention to face such as decreased attention to internal facial features. These specificities could be partly explained by disorders in the perception and integration of rapid and complex information such as that conveyed by facial movements and more broadly by biological and physical environment. Therefore, we wish to test whether slowing down facial dynamics may improve the way children with ASD attend to a face., Methods: We used an eye tracking method to examine gaze patterns of children with ASD aged 3 to 8 (n=23) and TD controls (n=29) while viewing the face of a speaker telling a story. The story was divided into 6 sequences that were randomly displayed at 3 different speeds, i.e. a real-time speed (RT), a slow speed (S70=70% of RT speed), a very slow speed (S50=50% of RT speed). S70 and S50 were displayed thanks to software called Logiral™, aimed at slowing down visual and auditory stimuli simultaneously and without tone distortion. The visual scene was divided into four regions of interest (ROI): eyes region; mouth region; whole face region; outside the face region. The total time, number and mean duration of visual fixations on the whole visual scene and the four ROI were measured between and within the two groups., Results: Compared to TD children, children with ASD spent significantly less time attending to the visual scenes and, when they looked at the scene, they spent less time scanning the speaker's face in general and her mouth in particular, and more time looking outside facial area. Within the ASD group mean duration of fixation increased on the whole scene and particularly on the mouth area, in R50 compared to RT. Children with mild autism spent more time looking at the face than the two other groups of ASD children, and spent more time attending to the face and mouth as well as longer mean duration of visual fixation on mouth and eyes, at slow speeds (S50 and/or S70) than at RT one., Conclusions: Slowing down facial dynamics enhances looking time on face, and particularly on mouth and/or eyes, in a group of 23 children with ASD and particularly in a small subgroup with mild autism. Given the crucial role of reading the eyes for emotional processing and that of lip-reading for language processing, our present result and other converging ones could pave the way for novel socio-emotional and verbal rehabilitation methods for autistic population. Further studies should investigate whether increased attention to face and particularly eyes and mouth is correlated to emotional/social and/or verbal/language improvements., (Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

With an onset under the age of 3 years, autism spectrum disorders (ASDs) are now understood as diseases arising from pre- and/or early postnatal brain developmental anomalies and/or early brain insults. To unveil the molecular mechanisms taking place during the misshaping of the developing brain, we chose to study cells that are representative of the very early stages of ontogenesis, namely stem cells. Here we report on MOlybdenum COfactor Sulfurase (MOCOS), an enzyme involved in purine metabolism, as a newly identified player in ASD. We found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders. Genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of MOCOS results in neurotransmission and synaptic defects. Furthermore, we found that MOCOS misexpression induces increased oxidative-stress sensitivity. Our results demonstrate that altered MOCOS expression is likely to have an impact on neurodevelopment and neurotransmission, and may explain comorbid conditions, including gastrointestinal disorders. We anticipate our discovery to be a fresh starting point for the study on the roles of MOCOS in brain development and its functional implications in ASD clinical symptoms. Moreover, our study suggests the possible development of new diagnostic tests based on MOCOS expression, and paves the way for drug screening targeting MOCOS and/or the purine metabolism to ultimately develop novel treatments in ASD.

Objective: The objective of the current study was to evaluate the whole-body kinematic response of the Total Human Model for Safety (THUMS) occupant model in controlled laboratory rollover tests by comparing the model response to postmortem human surrogate (PMHS) kinematic response targets published in 2014., Methods: A computational model of the parametric vehicle buck environment was developed and the AM50 THUMS occupant model (Ver 4.01) was subjected to a pure dynamic roll at 360°/s in trailing-side front-row seating position. A baseline configuration was defined by a baseline posture representing the average of all PMHS postures, with a friction coefficient of 0.4 for the belt and 0.6 for the seat. To encompass challenges in controlling boundary conditions from the PMHS tests and ensure the robustness of the model evaluation, a total of 12 simulations were performed to investigate the following: 1. The effect of initial posture by adding 3 additional postures representing PMHS extremes. 2. The effect of belt tension by varying tension from the nominal vehicle retractor belt tension of 5 N to the 35 N belt tension used in the PMHS tests. 3. The effect of friction between the environment (belt, seat) and THUMS. Trajectories (head, T1, T4, T10, L1, and sacrum), spinal segment rotations (head-to-T1, T1-to-T4, T4-to-T10, T10-to-L1, and L1-to-sacrum) relative to the rollover buck and spinal segment elongation/compression calculated from the simulations were compared to PMHS corridors using a correlation method (CORA)., Results: THUMS baseline response showed lower correlation (overall CORA score = 0.63) with the PMHS response in rollover compared to other crash modes. THUMS and PMHS demonstrated similar kinematic responses in the longitudinal axis and vertical axis but significantly different lateral excursion relative to the seat. In addition, no spinal elongation was observed for THUMS compared to the PMHS. The posture, pretension, and belt frictions were found to alter model kinematics, especially on THUMS lateral axis motion. The posture was judged to be the most sensitive parameter evaluated because a change of 30 mm in the lateral axis results in up to an 80 mm of change in observed displacement., Conclusions: Though the model response in the lateral axis is significantly different than that of the PMHS, it is unclear whether this difference is the result of extrinsic factors (posture, pretension, and friction), where exact values in experiment are unknown or by model intrinsic factors (e.g., spine stiffness). These differences in occupant kinematics could potentially subject the PMHS and THUMS to very different loading conditions under roof impact in rollover crashes: different occupant posture and different roof impact location. Therefore, different injury mechanisms and severity might be predicted by the current model relative to the PMHS. Consequently, though the information provided in the current study could be useful for improving model biofidelity for rollover crashes, additional studies are required to properly solve this issue.

