Exploring Differences in The Cargos of Placental Extracellular Vesicles in Physiological and Pathological Pregnancy

Introduction: Placental extracellular vesicles (pEVs) are lipid bilayer particles that carry various types of cargos from the placenta to the maternal circulation. Recognized as essential messengers in fetal-maternal communication, the pEVs have been reported to regulate vascular tone during normal pregnancy. However, it remains unclear whether these regulatory functions differ between pEVs from 1st and 3rd-trimesters placentae. Meanwhile, pEVs from preeclamptic pEVs have been shown to induce or exacerbate hypertension, the key presentation of this condition, suggesting they may be involved in the pathogenesis of preeclampsia via an unknown mechanism. Aims: To investigate the differences of pEVs during different gestational stages in physiological pregnancy, as well as the differences of pEVs during preeclampsia and normotensive pregnancy. Methods: Wire myography was performed on the mesenteric resistant arteries isolated from pregnant CD-1mice injected with 1st and 3rd-trimester pEVs to compare the vascular effects of pEVs from different gestational ages in normal pregnancy. Small RNAs sequencing was conducted on pEVs collected from 1) 1st and 3rd-trimester placentae and 2) early-onset preeclampsia (EOPE), late-onset preeclampsia (LOPE) and normotensive (NT) placentae, with the pEVs isolated from an ex vivo placental explant culture model. In parallel, Sequential Window Acquisition of All Theoretical Mass Spectrometry was employed to profile the proteomic content of EOPE, LOPE, and NT pEVs derived from the same explant model. To investigate the functional relevance of the significantly differentially abundant miRNAs in preeclamptic versus normotensive pEVs, human microvascular endothelial cells were transfected with specific miRNA inhibitors, followed by monocyte adhesion assays to assess endothelial activation. Additionally, the biomarker potential of altered membrane-associated proteins on pEVs was evaluated using a magnetic affinity sorting assay. Findings: 1st-trimester pEVs reduced the vascular sensitivity to vasoconstrictors and enhanced the vascular sensitivity to vasodilators, in comparison to 3rd-trimester pEVs. These functional differences may be partially explained by the differences in the miRNA profiles between the 1st and 3rd trimester pEVs. In preeclamptic pEVs, miRNAs and proteins with different abundance compared to normotensive pEVs are involved in various cardiovascular functions. Notably, the lower abundance of miR-148b-3p in preeclamptic pEVs compared to normotensive pEVs may lead to upregulation of Integrin α5 on endothelial cells, thereby enhancing monocyte adhesion. Additionally, TPBG, a membrane protein found to be more abundant in EOPE pEVs than in NT pEVs, was unable to sort pEVs via magnetic affinity assay, underscoring the complexity of EV surface biology. Conclusion: This study provides novel insights into the potential roles of pEVs in maternal cardiovascular adaptation during both physiological and pathological pregnancy. Collectively, this study, when combined with others, offers promising avenues for the identification of biomarkers and therapeutic targets for the clinical management of preeclampsia

Investigations into the Pathogenesis of Acute Rheumatic Fever

Acute rheumatic fever (ARF) is an autoimmune sequela to infection by Group A Streptococcus that can progress to chronic rheumatic heart disease (RHD) characterised by progressive heart damage. The pathogenesis of ARF is poorly understood, and there are no effective immunomodulating therapies to prevent progression to RHD. For this doctorate, immunological profiling of both the circulating immune system and rheumatic valve tissue was performed across a series of clinical cohorts. This provided an integrated perspective on immunological dysfunction with the aim of identifying targets for future therapeutic intervention. Immune cells in peripheral blood and serum markers were characterised using flow cytometry panels and bead-based immunoassays in a cross-sectional cohort of ARF cases with inflammatory and non-inflammatory control groups, as well as in a longitudinal cohort of ARF cases receiving low-dose hydroxychloroquine. In vitro stimulation assays evaluated immune cell cytokine production in this longitudinal cohort. A further observational cohort study was established to collect blood and valve tissue samples from rheumatic patients undergoing valve surgery. This combined profiling of peripheral blood with quantification of valve infiltrating immune cells by multiplex immunofluorescent staining. Peripheral profiling in ARF identified notable elevations in inflammatory cytokines (IL-6 and TNFα) in common with other inflammatory conditions. Concentrations of chemokine CCL5 and total immunoglobulin IgG3 were uniquely elevated in ARF and stratified by severity of inflammation. Perturbation of the circulating T cell compartment was also identified, with reduced expression of the homing receptor CXCR3 across multiple activated T cell populations indicating migration from the circulation into tissue. Immunofluorescent imaging confirmed this, demonstrating that reduced peripheral CXCR3 expression was associated with substantial CXCR3+ immune cell infiltrate in neo-vascularised rheumatic valve tissue. This mechanism of autoimmune attack, in combination with impaired peripheral tolerance (reduced T regulatory cell frequency) establishes new and essential features of immune dysregulation in inflammatory ARF. The pathological features of ARF defined here point to cytokine drivers of disease that could be appropriate for targeted intervention. Impaired peripheral tolerance, dysregulated humoral immunity, and inflammation may all be linked to elevated IL-6, highlighting the potential value of IL-6 blockade in ARF

