http://hdl.handle.net/11343/159 Tue, 18 Feb 2020 23:36:28 GMT 2020-02-18T23:36:28Z http://hdl.handle.net/11343/234292 The Surgeon's Role in the Opioid Crisis: A Narrative Review and Call to Action Shadbolt, C; Abbott, JH; Camacho, X; Clarke, P; Lohmander, LS; Spelman, T; Sun, EC; Thorlund, JB; Zhang, Y; Dowsey, MM; Choong, PFM http://hdl.handle.net/11343/234292 http://hdl.handle.net/11343/234291 Museums as assemblage: practice and potentiality Pfefferkorn, Jasmin In this dissertation, I explore the emergence of the Museum of Old and New Art (Mona). In contrast to the voluminous media reports on its ground-breaking and radical entry into the museum world, I set out to situate this museum within a wider historical and theoretical framework. I introduce the key concept of assemblage systems theory to illustrate contemporary museum practice through a philosophy of openness, rather than fixed-chronological or fixed-institutional approaches. A key aim of this body of work is to provide a new critical framework for understanding contemporary museum practice, using assemblage systems theory, before applying this method to a case study of Mona. This thesis is divided into three sections. Section one (chapters one to three) serves to map out the field and provide a method of reframing. Chapter one maps a genealogy of museums, while chapter two explores key threads of institutional critique. These provide a contextual grounding for my argument that current museum practice is best understood through multiple, non-linear narratives. In the third chapter, I develop my methodological approach and conceptual framework, drawing on Manuel DeLanda’s (2006) extension of Giles Deleuze and Felix Guattari’s (1986) concept of ‘assemblage’, Conal McCarthy’s (2015) outline of ‘museum practice’ and Duncan Grewcock’s (2014) ‘critical reflexive visitation’. I argue that by tracing the interactions occurring between components of a variety of museums understood as ‘assemblages’, we can identify four ‘common notions’, the ‘normative’, ‘responsive’, ‘affective’ and ‘emergent’. In section two (chapters four to seven), I explore each of these common notions in turn, illustrating their processes of territorialisation and de/reterritorialisation. Section three (chapters eight and nine) serves as my primary case study and concluding reflection. In chapter eight, I undertake a sustained engagement with Mona to crosscheck its practices against the assemblage systems theory framework outlined in the preceding chapters. I argue that the interactions at Mona are constituted by an elaborate and dynamic interplay with a larger cultural framework and visitor agencies, problematising the idea that Mona fits within a linear history or a typological set of museum practices. I conclude with a reflection on potentiality, arguing that by releasing the function of theory from its authoritative and structural foundations, we liberate both conceptualisation and practice. © 2019 Jasmin Pfefferkorn Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/11343/234291 2019-01-01T00:00:00Z http://hdl.handle.net/11343/234290 Implications of different patterns of non-symbolic and symbolic magnitude representations for children’s mathematical abilities Chew, Shu Wen Cindy It has been argued that early math ability rests on two core, putatively innate, number systems: a precise small number system that allows an accurate and rapid apprehension of the numerosity of small sets (i.e., subitizing), and an approximate magnitude representation that allows discrimination between quantities. Moreover, differences in core number systems functioning are claimed to underlie differences in math ability. It is, furthermore, claimed that non-symbolic magnitude representations scaffold symbolic magnitude representations and ipso facto, math abilities. While these claims are frequently made, evidence in support of them is less than convincing. One difficulty in clarifying the relationships between the two magnitude representations, or core number and maths abilities, is the large inter-individual variation in these abilities in young children which may obscure the relationships between them. Most research that has examined this issue has used variable-oriented analytic methods that treat variance as error or noise. It is proposed herein that using a person-centred analytic method (i.e., latent profile modelling) to explicate the variance may allow identification of different ability patterns (latent profiles) that reside within the overall variance distribution and, in turn, provide a more nuanced developmental model of numerical cognition. To this end, three studies were conducted that focus on the significance of different patterns of non-symbolic–symbolic magnitude representations (Studies 1 and 2), and the relationship between these patterns and different patterns of the apprehension of small sets (Study 3). In Study 1(a), 124 five- to seven-year-old children completed non-symbolic and symbolic magnitude judgement tasks, cognitive measures often associated with math ability (visuo-spatial working memory [VSWM], naming Hindu-Arabic numbers and processing speed) as well as transcoding, and a single digit addition (SDA) test. A latent profile analysis (LPA) of the magnitude judgment accuracies and response times revealed four different patterns of non-symbolic–symbolic magnitude ability relationships residing within the overall variance distribution. The cognitive measures were related to the four profiles in different ways; and the profiles predicted differences in SDA and transcoding abilities. In Study 2(b), a partial replication of Study 1, 109 