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    Exploring GPX2 as a Therapeutic Target in Colorectal Cancer: From Radiotherapy Sensitivity to Chemotherapy Response and Beyond

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    Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Cancer Medicine, La Trobe University, Victoria, Australia.</p

    Virtual Reality Immersion Therapy for the Treatment of Anxiety Disorders

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    Submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Computing, Engineering and Mathematical Sciences and School of Psychology and Public Health, La Trobe University, Victoria, Australia.</p

    Service Innovation Using Socially Assistive Robots in Early Learning

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    Submitted in total fulfillment of the requirements for the degree of Doctor of Philosophy to La Trobe Business School, La Trobe University, Victoria, Australia.</p

    Factors influencing the prioritisation of access to medicines in trade‐related intellectual property policymaking in Thailand

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    Abstract: Thailand is facing ongoing trade‐related challenges that threaten access to an affordable and sustainable supply of medicines. Despite Thailand's history of balancing trade pressures and public health priorities, little is known about the factors that enable or constrain a focus on access to medicines in trade‐related intellectual property (IP) decision making. Using document analysis and qualitative interviews, and drawing on Kingdon's Multiple Streams Framework, this qualitative study examines the factors that have enabled or constrained Thailand from focusing on access to medicines in three case studies of trade‐related IP policy: Thailand's patent law and its amendments; its issuance of compulsory licences; and its decision‐making about TRIPS‐plus trade agreements including potential membership of the Comprehensive and Progressive Agreement for Trans‐Pacific Partnership. The degree to which access to medicines has been prioritised in Thailand's trade‐related IP policymaking has varied across different types of policymaking and over time. Integral to its successes has been the involvement of the Ministry of Health and sustained advocacy by access to medicines coalitions which exert political pressure, generate evidence, and provide technical assistance to support evidence‐based policy reform. In addition, Thailand's compulsory licencing was made possible by a policy entrepreneur with the motivation and authority to implement policy change. Constraints to Thailand's focus on access to medicines have included its trade dependence on the United States (US), ongoing US trade pressure to implement TRIPS‐plus measures, and intense lobbying from Pharmaceutical Research and Manufacturers of America, the organisation representing US‐based major pharmaceutical companies, to increase IP protection for pharmaceuticals in Thailand. Through the use of Kingdon's framework, this study's focus on three different types of trade‐related IP policymaking has provided a detailed picture of the factors that have influenced the prioritisation of access to medicines and how these have played out in Thailand. Thailand's mixed history with regard to the prioritisation of access to medicines could provide lessons for other low‐ and middle‐income countries facing similar challenges to access to medicines by ensuring that the conditions are right in each of the three streams for windows of opportunity to emerge.</p

    C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD

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    Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.</p

    Sanctuary III

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    No description supplied.</p

    Methods of behavioral testing in dogs: a scoping review and analysis of test stimuli

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    BACKGROUND: Behavioral testing is widely used to measure individual differences in behavior and cognition among dogs and predict underlying psychological traits. However, the diverse applications, methodological variability, and lack of standardization in canine behavioral testing has posed challenges for researchers and practitioners seeking to use these tests. To address these complexities, this review sought to synthesize and describe behavioral testing methods by creating a framework that uses a "dog-centric" perspective to categorize the test stimuli used to elicit responses from dogs. METHODS: A scoping review was conducted to identify scientific literature that has reported behavioral testing to assess psychological traits in dogs. Five online databases were systematically searched. Following this, an inductive content analysis was conducted to evaluate and summarize the behavioral testing methods in the literature. RESULTS: A total of 392 publications met the selection criteria and were included in the analysis, collectively reporting 2,362 behavioral tests. These tests were individually evaluated and categorized. Our content analysis distinguished 29 subcategories of behavioral testing stimuli that have been used, grouped into three major categories: human-oriented stimuli; environmental stimuli; and motivator-oriented stimuli. CONCLUSION: Despite the methodological heterogeneity observed across behavioral testing methods, our study identified commonalities in many of the stimuli used in test protocols. The resulting framework provides a practical overview of published behavioral tests and their applications, which may assist researchers in selecting and designing appropriate tests for their purposes.</p

