Targeted foundational supports for people with psychosocial disability outside of the NDIS: model background and rationale

This paper provides further background and rationale for a proposed model for delivering targeted foundational supports for people with psychosocial disability who are outside the National Disability Insurance Scheme (NDIS). This paper supplements the summary paper by outlining key elements of available research and data that informed the development of this model

Rapid Analysis: Character AI & Children

This rapid analysis examines Character AI, a multimodal chatbot platform that has rapidly grown to over 20 million monthly active users, many of whom are under 18. Unlike productivity-focused AI tools, Character AI frames itself as an "AI entertainment company," offering user-generated characters for a range of purposes: from creative assistants, to games, to emotional support characters, to fantasy role-playing and more. Our audit highlights the platform’s unique dynamics: weak age verification, evolving youth-driven use cases that are signals for innovation (i.e. roleplay and 'comfort bots'), and platform risks. While Character AI enables creative and expressive play, it also presents new regulatory challenges. We identify critical gaps in youth protections, explore opportunities for youth-centered co-design, and propose action starters for policymakers seeking to balance innovation with safety in this new digital landscape

Carriers and Barriers of Voice in Teams: An Investigation into Team Voice and the Role of Team Voice Allies and Resistors in Influencing Voice Outcomes

As organisations increasingly rely on teams as foundational work units, understanding how voice unfolds within workgroups and teams has become a critical research topic. Moving beyond traditional, dyadic perspectives on employee voice, this thesis builds one merging perspectives to investigate team voice as a multifaceted and socially embedded process involving multiple actors. In this thesis, I present three empirical studies. In Study1, I conducted a comprehensive literature review and meta-analysis of 38 empirical studies on team voice, analysing key antecedents and consequences of team voice including both its promotive and prohibitive content. The results of this first study show that team voice is shaped by team leadership and team climate, and that team voice also influences team performance, team innovation and team viability. Study 2 uses an experimental design to investigate how team members, acting as voice allies or resistors, influence team voice and team wellbeing. The results of this second study showed that teams with voice allies showed higher voice, satisfaction, and positive affect, while teams with resistors showed lower voice and wellbeing. In Study 3, I investigated the intra-individual consequences of enacting voice allyship or resistance. The results of Study 3suggest that there are personal resource consequences to voice allies and resistors in enacting these roles. Overall, by integrating insights across multiple analytical levels and theoretical perspectives, I provide a richer understanding of how voice unfolds within modern, interdependent teams. Theoretically, I extend voice scholarship by highlighting the evolving roles of team members as collective voicers, voice allies, and resistors across both voice-related and emotional dimensions. Practically, I offer actionable insights into how organisations can foster sustainable voice by recognising and supporting the social dynamics that impact team voice and member wellbeing

Re-membering my Charrúa roots on unceded land: weaving new narratives

The framework for this thesis arises from my experiences cultivating relationship with Beada-o-Lajau an ancestral Ombú tree (Phytolacca dioica), native to Uruguay where I was born. My relationship with Lajau facilitates a journey of re-membering the knowledges held at the intersections of my ancestral lineages. Regular encounters with this particular plantcestor, who grows on Gadigal Country close to where I live, not only aided in my ancestral Charrúa re-membering but prompted a sentipensante/feel-thinking relationship with the land I inhabit. Taking an autoethnographic approach informed by a feel-thinking-doing methodology, a personal relational map emerges that spans multiple places and times, with Lajau at its center. Working predominantly in tejido /weaving using crochet, tapestry, coiling and beading, I dance between being practice-led and led by place to express and integrate my experiences. In the process of relating aspects of my story, the practice of re-membering becomes a way to counteract colonial narratives of erasure and reckon with my position as a settler-migrant inextricably implicated in the ongoing colonial project that is so-called Australia. Weaving becomes a language and a space for feeling and thinking through reclaiming ancestral practice and embodied ways of knowing whilst living away from my ancestral lands. The resultant artworks generate their own symbolic visual language in the form of woven cartographies, a series of physically impassable gateways that speak to connections across waterways. Although anchored in the personal, the themes in this research echo those who share in collective human concerns to be in right-relationship with ourselves, the communities we are part of and our environment. The lands and waterways affirm their role as living knowledge systems, facilitating re-membering and potential new perspectives on south-south global relationships and the intersections of Charrúa and Afro-descendant identities in Uruguay

A Beta Cauchy-Cauchy (BECCA) prior for sparse signal recovery in regression and graphical models.

