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Development and validation of IgG N-glycosylation-based nomograms for early diagnosis and postoperative recurrence risk prediction of colorectal cancer in Chinese Han population
No full textBackground: Colorectal cancer (CRC) is among the leading causes of cancer morbidity and mortality worldwide, with prognosis heavily determined by stage at the diagnosis and risk of postoperative recurrence. Immunoglobulin G (IgG) N-glycosylation has emerged as a promising source of biomarkers reflecting tumour-related immune and microenvironmental changes.
Study Overview: This dissertation presents two complementary studies conducted in a Chinese Han population, each focused on the development of a distinct IgG N-glycan–based nomogram:
1. A Diagnostic Nomogram for Early-Stage CRC (Study I);2. A Prognostic Nomogram for Postoperative Recurrence in CRC (Study II).
Study I: Diagnostic Nomogram for Early-Stage CRC (Stages I and II): A clinical case-control study recruited participants based on the following inclusion criteria: histologically confirmed CRC or colorectal adenoma (CRA), age- and sex[1]matched healthy controls, absence of autoimmune or other malignancies, and no prior CRC treatment. The prime cohort comprised 309 subjects (103 CRC, 103 CRA, and 103 controls) and further validated by an independent validation cohort (61 CRC and 61 controls). Plasma IgG N-glycan profiles were quantified by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC). LASSO selection identified key glycan traits, which were integrated via multivariate logistic regression into a diagnostic nomogram. Early-stage CRC (Stages I and II) patients exhibited elevated bisecting GlcNAc and agalactosylation alongside reduced sialylation and galactosylation (all p \u3c 0.01). The diagnostic nomogram demonstrated high discriminative performance, with AUCs of 0.922 (95% CI: 0.875-0.969) in the prime cohort and 0.857 (95% CI: 0.770-0.944) in the validation cohort, outperforming conventional markers such as CEA and CA19-9. Calibration curves and decision-curve analysis further supported its clinical utility.
Study II: Prognostic Nomogram for Postoperative Recurrence: In the retrospective longitudinal multicentre cohort, 296 CRC patients (Stages I-III) were selected from 431 initially recruited participants after applying the following exclusion criteria: incomplete follow‑up, or death from non‑CRC causes prior to recurrence. The cohort was split into a training set (n = 208) and a validation set (n = 88). Clinical risk factors (e.g., nodal status, tumor differentiation) and glycan traits were evaluated using univariate and multivariate Cox regression models. Bisecting GlcNAc (HR: 1.29, p = 3.7 × 10⁻⁵), N2 nodal stage (HR: 8.67, p = 0.003), and poor tumor differentiation (HR: 2.50, p = 9.9 × 10⁻⁴) were identified as independent predictors of recurrence. The resulting prognostic nomogram showed strong predictive accuracy, with 2-4-year AUCs of 0.763-0.832 (training) and 0.855-0.859 (validation). Brier scores were all ≤0.175, and Kaplan-Meier analysis revealed significant recurrence-free survival (RFS) stratification (log-rank p \u3c 0.001).
Conclusion: These two nomograms exploit distinct IgG N-glycosylation signatures for complementary purposes: one enhances early detection of CRC, and the other enables individualized prediction of postoperative recurrence risk. Both models outperform traditional biomarkers and offer practical tools for precision oncology. Future research will aim to validate these findings in diverse populations and investigate the biological mechanisms linking IgG glycosylation with CRC pathogenesis
Out of the Woods: Mount Lawley Teachers College, The first decade 1970 - 1980
No full textThis book focuses exclusively on the visions and contribution of Robert (Bob) G.Peter, the first Principal, appointed to build a radically new teachers’ college, the first new tertiary institution in Australia since the end of WWII.It covers the first decade or so of the College,1970-1979.The story describes how Bob Peter based his visions on modern educational thought and practices and how he enthused his selected foundation staff to work with public works department architects to incorporate these new ideas in the design and building of this new tertiary institution.https://ro.ecu.edu.au/ecubooks/1007/thumbnail.jp
Communities of practice: Transforming education in the health professions
No full textBackground: Transformation is needed across health professions education, to address both historical challenges, such as adopting best practice assessment, and evolving challenges, such as those presented by generative artificial intelligence (GenAI), and ensure that future health professionals meet the needs of health systems and communities. Importantly, this transformation must extend beyond changes at the level of individuals, to create change across institutions and wider infrastructure that make up health professions education. Yet, little is known about how to achieve such transformation in the sector. Communities of practice offer an approach underpinned by theory, with existing evidence to suggest they can facilitate a range of meaningful outcomes. However, limited studies and methodologies employed to evaluate communities of practice in health professions education to date have prevented an in depth understanding of their potential to enable institutional and system-wide change in this sector. Evaluation of communities of practice in health professions education using theory-based methodology can address this gap by allowing researchers to unpack the complex, contextual ways that communities of practice work, to inform their future use to drive transformations in health professions education.
