Minerva Elements Records
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ItemOn the Same Wavelength: A Co-Designed Podcast to Reduce Stigma Towards People Living with Complex Mental Health Issues( 2024-01)Stigma and discrimination disproportionately affect Australians living with complex mental health issues, such as schizophrenia, bipolar disorder, personality disorder, obsessive compulsive disorder, eating disorders, and severe depression and anxiety disorders. Many initiatives seek to reduce stigma, including educational and contact-based initiatives; however, their efficacy has been limited, with studies averaging only small, short-medium term improvements. Hence, there is a need to develop and test novel initiatives which are effective and can be disseminated at scale. Podcasts are an accessible medium which can facilitate intimate, immersive content and storytelling. This thesis aimed to understand the impact of a co-designed podcast on stigma towards people affected by complex mental health issues. First, a systematic scoping review (Chapter 3) summarised the methodology and results of 16 experimental studies which examined the impact of podcast-based interventions on mental health-related outcomes. Although studies were heterogeneous in content and length of intervention, outcomes included improvements in mindfulness, body image, and stigmatising attitudes. Then, a cross-sectional study (Chapter 4) surveyed Australian adult podcast listeners (n = 629). Logistic regression models demonstrated participants who had listened to a mental health-themed podcast held fewer stigmatising attitudes towards people experiencing mental health issues (OR 1.0, 95% CI 0.9-1.0, p < .001), and had higher levels of mental health knowledge (OR 1.1, 95% CI 1.0-1.2, p < .01). To inform a new podcast, a co-design study was held (Chapter 6), where key stakeholders collaborated over a series of focus groups. Stakeholders included people with lived experience, who were both beneficiaries as well as target audience members. Other target audience members involved in co-design represented life domains associated with high levels of stigma and discrimination: healthcare, media, and employment. Participants directly informed the focus, storyboard, and messaging of a new podcast, including the decision to focus on contextualised, narrative storytelling from people with lived experience. A six-episode podcast series was then produced, named On the Same Wavelength. Finally, a randomised controlled trial (n = 163), aimed to understand whether listening to the podcast could impact listeners’ degree of stigma (including attitudes, prejudice, and discriminatory intentions), and degree of state empathy towards people living with complex mental health issues (Chapter 8). The study found significant benefits of listening to the podcast on prejudice compared to control (t = -2.47, p = 0.015), though these findings were not maintained at follow-up. Participants who listened to On the Same Wavelength also experienced a significantly higher degree of empathy after Episode 2 compared to control (t = -1.99, p = .048). Listeners provided positive feedback on the podcast, and reported that the podcast prompted self-reflection. Overall, this thesis provides critical insights into how researchers, practitioners, and policy-makers can utilise podcasts for powerful storytelling from people with lived experience. On the Same Wavelength demonstrates positive, short-term benefits of listening. This thesis also highlights the importance of co-designing stigma reduction initiatives with people with lived experience and other target audience members. However, further research is needed to understand how podcast-based messaging could be refined for longer-term stigma reduction.
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ItemCommunication Between Health Professionals in the Operating Room and the Influence of Noise( 2024-03)Health professionals working in the operating room (OR) are required to communicate while undertaking surgical procedures. While delivering clinical tasks and multitasking, health professionals’ communication efforts often compete with noise in the OR. Research Question How is communication between health professionals in the operating room influenced by noise? Methods A multi-method design was chosen to explore understandings of communication and the influence of noise. The doctoral research was conducted in three distinct phases. The research was guided by a conceptual framework, the Quality of Care Framework, that involved structure, process, and outcome. Phase 1 involved a qualitative exploratory study with semi structured interviews to explore health professionals’ perceptions and experiences of communication and the influence of noise. The interviews were audio recorded, transcribed verbatim, and analysed using thematic analysis. Phase 2 comprised a quantitative prospective cohort study with non participatory observations of communication between health professionals during surgical procedures while simultaneously measuring sound pressure levels. Audio visual recordings and detailed field notes were undertaken of communication while simultaneously measuring sound pressure levels. Data were statistically analysed using descriptive and inferential statistics. Phase 3 involved a qualitative exploratory study with focus groups and an interview to explore health professionals’ understandings of communication in the presence of noise and strategies utilised to ensure effective communication. The sessions were audio recorded, transcribed verbatim, and analysed using thematic analysis. Results For Phase 1, 26 semi structured interviews were undertaken with surgeons, anaesthetists, registrars, nurses, and theatre technicians. Four interconnected and complex themes were analysed from the interviews including the dynamics of sounds, barriers to effective communication, facilitators of effective communication, and the consequences of communicating in the presence of noise. In Phase 2, 80 surgical procedures were observed with a representative range of procedures of the 10 surgical specialties at the research site. Observations comprised 2,274 communication events with repeated communication of 25% (576/2,274) and communication failures of 24% (554/2,274). During most communication, concurrent conversations were observed. The surgical specialty with the greatest mean maximum sound pressure level was vascular surgery, and the lowest was ophthalmic surgery. Noises were a constant and ongoing challenge to communication during all critical moments of surgery from induction to emergence. The most frequent type of communication failure was content failure, and the least frequent was purpose failure. Consequences were observed in nearly all communication failures including confusion, surgical delays, resource waste, and rush to complete tasks. Four focus groups were undertaken in Phase 3, recruiting perioperative nurses and anaesthetists, with one anaesthetist interviewed. Three themes were analysed including reactions to the influence of noise on communication, communication strategies, and awareness of the OR environment. Conclusion The OR was a dynamic environment with a constant cacophony of sounds. In this research, the noises emitted resulted in health professionals speaking with raised voices, experiencing difficulty comprehending verbal communication, and difficulty concentrating on complex cognitive tasks. Communication failures and repeated verbal communication occurred. Health professionals need to be aware of the noises emitted during surgery and ensure effective communication in the OR.
