http://hdl.handle.net/11343/159 2021-10-17T12:04:53Z http://hdl.handle.net/11343/288186 Anderson, J 2021-10-01 A Gamechanger for Giorgione The article discusses the reaction to the discovery of a rare drawing by Giorgione and an inscription about him on the last page of the 1497 edition of Dante's Commedia, in the library of the Sydney University. It examines the writing of Giorgione's pupils and contemporaries to see if the handwriting may be identified: Leonardo, Catena, Sebastiano del Piombo, Titian and others. Journal Article 2021-10-01T00:00:00Z http://hdl.handle.net/11343/288185 Atazadeh, B; Olfat, H; Rajabifard, A 2021 3D Cadastre in Australian and New Zealand Jurisdictions: Similarities and Differences Conference Paper 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288184 Gelder, K; Weaver, R 2021-09-30 **Irish Republicanism and the Colonial Australian Bushranger Narrative** Journal Article 2021-09-30T00:00:00Z http://hdl.handle.net/11343/288183 Costelloe, JF; Russell, KL 2014-12-01 Identifying conservation priorities for aquatic refugia in an arid zone, ephemeral catchment: a hydrological approach The conservation priorities for protecting aquatic habitat of arid zone rivers requires an understanding of the drivers of distribution, characteristics and persistence of aquatic refugia in ephemeral to intermittent arid zone rivers. We describe and analyse the aquatic refugia that persist during drought periods in a large, arid, ephemeral river, the Neales River of central Australia, concentrating on refugia for fish and the hydrological processes that influence their location, characteristics and persistence. Field data were collected on flow events, water-level fluctuations in waterbodies during periods of no flow, waterbody dimensions and salinity. Modelling of open-water evaporation rates, analysis of salinity changes and frequency of flow events were used to investigate the main processes determining the persistence of waterbodies. The catchment contained both fluvial waterholes and artesian springs providing aquatic refugia. In addition, anthropogenic refugia, in the form of small dams situated on the floodplain and uncontrolled flow from artesian bores, also provided potential refuge. The catchment only contained one waterhole that had a cease-to-flow depth sufficient to persist over a no-flow period of 24months, but this would also dry within 24-30months. The capacity of the artesian springs to act as refugia is limited by their shallow depths and limited connectivity with the main river system. These data illustrate the vulnerability of the fluvial ecology of ephemeral, arid zone rivers to long-term droughts and water resource use and assist in identifying specific refugia that require conservation management. Journal Article 2014-12-01T00:00:00Z http://hdl.handle.net/11343/288182 Anderson, E; Chen, B; Shao, L 2021-10-17 Capacity Games with Supply Function Competition Journal Article 2021-10-17T00:00:00Z http://hdl.handle.net/11343/288181 Hitchcock, L 2021-12-01 The Accidental Archaeologist Becoming Lawrence of Arabia My tongue and cheek biography Journal Article 2021-12-01T00:00:00Z http://hdl.handle.net/11343/288180 Russell, KL; Vietz, GJ; Fletcher, TD 2019-02-25 Urban sediment supply to streams from hillslope sources Coarse-grained sediments supplied to a stream, in concert with the flow regime, play an important role in channel form and functioning, but are poorly understood in urban catchments. Improved knowledge of coarse-grained (>0.5 mm) sediment sources and supply rates will underpin strategies to mitigate impacts of urbanization on streams. We quantified key hillslope (i.e. non-channel) sources of sediment in urban areas by monitoring coarse-grained sediment yields from nine street-scale stormwater catchments over one year. From our observations, we developed a suburban hillslope sediment budget and a conceptual model of the response of hillslope coarse-grained sediment supply to different levels of urbanization. Coarse-grained sediment supply from the urban land surface was substantial. The highest unit-area yields came from infill construction sites (2800 kg/ha/yr), followed by gravel surfaces (740 kg/ha/yr), grass/mulch surfaces (84 kg/ha/yr), then impervious surfaces (21 kg/ha/yr), with the latter still producing yields far above background conditions. In typical suburban catchments grass and mulch surfaces and construction areas were key sources, with gravel and impervious surfaces making smaller contributions. Small source areas were important, for example construction produced 32% of sediment from 0.5% of the area. Connectivity of sediment sources to impervious surfaces, and hence to drainage systems, was important in driving sediment yields. Our conceptual model indicates that hillslope coarse-grained sediment supply increases with urbanization from natural to suburban conditions as connectivity increases, then declines with higher levels of urbanization as sources become scarcer. Impervious surfaces provide sources and supply pathways of coarse sediment, but also increase sediment transport capacity, causing severely supply-limited conditions and reducing the persistence of bed sediments in streams. When reducing hydrological connectivity to address the urban flow regime, consideration should be given to maintaining coarse-grained sediment supply through bypass or replenishment arrangements, to help reduce stream degradation and maintain form and functioning. Journal Article 2019-02-25T00:00:00Z http://hdl.handle.net/11343/288179 Kermode, S; Vietz, G; Tippler, C; Russell, K; Fletcher, T; van der Sterran, M; Birtles, P; Dean, M 2020-10-23 Urban Streamflow Impact Assessment (USIA): a novel approach for protecting urbanising waterways and providing the justification for integrated water management As urban populations expand globally, the associated increase in urban land cover directly impacts the social and environmental