Type 2 diabetes mellitus (T2DM) is a major disease worldwide, causing significant mortality and morbidity. Currently, in Aotearoa, New Zealand, there is a high prevalence of T2DM, with a disproportionate impact on Māori and Pacific populations(1). Moreover, it has been predicted that the prevalence will continually increase. Research has shown that insulin resistance (IR) has been reported to play a critical role in the development of T2DM and other related cardiometabolic diseases(2). Therefore, managing IR is crucial to reducing the development of T2DM. Notably, bioactive compounds in various diets are known to modify the risk of T2DM by regulating IR. Among such dietary compounds include kawakawa (Piper excelsum), an indigenous species used by Māori in traditional medicine (Rongoā). Kawakawa is shown to contain several bioactive compounds that are shown to have insulin-sensitising effects. Research by our group has recently shown kawakawa to have potential anti-diabetic and anti-inflammatory effects in healthy human volunteers(3,4). However, how Kawakawa exerts these effects on insulin signalling and glucose uptake remains unknown. We hypothesise that kawakawa will enhance the glucose uptake in the treated cells and will differentially regulate key genes involved in insulin signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, across various tissues. To test our hypothesis, we aim to investigate the mechanistic action of kawakawa extract on insulin signalling pathways in different cell models from metabolically active organs. We will use the same kawakawa powder sample shown to improve postprandial insulin in a healthy population. Cell models representing different insulin-responsive organs: liver (HepG2), skeletal muscle (L6-GLUT4myc), pancreas (MIN6), and adipose (3T3-L1) will be used. The cells will be treated with different doses of kawakawa extract, and glucose uptake will be measured. Key signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, will be monitored using western blot and quantitative polymerase chain reaction (qPCR) analysis. The findings of this study have the potential to identify key targets of kawakawa action on insulin signalling in metabolically active organs. These outcomes will inform future research with kawakawa in clinical settings in people with cardiometabolic diseases such as T2DM and can form the basis for developing a dietary intervention for individuals at risk of these diseases. Additionally, Rongoā is an acceptable intervention by Māori, integrating this knowledge with evidence-based scientific interventions would aid in creating a holistic health paradigm that resonates within Māori communities.

Background: Epstein-Barr virus (EBV) infection is believed to be a critical prerequisite for the development of multiple sclerosis (MS). This study aims to investigate whether anti-EBV titres are elevated before the onset of MS symptoms in people with radiologically isolated syndrome (pwRIS) and to evaluate their association with markers of adverse clinical outcomes. Methods: Epstein-Barr nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) titres were quantified in a cohort of 47 pwRIS and 24 healthy controls using Enzyme-Linked Immuno-Sorbent Assay. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light protein (NfL) were measured using single-molecule array. MRI lesion metrics and the development of MS symptoms over time were also evaluated. Results: EBNA1 titres were higher pwRIS compared to healthy controls (p=0.038), while VCA titres were not (p=0.237). A positive correlation was observed between EBNA1 titres and plasma GFAP in pwRIS (p=0.005). Neither EBNA1 nor VCA titres correlated with NfL. MRI lesion measures and the development of MS symptoms did not show any significant relationship with EBNA1 or VCA titres. Conclusions: Eelevated EBNA1 titres are detectable prior to MS symptom onset and correlate with GFAP, a biomarker associated with worse clinical outcomes. However, their role in disease progression and clinical outcomes requires further investigation.

Background: Radiologically isolated syndrome (RIS) is characterized by incidental MRI findings suggestive of multiple sclerosis in asymptomatic individuals. Emerging blood biomarkers, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and chitinase 3-like 1 protein (CHI3L1) are promising tools for evaluating neuroinflammation and neurodegeneration. Methods: This cross-sectional analysis included 47 individuals with RIS who underwent MRI and plasma biomarker assessments. Plasma levels of CHI3L1, NfL, and GFAP were measured using highly sensitive assays. Correlations between biomarkers and MRI markers, including T1-black holes (BHs), central vein sign (CVS) positive lesions, paramagnetic rim lesions (PRLs), choroid plexus volume (CPV), and thalamic and hippocampal volumes, were analyzed using linear regression. Results: Plasma CHI3L1 levels correlated with increased CPV (β = 0.347, p = 0.017) and reduced thalamic (β = -0.309, p = 0.035) and hippocampal (β = -0.535, p < 0.001) volumes. Plasma GFAP levels were associated with BHs, CVS, and PRLs, whereas plasma NfL showed no correlations with MRI measures. Conclusions: Plasma CHI3L1 correlates with subcortical grey matter atrophy and CPV increase in RIS, distinct from correlations observed with GFAP or NfL. This suggests that plasma CHI3L1 may reflect neurodegeneration and inflammation in RIS and provide insights into disease activity not captured by other biomarkers.

