Minerva Elements Records
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ItemReal-world Management and Outcomes for Anaplastic Lymphoma Kinase (ALK)- rearranged Advanced Non-small Cell Lung Cancer and Impact of COVID-19 on Cancer Service Delivery( 2023-09)This thesis is divided into two parts. Part 1 - Real-world Management and Outcomes for Anaplastic Lymphoma Kinase (ALK)-rearranged Advanced Non-small Cell Lung Cancer (ALK+ aNSCLC) ALK-rearrangements are found in 4% of Non-small cell lung cancers (NSCLC). Although this condition remains incurable, survival appears to be improving over time, with a multitude of selective oral tyrosine kinase inhibitors (ALK-inhibitors) now available and with many patients receiving multiple lines of therapy. Whilst next-generation ALK-inhibitors are standard of care in the first line, how to best sequence available therapies beyond this remains unclear. This thesis examines outcomes for real-world patients with ALK+ aNSCLC, using cohorts from AURORA (Australia) and Flatiron health (United States). Key findings: median overall survival (mOS) of 84 months in the AURORA cohort (n=171) and 37 months in the Flatiron cohort (n=737). Positive prognostic factors: never-smoking history, treatment in an academic setting and initial early stage at diagnosis. Gender was not prognostic. Treatment patterns varied and changed over time. Initial treatment with 2nd generation ALK-inhibitor was associated with improved survival over chemotherapy; initial treatment with 1st generation ALK-inhibitor followed by 2nd generation ALK-inhibitor was associated with improved survival compared to initial chemotherapy followed by 1st generation ALK-inhibitor. These retrospective observational studies represent the largest for people with ALK+ aNSCLC in Australia (AURORA) and globally (Flatiron). Future research may focus on intensifying treatment for people with a smoking history. Further work is required to determine why treatment in a community setting correlated with poorer survival in the US. Identifying optimal treatment sequences will require larger contemporary patient databases; collaboration is required among research organisations and with pharmaceutical companies conducting post-marketing studies. Part 2 - Impact of COVID-19 on Cancer Service Delivery Amid the early stages of the COVID-19 pandemic, significant shifts in patient presentation and oncology health service provision for people with lung and other cancer-types were observed globally. This research aimed to obtain timely real-world data on how clinicians perceived alterations in cancer service delivery due to COVID-19. Surveys were distributed to oncology clinicians through international professional societies in 2020. Clinicians highlighted substantial changes in oncology services. In the early period (May-June 2020), 89% of clinicians reported altering their practice due to COVID-19; including being less likely to initiate and more likely to cease systemic therapy in palliative and curative settings. Telehealth use was rapidly expanded; many clinicians reported concerns that this may negatively impact patient outcomes. Clinicians reported seeing fewer new patients in clinic. In the later period (October-November 2020), clinicians reported more advanced disease presentations and a swing back towards pre-COVID practice. Clinicians’ reported concerns regarding potential negative impact on cancer-related outcomes are further substantiated by global reports of fewer cancer diagnoses across 2020 and modelling studies predicting increase cancer-related mortality and health-care costs due to such changes. For cancer-related outcomes to be optimised through future pandemic events, heath-systems and policy makers need to have implementable action plans to rapidly upscale mitigation strategies, such as public education campaigns, telehealth and hospital in the home.
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ItemPainting the Restless Space( 2023-11)Painting the Restless Space is a material examination of the unstable nature of embodiment. Sitting under the studio work are two ‘shocking’ events of ‘carnage’ that instilled in me a personal concern for the precarious condition of bodies. Instability has become the subject and the method of the work, reinforced in the way that distinct materials behave and relate to one another. Moving from flesh (the referent) to paint and text (the signifiers) the hope for replication fades in the fluidity of paint and the potential of ‘wandering’ words. My attempts can only approximate flesh, as stand-ins, prostheses, and failures. Unpicking the illusory nature of boundaries that demarcate the self, I am asking “What can bodies do?” What are their limits and entanglements? What can we know and feel about our bodies through the ways that we relate to objects? How can a creative practice engage with processes of bodily reconfiguration, recontextualisation, and reinterpretation, exploring subjectivity as porous, entangled, and contingent? As a painter, I seek to find painterly ways to respond to these questions and to enliven the possibilities for knowledges rooted in the uncertainty and messiness of embodiment. Through this research, I articulate how my studio practice draws on a range of personal experiences, theoretical fields, and artistic practices to consider how painting can help us discover new ways of unsettling existing modes of looking and thinking about bodies.
