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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.
Racial and ethnic variations in antibiotic utilization are well-reported in outpatient settings but little is known about inpatient settings. Our objective was to describe national inpatient antibiotic utilization among children by race and ethnicity.
Methods:
This study included hospital visit data from the Pediatric Health Information System between 01/01/2022 and 12/31/2022 for patients <20 years. Primary outcomes were the percentage of hospitalization encounters that received an antibiotic and antibiotic days of therapy (DOT) per 1000 patient days. Mixed-effect regression models were used to determine the association of race-ethnicity with outcomes, adjusting for covariates.
Results:
There were 846,530 hospitalizations. 45.2% of children were Non-Hispanic (NH) White, 27.1% were Hispanic, 19.2% were NH Black, 4.5% were NH Other, 3.5% were NH Asian, 0.3% were NH Native Hawaiian/Other Pacific Islander (NHPI) and 0.2% were NH American Indian. Adjusting for covariates, NH Black children had lower odds of receiving antibiotics compared to NH White children (aOR 0.96, 95%CI 0.94–0.97), while NH NHPI had higher odds of receiving antibiotics (aOR 1.16, 95%CI 1.05–1.29). Children who were Hispanic, NH Asian, NH American Indian, and children who were NH Other received antibiotic DOT compared to NH White children, while NH NHPI children received more antibiotic DOT.
Conclusions:
Antibiotic utilization in children’s hospitals differs by race and ethnicity. Hospitals should assess policies and practices that may contribute to disparities in treatment; antibiotic stewardship programs may play an important role in promoting inpatient pharmacoequity. Additional research is needed to examine individual diagnoses, clinical outcomes, and drivers of variation.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.
Objectives
The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.
Methods
We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.
Results
Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.
Conclusions
This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.
This article examines the development, early operation and subsequent failure of the Tot-Kolowa Red Cross irrigation scheme in Kenya’s Kerio Valley. Initially conceived as a technical solution to address regional food insecurity, the scheme aimed to scale up food production through the implementation of a fixed pipe irrigation system and the provision of agricultural inputs for cash cropping. A series of unfolding circumstances, however, necessitated numerous modifications to the original design as the project became increasingly entangled with deep and complex histories of land use patterns, resource allocation and conflict. Failure to understand the complexity of these dynamics ultimately led to the project’s collapse as the region spiralled into a period of significant unrest. In tracing these events, we aim to foreground the lived realities of imposed development, including both positive and negative responses to the scheme’s participatory obligations and its wider impact on community resilience.
Different fertilization strategies can be adopted to optimize the productive components of an integrated crop–livestock systems. The current research evaluated how the application of P and K to soybean (Glycine max (L.) Merr.) or Urochloa brizantha (Hochst. ex A. Rich.) R. D. Webster cv. BRS Piatã associated with nitrogen or without nitrogen in the pasture phase affects the accumulation and chemical composition of forage and animal productivity. The treatments were distributed in randomized blocks with three replications. Four fertilization strategies were tested: (1) conventional fertilization with P and K in the crop phase (CF–N); (2) conventional fertilization with nitrogen in the pasture phase (CF + N); (3) system fertilization with P and K in the pasture phase (SF–N); (4) system fertilization with nitrogen in the pasture phase (SF + N). System fertilization increased forage accumulation from 15 710 to 20 920 kg DM ha/year compared to conventional without nitrogen. Stocking rate (3.1 vs. 2.8 AU/ha; SEM = 0.12) and gain per area (458 vs. 413 kg BW/ha; SEM = 27.9) were higher in the SF–N than CF–N, although the average daily gain was lower (0.754 vs. 0.792 kg LW/day; SEM = 0.071). N application in the pasture phase, both, conventional and system fertilization resulted in higher crude protein, stocking rate and gain per area. Applying nitrogen and relocate P and K from crop to pasture phase increase animal productivity and improve forage chemical composition in integrated crop–livestock system.
In this work, we present a methodology and a corresponding code-base for constructing mock integral field spectrograph (IFS) observations of simulated galaxies in a consistent and reproducible way. Such methods are necessary to improve the collaboration and comparison of observation and theory results, and accelerate our understanding of how the kinematics of galaxies evolve over time. This code, SimSpin, is an open-source package written in R, but also with an API interface such that the code can be interacted with in any coding language. Documentation and individual examples can be found at the open-source website connected to the online repository. SimSpin is already being utilised by international IFS collaborations, including SAMI and MAGPI, for generating comparable data sets from a diverse suite of cosmological hydrodynamical simulations.