Game Localisation amid Geopolitical Tensions: Taiwanese Independent Game Developers in the Global Gaming Market

Independent (or “indie”) game developers, as counterparts to commercially oriented mainstream developers, are often characterised by greater creative autonomy due to reduced external control. In reality, independence typically entails limited resources, necessitating many to sell games beyond the domestic market. For indie developers from Taiwan, the escalating geopolitical tensions across the Strait complicate this global navigation, especially given China’s emergence in the global gaming industry. Grounded in game localisation research and informed by a sociological lens, this study investigates the impact of geopolitical dynamics on the development and circulation of Taiwanese-made games by eliciting Taiwanese indie developers’ perceptions of geopolitical tensions and their GILT strategies (globalisation, internationalisation, localisation and translation). The thesis is designed to first establish the context of research with a case study on controversy surrounding Red Candle Games, followed by an interview-based study of fifteen Taiwanese indie developers. It adopts Bourdieu’s Theory of Practice (1977) to understand the power structure and social interactions among the main actors of game development and circulation. This is complemented by Pym’s Translation Economics (2017) to analyse the financially driven dimension of GILT strategies to access global markets. The findings reveal a strong advantage in the sizable Chinese market, maximising translation economics, due to this market’s linguistic and cultural proximity for Taiwanese games, while over-reliance on this market exposes Taiwanese developers to geopolitical tensions. The interviewees demonstrate their awareness of the delicate balance where engagement with the Chinese market may call for careful industry relations management and design adjustments, especially for games expressing Taiwanese identity, putting at risk the very creative autonomy indie games epitomise. This precarious negotiation is discussed in terms of Bourdieu’s habitus, field and, in particular, capital, by extending Consalvo’s (2007) gaming capital. The thesis concludes by suggesting pointers for GILT strategies for Taiwanese developers, including the notion of “strategic ambiguity” (Brown 2024a) often referenced in diplomacy and political communication to manage geopolitical tensions. This research contributes to an empirically supported understanding of how geopolitics serves to shape the market mechanisms, likely transforming the global gaming industry and games over time

Ex Vivo Pullout Strength of Locking and Cortical Screws in the Femur and Tibiotarsus of the Pekin Duck (Anas platyrhynchos domesticus)

The development of smaller orthopedic plates and screws has facilitated their use in avian fracture repair. Avian bone differs from mammalian bone in its biomechanical properties due to adaptations for flight, necessitating avian-specific orthopedic biomechanical studies. Screw pullout strength has not been studied in avian bone. The aims of this study were to 1) compare the axial pullout strength of cortical and locking screw designs in the tibiotarsus and femur of the Pekin duck (Anas platyrhynchos domesticus) and 2) investigate the effects of sex and screw location in bone on screw pullout strength. Locking and cortical screws were inserted in 5 locations: the distal metaphysis, distal diaphysis, middiaphysis, proximal diaphysis, and proximal metaphysis of femora (n = 28) and tibiotarsi (n = 40) from 20 Pekin ducks. Screws were tested to failure in axial pullout and maximum force recorded. Data were analyzed by a linear mixed-effects model. There were no significant differences in screw pullout strength between locking and cortical screws or between sexes. On average, maximum force was highest at the middiaphysis in the femur and at the distal diaphysis of the tibiotarsus. These results suggest that when using 2.0-mm and 1.5-mm screws in avian femoral and tibiotarsal bones, respectively, screw positioning in denser diaphyseal regions may be more critical to screw pullout strength than the choice between cortical and locking screw designs

