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Sex-Differential Markers of Psychiatric Risk and Treatment Response Based on Premature Aging of Functional Brain Network Dynamics and Peripheral Physiology
No full textBACKGROUND: Aging is a multilevel process of gradual decline that predicts morbidity and mortality. Independent investigations have implicated senescence of brain and peripheral physiology in psychiatric risk, but it is unclear whether these effects stem from unique or shared mechanisms. METHODS: To address this question, we analyzed clinical, blood chemistry, and resting-state functional neuroimaging data in a healthy aging cohort (n = 427; ages 36-100 years) and 2 disorder-specific samples including patients with early psychosis (100 patients, 16-35 years) and major depressive disorder (MDD) (104 patients, 20-76 years). RESULTS: We identified sex-dependent coupling between blood chemistry markers of metabolic senescence (i.e., homeostatic dysregulation), functional brain network aging, and psychiatric risk. In females, premature aging of frontoparietal and somatomotor networks was linked to greater homeostatic dysregulation. It also predicted the severity and treatment resistance of mood symptoms (depression/anxiety [all 3 samples], anhedonia [MDD]) and social withdrawal/behavioral inhibition (avoidant personality disorder [healthy aging], negative symptoms [early psychosis]). In males, premature aging of the default mode, cingulo-opercular, and visual networks was linked to reduced homeostatic dysregulation and predicted the severity and treatment resistance of symptoms relevant to hostility/aggression (antisocial personality disorder [healthy aging], mania/positive symptoms [early psychosis]), impaired thought processes (early psychosis, MDD), and somatic problems (healthy aging, MDD). CONCLUSIONS: Our findings identify sexually dimorphic relationships between brain dynamics, peripheral physiology, and risk for psychiatric illness, suggesting that the specificity of putative risk biomarkers and precision therapeutics may be improved by considering sex and other relevant personal characteristics
Interprofessional Educational Interventions to Improve Pharmacological Knowledge and Prescribing Competency in Medical Students and Trainees: A Scoping Review
No full textIntroduction: Prescribing errors are the most common cause of preventable patient harm. In recent years, interprofessional education (IPE) has been increasingly utilised to improve knowledge and skills through promoting interprofessional collaboration. This scoping review aimed to evaluate the effectiveness of IPE interventions for pharmacological knowledge and prescribing skills in medical students and doctors-in-training. Methods: MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO, ERIC and Scopus were searched on 18 February 2025 for studies published since 2020. Keywords included interprofessional education, medical student, medical trainee, pharmacology and prescribing. Results: Of the 2254 citations identified, 42 studies were included. There were four main types of IPE interventions: case-based learning, work-integrated-learning, didactic, and simulation and role-plays. Outcomes were spread across pharmacological knowledge, prescribing skills and interprofessional attitudes, and all studies reported one or more positive findings at Kirkpatrick IPE level 1, 2a, 2b, 3 or 4b. No study reported outcomes at Kirkpatrick IPE 4a. Conclusions: IPE interventions targeting pharmacology and prescribing are positively viewed by medical learners. IPE is effective in improving interprofessional attitudes and collaboration, as well as pharmacological knowledge and prescribing competency. Logistical challenges can be barriers to larger-group IPE implementation; nonetheless, IPE work-integrated learning in authentic clinical settings may overcome these challenges
Compressive behavior of prestressed SFRCFST stub columns after heating: Effect of fresh concrete compression technique
No full textOne innovative and effective technique to enhance the compression response of concrete-filled steel tube (CFST) columns is the compression of the fresh concrete, which actively confines the concrete core by prestressed steel tubes. To utilize active confinement in structural design, the behavior of prestressed CFST columns under different conditions should be investigated. In this research, the compression response of steel fiber-reinforced concrete-filled steel tube (SFRCFST) stub columns prestressed by the fresh concrete compression (FCC) technique was assessed before and after experiencing heat. Toward this goal, 60 cylindrical SFRCFST specimens were fabricated, with key variables of the prestressing ratio, volume percentage of steel fibers, applied temperature, external diameter-to-wall thickness ratio (D/t) of steel tube, and water/cement ratio. Post-heating axial compression tests examined the loading capacity, ductility, peak strain, toughness, and load-strain response. It was revealed that due to prestressing and the temperature rise to 600 °C, the heat-induced reduction in load capacity was negligible, while this drop was notable in the specimens without prestressing. At a temperature of 600°C, the load-bearing capacity of the specimens with a prestressing ratio of 0.5 fy increased by 40 % compared to the non-confined specimens, while the axial and lateral strain capacities decreased by 40 and 49 %, respectively. With an increase in the prestressing ratio to 0.7 fy, the load-bearing capacity increased by 50 %, and the axial and lateral strain capacities decreased by 26 and 25 %, respectively. In prestressed and non-prestressed SFRCFST columns, with or without thermal exposure, a steel fiber content of up to 1.5 % improved toughness and increased peak strain and ductility in most specimens. Finally, the nonlinear regression analysis was employed to present a proper prediction model for the loading capacity of SFRCFST columns
Symptomatic Neonates With Tetralogy of Fallot: Shunt or Primary Repair?