amenity of natural assets, including waterways. The primary driver of urban waterway degradation changes in land uses which results in altered hydrology–from stormwater runoff, and where present, wastewater treatment plant discharge. Whilst the impacts of pollutants are relatively well regulated via public policy, a gap remains for the management of flow regime modification. The Urban Streamflow Impact Assessment (USIA) was developed to fill this management and planning knowledge gap. The approach begins with the identification of waterway values (social, ecological and geomorphic) then explicitly links these values to streamflow characteristics using hydraulic and hydrologic metrics. USIA was applied to a case study in Western Sydney and demonstrated the loss of values associated with ‘business-as-usual’ approaches to stormwater and wastewater management. Conventional stormwater management approaches do not remove enough excess flow to meet reasonable outcomes for the waterway. This excess runoff is increasingly seen as a resource and opportunity for improving water security and liveability. USIA is consistent with regulatory frameworks and can be applied across developing and established urban catchments to provide explicit input to planning controls. The approach is appropriate at multiple scales, informing urban planning from a broad strategic level through to detailed design. By linking social and ecological values with geomorphic and flow requirements, the approach enables an understanding of which management approaches could allow desirable waterway outcomes to be met. Journal Article 2020-10-23T00:00:00Z http://hdl.handle.net/11343/288178 Russell, KL; Vietz, GJ; Fletcher, TD 2017-05-01 Global sediment yields from urban and urbanizing watersheds Streams with urban watersheds are almost universally subject to degradation, largely driven by changes to flow and sediment inputs from the watershed. However, the impact of urbanization on sediment yields of urban watersheds is poorly understood. We undertook a comprehensive review of global responses of fine-grained and coarse-grained sediment yields to different phases of urbanization and compared them to a long-standing conceptual model. The summarized yields showed a great deal of variability, but were consistent with the widely-used conceptual model for watersheds with active construction. Importantly, however, the yields for established urban areas tended to be higher than previously assumed, and tended to remain higher than background levels. This is most likely because the urban drainage network has a very high sediment transport efficiency and because the increased runoff in urban watersheds is very effective at eroding the available sediment sources (mainly infill development, urban decay and renewal, and gravel surfaces in parks and gardens). The updated model provided here will assist in informing the extent to which sediment supply to stormwater drainage systems and urban streams needs to be addressed to assist the protection and restoration of streams in urban watersheds. Journal Article 2017-05-01T00:00:00Z http://hdl.handle.net/11343/288177 Makhoul, Christian 2021 Regulation of Golgi morphology and site-specific activation of mTORC1 During interphase, most vertebrate cells organise the Golgi apparatus into a twisted ribbon-like structure, formed by the lateral fusion of adjacent Golgi stacks into the elongated Golgi profile of the Golgi ribbon (De Matteis et al., 2008; Rios and Borens, 2003). Recent studies are just beginning to recognise a role for the Golgi ribbon architecture in the regulation of a range of higher-order cellular processes such as mitosis (Ayala et al., 2020) and autophagy (Gosavi et al., 2018; Guo et al., 2012). The morphology of the Golgi ribbon is highly dynamic. There are multiple pathways which regulate Golgi architecture and knowledge of these pathways is relevant to understanding the function of the Golgi morphology. Previous studies from the Gleeson laboratory showed that an increased level of the trans-Golgi network golgin, GRIP and coiled-coil domain-containing protein of 88 kDa (GCC88), resulted in the dispersal of the Golgi ribbon into Golgi mini-stacks (Gosavi et al., 2018; Luke et al., 2003). The mechanism by which GCC88 alters the Golgi morphology is unknown and a major aim of this thesis was to investigate the mechanism by which GCC88 regulates the architecture of the Golgi ribbon. Previous findings from the Gleeson laboratory have shown that the Golgi ribbon acts as platform for the recruitment and activation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) (Gosavi et al., 2018). Dispersal of the Golgi ribbon led to the loss of mTORC1 activation at the Golgi and promoted upregulation of autophagy. However, the spatial regulation of mTORC1 at the Golgi is not well-characterized. The signalling pathways and the molecular machinery that promote the translocation and activation of mTORC1 at the Golgi have not been well defined. Another major aim of this thesis was to elucidate the upstream signalling pathways that regulate mTORC1 activation at the Golgi and to identify mTORC1 interactors that facilitate its recruitment to the Golgi. The mechanism by which the peripherally-associated TGN golgin GCC88, modulates the morphology of the Golgi ribbon has not been characterized. In Chapter 3, I observed that GCC88-mediated dispersal of the Golgi ribbon was actin-dependent. Using BioID and mass spectrometry (Roux et al., 2012), I identified potential GCC88 novel binding partners that interact with the actin network. One of the hits, namely the long isoform of intersectin-1 (ITSN-1-L) was shown to link GCC88 to the actin network. The long isoform of ITSN-1 is a Cdc42 guanine nucleotide exchange factor (GEF), an important finding as Cdc42 is known to regulate localized actin polymerisation at the Golgi (Farhan and Hsu, 2016; Humphries et al., 2014; Matas et al., 2004). I