<p>Traumatic injuries are the leading cause of death to children between the ages of one to nineteen years in the United States. The primary source of these traumatic injuries is motor vehicle traffic, with the head being the primary region of the body to suffer injury. While the pediatric neck is also prone to injury, it is particularly notable since it governs head excursion and acceleration, thus influencing head impacts and injuries. Pediatric fatalities can be prevented through safety improvements to vehicle compartments and child restraints by way of advanced biofidelic pediatric anthropomorphic testing devices (ATDs) and a more complete understanding of pediatric biomechanics. Computer models of the pediatric head and neck provide a valuable tool to combine results from pediatric postmortem human specimen (PMHS), radiological, and human volunteer studies to investigate the dynamics of the pediatric head and neck. The current study produced the first validated computer model of the pediatric head and neck which were created using the framework of a validated adult model. Radiology studies were conducted to determine pediatric cervical muscle cross sectional areas, vertebral anthropometry, and vertebral inertial properties. The results of these studies were combined with available pediatric PMHS properties to create the six and ten year old models. The models were validated against pediatric volunteer low speed frontal impacts and were then used to simulate higher rate and injurious inducing loading scenarios. The six and ten year old flexion bending stiffnesses were found to be 36% and 45% of the adult bending stiffness, respectively. The pediatric tensile stiffnesses were found to be 67% and 76% of the adult tensile stiffness. The tensile failure tolerance of the six year old was between 1490 and 2300 N and of the ten year old between 2040 and 3170 N. The adult and pediatric Hybrid III ATDs were found to be on average 2.5 times stiffer in flexion bending than the computer models. Biofidelity corridors were created with the models to be used to guide future ATD designs. Overall, the pediatric models provide a general tool that can be used to assess the safety of children during motor vehicle crashes.</p> / Dissertation

This particular study is about the main boulevard of the city center of Tirana that is the capital of Albania since 1920. The main boulevard, which has a function of a &quot / spine&quot / of the central business district, was designed as an idea by the Italian architects in 1925. The new government needed immediately governmental buildings like minstries, a palace and a strong form that connects all of these facilities together in a monumental way. This &quot / spinal&quot / circulation system was inspired from the urban movements of that time like near city and city beautiful movement. Tirana is studied as the case by the light of historical developments of other cities. The power of the spine and its effect to the macro form of the whole city is analyzed and determined.

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This dissertation has two major parts; Analytical and Experimental. The analytical section contains a study using Finite Element Analysis of dynamic instrumentation to demonstrate stress reduction in adjacent level discs. The experimental section contains biomechanical testing of facet fusion allograft technique and finally a comparison between In Vivo and In Vitro intradiscal pressures to determine forces acting on Lumbar spine segment L4-L5. A comprehensive study of available data, technology and literature was done. Conventional fusion instrumentation is believed to accelerate the degeneration of adjacent discs due to the increased stresses caused by motion discontinuity. A three dimensional finite element model of the lumbar spine was obtained which simulated flexion and extension. Reduced stiffness and increased axial motion of dynamic posterior lumbar fusion instrumentation designs results in a ~10% cumulative stress reduction for each flexion cycle. The cumulative effect of this reduced amplitude and distribution of peak stresses in the adjacent disc may partially alleviate the problem of adjacent level disc degeneration. Traditionally a pedicle screw system has been used for fixation of the lumbar spine and this involves major surgery and recovery time. Facet fixation is a technique that has been used for stabilization of the lumbar spine. The cadaver segments were tested in axial rotation, combined flexion/extension and lateral bending. Implantation of the allograft dowel resulted in a significant increase in stiffness compared to control. Facet fusion allograft provides an effective minimally invasive method of treating debilitating pain caused by deteriorated facet joints by permanently fusing them. An In Vitro biomechanical study was conducted to determine the intradiscal pressure during spinal loading. The intradiscal pressures in flexion/extension, lateral bending and axial rotation was compared to In Vivo published data. There is no data that explains the actual forces acting on the spine during flexion, extension, lateral bending or axial rotation. The functional spinal units were tested in combined axial compression and flexion/extension, combined axial compression and lateral bending and combined axial compression and axial rotation using a nondestructive testing method. Overall, this study found a good correlation between In Vivo and In Vitro data. This can essentially be used to make physiological relation from experimental and analytical evaluations of the lumbar spine. It is important to know how much load needs to be controlled by an implant.

