Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

Background: Ischemic stroke is a major cause of morbidity and mortality in Canada. Since 2015, mechanical thrombectomy has been the standard of care for eligible large vessel occlusions (LVOs), though anesthetic strategies remain variable. Methods: We conducted a single-center retrospective review of patients undergoing mechanical thrombectomy for anterior circulation LVOs between 2021 and 2023. Patients were categorized by anesthetic strategy (general anesthesia vs. conscious sedation), and outcomes, including time to recanalization, angiographic results (mTICI), and 90-day functional status (mRS), were compared. Statistical analyses included Student’s t-test, Mann-Whitney U-test, and Fisher’s exact test. Results: Among 226 patients, 177 (78%) received general anesthesia and 49 (22%) underwent conscious sedation. Baseline characteristics including sex, age, NIHSS, ASPECTS, collaterals, and laterality were similar between groups. Conscious sedation was associated with a statistically significant shorter time from arrival to the angiography suite to groin puncture (p=0.007), but no differences in time to recanalization (p=0.893), angiographic outcomes (p=0.987), or 90-day functional status (p=0.795) were observed. Conclusions: Conscious sedation led to faster procedural initiation, though no difference in clinical or radiographic outcome was observed. Anesthetic choice should be individualized based on patient and physician factors in acute mechanical thrombectomy.

Background: Inuit children have been observed to have high rates of macrocephaly, which leads to burdensome travel for medical evaluation, often with no pathology identified. Given reports that WHO growth charts may not reflect all populations, we compared head circumference (HC) measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted HC data from a retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children, born between 2010-2013, and residing in Nunavut. We excluded children with preterm birth, documented neurologic/genetic disease, and most congenital anomalies. We compared HC values with the 2007 WHO charts. Results: We analyzed records of 1960 Inuit children (8866 data points). Most data were from ages 0-36 months. At all age points, the cohort had statistically significantly larger HC than WHO medians. At age 12 months, median HC were 1.3 cm and 1.5 cm larger for male and female Inuit children. Using WHO growth curves, macrocephaly was overdiagnosed and microcephaly underdiagnosed. Conclusions: Our results support the observation that Inuit children from Nunavut have larger HCs, and use of the WHO charts may lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population specific growth curves for Inuit children should be considered.

Background: The combination of PARP inhibitor and immune checkpoint inhibitors have been proposed as a potentially synergistic combinatorial treatment in IDH mutant glioma, targeting dysregulated homologous recombination repair pathways. This study analyzed the cell-free DNA methylome of patients in a phase 2 trial using the PARP inhibitor Olaparib and the PD-1 inhibitor Durvalumab. Methods: Patients with recurrent high-grade IDH-mutant gliomas were enrolled in a phase II open-label study (NCT03991832). Serum was collected at baseline and monthly and cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed. Binomial GLMnet models were developed and model performance was assessed using validation set data. Results: 29 patients were enrolled between 2020–2023. Patients received olaparib 300mg twice daily and durvalumab 1500mg IV every 4 weeks. The overall response rate was 10% via RANO criteria. 144 plasma samples were profiled with cfMeDIP-seq along with 30 healthy controls. The enriched circulating tumour DNA methylome during response periods exhibited a highly specific signature, accurately discriminating response versus failure (AUC 0.98 ± 0.03). Additionally, samples that were taken while on treatment were able to be discriminated from samples off therapy (AUC 0.74 ± 0.11). Conclusions: The cell-free plasma DNA methylome exhibits highly specific signatures that enable accurate prediction of response to therapy.

Depression, a leading cause of global disability, arises from a multifaceted combination of genetic and environmental components. This study explores the relationship between major depressive disorder (MDD) polygenic scores (PGS), characteristics and symptoms of depression, and community-shared socioeconomic factors derived from postal code data in a cohort of 12,646 individuals from the Australian Genetics of Depression Study (AGDS). Our findings reveal that people living in areas with relatively higher socioeconomic advantages and education/occupation scores are more likely to report experiencing fewer depressive symptoms during their worst depressive period, as well as fewer number of lifetime episodes. Additionally, participants who reported depression onset later in life tend to currently reside in wealthier areas. Interestingly, no significant interaction between genetic and socioeconomic factors was observed, suggesting their independent contribution to depression outcomes. This research underscores the importance of integrating socioeconomic factors into psychiatric evaluation and care, and points to the critical role of public policy in addressing mental health disparities driven by socioeconomic factors. Future research should aim to further elucidate the causal relationships within these associations and explore the potential for integrated genetic and socioeconomic approaches in mental health interventions.

Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Following the recent report of strongyloidiasis caused by Strongyloides fuelleborni within a semi-captive colony of baboons in a UK safari park, we investigated the genetic relationships of this isolate with other Strongyloides isolates across the world. Whole-genome sequencing data were generated with later phylogenetic analysis of mitochondrial (mt) cytochrome oxidase subunit 1 (cox1) and nuclear ribosomal 18S sequences against 300 published Strongyloides reference genotypes. The putative African origin of the UK S. fuelleborni was confirmed and full-length mt genome sequences were assembled to facilitate a more detailed phylogenetic analysis of 14 mt coding regions against all available Strongyloides species. Our analyses demonstrated that the UK isolate represented a novel African lineage not previously described. Additional complete mt genomes were assembled for several individual UK safari park worms to reveal a slightly altered mt genome gene arrangement, allowing clear separation from Asian S. fuelleborni. Furthermore, these UK worms possessed expanded intergenic regions of unknown function that increase their mt genome size to approximately 24 kilobases (kb) as compared with some 16 kb for Asian S. fuelleborni; this may have arisen from unique populational founder and genetic drift effects set within the peculiar mixed species baboon and drill ancestry of this semi-captive primate colony. A maximum likelihood phylogeny constructed from 14 mt coding regions also supported an evolutionary distinction between Asian and African S. fuelleborni.

