published_or_final_version / abstract / Anaesthesiology / Master / Master of Philosophy

published_or_final_version / abstract / Physiology / Master / Master of Philosophy

published_or_final_version / Biological Sciences / Master / Master of Philosophy

The purpose of this study is to examine the propagation of waves of finite deformation in rubbers through experiments and analysis. First, attention is focused on the propagation of one-dimensional dispersive waves in strips of latex and nitrile rubber. Tensile wave propagation experiments were conducted at high strain-rates by holding one end fixed and displacing the other end at a constant velocity. A high-speed video camera was used to monitor the motion and to determine the evolution of strain and particle velocity in rubber strips. Analysis of the response through the theory of finite wave propagation indicated a need for an appropriate constitutive model for rubber; by quantitative matching between the experimental observations and analytical predictions, an appropriate instantaneous elastic response for the rubbers was obtained. This matching process suggested that a simple power-law constitutive model was capable of representing the high strain-rate response for both rubbers used. Next, the propagation of one-dimensional shock waves in strips of latex and nitrile rubber is examined. Shock waves have been generated under tensile impact in pre-stretched rubber strips; analysis of the response yields the tensile shock adiabat for rubbers. The propagation of shocks is analyzed by developing an analogy with the theory of detonation. Attention is then focused on the propagation of unloading waves of finite deformation in a rubber specimen analytically and experimentally. A rubber strip stretched to many times its initial length is released at one end and the resulting unloading is examined. Dispersive waves as well as shock waves are observed in these experiments. Quantitative discrepancies between the analytical model and experimental observations are again used to motivate a power-law model. Hysteresis in the response is attributed to strain-induced crystallization and melting phase transitions in natural latex rubber, and to nonequilibrium microstructural deformation in nitrile rubber. Finally, a Kolsky experiment is conducted and analyzed under the framework of dispersive loading and unloading waves utilized in the previous experiments. In this experiment, a phase boundary is introduced separating low and high strain phases of the rubber and is demonstrated to persist as a stationary boundary in latex rubber. / text

The mean flowfield and time-dependent characteristics of a Mach 5 cylinder-induced transitional shock-wave/boundary-layer interaction have been studied experimentally. The objectives of the study were to: (i) provide a detailed description of the mean flow structure of the interaction, and (ii) characterize the unsteadiness of the interaction based on fluctuating pressure measurements. / text

The response of materials under extreme temperature and pressure conditions is a topic of great significance because of its relevance in astrophysics, geophysics, and inertial confinement fusion. In recent years, environments exceeding several hundred gigapascals in pressure have been produced in the laboratory via laser-based dynamic loading techniques. Shock-loading is of particular interest as the shock provides a fiducial for measuring time-dependent processes in the lattice such as phase transitions. Time-resolved x-ray diffraction is the only technique that offers an insight into these shock-induced processes at the relevant spatial (atomic) and temporal scales. In this study, nanosecond resolution x-ray diffraction techniques were developed and implemented towards the study of shock-induced phase transitions in polycrystalline materials. More specifically, the capability of a focusing x-ray diffraction geometry in high-resolution in situ lattice measurements was demonstrated by probing shock-compressed Cu and amorphous metallic glass samples. In addition, simultaneous lattice and free surface velocity measurements of shock-compressed Mg in the ambient hexagonal close packed (hcp) and shock-induced body centered cubic (bcc) phases between 12 and 45 GPa were performed. These measurements revealed x-ray diffraction signals consistent with a compressed bcc lattice above a shock pressure of 26.2±1.3 GPa, thus capturing for the first time direct lattice evidence of a shock-induced hcp to bcc phase transition in Mg. Our measurement of the hcp-bcc phase boundary in Mg was found to be consistent with the calculated boundary from generalized pseudopotential theory in the pressure and temperature region intersected by the principal shock Hugoniot. Furthermore, the subnanosecond timescale of the phase transition implied by the shock-loading conditions was in agreement with the kinetics of a martensitic transformation. In conclusion, we report on the progress and future work towards time-resolved x-ray diffraction measurements probing solid-liquid phase transitions in high Z polycrystalline materials, specifically Bi. / text

