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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 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.
In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.
Recruiting underrepresented people and communities in research is essential for generalizable findings. Ensuring representative participants can be particularly challenging for practice-level dissemination and implementation trials. Novel use of real-world data about practices and the communities they serve could promote more equitable and inclusive recruitment.
Methods:
We used a comprehensive primary care clinician and practice database, the Virginia All-Payers Claims Database, and the HealthLandscape Virginia mapping tool with community-level socio-ecological information to prospectively inform practice recruitment for a study to help primary care better screen and counsel for unhealthy alcohol use. Throughout recruitment, we measured how similar study practices were to primary care on average, mapped where practices’ patients lived, and iteratively adapted our recruitment strategies.
Results:
In response to practice and community data, we adapted our recruitment strategy three times; first leveraging relationships with residency graduates, then a health system and professional organization approach, followed by a community-targeted approach, and a concluding approach using all three approaches. We enrolled 76 practices whose patients live in 97.3% (1844 of 1907) of Virginia’s census tracts. Our overall patient sample had similar demographics to the state for race (21.7% vs 20.0% Black), ethnicity (9.5% vs 10.2% Hispanic), insurance status (6.4% vs 8.0% uninsured), and education (26.0% vs 32.5% high school graduate or less). Each practice recruitment approach uniquely included different communities and patients.
Discussion:
Data about primary care practices and the communities they serve can prospectively inform research recruitment of practices to yield more representative and inclusive patient cohorts for participation.
We present a broadband radio study of the transient jets ejected from the black hole candidate X-ray binary MAXI J1535–571, which underwent a prolonged outburst beginning on 2017 September 2. We monitored MAXI J1535–571 with the Murchison Widefield Array (MWA) at frequencies from 119 to 186 MHz over six epochs from 2017 September 20 to 2017 October 14. The source was quasi-simultaneously observed over the frequency range 0.84–19 GHz by UTMOST (the Upgraded Molonglo Observatory Synthesis Telescope) the Australian Square Kilometre Array Pathfinder (ASKAP), the Australia Telescope Compact Array (ATCA), and the Australian Long Baseline Array (LBA). Using the LBA observations from 2017 September 23, we measured the source size to be $34\pm1$ mas. During the brightest radio flare on 2017 September 21, the source was detected down to 119 MHz by the MWA, and the radio spectrum indicates a turnover between 250 and 500 MHz, which is most likely due to synchrotron self-absorption (SSA). By fitting the radio spectrum with a SSA model and using the LBA size measurement, we determined various physical parameters of the jet knot (identified in ATCA data), including the jet opening angle ($\phi_{\rm op} = 4.5\pm1.2^{\circ}$) and the magnetic field strength ($B_{\rm s} = 104^{+80}_{-78}$ mG). Our fitted magnetic field strength agrees reasonably well with that inferred from the standard equipartition approach, suggesting the jet knot to be close to equipartition. Our study highlights the capabilities of the Australian suite of radio telescopes to jointly probe radio jets in black hole X-ray binaries via simultaneous observations over a broad frequency range, and with differing angular resolutions. This suite allows us to determine the physical properties of X-ray binary jets. Finally, our study emphasises the potential contributions that can be made by the low-frequency part of the Square Kilometre Array (SKA-Low) in the study of black hole X-ray binaries.
A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.
Objectives:
To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.
Methods:
Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.
Results:
Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).
Conclusion:
Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.
