Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.

We present the first radio–continuum detection of the circumstellar shell around the well-known WN8 type Wolf-Rayet star WR16 at 943.5 MHz using the Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) survey. At this frequency, the shell has a measured flux density of 72.2$\pm$7.2 mJy. Using previous Australia Telescope Compact Array (ATCA) measurements at 2.4, 4.8, and 8.64 GHz, as well as the Evolutionary Map of the Universe (EMU) observations of the star itself, we determine a spectral index of $\alpha\,=\,+0.74\pm0.02$, indicating thermal emission. We propose that the shell and star both exhibit thermal emission, supported by the its appearance in near-infrared and H$\alpha$ observations. The latest Gaia parallax is used to determine a distance of 2.28$\pm$0.09 kpc. This star is well known for its surrounding circular nebulosity, and using the distance and an angular diameter of $8.^{\prime}42$, we determine the shell size to be 5.57$\pm$0.22 pc. We use the Gaia proper motion (PM) of WR16 to determine peculiar velocities of the star as $V_{\alpha}(pec) =$ –45.3$\pm$5.4 km s$^{-1}$ and $V_{\delta}(pec) =$ 22.8$\pm$4.7 km s$^{-1}$, which indicates that the star is moving in a north-west direction, and translates to a peculiar tangential velocity to be 50.7$\pm$6.9 km s$^{-1}$. We also use these proper motion (PM) to determine the shell’s origin, estimate an age of $\sim 9500\pm 1300$ yr, and determine its average expansion velocity to be $280\pm40$ km s$^{-1}$. This average expansion velocity suggests that the previous transitional phase is a Luminous Blue Variable (LBV) phase, rather than a Red Super Giant (RSG) phase. We also use the measured flux at 943.5 MHz to determine a mass-loss rate of $1.753\times 10^{-5}\,{\rm M}_\odot\,$yr$^{-1}$, and use this to determine a lower-limit on ionising photons of $N_{UV} \gt 1.406\times 10^{47}\,\textit{s}^{-1}$.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease process that represents a significant health shock for thousands of patients each year. Return to work outcomes and associated factors require evaluation to counsel patients and identify domains on which to focus clinical efforts. Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was performed using MEDLINE, EMBASE and Cochrane databases from inception to February 2024. Proportion of patients returning to work was collected from included studies. Odds ratios were pooled from studies evaluating the association between pre-rupture demographic variables, post-rupture clinical variables and return to work following aSAH. Results: Literature search yielded 3861 studies, of which 40 studies were included in the final analysis for a total of 6888 patients. On average, 55% (SD 17%) of all patients returned to work after an aSAH. Female sex (male sex OR 1.75), high grade aSAH on presentation (OR 0.30), and need for permanent CSF diversion (OR 0.50) are significantly associated with unemployment after aSAH. Conclusions: Female sex, high grade presentation, and permanent CSF diversion are associated with unemployment after aSAH. About half of all patients that experience aSAH return to work.

Background: Stroke survivors have a higher risk of depression and suicide, but how hospitalization for major depression modifies the risk of suicide after stroke is not well-known. Methods: We conducted a population-based matched cohort study of adults hospitalized with first-ever stroke between 2008 to 2017 matched 1:1 to the general Ontario population on age, sex, neighbourhood-level income, rurality, and comorbidities. Patients with major depression or deliberate self-harm prior to index event were excluded from both groups. We used cause-specific proportional hazards models to evaluate the association between stroke and suicide (defined as self-harm or death by suicide) and used an interaction term to assess effect modification of depression on stroke-suicide association. Results: We included 64,719 matched pairs of patients with stroke and without (45.5% female, mean age 71.4 years). Compared to matched controls, stroke survivors had a higher rate of suicide (11.1 vs. 3.2, HR 2.87 [2.35-3.51]). Depression was associated with a higher rate of suicide in both groups (HR 13.8 [8.82-21.61]). The interaction between stroke and depression was not significant (Pstroke*depression = 0.51). Conclusions: Hospitalization for depression does not modify the rate of suicide after stroke, suggesting the need to better understand the pathways leading to suicide after stroke.

High density should drive greater parasite exposure. However, evidence linking density with infection generally uses density proxies or measures of population size, rather than measures of individuals per space within a continuous population. We used a long-term study of wild sheep to link within-population spatiotemporal variation in host density with individual parasite counts. Although four parasites exhibited strong positive relationships with local density, these relationships were mostly restricted to juveniles and faded in adults. Furthermore, one ectoparasite showed strong negative relationships across all age classes. In contrast, population size – a measure of global density – had limited explanatory power, and its effects did not remove those of spatial density, but were distinct. These results indicate that local and global density can exhibit diverse and contrasting effects on infection within populations. Spatial measures of within-population local density may provide substantial additional insight to temporal metrics based on population size, and investigating them more widely could be revealing.

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.

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.

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.

Microbial mineral weathering has been predominantly investigated at shallow depths in humid and tropical environments. Much less is understood about its role in the deeper subsurface of arid and semi-arid environments where microbial weathering is limited by the availability of water and energy sources for microbial metabolism. However, the deep subsurface in these climate zones may host a microbial community that thrives on weathering of iron (Fe)-bearing minerals that serve as electron donors or acceptors.

To investigate the role of microorganisms in weathering of Fe-bearing minerals in a dry climate, we recovered a >80 m deep weathering profile in a semi-arid region of the Chilean Coastal Cordillera. The bedrock is rich in Fe-bearing minerals (hornblende, biotite, chlorite, magnetite and hematite) but lacks detectable organic carbon. We evaluated the bioavailability of Fe(III)-bearing minerals that may serve as an electron acceptor for Fe(III)-reducing microorganisms. Using geochemical, mineralogical and cultivation-based methods, we found enhanced Fe bioavailability and more in vitro microbial Fe(III) reduction at increased depth. We obtained an Fe(III)-reducing enrichment culture from the deepest weathered rock found at 77 m depth. This enrichment culture is capable of reducing ferrihydrite (up to 0.6 mM d–1) using lactate or dihydrogen as an electron donor and grows at circumneutral pH. The main organism in the enrichment culture is the spore-forming Desulfotomaculum ruminis (abundance of 98.5%) as revealed by 16S rRNA gene amplicon sequencing.

Our findings provide evidence for a microbial contribution to the weathering of Fe-bearing minerals in semi-arid environments. While microorganisms are probably not contributing to the weathering of Fe(II)-bearing silicate minerals, they are most likely of importance regarding reductive dissolution of secondary weathering products. The Fe(III) reduction quantified in this weathering profile by the in situ microbial community suggests that microorganisms are active weathering agents in semi-arid climates.

Quantum field theory predicts a nonlinear response of the vacuum to strong electromagnetic fields of macroscopic extent. This fundamental tenet has remained experimentally challenging and is yet to be tested in the laboratory. A particularly distinct signature of the resulting optical activity of the quantum vacuum is vacuum birefringence. This offers an excellent opportunity for a precision test of nonlinear quantum electrodynamics in an uncharted parameter regime. Recently, the operation of the high-intensity Relativistic Laser at the X-ray Free Electron Laser provided by the Helmholtz International Beamline for Extreme Fields has been inaugurated at the High Energy Density scientific instrument of the European X-ray Free Electron Laser. We make the case that this worldwide unique combination of an X-ray free-electron laser and an ultra-intense near-infrared laser together with recent advances in high-precision X-ray polarimetry, refinements of prospective discovery scenarios and progress in their accurate theoretical modelling have set the stage for performing an actual discovery experiment of quantum vacuum nonlinearity.