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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.
Biomedical research on advanced cryopreservation has spillover effects on innovation in the food and agricultural sector. Advanced biopreservation technology has three key domains of impact in the food system: (1) improving efficiencies in storage and utilization of gametes and organoids for plant and animal breeding; (2) isochoric methods for preservation of fresh food products; and (3) in biorepositories for storage of genetic resources for agriculturally significant plants and livestock species.
Circular shell rings along the South Atlantic coast of the United States are vestiges of the earliest sedentary villages in North America, dating to 4500–3000 BP. However, little is known about when Indigenous communities began constructing these shell-ring villages. This article presents data from the Hokfv-Mocvse Shell Ring on Ossabaw Island, Georgia. Although shell rings are often associated with the earliest ceramics in North America, no ceramics were encountered in our excavations at Hokfv-Mocvse, and the only materials recovered were projectile points similar to points found over 300 km inland. Bayesian modeling of radiocarbon dates indicates that the ring was occupied between 5090 and 4735 cal BP (95% confidence), making it the earliest dated shell ring in the region. Additionally, shell geochemistry and oyster paleobiology data suggest that inhabitants were living at the ring year-round and had established institutions at that time to manage oyster fisheries sustainably. Hokfv-Mocvse therefore provides evidence for Indigenous people settling in year-round villages and adapting to coastal environments in the region centuries before the adoption of pottery. The establishment of villages marks a visible archaeological shift toward settling down and occupying island ecosystems on a more permanent basis and in larger numbers than ever before in the region.
OBJECTIVES/GOALS: Clinical indicators predictive of venous thromboembolism (VTE) in trauma patients at multiple time points are not well outlined, particularly at time of discharge. We aimed to describe and predict inpatient and post-discharge risk factors of VTE after trauma using a multi-variate regression model and best of class machine learning (ML) models. METHODS/STUDY POPULATION: In a prospective, case-cohort study, all trauma patients (pts) who arrived as level 1 or 2 trauma activations, from June 2018 to February 2020 were considered for study inclusion. A subset of pts who developed incident, first time, VTE and those who did not develop VTE within 90 days of discharge were identified. VTE were confirmed either by imaging or at autopsy during inpatient stay or post-discharge. Outcomes were defined as the development of symptomatic VTE (DVT and/or PE) within 90 days of discharge.A multi-variate Cox regression model and a best in class of a set of 5 different ML models (support-vector machine, random-forest, naives Bayes, logistic regression, neural network]) were used to predict VTE using models applied a) at 24 hours of injury date or b) on day of patient discharge. RESULTS/ANTICIPATED RESULTS: Among 393 trauma pts (ISS=12.0, hospital LOS=4.0 days, age=48 years, 71% male, 96% with blunt mechanism, mortality 2.8%), 36 developed inpatient VTE and 36 developed VTE after discharge. In a weighted, multivariate Cox model, any type of surgery by day 1, increased age per 10 years, and BMI per 5 points were predictors of overall symptomatic VTE (C-stat 0.738). Prophylactic IVC filter placement (4.40), increased patient age per 10 years, and BMI per 5 points were predictors of post-discharge symptomatic VTE (C-stat= 0.698). A neural network ML model predicted VTE by day 1 with accuracy and AUC of 0.82 and 0.76, with performance exceeding those of a Cox model. A naīve Bayesian ML model predicted VTE at discharge, with accuracy and AUC of 0.81 and 0.77 at time of discharge, with performance exceeding those of a Cox model. DISCUSSION/SIGNIFICANCE: The rate of inpatient and post-discharge VTEs remain high. Limitations: single institution study, limited number of patients, internal validation only, with the use of limited number of ML models. We developed and internally validated a ML based tool.Future work will focus on external validation and expansion of ML techniques.
Helium or neopentane can be used as surrogate gas fill for deuterium (D2) or deuterium-tritium (DT) in laser-plasma interaction studies. Surrogates are convenient to avoid flammability hazards or the integration of cryogenics in an experiment. To test the degree of equivalency between deuterium and helium, experiments were conducted in the Pecos target chamber at Sandia National Laboratories. Observables such as laser propagation and signatures of laser-plasma instabilities (LPI) were recorded for multiple laser and target configurations. It was found that some observables can differ significantly despite the apparent similarity of the gases with respect to molecular charge and weight. While a qualitative behaviour of the interaction may very well be studied by finding a suitable compromise of laser absorption, electron density, and LPI cross sections, a quantitative investigation of expected values for deuterium fills at high laser intensities is not likely to succeed with surrogate gases.
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.
Prior research has identified altered brain structure and function in individuals at risk for self-directed violence thoughts and behaviors. However, these studies have largely utilized healthy controls and findings have been inconsistent. Thus, this study examined differences in resting-state functional network connectivity among individuals with lifetime suicide attempt(s) v. lifetime self-directed violence thoughts alone.
Methods
Using data from the UK Biobank, this study utilized a series of linear regressions to compare individuals with lifetime suicide attempt(s) (n = 566) v. lifetime self-directed violence thoughts alone (n = 3447) on within- and between- network resting-state functional connectivity subnetworks.
Results
There were no significant between-group differences for between-network, within-network, or whole-brain functional connectivity after adjusting for age, sex, ethnicity, and body mass index and performing statistical corrections for multiple comparisons. Resting-state network measures may not differentiate between individuals with lifetime suicide attempt(s) and lifetime self-directed violence thoughts alone.
