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Trends in Practice Patterns and Clinical Outcomes for Desmoid Tumors: A Large Single-Institutional Australian Cohort
No full textBACKGROUND: Desmoid tumors (DT) are rare, locally aggressive neoplasms that affect a young population and have a tendency for recurrence. There is sparse contemporary real-world data to guide practice for DT. Here, we report on a large cohort of DT patients, describing patterns of care and clinical outcomes. METHODS: Data on DT patients first seen between 2010 and 2021 were extracted from a prospective database and supplemented with a retrospective review of hospital records. Trends in treatment use were analyzed using the Cochran-Armitage test. Time-to-next intervention (TTNI) was estimated with the Kaplan-Meier method. Imaging response was categorized using the RECIST v1.1 criteria. RESULTS: A total of 135 patients, 265 treatment episodes were analyzed. Median follow-up was 4.3 years. The common tumor sites were abdominal wall (27%), upper limb (20%), lower limb (16%), and intra-abdominal (15%). Over time, the proportion of patients receiving no upfront treatment was stable (2010-2013: 31%, 2014-2017: 35%, 2018-2021: 29%; p = 0.5), but there was increasing first-line use of NSAID/tamoxifen (7%, 41%, 47%; p < 0.001), and decreasing first-line use of radiotherapy (35%, 14%, 4%; p < 0.001) and surgery (28%, 8%, 18%; p < 0.05). At 5 years, the proportion not requiring treatment switch was highest following surgery (72%), radiotherapy (66%), and no upfront therapy (52%). 12% and 5% of patients without treatment achieved partial and complete imaging responses at 2 years. CONCLUSION: We highlight the heterogeneity and trends in DT management over a 12-year period, affirming the role of active surveillance, radiotherapy, and surgery in selected patients. Medical therapies are evolving and may significantly influence the DT management paradigm
Authorship Across Media: Considering Wednesday Addams
No full textA storyworld across media presents scholars of authorship, creativity and cultural production with opportunities to consider how authorship and author ‘brand’ influence character, plot and audience interaction over time and across formats. This article explores authorship in transmedial storyworlds, employing three different but interrelated theoretical models–media franchises, artistic spawning and distributed authorship–to analyse Netflix’s 2022 teen drama series, Wednesday, and its position within contemporary culture and the Addams Family universe. Collaborating as literary studies, screen studies, publishing studies and cultural labour researchers, we demonstrate the strength of ‘close cross-disciplinarity’ as a method of analysis for authorship and transmedial storyworlds
Oxytocin in old age psychiatry: A systematic review of the safety of using intranasal oxytocin in older adults
No full textOBJECTIVES: To examine the literature for evidence of adverse events associated with the use of intranasal oxytocin in older adults (60+). METHODS: A systematic review was undertaken according to PRISMA guidelines. Peer-reviewed literature was searched for studies involving intranasal oxytocin use in older populations. The Joanna Briggs Institute's (JBI) critical appraisal tool was used to assess the quality of included studies. RESULTS: The search identified nine randomized controlled trials (RCTs) that investigated the effects of intranasal oxytocin on a total sample size of 331 older participants. Adverse effects associated with oxytocin administration were predominantly mild and varied inconsistently between studies. Compared to placebo intranasal oxytocin was not significantly associated with severe adverse outcomes in doses ranging from 24 to 72 IU after single dose and or repeated doses in the short-term. CONCLUSION: In a population of older adults, intranasal oxytocin is devoid of serious adverse events. Although this review offers valuable insights, it may not fully reflect the potential adverse events associated with the long-term administration of intranasal oxytocin such as would be expected in its clinical application if approved for the treatment of dementia
The diagnostic pathway of Parkinson’s disease: understanding patient perspectives in Australia