The intensive care unit treats the most critically ill patients in the hospital, and as such the clinical staff in the intensive care unit have to deal with complex, time-sensitive and life-critical situations. Commonly, patients present with multiple organ dysfunctions, require breathing and cardiovascular support, which make diagnosis and treatment even more challenging. As a result, clinical staff are faced with processing large quantities of often confusing information, and have to rely on experience and trial and error. This occurs despite the wealth of cardiovascular metrics that are available to the clinician. Computer models of the cardiovascular system can help enormously in an intensive care setting, as they can take the monitored data, and aggregate it in such a way as to present a clear and understandable picture of the cardiovascular system. With additional help that such systems can provide, diagnosis can be more accurate and arrived at faster, alone with better optimised treatment that can start sooner, all of which results in decreased mortality, length of stay and cost. This thesis presents a model of the cardiovascular system, which mimics a specific patient’s cardiovascular state, based on only metrics that are commonly measured in an intensive care setting. This intentional limitation gives rise to additional complexities and challenges in identifying the model, but do not stand in the way of achieving a model that can represent and track all the important cardiovascular dynamics of a specific patient. One important complication that comes from limiting the data set is need for an estimation for the ventricular time-varying elastance waveform. This waveform is central to the dynamics of the cardiovascular model and is far too invasive to measure in an intensive care setting. This thesis thus goes on to present a method in which the value-normalised ventricular time-varying elastance is estimated from only metrics which are commonly available in an intensive care setting. Both the left and the right ventricular time-varying elastance are estimated with good accuracy, capturing both the shape and timing through the progress of pulmonary embolism and septic shock. For pulmonary embolism, with the algorithm built from septic shock data, a time-varying elastance waveform with median error of 1.26% and 2.52% results for the left and right ventricles respectively. For septic shock, with the algorithm built from pulmonary embolism data, a time-varying elastance waveform with median error of 2.54% and 2.90% results for the left and right ventricles respectively. These results give confidence that the method will generalise to a wider set of cardiovascular dysfunctions. Furthermore, once the ventricular time-varying elastance is known, or estimated to a adequate degree of accuracy, the time-varying elastance can be used in its own right to access valuable information about the state of the cardiovascular system. Due to the centrality and energetic nature of the time-varying elastance waveform, much of the state of the cardiovascular system can be found within the waveform itself. In this manner this thesis presents three important metrics which can help a clinician distinguish between, and track the progress of, the cardiovascular dysfunctions of pulmonary embolism and septic shock, from estimations based of the monitored pressure waveforms. With these three metrics, a clinician can increase or decrease their probabilistic measure of pulmonary embolism and septic shock.

N-methyl-D-asparate (NMDA) receptors located within the basolateral complex of the amygdala are required for the consolidation and expression of Pavlovian conditioned fear. The events downstream of receptor activation that mediate these processes are not well defined. An intermediate step that may be of significance is the synthesis of the gas nitric oxide (NO). Nitric oxide is synthesised as a result of NMDA receptor activation and acts as an unconventional neurotransmitter freely diffusing across cell membranes interacting with its targets in a non-synaptic manner. The targets of NO include cellular components that play significant roles during the consolidation of conditioned fear and the neurotransmission associated with its expression. This implies that NO may be an important intermediary of NMDA receptor activation and both these processes. The current study sought to examine this possibility using fear potentiated startle to examine the expression of learned fear. Three experiments were conducted, fifty rats received intra-BSC microinfusions of the global nitric oxide synthase inhibitor L-NAME either prior to fear conditioning, fear testing, or examination of the shock sensitization of the acoustic startle affect. The results indicated that NO was indeed required for both the consolidation and expression of learned fear, whereas it was not required for shock enhanced startle responding. This study provides new information about the sub-cellular basis of conditioned fear, and highlights the pivotal role played by NO in processes associated with conditioned fear.

