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A long-standing question in planet formation is the origin of planetesimals, the kilometre-sized precursors to protoplanets. Asteroids and distant Kuiper Belt objects are believed to be remnant planetesimals from the beginnings of our Solar system. A leading mechanism for explaining the formation of these bodies directly from centimetre-sized dust pebbles is the streaming instability (SI). Using high resolution numerical simulations of protoplanetary discs, we probe the behavior of the non-linear SI and planetesimal formation in previously unexplored configurations. Small variations in initial state of the disc can lead to different macroscopic outcomes such as the total mass converted to planetesimals, or the distribution of planetesimal masses. These properties can vary considerably within large simulations, or across smaller simulations re-run with different initial perturbations. However, there is a similar spread in outcomes between multiple smaller simulations and between smaller sub-regions in larger simulations. In small simulations, filaments preferentially form rings while in larger simulations they are truncated. Larger domains permit dynamics on length scales inaccessible to the smaller domains. However, the overall mass concentrated in filaments across various length scales is consistent in all simulations. Small simulations in our suite struggle to resolve dynamics at the natural filament separation length scale, which restricts the possible filament configurations in these simulations. We also model discs with multiple grain species, sampling a size distribution predicted from theories of grain coagulation and fragmentation. The smallest grains do not participate in the formation of planetesimals or filaments, even while they co-exist with dust that readily forms such dense features. For both single-grain and multiple-grain models, we show that the clumping of dust into dense features results in saturated thermal emission, requiring an observational mass correction factor that can be as large as 20-80\%. Finally, we present preliminary work showing that the critical dust-to-gas mass ratio required to trigger the SI can vary between 3D and 2D simulations. / Thesis / Doctor of Philosophy (PhD)

Published Article / Rapid Manufacturing (RM) has emerged over the past few years as a potential technology to successfully produce patient-specific implants for maxilla/facial and cranial reconstructive surgeries. However, in the area of spinal implants, customization has not yet come to the forefront and with growing capabilities in both software and manufacturing technologies, these opportunities need to be investigated and developed wherever possible. The possibility of using Computed Tomography (CT) and Rapid Manufacturing (RM) technologies to design and manufacture a customized, patient-specific intervertebral implant, is investigated. Customized implants could aid in the efforts to reduce the risk of implant subsidence, which is a concern with existing standard implants. This article investigates how accurately the geometry of a customized artificial intervertebral disc (CAID) can represent the inverse geometry of a patient's vertebral endplates. The results indicate that the endplates of a customized disc implant can be manufactured to a calculated average error of 0.01mm within a confidence interval of 0.022mm, with 95% confidence, when using Direct Metal Laser Sintering.

I have carried out three-dimensional numerical simulations of self-gravitating discs to determine under what circumstances they fragment to form bound clumps that may grow into giant planets. Through radiation hydrodynamical simulations using a Smoothed Particle Hydrodynamics code, I find that the disc opacity plays a vital role in determining whether a disc fragments. Specifically, opacities that are smaller than interstellar Rosseland mean values promote fragmentation (even at small radii, R < 25AU) since low opacities allow a disc to cool quickly. This may occur if a disc has a low metallicity or if grain growth has occurred. Given that the standard core accretion model is less likely to form planets in a low metallicity environment, I predict that gravitational instability is the dominant planet formation mechanism in a low metallicity environment. In addition, I find that the presence of stellar irradiation generally acts to inhibit fragmentation (since the discs can only cool to the temperature defined by stellar irradiation). However, fragmentation may occur if the irradiation is sufficiently weak that it allows the disc to attain a low Toomre stability parameter. With specific reference to the HR 8799 planetary system, I find that it is only possible for fragments to form in the radial range where the HR 8799 planets are located (approximately 24-68 AU) if the disc is massive. In such a high mass regime, mass transport occurs in the disc causing the surface mass density to alter. Therefore, fragmentation is not only affected by the disc temperature and cooling, but also by any restructuring due to the gravitational torques. The high mass discs also pose a problem for the formation of this system because the protoplanets accrete from the disc and end up with masses greater than those inferred from observation and thus, the growth of planets would need to be inhibited. In addition, I find that further subsequent fragmentation at small radii also takes place. By way of analytical arguments in combination with hydrodynamical simulations using a parameterised cooling method, I explore the fragmentation criteria which in the past, has placed emphasis on the cooling timescale in units of the orbital timescale, beta. I find that at a given radius the surface mass density (i.e. disc mass and profile) and star mass also play a crucial role in determining whether a disc fragments or not as well as where in the disc fragments form. I find that for shallow surface mass density profiles (p<2, where the surface mass density is proportional to R^{-p}), fragments form in the outer regions of the disc. However for steep surface mass density profiles (p is greater than or similar to 2), fragments form in the inner regions of a disc. In addition, I find that the critical value of the cooling timescale in units of the orbital timescale, beta_crit, found in previous simulations is only applicable to certain disc surface mass density profiles and for particular disc radii and is not a general rule for all discs. I obtain an empirical fragmentation criteria between the cooling timescale in units of the orbital timescale, beta, the surface mass density, the star mass and the radius. Finally, I carry out crucial resolution testing by performing the highest resolution disc simulations to date. My results cast some serious doubts on previous conclusions concerning fragmentation of self-gravitating discs.

