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(2022)ThesisThe adoption of the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances 1988 (“the 1988 Convention”) has been widely viewed as the final step in establishing global drug prohibition. This thesis provides an examination of Australia’s decision to support and sign the Convention which has not been analysied before. It also provides a detailed history of the development of the Convention as Australia was a key participant in UN drug meetings at the time. This thesis is based on the first research to access archival files, primarily from Foreign Affairs but also from the AFP and Department of Health. Nearly 180 folders, totalling approximately 35,000 pages, were copied from the Australian archives. These files provide detailed reports of almost all meetings and drafts that progressed the 1988 Convention. Interviews with key participants were also conducted. It provides an interdisciplinary legal history of Australia’s involvement in the 1988 Convention using the lens of the international relations theory of neorealism and the political theory of historical institutionalism. Through process tracing, it uses the theories to examine whether neorealist geopolitical forces and institutional forces caused Australia to support and sign the Convention. The analysis finds that geopolitical considerations trumped early concerns that a third convention was not necessary. The analysis also demonstrates that institutional forces within the UN benefitted financially from drug prohibition and played an unusually strong role in encouraging the development of the 1988 Convention. It also finds that institutional forces within the Australian government, such as the AFP and Foreign Affairs, supported the new Convention to increase their own jurisdiction and powers. Lastly, it looks at whether alternative policies such as regulation or decriminalization were considered by key policymakers. It finds that key individuals did support decriminalization but were overpowered by institutional and geopolitical forces. The significance of the dissertation includes: large amounts of new data to explain the development of the 1988 Convention; it increases knowledge around the institutional forces of criminalization and global criminalization; it significantly increases our knowledge of the role of the United Nations in waging the War on Drugs; and it increases knowledge around how mid-level nations interact with global institutions.
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(2023)ThesisPluripotent stem cell-derived cardiomyocytes (hPSC–CM) have great importance for predicting safety parameters for pharmaceutical compounds and models of healthy versus disease states of the human heart. In recent years, there has been an insistence that all new pharmaceutical products are tested on in vitro models for potential proarrhythmic effects and the increased demand for improved biomimetic hPSC-CM in pharmaceutical safety assays such as the Comprehensive in vitro Proarrhythmic Assay (CiPA). In addition, hPSC-CM are being utilised in cell therapies to treat and reverse the effects of ischaemic heart disease, offering potential cures for cardiovascular diseases instead of treatments for delaying progressive heart failure. In the first part of this thesis, I will examine how purified extracellular matrix proteins (ECMPs) can influence pluripotent stem cell (PSC) behaviour and how we may use this to precondition cardiac progenitor lineage specifications. I use array-based techniques to investigate how protein combinations affect proliferation, pluripotency, germ layer, and cardiac progenitors. This method allows us to visualise how individual proteins can affect cells' behaviour in a larger array whilst highlighting how specific combinations can precondition pluripotent cells towards a cardiomyocyte lineage. This combinatorial approach led to the identification of several unique matrices that promote differentiation, which will aid efforts at producing therapeutically useful cell types with greater efficiency. In the second part of this thesis, I demonstrate a novel bioreactor that attenuates a magnetic field to dynamically modulate the stiffness of magnetoactive hydrogel to look at how biomimetic dynamic stiffening of a substrate can influence cardiomyocyte lineage specification. We investigate how biomimetic in vivo mechanics may influence cell fate by following the expression profiles of cells in different dynamic environments. Non-invasive electromagnetic signals affect substrate stiffness when combined with magnetic particles and magnetic fibres and how this can help direct cell orientation and accompanying lineage specification Finally, I investigate how variability in cell phenotypes and expression patterns are influenced by biomimetic cues and how these variabilities could be utilised in future safety assessment protocols and cell therapy treatments for cardiovascular disease.