Aims: The aim of this research was to develop explanatory theory about communities of practice in health professions education that addressed the central research question ‘How might communities of practice facilitate change at the individual, interpersonal, institutional, and infrastructural level in higher education for health professionals, for whom, under what circumstances, and why?
Method: The research was conducted in two parts, using two specific forms of realist research. Study 1 was a realist synthesis of the existing literature on communities of practice that have brought together faculty members within health professions education, conducted according to the RAMESES (Realist and Meta-narrative Evidence Synthesis: Evolving Standards) standards and steps described by Pawson and colleagues. Study 2 was a realist evaluation of an existing Community of Practice for Dietetic Educators in Australia and New Zealand. Study 2 was conducted longitudinally, using multiple methods, including analysis of both qualitative and quantitative data, over nine years of the Community of Practice. Data analysis in both studies focused on developing and refining theory about communities of practice in health professions education, expressed as context-mechanism-outcome configurations (CMOCs), and integrating relevant formal theory, to develop theory that is both practical and transferable.
Results: The realist synthesis (Study 1) resulted in theory about communities of practice in health professions education, comprised of ten CMOCs that describe how contexts and mechanisms interact to contribute to a range of individual, interpersonal, and institutional outcomes. The realist evaluation (Study 2) resulted in six CMOCs that describe how the Community of Practice for Dietetic Educators in Australia and New Zealand operated to create similar outcomes, as well as infrastructural level change, such as shifting institutional and discipline culture. Relevant substantive theories were integrated into a final theory illustrating how communities of practice in health professions education work best. In line with existing theory, communities of practice in health professions education can cultivate a shared repertoire of thinking and practice amongst members, through voluntary sustained mutual engagement, where they regularly meet to share and reflect around the joint enterprise of health professions education. Further, where the direction of a community of practice is shaped by members’ shared interests, and when feedback and debriefing is supported by a relaxed, supportive, and inclusive facilitator, members experience increased intrinsic motivation and commitment to apply learning to change practice, through a process of self-determination. Members may also experience a shift in identity, becoming future leaders that are empowered to make change. Diverse, cross institutional communities of practice, with a well-known and respected facilitator, can enable interactions across multiple, interacting landscapes of practice, including opportunities for members to interpret and contextualise evidence, and negotiate change within and beyond the community of practice. This can lead to broader outcomes across institutions and disciplines, including curricular change, cross-institutional collaboration, culture change, and advocacy.
Conclusion: The results of this research have shown how communities of practice have the potential to drive transformative change needed in health professions education, and informed a practical, yet transferable theory describing how, why, and in what circumstances they best do so. This theory can guide those in health professions education to design and evaluate communities of practice to optimise system-wide outcomes, and strengthen health professions education, and the future health workforce, to meet health care needs
Acoustic and IMU-based integrated tracking for underwater navigation
No full textAccurate navigation is essential for underwater vehicles like AUVs, which often operate in deep or remote areas. However, complex ocean dynamics, cumulative inertial-measurement unit (IMU) drift, and diverse noise sources often result in erratic and unreliable position estimates. To overcome these challenges, this thesis presents a method that combines underwater acoustic signals with onboard motion sensor data to improve the underwater position tracking system. The developed system uses a long baseline (LBL) acoustic array of surface buoys to capture the Time-difference-of-Arrival (TDoA) of a multi-pulse beacon. We extract arrival times using a superimposed-envelope-spectrum (SES) detector, which exploits the beacon’s periodic structure to stay reliable even in heavy noise. These acoustic measurements are fused with six-degree-of-freedom IMU data using a particle f ilter (PF). The filter suppresses IMU drift and reveals how long dead-reckoning remains reliable before an acoustic update becomes essential. Simulation results demonstrated that our PF-TDoA fusion method achieved up to 40% reduction in mean localisation error compared to traditional fusion filters under harsh conditions. In our experiment, we compared the simulated IMU prediction with real-world acoustic measurements, and the resulting estimated fused positions remained within a 3m error throughout the experiment, demonstrating robust performance under operational conditions
Impact of exercise in patients with pancreatic cancer across different treatment phases: A systematic review