Acute Respiratory Distress Syndrome (ARDS) following hemorrhagic shock/resuscitation (S/R) is an important contributor to late morbidity and mortality in trauma patients. S/R promotes ARDS by inducing oxidative stress that primes cells of the innate immune system for excessive responsiveness to small inflammatory stimuli, termed the “twohit” hypothesis. Activated alveolar macrophages (AM) play a central role and when recovered from S/R animals exhibit an exaggerated responsiveness to lipopolysaccharide (LPS) with increased activation of the proinflammatory transcription factor NF-κB, and augmented expression of cytokines. LPS triggers AM signalling through Toll like receptor 4 (TLR4), which resides in plasma membrane lipid rafts. The objective of this work is to define cellular mechanisms of macrophage priming by oxidative stress following shock resuscitation. The main hypothesis investigated is that altered cellular distribution of TLR4 can lead to macrophage priming and antioxidant resuscitation strategies can diminish these effects. AM of rodents, exposed in vivo to oxidant stress following S/R, increase their surface levels of TLR4, which in turn results in augmented NF-κB translocation in response to small doses of LPS. Furthermore, in vitro H2O2 treatment of RAW 264.7 macrophages results in similar TLR4 surface translocation. Depletion of intracellular calcium, disruption of the cytoskeleton or inhibition of the Src kinases prevents the H2O2-induced TLR4 translocation, suggesting the involvement of receptor exocytosis. Further, fluorescent resonance energy iii transfer between TLR4 and lipid rafts as well as biochemical raft analysis demonstrated that oxidative stress redistributes TLR4 to surface lipid rafts. Preventing the oxidant-induced movement of TLR4 to lipid rafts using methyl-ß-cyclodextrin precluded the increased responsiveness of cells to LPS after H2O2 treatment. Further, AM priming by oxidative stress can be diminished by early exposure to resuscitation regimens with direct or indirect systemic antioxidant effects, such as 25% albumin, N-acetylcysteine and hypertonic saline. Hyperosmolarity was found to modulate AM TLR4 gene and protein expression. Collectively, these studies suggest a novel mechanism whereby oxidative stress might prime the responsiveness of cells of the innate immune system. Targeting the TLR4 signalling pathway early during shock resuscitation may represent an anti-inflammatory strategy able to ameliorate late morbidity and mortality following S/R.

In 2013 around 289,000 women died from what was categorised as maternal complications. This figure is likely to be higher as only 40% of the world has an adequately function health reporting system (WHO et al 2014, p.1). Severe bleeding causes around 27% of all maternal deaths; this is the single biggest threat to pregnancy and childbirth. Moreover, maternal complications are the second biggest cause of death for women of reproductive age globally. The risks women and girls face through pregnancy and childbirth are the outcome of socio-cultural structures and norms, which increase the inequalities in many societies. The decisions we make, the choices we have, and the actions we carry out are a product of our social system’s structures and norms. Humanitarian crises painfully display the divisiveness and destruction that these structures and norms can have on the members of that system. But, crises also offer an opportunity to either, rebuild structures and norms in a way that reduces inequality and protects the vulnerable, or a regression to more traditional, more patriarchal and more hierarchical structures and norms which will ultimately disadvantage women and girls further in their plight for equality. There is a vicious circle of poverty and mortality that can be triggered by maternal death. In order to prevent these cycles from continuing, creative, simple and appropriate strategies need to be developed for humanitarian response that build on the knowledge systems and capacities of those affected, as well as the experience and expertise of practitioners. Instead of a discussion between development or humanitarian, the conversation should try to find ways for all interventions to be more homophilious with those affected and ensure that they do not worsen the structures protecting the most vulnerable. Innovation has long since been seen as a process for those who ‘have’, and not for those who ‘have not’. Criticisms of increasing inequality through a division based on socio-economic markers have only led to self-fulfilling stereotypes of who is innovative and who is not. This research is trying to shift the focus from one that is divisive to a more inclusionary approach. To address maternal mortality caused by severe bleeding, it is imperative to understand the context in which it is happening. Who is affected? Why? What do they think and believe? What happens to the family, the community? How are the structures and norms of the society affecting it? What solutions have been offered? In answering these questions it is clear how far the impact of maternal mortality can reach. It is the hope of this research, that its can be used to reduce and lessen this impact through better-targeted and tailored responses using appropriate tools – such as the non-pneumatic anti-shock garment, implemented in a mind frame of sustainability and resilience in an environment receptive to innovation. There is a need for fresh ideas and approaches to reduce a burden that does not exist in resource stable parts of the world, and a burden that has come to be seen as a problem of the poor. The non-pneumatic anti-shock garment is a game changer. It has the potential to inspire interest and access health systems, yet implementation thus far has been limited in humanitarian response. This research investigates maternal mortality caused by postpartum haemorrhage in humanitarian crises, in an endeavour to improve the discussion on including the NASG into the MISP as an appropriate tool to fight maternal mortality and the inequality that is found at its root.