Conclusions
Null findings diverge from results reported in smaller neuroimaging studies of suicide risk, but are consistent with null findings in other large-scale studies and meta-analyses. Strengths of the study include its large sample size and stringent control group. Future research on a wider array of imaging, genetic, and psychosocial risk factors can clarify relative contributions of individual and combined variables to suicide risk and inform scientific understanding of ideation-to-action framework.
OBJECTIVES/GOALS: To test the effect of a trusted Community Health Worker (CHW) support model to increase accessibility, feasibility and completion of COVID-19 home-testing in Native American and Latino communities. METHODS/STUDY POPULATION: We conducted a multi-site pragmatic randomized controlled trial among adult Native Americans and Latinos from the Flathead reservation in Montana and Yakima Valley in Washington. Participants were block randomized by site location and age to either an active or passive study arm. Participants in the active arm received assistance with online COVID-19 test kit registration and virtual swabbing support from CHWs, while the passive study arm received the standard-of-care support from the COVID-19 home testing kit vendor. Simple and multivariate logistic regression modeled the association between home-testing distribution mechanism and test completion. Multivariate models included community and sex as covariates. Descriptive feedback was collected in a post-test survey. RESULTS/ANTICIPATED RESULTS: Overall, 63% of the 268 enrolled participants completed COVID-19 tests, and 50% completed tests yielding a valid result. Active arm participants had significantly higher odds of test completion (OR 1.66, 95% CI: [1.01, 2.75], p-value=0.04). Differences were most pronounced among adults ≥60 years, with 84% completing testing kits in the active arm, compared to 58% in the passive arm (p=0.07). Ease of use and not having to leave home were top positive aspects of the home-based test while transporting and mailing samples to lab and long/overwhelming instructions were cited as negative aspects. Most test completers (93%) were satisfied with their experience and 95% found CHW assistance useful. Sample expiration and insufficient identifiers were top causes of non-valid test results. DISCUSSION/SIGNIFICANCE: While test completion rates were low in both study arms, the CHW support led to a higher COVID-19 test completion rate, particularly among older adults. Still, CHW support alone does not fully eliminate testing barriers. Socio-economic differences must be accounted for in future product development for home-based testing to improve health equity.
Starting from the biblical depiction of Christ’s incarnate personhood, this chapter traces the early church’s discernment of the deity and humanity of Christ that culminated in the Chalcedonian definition. Exploring the range of christological options, the chapter emphasizes the promise of a kenotic christology for making sense of Chalcedon’s intentions and parameters, including a fuller appreciation of Christ’s humanity.
This chapter articulates the identity of the church by way of key biblical metaphors and the Nicene Creed. It then examines the church’s mission, the role of proclamation and the sacraments, and the missional shape of the doctrine of election.
This chapter considers the meaning of the claim that human beings are created in God’s image (imago Dei), offering a representational-relational conception of the doctrine. It also examines how the corruptive effects of sin deface humanity’s image-bearing, pointing to the need for the image to be restored through the person of Jesus Christ, the true image of God.
This chapter takes up the doctrine of God generally, concentrating on the traditional understanding of divine being as a complex of attributes derived via positiva and via negative (i.e., “classical theism”). Given classical theism’s tensions with the biblical narrative, as well as its role in helping to foster the rise of modern atheism, the chapter argues for a rigorous trinitarian rethinking of key traditional divine attributes.
This chapter looks at the reality of religious plurality – more particularly, the relationship between the Christian church and other religious traditions – including the common typology of exclusivism, inclusivism, and pluralism. It also explores the significance of the fact that the Christian church’s numerical center has shifted from the West to the South and East, with significant consequences for the mission and theology of the church.
This chapter explores how the life, death, and resurrection of Jesus Christ make reconciliation possible. It surveys the diverse biblical motifs surrounding reconciliation/atonement, the variety of traditional “atonement theories” that flowed out of those motifs, and a way of coherently integrating a variety of atonement approaches.
This chapter analyzes the context and theology of the Protestant Reformation, focusing on key theologians such as Luther, Melanchthon, Zwingli, and Calvin. It also examines responses to the Protestant Reformation, such as the radical reformers and forms of Catholic reformation, concluding with an exploration of the connection between Reformation theology and the rise of Protestant orthodoxy, pietism, and new forms of rationalism.
This chapter elaborates four pillars of an “ecumenical eschatology”: (1) the second coming of Christ (vis-à-vis “going to” heaven); (2) resurrection of the body (vis-à-vis an exclusive emphasis on an immortal soul); (3) final judgment/justice that is historical and public (vis-à-vis one that is heavenly and private); and (4) new heaven and earth (vis-à-vis an exclusive emphasis on heaven). It contends for a creational understanding of this doctrine, which implies that eschatology, rather than being merely a theological afterthought, is a central and mobilizing theme.
This chapter charts the medieval consolidation of the Christian world’s inheritance from the patristic tradition, giving some attention to the Byzantine East but primarily focusing on western theology. It examines important theological debates of the early Middle Ages, describes the development of scholastic theology, and explores the theology produced by the mendicant orders, especially that of Thomas Aquinas.
This chapter explores the contextual situation of theology today, engaging the set of challenges inherent in being caught between modernity (with challenges such as secularization, atheism, dehumanization, suffering, and the ecological crisis) and so-called postmodernity (with issues such as the demise of truth, the crisis of meaning, and a deepened global consciousness).