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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.

To evaluate the association between psychotropic medication and inflammatory biomarkers in women with antenatal depressive symptoms (ADS). In this cross-sectional secondary analysis of a prospective multicenter observational study, 723 pregnant women underwent a depression screen using the Center for Epidemiologic Studies Depression Scale (CES-D) between 12 and 21 weeks gestation. Self-reported use of medications for depression and/or anxiety was corroborated with the medical record to document exposure to pharmacotherapy. Serum was collected and inflammatory biomarkers (IFNγ, IL13, IL6, IL8, TNFα, CRP) were measured concomitantly. Women were included if they fell into one of three categories: ADS responsive to treatment (CES-D

The misfolding and accumulation of tau protein into intracellular aggregates known as neurofibrillary tangles is a pathological hallmark of neurodegenerative diseases such as Alzheimer's disease. However, while tau propagation is a known marker for disease progression, exactly how tau propagates from one cell to another and what mechanisms govern this spread are still unclear. Here, we report that cellular internalization of tau is regulated by quaternary structure and have developed a cellular assay to screen for genetic modulators of tau uptake. Using CRISPRi technology we have tested 3200 genes for their ability to regulate tau entry and identified enzymes in the heparan sulfate proteoglycan biosynthetic pathway as key regulators. We show that 6-O-sulfation is critical for tau-heparan sulfate interactions and that this modification regulates uptake in human central nervous system cell lines, iPS-derived neurons, and mouse brain slice culture. Together, these results suggest novel strategies to halt tau transmission.

OBJECTIVE: Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. METHOD: P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures. RESULTS: Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed. CONCLUSIONS: Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Given that novice drivers tend to be young, and teenagers and young adult drivers are involved in the greatest number of accidents, it is important that we understand what factors impact the driving skills of this population of drivers. The primary aim of the present study was to understand the impact of gender, organized athletics, and video gaming on driving skills of novice drivers under real-world driving conditions. Novice driving students having less than five hours driving experience previous to a normal driving lesson were evaluated on their self-confidence (self-reported) prior to the lesson and driving skill evaluated by their instructor during the course of the lesson. Information was collected about gender, age, whether or not the students were involved in organized athletics, and the extent of their video game playing. There was no impact of gender or extent of video game playing on driving skills. Females were significantly less self-confident with driving than males, but this did not translate to gender differences in driving skills. Being involved in organized athletics-either currently or in the past-significantly enhanced driving skills in both females and males. Finally, novice drivers' age was negatively correlated with driving skills. That is, younger novice drivers (especially males) had better driving skills than older novice drivers. This is counter to popular belief that young drivers lack technical driving skills because they have less experience behind the wheel. Based on the results of the current study, we hypothesize that the relatively high accident rate of younger drivers (especially male drivers) is most likely due to inattention to safety considerations rather than lack of technical driving ability.

Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

A quarter of the global population meets diagnostic criteria for metabolic syndrome (MetS). MetS prevalence stratifies by socioeconomic status (SES), such that low SES is associated with higher MetS risk starting in childhood. Despite this trend, some low-SES children maintain good metabolic health across the life span, but the factors responsible for their resilience are not well understood. This study examined the role of threat vigilance as either a moderator or a mediator of the effects of low early life SES on adult metabolic risk. Three hundred twenty-five Canadians aged 15-55 participated (M = 36.4 years, SD = 10.7; 55.4% female). We coded parental occupational status between the ages of 0 and 5 to index early life SES. We used the International Diabetes Federation case definition for MetS based on waist circumference, blood pressure, triglyceride levels, HDL cholesterol, and glycosylated hemoglobin measures. Threat vigilance was assessed using the Weapons Identification Procedure, a visual discrimination paradigm that captures implicit perceptions of threat. Analyses supported the moderator hypothesis: low early life SES was associated with MetS diagnosis exclusively among those with high levels of threat vigilance. This suggests that low early life SES environments that heighten vigilance to threat might be particularly detrimental for metabolic health. Conversely, low threat vigilance may buffer against the metabolic risks associated with socioeconomic disadvantage.

