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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.
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.
Objectives/Goals: This study aims to evaluate the performance of a third-party artificial intelligence (AI) product in predicting diagnosis-related groups (DRGs) in a community healthcare system. We highlight a use case illustrating how clinical practice leverages AI-predicted information in unexpected yet advantageous ways and assess the AI predictions accuracy and practical application. Methods/Study Population: DRGs are crucial for hospital reimbursement under the prospective payment model. The Mayo Clinic Health System (MCHS), a network of clinics and hospitals serving a substantial rural population in Minnesota and Wisconsin, has recently adopted an AI algorithm developed by Xsolis (an AI-focused healthcare solution provider). This algorithm, a 1D convolutional neural network, predicts DRGs based on clinical documentation. To assess the accuracy of AI-generated DRG predictions for inpatient discharges, we analyzed data from 930 patients hospitalized at MCHS Mankato between March 2 and May 13, 2024. The Xsolis platform provided the top three DRG predictions for the first 48 hours of each inpatient stay. The accuracy of these predictions was then compared against the final billed DRG codes from the hospital’s records. Results/Anticipated Results: In our validation set, Xsolis achieved a top-3 DRG prediction accuracy of 71% at 24 hours and 81% at 48 hours, which is lower than the originally reported accuracy of 81.1% and 83.3%, respectively. Interestingly, discussions with clinical practice leaders revealed that the most valuable information derived from the AI predictions was the expected geometric mean length of stay (GMLOS), which Xsolis was perceived to predict accurately. In the Medicare system, each DRG is associated with an expected GMLOS, a critical factor for efficient hospital flow planning. A subsequent analysis comparing predicted GMLOS with the actual length of stay showed variances of -0.10 days on day 1 and 0.14 days on day 2, indicating a high degree of accuracy and aligning with clinical practice perceptions. Discussion/Significance of Impact: Our research underscores that clinical practice can leverage AI predictions in unexpected yet beneficial ways. While initially focused on DRG prediction, the associated GMLOS emerged as more significant. This suggests that AI algorithm validation should be tailored to specific clinical needs rather than relying solely on generalized benchmarks.
The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth- or internet-delivered CBTi are alternative ways to increase access. To date, these intervention modalities have never been compared within a single study. Further, few studies have examined (a) predictors of response to the different modalities, (b) whether successfully treating insomnia can result in improvement of health-related biomarkers, and (c) mechanisms of change in CBTi. This protocol was designed to compare the three CBTi modalities to each other and a waitlist control for adults aged 50–65 years (N = 100). Participants are randomly assigned to one of four study arms: in-person- (n = 30), telehealth- (n = 30) internet-delivered (n = 30) CBTi, or 12-week waitlist control (n = 10). Outcomes include self-reported insomnia symptom severity, polysomnography, circadian rhythms of activity and core body temperature, blood- and sweat-based biomarkers, cognitive functioning and magnetic resonance imaging.
The spotted hyaena Crocuta crocuta is relatively understudied across its range despite evidence of widespread declines. It is therefore essential that robust baseline population density assessments are conducted to inform current management and future conservation policy. In Mozambique this is urgent as decades of armed conflict followed by unchecked poaching have resulted in large-scale wildlife declines and extirpations. We conducted the first robust population density estimate for a spotted hyaena population in Mozambique using spatially explicit capture–recapture methodologies. We recorded a relatively low population density of 0.8–2.1 hyaenas/100 km2 in the wildlife management area Coutada 11 in the Zambezi Delta of central Mozambique in 2021. These densities are well below the estimated carrying capacity for the landscape and are comparable to published densities in high human-impact, miombo woodland-dominated and arid environments. The combination of historical armed conflict, marginal trophy hunting and bushmeat poaching using wire snares and gin traps (with physical injuries evident in 9% of identified individuals) presents persistent anthropogenic pressure, limiting the post-war recovery of this resident hyaena population. We provide insights into the dynamics of hyaena population status and recovery in such post-war landscapes, adding to mounting evidence that the species is less resilient to severe anthropogenic disturbances than previously believed. We recommend long-term monitoring of this and other carnivore populations in post-war landscapes to ascertain demographic trends and implement effective conservation interventions for population recovery.
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.
