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Predicting the evolution of fractured media is challenging due to coupled thermal, hydrological, chemical and mechanical processes that occur over a broad range of spatial scales, from the microscopic pore scale to field scale. We present a software framework and scientific workflow that couples the pore scale flow and reactive transport simulator Chombo-Crunch with the field scale geomechanics solver in GEOS to simulate fracture evolution in subsurface fluid-rock systems. This new multiphysics coupling capability comprises several novel features. An HDF5 data schema for coupling fracture positions between the two codes is employed and leverages the coarse resolution of the GEOS mechanics solver which limits the size of data coupled, and is, thus, not taxed by data resulting from the high resolution pore scale Chombo-Crunch solver. The coupling framework requires tracking of both before and after coarse nodal positions in GEOS as well as the resolved embedded boundary in Chombo-Crunch. We accomplished this by developing an approach to geometry generation that tracks the fracture interface between the two different methodologies. The GEOS quadrilateral mesh is converted to triangles which are organized into bins and an accessible tree structure; the nodes are then mapped to the Chombo representation using a continuous signed distance function that determines locations inside, on and outside of the fracture boundary. The GEOS positions are retained in memory on the Chombo-Crunch side of the coupling. The time stepping cadence for coupled multiphysics processes of flow, transport, reactions and mechanics is stable and demonstrates temporal reach to experimental time scales. The approach is validated by demonstration of 9 days of simulated time of a core flood experiment with fracture aperture evolution due to invasion of carbonated brine in wellbore-cement and sandstone. We also demonstrate usage of exascale computing resources by simulating a high resolution version of the validation problem on OLCF Frontier.

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were

Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

The perceived salience of errors can be influenced by individual-level motivational factors. Specifically, those who endorse a high degree of collectivism, a cultural value that emphasizes prioritization of interpersonal relationships, may find errors occurring in a social context to be more aversive than individuals who endorse collectivism to a lesser degree, resulting in upregulation of a neural correlate of error-monitoring, the error-related negativity (ERN). This study aimed to identify cultural variation in neural response to errors occurring in a social context in a sample of diverse adolescents. It was predicted that greater collectivism would be associated with enhanced neural response to errors occurring as part of a team. Participants were 95 Latinx (n = 35), Asian American (n = 20) and non-Latinx White (n = 40) adolescents (ages 13-17) who completed a go/no-go task while continuous electroencephalogram was recorded. The task included social (team) and non-social (individual) conditions. ERN was quantified using mean amplitude measures. Regression models demonstrated that collectivism modulated neural response to errors occurring in a social context, an effect that was most robust for Latinx adolescents. Understanding cultural variation in neural sensitivity to social context could inform understanding of both normative and maladaptive processes associated with self-regulation.

Social anxiety disproportionately impacts individuals from certain cultural and developmental groups, namely those from Latinx and Asian American cultures and adolescents. Neural sensitivity to social feedback has been shown to vary across individuals and could contribute to this disparity by further exacerbating differences; thus, this could be an important phenomenon for understanding, preventing, and treating social anxiety. The goal of the present study was to examine the association of social anxiety with a neural correlate of feedback processing, the feedback-related negativity (FRN), and determine if there was a moderating effect of racial/ethnic group. A community sample of 104 Latinx (n = 41), Asian American (n = 24), and non-Latinx White (NLW; n = 39) adolescents (ages 13-17) completed a computerized peer feedback task while continuous electroencephalogram was recorded. Social anxiety and FRN measures were differentially associated as a function of race/ethnicity. NLW adolescents demonstrated greater FRN responses to acceptance feedback as social anxiety increased, whereas FRN responses to both rejection and acceptance feedback were related to greater social anxiety for Asian American adolescents. Notably, the Latinx group showed the greatest FRN responses yet endorsed the least amount of social anxiety, with no relation between social anxiety and FRN detected. Results highlight cultural variation in the relation between neural correlates of self-regulatory processes and social anxiety. This information could guide culturally-informed models of social anxiety that adopt a multiple units of analysis framework.