Anxiety and depressive disorders can be chronic and disabling. Although there are effective treatments, only a fraction of those impaired receive treatment. Predictors of treatment-seeking and treatment receipt could be informative for initiatives aiming to tackle the burden of untreated anxiety and depression.
Aims
To investigate sociodemographic characteristics associated with treatment-seeking and treatment receipt.
Method
Two binary retrospective reports of lifetime treatment-seeking (n = 44 810) and treatment receipt (n = 37 346) were regressed on sociodemographic factors (age, gender, UK ethnic minority background, educational attainment, household income, neighbourhood deprivation and social isolation) and alternative coping strategies (self-medication with alcohol/drugs and self-help) in UK Biobank participants with lifetime generalised anxiety or major depressive disorder. Analyses were also stratified by gender.
Results
Treatment access was more likely in those who reported use of self-help strategies, with university-level education and those from less economically advantaged circumstances (household income <£30 000 and greater neighbourhood deprivation). Treatment access was less likely in those who were male, from a UK ethnic minority background and with high household incomes (>£100 000). Men who self-medicated and/or had a vocational qualification were also less likely to seek treatment.
Conclusions
This work on retrospective reports of treatment-seeking and treatment receipt at any time of life replicates known associations with treatment-seeking and treatment receipt during time of treatment need. More work is required to understand whether improving rates of treatment-seeking improves prognostic outcomes for individuals with anxiety or depression.
Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.
A study of turbulent impurity transport by means of quasilinear and nonlinear gyrokinetic simulations is presented for Wendelstein 7-X (W7-X). The calculations have been carried out with the recently developed gyrokinetic code stella. Different impurity species are considered in the presence of various types of background instabilities: ion temperature gradient (ITG), trapped electron mode (TEM) and electron temperature gradient (ETG) modes for the quasilinear part of the work; ITG and TEM for the nonlinear results. While the quasilinear approach allows one to draw qualitative conclusions about the sign or relative importance of the various contributions to the flux, the nonlinear simulations quantitatively determine the size of the turbulent flux and check the extent to which the quasilinear conclusions hold. Although the bulk of the nonlinear simulations are performed at trace impurity concentration, nonlinear simulations are also carried out at realistic effective charge values, in order to know to what degree the conclusions based on the simulations performed for trace impurities can be extrapolated to realistic impurity concentrations. The presented results conclude that the turbulent radial impurity transport in W7-X is mainly dominated by ordinary diffusion, which is close to that measured during the recent W7-X experimental campaigns. It is also confirmed that thermodiffusion adds a weak inward flux contribution and that, in the absence of impurity temperature and density gradients, ITG- and TEM-driven turbulence push the impurities inwards and outwards, respectively.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
To examine whether drug use (DU) is higher in people with eating disorders (EDs) than in matched comparison groups and to collate, summarize and perform a meta analysis where possible on the literature related to DU in people with EDs.
Method:
We searched electronic databases including Medline, PsycINFO, Web of Science and CINAHL and reviewed studies published from 1994 to August, 2007, in English, German or Spanish against a priori inclusion/exclusion criteria. A total of 248 papers were eligible for inclusion. Only a total of 16 papers fulfilled all the inclusion criteria and were finally included in the systematic review.
Results:
The meta-analysis including all the different drugs for every sort of ED revealed a negligible albeit significant (z=2.34, p<.05), pooled standardized effect size of 0.119. The data showed a high degree of heterogeneity across the studies (X2(74)= 1267.61, p<.001). When ED subdiagnoses were assessed individually, DU was found to be higher in people with bulimia nervosa (BN) as a moderate sized increase in DU was found in this ED subtype (δ =0.462, z=6.69, p=<.001). People with binge eating disorder (BED) had a small increased risk of DU (δ =0.14, z=2.28, p<.05). In contrast, people with anorexia nervosa (AN) had a lower risk of DU (δ=-.167, z=1.81, p=.070, p=NS).
Conclusion:
The differential risk observed in BN patients might be related to differences in temperament or might be the result of reward sensitisation as a result of the ED behaviours specifically associated with BN.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Aims
Describe the development, implementation and results of this questionnaire.
Method
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
Results
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
Conclusions
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
Light and intermittent smokers (LITS) represent almost 50% of all current smokers. Research is needed to understand smoking motives among adult light smokers.
Aims
To explore smoking cues and motivators among a racially diverse sample of adult LITS (≤10 CPD). In addition, we explored differences between native (always smoked ≤10), and converted (former heavier) LITS.
Methods
We used purposive sampling to recruit participants who were native and converted LITS and to include equal numbers of African Americans, Whites and Latinos. We coded and analyzed transcripts using a stage approach to identify themes.
