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Artificial Dissemination: The utility of virtual reality reconstructions in engaging and informative public outreach of archaeological research
No full text© 2025 Thomas James KeepReconstructing archaeological sites has been a significant medium for conveying interpretations of the past for centuries. With the growth of digital recording, reconstruction of archaeological sites within virtual reality has emerged as a new means of communicating research to the public. Unlike earlier reconstructions where the audience was placed outside the material, virtual reality places the viewer into a vision of a past: the ‘virtual time machine’. These reconstructions have typically focussed on the grandeur of major urban sites. Rural excavations of minor archaeological sites are underexplored in this emergent medium, yet these sites are most at risk of fading from public memory. Rural sites are less often preserved for public viewing and their materials are less often displayed in museum collections. As a result, the typical view of the past is urban-centric and skewed against understanding the experience of the common historical person whose life is best outlined through archaeology. This thesis argues that the availability of 3D modelling software and hardware have progressed to the point where small-scale projects can begin to explore virtual reality reconstructions to share and preserve knowledge of their excavations and interpretations, provided that such endeavours are evaluated for their effectiveness.
This thesis consists of three main sections to explore this possibility. The first is a chronological outline of the history of reconstructions and archaeology, arguing that visual representation is necessary for communicating archaeological thought. It begins with the painterly traditions of the Renaissance, moving to the growth of draughtsmanship in the Enlightenment and the emergence of photography and the scale-model in Modernity, culminating with the arrival of digital modelling and virtual reality in the contemporary world. The second section comprises two case studies created by the author to explore the practical realities of generating virtual reality reconstructions of rural archaeological sites. The first, the Mernda VR Project, is a reconstruction of a flour mill and cottage in rural Victoria, Australia, uncovered in a 2015 excavation by Heritage Victoria. The second, the Cinis Vulcani VR Experience, is based on the so-called ‘blacksmith’s workshop’ of Podere Marzuolo in rural Tuscany, Italy, uncovered over 2018 and 2019 by the Marzuolo Archaeological Project. The third section outlines the evaluation of these case studies and discusses the role that the sense of presence plays in their effectiveness as enjoyable and informative outreach and education tools, and how presence can be established working within the time and budgetary confines experienced by many smaller archaeological projects. It is argued that virtual reality reconstructions of rural sites that engender presence in the experience provide an avenue for public engagement and education with these often-overlooked site
Dual-use virulence factors of the opportunistic pathogen Chromobacterium haemolyticum mediate hemolysis and colonization
No full textChromobacterium haemolyticum is an environmental bacterium that can cause severe and fatal opportunistic infections in humans and animals. Although C. haemolyticum is characterized by its strong β-hemolytic activity, the molecular basis of this phenotype has remained elusive over the more than 15 years since the species was first described. Herein, we report a family of cyclic lipodepsipeptides, the jagaricins, that are responsible for the potent hemolytic activity of C. haemolyticum. Comparative genomics of C. haemolyticum strains revealed a completely conserved gene locus (hml) encoding a nonribosomal peptide synthetase. Metabolic profiling of C. haemolyticum DSM 19808 identified a suite of cyclic lipodepsipeptides as the products, with the three main congeners (jagaricin A-C) being elucidated by a combination of tandem mass spectrometry, chemical derivatization, and nuclear magnetic resonance spectroscopy. Significantly, a C. haemolyticum hml deletion mutant is devoid of hemolytic activity. Moreover, purified jagaricins are hemolytic at low micromolar concentrations in an erythrocyte lysis assay. Further bioassays demonstrated that the cyclic lipodepsipeptides are crucial for the biofilm-forming and swarming behavior of C. haemolyticum. Matrix-assisted laser desorption ionization mass spectrometry imaging showed that primarily jagaricin B and C are involved in these processes in vitro. Our data shed light on the bioactivities of jagaricins, specialized metabolites that likely contribute to both successful niche colonization and the virulence potential of C. haemolyticum.IMPORTANCEDespite the rising incidence of Chromobacterium haemolyticum as a serious opportunistic pathogen, there is limited information on whether the competitive traits that ensure its survival in its freshwater niche also influence host infection. We reveal that C. haemolyticum produces specialized metabolites that not only cause its pronounced hemolytic phenotype but are also crucial for biofilm formation and swarming motility. These results exemplify a case of coincidental evolution, wherein the selective pressures encountered in a primary environmental niche drive the evolution of a trait impacting virulence. This knowledge provides a foundation for the development of antivirulence therapies against the emerging pathogen C. haemolyticum
Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
No full textApolipoprotein E (APOE- gene; apoE- protein) is the strongest genetic modulator of late-onset Alzheimer’s disease (AD), with its three major isoforms conferring risk for disease ε2 < ε3 < ε4. Emerging protective gene variants, such as APOE Christchurch and the COLBOS variant of REELIN, an alternative target of certain apoE receptors, offer novel insights into resilience against AD. In recent years, the role of apoE has been shown to extend beyond its primary function in lipid transport, influencing multiple biological processes, including amyloid-β (Aβ) aggregation, tau pathology, neuroinflammation, autophagy, cerebrovascular integrity and protection from lipid peroxidation and the resulting ferroptotic cell death. While the detrimental influence of apoE ε4 on these and other processes has been well described, the molecular mechanisms underpinning this disadvantage require further enunciation, particularly to realize therapeutic opportunities related to apoE. This review explores the multifaceted roles of apoE in AD pathogenesis, emphasizing recent discoveries and translational approaches to target apoE-mediated pathways. These findings underscore the potential for apoE-based therapeutic strategies to prevent or mitigate AD in genetically at-risk populations
Neonatal electroencephalography in critical care: refining measurement and characterising changes with general anaesthesia
No full text© 2025 Sebastian John CorletteThis thesis addresses critical challenges in neonatal anaesthesia, focusing on the application of electroencephalography (EEG) to understand the effects of general anaesthesia on the neonatal brain. Neonates undergoing anaesthesia represent a vulnerable population with unique neurodevelopmental and physiological profiles, requiring precise management to minimise pain, distress, and the risk of complications. Despite its importance, the field of neonatal anaesthesia lacks robust, evidence-based tools for assessing anaesthetic effects directly on the brain. This research aims to fill that gap by investigating EEG as a potential biomarker for anaesthetic effects on neonatal brain activity.
The study's primary objective was to develop a framework for high-resolution, low-noise EEG acquisition in neonates. It ultimately focussed on improving electrode design, refining EEG measurement techniques, and characterising anaesthesia-induced changes in EEG patterns. The development of an innovative needle-based electrode system emerged as a key outcome, addressing technical and logistical challenges associated with conventional electrodes. This new technology was validated through benchtop testing and preliminary clinical applications, demonstrating improved signal quality, ease of use, and adaptability to complex neonatal care environments.
Initial findings suggest that EEG can reliably reflect anaesthesia-related changes in neonatal brain activity. A novel EEG feature, Relative Anaesthesia Discontinuity (RAD), was identified as a potential biomarker for dose-related anaesthetic effects. Although based on a limited dataset, RAD and the associated RAD-Index demonstrate promise for quantifying anaesthesia effects directly in the brain, offering a more nuanced approach to monitoring than traditional physiological indicators.
The research highlights the feasibility of perioperative EEG monitoring in neonates and proposes practical solutions to overcome the technical and environmental challenges of data collection in this population. The insights gained pave the way for broader integration of EEG into neonatal anaesthetic care, potentially enabling more precise dosing, reducing risks of under- and over-dosing, and improving clinical outcomes.
Future directions include refining the electrode technology for adoption in both research and clinical settings, validating RAD in larger datasets, and exploring new questions about anaesthesia and the neonatal EEG. This thesis contributes to a growing body of knowledge on neonatal anaesthesia, providing a foundation for future research and technological advancements that may transform clinical practice and enhance the care of neonates undergoing surgery
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
No full textIn the context of global ageing, the prevalence of neurodegenerative diseases and dementia, such as Alzheimer's disease (AD), is increasing. However, the current symptomatic and disease-modifying therapies have achieved limited benefits for neurodegenerative diseases in clinical settings. Halting the progress of neurodegeneration and cognitive decline or even improving impaired cognition and function are the clinically meaningful goals of treatments for neurodegenerative diseases. Ageing is the primary risk factor for neurodegenerative diseases and their associated comorbidities, such as vascular pathologies, in elderly individuals. Thus, we aim to elucidate the role of ageing in neurodegenerative diseases from the perspective of a complex system, in which the brain is the core and peripheral organs and tissues form a holistic network to support brain functions. During ageing, the progressive deterioration of the structure and function of the entire body hampers its active and adaptive responses to various stimuli, thereby rendering individuals more vulnerable to neurodegenerative diseases. Consequently, we propose that the prevention and treatment of neurodegenerative diseases should be grounded in holistic antiageing and rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach is a promising strategy to effectively prevent, pause or slow down the progression of neurodegenerative diseases
