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‘The seagull theory: Where people fly in, gather information… fly out and nothing ever comes about’: A qualitative exploration of barriers and enablers to research participation among adults with type 2 diabetes living in Australian rural communities
No full textAIM: Rural communities are under-represented in diabetes research, with implications for the generalisability, implementation and reach of research outcomes. Increased efforts to conduct diabetes research in, or inclusive of, rural communities are predicated on effective participant recruitment. This study explores the motivations for, barriers to and enablers of research participation among adults with type 2 diabetes (T2D) in Australian rural communities. METHOD: A phenomenological qualitative study was conducted involving adults (18+ years) living with T2D in rural communities, using multi-modal recruitment approaches and purposeful sampling across Australian states and gender. Audio-recorded, semi-structured interviews explored participants' perceptions of research participation. An abductive coding approach was undertaken to identify salient themes. RESULTS: Twenty-one participants were recruited across all six Australian states, median (range) age of 63 (41-78) years and 65% were women. Barriers to research participation include diabetes stigma, lack of community awareness of T2D, few research opportunities, geographical distances of rural communities from research sites and individual time and resource constraints. Enablers strongly focused on increased engagement and involvement of rural communities in research and offering education or access to diabetes care as part of research activities. Motivations for research participation included opportunities to help or advocate for rural and T2D communities and highlight under-resourcing of rural healthcare services. CONCLUSION: Study findings inform practical strategies that may improve recruitment mechanisms for T2D research in rural communities, for example, community-driven recruitment methods. Evaluation of the effectiveness of such strategies in research practice will be needed
The late-stage steps of Burkholderia cenocepacia protein O-linked glycan biosynthesis are conditionally essential
No full textPeriplasmic O-linked protein glycosylation is a highly conserved process observed across the Burkholderia genus. Within Burkholderia, protein glycosylation requires the five-gene cluster known as the O-glycosylation cluster (OGC, ogcXABEI), which facilitates the construction of the O-linked trisaccharide attached to periplasmic proteins. Previous studies have reported conflicting results regarding the essentiality of ogcA, predicted to be responsible for the addition of the final carbohydrate of the O-linked trisaccharide, and ogcX, the putative O-linked glycan flippase. Within this work, we aimed to dissect the impact of the loss of ogcA and ogcX on Burkholderia cenocepacia viability. We demonstrate that the loss of either ogcA or ogcX is detrimental if glycosylation is initiated, leading to marked phenotypic effects. Proteomic analysis supports that the loss of ogcA/ogcX both blocks glycosylation and drives pleotropic effects in the membrane proteome, resulting in the loss of membrane integrity. Consistent with this, strains lacking ogcA and ogcX exhibit increased sensitivity to membrane stressors, including antibiotics, and demonstrate marked changes in membrane permeability. These effects are consistent with the fouling of the undecaprenyl pool due to dead-end O-linked glycan intermediates, and consistent with this, we show that modulation of the undecaprenyl pool through the overexpression of undecaprenyl pyrophosphate synthase (UppS) or the OGC flippase (OgcX) restores viability, while expression of early-stage OGC biosynthesis genes (ogcI and ogcB) reduces B. cenocepacia viability. These findings demonstrate that disrupting O-linked glycan biosynthesis or transport appears to dramatically impact B. cenocepacia viability, supporting the assignment of ogcA and ogcX as conditionally essential
Comparing Iterations of National Identity in History Curricula in Post-Colonial Hong Kong and Macau, 2017-2022
No full text© 2025 Leiheng WangThis dissertation addresses a central research question: How did the iterations of “Chinese national identity” in the most recent history curricula of Hong Kong (2022) and Macau (2019) compare with each other, and why were they different? Through comparing the history curricula of Hong Kong (2022) and Macau (2019) [based on their history education reforms in 2019 and 2017 respectively], it argues that the respective reconstructed forms of Chinese national identity in the latest history curricula of Hong Kong and Macau (as of the time of writing) were tailored by their distinct historical trajectories that reflected their respective responses to Beijing’s directives, and were embedded in their local contexts. Comparatively, Hong Kong’s official iteration of Chinese national identity intended to prioritise local interpretations over Beijing’s expectations; it was based on a Hong Kong-centred discourse centred around “Hong Kong’s Chineseness”. Contrastingly, in Macau’s case, a weakened version of Beijing’s state-sanctioned national identity, based on “patriotic Chinese (zhongguo ren) in Macau”, was promoted. This was overlaid with Macanese consciousness punctuated by an international and multicultural outlook.
