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Four years on: Pregnancy and birth outcomes reported in the MSBase pregnancy, neonatal outcomes, and Women’s Health Registry (2020–2024)
No full textBACKGROUND: Family planning is an important aspect of multiple sclerosis (MS), and neuromyelitis optica spectrum disorder (NMOSD) management. Knowledge gaps remain, including optimal perinatal management strategies, and fetal risks associated with disease-modifying therapy (DMT) exposure. OBJECTIVE: To describe perinatal DMT use, together with pregnancy and neonatal outcomes prospectively recorded in the International MSBase Pregnancy and Women's Health Registry. METHODS: We report summary statistics for data collected between May 2020 and August 2024. RESULTS: A total of 1887 relapsing-remitting MS (RRMS), 12 primary-progressive MS (PPMS), 2 radiologically isolated syndrome (RIS) and 21 NMOSD completed pregnancies were recorded, including 1644 (85.5%) live births, 208 (10.8%) miscarriages, and 6 (0.3%) neonatal deaths. Most women had unassisted (53.8%) or assisted (7.4%) vaginal births. Seventy five percent of pregnancies had DMT exposures within 6 months preconception; 19% of NMOSD, and 62% of MS pregnancies were DMT-exposed during gestation; 18.1% of pregnancies reported in-pregnancy monoclonal antibody DMT exposure. No overt safety signals were seen. CONCLUSION: This first report from the newly launched MSBase pregnancy registry, establishes an increasing number of pregnancies being conceived on monoclonal antibody therapies. Although no safety signals were observed, it is important to continue monitoring for safety signals in real-world databases as the use of highly effective therapies continues to increase perinatally
Electrospun Carboxymethylcellulose as a Scaffold for Biomedical Applications
No full textAbstract
Electrospinning of pure carboxymethylcellulose (CMC) and its derivatives for biomedical applications is attractive due to their interesting biology and biomimetic properties. However, the main challenges in electrospinning pure CMC are strong electrostatic repulsions and its highly viscous nature. In this research, electrospun membranes consisting of grafted CMC-polyethylene glycol (CMC-PEG) and polycaprolactone (PCL) were successfully fabricated using emulsion electrospinning. Membranes with a PCL:CMC-PEG ratio of 80:20 formed uniform fiber with an average diameter of 930.2 ± 31.0 nm. Furthermore, PCL/CMC-PEG membranes demonstrated excellent mechanical properties suitable for use as scaffolds for soft tissue repair and skin wound healing. Water contact angle analysis showed that the incorporation of grafted CMC-PEG improved the membrane wettability. Electrospun membranes with a PCL: CMC-PEG ratio of 80:20 exhibited the highest in vitro degradation, with 82.0 ± 8.7% weight loss over 10 weeks of incubation. In vitro studies confirmed the non-cytotoxic properties of PCL:CMC-PEG (80:20) membranes when tested with normal human dermal fibroblast (NHDF) cells. Morphological analysis further confirmed the attachment of NHDF cells followed by cell proliferation and migration. These membranes demonstrated optimal mechanical properties, hydrophilicity, and biocompatibility, making them promising tissue scaffolds for tissue engineering and regenerative medicine applications.
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Mean-variance longevity risk-sharing for annuity contracts
No full textThis paper investigates longevity risk-sharing as a solution to the sustainability and affordability problems in the annuity market, and in particular how much longevity risk could be transferred back to policyholders assuming mean-variance preference functions. First, it provides dynamic risk-sharing rules for annuities. Second, it studies the contract properties from the perspectives of both the provider and individual policyholders. Third, it highlights and accounts for two levels of uncertainty and two levels of correlation induced by systematic longevity risk. Fourth, it provides necessary and sufficient conditions on the premium loading and the share of transferred risk, such that both parties prefer risk-sharing. The analytical and numerical results of the paper offer a deeper understanding of the effects of systematic and diversifiable risks on those preferences, and show that the products presented in this paper are suitable retirement solutions
Effect of ocean surface waves on sea ice using coupled wave–ice–ocean modelling
No full textThe reduction of ice content in the context of climate change in polar oceans has sparked strong scientific interest in wave–ice interactions. To study the wave effect on sea ice in the marginal ice zone (MIZ), wave model WW3 and ocean–ice model MOM6-SIS2 are fully coupled by implementing schemes to account for non-breaking wave-induced turbulence and wave stress on ice. Improved estimations of ocean mixed layer depth and sea ice extent are achieved by incorporating the parameterizations of wave effects. The results also show that wave-induced turbulence enhances upper ocean mixing and significantly impedes ice growth with warmed sea surface in winter. Conversely, the sea surface is cooled in summer and the sea ice melt is slowed down. The wave stress on ice is predominantly directed towards the ice field and is comparable in magnitude to the wind stress. The sea ice extent is increased due to the wave stress
Reversal of metformin’s anti-proliferative effect in fission yeast efr3 and dnm1 (DRP1) mutants with elongated mitochondria
No full textMetformin is a well-tolerated drug frequently prescribed for managing type 2 diabetes. Extended metformin use has been linked to a significant decrease in cancer incidence across both diabetic and non-diabetic populations. Here we investigate the anti-proliferative effects of metformin on fission yeast S. pombe. Our findings demonstrate that metformin’s inhibitory impact on cell proliferation is effective in the absence of AMP-activated protein kinase (AMPK). Using an unbiased genetic screen we identified the plasma membrane signalling scaffold Efr3, critical for phosphatidylinositol signalling and the generation of PI4Ps, as a key determinant of resistance to the anti-proliferative effect of metformin. Deletion of efr3 resulted in both AMPK-dependent and AMPK-independent resistance to metformin. We show that Efr3 does not influence cell proliferation by controlling Ras1 activity or its cellular localization in yeast. We observe that dnm1 (DRP1) mutants with elongated mitochondria are also resistant to the anti-proliferative effect of metformin and that metformin treatment promotes mitochondrial fusion. Metabolic measurements after prolonged metformin exposure demonstrated a reduction in respiration in both wild type and the efr3 deletion, however, that reduction is less pronounced in the efr3 deletion, which also contained elongated mitochondria. It is likely that mitochondrial fusion enhances yeast fitness in response to metformin exposure. Together we provide a new perspective on the cellular response to metformin