five- to six-year-old children completed the same tasks as Study 1 twice–one year apart. Latent transition analysis, a longitudinal extension of LPA, examined change and stability patterns in the four profiles over time. Similar to Study 1, the findings showed the patterns were differentially associated with cognitive and math abilities. Study 3 examined the relationship between non-symbolic–symbolic magnitude ability patterns and small precise number ability patterns. The findings replicated those of Studies 1 and 2, and also showed an overlap in the two core number abilities. While only VSWM and magnitude ability patterns predicted SDA abilities (over and above small precise number abilities); both magnitude ability and small precise number ability patterns predicted single-digit subtraction abilities over and above the other cognitive factors. In summary, the findings reported herein confirm the existence of different magnitude ability relation patterns which are differentially associated with different cognitive and math abilities. Examining the change/stability pathways in these ability patterns may reveal typical and atypical pathways of math development. It is evident that different magnitude ability relation patterns partially overlap with the small precise number ability patterns. Nonetheless, differences in the patterns in the two core number indices, along with differences in cognitive indices, predict different math abilities (i.e., single-digit addition and subtraction). The overall pattern of findings is discussed in terms of a more nuanced model of numerical cognition, as well as the value of the findings for specifying diagnostic markers of early math difficulties. (a) Chew, C. S., Forte, J. D., & Reeve, R. A. (2016). Cognitive factors affecting children’s nonsymbolic and symbolic magnitude judgment abilities: A latent profile analysis. Journal of Experimental Child Psychology, 152, 173-191. https://doi.org/10.1016/j.jecp.2016.07.001 (b) Chew, C. S., Forte, J. D., & Reeve, R. A. (2019). Implications of change/stability patterns in children’s non-symbolic and symbolic magnitude judgement abilities over one year: A latent transition analysis. Frontiers in Psychology, 10, 441. https://doi.org/10.3389/fpsyg.2019.00441 © 2019 Shu Wen Cindy Chew Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/11343/234290 2019-01-01T00:00:00Z http://hdl.handle.net/11343/234287 Exploring the immunology of small molecule inhibitors in chronic lymphocytic leukaemia Sharpe, Chia Elizabeth Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia in the western world. CLL is associated with profound immunodeficiency which leaves patients with insufficient anti-tumour immunity and is often compounded by immunosuppressive treatments. Recent advances in the development of targeted small molecule inhibitors, including Bruton’s tyrosine kinase (BTK) and B-cell lymphoma 2 (Bcl-2) inhibitors, has provided new, highly effective and less immunosuppressive treatment options. However, targeted therapies have not yet provided a cure for CLL, and there is still a need to improve the depth and durability of patient responses. Immunotherapies harness the patient’s own immune system to target cancer cells and are an attractive modality for combination with targeted therapies. However, by both on- or off-target mechanisms targeted therapies also been shown to have the potential to disrupt normal immune populations. This study aimed to understand the effects of targeted therapies on the immune system, thereby providing insight into the potential opportunities and pitfalls for the combination of immunotherapy with targeted therapies in CLL. This thesis explored the immunological impacts of the first-generation BTK inhibitor ibrutinib, as well as two more selective second-generation inhibitors zanubrutinib and acalabrutinib. The Bcl-2 inhibitor venetoclax was also investigated both as monotherapy and in combination with BTK inhibition. In Chapter 3, gene expression analysis was used to faithfully replicate a comprehensive immune profile comparable to more time consuming and costly flow cytometry analysis. Chapter 4 demonstrated that BTK and Bcl2 inhibitors had distinct effects on the immune profile of patients after long-term treatment with targeted therapies. Chapter 5 utilised in vitro functional assays to demonstrate how effector functions of T cells and natural killer (NK) cells, including cytotoxicity, cytokine production, and proliferation, are impaired by BTK inhibitors whereas NK cells, but not T cells were sensitive to venetoclax treatment. Subsequently, Chapter 6 explored the effect of the immunomodulatory drugs lenalidomide and a PD-1 inhibitor BGB-A317 in combination with ibrutinib, showing that T cell activation is modulated by both ibrutinib and the immunotherapies. These finding presented in this thesis demonstrate that targeted therapies have clear and distinct immunological effects. Ibrutinib broadly impair the function of multiple immune populations and in particular cellular cytotoxicity, suggesting that more selective BTK inhibitors are better candidates for combination with immunotherapies. Venetoclax affected the survival of specific T cell and NK cell populations, suggesting that long-term venetoclax treatment may result in alterations in the immune profile that may be exploited by combination therapy. These findings highlight the importance of understanding the immunological impacts of targeted therapies when incorporating immunotherapies into treatment combinations. © 2019 Chia Elizabeth Sharpe Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/11343/234287 2019-01-01T00:00:00Z