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2008. / Lumbar disc replacement is a rapidly expanding surgical treatment modality for longstanding back and leg pain due to intervertebral disc degeneration. Compared to fusion surgery, it has the advantage of preserving segmental mobility, but convincing evidence of superiority over fusion surgery is missing. As part of this research project, I participated in the development of a new intervertebral disc prosthesis, with several international patents attached to the design of the prosthesis, the instrumentation and the insertion technique. The Kineflex (Centurion) lumbar disc is a mechanical, un-constrained, re-centering disc prosthesis developed in South Africa. After the development and manufacturing of the disc, prototype test racks were custom-made at the premises of the manufacturer and the disc was extensively tested for mechanical wear and fatigue. The first implantation took place in October 2002. I prospectively captured all cases performed by our centre, with documentation including demographic data, co-morbidities, clinical history, symptoms and signs. The completed consent forms were filed. The outcome was monitored, pre-operatively and in follow-up, with complete radiological documentation of all radiographs on JPEG files. Clinical outcome results were documented using two different internationally validated questionnaires as well as our own questionnaire, which expands further on work and demographic details, previous operative and conservative treatment, and satisfaction with the treatment outcome. The aim of the this project was to develop a disc prosthesis that is suitable and safe for human implantation into the lumbar spine disc space, even in severely advanced disc degeneration and to verify this in the outcome studies presented in this thesis. Existing indications and contra-indications for artificial disc replacement were critically evaluated regarding their validity for this particular implant. Results: Chapter 3 elaborates on the extensive pre-clinical mechanical wear and fatigue testing protocol to which the Centurion (Kineflex) lumbar disc prosthesis was subjected. The results of this testing protocol, together with our early clinical outcome results, formed the basis for the awarding of the European quality recognition (CE-Mark). In these extensive in vitro studies, we were able to show the durability of the Kineflex disc prosthesis in the long term. This, together with our initial clinical outcome results, formed the basis for the acceptance into a “prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the KINEFLEX Lumbar Artificial Disc versus the CHARITÉ™ Artificial Disc”. Chapter 4 is compiled from an invited submission to a new book on motion preservation surgery in the human spine, edited by leading spine surgeons in the field (James J. Yue, Rudolf Bertagnoli, Paul McAfee, and Howard An) and published by Elsevier Publishers: Chapter 42: Kineflex. In this chapter, an overview is given of the ideas behind the Kineflex disc development, as well as of the insertion instrumentation used for disc implantation. It further reports on early clinical outcome results of the first patients implanted with the device in our centre (the first 40 implantations worldwide were all performed by me). Chapter 5, our first peer reviewed international publication, reports on clinical and radiological 2-year outcome results of our first 100 patients. With the Kineflex implant, we could demonstrate equally good radiological placement accuracy in patients with severe and less severe disc degeneration of the index level, rendering the implant suitable even in severe degeneration of a spinal motion segment. Chapter 6 and Chapter 7 of this thesis consist of two further peer-reviewed publications. They both report on so-called “off-label” patient sub-groups in our disc replacement series. In Chapter 6 we present the second published series on a larger group of patients presenting with adjacent segment disease after previous lumbar fusion surgery as well as the first publication, which investigated the radiological changes in alignment parameters secondary to the disc replacement surgery in this patient group. Chapter 7 consists of the first published series on patients with “degenerative spondylolisthesis” treated with disc replacement surgery. A detailed description of the operative reduction technique is provided, which is unique to the Kineflex disc and its insertion instrumentation. In this pilot study, two-year results on a limited patient group are presented. This thesis concludes with the overall discussion in Chapter 8. It outlines the current knowledge on artificial disc replacement and places my results into perspective with recent discoveries published in the literature. It finishes with my assessment of what future research should concentrate on.