No full textBACKGROUND: The optimal management strategy for symptomatic neonates with tetralogy of Fallot is unclear. We compared the outcomes of staged repair (SR) (shunt palliation followed by complete repair) and primary repair (PR) in two institutions that have each exclusively adopted one of these strategies. METHOD: We retrospectively compared 65 symptomatic neonates who underwent shunt palliation between 1993 and 2021 at the Royal Children's Hospital, Melbourne, Australia with 38 symptomatic neonates who underwent PR between 2005 and 2018 at the Children's National Hospital, Washington, USA. Median follow-up duration was 8.0 (interquartile range 2.9-13.5) years. RESULTS: After the initial procedure, hospital mortality (shunt 4.6% vs PR 7.9%; p=0.50) and 5-year survival (shunt 94%; 95% confidence interval [CI] 84%-98% vs PR 89%; 95% CI 72%-96%; p=0.21) were not significantly different. The SR group had shorter durations of cardiopulmonary bypass and intensive care admission during the neonatal period, but a higher burden of unplanned re-interventions before discharge. Five-year freedom from re-interventions was not significantly different (shunt 63%; 95% CI 49%-74% vs PR 49%; 95% CI 29%-66%; p=0.13). Postoperative morbidity, mortality, and re-interventions were not significantly different among 13 propensity score-matched pairs balanced for operative weight. For neonates weighing <3 kg, PR was associated with significantly more early re-interventions. CONCLUSIONS: In symptomatic neonates with tetralogy of Fallot operated at two institutions with distinct treatment protocols, no statistically significant difference in medium-term survival and re-intervention was observed between the two strategies. SR was associated with lower neonatal morbidity but more unplanned re-interventions before discharge. PR in neonates weighing <3 kg may result in more early re-interventions
Photomultiplier requirements and pre-calibration for the SABRE South Liquid Scintillator Veto
No full textAbstract
We present a study of the oil-proof base Hamamatsu R5912
photomultiplier tubes that will be used in the SABRE South
linear-alkylbenzene liquid scintillator veto. SABRE South is a dark
matter direct detection experiment at the Stawell Underground
Physics Laboratory, aiming to test the DAMA/LIBRA dark matter annual
modulation signal. We discuss the requirements of the liquid
scintillator system and its photomultipliers, outline the methods
and analysis used for the characterisation measurements, and results
from initial tests. We discuss the impact of these measurements on
the performance of the active veto system and explore analysis
methods to allow for low threshold operation. Finally, we include
results from a small scale liquid scintillator detector prototype
used to assess the future performance of pulse shape discrimination
in the liquid scintillator veto, and how well accommodated it is by
the R5912 PMTs
Distinct adaptation and epidemiological success of different genotypes within Salmonella enterica serovar Dublin.
No full textSalmonella Dublin is a host-adapted, invasive nontyphoidal Salmonella (iNTS) serovar that causes bloodstream infections in humans and demonstrates increasing prevalence of antimicrobial resistance (AMR). Using a global dataset of 1303 genomes, coupled with in vitro assays, we examined the evolutionary, resistance, and virulence characteristics of S. Dublin. Our analysis revealed strong geographical associations between AMR profiles and plasmid types, with highly resistant isolates confined predominantly to North America, linked to IncC plasmids co-encoding AMR and heavy metal resistance. By contrast, Australian isolates were largely antimicrobial-susceptible, reflecting differing AMR pressures. We identified two phylogenetically distinct Australian lineages, ST10 and ST74, with a small number of ST10 isolates harbouring a novel hybrid plasmid encoding both AMR and mercuric resistance. Whereas the ST10 lineage remains globally dominant, the ST74 lineage was less prevalent. ST74 exhibited unique genomic features including a larger pan genome compared to ST10 and the absence of key virulence loci, including Salmonella pathogenicity island (SPI)-19 which encodes a type VI secretion system (T6SS). Despite these genomic differences, the ST74 lineage displayed enhanced intracellular replication in human macrophages and induced less pro-inflammatory responses compared with ST10, suggesting alternative virulence strategies that may support systemic dissemination of ST74. The Vi antigen was absent in all ST10 and ST74 genomes, highlighting challenges for serotyping and vaccine development, and has implications for current diagnostic and control strategies for S. Dublin infections. Collectively, this study represents the most comprehensive investigation of S. Dublin to date and, importantly, has revealed distinct adaptations of two genotypes within the same serovar, leading to different epidemiological success. The regional emergence and evolution of distinct S. Dublin lineages highlight the need to understand the divergence of intra-serovar virulence mechanisms which may impact the development of effective control measures against this important global pathogen
Implementing without evaluating: The missing link in understanding the effectiveness of financial incentive programs for e-bikes