The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.

Low vegetable intake is a key contributor to the health burden experienced by young adults in rural communities(1). Digital interventions provide an accessible delivery model that can be personalised to meet the diverse preferences of young adults(2). This study aimed to determine the feasibility, acceptability and efficacy of a personalised digital intervention to increase vegetable intake (Veg4Me), co-designed to meet the needs of young adults living in rural Australian communities(3). A 12-week assessor-blinded, two-arm, parallel randomised controlled trial was undertaken from August 2023 until April 2024. Young adults (18–35 years; consuming < 5 serves of vegetables/day; with an internet-connected device) living in Loddon Campaspe or Colac Otway Shire in Victoria, Australia, were recruited via social media and local government networks. Participants were randomised to receive 12 weeks of personalised (intervention) or non-personalised (control) support via a free web application (app; Veg4Me). Key features included 1) recipes personalised to users’ dietary and cooking preferences, 2) geo-located food environment map, 3) healthy eating resources, 4) goal-setting portal and 5) personalised e-newsletters. The primary outcome was feasibility: recruitment, participation and retention rate. Secondary outcomes were usability and user experience, perceived changed in vegetable intake, self-reported vegetable intake, and confidence to cook fresh green and root vegetables. Regression analyses (adjusted for baseline) were used to test for significant differences between groups. A total of n = 536 individuals registered on the Veg4Me website. After excluding fraudulent and duplicate responses (n = 289), n = 124 were eligible and provided consent to participate, n = 116 were randomised and n = 83 completed postintervention data collection. The recruitment rate was 47%, participation rate was 93% and retention rate was 72%. Compared to the control, more intervention participants were satisfied with Veg4Me (76% vs 52%). Most intervention participants reported that access to personalised recipes gave them confidence to eat a wider variety of vegetables (83%), while 76% accessed the food environment map, 63% accessed the healthy eating resources, 78% accessed the goal-setting function and 90% reported that the e-newsletters prompted them to access Veg4Me. Compared to the control, more intervention participants perceived that their vegetable intake had changed in the last 12 weeks (85% vs 57%; p = 0.013). Mean vegetable intake at 12 weeks in intervention and control participants was 2.7 (SD 1.0) and 2.7 (SD 1.4) serves/day, respectively (p = 0.67). Confidence to cook fresh green vegetables at 12 weeks in intervention and control participants was 93% and 91%, respectively (p = 0.24), while for root vegetables this was 88% and 81%, respectively (p = 0.11). Findings demonstrate the feasibility and acceptability of the Veg4Me intervention, and some evidence of efficacy. This study introduces a new strategy that has promise for addressing diet and health inequities experienced by young adults living in rural communities.

Network meta-analysis allows the synthesis of relative effects from several treatments. Two broad approaches are available to synthesize the data: arm-synthesis and contrast-synthesis, with several models that can be fitted within each. Limited evaluations comparing these approaches are available. We re-analyzed 118 networks of interventions with binary outcomes using three contrast-synthesis models (CSM; one fitted in a frequentist framework and two in a Bayesian framework) and two arm-synthesis models (ASM; both fitted in a Bayesian framework). We compared the estimated log odds ratios, their standard errors, ranking measures and the between-trial heterogeneity using the different models and investigated if differences in the results were modified by network characteristics. In general, we observed good agreement with respect to the odds ratios, their standard errors and the ranking metrics between the two Bayesian CSMs. However, differences were observed when comparing the frequentist CSM and the ASMs to each other and to the Bayesian CSMs. The network characteristics that we investigated, which represented the connectedness of the networks and rareness of events, were associated with the differences observed between models, but no single factor was associated with the differences across all of the metrics. In conclusion, we found that different models used to synthesize evidence in a network meta-analysis (NMA) can yield different estimates of odds ratios and standard errors that can impact the final ranking of the treatment options compared.

Ochetosoma heterocoelium (Travassos, 1921) was collected from the mouth and oesophagus of a pit viper, Bothrops moojeni Hoge, 1966 in São Sebastião do Paraíso Farm (21°51’48.26" S, 48°26’56.78" W), municipality of Boa Esperança do Sul, São Paulo State, Brazil. In this study, we provide the first molecular characterisation of this digenean using 28S rDNA and COI sequences, and its phylogenetic position within the Plagiorchiida is assessed. Furthermore, new morphological features are added to the diagnosis of the species, and scanning electron microscopy photomicrographs are presented. Sequences of the 28S rRNA gene of O. heterocoelium were successfully obtained and aligned with 35 digenean species belonging to Plagiorchiida. Only three congeners – O. aniarum (Leidy, 1890), O elongatum (Seo et al. 2024), and O. kansense (Crow, 1913) – have been sequenced for this molecular marker. The newly sequenced individuals of O. heterocoelium are 98.7% and 99.4% similar to O. aniarum and O. kansensis, respectively, and Ochetosoma is not recovered as a monophyletic group. Dasymetra nicolli Holl and Allison, 1935 and Lechriorchis tygarti Talbot, 1933 are nested with Ochetosoma.