Mitigating resistance in smart health monitoring systems: the role of data governance and privacy concerns

Purpose: Smart health monitoring systems (SHMSs) have encountered resistance and limited adoption by various stakeholders. This study aims to investigate the impact of data governance on the associated privacy concerns in relation to barriers, thereby mitigating users' resistance to SHMSs. Design/methodology/approach: This mixed-methods study draws on innovation resistance theory and data governance mechanisms. We developed a research model based on 20 qualitative interviews with individuals from multiple stakeholder groups and empirically tested the model using 277 valid responses from potential and current SHMS users, collected through an online questionnaire survey. Findings: The findings reveal that data governance mechanisms–incorporating legislative protection, cultural and religious differences (procedural data governance mechanisms), transparency, and trust (relational data governance mechanisms)–are more influential than accountability and responsibility (structural data governance mechanisms) in reducing user resistance to SHMSs. Privacy concerns significantly influence functional barriers to SHMSs and ultimately positively affect users' resistance to SHMSs. Cultural and religious differences and trust mechanisms are significantly associated with privacy concerns among users with a high personal innovativeness level. Research limitations/implications: The study extends innovation resistance theory by integrating data governance, showing how theoretical models can be practically adapted for diverse health information technology (HIT) contexts. The findings offer societal implications, informing policies that promote SHMS development with robust privacy protections, inclusive design and trust-building governance. Originality/value: This is a pioneering study that extends innovation resistance theory by integrating data governance, demonstrating how theoretical models can be tailored to address diverse needs within the HIT domain

Influence of Ethnicity Classification Methods on Physical Activity Outcomes Among Adolescents

BackgroundPhysical activity (PA) is essential to adolescent health. International research has shown ethnic disparities in PA, and the method used to classify ethnicity may influence how disparities are detected and interpreted particularly in increasingly multiethnic societies. This study examined how different ethnicity classification methods affect adolescent PA outcomes.MethodsSecondary analysis was conducted using data from the 2023 Voice of Rangatahi survey in Aotearoa New Zealand (n = 19,776; ages 12-19 y). PA was measured using a discrete scale (0-7 d/wk) and a binary variable (>4 vs ≤4 d/wk). Ethnicity was self-identified and classified using 4 methods: Prioritized, Total Response, and Single/Combination (8- and 15-group). Analyses applied regression and nonparametric tests.ResultsOverall, 24.3% identified as multiethnicity. Asian adolescents consistently reported the lowest PA outcomes (mean = 3.51-3.67 d/wk; 34.4%-36.3% achieving >4 d/wk), while multiethnic Pacific Peoples/European reported the highest (mean = 4.34 d/wk; 52% achieving >4 d/wk). The Single/Combination 15-group method provided the greatest intergroup differentiation (χ2(13) = 218.65, P ConclusionsEthnicity classification strongly influences observed disparities in adolescent PA. The Single/Combination 8-group method may be most suitable for research applications due to better model fit and parsimony, while the 15-group method offers finer differentiation to guide policy and the design of targeted interventions. Selecting context-appropriate classification methods is critical for accurately identifying disparities and informing equitable, culturally responsive PA interventions

Crafting sustainability narratives in tourism on social media

As tourism firms increasingly adopt sustainable practices, effectively communicating their sustainable transitions has become essential yet challenging. This study explores how tourism operators use narrative structures and framings to communicate their sustainable transitions and their tensions to audiences on Instagram. Employing a comparative case study approach, this research analysed 2320 Instagram posts (from 2019 to 2024) and semi-structured interviews with three tourism operators in New Zealand. Findings indicate that tourism operators use ‘Romance’ and ‘The Quest’ narratives to engage consumers in sustainability dialogues. However, firms differ significantly in how they frame tensions, ranging from explicit acknowledgement to implicit or absent representation. Instagram's interactive and multimodal nature enables viewers to ignore, endorse, or contest firms’ sustainability narratives and to surface tensions in sustainability. This active engagement challenges assumptions that tensions in sustainability are too complex for public audiences to grasp. This study advances the literature on sustainability communication in tourism by highlighting how narrative complexity and audience interaction shape how tourism firms’ sustainability narratives are crafted, offering practical insights for effectively communicating sustainable transitions on social media platforms

