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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.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
We investigate the evolution of active galactic nucleus jets on kiloparsec-scales due to their interaction with the clumpy interstellar medium (ISM) of the host galaxy and, subsequently, the surrounding circumgalactic environment. Hydrodynamic simulations of this jet–environment interaction are presented for a range of jet kinetic powers, peak densities of the multiphase ISM, and scale radii of the larger-scale environment – characteristic of either a galaxy cluster or poor group. Synthetic radio images are generated by considering the combination of synchrotron radiation from the jet plasma and free-free absorption from the multiphase ISM. We find that jet propagation is slowed by interactions with a few very dense clouds in the host galaxy ISM, producing asymmetries in lobe length and brightness which persist to scales of tens of kpc for poor group environments. The classification of kiloparsec-scale jets is highly dependent on surface brightness sensitivity and resolution. Our simulations of young active sources can appear as restarted sources, showing double-double lobe morphology, high core prominence (CP $\gt 0.1$), and the expected radio spectra for both the inner- and outer-lobe components. We qualitatively reproduce the observed inverse correlation between peak frequency and source size and find that the peak frequency of the integrated radio spectrum depends on ISM density but not the jet power. Spectral turnover in resolved young radio sources therefore provides a new probe of the ISM.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Iron and zinc deficiencies are prevalent globally and have been found to co-exist within populations(1). Previous work from our laboratory found dual iron and zinc deficiency alters iron absorption compared with iron deficiency alone (unpublished). Iron deficient (FeD), zinc deficient (ZnD), dual iron and zinc deficient (FeZnD) and healthy Caco-2 cells demonstrated different rates of cell media acidification, indicative of altered cell metabolism. The aim of this study was to understand changes to energy substrate consumption and intracellular concentrations under individual and dual deficient conditions. Iron, zinc and dual iron and zinc deficiencies were induced in Caco-2 cells by Chelex-100 removal of minerals from FBS in the growth media and repleting all but the target mineral. Cell media was changed every second day for the first 9 days post seeding, then every day until day 14 due to increased rate of media acidification particularly in iron deficient cells. Glucose (Megazyme, GOPOD), lactate (Megazyme, K-LATE) and protein (Thermo Scientific, SKU# 23225) contents were analysed using commercial kits. Creatine and phosphocreatine were analysed by HPLC. ANOVA was used for statistical analyses using Tukey’s test for post-hoc analyses with a significance of p < 0.05. FeZnD cells had significantly higher intracellular glucose (p = 0.000), and lower lactate (p = 0.000) concentrations compared to healthy control cells. Intracellular glucose and lactate concentrations in cells were also significantly different to that in FeD and ZnD (p < 0.05) cells. Iron deficient and zinc deficient cells were not different to healthy cells (control) for either intracellular glucose (p(FeD) = 0.354, p(ZnD) = 0.996) or lactate (p(FeD) = 0.251, p(ZnD) = 1.000) concentrations. Iron deficient cells did not show a difference in glucose media loss compared to healthy (p = 0.715) cells, whereas zinc deficient (p = 0.000) and dual iron and zinc deficient (p = 0.000) cells had significantly lower glucose loss than healthy cells. Zinc deficiency and dual iron and zinc deficiency resulted in a significant reduction in total intracellular creatine (phosphocreatine + creatine) compared to control cells (p = 0.000). In contrast, zinc deficiency and dual iron and zinc deficiency resulted in a significant increase in phosphocreatine compared to control or iron deficient cells (p < 0.05). Changes to glucose, lactate and phosphocreatine found in this study indicate that dual iron and zinc deficient cells do not mirror changes in individual deficiency. How changes in energy substrates affect nutrient absorption is uncertain from this present work. Further research is required to improve understanding with the view to translate findings into effective treatment and prevention of micronutrient deficiencies.
Root research on field-grown crops is hindered by the difficulty of estimating root biomass in soil. Root washing, the current standard method is laborious and expensive. Biochemical methods to quantify root biomass in soil, targeting species-specific DNA, have potential as a more efficient assay. We combined an efficient DNA extraction method, designed specifically to extract DNA from soil, with well-established quantitative PCR methods to estimate the root biomass of 22 wheat varieties grown in field trials over two seasons. We also developed an assay for estimating root biomass for black-grass, a common weed of wheat cultivation.
Methods
Two robust qPCR assays were developed to estimate the quantity of plant root DNA in soil samples, one specific to wheat and barley, and a second specific to black-grass.
Results
The DNA qPCR method was comparable, with high correlations, with the results of root washing from soil cores taken from winter wheat field trials. The DNA qPCR assay showed both variety and depth as significant factors in the distribution of root biomass in replicated field trials.