No full textThere is limited data about experiences of people with Parkinson's (PwP) in Australia. This study, initiated and co-designed by PwP, surveyed 385 participants nationally (335 fully completed the questionnaire). Participants living in capital and regional city centers reported satisfaction with clinical care during diagnostic consultation at approximately 40%, with satisfaction less in rural areas (26%). 68% of participants reported inadequate involvement in discussions about treatment and care planning and 77% were dissatisfied with the support following diagnosis. Respondents reported low referral rates to allied health services such as physiotherapy (22%) and mental health services (17%). Feedback indicated support could improved by increased access to Parkinson's disease Clinical Nurse Specialists and to educational resources and support. Findings highlight the need to establish Australian guidelines for Parkinson's clinical management, greater resourcing for clinicians including development of educational programs, and creation of Australian-centric educational resources to improve quality of care for PwP
First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
No full textPredicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsing-remitting MS (RRMS). We recruited patients from MSBase Registry covering the period between 1996 and 2022. All patients were diagnosed with RRMS and actively followed-up for at least 5 years to explore the following outcomes: clinical relapses, confirmed disability worsening (CDW) and improvement (CDI), EDSS 3.0, EDSS 6.0, conversion to secondary progressive MS (SPMS), new MRI lesions, Progression Independent of Relapse Activity (PIRA). Predictors included demographic, clinical and radiological data, and sub-optimal response (SR) within the first year of treatment. Female sex (HR 1.27; 95 % CI 1.16–1.40) and EDSS at baseline (HR 1.19; 95 % CI 1.15–1.24) were independent risk factors for the occurrence of relapses during the first 5 years after diagnosis, while high-efficacy treatment (HR 0.78; 95 % CI 0.67–0.91) and age at diagnosis (HR 0.83; 95 % CI 0.79–0.86) significantly reduced the risk. SR predicted clinical relapses (HR = 3.84; 95 % CI 3.51–4.19), CDW (HR = 1.74; 95 % CI 1.56–1.93), EDSS 3.0 (HR = 3.01; 95 % CI 2.58–3.51), EDSS 6.0 (HR = 1.77; 95 % CI 1.43–2.20) and new brain (HR = 2.33; 95 % CI 2.04–2.66) and spinal (HR 1.65; 95 % CI 1.29–2.09) MRI lesions. This study highlights the importance of selecting the appropriate DMT for each patient soon after MS diagnosis, also providing clinicians with a practical tool able to calculate personalized risk estimates for different outcomes
Advances in Oxygen Evolution Reaction Electrocatalysts via Direct Oxygen–Oxygen Radical Coupling Pathway
No full textOxygen evolution reaction (OER) is a cornerstone of various electrochemical energy conversion and storage systems, including water splitting, CO2/N2 reduction, reversible fuel cells, and rechargeable metal-air batteries. OER typically proceeds through three primary mechanisms: adsorbate evolution mechanism (AEM), lattice oxygen oxidation mechanism (LOM), and oxide path mechanism (OPM). Unlike AEM and LOM, the OPM proceeds via direct oxygen–oxygen radical coupling that can bypass linear scaling relationships of reaction intermediates in AEM and avoid catalyst structural collapse in LOM, thereby enabling enhanced catalytic activity and stability. Despite its unique advantage, electrocatalysts that can drive OER via OPM remain nascent and are increasingly recognized as critical. This review discusses recent advances in OPM-based OER electrocatalysts. It starts by analyzing three reaction mechanisms that guide the design of electrocatalysts. Then, several types of novel materials, including atomic ensembles, metal oxides, perovskite oxides, and molecular complexes, are highlighted. Afterward, operando characterization techniques used to monitor the dynamic evolution of active sites and reaction intermediates are examined. The review concludes by discussing several research directions to advance OPM-based OER electrocatalysts toward practical applications
Modes and mechanisms for the inheritance of mitochondria and plastids in pathogenic protists
No full textPathogenic protists are responsible for many diseases that significantly impact human and animal health across the globe. Almost all protists possess mitochondria or mitochondrion-related organelles, and many contain plastids. These endosymbiotic organelles are crucial to survival and provide well-validated and widely utilised drug targets in parasitic protists such as Plasmodium and Toxoplasma. However, mutations within the organellar genomes of mitochondria and plastids can lead to drug resistance. Such mutations ultimately challenge our ability to control and eradicate the diseases caused by these pathogenic protists. Therefore, it is important to understand how organellar genomes, and the resistance mutations encoded within them, are inherited during protist sexual reproduction and how this may impact the spread of drug resistance and future therapeutic approaches to target these organelles. In this review, we detail what is known about mitochondrial and plastid inheritance during sexual reproduction across different pathogenic protists, often turning to their better studied, nonpathogenic relatives for insight
