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Chromatin remodeling factor BAF155 coordinates oligodendroglial-neuronal communications linked to regional myelination and autism-like behavioral deficits in mice.
Get PDFAutism spectrum disorders (ASD) are neurodevelopmental disorders associated with synaptic deficits. Oligodendrocyte precursor cells (OPCs) are the only type of glial cells that establish direct synaptic connections with neurons within the central nervous system (CNS). However, the mechanism that results in the delicate construction of OPC-neuron synaptic connections remain poorly understood. Here we show in a mouse model that BAF155, a chromatin remodeling factor, is highly expressed in committed OPCs. BAF155 influences the OPC differentiation and myelination by coordinating the expression of multiple synapse-related genes that mediate OPC-neuron synaptic communication. The varying chromatin regulatory roles of BAF155 across brain regions give rise to local myelin deficits, contributing to the diverse clinical manifestations observed in individuals with ASD. Collectively, these results deepen our insight into OPC-neuron interactions under pathophysiological conditions and uncover a mechanism that integrates synaptic and ASD susceptibility genes, implying that abnormal OPC-neuron synaptogenesis could be an early instigator of ASD
Reducing inpatient deterioration and improving patient safety in emergency departments with a standardised nursing framework: A stepped-wedge cluster randomised controlled trial.
Get PDFBACKGROUND: Patients admitted via Emergency Departments (EDs) sustain twice as many in-hospital adverse events than non-emergency admissions. Unwarranted variation in care, that is, differences not explained by patient illness, care needs, or patient preferences, contributes to adverse patient outcomes. The HIRAID® framework [History including Infection risk, Red flags, Assessment, Interventions, Diagnostics, reassessment, and communication], standardises nursing assessment and management of patients in the ED. The aim of this study was to test the effect of HIRAID® on the quality and safety of emergency care. METHODS: A modified (staircase) stepped-wedge, cluster randomised controlled trial was conducted in 29 Australian metropolitan, regional, rural Emergency Departments involving 1377 nurses from June 2020 to February 2024. The 29 Emergency Departments were allocated to four clusters and randomised to one of four sequences, with three-six month intervention periods. HIRAID® was implemented with a multifaceted strategy comprising 21 behaviour change techniques including an education program, and modifications to nursing documentation. The primary outcome was inpatient deterioration as evidenced by a rapid response team call within 72 h of admission via ED. Secondary outcomes were the proportion of rapid response team calls where emergency nursing care was a contributor; time to first dose analgesia; patient/carer experience with emergency nursing care; and staff satisfaction with clinical handover. Contributing factors to 2211 inpatient rapid response team calls within 72 h of admission via emergency department were categorised using the Human Factors Classification Framework. Time to analgesia was extracted during medical record review (n = 1374). Patient experience (n = 2704) and clinical handover quality were measured using surveys (n = 1205 nurses). A regression approach was used to model the effect of HIRAID® implementation on primary outcomes adjusting for cluster effects and confounders. RESULTS: Of the 106,047 patients admitted via the ED, there were 2729 (1342 control, 1387 intervention) patients with a rapid response call within 72 h of admission. HIRAID® reduced the proportion of patients requiring a rapid response team call by 7.4 % (OR = 0.92, 95 % CI = 0.81-0.99) including 8.2 % fewer calls related to emergency nursing care (47 % to 38.8 %, OR = 0.72, 95 % CI = 0.56-0.93). Patient experience improved in all measures, particularly feeling more informed (OR = 1.74, 95 % CI = 1.37-2.19). There was no change in time to first analgesia. There was a 7.0 % improvement in handover of relevant history (t = 5.57, p < 0.001) and physical assessment (t = 4.72, p < 0.001). CONCLUSION: Emergency nurses' use of HIRAID® significantly reduced inpatient deterioration requiring a rapid response team call and improved patient experience and perceived quality of clinical handover. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 25 October 2021, (ACTRN12621001456842), recruitment commenced 6 November 2020. Social media abstract: Implementing HIRAID® reduces patient deterioration. More info here #HIRAID
Layered Exception: LGBT Life and Survival in Pandemic-lockdown China
Get PDFThis article examines how Chinese LGBT individuals experienced intensified marginalisation during the Covid-19 pandemic, arguing that queer life under lockdown was shaped by what we term “layered exception” – a condition produced by the intersection of state lockdown governance and heteronormative domestic discipline. Drawing on in-depth interviews with 55 queer individuals and HIV/AIDS NGO workers, alongside online observations from various LGBT forums, the study identifies three key findings. First, under China’s stringent lockdown policies, LGBT individuals were subjected to a new regime of control – “home-as the-rule” – in which the heteronormative family, rather than the state, became the primary site of surveillance, coercion, and moral discipline. Second, the prolonged lockdown disrupted everyday “technologies of the self,” suspending flexible identity expression, cross-border mobility and intimate autonomy. Digital intimacy practices such as textual love and flirtatious banter emerged as alternative forms of connection, amid heated online tensions between “lying flat” advocates normalising everyday risk and “zero-Covid” supporters endorsing state-imposed restraint. Third, the medical precarity faced by HIV-positive men who have sex with men (MSM) reveals an additional layer of exception: these individuals were not only excluded from familial and state recognition, but were also rendered invisible within China’s public health infrastructure, placing them at risk of being effectively “left to die.” Taken together, these findings demonstrate how the lockdown deepened queer precarity in China
Navigating grief Pedagogy in Midwifery: Insights from interviews with clinical midwifery educators.