demonstrated that ITSN-1 was localised to the TGN and partially dependent on GCC88 for its localisation. Furthermore, ITSN-1-L overexpression enhanced the actin network and its depletion rescued the dispersal of the Golgi ribbon in GCC88-overexpressing cells. This led to the proposal of a GCC88-ITSN-1-actin pathway that regulates the morphology of the Golgi ribbon in a myosin-IIA dependent manner. The upstream signalling pathways that promote mTORC1 activation at the Golgi are not well defined. In Chapter 4, I modified a previously validated Forster resonance energy transfer (FRET)-based mTORC1 biosensor to be targeted to the peripheral surface of the Golgi. This Golgi targeted biosensor was used to provide direct evidence of mTORC1 activation at the Golgi and supported previous findings that demonstrated reduced mTORC1 recruitment and activation on dispersed Golgi mini-stacks. In Chapter 5, I attempted to identify the molecular machinery required for mTORC1 recruitment by co-immunoprecipitation and mass spectrometry analysis of myc-tagged Raptor, a subunit of mTORC1 that could facilitate its recruitment to the Golgi. This attempt was unsuccessful in identifying Golgi-proteins responsible for mTORC1 recruitment, however, from this analysis, I identified ADP-ribosylation factor 5 (Arf5) as a regulator of mTORC1 recruitment and activation at plasma membrane ruffles. Arf5 was shown to localize with mTOR at membrane ruffles. Depletion of Arf5 reduced the recruitment of mTOR to membrane ruffles, downregulated mTORC1 signalling and, using a plasma membrane targeted biosensor, hindered direct activation of mTORC1 at the plasma membrane. These findings demonstrated a novel role for Arf5 in the recruitment and activation of mTORC1 at plasma membrane ruffles. In summary, this work has characterized a novel GCC88-mediated pathway that regulates the architecture of the Golgi ribbon, designed a FRET-based tool to measure the direct activation of mTORC1 at the Golgi and identified a novel mechanism that facilitates the spatial activation of mTORC1 at plasma membrane ruffles. © 2021 Christian Makhoul PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288176 Salazar Ruales, Carolina Alejandra 2021 Molecular and functional analysis of Mucinous Ovarian Carcinoma Mucinous ovarian carcinoma (MOC) is a rare subtype of ovarian cancer (OC) distinct from all other subtypes. MOC represents 3% of OC cases; however, it responds very poorly to conventional chemotherapies contributing to the poor outcome of OC. Moreover, there is a lack of effective therapies for MOC since treatments with platinum-based chemotherapy or PARP-inhibitors are unlikely to be effective. The recent description of the molecular landscape of MOC, including contributions by work in this thesis, allowed the identification of novel therapies that target the most recurrent genetic features of the disease. Nevertheless, there is still the need to develop accurate pre-clinical models in order to test the efficacy of these new therapies. This thesis evaluates the transcription factor ELF3 as a new MOC candidate driver gene. We performed a comprehensive analysis of 210 human mucinous ovarian tumours and identified that ELF3 was mutated in 8.2% of our sample cohort. To assess whether ELF3 acts as a tumour suppressor or oncogene in MOC and how its mutated function is expressed in cancer, we evaluated the ability of MOC cells to proliferate, migrate and invade, by introducing truncating mutations using CRISPR-Cas9 technology. It was found that ELF3 could possibly act as a tumour suppressor in MOC; however, its role might depend on coexisting mutations in the cells. This thesis also describes a novel 3D patient-derived therapeutic approach to pre-test the effectiveness of drugs, as monotherapy or in combination, before exposing patients to ineffective therapies or side effects. A mucinous ovarian tumour 3D platform that enables the correlation of patient genetic data with drug testing was established in the first result chapter of this thesis. MOC organoid development was based on the MOC genetic profile and characteristics as well as optimization that adapted human colorectal and pancreatic organoid culture systems. It was found that Wnt-3a is essential for mucinous ovarian tumour organoid long-term derivation. Moreover, MOC organoids faithfully recapitulate MOC primary tumours at the genomic level and retain histological characteristics of their corresponding primary tumours. The development of MOC organoids and 3D spheroids from cell lines together with the description of the genetic profile of MOC allowed the development and testing of a panel of novel therapies that targets the most frequent mutations found in MOC tumours, including a mutant TP53 activator, a Wnt inhibitor, RAF/EGFR/RAS/CDK4 and CDK6 inhibitors, and two antitumour compounds for HER2-overexpressing tumour cells (APR-246, OMP-18R5, BGB-283, BKM120, PD-0332991, PLX4032, Trastuzumab and Lapatinib). The organoids and spheroids showed different responses to the individual therapies tested, depending on the individual genetic features of the models. Spheroids showed sensitivity to PD-0332991, Trastuzumab, PLX4032 , and BKM-120 . MOC organoids also showed different responses: MOC organoid MOCOR-16 showed sensitivity to APR-246, and resistance to Trastuzumab; however, MOCOR-38 was sensitive to Trastuzumab but resistant to APR-246. This chapter also shows the first attempt of drug synergy scoring using automatic robots to create 3D MOC models. Synergistic combinations were identified for one of the spheroid lines when APR-246 and BKM-120 were combined. Interestingly, the spheroids were resistant to APR-246 in monotherapy. If validated independently, these results could potentially represent a more effective treatment for MOC. Antagonistic interactions were also found, with the strongest antagonism occurring between PLX4032 and BGB-283. The findings of this