This research investigates the national identities that authorities in Hong Kong and Macau sought to construct, and the strategies employed in their reconstructions. Applying a combination of Fairclough’s analytical framework of critical discourse analysis (CDA) and comparative analysis, this dissertation contends that the history curricula in Hong Kong and Macau leveraged a similar approach of utilising moderated and less emotive narratives on historical events and historical participants. They disengaged their narratives from the discourse of historical materialism commonly found in Mainland China’s historical narratives; both constituted their uniquely different Chinese civilisation-oriented Chinese (zhongguo ren) and placed emphasis on local expressions within the discourse of Chinese Great Unification (dayitong). There were major differences too. First, Macau’s history curriculum intended to constitute a weakened version of the PRC’s official ideological system while Hong Kong’s curriculum sought to construct an ideological framework that synthesised state-promoted ideological concepts with those embedded within Hong Kong’s existing “quasi-British” system. Second, in terms of citizenry cultivation, Hong Kong’s curriculum worked towards nurturing an engaged citizenry centred around a triad comprising of individual responsibility, political literacy and critically political participation in a “superior Hong Kong”, while Macau’s history curriculum sought to socialise a more “compliant” citizenry for Macau as a model SAR characterised by limited socialisation in political engagement. Third, Hong Kong’s history curriculum iterated national identity by using “Hong Kong’s Chineseness” as the focal point and setting the narratives within a multi-dimensional identity framework encompassing “Chinese dimension”, “Hong Kong dimension” and “international dimension (citizens with an international outlook)”. Comparatively, Macau’s history curriculum sought to promote “patriotic Chinese in Macau” (zai aomen de zhongguo ren) with Macanese consciousness punctuated by an international and multicultural outlook.
In sum, Hong Kong and Macau’s iterations of Chinese national identity resemble the concept of “one country, two systems”, manifested as “one country, multiple interpretations of Chinese national identity”; and their narratives also contribute to the evolving understanding of Chinese civilisation
Site-specific quantification of the in vivo UFMylome reveals myosin modification in ALS
No full textUFMylation is a ubiquitin-like protein modification of Ubiquitin Fold Modifier 1 (UFM1) applied to substrate proteins and regulates several cellular processes such as protein quality control. Here, we describe the development of an antibody-based enrichment approach to immunoprecipitate remnant UFMylated peptides and identification by mass spectrometry. We used this approach to identify >200 UFMylation sites from various mouse tissues, revealing extensive modification in skeletal muscle. In vivo knockdown of the E2 ligase, UFC1, followed by enrichment and analysis of remnant UFMylated peptides quantified concomitant down-regulation and validation of a subset of modification sites, particularly myosin UFMylation. Furthermore, we show that UFMylation is increased in skeletal muscle biopsies from people living with amyotrophic lateral sclerosis (plwALS). Quantification of UFMylation sites in these biopsies with multiplexed isotopic labeling reveal prominent increases in myosin UFMylation. Our data suggest that in vivo UFMylation is more complex than previously thought
Feasibility and Acceptability of the Fear-Less Screening and Stratified-Care Model for Fear of Cancer Recurrence Among People Affected by Early-Stage Cancer
No full textObjectives: Fear of cancer recurrence (FCR) is a prevalent unmet need for people affected by cancer, in the context of limited healthcare resources. Stratified-care models have potential to meet this need, while reducing resource demands. This study aimed to evaluate the feasibility and acceptability of screening procedures and interventions within the Fear-Less stratified-care model among those impacted by early-stage cancer. Methods: People affected by breast, head and neck, or gynaecological cancer, who had completed curative treatment, were screened for FCR. Individuals experiencing moderate FCR (scored 13–21 on the Fear of Cancer Recurrence Inventory-Short Form; FCRI-SF) were offered a purpose-developed clinician-guided self-management intervention, while those experiencing severe FCR (FCRI-SF score ≥ 22) were offered individual therapy (ConquerFear). Re-screening and evaluation measures were completed post-intervention. Results: Seventy-six (70%) of 109 eligible people completed screening, with 53/76 participating in the Fear-Less model evaluation. Thirty-nine of 53 participants reported FCR and were referred to an intervention; 30/39 (77%) accepted the referral. Fifteen (83%) of 18 participants completing the self-management intervention reported reading ≥ 75% of the resource at 5 weeks, with 10/18 (56%) reporting clinically meaningful (≥ 10%) reductions on the FCRI-SF post-intervention. Qualitative feedback indicated screening and the stratified-care received were acceptable. Conclusions: Screening procedures and interventions forming the Fear-Less model appear feasible and acceptable for identifying and treating FCR among people affected by early-stage cancer. Although further research is required to evaluate its efficacy, this model has the potential to meet a major unmet need, where psychosocial services are limited amid increased demand. Trial Registration: This study was retrospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12622000818730) on 10/6/2022