A polytherapy approach demonstrates therapeutic efficacy for the treatment of SOD1 associated amyotrophic lateral sclerosis
No full textBackground: SOD1 mutations are a significant contributor of familial amyotrophic lateral sclerosis (ALS) cases. SOD1 mutations increase the propensity for the protein to misfold and aggregate into insoluble proteinaceous deposits within motor neurons and neighbouring cells. The small molecule, CuATSM, has repeatedly shown in mouse models to be a promising therapeutic treatment for SOD1-associated ALS and is currently in Phase II/III clinical trials for the treatment of ALS. We have previously shown CuATSM stabilises various ALS-associated variants of the SOD1 protein, reducing misfolding and toxicity. Two additional FDA-approved small molecules, ebselen and telbivudine, have also been identified to reduce mutant SOD1 toxicity, providing additional potential therapeutic candidates that could be used in combination with CuATSM. Here, we aimed to investigate if CuATSM, ebselen and telbivudine (CET) polytherapy could improve on the therapeutic efficacy of CuATSM monotherapy for the treatment of SOD1-associated ALS. Methods: We utilised a 3D checkerboard approach to investigate whether a matrix of different concentrations CuATSM, ebselen and telbivudine could provide therapeutic improvements on cell survival, SOD1 folding and aggregation in SOD1G93A-transfected NSC-34 cells, compared to CuATSM alone. To progress the preclinical development of CET polytherapy, we evaluated the bioavailability and safety of in vivo polytherapy administration. Furthermore, we assessed and compared the effects of CET- and CuATSM-treatment on disease onset, motor function, survival and neuropathological features in SOD1G93A mice. Findings: CET polytherapy reduced inclusion formation and increased cell survival of NSC-34 cells overexpressing SOD1G93A compared to higher concentrations of CuATSM monotherapy. In addition, CET administration was bioavailable and tolerable in mice. CET treatment in SOD1G93A mice delayed disease onset, reduced motor impairments, and increased survival compared to vehicle- and CuATSM-treated mice. In line with these findings, biochemical analysis of lumbar spinal cords showed CET administration improved SOD1 folding, decreased misfolded SOD1 accumulation, and reduced motor neuron loss. Interpretation: These findings support CET polytherapy as an advantageous alternative compared to CuATSM monotherapy and highlight the potential of utilising small molecules targeting SOD1 as a polytherapy avenue for the treatment of SOD1-associated ALS. Funding: This work was supported by a FightMND Drug Development Grant, an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (No. 1194872) and a Motor Neuron Disease Research Institute of Australia Bill Gole Postdoctoral Fellowship
Parkinson-like wild-type superoxide dismutase 1 pathology induces nigral dopamine neuron degeneration in a novel murine model
No full textAtypical wild-type superoxide dismutase 1 (SOD1) protein misfolding and deposition occurs specifically within the degenerating substantia nigra pars compacta (SNc) in Parkinson disease. Mechanisms driving the formation of this pathology and relationship with SNc dopamine neuron health are yet to be fully understood. We applied proteomic mass spectrometry and synchrotron-based biometal quantification to post-mortem brain tissues from the SNc of Parkinson disease patients and age-matched controls to uncover key factors underlying the formation of wild-type SOD1 pathology in this disorder. We also engineered two of these factors - brain copper deficiency and upregulated SOD1 protein levels - into a novel mouse strain, termed the SOCK mouse, to verify their involvement in the development of Parkinson-like wild-type SOD1 pathology and their impact on dopamine neuron health. Soluble SOD1 protein in the degenerating Parkinson disease SNc exhibited altered post-translational modifications, which may underlie changes to the enzymatic activity and aggregation of the protein in this region. These include decreased copper binding, dysregulation of physiological glycosylation, and atypical oxidation and glycation of key SOD1 amino acid residues. We demonstrated that the biochemical profile introduced in SOCK mice promotes the same post-translational modifications and the development of Parkinson-like wild-type SOD1 pathology in the midbrain and cortex. This pathology