study substantially increase our understanding of mucinous ovarian tumours together with potential personalized therapeutic targets to improve the survival outcomes for women with this deadly disease. © 2021 Carolina Alejandra Salazar Ruales PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288175 2021-09-23 Bringing Together Forms of Collective Engagement in Youth Transitions Chapter 2021-09-23T00:00:00Z http://hdl.handle.net/11343/288174 Fu, J 2021 Digital Citizenship in China Book 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288173 Gurner, KH; Richardson, JJ; Harvey, AJ; Gardner, DK 2021-06-18 A pilot study investigating a novel particle-based growth factor delivery system for preimplantation embryo culture. STUDY QUESTION: Can vascular endothelial growth factor (VEGF)-loaded silica supraparticles (V-SPs) be used as a novel mode of delivering VEGF to the developing preimplantation embryo in vitro? SUMMARY ANSWER: Supplementation of embryo culture media with V-SPs promoted embryonic development in a manner equivalent to media supplemented with free VEGF. WHAT IS KNOWN ALREADY: VEGF is a maternally derived growth factor that promotes preimplantation embryonic development in vitro. However, its use in clinical media has limitations due to its low stability in solution. STUDY DESIGN, SIZE, DURATION: This study was a laboratory-based analysis utilising a mouse model. V-SPs were prepared in vitro and supplemented to embryonic culture media. The bioactivity of V-SPs was determined by analysis of blastocyst developmental outcomes (blastocyst development rate and total cell number). PARTICIPANTS/MATERIALS, SETTING, METHODS: SPs were loaded with fluorescently labelled VEGF and release kinetics were characterised. Bioactivity of unlabelled VEGF released from V-SPs was determined by analysis of embryo developmental outcomes (blastocyst developmental rate and total cell number) following individual mouse embryo culture in 20 µl of G1/G2 media at 5% oxygen, supplemented with 10 ng/ml recombinant mouse VEGF in solution or with V-SPs. The bioactivity of freeze-dried V-SPs was also assessed to determine the efficacy of cryostorage. MAIN RESULTS AND THE ROLE OF CHANCE: VEGF release kinetics were characterised by an initial burst of VEGF from loaded spheres followed by a consistent lower level of VEGF release over 48 h. VEGF released from V-SPs resulted in significant increases in total blastocyst cell number relative to the control (P < 0.001), replicating the effects of medium freely supplemented with fresh VEGF (P < 0.001). Similarly, freeze dried V-SPs exerted comparable effects on embryonic development (P < 0.05). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this proof of principle study, the effects of V-SPs on embryonic development were only analysed in a mouse model. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that SPs represent a novel method by which a targeted dose of therapeutic agents (e.g. bioactive VEGF) can be delivered to the developing in vitro embryo to promote embryonic development, an approach that negates the breakdown of VEGF associated with storage in solution. As such, V-SPs may be an alternative and effective method of delivering bioactive VEGF to the developing in vitro embryo; however, the potential use of V-SPs in clinical IVF requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the University of Melbourne. The authors have no conflict of interest to declare. Journal Article 2021-06-18T00:00:00Z http://hdl.handle.net/11343/288171 Devereux, T 2021 New book 14/10/21 Book 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288170 Bradhurst, R; Garner, G; East, I; Death, C; Dodd, A; Kompas, T 2021-04-28 Post-outbreak surveillance strategies to support proof of freedom from foot-and-mouth disease Abstract Whilst emergency vaccination may help contain foot-and-mouth disease in a previously FMD-free country, its use complicates post-outbreak surveillance and the recovery of FMD-free status. A structured surveillance program is required that can distinguish between vaccinated and residually infected animals, and provide statistical confidence that the virus is no longer circulating in previously infected areas. Epidemiological models have been well-used to investigate the potential benefits of emergency vaccination during a control progam and when/where/whom to vaccinate in the face of finite supplies of vaccine and personnel. Less well studied are post-outbreak issues such as the management of vaccinated animals and the implications of having used vaccination during surveillance regimes to support proof-of-freedom. This paper presents enhancements to the Australian Animal Disease Model (AADIS) that allow comparisons of different post-outbreak surveillance sampling regimes for establishing proof-of-freedom from FMD. A case study is provided that compares a baseline surveillance sampling regime (derived from current OIE guidelines), with an alternative less intensive sampling regime. It was found that when vaccination was not part of the control program, a reduced sampling intensity significantly reduced the number of samples collected and the cost of the post-outbreak surveillance program, without increasing the risk of missing residual infected herds. Journal Article 2021-04-28T00:00:00Z http://hdl.handle.net/11343/288134 Gabriel, J 2021-10-02 Reimagining China in Interwar German Opera: Eugen d’Albert’s Mister Wu and Ernst Toch’s Der Fächer This chapter examines how Germany and China’s changed relationship after World War I and Germany’s forced decolonization affected representations of China in German opera through analysis of two operas. The first, Eugen d’Albert and M. Karlev’s Mister Wu (1930–1932), reconfigured the tropes of the Yellow Peril, reflecting the social upheavals experienced by Germany after the war and Germany’s new relationship with its former colonies. The second, Ernst Toch and Ferdinand Lion’s Der