Dates from recently excavated Gangetic site of Sakas in Bihar, India, place it at ca.1800–1100 BC. The ceramic and lithic chronologies have been interpreted as Early Farming, Transitional and Chalcolithic/Developed Farming in date. However, depending on where in the Ganges Plains is studied, the time frame of Early, Developed and Advanced Farming periods varies widely, from 7th millennium to 2nd millennium BC and beyond, making the chronological framing of absolute dates within a regional scheme highly complex. In this paper we report the new radiocarbon results from Sakas and note how while these are critical for cementing the absolute dating of the site, until such time as a more stable periodization linked not only to relative and absolute dates but also human lifeways within the different zones of the Ganges plains is created, there remains difficulties in understanding how Sakas and other sites of similar date fit into the changing social, cultural and economic systems in this region.
Scholars have long recognized that interpersonal networks play a role in mobilizing social movements. Yet, many questions remain. This Element addresses these questions by theorizing about three dimensions of ties: emotionally strong or weak, movement insider or outsider, and ingroup or cross-cleavage. The survey data on the 2020 Black Lives Matter protests show that weak and cross-cleavage ties among outsiders enabled the movement to evolve from a small provocation into a massive national mobilization. In particular, the authors find that Black people mobilized one another through social media and spurred their non-Black friends to protest by sharing their personal encounters with racism. These results depart from the established literature regarding the civil rights movement that emphasizes strong, movement-internal, and racially homogenous ties. The networks that mobilize appear to have changed in the social media era. This title is also available as Open Access on Cambridge Core.
Cognitive impairment is often comorbid with depression and anxiety, and the cognitive status of older adult patients can drastically impact depression treatment outcomes. The cognitive status of these patients invariably changes psychological treatment approaches that otherwise are viable and feasible in older adults. For example, although cognitive behavioral therapy is effective in treating cognitively intact patients with depression, it often relies on executive function (such as flexible thinking and problem solving) and other cognitive abilities that are impaired in patients with comorbid cognitive impairment. Practically, this results in unstandardized modifications to psychotherapy that may impact the fidelity—and thus effectiveness—of treatment. It is important to assess and classify cognitive dysfunction in depression treatment-seeking older adults in trials. This can help generalize research findings and identify potential barriers in transferring psychotherapeutic approaches for older adults with depression from treatment trials to practical clinical use, particularly in hard-to-treat populations with comorbid cognitive impairment.
Participants and Methods:
A systematic literature search was conducted in PubMed for the period 2000-2022. Study inclusion criteria was operationalised as follows: participants were identified as older adults (55 years and older), their primary psychiatric diagnosis was depression, and the study was a trial for depression treatment. Key search terms included: depression, treatment, psychotherapy, therapy, counseling, intervention, older adult, senior, late-life, elder, aged, clinical trial, and randomized controlled trial.
Results:
An initial search of the key terms returned 3,972 articles. 178 of these articles were subject to full text review. Of those, 45 articles met inclusion criteria. Overall study quality was acceptable. A portion of treatment trials did not assess for cognitive functioning. A majority of the articles excluded patients with cognitive impairment, with no further elaboration on the potential impact of cognitive functioning on treatment outcomes. A smaller portion of studies were more inclusive of the cognitive range of patient participants; however, they did not comment on the cognitive heterogeneity of their samples. Only three studies used a more extensive neuropsychological battery to examine cognitive profiles of patient participants. However, two of these studies also excluded individuals that fell below the cognitively intact range based on brief cognitive screening measures. Of the few studies that examined depression treatment in cognitively impaired and dementia patient populations, two trials examined cognitive functioning as a predictor or moderator of depression treatment outcome.
Conclusions:
Given that cognitive status can significantly impact depression treatment outcomes for older adults, there is a shocking dearth of inclusion of cognitively impaired patients in depression treatment clinical trials. Moreover, the limited studies that examined depression treatment in cognitively impaired populations, there is a lack of comprehensive cognitive assessment, and lack of exploration on how different types of cognitive dysfunction may contribute to variable depression treatment response. Future depression treatment trials in older adults should expand to include a variety of cognitive functioning ranges, as well as a more detailed assessment of how specific cognitive domains may impact treatment outcomes.
Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.