    Using Focussed Ethnography to Observe and Understand the Actions and Interactions of People With Prader-Willi Syndrome When They Exercise at a Community Gym: A Protocol

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    Exercise for people with Prader-Willi syndrome (PWS) is important for their health and wellbeing and can provide opportunities for community participation. However, they may find it difficult to participate in some contexts, such as community gyms because social and environmental barriers in these settings may compound difficulties caused by physical impairments or intellectual disability. This study aims to observe and understand the actions and interactions of people with PWS when they exercise in community gyms. A focussed ethnographic study will be conducted. Field notes will be taken in community gyms where people with PWS are participating in a structured exercise program for six months as part of a randomised control trial called PRESTO. Up to ten participants will be observed, with at least three observations planned per participation during the program. Gym sessions observed will be approximately 1 hour long. Within the framework of interpretive description, reflective thematic analysis will be used to interpret observational data. Our findings will inform how best to support people with PWS to exercise at a community gym. </p

    Dynamics of productivity in pigeonpea [Cajanus cajan (L.) Millsp.] in subtropical Australia

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    Pigeonpea productivity can be enhanced by optimally matching the physiology of genotypes to environmental conditions. Information on crop responses to the environment has been lacking for the short-duration pigeonpea genotypes, which are being trialed to develop the Australian pigeonpea industry. The objective of this study was to examine the dynamics of productivity in relation to radiation use efficiency (RUE) and its influence on yield partitioning. Seven field trials, employing three pigeonpea [Cajanus cajan (L.). Millsp.] genotypes, were established at the Gatton Campus, the University of Queensland, Australia, in 2017/2018 and 2018/2019 summer seasons. The study reveals that leaf area development, influenced by growing environment, genotypes, and their interactions, were the key factors for the differences in leaf area duration and RUE. Pigeonpea planted in December had higher seasonal (1.11 g MJ−1) as well as reproductive (0.71 g MJ−1) RUE, resulting in significant differences in total dry matter (TDM) and grain yield (GY). GY was positively associated with seasonal RUE (R2 = 0.62), and the relationship was stronger (R2 = 0.83) for the reproductive phase (RUE(R)). The positive association between GY and RUE(R) suggested that maintaining optimum leaf area during the grain filling period is crucial to achieve higher productivity. Variations in GY were related to amount and rate of TDM accumulation before flowering (R2 = 0.51 and R2=0.53, respectively). Hence, achieving greater TDM before flowering was determinant for achieving higher productivity. The present study provided updated information on dynamics of productivity that will enable more comprehensive modelling of pigeonpea adaptation under subtropical conditions.</p

    Life course predictors of child emotional distress during the COVID‐19 pandemic: Findings from a prospective intergenerational cohort study

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    Background: We examine precursors of child emotional distress during the COVID-19 pandemic in a prospective intergenerational Australian cohort study. Methods: Parents (N = 549, 60% mothers) of 934 1–9-year-old children completed a COVID-19 specific module in 2020 and/or 2021. Decades prior, a broad range of individual, relational and contextual factors were assessed during parents' own childhood, adolescence and young adulthood (7–8 to 27–28 years old; 1990–2010) and again when their children were 1 year old (2012–2019). Results: After controlling for pre-pandemic socio-emotional behaviour problems, COVID-19 child emotional distress was associated with a range of pre-pandemic parental life course factors including internalising difficulties, lower conscientiousness, social skills problems, poorer relational health and lower trust and tolerance. Additionally, in the postpartum period, pre-pandemic parental internalising difficulties, lower parental warmth, lower cooperation and fewer behavioural competencies predicted child COVID-19 emotional distress. Conclusions: Findings highlight the importance of taking a larger, intergenerational perspective to better equip young populations for future adversities. This involves not only investing in child, adolescent, and young adult emotional and relational health, but also in parents raising young families.</p

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