Robust human body model injury prediction in simulated side impact crashes

This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries.     

A monoclonal antibody specific for the cellular receptor for the group B coxsackieviruses.

A 50-kilodalton receptor protein (Rp-a) for the group B coxsackieviruses (CB) was isolated in a virus-receptor complex from detergent-solubilized HeLa cells (J. E. Mapoles, D. L. Krah, and R. L. Crowell, J. Virol. 55:560-566, 1985). It was used as an immunogen for preparation of a mouse monoclonal antibody (RmcB) which protected HeLa cells and Buffalo green monkey kidney cells from infection by all six serotypes of CB. RmcB did not protect HeLa cells from infection by poliovirus, echovirus 6, or coxsackievirus A18. This monoclonal antibody differed in receptor epitope specificity from a previously isolated antibody (RmcA) (R. L. Crowell, A. K. Field, W. A. Schleif, W. L. Long, R. J. Colonno, J. E. Mapoles, and E. A. Emini, J. Virol. 57:438-445, 1986) which blocked receptors only for type 1 CB (CB1), CB3, CB5, and echovirus 6. RmcA and RmcB recognized two distinct saturable receptors on HeLa cells, designated HR2 and HR1, respectively. Human rhabdomyosarcoma (RD) cells have the HR2 receptor for CB3-RD (a variant of CB3), but lack the HR1 receptor for CB3. Therefore, RD cells were resistant to infection by CB3. Although binding of CB3-RD to the HR2 receptor on RD cells can lead to infection, binding of CB3-RD to the HR2 receptor on HeLa cells did not lead to infection. Apparently, both CB3 and CB3-RD use only the HR1 receptor for infection of HeLa cells. Thus, a given virus may use two distinct receptors to bind to cells when only one virus-receptor interaction leads to infection.     

Bioconversion of 3-chlorobenzoate to 2-chloromuconate controlled by on line HPLC

Summary Strain RD330 a transposon mutant of Alcaligenes eutrophus JMP134 was considered to be dienelactone hydrolase defective (Don et al. 1985). During a bioconversion experiment with 3CB (3-chlorobenzoate) 2CMA (2-chloro-cis,cis-muconate) was accumulated by RD330 with an overall amount of 31%, but no dienelactone could be detected. Enzyme tests revealed that both enzymes 2CMA-cycloisomerase and dienelactone-hydrolase were induced at low levels in RD330 by 3CB and its metabolites.The control of 3CB addition during the bioconversion experiment was performed by on line HPLC (high pressure liquid chromatography).     

A viscous tolerance criterion for soft tissue injury assessment

Experiments in our laboratory have documented that high-speed impact can cause severe injury to internal organs before either of the currently accepted chest injury criteria, which are based on spinal acceleration or chest compression, approach their tolerance limit. Those studies demonstrate an interdependence between the velocity of deformation and compression of the body on injury risk. A tolerable level of chest compression at a low velocity can prove to be fatal at higher velocities of deformation. The observation of a rate-sensitive tolerable compression led to the introduction of the Viscous criterion, VCmax, which accounts for the importance of both parameters. VCmax is the maximum of the product of velocity of deformation (V) and compression (C), and is derivable from the chest deflection response. This paper presents the empirical evidence and theoretical basis supporting the Viscous criterion, and shows it to be an indicator of the energy dissipated by soft tissue deformation. The Viscous criterion accurately predicts the risk of vital organ and soft tissue injury when other criteria fail.     

Monoclonal antibody that inhibits infection of HeLa and rhabdomyosarcoma cells by selected enteroviruses through receptor blockade.

BALB/c mice were immunized with HeLa cells, and their spleen cells were fused with myeloma cells to produce hybridomas. Initial screening of culture fluids from 800 fusion products in a cell protection assay against coxsackievirus B3 (CB3) and the CB3-RD virus variant yielded five presumptive monoclonal antibodies with three specificities: protection against CB3 on HeLa, protection against CB3-RD on rhabdomyosarcoma (RD) cells, and protection against both viruses on the respective cells. Only one of the monoclonal antibodies (with dual specificity) survived two subclonings and was studied in detail. The antibody was determined to have an immunoglobulin G2a isotype and protected cells by blockade of cellular receptors, since attachment of [35S]methionine-labeled CB3 was inhibited by greater than 90%. The monoclonal antibody protected HeLa cells against infection by CB1, CB3, CB5, echovirus 6, and coxsackievirus A21 and RD cells against CB1-RD, CB3-RD, and CB5-RD virus variants. The monoclonal antibody did not protect either cell type against 16 other immunotypes of picornaviruses. The monoclonal antibody produced only positive fluorescence on those cells which were protected against infection, and 125I-labeled antibody confirmed the specific binding to HeLa and RD cells. The results suggest that this monoclonal antibody possesses some of the receptor specificity of the group B coxsackieviruses.     