Get PDFOBJECTIVE: To explore Australian Clinical Midwifery Educators' perceptions of the barriers and enablers to facilitating midwifery students' clinical learning experiences in perinatal loss and grief care. METHOD: A qualitative descriptive design was used. Ten Clinical Midwifery Educators participated in semi-structured Zoom interviews. Data were analysed using thematic analysis. RESULTS: Seven themes emerged, five barriers and two enablers. Barriers included the low prioritisation of perinatal loss education, protective attitudes toward students and women, the emotional and practical challenges of teaching this sensitive topic, and the impact of busy clinical environments. Enablers included students' emotional readiness and the role of universities as safe spaces to initiate learning and discussion. These findings highlight the complexity of preparing students for perinatal grief care and the need for systemic educational reform. CONCLUSION: Graduating midwifery students often lack the knowledge, skills, and confidence to provide evidence-informed, woman-centred care in the context of perinatal loss and grief. Limited clinical exposure contributes to this gap, leaving students underprepared for emotionally complex care situations. Midwifery students require structured, supported exposure to perinatal loss care to build emotional resilience and clinical competence. A shift in mindset is needed to balance protection with preparation. Strengthening university curricula, enhancing collaboration with clinical settings, and prioritising mental preparedness are essential. Future research should examine the impact of pre-registration exposure on graduate midwives' readiness to provide bereavement care
Clinician perspectives on the process of change in an adolescent eating disorder Day Program.
Get PDFBACKGROUND: Despite suggestions that Day Programs can be efficacious, little is understood about which mechanisms create positive change for young people and their family in this setting. The aim of this study was to explore clinician perspectives on how change occurs in an adolescent eating disorder Day Program in Australia. METHODS: Twelve clinicians working as a team on an adolescent Day Program participated in semi-structured qualitative focus groups. Focus groups explored the clinicians' perspectives on change processes in the Day Program treatment model and the impact on young people and their families. Data generated from each focus group was analysed using reflexive thematic analysis. RESULTS: The structure, predictability and intensity of the Day Program along with tailored and responsive treatment was perceived as leading to a main theme of structural containment. Additionally, the combination of a strong relational treatment focus with team mutuality was perceived as leading to a second main theme of relational containment. The combination of structural and relational containment for families was perceived by clinicians as the leading mechanisms in supporting parental effectiveness in treatment and the settling and engaging of the young people. Levels of containment were also understood to create safety for all (parents, young people, and clinicians) providing a wraparound approach allowing effective treatment to be delivered. CONCLUSIONS: The findings of this study speak to the importance of safety as a foundation for working with families needing higher levels of care. Treatment approaches that are both structurally and relationally containing might be needed for families requiring more intensive care. Findings also highlight the importance of the clinical team working cohesively and the potential need for clinicians/services to consider how to create a therapeutically supportive environment that maximises the effectiveness of treatment
The effect of exercise on left ventricular global longitudinal strain.