The Australian SKA Pathfinder (ASKAP) radio telescope has carried out a survey of the entire Southern Sky at 887.5 MHz. The wide area, high angular resolution, and broad bandwidth provided by the low-band Rapid ASKAP Continuum Survey (RACS-low) allow the production of a next-generation rotation measure (RM) grid across the entire Southern Sky. Here we introduce this project as Spectral and Polarisation in Cutouts of Extragalactic sources from RACS (SPICE-RACS). In our first data release, we image 30 RACS-low fields in Stokes I, Q, U at 25$^{\prime\prime}$ angular resolution, across 744–1032 MHz with 1 MHz spectral resolution. Using a bespoke, highly parallelised, software pipeline we are able to rapidly process wide-area spectro-polarimetric ASKAP observations. Notably, we use ‘postage stamp’ cutouts to assess the polarisation properties of 105912 radio components detected in total intensity. We find that our Stokes Q and U images have an rms noise of $\sim$80 $\unicode{x03BC}$Jy PSF$^{-1}$, and our correction for instrumental polarisation leakage allows us to characterise components with $\gtrsim$1% polarisation fraction over most of the field of view. We produce a broadband polarised radio component catalogue that contains 5818 RM measurements over an area of $\sim$1300 deg$^{2}$ with an average error in RM of $1.6^{+1.1}_{-1.0}$ rad m$^{-2}$, and an average linear polarisation fraction $3.4^{+3.0}_{-1.6}$ %. We determine this subset of components using the conditions that the polarised signal-to-noise ratio is $>$8, the polarisation fraction is above our estimated polarised leakage, and the Stokes I spectrum has a reliable model. Our catalogue provides an areal density of $4\pm2$ RMs deg$^{-2}$; an increase of $\sim$4 times over the previous state-of-the-art (Taylor, Stil, Sunstrum 2009, ApJ, 702, 1230). Meaning that, having used just 3% of the RACS-low sky area, we have produced the 3rd largest RM catalogue to date. This catalogue has broad applications for studying astrophysical magnetic fields; notably revealing remarkable structure in the Galactic RM sky. We will explore this Galactic structure in a follow-up paper. We will also apply the techniques described here to produce an all-Southern-sky RM catalogue from RACS observations. Finally, we make our catalogue, spectra, images, and processing pipeline publicly available.
Patients diagnosed with coronavirus disease 2019 (COVID-19) aerosolize severe acute respiratory coronavirus virus 2 (SARS-CoV-2) via respiratory efforts, expose, and possibly infect healthcare personnel (HCP). To prevent transmission of SARS-CoV-2 HCP have been required to wear personal protective equipment (PPE) during patient care. Early in the COVID-19 pandemic, face shields were used as an approach to control HCP exposure to SARS-CoV-2, including eye protection.
Methods:
An MS2 bacteriophage was used as a surrogate for SARS-CoV-2 and was aerosolized using a coughing machine. A simulated HCP wearing a disposable plastic face shield was placed 0.41 m (16 inches) away from the coughing machine. The aerosolized virus was sampled using SKC biosamplers on the inside (near the mouth of the simulated HCP) and the outside of the face shield. The aerosolized virus collected by the SKC Biosampler was analyzed using a viability assay. Optical particle counters (OPCs) were placed next to the biosamplers to measure the particle concentration.
Results:
There was a statistically significant reduction (P < .0006) in viable virus concentration on the inside of the face shield compared to the outside of the face shield. The particle concentration was significantly lower on the inside of the face shield compared to the outside of the face shield for 12 of the 16 particle sizes measured (P < .05).
Conclusions:
Reductions in virus and particle concentrations were observed on the inside of the face shield; however, viable virus was measured on the inside of the face shield, in the breathing zone of the HCP. Therefore, other exposure control methods need to be used to prevent transmission from virus aerosol.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Social isolation in childhood can be detrimental to physical and mental health. Children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), may be particularly at risk for becoming socially isolated. Similarly, isolated children have limited opportunities to observe, model, and learn age-appropriate interpersonal interactions with other children which could increase ADHD behaviours.
Objectives
This study examined longitudinal associations between ADHD symptoms and social isolation across childhood. We tested the direction of this association across time, while accounting for pre-existing characteristics, and assessed whether this association varied by ADHD presentation, informant, sex, and socioeconomic status.
Methods
Participants included 2,232 children from the Environmental Risk (E-Risk) Longitudinal Twin Study. ADHD symptoms and social isolation were measured at ages 5, 7, 10, and 12. We used random-intercept cross-lagged panel models to assess the directionality of the association across childhood.
Results
Children with increased ADHD symptoms were consistently at increased risk of becoming socially isolated later in childhood, over and above stable characteristics (β=0.05-0.08). These longitudinal associations were not bidirectional; isolated children were not at risk of worsening ADHD symptoms later on. Children with a hyperactive ADHD presentation were more likely to become isolated, compared to an inattentive presentation. This was evident in the school setting, as observed by teachers, but not by mothers at home.
Conclusions
Our findings highlight the importance of enhancing peer social support and inclusion for children with ADHD, particularly in school settings. We add explanatory value over and above traditional longitudinal methods as our results represent how individual children change over time, relative to their own pre-existing characteristics.
We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.
The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described.
Methods:
Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3–5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter.
Results:
Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar.
Conclusions:
In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.