Cervical spinal cord deformation during simulated head-first impact injuries

The relationship between bony spinal column and spinal cord injury during an injury event is not well understood. While several studies have measured spinal canal occlusion during axial impact, there has been limited work done to quantify the spinal cord compression or deformation during simulated injury. Because the cord is a viscoelastic solid it may provide resistance to bone fragments, ligaments or other elements that move into the canal and impinge it during column injury. This would differentiate the measurement of cord compression from the measurement of occlusion of an empty canal. In the present study, a novel method of visualizing and quantifying spinal cord deformation during dynamic head-first impact of ex vivo human cervical spine specimens (N=6) was developed. A radiodense, biofidelic surrogate spinal cord was imaged in the spinal canal using high speed cineradiography at 1000 frames per second. The dorsal-ventral diameter of the cord was measured at 1.5mm increments along its length for each frame of the radiographic footage. The resulting cord deformations were used to determine the theoretical neurological outcome of the impact based on published in vivo ferret studies. The corresponding probability of recovery for the spinal cord deformations in these tests ranged between 8% for atlantoaxial dislocation injury and 95% for mid-cervical spine hyperextension injury (based on the ferret data). Clinically relevant spinal column fracture patterns were produced in this study.     

Single amino acid changes in the virus capsid permit coxsackievirus B3 to bind decay-accelerating factor

Many coxsackievirus B isolates bind to human decay-accelerating factor (DAF) as well as to the coxsackievirus and adenovirus receptor (CAR). The first-described DAF-binding isolate, coxsackievirus B3 (CB3)-RD, was obtained during passage of the prototype strain CB3-Nancy on RD cells, which express DAF but very little CAR. CB3-RD binds to human DAF, whereas CB3-Nancy does not. To determine the molecular basis for the specific interaction of CB3-RD with DAF, we produced cDNA clones encoding both CB3-RD and CB3-Nancy and mutated each of the sites at which the RD and Nancy sequences diverged. We found that a single amino acid change, the replacement of a glutamate within VP3 (VP3-234E) with a glutamine residue (Q), conferred upon CB3-Nancy the capacity to bind DAF and to infect RD cells. Readaptation of molecularly cloned CB3-Nancy to RD cells selected for a new virus with the same VP3-234Q residue. In experiments with CB3-H3, another virus isolate that does not bind measurably to DAF, adaptation to RD cells resulted in a DAF-binding isolate with a single amino acid change within VP2 (VP2-138 N to D). Both VP3-234Q and VP2-138D were required for binding of CB3-RD to DAF. In the structure of the CB3-RD-DAF complex determined by cryo-electron microscopy, both VP3-234Q and VP2-138D are located at the contact site between the virus and DAF.     

Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55).

A coxsackievirus B3 (CB3) isolate adapted to growth in RD cells shows an alteration in cell tropism as a result of its capacity to bind a 70-kDa cell surface molecule expressed on these cells. We now show that this molecule is the complement regulatory protein, decay-accelerating factor (DAF) (CD55). Anti-DAF antibodies prevented CB3 attachment to the cell surface. Radiolabeled CB3 adapted to growth in RD cells bound to CHO cells transfected with human DAF, whereas CB3 (strain Nancy), the parental strain, did not bind to DAF transfectants. These results indicate that growth of CB3 in RD cells selected for a virus strain that uses DAF for cell surface attachment.     

Altered receptor specificity of coxsackievirus B3 after growth in rhabdomyosarcoma cells.