The family caregiver-targeted web-based intervention “narstaende.se” facilitated everyday life for couples facing life-threatening illness: A qualitative study
No full textBACKGROUND: Life-threatening illness affects both patients and spouses, and spousal caregivers report high levels of distress. Web-based interventions could benefit spouses' and patients' needs and shared everyday life. AIM: To explore how a family caregiver-targeted web-based psychoeducational intervention influences couples' experiences of sharing everyday life at home while facing life-threatening illness. DESIGN: This qualitative sub-study involved dyadic interviews with couples (spouse-patient) where the spouse was allocated to the intervention arm of a randomized controlled trial evaluating a web-based family caregiver-targeted intervention. Data were analyzed using Interpretive description. SETTING/PARTICIPANTS: Participants were recruited from five specialized home care services in Sweden. In total, 32 participants, spouses (n = 16) and patients (n = 16) were interviewed as couples after the spouse had accessed the intervention for 4 weeks. RESULTS: Couples described how the spouses' access to the intervention had provided knowledge that enhanced the couple's understanding of each other's strategies for managing the impacts of the illness. The topics covered in the intervention prompted the spouses to initiate conversations that helped couples maintain a sense of mutuality. The intervention provided support to balance the tension between previous and new relational roles, which had changed due to the patient's illness. CONCLUSIONS: Altogether, the results show that the benefits of family caregiver-targeted interventions may extend from spouse to patient, facilitating their everyday life. Our findings complement previous intervention evaluations by providing insights into how they may be effective. The goal should be that interventions potentially benefit patients and family caregivers. TRIAL REGISTRY: The randomized controlled trial is registered at ClinicalTrials.gov, ID NCT05785494
Detection of Mycobacterium ulcerans with IS2404 loop-mediated isothermal amplification and a fluorescent reporter probe
No full textAn exquisitely sensitive quantitative PCR (qPCR) assay targeting the high-copy number insertion sequence, IS2404, is the gold standard diagnostic test for Mycobacterium ulcerans, the agent of the neglected tropical skin disease Buruli ulcer. Here, we designed and tested an alternative M. ulcerans diagnostic test, a fluorescent probe-based, loop-mediated isothermal amplification (P-LAMP) assay that also targets IS2404. Benchmarked against IS2404 qPCR, P-LAMP was equally specific and nearly as sensitive (analytical sensitivity of four vs two M. ulcerans genome copies). Clinical and environmental specimen validation against IS2404 qPCR showed P-LAMP had 100% sensitivity and specificity. P-LAMP was twice as fast as qPCR with an average time-to-positive at the limit-of-detection of 19 minutes. P-LAMP targeting IS2404 is a versatile assay that addresses the performance issues of previously described IS2404 LAMP formats. This study tackles a key research priority for Buruli ulcer and represents another avenue for the development of rapid and accessible molecular diagnostics for this neglected tropical disease
Developing a more accurate population frequency of Marfan syndrome from predicted pathogenic FBN1 variants in the gnomAD cohorts
No full textMarfan syndrome is an autosomal dominantly (AD)-inherited disease that results from pathogenic variants in the Fibrillin 1 (FBN1) gene, and is characterised by tall stature, elongated limbs and digits, lens abnormalities and aortic root dilatation, aneurysms and dissection, but milder forms also occur. Radiological imaging suggests that Marfan syndrome affects between one in 3000 and 5000 of the population. The aim of this study was to determine the population frequency of Marfan syndrome from the number of predicted pathogenic FBN1 changes found in a normal database. FBN1 variants were downloaded from gnomAD v2.1.1 and annotated with ANNOVAR. The population frequency was determined from the number of pathogenic null and structural variants, and the number of predicted pathogenic missense changes classified by rarity and computational scores. This population frequency was then compared with the frequencies in the control subset, and from gnomAD variants assessed as Pathogenic or Likely pathogenic in the ClinVar or LOVD databases. Our strategy identified predicted pathogenic FBN1 variants in one in 416 individuals, which was confirmed in the control subset (one in 356, p NS). Predicted pathogenic variants were most common in East Asian people (one in 243, p < 0.0001) and least common in Ashkenazim (one in 5185, p = 0.0082). The population frequencies based on pathogenic variants in the ClinVar or LOVD databases were one in 718 and one in 1014 respectively. Null variants which are associated with aortic aneurysms affected only one in 8624. Thus, Marfan syndrome is more common than previously recognised. Emergency departments and cardiac clinics in particular should be aware of undiagnosed Marfan syndrome and its cardiac risks, but many of those affected still have a milder phenotype
