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We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
This paper provides practical guidance to UK-based financial institutions (UKFIs) that are subject to the “operational resilience” guideline requirements of the Bank of England (BoE), Prudential Regulatory Authority and Financial Conduct Authority, issued in 2021, and fully effective for 31 March 2025. It contains practical suggestions and recommendations to assist UKFIs in implementing the guidelines. The scope of the paper covers issues related to (a) overviewing the latest equivalent operational resilience guidance in other countries and internationally (b) identifying key issues related to risk culture, risk appetite, information technology, tolerance setting, risk modelling, scenario planning and customer oriented operational resilience (c) identifying a framework for operational resilience based on a thorough understanding of these parameters and (d) designing and implementing an operational resilience maturity dashboard based on a sample of large UKIFs. The study also contains recommendations for further action, including enhanced controls and operational risk management frameworks. It concludes by identifying imperative policy actions to ensure that the implementation of the guidelines is more effective.
Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.
Vitamin A deficiency (VAD) poses significant health risks and is prevalent in children and adolescents in India. This study aimed to determine the effect of seasonal variation and availability of vitamin A-rich (VA-rich) foods on serum retinol in adolescents. Data on serum retinol levels from adolescents (n 2297, mean age 14 years) from the Comprehensive National Nutrition Survey (2016–2018) in India were analysed, with VAD defined as serum retinol < 0·7 µmol/L. Five states were selected based on a comparable under-five mortality rate and the seasonal spread of the data collection period. Dietary data from adolescents and children ≤ 4 years old were used to assess VA-rich food consumption. A linear mixed model framework was employed to analyse the relationship between serum retinol, month of the year and VA-rich food consumption, with a priori ranking to control for multiple hypothesis testing. Consumption of VA-rich foods, particularly fruits and vegetables/roots and tubers, showed seasonal patterns, with higher consumption during summer and monsoon months. Significant associations were found between serum retinol concentrations and age, month of sampling, consumption of VA-rich foods and fish. VAD prevalence was lowest in August, coinciding with higher consumption of VA-rich fruits and foods. Findings highlight the importance of considering seasonality in assessing VAD prevalence and careful interpretation of survey findings. Intentional design, analysis and reporting of surveys to capture seasonal variation is crucial for accurate assessment and interpretation of VAD prevalence, including during monitoring and evaluation of programmes, and to ensure that public health strategies are appropriately informed.
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 kinetic stability of collisionless, sloshing beam-ion ($45^\circ$ pitch angle) plasma is studied in a three-dimensional (3-D) simple magnetic mirror, mimicking the Wisconsin high-temperature superconductor axisymmetric mirror experiment. The collisional Fokker–Planck code CQL3D-m provides a slowing-down beam-ion distribution to initialize the kinetic-ion/fluid-electron code Hybrid-VPIC, which then simulates free plasma decay without external heating or fuelling. Over $1$–$10\;\mathrm{\unicode{x03BC} s}$, drift-cyclotron loss-cone (DCLC) modes grow and saturate in amplitude. The DCLC scatters ions to a marginally stable distribution with gas-dynamic rather than classical-mirror confinement. Sloshing ions can trap cool (low-energy) ions in an electrostatic potential well to stabilize DCLC, but DCLC itself does not scatter sloshing beam-ions into the said well. Instead, cool ions must come from external sources such as charge-exchange collisions with a low-density neutral population. Manually adding cool $\mathord {\sim } 1\;\mathrm{keV}$ ions improves beam-ion confinement several-fold in Hybrid-VPIC simulations, which qualitatively corroborates prior measurements from real mirror devices with sloshing ions.
An important component of post-release monitoring of biological control of invasive plants is the tracking of species interactions. During post-release monitoring following the initial releases of the weevil Ceutorhynchus scrobicollis Nerenscheimer and Wagner (Coleoptera: Curculionidae) on garlic mustard, Alliaria petiolata (Marschall von Bieberstein) Cavara and Grande (Brassicaceae), in Ontario, Canada, we identified the presence of larvae of the tumbling flower beetle, Mordellina ancilla Leconte (Coleoptera: Mordellidae), in garlic mustard stems. This study documents the life history of M. ancilla on garlic mustard to assess for potential interactions between M. ancilla and C. scrobicollis as a biological control agent. Garlic mustard stems were sampled at eight sites across southern Ontario and throughout the course of one year to record the prevalence of this association and to observe its life cycle on the plant. We found M. ancilla to be a widespread stem-borer of late second–year and dead garlic mustard plants across sampling locations. This is the first host record for M. ancilla on garlic mustard. The observed life cycle of M. ancilla indicates that it is unlikely to negatively impact the growth and reproduction of garlic mustard and that it is unlikely to affect the use of C. scrobicollis as a biological control agent.
Following democracy’s global advance in the late twentieth century, recent patterns of democratic “backsliding” have generated extensive scholarly debate. Since backsliding towards autocracy is often the work of elected leaders operating within democratic institutions, it challenges conventional thinking about democratic consolidation, the enforcement of institutional checks and balances, and the reproduction of democratic norms. Drawing insights from classic literature on democratic transitions and consolidation, this volume examines the nature of contemporary threats to democracy, recognizing that the central challenge is not always to induce the compliance of those who lose elections, but rather those who emerge victorious and turn the institutional leverage of incumbency into a source of ongoing competitive advantage. There is, then, both a “loser’s dilemma” and a “winner’s dilemma” embedded in the study of democratic resiliency. Patterns of backsliding have revealed the contingent and potentially contested underpinnings of democratic institutions in any political order, given the presence (whether latent or active) of authoritarian political and cultural currents. Democracy is, therefore, best understood not as a standardized regime template or a static endpoint of political development, but rather as a dialectical frontier that advances ‒ and sometimes recedes ‒ according to the dynamic interplay countervailing forces.
As explained in Chapter 1, state institutions are inevitably transformed into sites of regime contestation between democratic and autocratic forces when democratic backsliding is threatened or underway. That is especially the case in social and political contexts where exclusionary forms of majoritarian rule or ethnonationalism contest liberal and pluralist civil societies. The challenge for scholars is to identify the conditions under which key institutional sites serve as bastions of democratic accountability and resilience, and how and when these sites can be neutralized or even transformed into weapons of autocratization. Often referred to as “referee institutions” (such as constitutional courts and electoral commissions) and tools of horizontal accountability for checking executive aggrandizement (including ombudsman, investigative bureaus, and information commissions), key state agencies must be sufficiently capacious and nonpartisan to serve as guardrails in times of democratic contestation and regime uncertainty.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.