Get PDFExercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre-post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59; 95% CI 0.16-1.02; p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed
Explainable image segmentation for spatio-temporal and multivariate image data in precipitation nowcasting
Get PDFArtificial Intelligence (AI) systems are often opaque in nature, making it difficult to understand the region-of-interest in the input for the predictions. This creates a challenge in convincing people who rely on traditional methods to trust the outputs of automated systems. This study presents a novel framework based on Integrated Gradients (IG) with a U-Net to interpret multivariate, spatio-temporal input sequences for precipitation nowcasting. We utilize Integrated gradients methods to explain the predictions made by a deep learning model for precipitation nowcasting, which takes a multi-image sequence as its input. We use the Meteonet dataset by MeteoFrance and form it into a spatio-temporal multivariate dataset consisting of rain radar, satellite, and wind images to predict rainfall 30 minutes ahead. We employ the U-Net model and evaluate the model's explainability using Integrated gradients. The resulting system achieves an F1 score of 0.760 and a Critical Success Index of 0.613 on an unseen 2018 test set, matching state-of-the-art radar-only baselines while providing pixel-level attributions. Our results help to explain the reasons behind the predictions. The obtained visual representation offers potential explanations for the classification of spatio-temporal or multivariate datasets. Additionally, this study provides a comparative analysis of the level of contribution of each image in the input sequence to the final result. Removing the eight least-important frames identified by IG reduces the input by 73%, yet preserves performance (F1 = 0.759 vs 0.760). Consequently, the proposed approach shows its usability in dimensionality reduction, enhancing the interpretability and efficiency of the predictive model
Effects of Pre-cooling and Cooling Breaks on Thermoregulatory, Physiological and Match Running Responses During Football in Moderate and Hot Temperatures.
Get PDFPURPOSE: This study investigated the effects of pre-cooling and cooling breaks on thermoregulatory, hydration and running responses in football (soccer) players in moderate and hot temperatures. METHODS: Forty male youth footballers participated in at least two of four matches, during which core body temperature (Tcore), heart rate (HR), match running, hydration and perceptual responses were measured. Cooling breaks (CBs), consisting of ice-cold towels and drinks, were compared to drinking breaks (DBs), consisting of passive rest and a temperate drink, applied at the same timeframes. Both were used as pre-cooling for 10 min before the warm-up, before the pre-match, during half-time and during additional 3-min cooling breaks at the 25th minute of each half. Initially, 20 players performed two crossover matches in 25 °C wet-bulb globe temperature (WBGT) receiving cooling (CB25) and drinking (DB25). A second group of 20 players played a regular match in 25 °C WBGT with no breaks (NB25) and then a match in 33 °C WBGT during which they received either cooling (CB33) or drinking breaks (DB33). RESULTS: In CB25, players felt cooler (p 0.20), HRmean (p > 0.35) or Tcore (p > 0.09). Players in CB25 sweated less (p = 0.005) and drank less (p = 0.002), resulting in no significant difference in body mass loss compared to DB25. In CB33, players had lower HRmean (p = 0.007), similar total distance (p = 0.21), lower peak Tcore (p < 0.001) and lower body mass loss (p = 0.007) compared to NB25. In DB33, players reduced moderate (12-18 km/h; p = 0.007) and high-speed running distance (18-24 km/h; p = 0.002) but had similar peak Tcore (p = 0.71) and body mass loss (p = 0.95) to that in NB25. CONCLUSIONS: In general, high Tcore values and body mass losses were observed even when playing in moderate heat. Both drinking and cooling breaks attenuated the continuous Tcore rise, but using cooling also improved player perceptions in moderate temperatures. In hotter temperatures, cooling breaks further lowered Tcore and body mass loss compared to using only drinking breaks. TRIAL REGSISTRY: German Clinical Trials Register: DRKS00032208
Clinical service organisation for adults with atrial fibrillation: Cochrane systematic review and meta-analysis.