Social Announcement Logic

Social Announcement Logic (SAL) is a formal framework for modeling information dynamics in social networks, augmenting epistemic logic with operators for communication. A significant open challenge in this field is developing sound and complete finitary axiomatizations for logics that include arbitrary announcements, a problem underscored by known soundness issues in Arbitrary Public Announcement Logic (APAL). This thesis addresses this challenge by first establishing a novel semantic framework for SAL based on sets of propositions rather than standard Kripke models. The central contribution is the development of a new model transformation technique to prove the soundness of the inference rule for arbitrary announcement operators. This constructive, model-based method provides a transparent semantic justification for this crucial inference rule. This technique enables the primary result of the thesis: the first sound and complete finitary axiomatization for Arbitrary Social Announcement Logic (ASAL). The research further supports this system by developing a complementary tableau system for efficient theorem proving and model construction. Additionally, the thesis analyzes the expressive power of SAL, demonstrating how various classes of coherence models make it possible to define the social network’s following relationship using purely epistemic formulas. By establishing these formal systems and novel proof methods, this thesis provides a robust framework for analyzing belief dynamics in social networks. It offers a new, verifiable solution to persistent challenges in the logic of arbitrary communication, with implications for epistemology, computer science, and the analysis of multi-agent systems

Diabetes and the Female Heart

Type 2 diabetes is a major risk factor for heart failure, with diabetic women experiencing disproportionately severe outcomes compared to diabetic men. The mechanisms underlying these sex specific outcomes remain unclear. This thesis investigated how sex and type 2 diabetes interact to influence cardiac mechanics, energetics, and structure, focusing on cardiac excitation contraction coupling (ECC) - a critical cellular event that leads to heart muscle contraction. To achieve the project aim, I developed and applied an integrated experimental pipeline combining diabetic rat preparation, work loop calorimetry and immunofluorescence structural imaging. Four key objectives guided this work. First, I characterised, using a work-loop calorimeter, baseline sex‑differences in mechanoenergetics of isolated healthy trabeculae, to understand differences in indices of functional performance including activation heat, cross-bridge heat, force length work output, and mechanical efficiency between males and females. Second, I investigated to establish a type 2 diabetes model in both sexes using a high-fat diet and low-dose streptozotocin injections. Third, using the work-loop calorimeter, I studied isolated diabetic left ventricular trabeculae to assess whether cardiac mechanoenergetics were sex- and diabetes-dependent. Finally, I employed super-resolution Stimulated Emission Depletion (STED) microscopy and automated image analysis pipelines to quantify key ECC proteins organisation: transverse tubules (T tubule), ryanodine receptor type 2 (RyR2) clusters, and filamentous actin (F-actin). Results showed that while diabetic rats developed systemic dysfunction including glucose intolerance and alterations in plasma biomarkers, myocardial energetics were preserved at the trabecula level. Baseline comparisons revealed no sex differences in mechanoenergetic indices in healthy muscle. In the diabetic model, neither sex nor diabetes altered twitch kinetics, energetic cost, and mechanical efficiency over a wide range of workloads, indicating preserved mechanoenergetic performance despite systemic disease. Structural analyses revealed clear spatial disorganisation only in diabetic males, with reduced T-tubule area alongside enlarged RyR2 clusters. F-actin organisation remained unchanged in all groups. Collectively, this work provides the first direct quantification of sex-specific cardiac mechanoenergetic performance in type 2 diabetes and links structural to function. By integrating functional and structural investigation, this thesis establishes a framework for future research into diabetic cardiomyopathy and highlights the importance of incorporating sex as a biological variable in cardiovascular research