The current focus of research efforts in the area of the biomechanics of traumatic brain injury is the development of numerical (finite element) models of the human head. A validated numerical model of the human head may lead to better head injury criteria than those used currently in crashworthiness studies. A critical step in constructing a validated finite element model of the head is determining the mechanical threshold, should it exist, for various types of injury to brain tissue. This thesis describes a biomechanical study of axonal injury in the anaesthetised sheep. The study used the measurements of the mechanics of an impact to the living sheep, and a finite element model of the sheep skull and brain, to investigate the mechanics of the resulting axonal injury. Sheep were subjected to an impact to the left lateral region of the skull and were allowed to survive for four hours after the impact. The experiments were designed specifically with the numerical model in mind; sufficient data were collected to allow the mechanics of the impact to be faithfully reproduced in the numerical model. The axonal injury was identified using immunohistological methods and the injury was mapped and quantified. Axonal injury was produced consistently in all animals. Commonly injured regions included the sub-cortical and deep white matter, the hippocampi and the margins of the lateral ventricles. The degree of injury was closely related to the peak impact force and to kinematic measurements, particularly the peak change in linear and angular velocity. There was significantly more injury in animals receiving fractures. A three-dimensional finite element model of the sheep skull and brain was constructed to simulate the dynamics of the brain during the impact. The model was used to investigate different regimes of material properties and boundary conditions, in an effort to produce a realistic model of the skull and brain. Model validation was attempted by comparing pressure measurements in the experiment with those calculated by the model. The distribution of axonal injury was then compared with the output of the finite element model. The finite element model was able to account for approximately thirty per cent of the variation in the distribution and extent of axonal injury, using von Mises stress as the predictive variable. Logistic regression techniques were used to construct sets of curves which related the extent of injury, to the predictions of the finite element model, on a regional basis. The amount of observable axonal injury in the brains of the sheep was clearly related to the severity of the impact, and was related to the predictions of a finite element model of the impact. Future improvements to the fidelity of the finite element model may improve the degree to which the model can explain the variation in injury throughout the brain of the animal and variations between animals. This thesis presents results, and a methodological framework, that may be used to further our understanding of the limits of human endurance, in the tolerance of the brain to head impact. All experiments reported herein conformed with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. / Thesis (Ph.D.)--Mechanical Engineering, 2000.

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<p>The focus of this thesis was the role of fibrocytes in chronic lung disease. These bone marrow derived cells have been identified in the lung and the circulation in patient samples and animal models of lung injury. However, the precise mechanistic role of the fibrocyte is still to be elucidated.</p> <p>Live assessment of lung changes in animal models of chronic lung disease allows for real time observation of changes, and gives a readout which can be translated to humans who undergo similar tests. In this thesis, we adapted an existing model of lung injury, and delivered a discrete treatment to a single lung lobe while monitoring its successful delivery.</p> <p>I also developed a robust system to examine the relationship between fibrocyte response, and cytokine expression previously identified in chronic lung disease. We found a connection between cytokine expression and fibrocyte mobilisation. Our model showed that fibrocyte mobilisation in the presence of existing lung injury does not improve and rather can worsen existing lung injury. This was a significant finding as it confirms the role of the fibrocyte as a participator or conductor in fibrogenesis and it suggests that this cell may play a role in the development of chronic lung diseases.</p> <p>Finally, we contributed to the ongoing characterisation of the fibrocyte as a prospective biomarker. We confirmed the cell’s identity by characterising it by its known markers and biological characteristics. We also identified the presence of this cell in chronic lung disease and linked its presence to disease progression.</p> / Doctor of Philosophy (Medical Science)

Huvudsyftet med föreliggande studie var att undersöka på vilket sätt coacher inom tyngdlyftning, styrkelyft, Crossfit och kroppsbyggning implementerar preventiva strategier designade för att förebygga skador genom inverkan på psykologiska riskfaktorer. Vidare var det av intresse att undersöka vilka personlighetsdrag hos en idrottare som coacher upplevde ökade risken för skador. Ett ytterligare syfte var att studera coachernas erfarenheter av relationen mellan idrottares stressnivå och skaderisk. Totalt genomfördes nio semistrukturerade intervjuer med coacher på distrikt till internationell nivå lokaliserade i Sverige. Samtliga coacher hade tidigare erfarenhet med skadade idrottare. Resultatet sammanställdes genom en deduktiv innehållsanalys. Under intervjuerna identifierades flera interventionsstrategier som kunde relateras till Williams och Andersens (1998) stress­skademodell. Det framgick att coacherna i studien fokuserar mycket på fysiologiska och stressrelaterade aspekter och inte personlighetsdrag när de implementerar interventioner för att förebygga skador. Implikationer för skadeförebyggande träning samt förslag på framtida forskning ges.

Neutrophils are significant players in both acute and chronic inflammatory conditions, and function in infectious and autoimmune ailments. MicroRNAs regulate homeostasis in health and disease by fine tuning the expression of a network of genes through post transcriptional regulation. Many microRNAs are expressed in restricted tissues, regulated by physiological conditions such as stress and disease, and are emerging as mediators for intercellular communication that shape the tissue environments. MicroRNA profiles have been recently utilized as biomarkers for diagnosis and prognostic purposes for their stability in plasma and significant correlation with the disease progress. In addition, several microRNAs are in clinical trials for infectious diseases, cardiovascular disorders and cancer. As for neutrophil biology, microRNAs that regulate hematopoiesis and neutrophil development are well known. However, only a few microRNAs are characterized in the context of neutrophil migration and activation by loss of function studies either in mice or in cell culture. In this work we characterize the role of total microRNA regulation on neutrophil function through whole body and neutrophil specific Dicer1 knockout, and identify a microRNA regulator of neutrophil motility. MiR-722 downregulates the transcript level of rac2 through binding to a seed match in the rac2 3'UTR. Furthermore, miR-722 over-expressing larvae display improved outcomes in both sterile and bacterial systemic models. Finally, the miR-722 mimics protect zebrafish from lethal LPS challenge, providing evidence and mechanism of an anti-inflammatory microRNA that restrains detrimental systemic inflammation. We further investigated the role of the inflammatory response in an ischemia-reperfusion model. Extensive future work is required, especially in animal models, to illustrate the pivotal and complex microRNA mediated regulatory network in neutrophils, which is expected to provide the foundation for highly selective microRNA based therapy to control neutrophil behavior in infection and inflammatory disorders.

The dissertation deals with the analysis of roundabout design elements and their impact on accidents. The analysis objective was to identify the important elements of roundabouts that have impact on accidents. In order to achieve this goal, the multifactorial statistical safety assessment method was used on the basis of a representative sample of data, by developing several safety performance functions, verifying them and interpreting the result. Several design elements, which from the point of view of the traffic accident mechanism belong to the infrastructure factor, have been identified: AADT, average diameter, entrance width, entry angle, direct passage angle, location and many others. The original sample contained about 1200 roundabouts, which were reduced to 200 based on data availability. Accident frequencies were monitored between 2009 and 2016, i.e. for eight years, resulting in total 2674 roundabouts accidents. The result is an accident prediction model, developer based on roundabout approach design elements, and map of critical roundabouts, identified based on empirical Bayes estimate of accident frequency. Following approach parameters were identified: AADT, entry angle, distance between collision points, deviation of angles between approaches, presence of apron, presence of bypass, entry type, presence of pedestrian crossing and surrounding area type.