Social inequality is ubiquitous in contemporary human societies, and has deleterious social and ecological impacts. However, the factors that shape the emergence and maintenance of inequality remain widely debated. Here we conduct a global analysis of pathways to inequality by comparing 408 non-industrial societies in the anthropological record (described largely between 1860 and 1960) that vary in degree of inequality. We apply structural equation modelling to open-access environmental and ethnographic data and explore two alternative models varying in the links among factors proposed by prior literature, including environmental conditions, resource intensification, wealth transmission, population size and a well-documented form of inequality: social class hierarchies. We found support for a model in which the probability of social class hierarchies is associated directly with increases in population size, the propensity to use intensive agriculture and domesticated large mammals, unigeniture inheritance of real property and hereditary political succession. We suggest that influence of environmental variables on inequality is mediated by measures of resource intensification, which, in turn, may influence inequality directly or indirectly via effects on wealth transmission variables. Overall, we conclude that in our analysis a complex network of effects are associated with social class hierarchies.
With human influences driving populations of apex predators into decline, more information is required on how factors affect species at national and global scales. However, camera-trap studies are seldom executed at a broad spatial scale. We demonstrate how uniting fine-scale studies and utilizing camera-trap data of non-target species is an effective approach for broadscale assessments through a case study of the brown hyaena Parahyaena brunnea. We collated camera-trap data from 25 protected and unprotected sites across South Africa into the largest detection/non-detection dataset collected on the brown hyaena, and investigated the influence of biological and anthropogenic factors on brown hyaena occupancy. Spatial autocorrelation had a significant effect on the data, and was corrected using a Bayesian Gibbs sampler. We show that brown hyaena occupancy is driven by specific co-occurring apex predator species and human disturbance. The relative abundance of spotted hyaenas Crocuta crocuta and people on foot had a negative effect on brown hyaena occupancy, whereas the relative abundance of leopards Panthera pardus and vehicles had a positive influence. We estimated that brown hyaenas occur across 66% of the surveyed camera-trap station sites. Occupancy varied geographically, with lower estimates in eastern and southern South Africa. Our findings suggest that brown hyaena conservation is dependent upon a multi-species approach focussed on implementing conservation policies that better facilitate coexistence between people and hyaenas. We also validate the conservation value of pooling fine-scale datasets and utilizing bycatch data to examine species trends at broad spatial scales.
A dramatically increased interest in dissemination and implementation (D&I) science, with relatively few training programs for D&I scientists, highlights the need for innovative ways to deliver educational materials, training, and resources. We described nine interactive, web-based D&I science resources appropriate for trainees and Clinical and Translational Science Awards. We used audience feedback and design thinking to develop resources iteratively. Primary target users are T3–T4 researchers, although T2 researchers can benefit from “designing for dissemination” resources. Workforce development resources were used in D&I science workshops, as stand-alone, self-directed resources, and for consultations and trainings. We assessed resource design (purpose, functionality), usage, user experience and engagement. Educational resources addressed included: D&I science basics, pragmatic trials, getting proposals funded, designing for dissemination, and D&I science theory selection. We reviewed the purpose, functionality, status, and usage of these interactive resources. All resources engaged users; provided interactive feedback for learners; and linked users to additional learning resources. Online resources can be valuable for preparing clinical and translational mentees for research consultations, as follow-up training activities, and as D&I workforce development resources. The resources described are publicly available and we encourage their use, further development, and evaluation by Clinical and Translational Science Awards and other programs.
OBJECTIVES/SPECIFIC AIMS: Rodent models can be used to study neonatal abstinence syndrome (NAS), but the applicability of findings from the models to NAS in humans is not well understood. The objective of this study was to develop a rat model of norbuprenorphine-induced NAS and validate its translational value by comparing blood concentrations in the norbuprenorphine-treated pregnant rat to those previously reported in pregnant women undergoing buprenorphine treatment. METHODS/STUDY POPULATION: Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or norbuprenorphine (0.3–3 mg/kg/d) on gestation day 9. Within 12 hours of delivery, pups were tested for spontaneous or precipitated opioid withdrawal by injecting them with saline (10 mL/kg, i.p.) or naltrexone (1 or 10 mg/kg, i.p), respectively, and observing them for well-validated neonatal withdrawal signs. Blood was sampled via indwelling jugular catheters from a subset of norbuprenorphine-treated dams on gestation day 8, 10, 13, 17, and 20. Norbuprenorphine concentrations in whole blood samples were quantified using LC/MS/MS. RESULTS/ANTICIPATED RESULTS: Blood concentrations of norbuprenorphine in rats exposed to 1–3 mg/kg/d of norbuprenorphine were similar to levels previously reported in pregnant women undergoing buprenorphine treatment. Pups born to dams treated with these doses exhibited robust withdrawal signs. Blood concentrations of norbuprenorphine decreased across gestation, which is similar to previous reports in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that dosing dams with 1–3 mg/kg/day norbuprenorphine produces maternal blood concentrations and withdrawal severity similar to those previously reported in humans. This provides evidence that, at these doses, this model is useful for testing hypotheses about norbuprenorphine that are applicable to NAS in humans.