accumulates progressively with age and is accompanied by nigrostriatal degeneration and dysfunction, which occur in the absence of α-synuclein deposition. These mice do not exhibit weight loss nor spinal cord motor neuron degeneration, distinguishing them from transgenic mutant SOD1 mouse models. This study provides the first in vivo evidence that mismetallation and altered post-translational modifications precipitates wild-type SOD1 misfolding, dysfunction, and deposition in the Parkinson disease brain, which may contribute to SNc dopamine neuron degeneration. Our data position this pathology as a novel drug target for this disorder, with a particular focus on therapies capable of correcting alterations to SOD1 post-translational modifications
The effectiveness of a positive education program on the resilience and well-being of adolescents across different family structures
No full text© 2025 Peta Maria TaylorIncreasing rates of adolescent mental ill health and suboptimal wellbeing outcomes have prompted a growing emphasis on school based programs that aim to provide young people with the foundational skills needed to navigate this developmental phase successfully. Whilst programs aim to foster resilience and wellbeing, evidence of their effectiveness and relevance across diverse groups remains limited.
This thesis comprises two studies exploring the effectiveness of a customised Positive Education Program (PEP) on the resilience and well-being of adolescents within family unit, compared to a control group. Study One addressed the absence of a consistent definition of resilience by examining both a subjective measure (Connor-Davidson Resilience Scale) and an objective measure (Heart Rate Variability). It further explored the relationship between resilience and well-being to determine whether resilience predicts well-being outcomes. Correlational analyses revealed no significant relationship between the two resilience measures, indicating neither could serve as proxy for the other. Furthermore, they do not equally predict wellbeing outcomes. However, hierarchical regression analyses demonstrated that subjective resilience significantly predicted psychophysiological wellbeing. In contrast, the objective resilience measure appeared to reflect coping mechanisms rather than resilience itself.
Study Two, was a mixed-method study examining data from Year 10 cohorts at two Australian state high schools (N=282) across three time points: pre intervention, post intervention and 6 month follow-up. PEP participants reported improved levels of resilience and well-being outcomes (engagement, perseverance and optimism) compared to the control group. Program outcomes were further examined through the retrospective application of the RE AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). To systematically assess adherence to framework categories, three independent raters evaluated the framework’s application across factors using a pre agreed percentage-based rating scheme. Findings revealed that reach and engagement were strong, evidenced by high participation rates. However, adherence declined over time, with implementation weakened by inconsistent delivery and reduced fidelity, and maintenance hindered by declining participation and limited sustainability.
Given ongoing criticism in the literature regarding the ability of PEPs to produce significant and sustainable results, particularly for disadvantaged or at risk students, Study Two also examined family structure as a potential classification tool for differing student needs. A series of analyses of variance (ANOVAs) and analysis of covariance (ANCOVA) found that family structure alone was insufficient for effectively categorising students according to resilience and well-being outcomes.
Together, these findings highlight several implications. First, resilience is a multidimensional construct not adequately captured by a single measure; subjective self reports and physiological markers assess different phenomena and cannot substitute for each other. Second, PEPs can deliver short-term benefits in resilience and well being but face challenges with long-term implementation and sustainability, underscoring the need to apply the RE AIM framework to enhance program outcomes and address existing criticisms. Third, while family structure is a readily available data point, it is not a sufficient standalone indicator of student need. Combined with other indicators, it may inform program customisation to better support students. Given the critical importance of improving adolescent wellbeing and reducing rates of mental ill health, these considerations warrant important opportunities for future research and practice