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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.
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 $N_{UV} \gt 1.406\times 10^{47}\,\textit{s}^{-1}$.
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.
We present the Evolutionary Map of the Universe (EMU) survey conducted with the Australian Square Kilometre Array Pathfinder (ASKAP). EMU aims to deliver the touchstone radio atlas of the southern hemisphere. We introduce EMU and review its science drivers and key science goals, updated and tailored to the current ASKAP five-year survey plan. The development of the survey strategy and planned sky coverage is presented, along with the operational aspects of the survey and associated data analysis, together with a selection of diagnostics demonstrating the imaging quality and data characteristics. We give a general description of the value-added data pipeline and data products before concluding with a discussion of links to other surveys and projects and an outline of EMU’s legacy value.
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.
Australian children fall short of national dietary guidelines with only 63 % consuming adequate fruit and 10 % enough vegetables. Before school care operates as part of Out of School Hours Care (OSHC) services and provides opportunities to address poor dietary habits in children. The aim of this study was to describe the food and beverages provided in before school care and to explore how service-level factors influence food provision.
Design:
A cross-sectional study was conducted in OSHC services. Services had their before school care visited twice between March and June 2021. Direct observation was used to capture food and beverage provision and child and staff behaviour during breakfast. Interviews with staff collected information on service characteristics. Foods were categorised using the Australian Dietary Guidelines, and frequencies were calculated. Fisher’s exact test was used to compare food provision with service characteristics.
Setting:
The before school care of OSHC services in New South Wales, Australia.
Participants:
Twenty-five OSHC services.
Results:
Fruit was provided on 22 % (n 11) of days and vegetables on 12 % (n 6). Services with nutrition policies containing specific language on food provision (i.e. measurable) were more likely to provide fruit compared with those with policies using non-specific language (P= 0·027). Services that reported receiving training in healthy eating provided more vegetables than those who had not received training (P= 0·037).
Conclusions:
Before school care can be supported to improve food provision through staff professional development and advocating to regulatory bodies for increased specificity requirements in the nutrition policies of service providers.
To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
This study uses stable and radiogenic isotopic data from Chalcolithic (c. 3000–1900 bc) humans and animals recovered from the Rego da Murta dolmens (Alvaiázere, Portugal) to understand dietary and mobility patterns in the populations using these monuments. The results suggest diets based primarily on C3 plants and terrestrial animals, with some possible variation in protein intake by age or status. Analyses of 87Sr/86Sr values identify two individuals out of ten from Rego da Murta I and four individuals out of fifteen from Rego da Murta II as migrants. These data were compared to other Chalcolithic burials in south-western Portugal: while diets were found to be similar across the region, the very high 87Sr/86Sr values recorded for two migrant humans match no known settlement in the broader region. A recent mapping study of 87Sr/86Sr values in Portugal suggests their origins may lie to the north/north-east of the dolmens.
Clostridioides difficile infection (CDI) is a common and often nosocomial infection associated with increased mortality and morbidity. Antibiotic use is the most important modifiable risk factor, but many patients require empiric antibiotics. We estimated the increased risk of hospital-onset CDI with one daily dose-equivalent (DDE) of various empiric antibiotics compared to management without that daily dose-equivalent.
Methods:
Using a multicenter retrospective cohort of adults admitted between March 2, 2020 and February 11, 2021 for the treatment of SARS-CoV-2, we used a series of three-level logistic regression models to estimate the probability of receiving each of several antibiotics of interest. For each antibiotic, we then limited our data set to patient-days at intermediate probability of receipt and used augmented inverse-probability weighted models to estimate the average treatment effect of one daily dose-equivalent, compared to management without that daily dose-equivalent, on the probability of hospital-onset CDI.
Results:
In 24,406 patient-days at intermediate probability of receipt, parenteral vancomycin increased risk of hospital-onset CDI, with an average treatment effect of 0.0096 cases per daily dose-equivalent (95% CI: 0.0053—0.0138). In 38,003 patient-days at intermediate probability of receipt, cefepime also increased subsequent CDI risk, with an estimated effect of 0.0074 more cases per daily dose-equivalent (95% CI: 0.0022—0.0126).
Conclusions:
Among common empiric antibiotics, parenteral vancomycin and cefepime appeared to increase risk of hospital-onset CDI. Causal inference observational study designs can be used to estimate patient-level harms of interventions such as empiric antimicrobials.
The USDA has implemented policies to address inequities for socially disadvantaged farmers and ranchers. This research examines agricultural risk inequities and the impact of 2018 Farm Bill programs on crop insurance use among minority and veteran farmers. Results indicate that minority and veteran farmers are disproportionately located in regions of the U.S. with higher risks of drought and excess precipitation. Yet, these producer groups had lower use of crop insurance prior to the implementation of the 2018 Farm Bill. However, the incentive programs created under the 2018 Farm Bill have increased use of federal crop insurance among these vulnerable populations.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.
Clostridioides difficile infection (CDI) may be misdiagnosed if testing is performed in the absence of signs or symptoms of disease. This study sought to support appropriate testing by estimating the impact of signs, symptoms, and healthcare exposures on pre-test likelihood of CDI.
Methods:
A panel of fifteen experts in infectious diseases participated in a modified UCLA/RAND Delphi study to estimate likelihood of CDI. Consensus, defined as agreement by >70% of panelists, was assessed via a REDCap survey. Items without consensus were discussed in a virtual meeting followed by a second survey.
Results:
All fifteen panelists completed both surveys (100% response rate). In the initial survey, consensus was present on 6 of 15 (40%) items related to risk of CDI. After panel discussion and clarification of questions, consensus (>70% agreement) was reached on all remaining items in the second survey. Antibiotics were identified as the primary risk factor for CDI and grouped into three categories: high-risk (likelihood ratio [LR] 7, 93% agreement among panelists in first survey), low-risk (LR 3, 87% agreement in first survey), and minimal-risk (LR 1, 71% agreement in first survey). Other major factors included new or unexplained severe diarrhea (e.g., ≥ 10 liquid bowel movements per day; LR 5, 100% agreement in second survey) and severe immunosuppression (LR 5, 87% agreement in second survey).
Conclusion:
Infectious disease experts concurred on the importance of signs, symptoms, and healthcare exposures for diagnosing CDI. The resulting risk estimates can be used by clinicians to optimize CDI testing and treatment.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.
Aims
To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.
Method
We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model.
Results
We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723–0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism.
Conclusions
We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.
The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.