The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015–2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015–2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015–2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
To date, there has been no published textbook which takes into account changing sociolinguistic dynamics that have influenced South African society. Multilingualism and Intercultural Communication breaks new ground in this arena. The scope of this book ranges from macro-sociolinguistic questions pertaining to language policies and their implementation (or non-implementation) to micro-sociolinguistic observations of actual language-use in verbal interaction, mainly in multilingual contexts of Higher Education (HE). There is a gradual move for the study of language and culture to be taught in the context of (professional) disciplines in which they would be used, for example, Journalism and African languages, Education and African languages, etc. The book caters for this growing market. Because of its multilingual nature, it caters to English and Afrikaans language speakers, as well as the Sotho and Nguni language groups – the largest languages in South Africa [and also increasingly used in the context of South African Higher Education]. It brings together various inter-linked disciplines such as Sociolinguistics and Applied Language Studies, Media Studies and Journalism, History and Education, Social and Natural Sciences, Law, Human Language Technology, Music, Intercultural Communication and Literary Studies. The unique cross-cutting disciplinary features of the book will make it a must-have for twenty-first century South African students and scholars and those interested in applied language issues.
The shallow subsurface of Groningen, the Netherlands, is heterogeneous due to its formation in a Holocene tidal coastal setting on a periglacially and glacially inherited landscape with strong lateral variation in subsurface architecture. Soft sediments with low, small-strain shear wave velocities (VS30 around 200 m s−1) are known to amplify earthquake motions. Knowledge of the architecture and properties of the subsurface and the combined effect on the propagation of earthquake waves is imperative for the prediction of geohazards of ground shaking and liquefaction at the surface. In order to provide information for the seismic hazard and risk analysis, two geological models were constructed. The first is the ‘Geological model for Site response in Groningen’ (GSG model) and is based on the detailed 3D GeoTOP voxel model containing lithostratigraphy and lithoclass attributes. The GeoTOP model was combined with information from boreholes, cone penetration tests, regional digital geological and geohydrological models to cover the full range from the surface down to the base of the North Sea Supergroup (base Paleogene) at ~800 m depth. The GSG model consists of a microzonation based on geology and a stack of soil stratigraphy for each of the 140,000 grid cells (100 m × 100 m) to which properties (VS and parameters relevant for nonlinear soil behaviour) were assigned. The GSG model serves as input to the site response calculations that feed into the Ground Motion Model. The second model is the ‘Geological model for Liquefaction sensitivity in Groningen’ (GLG). Generally, loosely packed sands might be susceptible to liquefaction upon earthquake shaking. In order to delineate zones of loosely packed sand in the first 40 m below the surface, GeoTOP was combined with relative densities inferred from a large cone penetration test database. The marine Naaldwijk and Eem Formations have the highest proportion of loosely packed sand (31% and 38%, respectively) and thus are considered to be the most vulnerable to liquefaction; other units contain 5–17% loosely packed sand. The GLG model serves as one of the inputs for further research on the liquefaction potential in Groningen, such as the development of region-specific magnitude scaling factors (MSF) and depth–stress reduction relationships (rd).