Prognostic Value of Posttherapy SPECT/CT for Overall Survival in Patients Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy: Results from 3 Clinical Trials
No full textData are emerging on the prognostic significance of quantitative changes on posttherapy SPECT/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving [177Lu]Lu- PSMA-617. Our objective was to assess quantitative and visual changes on posttherapy SPECT/CT as prognostic biomarkers for overall survival (OS) among patients in 3 clinical trials: LuPSMA Phase 2 (ANZCTR12615000912583), LuPARP (NCT03874884), and PRINCE (NCT03658447)]. Methods: We segmented the total tumor burden on posttherapy [177Lu]Lu-PSMA-617 SPECT/CT using an SUV threshold of 3 to measure SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion activity (TLA).We assessed the prognostic value of changes in these quantitative parameters and new lesions identified visually on SPECT/CT after cycle 2 for OS using the Cox proportional hazards model, with age, Gleason score, and change in prostatespecific antigen (PSA) as covariates. Results: Eighty-five patients with mCRPC were analyzed (46 from LuPSMA Phase 2, 25 from PRINCE, and 14 from LuPARP). Patients eligible for inclusion had received at least 2 cycles of [177Lu]Lu-PSMA-617 with a follow-up time of at least 12 mo. Among these patients, 18 (21.2%) had new metastases visible on cycle 2 SPECT/CT, and this was prognostic for OS in univariate (hazard ratio [HR], 2.38; 95%CI, 1.36–4.18; P 5 0.002) and multivariate (HR, 2.85; 95% CI, 1.36–5.98; P 5 0.01) analyses. Seven (8.2%) patients with PSA reductions had new lesions on posttherapy SPECT/CT. Reductions in TLA (HR, 0.98; 95% CI, 0.97–1.00; P5 0.016) and MTV (HR, 0.98; 95% CI, 0.96–1.00; P 5 0.009) (per 10% increase for both) were associated with OS on univariate analysis but not on multivariate analysis. Changes in SUVmax and SUVmean were not associated with OS. There was moderate correlation among changes in PSA from cycle 1 to cycle 2 and MTV (correlation coefficient 5 0.55; 95% CI, 0.39–0.69; P, 0.001) and TLA (correlation coefficient 5 0.56; 95% CI, 0.40–0.69; P, 0.001). Conclusion: The presence of new metastases on posttherapy SPECT/CT after cycle 2 is an independent prognostic biomarker for OS in patients with mCRPC and could guide future prospective research to improve treatment strategies for patients with poor prognoses
Music as a collaborating actor: new insights into the nature and role of music in psychedelic-assisted psychotherapy
No full textBACKGROUND: Music has been identified as a central feature of psychedelic-assisted psychotherapy (PAP) and has hitherto been understood to amplify the psychedelic experience in a predictable way that has been codified into music recommendations and playlists. PURPOSE OF STUDY: To re-evaluate the nature and role of music within the participant's world during psychedelic-assisted psychotherapy. METHOD: Phenomenological analysis of participants' descriptions of music during a randomised control trial of PAP at end of life involving two doses and a semi-structured interview following each dose. FINDINGS: Music undergoes a profound change during PAP that radically transforms it from everyday recorded music into a series of internally generated multisensory and deeply personal experiences that arrive fully formed and are instantly known by the participant. Some of these are constituted into actors that collaborate with the participant and the psychotherapist in their ongoing psychotherapy endeavours. This stands in stark contrast with the everyday properties of music described by those in the placebo group. CONCLUSIONS: An alternate understanding of music in PAP is suggested that radically departs from the view that music is "administered" as part of PAP. There are profound implications for the practise of PAP and further research. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinician Trials Registry identifier, ACTRN12619001225101
Contribution of depression and cardiometabolic diseases and the role of depression treatment in survival and functioning in older adults