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ItemCost effectiveness of reducing length of stay for total joint arthroplasty( 2023-12)Background: The utilisation of total joint arthroplasty (TJA) and incidence of osteoarthritis are both increasing. Globally, marked increases in the rate of arthroplasty being performed are predicted within the next ten years. Reducing length of stay (LOS) has been proposed as a method of increasing throughput and to match demand. However, the cost-effectiveness of reducing LOS from the perspective of patients, clinicians, hospitals, and government stakeholders remains to be understood. Objectives: The overall aim of this thesis is to investigate the cost-effectiveness of reducing LOS for TJA. To comprehensively analyse this broad objective, this thesis aimed to: (1) identify factors that affect LOS for TJA; (2) explore strategies that can be utilised to reduce LOS; (3) understand the clinical and cost-effectiveness of earlier discharge; (4) explore trial characteristics and meta-bias amongst trials investigating enhanced recovery after surgery pathways. Methods: This thesis adopts a mixed-methods approach, incorporating multiple quantitative studies and a qualitative study. The perspective of key stakeholders was engaged through each phase of this thesis. Firstly, a narrative review was performed to identify patient-level, clinical, and hospital-level factors that may inform LOS for TJA. In addition, the effect of complications on economic and clinical outcomes, including LOS, was explored. Patients’ and surgeons’ opinions regarding LOS were engaged to explore barriers and enablers for short stay arthroplasty. The impact of enhanced recovery after surgery pathways on outcomes after TJA was systematically reviewed among randomised clinical trials. Expanding the scope to a hospital and government perspective, a policy-level change targeting a one-day reduction in LOS was simulated using overlap propensity score weighted analysis. Finally, a cross-sectional study was performed using registered randomised clinical trials to understand the trial characteristics and meta-biases amongst trials implementing enhanced recovery after surgery. Findings: A diverse array of patient, hospital, and clinical factors were associated with LOS. Expectations of patients and surgeons, which were reinforced by the healthcare system, helped to inform LOS. When specifically testing shorter stay, earlier discharge did not change odds of complication or readmission. Overall, earlier discharge was cost neutral as cost savings were shifted onto inpatient rehabilitation. Systematic review and meta-analysis of clinical pathways combining several factors thought to individually reduce LOS, in the form of enhanced recovery after surgery pathways, were significantly associated with reduced LOS without a commensurate change in complications, readmission, or mortality after arthroplasty. Very low certainty evidence in this systematic review was reinforced when assessing the broader landscape of randomised trials investigating enhanced recovery after surgery – finding poor registration practices, and evidence of publication bias and selective outcome reporting. Conclusion: This thesis demonstrated LOS is determined by a complex interplay of patient, clinician, hospital, and government factors. In the current model of care for arthroplasty, early discharge was cost neutral. For a true cost saving to be realised with earlier discharge, significant changes are required in patient expectations, practice of arthroplasty, and organisation of services for arthroplasty.
