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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
The savannah–forest mosaic of the Rupununi region of Guyana is a dispersal corridor between large tracts of intact Guiana Shield forests and a subsistence hunting ground for Indigenous Makushi and Wapichan communities. We conducted a camera-trap survey at 199 sites across four major forested habitat types and used multi-species occupancy modelling to determine regional-scale drivers of mammalian occupancy at both species and community levels, accounting for imperfect detection. We detected 47 savannah- and forest-dwelling mammal species, with the occupancy of medium- and large-bodied terrestrial mammal species (community occupancy) positively related to per cent forest cover and negatively to the presence of gallery forest habitat. The occupancy of 15 of 30 species was positively related to forest cover, suggesting the importance of maintaining forested habitat within the broader mosaic comprising savannahs and intermediate habitats for sustaining maximum mammal diversity. Jaguar Panthera onca occupancy was associated with the presence of livestock, and giant anteater Myrmecophaga tridactyla occupancy was negatively associated with distance to the nearest road, both results of concern in relation to potential human–wildlife conflict. The probability of detecting terrestrial mammal species (community detectability) increased away from villages, as did the detectability of two large-bodied, hunted species, the lowland tapir Tapirus terrestris and collared peccary Pecari tajacu, potentially indicating the negative effects of subsistence and commercial hunting in this savannah mosaic habitat. We use our findings to discuss how management strategies for hunting, fire, timber harvest and agriculture within Indigenous titled lands could help ensure the sustainability of these traditional livelihood activities.
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.
Despite nearly two centuries of actively stylizing itself as above the partisan fray of banal politics, the US Supreme Court faces increasing scrutiny over its ideological nature, ethical lapses, and perceived disconnection from democratic accountability. This article explores potential reforms including ethics guidelines, public affairs offices, and term limits to enhance the Court’s legitimacy. It also examines trends in judicial decision making, the Court’s relationship with public opinion, and the influence of identity politics on judicial perceptions through an examination of the scholarship on the Court. The article concludes by emphasizing the need for ongoing research and methodological innovation to address these challenges and ensure the Court’s role in American democracy.
A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.
Aims
We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.
Method
We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.
Results
Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.
Conclusions
Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.
This paper describes three collections of vertebrate fossils from the Lower Cretaceous Newark Canyon Formation of Eureka County, Nevada, made by the United States Geological Survey in 1961. Briefly mentioned in the prior literature, these specimens have gone unstudied for more than sixty years, until their recent transfer to the Smithsonian Institution. Re-examination of the materials reveals the first records of neoceratopsian and tyrannosauroid dinosaurs in the Newark Canyon Formation. In addition to augmenting the known vertebrate fauna from this poorly studied stratum, these occurrences provide important new data on otherwise rare taxa during a time of major faunal transition in North America.
From particle lifting in atmospheric boundary layers to dust ingestion in jet engines, the transport and deposition of inertial particles in wall-bounded turbulent flows are prevalent in both nature and industry. Due to triboelectrification during collisions, solid particles often acquire significant charges. However, the impacts of the resulting electrostatic interaction on the particle dynamics remain less understood. In this study, we present four-way coupled simulations to investigate the deposition of charged particles onto a grounded metal substrate through a fully developed turbulent boundary layer. Our numerical method tracks the dynamics of individual particles under the influence of turbulence, electrostatic forces and collisions. We first report a more pronounced near-wall accumulation and an increased wall-normal particle velocity due to particle charging. In addition, contrary to predictions from the classic Eulerian model, the wall-normal transport rate of inertial particles is significantly enhanced by electrostatic forces. A statistical approach is then applied to quantify the contributions from turbophoresis, biased sampling and electrostatic forces. For charged particles, a sharper gradient in wall-normal particle fluctuation velocity is observed, which substantially enhances turbophoresis and serves as the primary driving force of near-wall particle accumulation. Furthermore, charged particles are found to sample upward-moving fluids less frequently than neutral particles, thereby weakening the biased-sampling effect that typically pushes particles away from the wall. Finally, the wall-normal electric field is shown to depend on the competition between particle–wall and particle–particle electrostatic interactions, which helps to identify the dominant electrostatic force across a wide range of scenarios.
To investigate the use of rifampicin vials in Australian operating theaters (OT) to determine the method of administration and rationale for use.
Methods:
Retrospective (2022 and 2023) OT usage data for rifampicin 600 mg vials were analyzed to compare trends in use between Australian hospitals and between jurisdictions. An audit of rifampicin vials used in OT during 2023 was conducted at a large tertiary hospital.