Fächer (The Fan, 1927–1930), transported a Chinese fairy tale to present-day Shanghai. Modern China becomes an allegorical site whose similarities to Germany are a means of exploring Germany’s new postwar identity. However, this portrayal also subtly positioned Germany in a dominant role, anticipating post-World War II neocolonialism. Chapter 2021-10-02T00:00:00Z http://hdl.handle.net/11343/288111 Ohashi, J; Ohashi, H 2021-08-16 Learning Asian languages is about much more than trade and employability and universities should convey this Journal Article 2021-08-16T00:00:00Z http://hdl.handle.net/11343/288110 Riddiough, Georgina Ellen 2021 Tumour growth in the regenerating liver Post-partial hepatectomy liver regeneration (PHLR) facilitates major hepatic resection by reinstating liver volume and function. However, experimental and clinical data has linked PHLR to tumour progression and recurrence in the future liver remnant following liver resection. This presents a major hurdle for hepatobiliary surgeons seeking curative resections for their patients. This thesis explores the mechanisms underlying tumour recurrence in the regenerating liver and investigates the role of renin-angiotensin inhibitors (RASi) in attenuating the growth of colorectal liver metastasis (CRLM) using murine and human models of CRLM disease. RASi, captopril attenuated CRLM tumour burden in the regenerating liver in vivo and underlying mechanisms for this were identified and included reprogramming of the immune and metabolic responses, as well as tumour specific downregulation of the proto-oncogene c-myc. Captopril also attenuated growth of patient-derived CRLM organoids in vitro. In summary, captopril exerts an effective anti-tumour response in the regenerating liver and should be pursued as a treatment adjunct for patients undergoing liver resection for CRLM. © 2021 Georgina Ellen Riddiough PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288109 Gesha, Frederick Emanual Gesha 2021 Cultural Continuum of Aboriginal and Torres Strait Islander Cultural Practices This thesis investigates how Aboriginal and Torres Strait Islander knowledge and cultural traditions are remembered and practiced within the framework of a colonial society. I develop an Indigenous methodology utilising a participatory mode of enquiry through yarning, sharing and deep listening, drawing on my own experience and standpoint to relate to and elicit knowledge from collaborators. The research brings together investigations centring on practices utilised in remembering heritage and culture. I draw on original research including reflections on my experiences, living and working as an Indigenous musician, Arts Strategy writer and festival organiser in Perth, Sydney and Melbourne. My research takes into account interviews and research with elders and cultural practitioners in Canada and New Zealand as well as secondary sources in order to understand the methodology of colonisation and the ensuing disruptions to the cultural practices and knowledges of Aboriginal and Torres Strait Islanders within the colonisation continuum of Australia. © 2021 Frederick Emanual Gesha Gesha Masters Research thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288108 Kastrappis, Georgios Loizou 2021 Exploring Treatments to Inhibit tumour recurrence Following Resection of Colorectal Liver Metastases Background: Colorectal cancer (CRC) accounts for 9.2% of all cancer related deaths making it the second most common cause of cancer related death worldwide. The majority of CRC deaths are attributed to metastases, with liver being the most common metastatic site. Currently the best available treatment for colorectal liver metastasis (CRLM) that offers high survival rates and a potential for cure is liver resection surgery. However, only a small fraction of CRLM patients are eligible for surgery. Furthermore, liver resection and the ensuing liver regeneration (LR) upregulate growth factors and cytokines leading to a pro-inflammatory response, creating a favourable environment for any dormant tumours to grow. Thus, liver resected patients experience high tumour recurrence rates. Anti-inflammatory treatments administered perioperatively may reduce tumour recurrence. Previous experimental studies have shown that inhibition of the Renin Angiotensin System (RAS) classical pathway reduces tumour growth and accelerates liver regeneration together with a reduction in inflammation. This study investigates mechanisms by which captopril a RAS inhibitor (RASi) influences the environment of a regenerating liver to reduce inflammation. Additionally, it investigates the potential of a VEGFR-3 specific inhibitor, SAR131675, to inhibit tumour growth and reduce inflammation. Aims: 1) To investigate the effects Captopril, an angiotensin I converting enzyme (ACE) inhibitor, has on pro-inflammatory cytokines during LR. 2) To investigate the effect Captopril has on the global proteome and phosphoproteome of the liver during the early stages of LR 3) To investigate the effect SAR131675, a VEGFR-3 tyrosine kinase inhibitor, has on liver metastases in a CRLM mouse model and determine the likely mechanisms. Methods: Male CBA mice were used for all experiments in this study. For the liver regeneration study a 70% partial hepatectomy mouse model was used. Captopril (750mg/kg) was administered intraperitoneally and given daily starting 4 days before surgery until the endpoint (1 hour, 3 hours, 4 hours, 1 day and 2 days). Serum cytokine (IL-2, IL-6, IL-10, IL-12p70, IL-17A, TNF, IFNgamma and MCP-1) levels were assessed at the 1, 3 and 4 hour timepoints while liver regeneration was assessed at the day 1 and 2 timepoints, by measuring liver to body weight ratio and the liver regeneration rate. In addition, the 4 hour timepoint was used to conduct global proteomic and phosphoproteomic analyses. To investigate the effects SAR131675 had on CRLM and the mechanisms involved a mouse