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ItemManuel de Falla and The Guitar: A Discussion of Three New Transcriptions( 2023-09)This performance-based research project focuses on Spanish composer Manuel de Falla (1876-1946) and includes: a 70-minute performance recording; an 12,000-word written dissertation; and guitar transcriptions of three numbers from Falla’s orchestral ballets. The project explores how the Spanish guitar music influenced Falla’s compositions, his relationships with guitarists, and his music that has been transcribed for guitar. The performances include Falla’s compositions, works that were inspired by Falla, and two sonatas by Falla’s contemporaries – the Spanish composer Federico Moreno Torroba (1891-1982) and Mexican composer Manuel Maria Ponce (1882-1948), who were both the pioneers of guitar music in the twentieth century. Falla’s music has been very popular among guitarists, and he also worked closely with renowned guitarists such as Miguel Llobet (1878-1938) and Angel Barrios (1882-1964). Falla’s Homenaje a Debussy (1920) is regarded one of the most important guitar compositions of the twentieth century, while most of his orchestral works were strongly influenced by guitar music. Many guitarists such as Llobet, Emilio Pujol (1886-1980), Julian Bream (1933-2020), John Williams (1941- ) and Manuel Barrueco (1952- ) have arranged and performed transcriptions of Falla’s works for orchestra. An important part of this project is to create three new transcriptions selected from numbers from two of Falla’s most well-known ballets - El amor brujo (1915) and El sombrero de tres picos (1919). In the dissertation, the new transcriptions are discussed in relation to Falla’s orchestral scores, and compared to well-known published transcriptions. A performance guide for the transcriptions is also provided.
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ItemDissecting the role of gd T cells in T cell priming for liver stage immunity( 2023-11)Liver resident memory T cells (TRM) are poised for protection against repeat infection and rapidly form a robust defence against tissue-specific insults such as liver stage malaria. A direct correlation between liver stage immunity and gd T cells has been observed both in mice (Zaidi et al. 2017) and in humans (Seder et al. 2013; Ishizuka et al. 2016), but the precise molecular mechanisms by which these gd T cells exert their protective effect are yet to be defined. In mice, intravenous injection with radiation-attenuated sporozoites (RAS) confers sterile protection against challenge with live sporozoites. This protection is mediated by responding antigen-specific CD8+ and CD4+ T cells that migrate to the liver and form resident-memory T cells (TRM). In the absence of gd T cells, protective CD8+ liver TRM are not generated, leaving mice susceptible to reinfection. Using Plasmodium-specific T cells as a readout for effective immunity, we determined that IL-4 is important for the accumulation of CD8+ and CD4+ T cells. By utilising complex in vivo systems including mixed-bone marrow chimeras and adoptive transfer of gd T cells, we revealed that gd T cell-derived IL-4 is crucial for the expansion of antigen-specific CD8+ T cells. In addition, in vivo neutralisation of IL-12 or IFN-g confirmed a partial dependency for these cytokines, despite their traditionally opposing function to IL-4. Given IL-4, IFN-g and IL-12 all have a clear role in CD8+ T cell priming following RAS vaccination, we hypothesised that IL-4 and IFN-g synergise to enhance cDC1 activity. These findings led to our development of a novel model to reconstitute cDC1-deficient mice using CRISPR-edited primary dendritic cells. This model enabled the investigation of the mechanism by which gd T cell derived IL-4 leads to DC activation and therefore effective CD8+ T cell expansion for memory development. Collectively, this project has shown a significant role for IL-4 in the priming of malaria-specific CD8+ T cells and demonstrates a novel pathway for collaboration between gd T cells, cDC1s, and CD8+ T cells, revealing the potential for harnessing gd T cells in vaccination strategies against malaria.