Results:
Fifty-nine of 248 hospitals (24%) contributing data to the National Antimicrobial Utilisation Surveillance Program recorded OT use of rifampicin vials during 2022 and 2023. Excluding hospitals with no usage, the median use was 7 vials/annum/per hospital (IQR: 2–32). A wide variation in use was seen between Australian states and territories. An audit of OT use in 2023 at a large tertiary hospital found poor documentation of topical use; in most cases, documentation was in the operation note only, with no documentation on the medication charts, medical notes, or the anesthetic record. Of 33 rifampicin vials used in 2023, documented topical use was identified for 10 individual patients only, 4 of whom had a confirmed Staphylococcus aureus infection (1 methicillin-resistant and 3 methicillin-susceptible).
Conclusion:
Off-label, topical use of rifampicin during surgery is not uncommon in some Australian hospitals despite limited evidence of safety or efficacy. Given the potential for resistance, surgical use of rifampicin should be restricted to a named-patient basis, under the guidance of an infectious disease specialist/clinical microbiologist. Documentation of all medication use is recommended for patient safety.
Objectives/Goals: Undergraduate Medical Education (UME) may apply Just-in-Time training (JITT) to provide medical students with learning experiences closely aligned with real-time clinical needs. The purpose of this scoping review is to offer an overview of the implementation of JITT training in UME. Methods/Study Population: Following the five-stage framework by Arksey and O’Malley to methodically collect and analyze studies on JITT in UME, five electronic databases were searched, and a supplemental search for grey literature was conducted. Studies exploring the integration of JITT principles into UME clinical training and their time to follow-up after training were included. Bloom’s Taxonomy was used to assess educational goals of JITT interventions. Results/Anticipated Results: The review yielded 21 studies across 4 countries. The majority were cohort studies (13) and randomized control trials (5). Assessment definitions and use of JITT varied widely. Most studies focused on short-term outcomes, defined by being measured immediately after JITT session (15) or at the end of JITT-based rotation or clerkship (3). Three studies evaluated outcomes at a period longer than 2 weeks after completion of session or clerkship. Attitudes (9), followed by skills (8) were the most common educational goals of intervention. The efficacy and utility of JITT in improving educational goal acquisition was demonstrated in 90% (17/19) of the studies with reported outcomes. Discussion/Significance of Impact: The introduction of JITT in UME has been shown to meet the immediate needs of healthcare environments; however, evidence is limited in the evaluation of longer-term outcomes. Further research to determine the impact of JITT on long-term learning retention and education goal acquisition in UME is merited.
Objectives/Goals: Investigating the B-cell acute lymphoblastic leukemia (B-ALL)-associated germline SNP rs7090445, located in intron 3 of ARID5B, which is more frequently observed in individuals of Hispanic/Latino descent. Investigating the mechanisms behind this inherited single nucleotide polymorphisms (SNP) that may contribute to the higher incidence of B-ALL in this population. Methods/Study Population: Specific Aim 1: We hypothesize ARID5B SNP rs7090445 disrupts intrinsic enhancer function. Identification of critical DNA looping events impacted by ARID5B variants using Capture C. Affinity purification-mass spectrometry to identify potential ARID5B transcription mediators. Specific Aim 2: We hypothesize the B-ALL-associated SNP leads to a partial human B-cell differentiation block. Utilize Cas9-mediated homology-directed repair to create ARID5B SNP in primary human hematopoietic stem cells. Gene-edited HSCs will be differentiated into B cells using an ex vivo system. Fluorescence-activated cell sorting to sort our pool of cells into stages of B-cell development spectrum. Amplicon sequencing and variant allele frequency of rs7090445 SNP to evaluate its impact on B-cell development. Results/Anticipated Results: This proposal is conceptually innovative as it seeks to understand the mechanism by which the B-ALL-associated SNP rs7090445 in intron 3 of ARID5B disrupts enhancer function and investigates its impact on human B-cell development. Future research will investigate a tumor-suppressive role of ARID5B and whether it constitutes a “first-hit” of leukemogenesis. Discussion/Significance of Impact: Successful completion of this research will elucidate the critical role of the B-ALL-associated ARID5B SNP rs7090445 in human B-cell development and leukemogenesis. As this SNP is more prevalent in Hispanic/Latino populations, it will also provide crucial insights into the genetic factors behind the elevated incidence of B-ALL.
Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.