Results
Four main themes emerged that may be unique to light smokers and suggests potential strategies for intervention: (1) smoking in response to cues and control, (2) identifying as a smoker, (3) concern about health consequences, and (4) other priorities influencing smoking. There were some differences among smoking cues and motivators by race and ethnicity, and differences between native and converted LITS.
Conclusions
Overall, LITS reported drivers of smoking that were unrelated to symptoms of nicotine withdrawal. Even when experiencing salient cues, our LITS cohort expressed the ability to assert control over smoking by abstaining when situational contexts made smoking inconvenient.
Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.
In lifecourse studies that encompass the adolescent period, the assessment of pubertal status is important, but can be challenging. We aimed to identify current methods for pubertal assessment and assess their appropriateness for population-based research by combining a review of the literature with the views of experts in the field. We searched bibliographic databases, extracted data and assessed study quality to inform a workshop with 21 experts. Acceptability of different approaches was explored with a panel of ten adolescents. We screened 11,935 abstracts, assessed 157 articles and summarised results from 38 articles. Combining these with the opinions of experts, self-assessment was found to be a practical method for use in studies where agreement with the gold standard of clinical assessment by physical examination to within one Tanner stage was acceptable. Serial measures of height and foot size accurately indicated timing of the pubertal growth spurt and age at peak height velocity, and were seen as feasible within longitudinal studies. Hormonal and radiological methods did not offer a practical means of assessing pubertal status. Assessment of voice maturation was promising, but needed validation. Young people thought that self-assessment, foot size and voice assessments were acceptable, and preferred an assessor of the same sex for clinical assessment. This review thus informs researchers working in lifecourse and adolescent health, and identifies future directions in order to improve validity of the methods.
A power MOSFET-based push–pull configuration nanosecond-pulse generator has been designed, constructed, and characterized to permeabilize cells for biological and medical applications. The generator can deliver pulses with durations ranging from 80 ns up to 1 µs and pulse amplitudes up to 1.4 kV. The unit has been tested for in vitro experiments on a medulloblastoma cell line. Following the exposure of cells to 100, 200, and 300 ns electric field pulses, permeabilization tests were carried out, and viability tests were conducted to verify the performance of the generator. The maximum temperature rise of the biological load was also calculated based on Joule heating energy conservation and experimental validation. Our results indicate that the developed device has good capabilities to achieve well-controlled electro-manipulation in vitro.
Introduction: Many drugs, including cannabis and alcohol, cause impairment and contribute to motor vehicle collisions (MVCs). Policy makers require knowledge of the prevalence of drug use in crash-involved drivers, and types of drugs used in order to develop effective prevention programs. This issue is particularly relevant with the recent legalization of cannabis. We aim to study the prevalence of alcohol, cannabis, sedating medications, and other drugs in injured drivers from 4 Canadian Provinces. Methods: This prospective cohort study obtained excess clinical blood samples from consecutive injured drivers who attended a participating Canadian trauma centre following a MVC. Blood samples were analyzed using a broad spectrum toxicology screen capable of detecting cannabinoids, cocaine, amphetamines (including their major analogues), and opioids as well as psychotropic pharmaceuticals (including antihistamines, benzodiazepines, other hypnotics, and sedating antidepressants). Alcohol and cannabinoids were quantified. Health records were reviewed to extract demographic, medical, and MVC information using a standardized data collection tool. Results: This study has been collecting data in 4 trauma centres in British Columbia (BC) since 2011 and was launched in 2 trauma centres in Alberta (AB), 1 in Saskatchewan (SK), and 2 in Ontario (ON) in 2018. In preliminary results from BC (n = 2412), 8% of injured drivers tested positive for THC and 13% for alcohol. Preliminary results from other provinces (n = 301) suggest a regional variation in prevalence of drivers testing positive for THC (10% - 27%), alcohol (17% - 29%), and other drugs. By May 2018, an estimated 4500 cases from BC, 600 from AB, 150 from SK, and 650 from ON will have been analyzed. We will report the prevalence of positive tests for alcohol, THC, other recreational drugs, and sedating medications, pre and post cannabis legalization. The number of cases with alcohol and/or THC levels above Canadian per se limits will also be reported. Results will be reported according to province, driver sex, age, single vs. multi vehicle crashes, and requirement for hospital admission. Conclusion: This will be among the largest international datasets on drug use by injured drivers. Our findings will provide patterns of drug and alcohol impairment in 4 Canadian provinces pre and post cannabis legalization. The significance of these findings and implication for impaired driving policy and prevention programs in Canada will be discussed.