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Next-generation X-ray satellite telescopes such as XRISM, NewAthena and Lynx will enable observations of exotic astrophysical sources at unprecedented spectral and spatial resolution. Proper interpretation of these data demands that the accuracy of the models is at least within the uncertainty of the observations. One set of quantities that might not currently meet this requirement is transition energies of various astrophysically relevant ions. Current databases are populated with many untested theoretical calculations. Accurate laboratory benchmarks are required to better understand the coming data. We obtained laboratory spectra of X-ray lines from a silicon plasma at an average spectral resolving power of $\sim$7500 with a spherically bent crystal spectrometer on the Z facility at Sandia National Laboratories. Many of the lines in the data are measured here for the first time. We report measurements of 53 transitions originating from the K-shells of He-like to B-like silicon in the energy range between $\sim$1795 and 1880 eV (6.6–6.9 Å). The lines were identified by qualitative comparison against a full synthetic spectrum calculated with ATOMIC. The average fractional uncertainty (uncertainty/energy) for all reported lines is ${\sim}5.4 \times 10^{-5}$. We compare the measured quantities against transition energies calculated with RATS and FAC as well as those reported in the NIST ASD and XSTAR’s uaDB. Average absolute differences relative to experimentally measured values are 0.20, 0.32, 0.17 and 0.38 eV, respectively. All calculations/databases show good agreement with the experimental values; NIST ASD shows the closest match overall.
Clinical guidelines for personality disorder emphasise the importance of patients being supported to develop psychological skills to help them manage their symptoms and behaviours. But where these mechanisms fail, and hospital admission occurs, little is known about how episodes of acutely disturbed behaviour are managed.
Aims
To explore the clinical characteristics and management of episodes of acutely disturbed behaviour requiring medication in in-patients with a diagnosis of personality disorder.
Method
Analysis of clinical audit data collected in 2024 by the Prescribing Observatory for Mental Health, as part of a quality improvement programme addressing the pharmacological management of acutely disturbed behaviour. Data were collected from clinical records using a bespoke proforma.
Results
Sixty-two mental health Trusts submitted data on 951 episodes of acutely disturbed behaviour involving patients with a personality disorder, with this being the sole psychiatric diagnosis in 471 (50%). Of the total, 782 (82%) episodes occurred in female patients. Compared with males, episodes in females were three times more likely to involve self-harming behaviour or be considered to pose such a risk (22% and 70% respectively: p < 0.001). Parenteral medication (rapid tranquillisation) was administered twice as often in episodes involving females than in males (64 and 34% respectively: p < 0.001).
Conclusions
Our findings suggest that there are a large number of episodes of acutely disturbed behaviour on psychiatric wards in women with a diagnosis of personality disorder. These episodes are characterised by self-harm and regularly prompt the administration of rapid tranquillisation. This has potential implications for service design, staff training, and research.
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 $N_{UV} \gt 1.406\times 10^{47}\,\textit{s}^{-1}$.
Inadequate recruitment and retention impede clinical trial goals. Emerging decentralized clinical trials (DCTs) leveraging digital health technologies (DHTs) for remote recruitment and data collection aim to address barriers to participation in traditional trials. The ACTIV-6 trial is a DCT using DHTs, but participants’ experiences of such trials remain largely unknown. This study explored participants’ perspectives of the ACTIV-6 DCT that tested outpatient COVID-19 therapeutics.
Methods:
Participants in the ACTIV-6 study were recruited via email to share their day-to-day trial experiences during 1-hour virtual focus groups. Two human factors researchers guided group discussions through a semi-structured script that probed expectations and perceptions of study activities. Qualitative data analysis was conducted using a grounded theory approach with open coding to identify key themes.
Results:
Twenty-eight ACTIV-6 study participants aged 30+ years completed a virtual focus group including 1–4 participants each. Analysis yielded three major themes: perceptions of the DCT experience, study activity engagement, and trust. Participants perceived the use of remote DCT procedures supported by DHTs as an acceptable and efficient method of organizing and tracking study activities, communicating with study personnel, and managing study medications at home. Use of social media was effective in supporting geographically dispersed participant recruitment but also raised issues with trust and study legitimacy.
Conclusions:
While participants in this qualitative study viewed the DCT-with-DHT approach as reasonably efficient and engaging, they also identified challenges to address. Understanding facilitators and barriers to DCT participation and DHT interaction can help improve future research design.