Crystallizing the Territorial Infra-Assemblage:: A M(m)inor Dialogue on Becoming an Intra-Active Citizen within Innovative Learning Environments
No full textThis study undertakes a conceptual journey—metaphorically mapped along a river—to explore the Innovative Learning Environments (ILEs) through the lens of assemblage thinking. By focusing on how these environments are built and organized, the research contributes to the broader discourse on the development of intra-active citizenship within ILEs from the perspective of new materialism. The aim is to reveal new synergies and build upon the existing body of literature in this field. Employing a comprehensive rhizomatic review, the study analyzed 45 documents using a Spinozist-Deleuzian toolkit grounded in new materialist thinking. The findings indicate a shift towards the idea of infra-assemblage, which plays a key role in how these environments come together. Using Hjelmslev’s linguistic model, the study explored how ideas move through four different research strata. The results highlight the need to consider social mobility when forming [minor] citizenship within ILEs, particularly in relation to gender, race, ethnicity, and physical ability. These factors are closely linked to how well educational institutions can adapt to larger social and cultural changes, especially regarding themes such as posthumanism and neoliberal influences. By introducing a new framework for understanding ILEs, this research provides valuable insights into the ethical and political aspects of knowledge creation and offers methods that are relevant to this field of study
Cognitive Assets and Risk Evaluation (CARE) Tools to Support Detection of Dementia for Aboriginal and Torres Strait Islander Peoples in Primary Care
No full text© 2025 Huong Xuan Thi NguyenBackground
Dementia is a progressive condition with substantial personal and societal impacts, but up to half of cases may be preventable by addressing modifiable risk factors across the life course. In Australia, Aboriginal and Torres Strait Islander peoples experience dementia at three to five times the rate of non-Indigenous Australians, driven by complex social, economic, and historical factors. As this population ages, there is an urgent need to promote brain health and reduce dementia risk. Primary care is central to this effort, serving as a key setting for the early identification of risk factors, implementation of preventive strategies, promotion of brain health and facilitation of timely detection and diagnosis within communities.
Aims
To i) review global evidence on dementia risk, protective factors, and biomarkers in Indigenous populations; ii) identify factors associated with dementia in harmonised datasets of Aboriginal and Torres Strait Islander participants; iii) develop tailored tools to improve dementia detection in primary care; and iv) explore community perspectives on dementia biomarker and genetic research.
Methods
A i) narrative review synthesised global published evidence on dementia risk, protective factors, and biomarkers in Indigenous populations. ii) Cross-sectional (n = 898) and longitudinal (n = 354) analyses of harmonised cohorts identified factors associated with dementia and cognitive impairment not dementia (CIND) and informed the iii) development of the Cognitive Assets and Risk Evaluation (CARE) tools: a rapid screen based on the Kimberley Indigenous Cognitive Assessment (KICA-Cog), CARE score, and CARE index. Psychometric performance was assessed using Receiver Operative Characteristic analyses and validated in an external cohort. iv) Community views on dementia biomarker and genetic research were explored using collaborative yarning methodology.
Results
The literature review revealed a focus on biomedical risks with limited evidence to cultural and psychosocial protective factors; biomarker studies involving Indigenous peoples were scarce. In the harmonised cross-sectional dataset, dementia was associated with older age, lower education, stroke, head injury with loss of consciousness, epilepsy, absence of obesity, and antidepressant use. In longitudinal analyses, age, residing in urban and regional settings compared to remote settings and hearing impairment were associated with incident dementia. A prototype scale utilising four KICA-Cog items 1,3,9 and 13 showed high diagnostic accuracy (sensitivity 82.6%, specificity 83.2%, Area Under the Curve (AUC) = 0.90) for dementia at the cut-off point of 7/8 out of 10, with favourable psychometrics when validated in an external cohort. The CARE score (AUC = 0.86) and CARE index (AUC = 0.80) demonstrated good discrimination but underperformed in preliminary validation. Aboriginal Elders and older participants of our yarning circles were receptive to dementia biomarker research when they perceived the research as valuable and trusted that it would be conducted ethically and in a culturally safe manner by the research teams involved.
Conclusions
Early detection of dementia in primary care is essential to reducing its impact and supports the broader goal of ‘Closing the Gap’ in health outcomes for Aboriginal and Torres Strait Islander peoples. While the CARE tools highlight the potential of tailored risk stratification approaches, they also reveal current limitations in effectively serving these communities. Strengthening culturally safe and ethically grounded dementia biomarker research, developed in genuine partnership with communities, can advance understanding, improve diagnostics, and support more personalised approaches to prevention and intervention in the future