Serial "blind" passages in human rhabdomyosarcoma (RD) cells of prototype viruses from each of the six immunotypes of the group B coxsackieviruses (CB) resulted in the isolation of intratypic variants of CB1, CB3, CB5, and CB6. Each variant virus strain acquired the capacity to agglutinate human erythrocytes and produce small plaques on HeLa cells, although their serological specificity remained unchanged. An alteration in VP1 mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis was noted for CB3-RD. The CB3-RD variant was plaque purified on RD cells and studied for receptor interactions on both HeLa and RD cells. An attachment restriction appeared to exist for prototype CB3 on RD cells, whereas CB3-RD attached well to both cells. In attachment interference assays, HeLa cells saturated with CB3-RD blocked the attachment of CB3. In contrast, saturation of cells with CB1 (which shares a common receptor with parental CB3) failed to block the attachment of CB3-RD. This unidirectional receptor blockade suggested that a second site for the attachment of virions to receptors was acquired by the CB3-RD variant. Thus, more than one virus receptor specificity may be operative in the selection of host range virus mutants. The implications of this phenomenon as they may relate to pathogenesis are discussed.     

Finite element analysis for the evaluation of protective functions of helmets against ballistic impact

The ballistic impact of a human head model protected by a Personnel Armor System Ground Troops Kevlar^® helmet is analysed using the finite element method. The emphasis is to examine the effect of the interior cushioning system as a shock absorber in mitigating ballistic impact to the head. The simulations of the frontal and side impacts of the full metal jacket (FMJ) and fragment-simulating projectile (FSP) were carried out using LS-DYNA. It was found that the Kevlar^® helmet with its interior nylon and leather strap was able to defeat both the FMJ and FSP without the projectiles penetrating the helmet. However, the head injuries caused by the FMJ impact can be fatal due to the high stiffness of the interior strap. The bulge section at the side of the Kevlar^® helmet had more room for deformation that resulted in less serious head injuries.     

Age-related effects of compression rate and duration in cardiopulmonary resuscitation

The effects of various compression rate and duration combinations on chest geometry and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) were studied in immature swine. Pentobarbital-anesthetized 2- and 8-wk-old piglets received CPR after ventricular fibrillation. At compression rates of 40, 60, 80, 100, 120, and 150/min, duty cycle (compression duration/total cycle time) was increased from 10 to 80% by 10% increments. Mean aortic and sagittal sinus pressures, pulsatile displacement, and deformity of the anterior chest wall were measured. Increasing duty cycle increased cerebral perfusion pressure until chest relaxation time was compromised. Inadequate chest recoil, development of static chest deformation, and limitation of pulsatile chest wall movement occurred in both age groups when relaxation time was very short (150-200 ms in 2-wk-old piglets, 250-300 ms in 8-wk-old piglets). These changes in chest geometry correlated with deterioration of cerebral perfusion pressure only in 8-wk-old piglets. In the younger group, perfusion pressures plateaued but did not deteriorate. These data emphasize the importance of duty cycle in generating cerebral perfusion pressure and indicate that younger animals can tolerate high compression rates except at extremely long duty cycles.     

Biomechanical response of the pubic symphysis in lateral pelvic impacts: a finite element study

Automotive side impacts are a leading cause of injuries to the pubic symphysis, yet the mechanisms of those injuries have not been clearly established. Previous mechanical testing of isolated symphyses revealed increased joint laxity following drop tower lateral impacts to isolated pelvic bone structures, which suggested that the joints were damaged by excessive stresses and/or deformations during the impact tests. In the present study, a finite element (FE) model of a female pelvis including a previously validated symphysis sub-model was developed from computed tomography data. The full pelvis model was validated against measured force-time impact responses from drop tower experiments and then used to study the biomechanical response of the symphysis during the experimental impacts. The FE models predicted that the joint underwent a combination of lateral compression, posterior bending, anterior/posterior and superior/inferior shear that exceeded normal physiological levels prior to the onset of bony fractures. Large strains occurred concurrently within the pubic ligaments. Removal of the contralateral constraints to better approximate the boundary conditions of a seated motor vehicle occupant reduced cortical stresses and deformations of the pubic symphysis; however, ligament strains, compressive and shear stresses in the interpubic disc, as well as posterior bending of the joint structure remained as potential sources of joint damage during automotive side impacts.     

Human shoulder response to side impacts: a finite element study

This study aimed at developing a shoulder finite element (FE) model able to simulate the dynamic behaviour and to predict injuries in case of side impacts. This model is an updated version of the initial Human Model for Safety (HUMOS) FE model of the human body. Simulations performed with the model have been compared to experimental results of side impact tests conducted previously at INRETS. The shoulder model response under lateral impact appears to be in good agreement with experimental data such as impact force and shoulder deflections for different impact speeds and impact directions. These results seem promising for future applications such as shoulder injury prediction in simulated car crashes.     