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ItemNo Preview AvailableHaematopoiesis at a clonal level using novel barcoding technologies( 2024-03)Haematopoiesis is the process through which hematopoietic stem and progenitor cells (HSPCs) divide and differentiate to generate all mature blood cell types. Originally conceptualized as a hierarchy, haematopoiesis begins with hematopoietic stem cells (HSCs) at the apex which possess the ability to self-renew, as well as to give rise to all other progenitors and mature blood cells. Due to the challenges in accessing adult HSCs in humans, murine models have served as valuable tools for in vivo studies of hematopoietic stem and progenitor cells (HSPCs). The transplantation setting has been pivotal in characterizing the fate potential of various progenitor populations. However, to comprehensively understand their behaviour in the native environment, novel approaches are essential. Moreover, the advent of single-cell technologies has revealed a great deal of heterogeneity in both the transcriptional profiles and clonal lineage potential of different HSPC populations, highlighting the importance of studying HSPCs at a clonal level instead of in bulk. Few studies have investigated haematopoiesis at a clonal level in relevant human in vitro models, or in mice in a native unperturbed setting. To tackle these challenges, our lab has developed novel tools and approaches in both these domains. Here, I employed innovative barcoding technologies to examine HSC behaviour in both murine and human contexts. First, I utilised the LoxCode mouse, an in vivo murine barcoding model to assess the clonal contribution of HSCs to native haematopoiesis. From this data, I could establish that while HSCs proliferate in steady-state conditions, self-renewing HSCs were not the primary contributors to downstream HSPC populations. Further, by using HSC-specific LoxCode barcoding I identified that the major contribution of HSCs to mature cell types came from HSC that are lost from the HSC pool. Second, I sought surface markers that corresponded to the transcriptional heterogeneity seen in mouse HSPCs by scRNA-seq. Here we found that CD69 was a marker for a subset of multipotent progenitors with lymphoid bias. I then discovered further heterogeneity for Irf8 expression in the same CD69+ population. Through functional assays, I was able to place these cells on a likely continuum from CD69–Irf8–to CD69+Irf8– CD69+Irf8+. Third, I used a clone splitting technique called SIS-seq to understand which are the genes that primed fate choices in HSPCs. I first used it in a murine setting to assess which genes regulate the development of the different DC subtypes. With this technique I was able to find and validate Bcor as molecular regulator of cDC2 and pDC fate both in vitro and in vivo. I then used the same approach to understand which genes regulate haematopoiesis in human in a newly optimised an in vitro human multilineage culture system. Remarkably, I found that HSPC populations that were transcriptionally similar, had very different fate biases at a clonal level. Stephen Zhang then used factor analysis, a machine learning algorithm that incorporates transcriptional signatures, surface marker expression levels, and clone fate, to identify genes that correlate with lineage commitment and kinetics of production. This approach enabled the prediction of the fate of single HSPC clones based solely on their transcriptional signature. Overall, my research has helped unravel the hematopoietic process and identify key genes associated with HSC fate determination. This knowledge will help provide insight into genes crucial for the production of specific immune cell types, which may translate to novel opportunities for manipulating human HSCs to enhance or inhibit the production of desired cell populations in the clinic for cancer, immune deficiency and immunotherapy.
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ItemSelf-Healing Paint: Functionalizing an Acrylic Coating with a Quadruple Hydrogen Bonding Network( 2023-12)Paints are coatings which serve to both protect surfaces from damage and impart a variety of aesthetic qualities. They are composed of a matrix of interlocking hydrophobic acrylic polymers which constitute the body of the coating, while binding together a myriad of other additives including pigment particles. Paints represent the majority fraction of a vast global coatings market, and, like all coatings, are exposed to a variety of stresses that can lead to long term damage in the form of microcracks. To date, the only method to repair such damage is to simply replace the paint with a new coat, which is expensive and time consuming. Self-healing technology is perhaps the most promising solution to this problem, as it offers the ability to heal damage spontaneously and without external diagnosis. However, neither a self-healing paint, nor any viable self-healing acrylic coating currently exists. The work presented herein represents a 3-and-a-half-year research effort to successfully design both a self-healing acrylic coating and a feasible self-healing paint. The strong quadruple hydrogen bonding unit 2-ureido-4[1H]-pyrimidinone (UPy) was incorporated into an acrylic coating to form a hydrogen bonding network. Upon damage to the coating, the strong attractive forces between the broken UPy units in the network prompted self-healing through polymer rearrangement and the reformation of UPy–UPy bonds. This was achieved first through the design of an UPy functionalized acrylic monomer with a long amphiphilic spacer. This monomer, at a concentration of only 2.5 wt%, was able to successfully imbue a typical acrylic coating with efficient self-healing (~25%) at room temperature. Then, in order to enhance self-healing efficiency, a UPy functionalized crosslinker system with exotic architecture was designed. One crosslinker design in particular successfully enhanced self- healing efficiency by over 10%. Finally, in collaboration with the international paint company DuluxGroup, this self-healing acrylic coating design was incorporated into a paint formulation according to the product range WeathershieldTM. The resulting UPy-Paint was subjected to range of industry specific paint tests, and its optical and mechanical self-healing performance was evaluated.
