Background: Neurofibromatosis 1 (NF1) is a multisystem neurocutaneous disorder. Treatment involves multiple specialists. There are currently no multidisciplinary clinics for adults with NF1 in BC, which impacts communication between subspecialties. We sought perspectives of patients and providers to identify the impact of and solutions to gaps in care. Methods: Focus groups with patients (2 groups; 9 patients) and physicians (10) who see people with NF1 were conducted. Thematic content analysis was applied to the data to derive major themes. Concurrently, quarterly NF multidisciplinary rounds were initiated to enhance coordination of care. Results: Major themes emerged around the need for increased coordination and communication amongst providers. Specifically, physicians identified working in “siloed care structures”, and patients and providers identified lack of awareness of expertise and barriers to accessing care. Conclusions: Focus groups enable inclusion of patient and provider perspectives in developing solutions to gaps in care. The importance of supporting interdisciplinary communication in caring for NF1 patients was confirmed in focus groups. To date, we have held multidisciplinary NF rounds, with 12 cases discussed. Disciplines represented include neurology, pediatrics, radiology, neuro-ophthalmology, neuro-otology, pathology, orthopedic plastic and neurosurgery, medical and radiation oncology, and the hereditary cancer program. Telehealth format enables participation from distributed centres across BC.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

Optimal vitamin D status is important for growth and development during childhood(1). Children with a circulating concentration of 25-hydroxyvitamin D [25(OH)D] below 25 nmol/L are at increased risk of rickets. In order to maintain 25(OH)D > 25nmol/L, a dietary intake of 10µg/d vitamin D is recommended for children aged 4 years and above(2,3). The aim of this study was to determine vitamin D status in healthy children and to investigate associations between 25(OH)D concentrations and muscle health, cognitive function, and parental knowledge of vitamin D, vitamin D habits, perceptions, and practices.

A cross-sectional study of healthy children aged 4 – 11 years conducted between 2019 – 2023 examined vitamin D status by measuring plasma 25(OH)D via the gold standard liquid chromatography tandem mass spectrometry and parathyroid hormone concentrations. Muscle strength (hand grip and balance) was determined by dynamometer, single and tandem stance balancing whilst cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery. Parents completed questionnaires to assess vitamin D knowledge, and perceptions, habits, and attitude towards vitamin D.

A total of 192 children (91 boys; 101 girls) with an average age of 8.2 years were recruited. Plasma 25(OH)D concentrations were 61.10±18.75 nmol/L (n = 190), with 68.4% of children defined as vitamin D sufficient (25(OH)D>50nmol/L). When stratified by winter months, only 58% of children were vitamin D sufficient. In single linear regression, plasma 25(OH)D concentrations were positively associated with dominant hand grip strength, single leg balance and the cognitive test ‘5choice movement time’ (p<0.05). Overall, there was a reported mean score of 41.9% for parental vitamin D knowledge and 68% of parents thought there was no harm in giving their child vitamin D fortified foods.

Approximately 70% of this sample of children were vitamin D sufficient, however insufficiency was prevalent in almost half of the cohort during the winter months. Benefits of optimal vitamin D for muscle and cognitive function were evident. These results support the promotion of the existing vitamin D dietary recommendations during the winter months for optimal child growth and development.

Sufficient vitamin D status is required in childhood for normal skeletal health and the development of muscle and motor function(1). Vitamin D primarily acts through the promotion of calcium absorption from the gut and mobilisation from bone tissue(2). Childrens’ vitamin D dietary intakes are currently below the recommended guidelines within the UK and Ireland suggesting a need for vitamin D3 supplementation to prevent the risk of developing vitamin D deficiency(3). The aim of this study was to examine the effect of 12 weeks’ supplementation with 10µg/d vitamin D3 vs placebo control on vitamin D status and to determine if improved vitamin D status impacted muscle function and cognition in children aged 4-11 years.

In the D-VinCHI randomised, double-blind, placebo-controlled trial, healthy children (n = 118; mean age 8.1±1.8 y; 51% girls) were randomly assigned to either placebo or 10µg/day of vitamin D3 for 12 weeks (year-round). Baseline and endpoint measures included anthropometric measures, hand grip strength, balance, and cognitive assessment. Blood samples were analysed for plasma 25hydroxyvitamin D [25(OH)D], and parathyroid hormone. Vitamin D consumption from food sources was assessed via a 13-item food frequency questionnaire.

Following the 12-week intervention vitamin D status [25(OH)D concentration] increased in the treatment group from 66.31 ± 17.25 nmol/L to 69.04 ± 16.92 nmol/L. Change in status was significantly different compared to the placebo group within which a decrease in 25(OH)D was observed from 63.67 ± 19.48 to 56.29 ± 18.58 nmol/L, p<0.001. Supplementation with vitamin D3 prevented deficiency of plasma 25(OH)D during the winter months. Vitamin D3supplementation had a positive effect on cognitive function, improving simple movement time from 707±380 to 599±207 milliseconds, compared to the placebo group within which time increased from 680±284 to 728±372 milliseconds, p = 0.017. Vitamin D mean dietary intake from food sources alone was 2.68µg/day. There was no effect of supplementation on muscle function.