model of CRLM was used where metastases were established via intrasplenic injection of tumour cells. Immunohistochemistry was used for the analysis of proliferation, apoptosis, lymphatic and blood vessel densities, macrophage and T-cell tumour infiltration. Furthermore, FACS analysis was used to investigate changes in immune lymphoid and myeloid cell populations due to SAR131675 treatment. Results: Captopril treatment significantly reduced IL-6 levels in the serum of mice in the early phase of liver regeneration. This result was reinforced by the results of the global proteomic and phospho-proteomic study indicating that Captopril induced changes in a great number of proteins involved in inflammatory pathways in almost every cell process including cell proliferation, apoptosis transcription, translation and stress response. Interestingly, the largest proportion of protein changes were associated with lipid metabolism which is also closely associated with inflammatory pathways. SAR131675 treatment significantly reduced tumour growth in the mouse model of liver metastases. Mechanistically SAR131675 treatment changed the tumour microenvironment and promoted anti-tumour immune responses by modulating the tumour infiltrating immune cell composition; increasing the ratio of T lymphocytes to monocytes and by modifying the T-cell and myeloid cell subtype and activation to that favouring an anti-tumour immune response. Conclusion: Both Captopril and SAR131675 were able to modulate inflammatory pathways creating a microenvironment that is inhibitory towards tumour growth. These treatments have potential to be used in order to reduce tumour recurrence in patients that have undergone liver resection surgery. © 2021 Georgios Loizou Kastrappis PhD thesis 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288107 Day, A; Tamatea, A 2021 Te Tūāpapa Whakaharatau Understanding Prison Violence in Aotearoa As National Commissioner of Ara Poutama Aotearoa, the safety of our Corrections whānau - our staff and the people in our prisons - has always been a top priority for me. We are committed to ensuring we operate prisons that protect the safety of those in our care, our staff, and our communities. A number of highly complex factors contribute to violence in our prison environments. Corrections continues to implement initiatives to maintain safe prisons and address the rate of interpersonal violence across our prisons. Forging strong and collaborative partnerships with partner agencies and learning from our differing perspectives is key to making progress on this issue. Since my involvement in the Governance Committee of Nga Tūmanakotanga I’ve been encouraged with the commitment to partner with Māori in this area, which closely aligns with our own Ara Poutama Hōkai Rangi strategy. The Nga Tūmanakotanga online symposium, Understanding Prison Violence in Aotearoa, was held in December 2020 and was the result of a collaborative and ongoing partnership between Ara Poutama Aotearoa, Nga Tūmanakotanga, and Waikato University. This symposium provided a valued and much needed opportunity to discuss the complex issues of prison violence with a wider and public audience. The insightful kōrero, experiences, and expertise of the speakers brought voices from diverse perspectives to the fore. This book has been transcribed from the symposium and provides the opportunity to engage and educate readers on the less visible aspects of prison violence. Conference Paper 2021-01-01T00:00:00Z http://hdl.handle.net/11343/288106 Dawson, LP; Biswas, S; Lefkovits, J; Stub, D; Burchill, L; Evans, SM; Reid, C; Eccleston, D 2021-09-01 Characteristics and Quality of National Cardiac Registries: A Systematic Review BACKGROUND: National cardiac registries are increasingly used for informing health policy, improving the quality and cost-effectiveness of patient care, clinical research, and monitoring the safety of novel treatments. However, the quality of registries is variable. We aimed to assess the characteristics and quality of national cardiac registries across all subspecialties of cardiac care. METHODS: Publications relating to national cardiac registries across six cardiac subspecialty domains were identified by searching MEDLINE and the Google advanced search function with 26 438 citations and 4812 full-text articles reviewed. RESULTS: A total of 155 registries, representing 49 countries, were included in the study. Of these, 45 related to coronary disease or percutaneous coronary intervention, 28 related to devices, arrhythmia, and electrophysiology, 24 related to heart failure, transplant, and mechanical support, 21 related to structural heart disease, 21 related to congenital heart disease, and 16 related to cardiac surgery. Enrollment was procedure-based in 60% and disease-based in 40%. A total of 73.10 million patients were estimated to have been enrolled in cardiac registries. Quality scoring was performed using a validated registry grading system, with registries performing best in the use of explicit variable definitions and worst in assessment of data reliability. Higher quality scores were associated with government funding, mandated enrollment, linkage to other registries, and outcome risk adjustment. Quality scores and number of registries within a country were positively correlated with each other and with measures of national economic output, health expenditure, and urbanization. CONCLUSIONS: There has been remarkable growth in the uptake of national cardiac registries across the last few decades. However, the quality of processes used to ensure data completeness and accuracy remain variable and few countries have integrated registries covering multiple subspecialty domains. Clinicians, funders, and health policymakers should be encouraged to focus on the range, quality, and integration of these registries. Registration: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020204224. Journal