Background: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders caused by the interaction between genetic vulnerability and environmental factors. MicroRNAs (miRNAs) are key posttranscriptional regulators involved in multiple aspects of brain development and function. Previous studies have investigated miRNAs expression in ASD using non-neural cells like lymphoblastoid cell lines (LCL) or postmortem tissues. However, the relevance of LCLs is questionable in the context of a neurodevelopmental disorder, and the impact of the cause of death and/or post-death handling of tissue likely contributes to the variations observed between studies on brain samples., Methods: miRNA profiling using TLDA high-throughput real-time qPCR was performed on miRNAs extracted from olfactory mucosal stem cells (OMSCs) biopsied from eight patients and six controls. This tissue is considered as a closer tissue to neural stem cells that could be sampled in living patients and was never investigated for such a purpose before. Real-time PCR was used to validate a set of differentially expressed miRNAs, and bioinformatics analysis determined common pathways and gene targets. Luciferase assays and real-time PCR analysis were used to evaluate the effect of miRNAs misregulation on the expression and translation of several autism-related transcripts. Viral vector-mediated expression was used to evaluate the impact of miRNAs deregulation on neuronal or glial cells functions., Results: We identified a signature of four miRNAs (miR-146a, miR-221, miR-654-5p, and miR-656) commonly deregulated in ASD. This signature is conserved in primary skin fibroblasts and may allow discriminating between ASD and intellectual disability samples. Putative target genes of the differentially expressed miRNAs were enriched for pathways previously associated to ASD, and altered levels of neuronal transcripts targeted by miR-146a, miR-221, and miR-656 were observed in patients' cells. In the mouse brain, miR-146a, and miR-221 display strong neuronal expression in regions important for high cognitive functions, and we demonstrated that reproducing abnormal miR-146a expression in mouse primary cell cultures leads to impaired neuronal dendritic arborization and increased astrocyte glutamate uptake capacities., Conclusions: While independent replication experiments are needed to clarify whether these four miRNAS could serve as early biomarkers of ASD, these findings may have important diagnostic implications. They also provide mechanistic connection between miRNA dysregulation and ASD pathophysiology and may open up new opportunities for therapeutic.

The olfactory mucosa, located in the nasal cavity, is in charge of detecting odours. It is also the only nervous tissue that is exposed to the external environment and easily accessible in every living individual. As a result, this tissue is unique for anyone aiming to identify molecular anomalies in the pathological brain or isolate adult stem cells for cell therapy. Molecular abnormalities in brain diseases are often studied using nervous tissue samples collected post-mortem. However, this material has numerous limitations. In contrast, the olfactory mucosa is readily accessible and can be biopsied safely without any loss of sense of smell(1). Accordingly, the olfactory mucosa provides an "open window" in the adult human through which one can study developmental (e.g. autism, schizophrenia)(2-4) or neurodegenerative (e.g. Parkinson, Alzheimer) diseases(4,5). Olfactory mucosa can be used for either comparative molecular studies(4,6) or in vitro experiments on neurogenesis(3,7). The olfactory epithelium is also a nervous tissue that produces new neurons every day to replace those that are damaged by pollution, bacterial of viral infections. This permanent neurogenesis is sustained by progenitors but also stem cells residing within both compartments of the mucosa, namely the neuroepithelium and the underlying lamina propria(8-10). We recently developed a method to purify the adult stem cells located in the lamina propria and, after having demonstrated that they are closely related to bone marrow mesenchymal stem cells (BM-MSC), we named them olfactory ecto-mesenchymal stem cells (OE-MSC)(11). Interestingly, when compared to BM-MSCs, OE-MSCs display a high proliferation rate, an elevated clonogenicity and an inclination to differentiate into neural cells. We took advantage of these characteristics to perform studies dedicated to unveil new candidate genes in schizophrenia and Parkinson's disease(4). We and others have also shown that OE-MSCs are promising candidates for cell therapy, after a spinal cord trauma(12,13), a cochlear damage(14) or in an animal models of Parkinson's disease(15) or amnesia(16). In this study, we present methods to biopsy olfactory mucosa in rats and humans. After collection, the lamina propria is enzymatically separated from the epithelium and stem cells are purified using an enzymatic or a non-enzymatic method. Purified olfactory stem cells can then be either grown in large numbers and banked in liquid nitrogen or induced to form spheres or differentiated into neural cells. These stem cells can also be used for comparative omics (genomic, transcriptomic, epigenomic, proteomic) studies.