Apoptose, der programmierte Zelltod, spielt eine wichtige Rolle für das Gleichgewicht zwischen Proliferation und Sterben von Zellen und ist außerdem an der Beseitigung von infizierten und geschädigten Zellen beteiligt. Apoptose kann durch Stimulation von Rezeptoren aus der Familie der TNF-Rezeptoren wie CD95, ausgelöst werden. Nach Liganden-induzierter Trimerisierung der Rezeptoren bindet FADD an den zytoplasmatischen Teil des Rezeptors und rekrutiert Caspase-8 und/oder -10. Die räumliche Nähe der Caspasen in diesem als DISC bezeichneten Komplex führt zu ihrer auto- und transkatalytischen Spaltung und damit Aktivierung. Dadurch wird das apoptotische Programm gestartet, welches zum Tod der Zelle führt. Kontrolliert wird dieser Vorgang von einer Vielzahl anti-apoptotischer Proteine. Störungen in diesem System sind an der Entstehung einer Reihe von Krankheiten beteiligt. Die Blockade der Apoptoseinduktion kann zur Entstehung von Tumoren beitragen. Das klassische Hodgkin Lymphom ist eine maligne Erkrankung des lymphatischen Systems. Die Tumorzellen sind große, einkernige Hodgkin- oder mehrkernige Reed/Sternbergzellen (HRS-Zellen). Sie leiten sich von Keimzentrum-B-Zellen ab. In HRS-Zellen fehlt die Expression einer Vielzahl von typischen B-Zellmarkern, darunter die des B-Zellrezeptors. Solche B-Zellen sterben normalerweise während der Keimzentrumsreaktion durch Apoptose. An diesem Prozess ist CD95 beteiligt. In einer Reihe von malignen Erkrankungen wurden eine Herunterregulation der CD95-Expression oder Mutationen im CD95-Gen beobachtet. Es wird daher vermutet, dass CD95-induzierte Apoptose zur Entfernung von Tumorzellen beiträgt. Im Gegensatz dazu exprimieren sowohl primäre HRS-Zellen als auch etablierte HRS-Zelllinien in der Regel Wildtyp-CD95, sind aber trotzdem CD95-resistent. In dieser Arbeit konnte gezeigt werden, dass Komponenten des CD95-Systems, im Gegensatz zu anderen malignen Erkrankungen, in den HRS-Zellen hochreguliert sind, darunter CD95 selbst. In immunpräzipitierten DISCs von CD95-stimulierten HRS-Zellen wurde neben FADD und Caspase-8/-10 auch c-FLIP nachgewiesen. c-FLIP ist ein Caspase-8/-10-Homolog, das ebenfalls an FADD bindet, aber aufgrund fehlender katalytischer Aktivität die Aktivierung der Caspasen im DISC und damit die Apoptoseinduktion verhindert. Eine starke c-FLIP-Expression konnte in allen HRS-Zelllinien und in den HRS-Zellen nahezu aller untersuchter primärer Hodgkinfälle (55/59) gezeigt werden. Durch siRNA-vermittelte Herunterregulation von c-FLIP war es möglich, HRS-Zelllinien gegenüber CD95-induzierter Apoptose zu sensitivieren. Dies zeigt, dass die CD95-Rezeptor-induzierte Apoptose in den HRS-Zellen nicht strukturell, sondern funktionell inhibiert ist und c-FLIP stark zu dieser Inhibition beiträgt. Darüber hinaus konnte gezeigt werden, dass die c-FLIP-Expression in den HRS-Zellen von der konstitutiven Aktivität des Transkriptionsfaktors NF-κB abhängt, die charakteristisch für diese Zellen ist. Normalerweise wird NF-κB von Inhibitorproteinen, den IκBs, im Zytoplasma zurückgehalten. Diverse Stimuli können den IKK-Komplex aktivieren, der die IκBs an bestimmten Serinresten phosphoryliert. Dies hat die Ubiquitinylierung und den Abbau der IκBs zur Folge, wodurch NF-κB frei wird, in den Kern wandert und dort seine Zielgene aktiviert. Es wird angenommen, dass in HRS-Zellen ein konstitutiv aktiver IKK-Komplex und teilweise Mutationen der IκB-Proteine zur konstitutiven NF-κB-Aktivität beitragen. Zu den NF-κB-abhängigen Genen in den HRS-Zellen gehören solche mit anti-apoptotischer und Zellzyklus-treibender Wirkung. Die Inhibition der NF-κB-Aktivität in den HRS-Zellen führt zu Apoptose und eingeschränkter Proliferation. Von dreiwertigem Arsen ist bekannt, dass es die Induzierbarkeit des IKK-Komplexes inhibieren kann und damit letztendlich die Aktivierung von NF-κB. In dieser Arbeit konnte gezeigt werden, dass Arsen in HRS-Zellen den konstitutiv aktiven IKK-Komplex inhibiert. In Zelllinien mit intakten IκB-Proteinen führte dies zur NF-κB-Inhibition und Apoptoseinduktion. Die Reduktion der NF-κB-Aktivität ging mit der Herunterregulation von anti-apoptotischen und Proliferations-fördernden Zielgenen einher. Die ektope Überexpression von NF-κB hob die Apoptose-induzierende Wirkung von Arsen teilweise auf. Durch Arsen-Behandlung von Mäusen konnte das Tumorwachstum xenotransplantierter HRS-Zellen stark verlangsamt werden. In explantierten Tumorzellen konnte ebenfalls eine NF-κB-Inhibition nachgewiesen werden. Die NF-κB-Inhibition durch Arsen trägt also stark zur Apoptoseinduktion in den HRS-Zellen bei. Zusammengefasst zeigen die Ergebnisse dieser Arbeit, dass die Modulation der Apoptoseresistenz neue therapeutische Ansätze für die Behandlung des Hodgkin Lymphoms bieten könnte. Der Einsatz von Arsen