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ItemFictions, Knowledge, and Justice( 2023-10)Fictions are a cornerstone of human cultures: they are created, shared, discussed, modified, and valued. Yet, philosophical accounts which privilege the ‘classical knower’ struggle to explain how fictions can affect us so deeply. Further, the fact that fictions seem to impact broader society and whole populations is largely overlooked, despite being observed in other disciplines. In this talk, I will draw on theories from philosophy of language, philosophy of mind, aesthetics, and epistemology to argue that fictions offer us epistemic resources of a unique kind, and that these resources lead to knowledge practices which can eventuate in harm."
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Item"There's more to care than just healing from incisions" Examining the health care experiences of gynaecology patients with a history of trauma( 2023-12)This qualitative study examined the health care experiences of fifteen gynaecology patients who have experienced traumatic life events. Semi-structured interviews were conducted, and data analysed using a trauma-informed lens. Current research suggests that hospitalisation can expose this patient group to re-traumatisation, however there is little research on their perspectives and care preferences. This study provides an original contribution to the knowledge of the care experience of gynaecology patients with a history of trauma, particularly those with endometriosis.
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ItemTracing The Drop: composing with an ethics of affirmation( 2023-10)This portfolio showcases works that reflect my compositional processes, which are informed by my practice as a contrabass guitarist and improviser, my regional and working-class origins, as well as my technical, conceptual, and philosophical grounding(s).
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ItemRepetitions That Differ: A Recording Analysis of Repeated Musical Material in Schubert’s G-major Piano Sonata, D. 894 and Schumann’s Davidsbündlertänze, Op. 6( 2023-12)Many of Schubert’s and Schumann’s piano works are characterised by a profusion of repeated musical materials, which poses challenges for pianists as to how to repeat them creatively and whether or not to repeat them. While a substantial amount of literature has recognised repetition as the hallmark of Schubert’s music, there have only been scattered scholarly allusions to the repetitive attribute of Schumann’s music. Despite the relative inattention to the latter, two piano works prove to be remarkable examples of both composers’ deep engagement with repetition: Schubert’s G-major piano sonata, D. 894 and Schumann’s Davidsbündlertänze, Op. 6. This thesis presents a practice-led recording analysis that examines divergent manners in which some of the repeated musical materials in the first movement of Schubert’s G-major piano sonata and three pieces from Schumann’s Davidsbündlertänze, Op. 6, Book 1, No. 2 and No. 7 and Book 2, No. 2, are performed by a selection of pianists, including Alfred Cortot, Ernst von Dohnányi, and Mitsuko Uchida, among others. More precisely, this analysis examines, within the aforementioned scope of written music, 1) whether the written repeat sign is actualised by the pianists and 2) the sounding differences between the pianists’ performances of the same musical material. Unlike most of the existing literature which only concerns repetitions in their written form, this recording analysis takes as its analytical object the sounding repetition that the act of playing produces. The analysis entails a practice-led research process, for which my musical intuition, my haptic knowledge of this repertoire and insights formed through my extensive musical practice, serve as the precondition. It is my hope that this recording analysis will become a source of inspiration for pianists who are facing the decision-making on whether or not to repeat, and who are searching for creative ways of repeating the repeated material.