No full textBackground: With a dismal prognosis of 8–10 % 5-year survival since diagnosis, pancreatic cancer remains one of the most aggressive oncological diseases. This work aimed to evaluate the effects of exercise medicine on safety and feasibility, physical fitness, body composition, patient-reported outcomes, and clinical outcomes across different treatment phases in patients with pancreatic cancer. Method: PubMed, Cochrane, and Scopus databases were systematically screened to identify single-arm studies and randomized/non-randomized controlled trials investigating a physical exercise intervention in patients with pancreatic cancer. The RoB 2 and ROBINS-I tools were used to evaluate study quality for randomized and non-randomized studies, respectively. Qualitative and quantitative synthesis approaches were used. Results: Among the 5550 identified records, 11 randomized controlled trials and 6 non-randomized studies were considered eligible. Five investigations were conducted in the neoadjuvant setting, eight in the rehabilitative and three during palliative phases. Regarding neoadjuvant exercise, there were no significant changes in cardiorespiratory fitness and muscle strength, whilst a gain in muscle mass was detected. Similarly, in the rehabilitative setting, mixed results were observed for cardiorespiratory fitness and body composition; a positive impact was registered in strength, glucose levels, tryptophan metabolism, and quality of life after 3 months of intervention. In the palliative setting, significant improvements were observed for muscle strength and quality of life, but not for clinical outcomes. Conclusion: Although physical exercise may ameliorate sequelae of pancreatic cancer, further investigation is necessary to understand the real impact of exercise medicine interventions in this population and across different treatment phases
An exploration of turnover and retention of teachers in Western Australia who have experienced teacher directed violence (TDV)
No full textTeacher directed violence (TDV) has been defined as harmful physical or verbal aggression directed at teachers by students, parents, or colleagues. Whilst there is wide-ranging literature in student-to-student violence, TDV is an under-researched topic and yet is commonly reported in the Australian media. The limited research in this field suggests that TDV impacts teachers’ mental and physical health, the quality of teaching and learning, and financial and reputational cost for the school. To contribute to the limited research in this area, which has focused on quantitative data, this qualitative study explored TDV through the perspectives of Australian teachers to understand how their experiences influence their employment decisions. Underpinned by attribution theory, this study used an interpretative phenomenological approach (IPA) to interview 14 classroom teachers from both the primary and secondary school sectors in Western Australia. Semi-structured interviews were the source of data collection employed to investigate the types of TDV experienced, the perceived causes of TDV, and how these attributions affected teachers’ decisions to remain in the educational context or leave the profession completely. The data were analysed using IPA and the findings were categorised into seven group experiential themes. These themes were: blame; perpetrators; perpetrator behaviour; participant behaviour during the incident; participant behaviour after the incident; school leadership responses to TDV; and employment decisions after TDV. The significance of this research is to increase understanding of the implications of TDV and offer suggestions to staff and schools to support the welfare of teachers and reduce turnover and attrition. Three recommendations are offered; these concern what teachers need after a TDV incident; what the leadership team at school can do to support a teacher who has experienced TDV; and how this research can guide policy. Conclusions drawn from this research may inform policies and procedures within education and provide ideas regarding training for educators within the school environment
Bridging Traditions: A Mixed Methods Systematic Review Of Yoga For Trauma Recovery In Indigenous People
No full textObjective: The aim of this mixed methods systematic review was to explore if Yoga can alleviate mental health issues for Indigenous people, and how participants experience the effects.
Methods: Peer-reviewed primary research published in English retrieved from 2002 to March 2024 was identified using the databases Medline, Scopus, Informit, ProQuest and PsycINFO. Qualitative, quantitative and mixed method studies with Indigenous populations, where the primary intervention was Yoga or mindfulness programs with significant yoga components that reported on mental health outcomes were included.
Results: Only 5 studies met the inclusion criteria. The studies demonstrated significant improvements in mental health outcomes, including reductions in negative behaviors, psychological distress, perceived stress, and suicidality along with enhancements in quality of life, wellness, and self-regulation. The main theme through which participants understood the impacts of Yoga was through ‘Connection to body’ and its sub-themes of emotion regulation, positive emotions, and social and cultural connections. The review was limited by the small number of studies exploring the effects of Yoga in Indigenous populations.