No full textBACKGROUND: Achieving survival free from physical disability or neurocognitive impairment, known as disability-free survival (DFS), is a key public health goal. This study aimed to (1) determine the long-term interactive effects of depression and cardiometabolic diseases (CMDs) on DFS, and (2) explore any associated antidepressant treatment effect on improvements in DFS among older adults. METHODS: We used data from the ASPREE trial and its observational follow-ups (2010-2019), involving community-dwelling adults aged ≥ 70 years (≥65 for U.S. minorities). Time-updated Cox models were used to estimate the combined effect of depression and CMDs (type 2 diabetes, dyslipidemia, hypertension, chronic kidney disease, metabolic-associated steatotic liver disease, and major adverse cardiovascular events) as well as cardiometabolic multimorbidity (≥2 CMDs) on DFS. To evaluate the improvement in DFS associated with antidepressant treatment in individuals with depression, we estimated the number needed to treat (NNT) to achieve a one-year increase in DFS through antidepressant therapy. FINDINGS: 18,739 participants (mean [SD] age, 75.1 [4.6] years; 56.0% female) were included, with a median follow-up of seven years; individuals with both depression and CMDs demonstrated a significantly lower DFS compared to those without either condition. In individuals with depressive symptoms, antidepressant use was associated with a median increase in DFS of 2.95 years (95% CI, 2.12-3.04), with an estimated NNT of 8.05 (95% CI, 5.63-14.86) associated with a one-year increase in DFS. INTERPRETATION: Integrating depression treatment into chronic disease management, when appropriate, is associated with an improvement in DFS among older adults. FUNDING: Deakin University Postgraduate Research Scholarship
Long-term impacts of captivity on skull morphology and endocranial volume in a marsupial carnivore
No full textA challenge in modern conservation is maintaining ecological roles and natural behaviours of wildlife in an anthropogenic world. Captive breeding has been linked to morphological changes that may impact individual fitness for reintroduction to the wild. Changes in skull morphology and brain size may be linked to functional and behavioural changes, influencing survival outcomes. These issues have been explored in numerous eutherian mammals, but rarely in metatherians. We compared skull morphology and endocranial volume in a carnivorous marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata), between wild-derived and captive individuals maintained in a university laboratory colony over tens of generations. Skulls from captive dunnarts were brachycephalic, with significantly shorter basal and upper molar lengths, broader zygomatic widths and longer palate and toothrow lengths, compared with wild counterparts. Captive-bred dunnarts also had a mean endocranial volume 3.8% larger than wild individuals. These traits relate to dietary, cognitive and sensory capabilities and can be linked to functional differences within captive and wild populations. Therefore, changes to these regions could have substantial fitness consequences in natural habitats. By addressing the ways laboratory management can influence morphological traits, we can reassess broader captive management techniques to improve the success of future breeding and reintroduction programmes
Negative Healthcare Impacts of Management of Presumed Early-Onset Sepsis in Moderate to Late Preterm Infants on Feeding, Jaundice, and Hospital Length of Stay
No full textBACKGROUND/OBJECTIVES: Early-onset sepsis in neonates is a potentially catastrophic condition that demands prompt management. However, laboratory diagnosis via cerebral spinal fluid and blood tests is often inconclusive, so diagnosis on the basis of clinical symptoms and risk factors is frequently required, and the majority of neonates treated with antibiotics for presumed early-onset sepsis (PEOS) do not have culture-proven sepsis. The management of such PEOS is mainly achieved via antibiotic therapy, which itself has adverse effects, creating a dilemma for clinicians in optimising healthcare. This study aimed to assess the impact of PEOS management on the common neonatal concerns of feeding tolerance, hyperbilirubinaemia, weight gain, and length of stay (LoS) in moderate to late preterm infants. METHODS: A single-site, matched-cohort, retrospective study was performed on infants born between 32+3 and 36+6 weeks (2016 to 2019) admitted to the Neonatal Unit. PEOS infants on antibiotics (PEOS) were strictly matched by gestational age (±1 day) and birthweight (±5%) against a non-PEOS reference group (NPEOS). The key outcomes included the following: enteral feeding commencement and achievement; feeding intolerance (FI); phototherapy commencement and duration; antibiotic therapy duration; maximum bilirubin (MaxBili); LoS; and net postbirth weight gain. RESULTS: There were no cases of culture-proven early-onset sepsis. PEOS (n = 185): NPEOS (n = 185) via multivariable analysis showed delayed enteral feed commencement (adjusted Odds Ratio [aOR]: 2.75; 95% confidence interval [CI]: 2.32, 3.27); there was no difference in FI, delayed onset of peak jaundice (aOR: 1.24; 95%CI: 1.12, 1.37), increased duration of phototherapy (aOR: 1.24; 95%CI: 1.10, 1.41), and increased LoS (aOR: 1.31; 95%CI; 1.02, 1.67). A univariate analysis also showed the following results (PEOS: NPEOS): no significant difference in MaxBili and delayed full enteral feed achievement (p = 0.010). Univariant or multivariable analysis showed no difference in irradiance levels. However, for NPEOS infants undergoing 0 or 1 phototherapy light treatment, there was an increased irradiance for PEOS (<0.001, 0.037, respectively). CONCLUSIONS: In moderate to late preterm infants, while PEOS diagnosis and management resolve the negative health impacts of potential sepsis, they are associated with negative healthcare outcomes on feeding, jaundice, and hospital length of stay