This PhD thesis introduces a novel Bayesian approach for variable selection in high- dimensional regression settings, along with its potential extension to learning the structure of an undirected graphical model. Our proposed method, which we call the Beta Cauchy-Cauchy (BECCA) prior, replaces the indicator variables in the traditional spike and slab prior with continuous, Beta-distributed random variable and places half-Cauchy priors over the para-meters of the Beta distribution, which significantly improves the predictive and inferential performance of the technique. Similar to shrinkage methods, our continuous analog of the Spike-and-Slab (SS) prior enables posterior exploration using gradient-based methods, such as Hamiltonian Monte Carlo (HMC), while at the same time explicitly allowing for variable selection in a principled Bayesian framework. Building on the strong performance of the proposed approach in linear regression, we apply it to logistic regression context and further extend it to structure learning in Gaussian Graphical Models (GGMs) using a regression based framework. We evaluate the frequentist properties of our model through simulations and demonstrate that our technique not only outperforms the latest Bayesian variable selection methods in linear regression, but also performs comparably or better than existing methods for variable selection in logistic regression and structure learning in graphical models. The efficacy, applicability and performance of our approach, are further underscored through its implementation on real datasets

Healthy ageing and active travel: Identifying age-related barriers to walking and cycling

In a period of increasing mobility technologies, sustainable transport options, and healthy ageing concerns it is timely to better understand the barriers to active travel, particularly for older adults. Drawing from a survey of 1,522 Sydney residents, we compare travel patterns and perceived barriers to walking and cycling for older adults (60+) and younger adults (18-59). Car/motorbike/Uber use and walking have frequent and consistent use across both age groups. In contrast, public transport and bicycle/e-bicycle use both decline with age. Perceived barriers to walking and cycling are analysed across age groups using logistic regression. Relative to younger adults, older adults are more likely to identify an injury or disability (OR 1.45, 95% CI 1.02 to 2.04) and the convenience of driving (OR 1.35, 95% CI 1.05 to 1.73) as barriers to walking/walking more. Conversely, older adults are less likely to identify no-one to walk with (OR 0.47, 95% CI 0.33 to 0.68), personal safety (OR, 0.28, 95% 0.17 to 0.45), traffic (OR 0.26, 95% CI 0.17 to 0.41), inadequate street lighting (OR 0.50, 95% CI 0.27 to 0.90), no footpaths (OR 0.41, 95% CI 0.24 to 0.70), and distance (OR 0.74, 95% CI 0.58 to 0.96) as barriers to walking/walking more. For cycling, lack of access to a bicycle (OR 2.74, 95% CI 2.15 to 3.48), and insufficient skills (OR 2.9, 95% CI 2.1 to 3.99) are key issues for older adults, while sociocultural and built environment barriers are again perceived as less of a barrier. Practical issues (distance, transport availability, skills development), personal limitations, and potentially the nature/purpose of travel are key factors associated with active travel among older adults in Sydney. Policymakers need to ensure sociocultural and built environment barriers are lowered to ensure those already walking and cycling maintain this into old age

Targeting inflammatory skin disease using a novel immune modulating agent

Chronic inflammatory skin diseases such as psoriasis and atopic dermatitis (AD) are growing global health concerns and developing new therapeutics is much needed. RP23, a human self-derived peptide, has novel anti-inflammatory properties as an injected therapeutic in contact hypersensitivity and psoriasis mouse models. In this thesis, we have conducted further experiments to determine mechanistic insight of RP23 and optimised a topical therapy for its therapeutic use in inflammatory skin diseases. We found that murine BMDMs treated in vitro with RP23 had suppressed LPS-induced IL-6, IL-12p40 and IL-12p70 responses and increased IL-10. Reduction in IL-6 and IL-12p40 was also seen in human MDMs. Further, we observe cellular changes that resemble necrotic-like cell death in murine BMDMs. Induction of cell death required uptake of the peptide by phagocytosis, as it could be inhibited with cytochalasin D. Proteomic analysis showed upregulated M2 markers, antioxidant and metabolic proteins and downregulated interferon-inducible proteins. We have also developed a topical delivery system that penetrates both human and murine skin explants and offers superior protection from imiquimod-induced psoriasis applied daily, compared to a single injected dose. Topical RP23 also offers moderate protection from disease in the oxazolone-induced AD model. Use in either model did not affect spleen/ILN weights, suggesting localised suppression of inflammation. Topical RP23 treatment of inflamed and non-inflamed skin showed uptake by CD64+ macrophages and DCs and reduced proportions of total DCs. We also observed reduced IL-6, IL-12p40 and IL-17A/F production, neutrophil and Rorγt+ γδ T cell proportions in psoriatic murine skin and reduced CD11b+ cells in skin-draining lymph nodes. To conclude, we have demonstrated RP23 has significant therapeutic potential as a topical therapy for psoriasis and AD and identified molecular and cellular mechanisms that warrant further investigation