Research suggests the health consequences of economic hardship can be transmitted across generations. Some of these disparities are thought to be passed to offspring during gestation. But this hypothesis has not been tested in contemporary American samples, and the mechanisms of transmission have not been characterized. Accordingly, this study had two goals: first, to determine if women exposed to economic hardship during childhood showed higher rates of adverse birth outcomes; and second, to evaluate the contribution of inflammation, psychosocial, lifestyle, and obstetric characteristics to this phenomenon. This prospective study enrolled 744 women with singleton pregnancies (59.1% White; 16.3% Black; 18.7% Latina; 5.9% Other). Childhood economic hardship was measured by self-report. Birth outcomes included length of gestation and incidence of preterm birth; birth weight percentile and small for gestational age; length of hospital stay and admission to Special Care Nursery. Analyses revealed that mothers' childhood economic hardship was independently associated with multiple adverse birth outcomes, even following adjustment for demographics, maternal education, and obstetrical confounders. Women raised in economically disadvantaged conditions had shorter gestation length and higher preterm delivery rates. Their babies had lower birth weights, were more likely to be small for gestational age, stayed in the hospital longer, and had more Special Care Nursery admissions. Mediation analyses suggested these associations arose through multiple pathways, and highlighted roles for inflammation, education, adiposity, and obstetric complications. Collectively, these findings suggest that childhood economic hardship predisposes women to adverse birth outcomes, and highlights likely behavioral and biological mechanisms.

OBJECTIVE: A quarter of the worlds population have metabolic syndrome (MetS). MetS prevalence is stratified by socioeconomic status (SES), such that low SES is associated with higher MetS risk. The present study examined the relative roles of early-life SES and current SES in explaining MetS risk. METHODS: Participants (N = 354; ages = 15-55 years, M [SD] = 36.5 [10.7] years; 55% female; 72.9% white, 16.9% Asian, 10.2% others) were evaluated for SES and MetS. All were in good health, defined as free of chronic medical illness and acute infectious disease. Using occupational status as a proxy for SES, we recruited roughly equal numbers of participants with low-low, low-high, high-low, and high-high combinations of early-life and current SES. We used the International Diabetes Federation definition for MetS using race- and sex-specific cutoffs for waist circumference, triglyceride levels, high-density lipoprotein cholesterol, blood pressure, and glycosylated hemoglobin levels. RESULTS: Analyses revealed a main effect of low early-life SES on increased MetS risk according to the three separate definitions. They included the traditional MetS diagnosis (odds ratio [OR] = 1.53, confidence interval [CI] = 1.01-2.33, p = .044), the number of MetS components for which diagnostic thresholds were met (OR = 1.61, CI = 1.10-2.38, p = .015), and a continuous indicator of metabolic risk based on factor analysis (F(1,350) = 6.71, p = .010, partial η = .019). There was also a significant interaction of early-life SES and current SES in predicting MetS diagnosis (OR = 1.54, CI = 1.02-2.34). The main effects of current SES were nonsignificant in all analyses. CONCLUSIONS: These findings suggest that MetS health disparities originate in childhood, which may be an opportune period for interventions.

The evolution of porous media due to mineral dissolution and precipitation can change the bulk properties of subsurface materials. The pore-scale structure of the media, including its physical and mineralogical heterogeneity, exerts controls on porous media evolution via transport limitations to reactive surfaces and mineral accessibility. Here we explore how these controls affect the evolution of the texture in porous media at the pore scale. For this purpose, a pore-scale flow and reactive transport model is developed that explicitly tracks mineral surfaces as they evolve using a direct numerical simulation approach. Simulations of dissolution in single-mineral domains provide insights into the transport controls at the pore scale, while the simulation of a fracture surface composed of bands of faster-dissolving calcite and slower-dissolving dolomite provides insights into the mineralogical controls on evolution. Transport-limited conditions at the grain-pack scale may result in unstable evolution, a situation in which dissolution is focused in a fast-flowing, fast-dissolving path. Due to increasing velocities, the evolution in these regions is like that observed under conditions closer to strict surface control at the pore scale. That is, grains evolve to have oblong shapes with their long dimensions aligning with the local flow directions. Another example of an evolving reactive transport regime that affects local rates is seen in the evolution of the fracture surface. As calcite dissolves, the diffusive length between the fracture flow path and the receding calcite surfaces increases. Thus, the calcite dissolution reaction becomes increasingly limited by diffusion.