Mentored undergraduate research experiences (UREs) can play a critical role in developing science identity and skills, especially for students from historically underrepresented backgrounds. This study investigates science identity and responsibility for scientific roles among scholars in a program aiming to diversify the biomedical workforce. Scholars were placed in UREs at either their home institution (a minority-serving institution [MSI]) or at a research-intensive medical institution with a Clinical and Translational Science Award (CTSA).
Methods:
We analyze data from surveys administered annually to the scholars. We first compare changes in science identity for scholars placed at the MSI and the CTSA site from the term after the scholar started their URE to one year later. We then analyze differences in responsibility in scientific roles performed by scholars at the two institutions.
Results:
We found evidence of gains in science identity after a year for scholars placed at both institutions but of a somewhat larger magnitude at the CTSA site. However, no significant differences were observed across institutions on science identity at the endpoint. An exploration of scientific roles suggests that scholars at the CTSA site assumed more responsibility in roles related to data curation and analysis, while scholars at the MSI had higher responsibility for resource acquisition-related roles.
Conclusion:
These results suggest that CTSA site URE placements may offer distinct opportunities for both identity formation and skill development beyond placements at home institutions. Overall, these results suggest opportunities for partnerships between MSIs and CTSA sites in the training of biomedical researchers.
To compare rates of clinical response in children with Clostridioides difficile infection (CDI) treated with metronidazole vs vancomycin.
Design:
Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2–17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response.
Results:
One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response (P = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin (P = 0.105).
Conclusions:
In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.
Sodium-glucose cotransporter-2 inhibitors reduce cardiovascular outcomes in patients with congestive heart failure and a biventricular circulation. Congestive heart failure in Fontan univentricular circulation is distinctly different. Experience with sodium-glucose cotransporter-2 inhibitors in this group has not yet been well described.
Objectives:
This work describes safety and tolerability of sodium-glucose cotransporter-2 inhibitors in patients with Fontan circulation.
Methods:
Single-centre review of patients with Fontan circulation prescribed a sodium-glucose cotransporter-2 inhibitors for congestive heart failure. Primary outcome was tolerability or need for discontinuation. Secondary outcomes were changes in New York Heart Association class, congestive heart failure hospitalisation, ventricular function, exercise performance, and laboratory values.
Results:
We identified 25 patients with Fontan circulation prescribed an sodium-glucose cotransporter-2 inhibitors, most with a systemic right ventricle. Over a third of subjects had at least moderately reduced baseline ventricular function. Baseline catheterisation showed a mean Fontan pressure of 17.1 ± 3.7 mmHg and pulmonary capillary wedge pressure 11.7 ± 3.2 mmHg at rest; 59% had occult diastolic dysfunction with abnormal pulmonary capillary wedge pressure elevation following volume expansion. Most were on congestive heart failure medications and/or a pulmonary vasodilator prior to sodium-glucose cotransporter-2 inhibitors addition, and three had a congestive heart failure hospitalisation within the previous year. All reported good medication tolerance except one patient was nonadherent to medications and two discontinued sodium-glucose cotransporter-2 inhibitors for perceived side effects. There were no significant differences in secondary outcomes. There was, however, a downward trend of serum brain natriuretic peptide (n = 13) and improved peak VO2 (n = 6), though neither statistically significant (p > 0.05).
Conclusion:
This series, the largest published to date, suggests that sodium-glucose cotransporter-2 inhibitors are safe and tolerable congestive heart failure therapy in Fontan circulation. Further research is warranted to explore therapy in this unique population.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
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.
Loneliness has become a major public health issue of the recent decades due to its severe impact on health and mortality. Little is known about the relation between loneliness and social anxiety. This study aimed (1) to explore levels of loneliness and social anxiety in the general population, and (2) to assess whether and how loneliness affects symptoms of social anxiety and vice versa over a period of five years.
Methods
The study combined data from the baseline assessment and the five-year follow-up of the population-based Gutenberg Health Study. Data of N = 15 010 participants at baseline (Mage = 55.01, s.d.age = 11.10) were analyzed. Multiple regression analyses with loneliness and symptoms of social anxiety at follow-up including sociodemographic, physical illnesses, and mental health indicators at baseline were used to test relevant covariates. Effects of loneliness on symptoms of social anxiety over five years and vice versa were analyzed by autoregressive cross-lagged structural equation models.
Results
At baseline, 1076 participants (7.41%) showed symptoms of social anxiety and 1537 (10.48%) participants reported feelings of loneliness. Controlling for relevant covariates, symptoms of social anxiety had a small significant effect on loneliness five years later (standardized estimate of 0.164, p < 0.001). Vice versa, there was no significant effect of loneliness on symptoms of social anxiety taking relevant covariates into account.