Vitamin D3 supplementation maintained year-round sufficiency in children and importantly, prevented deficiency during the extended winter months. Vitamin D supplementation may enhance cognitive function via improvements in attention and psychomotor speed. The reported intakes of vitamin D food sources were low and were well below the current dietary reference value for this age group. Further health promotion policies and (bio)fortification strategies should be considered within this age group to maximise vitamin D status for optimal growth and development.

Higher consumption of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced severity of cardiovascular disease (CVD) and autoimmunity(1). The n-3 index (O3I), which correlates to n-3 PUFA habitual intake, is a useful clinical biomarker in determining cardiovascular risk(2). Individuals with an O3I <4% are considered to have higher cardiovascular risk, with 4-8% characterised as medium risk. The desirable O3I is >8% and deemed low risk for a cardiovascular event(3). Yet, little is known about O3I in systemic lupus erythematosus (SLE) patients who have a higher risk of CVD associated with their disease. This analysis aimed to determine the O3I of SLE patients, and its associations with disease activity.

A non-fasted blood sample was collected from SLE patients (n = 15) and healthy participants (n = 15). Isolated red blood cells were used to determine O3I and expressed as %. Habitual intake of fish, a rich source of n-3 PUFAs was assessed by questionnaire. Disease activity of SLE patients was assessed by a clinician using the British Isle Lupus Assessment Group (BILAG), Systemic Lupus Activity Measure-Revised (SLAM-R) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Mann-Whitney U was used to evaluate O3I differences between SLE patients and healthy participants. Spearman’s rank coefficient assessed associations between O3I and SLE disease activity.

SLE patients had an O3I of 4.38% and categorised to have a medium risk of a cardiovascular event, which was significantly lower compared to healthy participants for cardiovascular risk (5.48%; p<0.01). Some 67% SLE patients (n = 10) reported to never/rarely consume fish (≤1 portion per month) whereas 53% healthy participants (n = 8) reported that they consumer >2 portions of fish per month. Correlation analysis showed O3I was negatively associated with BILAG (rho=−0.061), SLAM-R (rho=−0.215) and SLEDAI (rho=−0.122); albeit these associations were not significant (p>0.05).

This is the first report of O3I in SLE patients and identified lower O3I compared to healthy participants, suggesting that SLE patients might benefit from increasing fish consumption to reduce their risk of CVD. Further research is required to fully elucidate associations between O3I and SLE disease activity.

Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Aviation passenger screening has been used worldwide to mitigate the translocation risk of SARS-CoV-2. We present a model that evaluates factors in screening strategies used in air travel and assess their relative sensitivity and importance in identifying infectious passengers. We use adapted Monte Carlo simulations to produce hypothetical disease timelines for the Omicron variant of SARS-CoV-2 for travelling passengers. Screening strategy factors assessed include having one or two RT-PCR and/or antigen tests prior to departure and/or post-arrival, and quarantine length and compliance upon arrival. One or more post-arrival tests and high quarantine compliance were the most important factors in reducing pathogen translocation. Screening that combines quarantine and post-arrival testing can shorten the length of quarantine for travelers, and variability and mean testing sensitivity in post-arrival RT-PCR and antigen tests decrease and increase with the greater time between the first and second post-arrival test, respectively. This study provides insight into the role various screening strategy factors have in preventing the translocation of infectious diseases and a flexible framework adaptable to other existing or emerging diseases. Such findings may help in public health policy and decision-making in present and future evidence-based practices for passenger screening and pandemic preparedness.

Observational studies suggest that 25-hydroxy vitamin D (25(OH)D) concentration is inversely associated with pain. However, findings from intervention trials are inconsistent. We assessed the effect of vitamin D supplementation on pain using data from a large, double-blind, population-based, placebo-controlled trial (the D-Health Trial). 21 315 participants (aged 60–84 years) were randomly assigned to a monthly dose of 60 000 IU vitamin D3 or matching placebo. Pain was measured using the six-item Pain Impact Questionnaire (PIQ-6), administered 1, 2 and 5 years after enrolment. We used regression models (linear for continuous PIQ-6 score and log-binomial for binary categorisations of the score, namely ‘some or more pain impact’ and ‘presence of any bodily pain’) to estimate the effect of vitamin D on pain. We included 20 423 participants who completed ≥1 PIQ-6. In blood samples collected from 3943 randomly selected participants (∼800 per year), the mean (sd) 25(OH)D concentrations were 77 (sd 25) and 115 (sd 30) nmol/l in the placebo and vitamin D groups, respectively. Most (76 %) participants were predicted to have 25(OH)D concentration >50 nmol/l at baseline. The mean PIQ-6 was similar in all surveys (∼50·4). The adjusted mean difference in PIQ-6 score (vitamin D cf placebo) was 0·02 (95 % CI (−0·20, 0·25)). The proportion of participants with some or more pain impact and with the presence of bodily pain was also similar between groups (both prevalence ratios 1·01, 95 % CI (0·99, 1·03)). In conclusion, supplementation with 60 000 IU of vitamin D3/month had negligible effect on bodily pain.