Self-injurious behaviors (SIB) are common in autistic people. SIB is mainly studied as a broad category, rather than by specific SIB types. We aimed to determine associations of distinct SIB types with common psychiatric, emotional, medical, and socio-demographic factors.
Methods
Participants included 323 autistic youth (~50% non−/minimally-speaking) with high-confidence autism diagnoses ages 4–21 years. Data were collected by the Autism Inpatient Collection during admission to a specialized psychiatric inpatient unit (www.sfari.org/resource/autism-inpatient-collection/). Caregivers completed questionnaires about their child, including SIB type and severity. The youth completed assessments with clinicians. Elastic net regressions identified associations between SIB types and factors.
Results
No single factor relates to all SIB types. SIB types have unique sets of associations. Consistent with previous work, more repetitive motor movements and lower adaptive skills are associated with most types of SIB; female sex is associated with hair/skin pulling and self-rubbing/scratching. More attention-deficit/hyperactivity disorder symptoms are associated with self-rubbing/scratching, skin picking, hair/skin pulling, and inserts finger/object. Inserts finger/object has the most medical condition associations. Self-hitting against surface/object has the most emotion dysregulation associations.
Conclusions
Specific SIB types have unique sets of associations. Future work can develop clinical likelihood scores for specific SIB types in inpatient settings, which can be tested with large community samples. Current approaches for SIB focus on the behavior functions, but there is an opportunity to further develop interventions by considering the specific SIB type in assessment and treatment. Identifying factors associated with specific SIB types may aid with screening, prevention, and treatment of these often-impairing behaviors.
There is an “underrepresentation problem” in philosophy departments and journals. Empirical data suggest that while we have seen some improvements since the 1990s, the rate of change has slowed down. Some posit that philosophy has disciplinary norms making it uniquely resistant to change. We present results from an empirical case study of a philosophy department that achieved and maintained male-female gender parity among its faculty as early as 2014. Our analysis extends beyond matters of gender parity because that is only one, albeit important, dimension of inclusion. We build from the study to reflect on strategies that may catalyze change.
The Asia Pacific Journal presents a link to an extraordinary 12-minute video by Matthew Carney of the Australian Broadcasting Corporation discussing the death penalty and the problem of wrongful convictions in Japanese criminal justice. This video explains what went wrong in three cases involving men who were victimized in the worst kind of way by Japan's criminal justice system, and it raises the possibility that these cases could stimulate reform in Japan's system of capital punishment and in the criminal justice system more generally.
Integral to the fabric of human technology, knots have shaped survival strategies since their first invention. As the ties that bind, their evolution and diversity have afforded human cultural change and expression. This study examines knotting traditions over time and space. We analyse a sample of 338 knots from 86 ethnographically or archaeologically documented societies over 12 millennia. Utilizing a novel approach that combines knot theory with computational string matching, we show that knotted structures can be precisely represented and compared across cultures. This methodology reveals a staple set of knots that occur cross-culturally, and our analysis offers insights into their cultural transmission and the reasons behind their ubiquity. We discuss knots in the context of cultural evolution, illustrating how the ethnographic and archaeological records suggest considerable know-how in knot-tying across societies spanning from the deep past to contemporary times. The study also highlights the potential of this methodology to extend beyond knots, proposing its applicability to a broader range of string and fibre technologies.
We examined the association between influenza vaccination policies at acute care hospitals and influenza vaccination coverage among healthcare personnel for the 2021–22 influenza season. Mandatory vaccination and masking for unvaccinated personnel were associated with increased odds of vaccination. Hospital employees had higher vaccination coverage than licensed independent practitioners.
Resilience of the healthcare system has been described as the ability to absorb, adapt, and respond to stress while maintaining the provision of safe patient care. We quantified the impact that stressors associated with the COVID-19 pandemic had on patient safety, as measured by central line-associated bloodstream infections (CLABSIs) reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network.
Design:
Acute care hospitals were mandated to report markers of resource availability (staffing and hospital occupancy with COVID-19 inpatients) to the federal government between July 2020 and June 2021. These data were used with community levels of COVID-19 to develop a statistical model to assess factors influencing rates of CLABSIs among inpatients during the pandemic.
Results:
After risk adjustment for hospital characteristics, measured stressors were associated with increased CLABSIs. Staff shortages for more than 10% of days per month were associated with a statistically significant increase of 2 CLABSIs per 10,000 central line days versus hospitals reporting staff shortages of less than 10% of days per month. CLABSIs increased with a higher inpatient COVID-19 occupancy rate; when COVID-19 occupancy was 20% or more, there were 5 more CLABSIs per 10,000 central line days versus the referent (less than 5%).