Strain energy density as a rupture criterion for the kidney: impact tests on porcine organs, finite element simulation, and a baseline comparison between human and porcine tissues

High-velocity (up to 25 m/s) impact tests were performed on pig kidneys to characterize failure behavior at deformation rates associated with traumatic injury. Cylindrical tissue samples (n = 45) and whole perfused organs (n = 34) were impacted using both falling weights and a high-velocity pneumatic projectile impactor. Impact energy was incrementally increased until visible rupture occurred. The strain energy density failure threshold fell between 25 and 60 kJ/m3 for excised porcine tissue samples, and between 15 and 30 kJ/m3 for whole, perfused organs. The relationship between localized failure in whole organ impacts and tissue level failure thresholds observed in cylindrical tissue samples was explored using a detailed finite element model of the human kidney. The model showed good correlation between experimentally observed injury patterns and predicted strain energy density distributions within the renal parenchyma. Finally, to facilitate interpretation of the porcine renal impact results with regard to human trauma, quasi-static compression test results of freshly excised human kidney cortex samples (n = 30) were compared against similar tests on pig kidneys. Human tissues failed at Lagrange strain levels similar to porcine tissue (63+/-6.3%), but at 52% lower Lagrange stress (116+/-28 kPa), and 35% lower strain energy density (17.1+/-4.4 kJ/m3). Thus conservative interpretation of porcine test results is recommended.     

Development and validation of subject-specific finite element models for blunt trauma study

This study developed and validated finite element (FE) models of swine and human thoraxes and abdomens that had subject-specific anatomies and could accurately and efficiently predict body responses to blunt impacts. Anatomies of the rib cage, torso walls, thoracic, and abdominal organs were reconstructed from X-ray computed tomography (CT) images and extracted into geometries to build FE meshes. The rib cage was modeled as an inhomogeneous beam structure with geometry and bone material parameters determined directly from CT images. Meshes of soft components were generated by mapping structured mesh templates representative of organ topologies onto the geometries. The swine models were developed from and validated by 30 animal tests in which blunt insults were applied to swine subjects and CT images, chest wall motions, lung pressures, and pathological data were acquired. A comparison of the FE calculations of animal responses and experimental measurements showed a good agreement. The errors in calculated response time traces were within 10% for most tests. Calculated peak responses showed strong correlations with the experimental values. The stress concentration inside the ribs, lungs, and livers produced by FE simulations also compared favorably to the injury locations. A human FE model was developed from CT images from the Visible Human project and was scaled to simulate historical frontal and side post mortem human subject (PMHS) impact tests. The calculated chest deformation also showed a good agreement with the measurements. The models developed in this study can be of great value for studying blunt thoracic and abdominal trauma and for designing injury prevention techniques, equipments, and devices.     

Changes of calcium binding protein expression in spinothalamic tract neurons after peripheral inflammation

Specific neuronal populations are known to express calcium binding proteins (CBP) such as calbindin (CB), parvalbumin (PV) and calretinin (CR). These CBP can act as calcium buffers that modify spatiotemporal characteristics of intracellular calcium transients and affect calcium homeostasis in neurons. It was recently shown that changes in neuronal CBP expression can have significant modulatory effect on synaptic transmission. Spinothalamic tract (STT) neurons form a major nociceptive pathway and they become sensitized after peripheral inflammation. In our experiments, expression of CBP in STT neurons was studied in a model of unilateral acute knee joint arthritis in rats. Altogether 377, 374 and 358 STT neurons in the segments L3-4 were evaluated for the presence of CB, PV and CR. On the contralateral (control) side 1%, 9% and 47% of the retrogradely labeled STT neurons expressed CB, PV and CR, respectively. On the ipsilateral (arthritic) side there was significantly more CB (23%) and PV (25%) expressing STT neurons, while the number of CR positive neurons (50%) did not differ. Our results show increased expression of fast (CB) and slow (PV) calcium binding proteins in STT neurons after induction of experimental arthritis. This suggests that change in CBP expression could have a significant effect on calcium homeostasis and possibly modulation of synaptic activity in STT neurons.     