No full textThe surging popularity of electric bicycles aligns with global objectives for active and sustainable mobility, a cornerstone of transportation policy. However, persistent barriers such as inadequate infrastructure and safety concerns, coupled with the steep cost of e-bikes, hinder their widespread adoption. To address the latter issue, various financial incentive programs have been implemented with the aim of increasing e-bike use. This review synthesises existing evidence to assess the effectiveness of these incentives in promoting modal shift to e-bikes. The review highlights the scarcity of published evidence on the effectiveness of financial incentive programs, which limits our understanding of the most effective design and structure of such schemes to inform policy. Despite this, findings from available studies indicate an increase in e-bike use and a corresponding decrease in car use among participants in the reviewed programs. There is a critical need for more rigorous studies, preferably employing experimental or quasi-experimental longitudinal designs, to comprehensively assess the effectiveness of e-bike financial incentive programs in delivering e-bike uptake and modal shift away from cars
Offshore turbidity currents forecasting (part I): Integrating deep learning and computational fluid dynamics
No full textThis study introduces a novel methodology for real-time forecasting of turbidity currents, a significant geohazard to offshore infrastructures such as pipelines and submarine telecommunication networks. Numerical modeling, deeap learning (DL) techniques, and field measurements were incorporated to provide accurate predictions of upcoming turbidity current events. A forecasting model was developed using a combination of two DL methods, Convolutional Neural Networks (CNNs) and Long Short-Term Memory networks (LSTMs). This combination is helpful in capturing both spatial features and temporal sequences in the data, making it well-suited for predicting the movement and behavior of turbidity currents. The DL models (CNN-LSTM) were initially trained using synthetic data from Computational Fluid Dynamics (CFD) analyses, and then real field dataset from an Acoustic Doppler Current Profiler (ADCP) in the Congo Canyon, West Africa. The CFD analysis incorporated a turbulence model known as the renormalization group k-epsilon model to enhance accuracy, and it was validated with an experimental dataset. To fine-tune the DL models, Bayesian hyperparameter tuning was employed, a method that systematically adjusts the settings of the model to enhance performance. Also, employing transfer learning, a technique that transfers knowledge from simulated data to actual field data, reduced prediction errors by 50 %. The pretrained models were fine-tuned and the impacts of the key hyperparameters such as input-label width ratio, forecast window length, and data resolution were investigated. After fine-tuning, the optimized models achieved prediction accuracies with less than 10 % error, utilizing data sampled every 480 s across a forecasting window of 40 h. Overall, the proposed DL methodology presents a promising basis for an AI-based early warning system against turbidity current hazards for offshore and marine infrastructures
686. Schizophrenia-like endophenotypes in amyloid precursor protein knock out mice
No full textAbstract
Background
Schizophrenia is a complex mental health condition that impacts an estimated 1% of the global population. The exact causes remain largely unclear. Recent findings from our research group have found evidence for the presence of iron dyshomeostasis and ubiquitin protein stress in the prefrontal cortex (PFC) of a group of individuals with schizophrenia. These iron-perturbations were characterised by excess iron, elevated levels of ubiquitinated proteins and downregulation of Amyloid Precursor Protein (APP). Remarkably, APP knock out mice accumulate iron in the brain and display schizophrenia-like endophenotypes.
Aims & Objectives
This study aims to evaluate behavioral, brain structural and protein changes in the APP knock out (APP-KO) mice.
Method
We analyzed the iron levels in brain samples from age-matched control and APP-KO mice by ICP-MS. Protein levels were assessed by Western blot. The behavior of these animals was monitored by prepulse inhibition assessment (a schizophrenia phenotype) and clasping scores. Brain structural changes were monitored by magnetic resonance imaging.
Results
We found that the frontal cortex of these animals are characterized by elevated iron in the soluble fraction and accumulation of ubiquitinated proteins in the insoluble fraction. In addition, we detected altered levels of proteins involved in iron homeostasis. Surprisingly, we observed that male APP-KO mice displayed increased startle response and high clasping scores. Importantly, these animals expressed a specific and significant decrease in the volume of thalamus.
Discussion & Conclusions
Iron dyshomeostasis can disrupt neurodevelopment, leading to oxidative and protein stress, which in turn may lead to neuronal dysfunction, culminating in ferroptosis and neurodegeneration. Here we identify novel schizophrenia-like endophenotypes in an animal model exhibiting brain iron accumulation driven by the absence of APP. These results suggest that stressors in ubiquitin signalling, iron metabolism and APP homeostasis are candidate factors that could impact the neurobiology of schizophrenia