Get PDFAIMS: This study aims to assess the effects of organized clinical service delivery models for atrial fibrillation (AF) on all-cause mortality and hospitalization, as well as cardiovascular outcomes, thromboembolic events, bleeding complications, quality of life, symptom burden, healthcare costs, and length of hospital stay. METHODS AND RESULTS: A systematic search was conducted across several databases, including Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL, and clinical trial registries. Randomized controlled trials involving adults (≥18 years) with any type of AF were included. Primary outcomes were all-cause mortality and all-cause hospitalization. Secondary outcomes included cardiovascular mortality and hospitalization, AF-related emergency department visits, thromboembolic and bleeding events, quality of life, symptom burden, cost of intervention, and length of hospital stay. Eight studies (8205 participants) investigating collaborative, multidisciplinary, or virtual care models for AF were included. The mean age of participants ranged from 60 to 73 years. Organized AF clinical services likely resulted in a substantial reduction in all-cause mortality [risk ratio (RR) 0.64, 95% confidence interval (CI) 0.46-0.89; moderate certainty] and cardiovascular hospitalization (RR 0.83, 95% CI 0.71-0.96; high certainty) compared with usual care. However, these services probably made little to no difference to all-cause hospitalization (RR 0.94, 95% CI 0.88-1.02; moderate certainty) and may not reduce cardiovascular mortality (RR 0.64, 95% CI 0.35-1.19; low certainty). The effect on thromboembolic complications and major cerebrovascular events appeared minimal. Minor cerebrovascular events were not reported in any of the included studies. CONCLUSION: Moderate certainty evidence suggests that organized clinical services for AF likely lead to a large decrease in all-cause mortality but probably have minimal impact on all-cause hospitalization. Whilst cardiovascular hospitalizations were reduced, the effect on cardiovascular mortality remains uncertain. Further research is needed to compare different care organization models and to confirm findings for inconclusive outcomes, particularly regarding the role of mHealth in AF management. The findings highlight the importance of coordinated care through collaborative, multidisciplinary, and virtual approaches. REGISTRATION: Cochrane Database for Systematic Reviews (2019): https://doi.org/10.1002/14651858.CD013408. Citation to published full Cochrane review: Ferguson C, Shaikh F, Allida SM, Hendriks J, Gallagher C, Bajorek BV, Donkor A, Inglis SC. Clinical service organisation for adults with atrial fibrillation. Cochrane Database of Systematic Reviews 2024, Issue 7, Art. No.: CD013408. https://doi.org/10.1002/14651858.CD013408.pub2. Citation to published Cochrane review protocol: Ferguson C, Hendriks J, Gallagher C, Bajorek BV, Inglis SC. 2019. Clinical Service organisation for adults with atrial fibrillation: Protocol - Intervention. 2019, Issue 8, Art No.: CD013408. https://doi.org/10.1002/14651858.CD013408
Chronic interferon-alpha overexpression induces white matter damage and neurovascular abnormalities in a mouse model of Aicardi-Goutières syndrome.
Get PDFBACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare leukodystrophy marked by chronic neuroinflammation, white matter (WM) injury, cerebral vasculopathy with calcifications, and progressive neurological decline. A central feature of AGS is sustained overexpression of interferon-alpha (IFN-α), yet its long-term impact on WM integrity remains poorly understood. To investigate this, we used a transgenic mouse model (GIFN) with astrocyte-specific expression of IFN-α that recapitulates key features of AGS. METHODS: Brain tissue from GIFN mice at 2 and 7 months of age, reflecting early and advanced disease stages, was analysed using haematoxylin and eosin (H&E), Alizarin Red S (ARS), Luxol Fast Blue (LFB), and immunofluorescence (IF) for IBA1 and ASPA. Quantitative PCR was used to assess expression of myelin-associated genes in the corpus callosum and cerebellum. RESULTS: H&E revealed microvascular abnormalities near WM tracts. ARS identified age-dependent calcifications in the corpus callosum and cerebellum. IF confirmed persistent microgliosis and neuroinflammation. WM degeneration was evidenced by demyelination and a significant reduction in OLIG2+ and ASPA+ oligodendrocytes. Gene expression analysis showed downregulation of key myelin-related genes (MBP, PLP1, MOG, OLIG2, SOX10), consistent with histological changes. CONCLUSION: Chronic astrocyte-driven IFN-α exposure leads to progressive WM pathology, including inflammation, demyelination, and oligodendrocyte loss. GIFN mice provide a robust model of AGS and offer new insights into the mechanisms by which sustained IFN-α disrupts myelin homeostasis. This model may aid in the development of therapeutic strategies for AGS and related interferonopathies
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