Aggregating proteoglycans (PG) bearing chondroitin sulfate (CS) side chains are well-known inhibitors of neural plasticity and associate with hyaluronan and tenascin-R to form a complex of extracellular matrix (ECM) in the central nervous system (CNS). Little is known about whether proteolytic cleavage of the core protein affects neural plasticity. Several members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of metalloproteinases are glutamyl-endopeptidases that cleave aggregating PGs. Our initial studies determined that neural cultures secrete a brevican-containing matrix, and that these neural cultures also produced ADAMTS4, a protease that cleaves brevican. Furthermore, this brevican-containing matrix in astrocytes could be modulated by treatment with transforming growth factor beta (TGFbeta) through the inhibition of the activity of the ADAMTSs.Once it was established that neural cultures produce a brevican-rich matrix, we s ought to utilize this matrix to determine whether cleavage of aggregating PGs, especially brevican, by the ADAMTSs influences neurite outgrowth in cultured neurons. Transfection of rat neurons with ADAMTS4 cDNA induced longer neurites, and interestingly, this effect proved to be independent of the proteolytic action of the ADAMTSs. Addition of recombinant ADAMTS4 or ADAMTS5 protein to immature neuronal cultures similarly enhanced neurite extension, an action dependent on the activation of extracellular signal-related kinase (ERK)1/2 (MAP kinase 42/44), resulting in the first evidence that ADAMTSs may induce intracellular signaling events. Studies of dendritic spine morphology and levels of synaptic proteins in response to ADAMTS4 treatment were also undertaken. Neuronal cultures treated with ADAMTS4 showed increased length of dendritic spines and increased percent of immature spines detected. A concurrent decrease in post-synaptic protein staining was detected on the neurites of yo ung neurons overexpressing ADAMTS4 or expressing proteolytically-inactive mutant ADAMTS4 protein. Thus, ADAMTS4 may promote plasticity in neurons in vitro by preventing the formation, maturation, and/or stabilization of synapses. Overall, these experiments provide evidence that implicate the ADAMTSs as mediators of neural plasticity, and while primarily known only as proteases, these studies demonstrate that the ADAMTSs exert actions distinct from these proteolytic properties that require the induction of intracellular signaling events.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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1. INTRODUCTION Injuries of the lower cervical spine can be among the most devastating injuries of the musculoskeletal system because of the increased risk of the injury to the spinal cord, and also because they so often occur to the younger members of the population (Jones A.A.M. et al., 2003; Sekhon H.S.L. et al., 2001; Ball P.A., 2001). The cervical spine is the most vulnerable spinal segment (Sekhon H.S.L. et al., 2001). The mechanism of cervical spine trauma is defined by the direction and magnitude of the forces that have been applied externally to the head and neck complex resulting in injury (Allen B.L.Jr., 1982). Common injury vectors include flexion, compression, rotation and extension (Allen B.L.Jr., 1982). The pattern of injury is related not only to the external applied force, but also to the initial position or posture of the head and neck at the time of injury (Allen B.L.Jr., 1982). One pattern of these injuries of the lower cervical spine is a facet dislocations (Allen B.L.Jr., 1982). The facet dislocation of the cervical spine result from a hyperflexion injury of the neck (Allen B.L.Jr., 1982). These injuries are characterized radiographically by anterolisthesis of one cervical vertebrae over the other and include the slide anteriorly of the inferior facet of the upper dislocated vertebra over the superior facet of the vertebra below (Allen B.L.Jr., 1982; Razack N. et al., 2000). The facet dislocations of the lower cervical spine represent from 4% to 50% of... [to full text]

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