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ItemThe impact of housing insecurity on mental health, sleep and hypertension: Analysis of the UK Household Longitudinal Study and linked data, 2009-2019(PERGAMON-ELSEVIER SCIENCE LTD, 2024-06)BACKGROUND: Housing insecurity is an escalating problem in the UK but there is limited evidence about its health impacts. Using nationally representative panel data and causally focussed methods, we examined the effect of insecure housing on mental health, sleep and blood pressure, during a period of government austerity. METHODS: We used longitudinal survey data (2009-2019, n = 11,164 individuals with annual data) from the UK Household Longitudinal Study. Outcomes were probable common mental disorder (GHQ-12), sleep disturbance due to worry, and new diagnoses of hypertension. The primary exposure was housing payment problems in the past year. Using doubly robust marginal structural models with inverse probability of treatment weights, we estimated absolute and relative health effects of housing payment problems, and population attributable fractions. In stratified analyses we assessed potentially heterogeneous impacts across the population, and potential modifying effects of government austerity measures. A negative control analysis was conducted to detect bias due to unmeasured confounding. RESULTS: Housing payment problems were associated with a 2.5 percentage point increased risk of experiencing a common mental disorder (95% CI 1.1%, 3.8%) and 2.0% increased risk of sleep disturbance (95% CI 0.7%, 3.3%). Estimates were larger for renters, younger people, less educated, households with children, and people living in areas most affected by austerity-related cuts to housing support services. We did not find consistent evidence for an association with hypertension (risk difference = 0.4%; 95% CI -0.1%, 0.9%). The negative control analysis was not indicative of unmeasured confounding. CONCLUSIONS: Housing payment problems were associated with worse mental health and sleep disturbance in a large UK sample. Households at risk of falling into rent or mortgage arrears need more support, especially in areas where housing support services have been diminished. Substantial investment is urgently needed to improve supply of social and affordable housing.
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ItemA systematic review of the modelling and economic evaluation studies assessing regulatory options for e-cigarette use.(Elsevier BV, 2024-06-07)BACKGROUND: Governments around the world are considering regulating access to nicotine e-cigarettes to prevent uptake among youth however people that smoke tobacco may use them to assist with smoking cessation. The health and cost implications of regulating e-cigarette use among populations are unknown but have been explored in modelling studies. We reviewed health economic evaluation and simulation modelling studies that assessed long-term consequences and interpret their potential usefulness for decision-makers. METHODS: A systematic review with a narrative synthesis was undertaken. Six databases were searched for modelling studies evaluating population-level e-cigarette control policies or interventions restricting e-cigarette use versus more liberalized use. Studies were required to report the outcomes of life years, quality-adjusted life years (QALYs) and/or healthcare costs. The quality of the studies was assessed using two quality assessment tools. RESULTS: In total, 15 studies were included with nine for the United States and one each for the United Kingdom, Italy, Australia, Singapore, Canada, and New Zealand. Three studies included cost-utility analyses. Most studies involved health state transition (or Markov) closed cohort models. Many studies had limitations with their model structures, data input quality and transparency, and insufficient analyses handling model uncertainty. Findings were mixed with 11 studies concluding that policies permitting e-cigarette use lead to net benefits and 4 studies concluding net losses in life-years or QALYs and/or healthcare costs.Five studies had industry conflicts of interest. CONCLUSIONS: While authors did conclude net benefit than net harm in more of the studies so far conducted, the significant limitations that we identified with many of the studies in this review, make it uncertain whether or not countries can expect net population harms or benefits of restrictive versus unrestrictive e-cigarette policies. The generalizability of the findings is limited for decision-makers. In light of the deep uncertainty around the health and economic outcomes of e-cigarettes, simulation modelling methods and uncertainty analyses should be strengthened.