Conclusions
The results suggest that these DNA qPCR assays are a useful, high-throughput tool for investigating the genetic basis of wheat root biomass distribution in field-grown crops, and the impact of black-grass root systems on crop production.
Adolescence is a key developmental period associated with an increased risk of experiencing cannabis-related problems. Identifying modifiable risk factors prior to the onset of cannabis use could help inform preventative interventions.
Method
Analysis nested within a UK prospective birth cohort study, the Avon Longitudinal Study of Parents and Children. Participants (n = 6,049) provided data on cannabis use and symptoms of cannabis problems using the Cannabis Abuse Screening Test at two or more time points between the ages of 15–24 years. Risk factors included internalizing and externalizing disorders assessed at age 10 years, and cognitive function assessed at age 8 years via short-term memory, emotion recognition, divided attention, and listening comprehension.
Results
Participants were mostly female (59.1%) and white (95.73%). Five patterns of adolescent cannabis use problems were identified using longitudinal latent class analysis: stable-no problems (n = 5,157, 85%), early-onset high (n = 104, 2%), late-onset high (n = 153, 3%), early onset low (n = 348, 6%), and late-onset low (n = 287, 5%). In adjusted models, externalizing disorders were associated with early-onset high [RR, 95% CI: 2.82 (1.72, 4.63)], late-onset high [RR, 95% CI: 1.62 (1.02, 2.57)], and early-onset low [RR, 95% CI: 1.82 (1.30, 2.55)] compared to the stable-no problems class. Internalizing disorders were associated with late-onset low only [RR, 95% CI: .50 (.26, .96)], and short-term memory with late-onset high only [RR, 95% CI: 1.09 (1.01, 1.18) compared to the stable-no problems class.
Conclusions
Childhood externalizing disorders were consistently associated with increased risk of problematic patterns of cannabis use over adolescence, particularly early-onset and high levels of problems.
The threat of novel pathogens and natural hazards is increasing as global temperatures warm, leading to more frequent and severe occurrences of infectious disease outbreaks and major hurricanes. The COVID-19 pandemic amplified the need to examine how risk perceptions related to hurricane evacuations shift when vaccines become available. This study explores individuals’ expected evacuation plans during the early stages of COVID-19 vaccine availability.
Methods
In March 2021, an online survey was disseminated in Puerto Rico and the US Virgin Islands.
Results
An overwhelming majority (72.6%) of respondents said that their vaccination status would not affect their hurricane evacuation intentions. The unvaccinated were significantly more likely to consider evacuating during a hurricane than the vaccinated. Even with vaccines available, respondents suggested they were less likely to evacuate to a shelter during the 2021 season than prior to the COVID-19 pandemic. Respondents generally believed that the risk of contracting COVID-19 at a shelter was greater than the risk of sheltering-in-place during a hurricane.
Conclusions
Government officials need to develop and communicate clear information regarding evacuation orders for municipalities that may be more impacted than others based on the trajectory of the storm, social determinants of health, and other factors like living in a flood zone.
We construct a Divisia money measure for U.K. households and private non-financial corporations and a corresponding dual user cost index employing a consistent methodology from 1977 up to the present. Our joint construction of both the Divisia quantity index and the Divisia price dual facilitates an investigation of structural vector autoregresssion models (SVARs) over a long sample period of the type of non-recursive identifications explored by Belongia and Ireland (2016, 2018), as well as the block triangular specification advanced by Keating et al. (2019). An examination of the U.K. economy reveals that structures that consider a short-term interest rate to be the monetary policy indicator generate unremitting price puzzles. In contrast, we find sensible economic responses in various specifications that treat our Divisia measure as the indicator variable.
The marketing of unhealthy foods has been implicated in poor diet and rising levels of obesity. Rapid developments in the digital food marketing ecosystem and associated research mean that contemporary review of the evidence is warranted. This preregistered (CRD420212337091)1 systematic review and meta-analysis aimed to provide an updated synthesis of the evidence for behavioural and health impacts of food marketing on both children and adults, using the 4Ps framework (Promotion, Product, Price, Place). Ten databases were searched from 2014 to 2021 for primary data articles of quantitative or mixed design, reporting on one or more outcome of interest following food marketing exposure compared with a relevant control. Reviews, abstracts, letters/editorials and qualitative studies were excluded. Eighty-two studies were included in the narrative review and twenty-three in the meta-analyses. Study quality (RoB2/Newcastle–Ottawa scale) was mixed. Studies examined ‘promotion’ (n 55), ‘product’ (n 17), ‘price’ (n 15) and ‘place’ (n 2) (some > 1 category). There is evidence of impacts of food marketing in multiple media and settings on outcomes, including increased purchase intention, purchase requests, purchase, preference, choice, and consumption in children and adults. Meta-analysis demonstrated a significant impact of food marketing on increased choice of unhealthy foods (OR = 2·45 (95 % CI 1·41, 4·27), Z = 3·18, P = 0·002, I2 = 93·1 %) and increased food consumption (standardised mean difference = 0·311 (95 % CI 0·185, 0·437), Z = 4·83, P < 0·001, I2 = 53·0 %). Evidence gaps were identified for the impact of brand-only and outdoor streetscape food marketing, and for data on the extent to which food marketing may contribute to health inequalities which, if available, would support UK and international public health policy development.