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ItemWhat is logical deduction, in relation to physics, and how can students improve in this?( 2023-11)This research was done in the context of the increasing emphasis on thinking in education and the contention by many researchers that improvement in thinking leads to improvement in learning. The other context is the difficulty of physics as a subject at high school and the constant search for better methods of teaching the subject. The objective was to investigate the suitability of logic education as a method to improve students understanding of physics. The current state of physics and thinking education was explored in the Literature Review. This included an analysis of methods aimed at improving student performance in physics, improving thinking and improving performance in physics by improving the thinking that occurs in this subject. Consequently, logical deduction in physics was deemed an area with the potential to support such improvement. As well, the process of logical deduction was found to need clarification. The nature of logical deduction was, therefore, explored using a philosophical method. The first outcome of this was that the process usually thought of as ‘logical deduction’ was reconceptualised as ‘deductive inferring’. This was to better reflect its nature as a thinking process. Wittgenstein’s critique of solitary rule-following was then applied to the processes of deductive and inductive inferring, and they were problematised accordingly. Consequently, a more accurate delineation of these processes was given as deductive-like and inductive-like inferring. To assess the suitability of logic education for physics education, the thinking involved in physics problem-solving was investigated empirically using a think-aloud method. It was found that deductive-like inferring played a key role in this thinking. For instance, it was implicated in moving from the information given in a question, alongside assumed knowledge, towards an answer. The results strongly suggested that logical deduction should be an element in a suite of thinking skills explicitly taught to high school physics students, and that more emphasis should be placed on logic and thinking more generally in education. The results of these analyses also motivate further research in this area and suggestions for these were made.
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ItemBe a body: from experiential self-awareness to a truly bodily self( 2023-08)Dan Zahavi has defended a systematic and influential account of our most basic form of experiential self-consciousness, pre-reflective self-awareness (PRSA). For Zahavi, PRSA explicates the subtle way in which we are always immediately aware of the experiences we are having, are aware of them as being our experiences, and, in being so aware, are minimally self-aware. Zahavi’s model of PRSA (hereafter Z-PRSA) has proven influential in contemporary debates on the nature of self-consciousness and selfhood across analytic, Buddhist and continental philosophical traditions. However, one aspect of Zahavi’s model that is underdeveloped is its relation to the body. In his first major work, Self-Awareness and Alterity ([1999] 2020), Zahavi argued that Z-PRSA is intrinsically bodily by drawing on the analyses of bodily self-experience developed by Husserl and Merleau-Ponty. Yet, in more recent works, Zahavi has either remained silent on the topic of the body or indicated newfound neutrality on the question of embodiment, without adequately accounting for this change. By contrast, over this period, body awareness has become the focal point of philosophical and empirical investigations into self-consciousness and minimal phenomenal selfhood. Various forms of body awareness have been proposed to play a foundational role in grounding self-consciousness: the sense of body ownership, proprioceptive self-awareness, interoceptive self-awareness, spatial self-awareness, and the implicit self-awareness we have in perceiving the world as ripe for bodily action. An important question arises of how these modalities of bodily self-consciousness relate to Z-PRSA. Should we identify Z-PRSA with one of these forms of bodily self-consciousness, in a deflationary move? Alternatively, does bodily self-consciousness constitute a phenomenological condition of possibility for Z-PRSA? To find an answer, in this thesis I examine a series of descriptive and transcendental phenomenological arguments to determine whether, as Zahavi originally claimed, Z-PRSA is intrinsically bodily. I show first that Z-PRSA should not be identified with any of the above forms of bodily self-consciousness. Except for spatial self-awareness, they do not share with Z-PRSA its key phenomenological characteristics as a mode of awareness. While spatial self-awareness does, Zahavi’s strident opposition to any identity between it and Z-PRSA motivates me to consider an alternative connection between them: transcendental dependence. In evaluating Zahavi’s Husserlian enactivist argument from Self-Awareness and Alterity, I consider objections to its claim that object perception depends on spatial self-awareness, bodily movement, and kinaesthetic self-awareness. I show that Zahavi’s original argument for embodying Z-PRSA must be adapted to overcome an empirical challenge from cases of locked-in syndrome. While identifying a path for future research to more definitively determine the character of bodily experience in long-term locked-in syndrome, I provisionally conclude that the adapted argument succeeds in proving that Z-PRSA is only possible for a bodily subject of experience. Through my investigations, I aim to bring together a diversity of philosophical and empirical perspectives towards a perspicuous understanding of pre-reflective self-awareness and bodily self-experience.