卡车与卡车前部碰撞驾驶员与前排乘车人损伤特征的研究

目的：研究道路交通事故卡车与卡车前部碰撞驾乘人员损伤特征,分析比较驾乘人员的损伤及损伤分布特点。方法：应用统计学方法对2001年-2010年昆明地区卡车与卡车200例前部碰撞人员损伤的法医学鉴定资料进行系统分析性研究。结果：1.驾驶员易发生损伤的部位是下肢、头颈部,其次为胸、腹部损伤。驾驶员易发生右下肢的损伤及骨折。驾驶员易发生颅骨骨折和肋骨骨折。2.前排乘车人员易发生损伤的部位是上肢、头颈部,其次为下肢,而胸腹部损伤较少见。前排乘车人员易发生上肢的损伤及双侧尺桡骨的骨折。前排乘车人员左侧头颈部受伤的几率大于驾驶员的相对部位。前排乘车人员易发生右肱骨骨折。结论：1.与前排乘车人相比,驾驶员易造成胸部、腹部及盆部、右侧下肢的损伤及右股骨胫腓骨的骨折,发生双侧上肢的体表损伤及尺桡骨骨折均明显少。在身体体表出现胸部、腹部及盆部多部位连续的损伤,有助于提高认定卡车驾驶员的准确性。2.与驾驶员相比,前排乘车人易形成左侧头颈部的损伤,上肢双侧尺桡骨骨折,右侧肱骨的骨折。当损伤位于身体左侧头颈部且有右侧肱骨的骨折,有助于提高认定卡车前排乘车人的准确性。     

Gelation of gellan gum aqueous solutions studied by polarization modulation spectroscopy

Circular birefringence (CB, or optical rotation) and linear birefringence (LB) were measured for gellan gum aqueous solutions with and without salt to examine the gelling system in the helical structure as well as in the orientation. It was found that gelling samples with salt show nonzero LB values, whereas LB is zero for the samples without salt even in the gel state. This difference can be explained by the thermal deformation of the system containing anisotropic aggregations of helices formed with the shielding effect of the added salt on the intramolecular and intermolecular electrostatic repulsions. Considering that the presence of LB in the system affects the estimation of CB, we developed an original procedure of the CB measurement to eliminate the contribution of LB. It was shown that our methods for eliminating the contribution of LB can improve the CB measurement for the gellan gum gel. The temperature dependence of [alpha] for the samples with salt in the gel state is quite different from that for the samples without salt, suggesting that the aggregates of helices in the samples containing a high concentration of salt form a supramolecular structure that contributes to CB.     

Effect of assumed stiffness and mass density on the impact response of the human chest using a three-dimensional FE model of the human body

The mass density, Young's modulus (E), tangent modulus (Et), and yield stress (sigma y) of the human ribs, sternum, internal organs, and muscles play important roles when determining impact responses of the chest associated with pendulum impact. A series of parametric studies was conducted using a commercially available three-dimensional finite element (FE) model, Total HUman Model for Safety (THUMS) of the whole human body, to determine the effect of changing these material properties on the predicted impact force, chest deflection, and the number of rib fractures and fractured ribs. Results from this parametric study indicate that the initial chest apparent stiffness was mainly influenced by the stiffness and mass density of the superficial muscles covering the torso. The number of rib fractures and fractured ribs was primarily determined by the stiffness of the ribcage. Similarly, the stiffness of the ribcage and internal organs contributed to the maximum chest deflection in frontal impact, while the maximum chest deflection for lateral impact was mainly affected by the stiffness of the ribcage. Additionally, the total mass of the whole chest had a moderately effect on the number of rib fractures.     

LRP5 mutations linked to high bone mass diseases cause reduced LRP5 binding and inhibition by SOST

The low density lipoprotein (LDL) receptor-related protein 5 (LRP5) is a co-receptor for Wnt proteins and a major regulator in bone homeostasis. Human genetic studies have shown that recessive loss-of-function mutations in LRP5 are linked to osteoporosis, while on the contrary, dominant missense LRP5 mutations are associated with high bone mass (HBM) diseases. All LRP5 HBM mutations are clustered in a single region in the LRP5 extracellular domain and presumably result in elevated Wnt signaling in bone forming cells. Here we show that LRP5 HBM mutant proteins exhibit reduced binding to a secreted bone-specific LRP5 antagonist, SOST, and consequently are more refractory to inhibition by SOST. As loss-of-function mutations in the SOST gene are associated with Sclerosteosis, another disorder of excessive bone growth, our study suggests that the SOST-LRP5 antagonistic interaction plays a central role in bone mass regulation and may represent a nodal point for therapeutic intervention for osteoporosis and other bone diseases.