When the world’s leading human rights advocates violate international norms, how does this affect support for those norms around the world? Rather than diffusing norm breaking across borders, I argue that authoritarian states’ propaganda about liberal states’ violations may increase the salience of human rights norms in places where those norms are normally censored. Focusing on American racial discrimination, I find that the Chinese Communist Party publicizes American human rights violations on to its citizens for strategic political reasons. Through two survey experiments I show that while exposure to news about American discrimination does provide substantial propaganda benefits to the regime, it also makes Chinese respondents more supportive of minority rights and more critical of their own country’s respect for those rights. The study shows how prominent violations of international norms may be an underappreciated means of strengthening global public support for those norms.
As the Arctic warms and growing seasons start to lengthen, governments and producers are speculating about northern “climate-driven agricultural frontiers” as a potential solution to food insecurity. One of the central ecological factors in northern spaces, however, is permafrost (perennial frozen ground), which can drive cascading environmental changes upon thaw. Considering the land requirements for expanded agriculture and the unique challenges of northern farming, national and subnational governments are grappling with and facilitating this speculative boom in different ways. Analysing agricultural land use policy instruments from the US State of Alaska and the Republic of Sakha (Yakutia) in Russia, this paper investigates if and how permafrost factors into their legal frameworks and what impacts this has on agricultural development, conservation, and food security. Alaska and the Republic of Sakha were chosen for reasons including both having at least 100 years of agricultural history on permafrost soils, both containing extensive amounts of permafrost within their landmasses and both containing permafrost that is ice-rich. Comparing legal texts as indicative of state capacities and strategies to govern, the paper finds that the two regions diverge in how they understand and regulate permafrost, and suggests that these approaches could benefit from one another. Bringing together geoclimatic and sociocultural concerns to problematise static policy divisions, this paper gestures to a path forward wherein subnational policy can balance needs for food, environmental, and cultural security in the North.
Wetlands in hypersaline environments are especially vulnerable to loss and degradation, as increasing coastal urbanization and climate change rapidly exacerbate freshwater supply stressors. Hypersaline wetlands pose unique management challenges that require innovative restoration perspectives and approaches that consider complex local and regional socioecological dynamics. In part, this challenge stems from multiple co-occurring stressors and anthropogenic alterations, including estuary mouth closure and freshwater diversions at the catchment scale. In this article, we discuss challenges and opportunities in the restoration of hypersaline coastal wetland systems, including management of freshwater inflow, shoreline modification, the occurrence of concurrent or sequential stressors, and the knowledge and values of stakeholders and Indigenous peoples. Areas needing additional research and integration into practice are described, and paths forward in adaptive management are discussed. There is a broad need for actionable research on adaptively managing hypersaline wetlands, where outputs will enhance the sustainability and effectiveness of future restoration efforts. Applying a collaborative approach that integrates best practices across a diversity of socio-ecological settings will have global benefits for the effective management of hypersaline coastal wetlands.
Clinical translational neuroscience (CTN) is positioned to generate novel discoveries for advancing treatments for mental health disorders, but it is held back today by the siloing of bioethical considerations from critical consciousness. In this article, we suggest that bioethical and critical consciousness can be paired to intersect with structures of power within which science and clinical practice are conducted. We examine barriers to the adoption of neuroscience findings in mental health from this perspective, especially in the context of current collective attention to widespread disparities in the access to and outcomes of mental health services, lack of representation of marginalized populations in the relevant sectors of the workforce, and the importance of knowledge that draws upon multicultural perspectives. We provide 10 actionable solutions to confront these barriers in CTN research, as informed by existing frameworks such as structural competency, adaptive calibration models, and community-based participatory research. By integrating critical consciousness with bioethical considerations, we believe that practitioners will be better positioned to benefit from cutting-edge research in the biological and social sciences than in the past, alert to biases and equipped to mitigate them, and poised to shepherd in a robust generation of future translational therapies and practitioners.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
This note seeks to bring awareness to the wide variety of archival documents available for research in urban history in Kumase, Ghana’s second city and capital of the historic Asante Kingdom. We draw mainly on our experiences researching the history of Jackson Park, one of colonial Kumase’s earliest public parks.
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.