Article 2021-09-01T00:00:00Z http://hdl.handle.net/11343/288105 Duncan, AJ; Peric, I; Boston, R; Seneviratne, U 2021-09-22 Predictive semiology of psychogenic non-epileptic seizures in an epilepsy monitoring unit INTRODUCTION: The diagnosis of psychogenic nonepileptic seizures (PNES) is a common clinical dilemma. We sought to assess the diagnostic value of four ictal signs commonly used in differentiating PNES from epileptic seizures (ES). METHODS: We retrospectively reviewed consecutive adult video-electroencephalogram (VEM) studies conducted at a single tertiary epilepsy center between May 2009 and August 2016. Each event was assessed by a blinded rater for the presence of four signs: fluctuating course, head shaking, hip thrusting, and back arching. The final diagnosis of PNES or ES was established for each event based on clinical and VEM characteristics. All ES were pooled regardless of focal or generalized onset. We analyzed the odds ratio of each sign in PNES in comparison to ES with adjustment for repeated measures using logistic regression. Additionally, we calculated the sensitivity, specificity, predictive values, and likelihood ratios of each sign to diagnose PNES. RESULTS: A total of 742 events from 140 VEM studies were assessed. Fluctuating course (odds ratio (OR) 37.37, 95% confidence interval (CI) 13.56-102.96, P < 0.0001), head shaking (OR 2.95, 95% CI 1.26-6.79, P = 0.012), and hip thrusting (OR 4.28, 95% CI 1.21-15.18, P = 0.02) were each significantly predictive of PNES. Fluctuating course had the highest sensitivity (76.16%). Back arching (OR 1.06, 95% CI 0.35-3.20, P = 0.92) was not significantly associated with PNES. CONCLUSION: Fluctuating course, head shaking, and hip thrusting are semiological features significantly more common in PNES than ES. Fluctuating course is the most reliable sign. Back arching does not appear to differentiate PNES from ES. Journal Article 2021-09-22T00:00:00Z http://hdl.handle.net/11343/288104 Elbourne, H; Soo, WK; O'Reilly, V; Moran, A; Steer, CB 2021-09-14 Exercise as a supportive care strategy in men with prostate cancer receiving androgen deprivation therapy at a regional cancer centre: a survey of patients and clinicians. PURPOSE: To understand how frequently exercise is discussed and/or prescribed as a supportive care measure and the barriers and facilitators to exercise uptake for men with prostate cancer receiving androgen deprivation therapy (ADT) at a regional cancer centre. METHODS: An observational, cross-sectional study was conducted at a regional cancer centre in three stages: (1) Retrospective chart review of men with prostate cancer undergoing ADT to identify the frequency of discussion and/or prescription of supportive care measures; (2) prospective patient survey exploring barriers and facilitators to exercise; and (3) prospective clinician survey exploring barriers, facilitators and awareness of exercise guidelines in men with prostate cancer. RESULTS: Files of 100 men receiving ADT (mean age 73 years; mean ADT duration =12 months) in the medical oncology (n = 50) and radiation oncology (n = 50) clinics were reviewed. Exercise was discussed with 16% of patients and prescribed directly to 5%. Patient survey (n = 49). 44.2% of patients reported participating in exercise at a high level. Common barriers to exercise participation included fatigue (51.0%), cancer/treatment-related weakness (46.9%) and joint stiffness (44.9%). 36.7% of patients reported interest in a supervised exercise program. Clinician survey (n = 22). 36.4% identified one or more exercise guidelines, and 40.9% correctly identified national exercise guidelines. Clinicians reported low knowledge of referral pathways to a supervised exercise program (27.3%). Clinicians believe physiotherapists (95.5%) are most suited to exercise prescription and 72.7% stated that exercise counselling should be part of supportive care. Limited time (63.6%) and patient safety (59.1%) were the two most common barriers to discussing exercise with patients. Clinicians reported that only 21.9% of their patients asked about exercise. The most endorsed facilitators to increase exercise uptake were patient handouts (90.9%) and integration of exercise specialists into the clinical team (86.4%). CONCLUSION: Despite a third of patient respondents indicating an interest in a supervised exercise program, only 16% of patients with prostate cancer undergoing ADT at a regional cancer centre engaged in a discussion about exercise with their treating clinicians. Physical limitations and fatigue were the greatest barriers for patients. Clinicians indicated a need for more clinician education and better integration of exercise specialists into clinical care. A tailored, integrated approach is needed to improve the uptake of exercise in men with prostate cancer. Journal Article 2021-09-14T00:00:00Z http://hdl.handle.net/11343/288103 Kent, SJ; Juno, JA 2021-09-15 Vaccination after prior COVID-19 infection: Implications for dose sparing and booster shots. Journal Article 2021-09-15T00:00:00Z http://hdl.handle.net/11343/288102 Fornaro, M; De Prisco, M; Billeci, M; Ermini, E; Young, AH; Lafer, B; Soares, JC; Vieta, E; Quevedo, J; de Bartolomeis, A; Sim, K; Yatham, LN; Bauer, M; Stein, DJ; Solmi, M; Berk, M; Carvalho, AF 2021-09-04 Implications of the COVID-19 pandemic for people with bipolar disorders: A scoping review. INTRODUCTION: The COVID-19 (coronavirus disease 2019)-related pandemic represents a global source of societal and health burden. Yet, the impact of the pandemic on people with severe mental illness, including bipolar disorder (BD), remains unclear, warranting scoping review on the matter. METHODS: The MEDLINE and EMBASE databases were systematically searched from inception up to April 24, 2021, adopting broad inclusion criteria to assess a variety of clinical and public health themes related to people with a primary diagnosis of BD during the COVID-19 