Imitation deficits observed among individuals with autism could be partly explained by the excessive speed of biological movements to be perceived and then reproduced. Along with this assumption, slowing down the speed of presentation of these movements might improve their imitative performances. To test this hypothesis, 19 children with autism, 37 typically-developing children and 17 children with Down syndrome were asked to reproduce facial and body movements presented on a computer at a normal/ecological and two slowed down speeds. Our main result showed that a subgroup of individuals with severe autism better reproduced the movements when presented slowly than at the ecological speed. This finding opens a new window for comprehension and rehabilitation of perceptual and imitative deficits in autism.

Disorders in verbal and emotional communication and imitation, social reciprocity and higher order cognition observed in individuals with autism spectrum disorders (ASD) are presented here as phenotypic expressions of temporo-spatial processing disorders (TSPDs). TSPDs include various degrees of disability in (i) processing multi-sensory dynamic stimuli online, (ii) associating them into meaningful and coherent patterns and (iii) producing real-time sensory-motor adjustments and motor outputs. In line with this theory, we found that slowing down the speed of facial and vocal events enhanced imitative, verbal and cognitive abilities in some ASD children, particularly those with low functioning autism. We then argue that TSPDs may result from Multi-system Brain Disconnectivity-Dissynchrony (MBD), defined as an increase or decrease in functional connectivity and neuronal synchronization within/between multiple neurofunctional territories and pathways. Recent functional magnetic resonance imaging (fMRI) and electrophysiological studies supporting MBD are outlined. Finally, we review the suspected underlying neurobiological mechanisms of MBD as evidenced in neuroimaging, genetic, environmental and epigenetic studies. Overall, our TSPD/MBD approach to ASD may open new promising avenues for a better understanding of neuro-physio-psychopathology of ASD and clinical rehabilitation of people affected by these syndromes.

Several recent studies suggest that autism may result from abnormal communication between brain regions. We directly assessed this hypothesis by testing the presence of abnormalities in a model of the functional cerebral network engaged during explicit emotion processing in adults with high functioning autism or Asperger syndrome. Comparison of structural equation models revealed abnormal patterns of effective connectivity, with the prefrontal cortex as a key site of dysfunction. These findings provide evidence that abnormal long-range connectivity between structures of the 'social brain' could explain the socio-emotional troubles that characterize the autistic pathology.

This study examined the effects of slowing down presentation of facial expressions and their corresponding vocal sounds on facial expression recognition and facial and/or vocal imitation in children with autism. Twelve autistic children and twenty-four normal control children were presented with emotional and non-emotional facial expressions on CD-Rom, under audio or silent conditions, and under dynamic visual conditions (slowly, very slowly, at normal speed) plus a static control. Overall, children with autism showed lower performance in expression recognition and more induced facial-vocal imitation than controls. In the autistic group, facial expression recognition and induced facial-vocal imitation were significantly enhanced in slow conditions. Findings may give new perspectives for understanding and intervention for verbal and emotional perceptive and communicative impairments in autistic populations.

Possible peculiarities in face perception in the autistic population were explored through two experiments. Fourteen autistic children (mean age=10 years 1 month) were individually matched to verbal mental age (VMA) and chronological age (CA) subjects. In a first experiment, subjects were to match faces on the basis of either their outer (hair, chin, ears) or their inner (eyes, nose, mouth) aspects. Autistic children performed equally well in both conditions, while VMA-matched children performed better in the outer than the inner part condition. In a second experiment, chimeric faces consisting of the outer part of an individual's face and the inner part of another individual's face were presented to the subjects. None of the groups showed a preference for neither the outer nor the inner part of the face in this condition. Results were discussed in terms of the existence of a local visual processing strategy in this population.