Conclusions
Findings provided evidence that symptoms of social anxiety are predictive for loneliness. Thus, prevention and intervention efforts for loneliness need to address symptoms of social anxiety.
Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.
Aims
We investigated employment and relationship status changes among patients across the affective and psychotic spectrum – in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.
Method
The sample from the longitudinal multicentric PsyCourse Study comprised 1260 patients with affective and psychotic spectrum disorders and 441 controls (mean age ± s.d., 39.91 ± 12.65 years; 48.9% female). Multistate models (Markov) were used to analyse transitions in employment and relationship status, focusing on transition intensities. Analyses contained multiple multistate models adjusted for age, gender, job or partner, diagnostic group and Global Assessment of Functioning (GAF) in different combinations to analyse the impact of the covariates on the hazard ratio of changing employment or relationship status.
Results
The clinical group had a higher hazard ratio of losing partner (hazard ratio 1.46, P < 0.001) and job (hazard ratio 4.18, P < 0.001) than the control group (corrected for age/gender). Compared with controls, clinical groups had a higher hazard of losing partner (affective group, hazard ratio 2.69, P = 0.003; psychotic group, hazard ratio 3.06, P = 0.001) and job (affective group, hazard ratio 3.43, P < 0.001; psychotic group, hazard ratio 4.11, P < 0.001). Adjusting for GAF, the hazard ratio of losing partner and job decreased in both clinical groups compared with controls.
Conclusion
Patients face an increased hazard of job loss and relationship dissolution compared with healthy controls, and this is partially conditioned by the diagnosis and functional level. These findings underscore a high demand for destigmatisation and support for individuals in managing their functional limitations.
To understand healthcare workers’ (HCWs) beliefs and practices toward blood culture (BCx) use.
Design:
Cross-sectional electronic survey and semi-structured interviews.
Setting:
Academic hospitals in the United States.
Participants:
HCWs involved in BCx ordering and collection in adult intensive care units (ICU) and wards.
Methods:
We administered an anonymous electronic survey to HCWs and conducted semi-structured interviews with unit staff and quality improvement (QI) leaders in these institutions to understand their perspectives regarding BCx stewardship between February and November 2023.
Results:
Of 314 HCWs who responded to the survey, most (67.4%) were physicians and were involved in BCx ordering (82.3%). Most survey respondents reported that clinicians had a low threshold to culture patients for fever (84.4%) and agreed they could safely reduce the number of BCx obtained in their units (65%). However, only half of them believed BCx was overused. Although most made BCx decisions as a team (74.1%), a minority reported these team discussions occurred daily (42.4%). A third of respondents reported not usually collecting the correct volume per BCx bottle, half were unaware of the improved sensitivity of 2 BCx sets, and most were unsure of the nationally recommended BCx contamination threshold (87.5%). Knowledge regarding the utility of BCx for common infections was limited.
Conclusions:
HCWs’ understanding of best collection practices and yield of BCx was limited.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.
This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public–private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives’ involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic.
Soybean [Glycine max (L.) Merr.] that lack resistance to auxin herbicides [i.e., not genetically modified for resistance] have well-documented responses to those particular herbicides, with yield loss being probable. When a soybean field is injured by auxin herbicides, regulatory authorities often collect a plant sample from that field. This research attempted to simulate soybean exposures due to accidental mixing of incorrect herbicides, tank contamination, or particle drift. This research examined whether analytical testing of herbicide residues on soybean to aminocyclopyrachlor (ACP), aminopyralid, 2,4-D, or dicamba would be related to the visual observations and yield responses from these herbicides. ACP and aminopyralid were applied to R1 soybean at 0.1, 1, and 10 g ae ha−1; 2,4-D and dicamba were applied at 1, 10, and 100 g ae ha−1. Visual evaluations and plant sample collections were undertaken at 1, 3, 7, 14, and 21 d after treatment (DAT), and yield was measured. The conservative limits of detection for the four herbicides in this project were 5, 10, 5, and 5 ng g−1 fresh weight of soybean for ACP, aminopyralid, 2,4-D, and dicamba, respectively. Many of the plant samples were non-detects, especially at lower application dosages. All herbicide concentrations rapidly declined soon after application, and many reached nondetectable limits by 14 DAT. All herbicide treatments caused soybean injury, although the response to 2,4-D was markedly lower than the responses to the other three herbicides. There was no apparent correlation between herbicide concentrations (which were declining over time) and the observed soybean injury (which was increasing over time or staying the same). This research indicated that plant samples should be collected as soon as possible after soybean exposure to auxin herbicides.