Background: In multiple sclerosis (MS), soluble mediators of neuroinflammation are released by activated lymphocytes and resident immune cells, leading to demyelination and neurodegeneration. Radiologically isolated syndrome (RIS) is an entity in which white matter lesions fulfilling criteria for MS occur in individuals without any suggestive symptoms. The exact nature of pro- and anti-inflammatory cytokines in blood, and their association with disease activity in RIS/MS requires further clarification. Methods: Plasma was collected and cryopreserved from healthy controls (HCs), people with RIS and relapsing-remitting MS (RRMS) at the Barlo MS Centre. All samples were analyzed with OLink Target 96 Inflammation Multiplex Immunoassay Panel. Results: Individuals with RIS (p=0.0001; p= 0.0007; p= 0.0012) and RRMS (p<0.0001; p= 0.0003; p= 0.00112) had significantly higher concentrations of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and chemokine ligand 23 (CCL23) in plasma compared to HCs, and patients with RRMS (p=0.0087) had significantly higher concentrations of HGF compared to individuals with RIS. Conclusions: Our study demonstrates that HGF, IL-6 and CCL23 are significantly increased in the plasma of patients with RIS and RRMS compared to HCs. Our observations suggest that the biology of MS is present in those with RIS, and these neuroinflammatory mediators may serve as a biomarker of disease activity.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.

This study examined associations between paternal, maternal, and dual-parental attention deficit hyperactivity disorder (ADHD) symptoms and child socioemotional functioning over the first two years of life, combined and separated by child sex. The sample included mothers (N = 3,207) and fathers (N = 3,211) from a prospective cohort in Canada. Parents completed the Adult ADHD Self-Report Scale within two weeks of childbirth. Children’s socioemotional functioning was assessed using the ASQ-SE at 6 months and the BITSEA at 12, 18, and 24 months. Paternal and maternal ADHD symptoms were associated with problems in child socioemotional development in the first two years of life, with significant differences based on parent and child sex. Paternal ADHD symptoms were associated with more socioemotional difficulties in boys (aOR 1.68, 95% CI 1.13–2.51) and fewer socioemotional difficulties in girls, while maternal ADHD symptoms were associated with more socioemotional problems in girls (aOR 2.09, 95% CI 1.24–3.52) and the entire sample, including both boys and girls, between 12 and 24 months. Dual-parental ADHD symptoms had the largest effect on socioemotional development (OR 4.43, 95% CI 1.14–17.16). Our findings provide evidence that exposure to paternal and maternal ADHD symptoms, especially when both parents exhibit symptoms, is associated with worse socioemotional outcomes during early childhood.

We study the planar FitzHugh–Nagumo system with an attracting periodic orbit that surrounds a repelling focus equilibrium. When the associated oscillation of the system is perturbed, in a given direction and with a given amplitude, there will generally be a change in phase of the perturbed oscillation with respect to the unperturbed one. This is recorded by the phase transition curve (PTC), which relates the old phase (along the periodic orbit) to the new phase (after perturbation). We take a geometric point of view and consider the phase-resetting surface comprising all PTCs as a function of the perturbation amplitude. This surface has a singularity when the perturbation maps a point on the periodic orbit exactly onto the repelling focus, which is the only point that does not return to stable oscillation. We also consider the PTC as a function of the direction of the perturbation and present how the corresponding phase-resetting surface changes with increasing perturbation amplitude. In this way, we provide a complete geometric interpretation of how the PTC changes for any perturbation direction. Unlike other examples discussed in the literature so far, the FitzHugh–Nagumo system is a generic example and, hence, representative for planar vector fields.

We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.