Conclusions: This review shows that Yoga, alone and as part of MBSR, has the potential to significantly improve mental health outcomes for Indigenous people by enhancing emotion regulation, positive emotions, and social and cultural connections through a strong connection to the body
Addressing system strength shortfall in renewable energy integrated weak grid systems
No full textTo meet net-zero carbon emission targets, the energy sector is rapidly adopting renewable energy generators (REGs), such as solar farms, wind farms and battery storage systems. Consequently, conventional coal-based synchronous generators (SGs) are being phased out of generation fleets, which raises concerns about system strength and reliability shortfall. Along with increasing load demand, the deficiency of system strength poses a significant risk to system stability and can eventually lead to blackouts by disconnecting REGs from grid systems. Researchers and power engineers have suggested to deploy synchronous condensers (SynCons) as a mitigation strategy to address these system strength and reliability challenges. However, SynCons are expensive and require thorough investigation to ensure higher reliability before installation.
In this thesis, optimal sizes, placement and reliability assessment of SynCons are investigated. This thesis presents a solution that retains low SynCons-related costs and minimizes the loss of load probability (LOLP) while keeping the system strength above satisfactory levels. This thesis also investigates the long-term techno-economic feasibility of SynCons in terms of voltage recovery time, net present value and net profit for the next thirty years. A hybrid gated recurrent unit (GRU) optimisation framework is used to address the research questions.
To ensure post-fault operational stability, SynCons’ exciter controllers play a critical role. This thesis also investigates and presents a data-driven strategy for the optimal design of a H∞ exciter controller. Further to this, a system strength forecasting method is presented in this thesis. The developed method uses an online deep learning process comprised of a hedge feedforward feedback (HFF)- based online gated recurrent unit (GRU) learning algorithm.
The proposed solutions are validated in a modified IEEE 39 bus system. The obtained results show that the developed solutions reduced voltage recovery time in post-fault conditions and SynCons overall installation costs, representing higher economic benefit, improved control technique and higher forecasting accuracy
Bayesian Belief Networks: Redefining wholesale electricity price modelling in high penetration non-firm renewable generation power systems
Get PDFThe transition of electricity generation from firm to non-firm renewable generation is driving changes in wholesale electricity price dynamics that are increasingly challenging to model due to the stochastic nature of wind and solar as the primary energy source. Robust pricing models are essential for optimising financial performance in liberalised electricity markets. The novelty of this paper is the application of Bayesian Belief Networks in the modelling of wholesale electricity price formation, specifically in power systems with a high penetration of non-firm renewable generation. This paper links the mathematical Bayesian representation to established statistical and computational approaches using a functional supply-side wholesale electricity market pricing model. In addition, the paper introduces a novel validation method employing volatility analysis to assess the case study\u27s performance. The case study revealed that when the proportion of stochastic generation was ≥40 % penetration in a trading interval, the Bayesian Belief Network model\u27s accuracy considerably outperformed the benchmark model with a Mean Absolute Scale Error of 1.43 compared to 1.63 in those intervals. Finally, the volatility analysis results challenged the prevailing notion of a positive causal relationship between non-firm renewable penetration and price volatility
Circulating medium- and long-chain acylcarnitines are associated with plasma P-tau181 in cognitively normal older adults
Get PDFAlzheimer\u27s disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P-tau181), a recognised AD biomarker, has been described to reflect early-stage cortical amyloid-β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P-tau181 at the pre-clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P-tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted-mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)-Aβ load. In addition, the P-tau181-linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN Aβ− and CN Aβ+ individuals. Significant positive associations of medium- and long-chain acylcarnitines (ACs) were observed with P-tau181 in the entire cohort, CN Aβ− and CN Aβ+, suggesting a link between initial Aβ pathology and fatty acid oxidation-mediated energy metabolism pathways. However, in CN Aβ−, additional linear associations of P-tau181 were observed with muscle metabolism and nitric oxide homeostasis-associated metabolites. Upon investigating the P-tau181-linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN Aβ+ with medium- and long-chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET-Aβ load and inverse associations with hippocampal volume in CN Aβ+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET-Aβ status in older adults. Therefore, plasma P-tau181-linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross-sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings. (Figure presented.