ist dabei besonders interessant, da Arsen schon für die Behandlung anderer maligner Erkrankungen eingesetzt wird. / Apoptosis, the programmed cell death, is important for the balance between proliferation and dying of cells. It is also involved in the removal of infected and damaged cells. Apoptosis can be induced by stimulation of receptors of the TNF-receptor family like CD95. After ligand-induced trimerisation of these receptors, FADD binds to the cytoplasmic part of the receptor and recruits Caspase-8 and/or -10. The induced proximity of the caspases in this complex, called DISC, leads to their auto- and transcatalytic cleavage and subsequently to their activation. This starts the apoptotic program which leads to the death of the cell. A number of anti-apoptotic proteins control this process. The deregulation of this system is involved in a variety of diseases. The disruption of the apoptotic program can contribute to the development of tumors. Classical Hodgkin Lymphoma is a malignant disease of the lymphatic system, characterized by mononucleated Hodgkin or multinucleated Reed/Sternberg (HRS) cells. These tumor cells are derived from germinal-center B-cells. However, HRS cells lack the expression of typical B cell markers, such as the B-cell receptor. Usually, B-cells without B-cell receptor expression die by apoptosis during the germinal-center reaction. CD95 is involved in this process. It has been shown previously that in many malignant diseases CD95 is down-regulated or mutated, indicating that CD95 is involved in the removal of tumor cells. In opposite to these findings, primary HRS cells and Hodgkin-derived cell lines usually express wild type CD95, but are resistant to CD95 induced apoptosis. In this work, it could be demonstrated that in contrast to other malignant diseases components of the CD95 system are up-regulated in HRS cells, including CD95 itself. By immunoprecipitation it was shown that, in addition to FADD and Caspase-8/-10, c-FLIP is a component of the DISC in CD95-stimulated cells. c-FLIP is a caspase homolog which, like caspases, binds to FADD, but lacks proteolytic activity. It inhibits the activation of caspases in the DISC and thus prevents apoptosis induction. A strong c-FLIP expression was shown in all HRS cell lines and in HRS cells of nearly all investigated primary cases of Hodgkin Lymphoma (55/59). siRNA-mediated (small interfering RNA) down-regulation of c-FLIP sensitized HRS cell lines to CD95-induced apoptosis. This shows that the CD95 receptor-induced apoptosis in HRS cells is not structurally but functionally inhibited and that c-FLIP strongly contributes to this inhibition. In addition, it was shown that c-FLIP expression depends on the constitutive activity of the transcription factor NF-κB which is characteristic for HRS cells. Usually, NF-κB is sequestered in the cytoplasm by inhibitor proteins, the IκBs. A variety of stimuli can activate the IKK-complex which subsequently phosphorylates the IκBs, leading to their ubiquitinylation and degradation. The released NF-κB translocates to the nucleus where it activates the transcription of target genes. It is supposed that a constitutively activated IKK complex and, in some cases, mutated IκB proteins contribute to the constitutive NF-κB activity in HRS cells. To the NF-κB dependent genes in HRS cells belong those with anti-apoptotic and cell cycle promoting activities. Inhibition of the NF-κB activity in HRS cells leads to apoptosis and decreased proliferation. Trivalent arsenic is known to inhibit the induction of the IKK complex and thus the activation of NF-κB. In this work, it was shown that arsenic inhibits the constitutively active IKK complex in HRS cells. This led to an inhibition of NF-κB and induction of apoptosis in HRS cell lines with non-mutated IκB proteins. The NF-κB inhibition was accompanied by the down-regulation of anti-apoptotic and cell cycle promoting genes. Ectopic overexpression of NF-κB partially reverted the apoptotic effect of arsenic. Treatment of mice with arsenic reduced the growth of subcutaneously xenotransplanted HRS cells. In explanted tumor cells, a reduced NF-κB activity could be demonstrated following treatment with arsenic. Thus, the inhibition of NF-κB by arsenic contributes to the induction of apoptosis in HRS cells. Taken together, the results indicate that modulation of the apoptosis resistance may offer new strategies for the treatment of Hodgkin Lymphoma. Of particular interest is the application of arsenic because it is already used in the treatment of other malignant disorders.