Conclusions:
Reporting of data pertaining to hospital operations during the COVID-19 pandemic afforded an opportunity to evaluate resilience of US hospitals. We demonstrate how the stressors of staffing shortages and high numbers of patients with COVID-19 negatively impacted patient safety, demonstrating poor resilience. Understanding stress in hospitals may allow for the development of policies that support resilience and drive safe care.
The authors offer reflections and lessons learned in a single pediatric tertiary center’s experience during a pediatric mass casualty incident (MCI). The MCI occurred at a holiday parade and the patients were brought to multiple community emergency departments for initial resuscitation prior to transfer to the Pediatric level 1 trauma center. In total, 18 children presented with severe blunt force trauma after a motor vehicle entered the parade route. Following initial triage in emergency departments, 10 of 18 children injured during the incident were admitted to the Pediatric Intensive Care Unit, collectively representing a system-wide stressor of emergency medicine, critical care, and surgical services. Institutional characteristics, activation of personnel and supplies, and psychosocial support for families during an MCI are important to consider in children’s hospitals’ disaster preparedness planning.
We have conducted a widefield, wideband, snapshot survey using the Australian SKA Pathfinder (ASKAP) referred to as the Rapid ASKAP Continuum Survey (RACS). RACS covers $\approx 90$% of the sky, with multiple observing epochs in three frequency bands sampling the ASKAP frequency range of 700–1 800 MHz. This paper describes the third major epoch at 1 655.5 MHz, RACS-high, and the subsequent imaging and catalogue data release. The RACS-high observations at 1 655.5 MHz are otherwise similar to the previously released RACS-mid (at 1 367.5 MHz) and were calibrated and imaged with minimal changes. From the 1 493 images covering the sky up to declination $\approx +48^\circ$, we present a catalogue of 2 677 509 radio sources. The catalogue is constructed from images with a median root-mean-square noise of $\approx 195$$\unicode{x03BC}$Jy PSF$^{-1}$ (point-spread function) and a median angular resolution of $11{\stackrel{\prime\prime}{\raise-0pt\hbox{.}}}8 \times 8{\stackrel{\prime\prime}{\raise-0pt\hbox{.}}}1$. The overall reliability of the catalogue is estimated to be 99.18%, and we find a decrease in reliability as angular resolution improves. We estimate the brightness scale to be accurate to 10%, and the astrometric accuracy to be within $\approx 0{\stackrel{\prime\prime}{\raise-0pt\hbox{.}}}6$ in right ascension and $\approx 0{\stackrel{\prime\prime}{\raise-0pt\hbox{.}}}7$ in declination after correction of a systematic declination-dependent offset. All data products from RACS-high, including calibrated visibility datasets, images from individual observations, full-sensitivity mosaics, and the all-sky catalogue are available at the CSIRO ASKAP Science Data Archive.
Previous studies have linked social behaviors to COVID-19 risk in the general population. The impact of these behaviors among healthcare personnel, who face higher workplace exposure risks and possess greater prevention awareness, remains less explored.
Design:
We conducted a Prospective cohort study from December 2021 to May 2022, using monthly surveys. Exposures included (1) a composite of nine common social activities in the past month and (2) similarity of social behavior compared to pre-pandemic. Outcomes included self-reported SARS-CoV-2 infection (primary)and testing for SARS-CoV-2 (secondary). Mixed-effect logistic regression assessed the association between social behavior and outcomes, adjusting for baseline and time-dependent covariates. To account for missed surveys, we employed inverse probability-of-censoring weighting with a propensity score approach.
Setting:
An academic healthcare system.
Participants:
Healthcare personnel.
Results:
Of 1,302 healthcare personnel who completed ≥2 surveys, 244 reported ≥1 positive test during the study, resulting in a cumulative incidence of 19%. More social activities in the past month and social behavior similar to pre-pandemic levels were associated with increased likelihood of SARS-CoV-2 infection (recent social activity composite: OR = 1.11, 95% CI 1.02–1.21; pre-pandemic social similarity: OR = 1.14, 95% CI 1.07–1.21). Neither was significantly associated with testing for SARS-CoV-2.
Conclusions:
Healthcare personnel social behavior outside work was associated with a higher risk for COVID-19. To protect the hospital workforce, risk mitigation strategies for healthcare personnel should focus on both the community and workplace.