Frontal EEG asymmetry is thought to reflect variations in affective style, such that greater relative right frontal activity at rest predicts enhanced emotional responding to threatening or negative stimuli, and risk of depression and anxiety disorders. A diathesis-stress model has been proposed to explain how this neuro-affective style might predispose to psychopathology, with greater right frontal activity being a vulnerability factor especially under stressful conditions. Less is known about the extent to which greater relative right frontal activity at rest might be associated with or be a diathesis for deleterious physical health outcomes. The present study examined the association between resting frontal EEG asymmetry and systemic, low-grade inflammation and tested the diathesis-stress model by examining whether childhood maltreatment exposure interacts with resting frontal asymmetry in explaining inflammation. Resting EEG, serum inflammatory biomarkers (interleukin-6, C-reactive protein, and fibrinogen) and self-reported psychological measures were available for 314 middle-aged adults (age M=55.3years, SD=11.2, 55.7% female). Analyses supported the diathesis-stress model and revealed that resting frontal EEG asymmetry was significantly associated with inflammation, but only in individuals who had experienced moderate to severe levels of childhood maltreatment. These findings suggest that, in the context of severe adversity, a trait-like tendency towards greater relative right prefrontal activity may predispose to low-grade inflammation, a risk factor for conditions with inflammatory underpinnings such as coronary heart disease.

ImportanceThis study was designed to determine whether a preventive intervention focused on enhancing supportive parenting could ameliorate the association between exposure to poverty and brain development in low socioeconomic status African American individuals from the rural South.ObjectiveTo determine whether participation in an efficacious prevention program designed to enhance supportive parenting for rural African American children will ameliorate the association between living in poverty and reduced hippocampal and amygdalar volumes in adulthood.Design, setting, and participantsIn the rural southeastern United States, African American parents and their 11-year-old children were assigned randomly to the Strong African American Families randomized prevention trial or to a control condition. Parents provided data used to calculate income-to-needs ratios when children were aged 11 to 13 years and 16 to 18 years. When the participants were aged 25 years, hippocampal and amygdalar volumes were measured using magnetic resonance imaging.ExposuresHousehold poverty was measured by income-to-needs ratios.Main outcomes and measuresYoung adults' whole hippocampal, dentate gyrus, and CA3 hippocampal subfields as well as amygdalar volumes were assessed using magnetic resonance imaging.ResultsOf the 667 participants in the Strong African American Families randomized prevention trial, 119 right-handed African American individuals aged 25 years living in rural areas were recruited. Years lived in poverty across ages 11 to 18 years forecasted diminished left dentate gyrus (simple slope, -14.20; standard error, 5.22; P = .008) and CA3 (simple slope, -6.42; standard error, 2.42; P = .009) hippocampal subfields and left amygdalar (simple slope, -34.62; standard error, 12.74; P = .008) volumes among young adults in the control condition (mean [SD] time, 2.04 [1.88] years) but not among those who participated in the Strong African American Families program (mean [SD] time, 2.61 [1.77] years).Conclusions and relevanceIn this study, we described how participation in a randomized clinical trial designed to enhance supportive parenting ameliorated the association of years lived in poverty with left dentate gyrus and CA3 hippocampal subfields and left amygdalar volumes. These findings are consistent with a possible role for supportive parenting and suggest a strategy for narrowing social disparities.