Modified design of a planter to be attached to a mobile robot, was the main objective of this project. This research project was part of a larger project, called “Developing robotics assisted technology for farming”. The main motivation for this research project is the fact that mobile robot, is an electric powered vehicle with limited power and pulling force. Thus, a customized planter with a customized connection mechanism should be designed. Besides, it should require less draft force compared to existing planters so that it can be pulled by the mobile robot. The developed planter should have the same efficiency as the existing planters in seeding. To find the forces between soil engagement tool (disc coulter) and soil, experiments were designed and performed in the Linear Soil Bin at University of Saskatchewan. Disc and tilt angle of a disc coulter was changed and draft, vertical and side forces applied to it were measured to find the disc and tilt angle combinations that results in minimum draft force. Experiments showed that 7° disc angle and 25° tilt angle provides the least draft force compared to other disc angle and tilt angle combinations. Then, using the knowledge obtained from literature and the soil bin experiments, a planter was designed conceptually and in detail, based on the existing CNH planter. For further analyses computer modeling was performed. The whole planter was modeled in 3D, using SolidWorks. Stress analysis was performed in ANSYS Workbench to calculate safety factor of the designed parts. Two prototypes were fabricated and were attached to the mobile robot for field tests. Tests were performed in indoor settings to measure the total draft force required to pull developed planters. Draft force was very close to the value that was calculated in design stage. Results showed that an average of 460 N pulling force is required to pull one row planter for 50 mm depth of cut, which can be compared to n existing CNH corn planter that requires a pulling force of between 900 N to 1300 N. Seed drop accuracy and function of the developed planters in opening and closing a packed soil in presence of residue, were also observed in outdoor tests.

This thesis is an investigation of the access provided to the vertebral canal in dogs by the hemilaminectomy and mini-hemilaminectomy surgical techniques using computed tomography (CT), and the completeness of evacuating extruded material in dogs with intervertebral disc (IVD) extrusion using magnetic resonance imaging (MRI). Hemilaminectomy and mini-hemilaminectomy were performed on opposite sides of the spine at T11-T12, T13-L1, and L2-L3 in 10 cadavers. Measurements of the vertebral canal height, defect height, and any dorsal and ventral remnants of the vertebral arch were obtained by CT. A covariate analysis was used to compare measurements with the surgical technique, surgical site, and side of the vertebral column. Defect height was greater with hemilaminectomy due to a smaller dorsal lamina remnant. There was no statistical difference in the height of the ventral remnant, or with surgical site. Nineteen prospectively recruited dogs with suspected IVD extrusion were randomly assigned to hemilaminectomy (10 dogs) or mini-hemilaminectomy (9 dogs) groups. Intervertebral disc extrusion was identified pre-operatively with MRI and later confirmed surgically, and immediate post-operative MRI was performed at the surgical site. The volume of extruded IVD material pre- and post-operative was calculated from transverse T2 images. Although residual IVD material was present in post-operative images from all dogs in the hemilaminectomy group and only 4 in the mini-hemilaminectomy group, there was no statistically significant difference between the proportionate volumes of material removed by either technique. The median residual volume with hemilaminectomy was 13.6% (confidence interval: 7.8 – 23.6%), and with mini-hemilaminectomy was 7.7% (4.3 – 13.8%). The results of this study confirm that the difference in the defect height between techniques is related to the removal of the articular processes creating a larger defect along the dorsal vertebral canal, while no difference in access to the ventral canal was observed. No effect of vertebral site was detected suggesting neither procedure provides an advantage over the other due to location of the lesion along the thoracolumbar spine. Residual extruded IVD material occurs with both techniques; while no statistical difference was noted, a larger population should be examined. / Ontario Veterinary College Pet Trust