The angiopoietin (Ang)-Tie pathway is essential for the proper maturation and remodeling of the vasculature. Despite its importance in disease, the mechanisms that control signal transduction through this pathway are poorly understood. Here, we demonstrate that heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang-Tie signaling through direct interactions with both Ang ligands and Tie1 receptors. HS GAGs formed ternary complexes with Ang1 or Ang4 and Tie2 receptors, resulting in potentiation of endothelial survival signaling. In addition, HS GAGs served as ligands for the orphan receptor Tie1. The HS-Tie1 interaction promoted Tie1-Tie2 heterodimerization and enhanced Tie1 stability within the mature vasculature. Loss of HS-Tie1 binding using CRISPR-Cas9-mediated mutagenesis in vivo led to decreased Tie protein levels, pathway suppression and aberrant retinal vascularization. Together, these results reveal that sulfated glycans use dual mechanisms to regulate Ang-Tie signaling and are important for the development and maintenance of the vasculature.

Schizophrenia (SZ) is associated with impaired adaptive functioning, including difficulties managing the demands of independent living, work, school, and interpersonal relationships. Prior studies have linked the physiological stress response with less effective coping in daily life. Differences in stress-response tendencies may also support heterogeneity in daily functioning in SZ. The present study examined two established measures of the stress response in patients with first-episode SZ. Salivary cortisol was included as an index of hypothalamic-pituitary-adrenal response. Vagal suppression (VS), a measure of stress-related reduction in heart rate variability, was used to assess parasympathetic flexibility. Greater cortisol response and VS to social-evaluative stress were predicted to be associated with better functioning in SZ over and above relationships with social cognition and neurocognition, two well-established predictors of functional outcome. Thirty-eight first-episode SZ outpatients and 29 healthy comparison subjects (HC) provided social cognitive, neurocognitive, and physiological measurements before and after the Trier Social Stress Test (TSST). Although SZ and HC did not differ on VS to the TSST, patients exhibited significant associations between VS and functioning across all four domains of the Role Functioning Scale. Furthermore, greater VS predicted more effective functioning with friends, beyond the contributions associated with social cognition and neurocognition, and strengthened the positive effects of higher levels of social cognition on independent living/self-care. VS elicited by social-evaluative stress in the laboratory may reflect stress-response tendencies in daily life that are relevant for daily functioning in first-episode SZ.

Economic hardship during childhood is associated with worse mental and physical health across the life span. Over the past decade, interdisciplinary research has started to elucidate the behavioral and biological pathways that underlie these disparities and identify protective factors that mitigate against their occurrence. In this integrative review we describe these advances, highlight remaining gaps in knowledge, and outline a research agenda for psychologists. This article has 3 aims. First, we consider the evolving psychobiological literature on protective factors and conclude that supportive relationships can mitigate against the physical health problems often associated with economic hardship. Second, we discuss recent empirical developments in health psychology, public health, and the biological sciences, which reveal trade-offs associated with adaptation and challenge the conception of what it means to be resilient. Finally, we outline a research agenda that attempts to integrate existing knowledge on health disparities with these newer challenges to inform both policy and practice for youth experiencing economic hardship. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Author(s): Blanca Noriega Esquives [sup.1] , Tae K. Lee [sup.2] , Patricia I. Moreno [sup.1] , Rina S. Fox [sup.3] , Betina Yanez [sup.4] , Gregory E. Miller [sup.5] , [...], To identify symptom burden profiles among men with advanced prostate cancer undergoing androgen-deprivation therapy and examine their association with baseline sociodemographic and medical characteristics and psychosocial outcomes over time. Latent profile analysis was employed to identify distinct groups based on the Expanded Prostate Index Composite and the McGill Pain Questionnaire at baseline. Psychosocial outcomes were assessed at baseline, 6- and 12-month follow-ups. Three profiles emerged: "high symptom burden," "high sexual bother," and "low symptom burden." Men with "high symptom burden" were younger and exhibited higher baseline levels of depression, stress, cancer-specific distress, and anxiety than men in the other two groups. However, men with "high symptom burden" also demonstrated improvement in these psychosocial outcomes over time. Men with advanced prostate cancer who experience multiple co-occurring symptoms demonstrate worse psychosocial adjustment. Patients with substantial symptom burden, and specifically young men, may benefit from prompt referral to supportive care services.

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