Evidence for increased animal pollination during the Paleocene-Eocene thermal maximum
No full textAbstract
The Paleocene–Eocene thermal maximum (PETM) was the largest early Cenozoic hyperthermal event, one of a series of carbon cycle and climate perturbations marked by massive releases of carbon into the atmosphere and spikes in global temperature. Previous studies have documented major changes in the composition of terrestrial plant and animal communities during the PETM, as well as changes in arthropod herbivory. Here, we examine possible changes in pollination mode during the PETM in the Bighorn Basin, Wyoming, USA, as inferred from three lines of evidence: (1) the prevalence of fossil pollen preserved as clumps, (2) the pollination mode of nearest living relatives (NLR), and (3) angiosperm pollen morphological diversity. These suggest animal pollination became more common and wind pollination less common during the PETM. The decrease in wind pollination during the PETM reflects the basin-scale extirpation of wind-pollinated lineages and their replacement by dominantly animal-pollinated lineages concomitant with rapid warming and drying. The hotter and seasonally drier climates not only facilitated the northward range shift of plant taxa, but likely their insect and/or vertebrate pollinators as well. The dramatic floral changes during the PETM in the Bighorn Basin may also have changed available resources for insect and/or vertebrate pollinators
Using Codesign to Develop a Health Literacy Intervention to Improve the Accessibility and Acceptability of Cardiac Services: The Equal Hearts Study
No full textINTRODUCTION: The burden of coronary heart disease (CHD) is disproportionately greater among socio-economically disadvantaged groups. Health services play a crucial role in addressing this social gradient by ensuring equitable access to care. However, there is limited evidence on effective strategies to improve health service accessibility for CHD patients, particularly those that are codesigned with people with lived experience and clinicians. The Equal Hearts study aimed to codesign a health literacy-based intervention to improve the accessibility of hospital-based cardiac services for underserved population groups with CHD. METHODS: This study employed a mixed-methods approach based on codesign principles. The study comprises three phases: identifying and understanding the problem, codeveloping an intervention, and translating the intervention into practice. Phases 1 and 2 are reported in this paper and included focus groups, interviews and an intervention development workshop. Participants for focus groups and interviews were recruited from four health services in [Victoria] and included patients with CHD, health consumers from culturally diverse communities and clinicians. Findings from focus groups and interviews were analysed via thematic analysis using Levesque's conceptual framework to identify health literacy barriers to accessibility of cardiac services. These barriers were prioritised in a codesign workshop with cardiac patients, health consumers and clinicians. RESULTS: Thirty-seven cardiac patients, 10 clinicians and 44 culturally diverse health consumers participated in focus groups/interviews. Among these participants, eight cardiac patients/carers and five clinicians attended the workshop. Cardiac patients reported a lack of preparedness for hospital discharge and feeling 'lost' and uncertain about how to confidently manage their health at home after a cardiac event. A codesigned intervention-The Patient Discharge Action Plan-aims to improve patients' transition from hospital to home. CONCLUSION: Using a codesign approach and health literacy principles, a health service intervention was developed to improve accessibility of cardiac services. The Patient Discharge Action Plan is currently being evaluated in a pilot RCT. PATIENT OR PUBLIC CONTRIBUTION: Two consumer co-authors [L.F.J. and J.H.] informed the development of the study protocol. A Stakeholder Advisory Panel, including six people with lived experience of CHD and four clinicians/health service managers from participating sites, guided all steps within this study. TRIAL REGISTRATION: ACTRN12624000780550p (Australian and New Zealand Clinical Trials Registry). Registered on 25 June 2024
Interleaved iTBS-fMRI for assessing neural circuit engagement in ultra treatment-resistant depression
No full textAddressing the unmet needs of bipolar disorder in Australia and beyond
No full textPeople impacted by bipolar disorder are confronted by many unmet needs that contribute to the overall burden associated with the disorder. We do not have a good understanding of the underlying pathology of bipolar disorder, so we do not have biomarkers to accurately identify those who are at risk of developing the disorder. Delayed diagnosis is the norm, and it can take a decade or more for an individual to receive a diagnosis and to start appropriate treatment. We have evidence-based treatments such as lithium and psychosocial therapies; however, their availability and use are limited. We need a consolidated approach to advance indicated prevention and early intervention for bipolar disorder. In this viewpoint article, we describe these barriers in detail as well as introduce international and national work that is being done to progress the field. At the national level, we introduce the National Health and Medical Research Council Centre for Research Excellence in Bipolar Disorder. The Centre for Research Excellence in Bipolar Disorder comprises a multidisciplinary team of experts from Australia and internationally who are working together to develop a better understanding of opportunities for indicated prevention and early intervention as well as to improve interventions for those impacted by the disorder. Here we describe our research framework, stakeholder engagement activities and strategies for workforce development and capacity building. Ultimately by working together we will attempt to address many of issues faced by individuals impacted by bipolar disorder