Fully relativistic particle-in-cell (PIC) simulations are crucial for advancing our knowledge of plasma physics. Modern supercomputers based on graphics processing units (GPUs) offer the potential to perform PIC simulations of unprecedented scale, but require robust and feature-rich codes that can fully leverage their computational resources. In this work, this demand is addressed by adding GPU acceleration to the PIC code Osiris. An overview of the algorithm, which features a CUDA extension to the underlying Fortran architecture, is given. Detailed performance benchmarks for thermal plasmas are presented, which demonstrate excellent weak scaling on NERSC's Perlmutter supercomputer and high levels of absolute performance. The robustness of the code to model a variety of physical systems is demonstrated via simulations of Weibel filamentation and laser-wakefield acceleration run with dynamic load balancing. Finally, measurements and analysis of energy consumption are provided that indicate that the GPU algorithm is up to ${\sim }$14 times faster and $\sim$7 times more energy efficient than the optimized CPU algorithm on a node-to-node basis. The described development addresses the PIC simulation community's computational demands both by contributing a robust and performant GPU-accelerated PIC code and by providing insight into efficient use of GPU hardware.

Viruses are highly dynamic macromolecular assemblies. They undergo large-scale changes in structure and organization at nearly every stage of their infectious cycles from virion assembly to maturation, receptor docking, cell entry, uncoating and genome delivery. Understanding structural transformations and dynamics across the virus infectious cycle is an expansive area for research that that can also provide insight into mechanisms for blocking infection, replication, and transmission. Additionally, the processes viruses carry out serve as excellent model systems for analogous cellular processes, but in more accessible form. Capturing and analyzing these dynamic events poses a major challenge for many structural biological approaches due to the size and complexity of the assemblies and the heterogeneity and transience of the functional states that are populated. Here we examine the process of protein-mediated membrane fusion, which is carried out by specialized machinery on enveloped virus surfaces leading to delivery of the viral genome. Application of two complementary methods, cryo-electron tomography and structural mass spectrometry enable dynamic intermediate states in intact fusion systems to be imaged and probed, providing a new understanding of the mechanisms and machinery that drive this fundamental biological process.

Education can be viewed as a control theory problem in which students seek ongoing exogenous input—either through traditional classroom teaching or other alternative training resources—to minimize the discrepancies between their actual and target (reference) performance levels. Using illustrative data from $n=784$\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$n=784$$\end{document} Dutch elementary school students as measured using the Math Garden, a web-based computer adaptive practice and monitoring system, we simulate and evaluate the outcomes of using off-line and finite memory linear quadratic controllers with constraintsto forecast students’ optimal training durations. By integrating population standards with each student’s own latent change information, we demonstrate that adoption of the control theory-guided, person- and time-specific training dosages could yield increased training benefits at reduced costs compared to students’ actual observed training durations, and a fixed-duration training scheme. The control theory approach also outperforms a linear scheme that provides training recommendations based on observed scores under noisy and the presence of missing data. Design-related issues such as ways to determine the penalty cost of input administration and the size of the control horizon window are addressed through a series of illustrative and empirically (Math Garden) motivated simulations.

Galaxy Zoo is an online project to classify morphological features in extra-galactic imaging surveys with public voting. In this paper, we compare the classifications made for two different surveys, the Dark Energy Spectroscopic Instrument (DESI) imaging survey and a part of the Kilo-Degree Survey (KiDS), in the equatorial fields of the Galaxy And Mass Assembly (GAMA) survey. Our aim is to cross-validate and compare the classifications based on different imaging quality and depth. We find that generally the voting agrees globally but with substantial scatter, that is, substantial differences for individual galaxies. There is a notable higher voting fraction in favour of ‘smooth’ galaxies in the DESI+zoobot classifications, most likely due to the difference between imaging depth. DESI imaging is shallower and slightly lower resolution than KiDS and the Galaxy Zoo images do not reveal details such as disc features and thus are missed in the zoobot training sample. We check against expert visual classifications and find good agreement with KiDS-based Galaxy Zoo voting. We reproduce the results from Porter-Temple+ (2022), on the dependence of stellar mass, star formation, and specific star formation on the number of spiral arms. This shows that once corrected for redshift, the DESI Galaxy Zoo and KiDS Galaxy Zoo classifications agree well on population properties. The zoobot cross-validation increases confidence in its ability to compliment Galaxy Zoo classifications and its ability for transfer learning across surveys.