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ItemInvestigation of immunology and neuropathology of influenza virus and arbovirus co-infection( 2024-02)Viral co-infections can substantially impact antiviral responses, reduce protection and enhance immunopathology. Limited data exist on whether co-infection with influenza and other non-respiratory viruses affect disease outcomes and/or immune responses towards sequential or concurrent co-infections. As influenza viruses are prevalent worldwide, their geographical distribution overlap with neurotropic arboviruses. Hence, it is of key importance to investigate influenza and encephalitic arbovirus co-infections. The aim of this PhD thesis is to investigate the immune responses and immunopathology during co-infection with a respiratory influenza virus and neurotropic Alphavirus. We established a novel mouse model to study co-infection with unrelated viruses, influenza A virus (IAV) and Semliki Forest virus (SFV), causing disease in different organ systems, respiratory and central nervous systems. In Chapter 3, we sought to define how sequential co-infection of Alphavirus and influenza virus affects host immunity towards influenza virus. Mice were given SFV infection eight days before IAV infection (SFV->IAV). We provided evidence that SFV->IAV co-infection resulted in compromised IAV immune responses, leading to inefficient clearing of pulmonary IAV, subsequently causing increased lung inflammation, measured by the elevated cytokine/chemokine levels and exacerbated lung pathology. This was associated with impaired lung IAV-specific CD8+ T cell responses, stemming from suboptimal CD8+ T cell activation and proliferation in draining lymph nodes, as well as dendritic cell paralysis. Furthermore, IAV CD8+ T cell were detected in the brain of SFV->IAV infected mice. Ex vivo IAV epitope-specific TCR analysis performed in the brain and lungs during single IAV and sequential SFV->IAV co-infection not only showed remodelled TCR repertoire in co-infected mice, but corroborates the presence of these IAV-specific CD8+ T cells in the brain during co-infection. Adoptive transfer experiments highlighted that recruitment of these IAV-specific CD8+ T cells were antigen-specific and not a of bystander event. In the long term, CD8+ T cell memory pool establishment and magnitude of recall CD8+ T cell responses were comparable between IAV-only and SFV->IAV infection. However, reversing the sequence of co-infection (IAV->SFV) significantly diminished long-term IAV-specific immune responses, and also abolished the immunodominance hierarchy of CD8+ T cell responses to DbNP366 and DbPA224 epitopes. In Chapter 4, we determined how sequential co-infection of influenza virus and Alphavirus affects host immunity towards Alphavirus. Here, mice were given IAV infection 8 days prior SFV infection (IAV->SFV). Our findings demonstrated that IAV->SFV co-infection led to milder disease compared to SFV-only infection. Contrary to previous findings in Chapter 3, IAV->SFV infection resulted in reduced overall brain SFV viral titre and hence, lower cytokine/chemokine levels in the CNS. While viremia in both IAV->SFV and SFV-only mice were comparable, the trend of increased levels of type I IFN in the CNS after influenza virus infection might have been sufficient to mediate protection towards SFV infection in the CNS. Further investigation revealed that the acute and long-term adaptive immune responses in the CNS of both SFV-only and IAV->SFV mice were comparable, suggesting that the early control of SFV replication in the CNS in IAV->SFV by IFN has led to an overall reduced adaptive response, given the lower number of innate immune cells and CD8+ T cells that were recruited to the brain in IAV->SFV infection. Taken together, Chapter 4 established that the order of sequential co-infection significantly impacts the immune response and thus disease aetiology. In Chapter 5, we investigated how simultaneous co-infection of influenza virus and Alphavirus affects host immunity towards both pathogens. Mice were given both SFV and IAV simultaneously at different site of infection and monitored across different time points (SFV+IAV). We demonstrated that SFV+IAV infection did not lead to exacerbated or attenuated disease compared to both the single infection groups. Our studies showed that the overall immune responses and inflammation in the brain in SFV+IAV co-infection were comparable to that of SFV-only. On the contrary, despite prolonged pulmonary IAV replication in SFV+IAV infection, we did not observe exacerbated lung pathology in SFV+IAV compared to IAV-only infection. However, the magnitude of IAV-specific CD8+ T cell responses in the lungs were diminished in SFV+IAV infection compared to that of IAV-only infection. Despite this, SFV+IAV infected mice had comparable brain and lung pathology to SFV- and IAV-only infection. The prolonged clearance of pulmonary IAV and reduced magnitude of IAV-specific responses in the lungs in SFV+IAV co-infection was parallel to our findings in Chapter 3, suggesting that SFV infection, whether given in combination or consecutively with IAV, hampers IAV immune responses. Thus, Chapter 5 highlighted the significance of timing in co-infection, influencing immune responses and disease trajectory. Overall, the knowledge from research performed in this PhD thesis provides key insights into our understanding of how infection with one virus can alter immunity towards the second virus, following sequential or concurrent viral co-infections. Furthermore, expanding our existing knowledge on immune responses towards viral co-infections can facilitate a rational design of successful vaccine regimens directed towards multiple viral diseases.
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