Background: Children with pathogenic variations in SCN8A can present with early infantile epileptic encephalopathy-13, benign familial infantile seizures-5 or intellectual disability alone without epilepsy. In this case series, we discuss six children with variants in SCN8A managed at BC Children’s Hospital. Methods: We describe clinical and genetic results on six individuals with SCN8A variants identified via clinical or research next-generation sequencing. Functional consequences of two SCN8A variants were assessed using electrophysiological analyses in transfected cells. Results: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Phenotypes and genotypes in our cohort are described in the table below. Functional analysis supported gain-of-function in P2 and loss-of-function in P4. Conclusions: Our cohort expands the clinical and genotypic spectrum of SCN8A-related disorders. We establish functional evidence for two missense variants in SCN8A, including LoF variant in a patient with intellectual disability, and autism spectrum disorder without seizures.

Table for P.120

Zn is an essential nutrient for humans; however, a sensitive biomarker to assess Zn status has not been identified. The objective of this study was to determine the reliability and sensitivity of Zn transporter and metallothionein (MT) genes in peripheral blood mononuclear cells (PBMCs) to Zn exposure ex vivo and to habitual Zn intake in human subjects. In study 1, human PBMCs were cultured for 24 h with 0–50 µm ZnSO4 with or without 5 µm N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and mRNA expression of SLC30A1-10, SLC39A1-14, MT1 subtypes (A, B, E, F, G, H, L, M and X), MT2A, MT3 and MT4 mRNA was determined. In study 2, fifty-four healthy male and female volunteers (31·9 (sd 13·8) years, BMI 25·7 (sd 2·9) kg/m2) completed a FFQ, blood was collected, PBMCs were isolated and mRNA expression of selected Zn transporters and MT isoforms was determined. Study 1: MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A and SLC30A1 increased with increasing concentrations of Zn and declined with the addition of TPEN. Study 2: Average daily Zn intake was 16·0 (sd 5·3) mg/d (range: 9–31 mg/d), and plasma Zn concentrations were 15·5 (SD 2·8) μmol/l (range 11–23 μmol/l). PBMC MT2A was positively correlated with dietary Zn intake (r 0·306, P = 0·03) and total Zn intake (r 0·382, P < 0·01), whereas plasma Zn was not (P > 0·05 for both). Findings suggest that MT2A mRNA in PBMCs reflects dietary Zn intake in healthy adults and may be a component in determining Zn status.

Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a $(20\pm 3)~\unicode[STIX]{x03BC}\text{m}$ X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.

Despite aspirations to be a world-class national curriculum, the Australian Curriculum (AC) has been criticised as ‘manifestly deficient’ (Australian Government Department of Education and Training, 2014 p. 5) as an inclusive curriculum, failing to meet the needs of all students with disabilities (SWD) and their teachers. There is a need for research into the daily attempts of educators to navigate the tension between a ‘top-down’ system-wide curriculum and a ‘bottom-up’ regard for individual student needs, with a view to informing both policy and practice. This article is the first of two research papers in which we report the findings from a national online Research in Special Education (RISE) Australian Curriculum Survey of special educators in special schools, classes, and units regarding their experience using the AC to plan for and teach SWD. Survey results indicated (a) inconsistent use of the AC as the primary basis for developing learning objectives and designing learning experiences, (b) infrequent use of the achievement standards to support assessment and reporting, and (c) considerable supplementation of the AC from other resources when educating SWD. Overall, participants expressed a lack of confidence in translating the AC framework into a meaningful curriculum for SWD. Implications for policy, practice, and future research are discussed.

Aeronautics faces new and increased challenges in the 21st century. These include climate change, long-term fuel supply, traffic congestion, and noise pollution. Radical technological steps will be demanded of the industry in order to maintain a sustainable transportation system.

In setting out its ideas for a Sonic Cruiser, Boeing has recently acknowledged that there is a need to look beyond the high-aspect-ratio wing with separate fuselage and podded engine configuration, which it pioneered at the start of the Jet era.

This paper sets out the case for the broad delta including its advantages as a basis for achieving higher transonic cruising speeds, with very long range and large payloads, while providing progressive and significantly improved environmental impact. The work is based on concept designs drawing on flight and weight data from the Vulcan bomber and the Concorde aircraft – both pioneering designs, by no means at the end of their technical potential.

A broad delta is taken to mean an aircraft of aspect ratio in the range 2 to 4. Not only does such a planform have application to many sizes of airliner, cruising at various high subsonic speeds, but also it is inherently well suited to later application of laminar flow. Wing surfaces undisturbed by flaps and slots and unhampered by very thick wing skins, together with favourable engine inlet locations, could be a basis for improved overall aerodynamic efficiency.

Airliners designed for operation in the region of Mach 1 are likely to pose more difficult problems for the aerodynamicist. Designs must cater for both cruise and maximum design speeds, which may encompass the Mach 1 condition.