The thesis presents research into the understanding and improvement of heat dissipation from friction brakes. The investigations involved two brake types, considered to be the most thermally loaded and therefore most challenging; axle mounted high speed railway and commercial vehicle disc brakes. All three modes of heat transfer (conduction, convection and radiation) and airflow characteristics have been analysed experimentally and theoretically in order to increase the understanding of heat dissipation. Despite the very practical aspects of this research, a 'generic heat transfer approach' was applied, enabling wider engineering applications of the results. Experimental analyses conducted on a specially developed Spin Rig allowed measurements of cooling and airflow characteristics for different designs. Methodologies have been developed to determine thermal contact resistance, heat transfer coefficients, emissivity and aerodynamic (pumping) losses. Established values and relationships compared very favourably with theoretical work. Analytical, FE and CFD analyses were employed to further investigate design variations and perform sensitivity studies. Inertia dynamometer route simulations provided disc temperatures for validation of the overall work. Recommendations have been made for optimising heat dissipation, by proposing practically acceptable and economically viable design solutions. A proposed ventilated disc design efficiency ratio allows large, high speed ventilated disc designs, to be efficiently and accurately evaluated and compared, providing a valuable disc design optimisation tool. The determination of the methodologies, parameters and functions defining cooling characteristics, enable heat dissipation to be predicted confidently and accurately for brakes and other engineering assemblies at early design stages.

The association between age-related vertebral fractures (VFx) and disc degeneration (DD) is not clear, despite the high prevalence of both conditions. Load is transferred to the vertebra by the adjacent intervertebral discs, and degenerative changes within the disc alter how the net force is distributed over the interface between vertebra and disc, known as the vertebral endplate (EP). The ability of the vertebra to resist fracture depends not only on the magnitude of the net force, but also on the distribution. Multiple lines of evidence suggest that the ability of the vertebra to withstand the distribution of applied force depends on the spatial distribution of bone mineral density (BMD) within the vertebra. First, the strength and stiffness of a region of bone in the vertebra are highly correlated with the BMD of that region. Second, changes in the spatial distribution of regional BMD have been associated with aging and DD. Thirdly, some of these observed changes have been replicated in computer models bone adaption with in the presence of progressive DD, suggesting that bone adaption is occurring in response to the altered force distribution associated with DD, and that maladaptation could elevate the risk of fracture. Notably, the current clinical method of identifying patients at risk of fracture is to use an average measure of BMD for the entire vertebra. The lack of consideration of the spatial distribution of BMD may explain why the clinical method used at present does not adequately identify those at risk of fracture. The possible relationship among spatial distribution of BMD, DD, force distribution across the endplate, and vertebral strength suggests that characterizing the spatial distribution of BMD within a vertebra could add to the understanding of why some vertebra are more likely to fracture. This project sought to determine if an association exists between the spatial distribution of vertebral BMD and disc health in order to provide an improved perspective of the clinical sequelae of DD and to improve the ability of clinicians to identify those who would benefit most from intervention. This study found evidence that the distribution of bone in the vertebral body and EP depend on the health of the adjacent disc. The distribution of pressure in discs favors the anterior most portion of the disc in anteriorly flexed postures and the density in the anterior most portion of the EP appears to respond to this shift, suggesting that bone is adapting to loading patterns associated with certain postures more than others. This study also found association between reduced regional disc height and altered distribution of trabecular density which was positive in the nuclear region and negative in the annular region. In some cases there was a lack of association between disc height and density distribution that may indicate maladaptation and thus increased risk of fracture. This study, being cross-sectional could not identify whether the observed alterations in density and degeneration initiated in the vertebra or the disc. However, this study contributes to the understanding of the relationship between the distribution of vertebral density and the functional properties of the adjacent disc that may ultimately improve the clinician's ability to predict VFx. / 2017-06-21T00:00:00Z