Safety, Usability, and Acceptability of Microarray Patches for Vaccination

Background: Microarray patches (MAPs) are a needle-free vaccine delivery device that targets the epidermis and upper dermis. This thesis aimed to investigate the safety, usability, and acceptability of MAPs for vaccination among older adults, the general public, and healthcare professionals (HCPs). Methods: A review was conducted to assess the immunogenicity, safety, usability, and acceptability of MAPs. Semi-structured interviews with older adults explored MAP benefits and challenges. The MAP for Vaccination Scale (MAPVac) was developed through literature reviews, expert assessments, and interviews to evaluate perceptions of MAP safety, usability, and acceptability. Surveys were administered in Australia, Canada, New Zealand, and the United Kingdom. Descriptive statistics were used for survey analysis, and thematic analysis was applied to interview data. Results: Clinical trials with influenza and Japanese encephalitis vaccines demonstrated that MAPs were immunogenic, with mild erythema as the only reported side effect. Pain scores were lower for MAPs compared to needle and syringe (N&S). In interviews with older adults (n=44), MAPs were viewed as convenient due to their ease of use, with potential to reduce healthcare burden. Concerns included the safety of unsupervised use and immunisation recording accuracy. The MAPVac scale showed high internal consistency (Cronbach’s alpha=0.90) and repeatability. Survey results from 403 members of the general public and 184 HCPs indicated that MAPs were considered safe, usable, and acceptable. Thematic analysis of interviews (n=27) revealed that MAPs were beneficial for individuals with needle-related anxiety, and HCPs showed interest in using MAPs in practice. Conclusion: MAPs were generally found to be safe, effective, and user-friendly alternatives to N&S. The availability and accessibility of vaccine MAPs could enhance vaccination rates among key populations and those in low-resource settings

Development of fragment-bearing cyclic peptides as first-in-class therapeutics against ALT-positive osteosarcomas

Osteosarcoma is the most common type of primary bone malignancy that arises during the adolescent growth spurt and disproportionately affects young people. With no targeted therapy available, patients diagnosed with osteosarcoma are predominantly treated with high-dose chemotherapy combined with disabling amputation or limb salvage surgery, leaving significant burden on survivors. A novel strategy for treating osteosarcoma is to target a DNA repair mechanism known as Alternative Lengthening of Telomeres (ALT), which is required by over 60% of osteosarcomas for continued growth. Since there is no evidence of ALT activation in healthy somatic cells, inhibition of ALT offers a significant window for therapeutic intervention against osteosarcoma. ALT activity can be targeted by disrupting two well-defined protein-protein interactions (PPIs), FANCM-BTR and TRF2. Both PPIs exhibit well-defined binding interfaces, each providing a suitable site for competitive targeting that is structurally defined and ready for novel inhibitor discovery. The FANCM-BTR target is mediated by hydrophobic interactions between a 12-mer peptide from the FANCMMM2 domain and the RMI1/2 heterodimer, while TRF2 recruits other telomeric protein components via its TRFH domain that prefers a conserved binding motif. This thesis reports first-in-class de novo cyclic peptide inhibitors against FANCM-BTR and TRF2TRFH by implementation of fragment-based drug discovery and mRNA display. These cyclic peptides serve as novel chemical tools for further investigation on the biochemical mechanism of FANCM-RMI1/2 and TRF2TRFH in regulating ALT activity and potential targeted therapy for ALTpositive osteosarcomas. The proof-of-concept fragment-incorporated RaPID screen also provides a novel platform for hit-to-lead generation and structure-activity relationship studies of de novo cyclic peptides containing fragment-bearing amino acids as intracellular PPI inhibitors with high affinity and target specificity

Guitars not Greeks: The early chitarrone and its use in the 1589 La Pellegrina intermedii

Today, the early chitarrone is assumed to be the same in form and tuning as the later designated instrument, the tiorba, a fundamental part of which is a neck extension to a second pegbox to allow for an extended bass string range. Foundational research into the nascence of the chitarrone has been dominated by related research into the origins of monody, with a focus on the influence of contemporaneous research into Ancient Greek practice; an influence which has since been disputed. Early chitarrone research is hampered by a complete lack of organological or iconographical evidence; however, the centrality of the chitarrone within the development of monody and basso continuo demands closer attention. Clear descriptions by Alessandro Piccinini on the application of his arcilituto neck extension to the chitarrone sometime after 1595 have been contested or ignored but are here reexamined in the context of the chitarrone’s first documented appearance in the 1589 La pellegrina intermedii. This thesis aims to critique research that retrospectively applies to the early chitarrone the characteristics of a chronologically later codified form in the tiorba. A framework of practice for the early chitarrone will be formulated, with particular attention being given to the underlying impetus for the creation of the new instrument. We contextualise the vocalists and instrumentalists that participated in the intermedii with contemporaneous collaborative instrumental performance practices, with a focus on the guitar. This new approach to the origins of the instrument forms the basis for speculation on the form and tuning of the early chitarrone. The implications of the influence of the chitarrone as a collaborative instrument on vocal performance practice and notational practices, such as monody and basso continuo, will be explored