pandemics. The present work complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) registered in the Open Science Framework (OSF) repository (https://osf.io/7evpx/). RESULTS: Fourteen papers informed the present scoping review. Four major themes were identified: (i) impact of COVID-19-related stressors on BD; (ii) impact of COVID-19 on mental health service utilization among people with BD; (iii) impact of BD on the risk of acquiring SARS-CoV-2 infection; (iv) engagement in preventative behaviors among people with BD. Additional themes warranting further research were nonetheless detected. LIMITATIONS: Further original studies are needed. CONCLUSION: The present study confirmed the high-vulnerability hypothesis concerning people with BD versus the general population, reinforcing the need for further research related to the COVID-19 pandemic. Additional information is warranted to compare the impact of the pandemic period among BD people against pre-pandemic records, the general population, and other severe mental illnesses, namely people with schizophrenia or major depressive disorder, to inform the public health and the delivery of patient-tailored interventions. Journal Article 2021-09-04T00:00:00Z http://hdl.handle.net/11343/288101 Wilson, I 2006 Depression in the patient with COPD. This paper explores the recent literature surrounding comorbid depression and COPD. The literature reveals a high prevalence of depression in patients with COPD and some evidence that the depression is a result of the disease. The literature highlights the negative impact of depression on quality of life and a possible impact on mortality. Depression also negatively impacts on compliance and smoking cessation. Treatment of depression in COPD, particularly by cognitive behavioral therapy, has positive impact on quality of life. Tricyclic antidepressants have a positive impact on mood and COPD, but side effects limit their use. The advent of the new antidepressants may improve acceptability and outcomes, but the research is yet to be undertaken. Physical rehabilitation may have a positive impact on mood. This paper highlights the difficulty in screening for depression in patients with COPD due to the overlap of symptoms between the two diseases. Despite the difficulties, it is important to recognize and treat depression in patients with COPD because of the significant likelihood of improvement in quality of life. Journal Article 2006-01-01T00:00:00Z http://hdl.handle.net/11343/288100 Sarker, M; Shin, S; Jhung, SH 2019-06-30 Synthesis and Functionalization of Porous Zr-Diaminostilbenedicarboxylate Metal-Organic Framework for Storage and Stable Delivery of Ibuprofen. A stable porous metal-organic framework (MOF), Zr-diaminostilbenedicarboxylate (Zr-DASDCA), was synthesized and modified with oxalyl chloride (OC) or terephthaloyl chloride (TC) to introduce various functional groups onto the Zr-DASDCA. Both pristine and functionalized Zr-DASDCAs, together with activated carbon, were used as a potential carrier for ibuprofen (IBU) storage and delivery. Zr-DASDCAs, especially the modified ones (OC-Zr-DASDCA and TC-Zr-DASDCA), showed competitive results in IBU delivery. Specifically, the release rate in phosphate-buffered saline solution at pH 7.4 was nearly constant (R 2 ≈ 0.98) for up to 10 days, which would be very effective in IBU dosing to the human body. Moreover, the release rate could be controlled by changing the pH of the releasing solution. The rate of IBU release from both pristine and modified Zr-DASDCAs at pH 7.4 and 3.0 was also explained with a few interactions such as H-bonding and electrostatic repulsion, together with the relative pore size of the Zr-DASDCAs. Therefore, the results suggested that functionalization of MOFs via postsynthetic modification, especially with OC and TC, to introduce various functional groups onto MOFs is an effective approach to not only reducing the release rate of IBU but also inducing a constant release of IBU for as long as 10 days. Journal Article 2019-06-30T00:00:00Z http://hdl.handle.net/11343/288099 Phillipou, A; Tan, EJ; Toh, WL; Van Rheenen, TE; Meyer, D; Neill, E; Sumner, P; Rossell, SL 2021-12-01 Mental health of individuals with and without eating disorders across six months and two waves of COVID-19 PURPOSE: The COVID-19 global pandemic has resulted in a significant mental health toll, and recent findings suggest that individuals with an eating disorder (ED) history may be particularly vulnerable. The current study aimed to: (1) identify changes in the pattern of mental health symptoms over the first six months of the pandemic between individuals with an ED history, compared to a community sample without an ED history (non-ED); and (2) identify differences in mental health symptoms and concerns between two waves of the virus and associated lockdowns. METHOD: Data from 4915 respondents - 231 with an ED history - were compared across monthly time points from April to September 2020 on psychological symptoms including negative mood, quality of life, coping and hopefulness, as well as changes to eating and exercise behaviours. RESULTS: Mental health symptoms were increased in the ED group, but generally did not differ from non-ED in the pattern of symptoms reported over time. Increased depressive symptoms and restrictive eating behaviours were found across both groups in relation to the second wave/lockdown, as well as decreased hopefulness and quality of life. Respondents in both groups also reported coping worse during the second wave of the virus compared to the first wave. CONCLUSION: Although non-ED and ED groups tended to generally show the same pattern of symptoms, the mental health status of the ED group was significantly poorer than the non-ED group throughout the pandemic, and exacerbations in some symptoms (i.e. increased food restriction and depressive symptoms) is cause for concern. Journal Article 2021-12-01T00:00:00Z