Sleep quality impacts the link between reactivity to uncertain threat and anxiety and alcohol use in youth.

Individual differences in reactivity to unpredictable threat (U-threat) have repeatedly been linked to symptoms of anxiety and drinking behavior. An emerging theory is that individuals who are hyper-reactive to U-threat experience chronic anticipatory anxiety, hyperarousal, and are vulnerable to excessive alcohol use via negative reinforcement processes. Notably, anxiety and alcohol use commonly relate to disruptions in sleep behavior and recent findings suggest that sleep quality may impact the link between reactivity to U-threat and psychiatric symptoms and behaviors. The aim of the current study was to examine the unique and interactive effects of reactivity to U-threat and sleep quality on anxiety symptoms and drinking behavior in a cohort of youth, ages 16-19 years. Participants (N = 112) completed a well-validated threat-of-shock task designed to probe individual differences in reactivity to U-threat and predictable threat (P-threat). Startle eyeblink potentiation was recorded during the task as an index of aversive reactivity. Participants also completed well-validated self-report measures of anxiety and depression symptoms, lifetime alcohol use, and current sleep quality. Results revealed significant startle reactivity to U-threat by sleep quality interactions on anxiety symptoms and lifetime drinking behavior. At high levels of sleep disturbance (only), greater reactivity to U-threat was associated with greater anxiety symptoms and total number of lifetime alcoholic beverages. These results suggest that sensitivity to uncertainty and chronic hyperarousal increases anxiety symptoms and alcohol use behavior, particularly in the context of poor sleep quality.

Everyday co-presence with a romantic partner is associated with lower C-reactive protein.

Social relationships are an important driver of health, and inflammation has been proposed as a key neurobiological mechanism to explain this effect. Behavioral researchers have focused on social relationship quality to further explain the association, yet recent research indicates that relationship quality may not be as robust a predictor as previously thought. Here, building on animal models of social bonds and recent theory on close relationships, we instead investigated merely being in the physical presence of one's romantic partner. Specifically, we tested the hypothesis that spending more time co-present with a loved partner in everyday life would be associated with lower C-reactive protein (CRP). Three times over the course of one month, 100 people in romantic relationships reported how much time they spent in the same physical space as their partner in the prior 24 h, in minutes, and provided a sample of blood for CRP assay (n observations = 296). Results from multi-level models showed that when one reported spending more time in the physical presence of their partner they had lower CRP - an effect that was independent from social relationship quality explanations from the prior literature, including romantic relationship quality, hostility, and loneliness. These findings move past global assessments of social isolation to consider a novel everyday behavior that is of great interest in the non-human animal literature - spending time together -- as a potential mechanism linking high-quality relationships and physical health in adult humans. The findings also point to future research on additional behavioral mechanisms that are not dependent on stress pathways: people in high-quality relationships tend to spend enjoyable and affectionate time with one another, which may impact inflammation.

Can inflammation predict social media use? Linking a biological marker of systemic inflammation with social media use among college students and middle-aged adults.

Drawing on recent evidence that inflammation may promote social affiliative motivation, the present research proposes a novel perspective that inflammation may be associated with more social media use. In a cross-sectional analysis of a nationally representative sample, Study 1 (N = 863) found a positive association between C-reactive protein (CRP), a biomarker of systemic inflammation, and the amount of social media use by middle-aged adults. Study 2 (N = 228) showed that among college students CRP was prospectively associated with more social media use 6 weeks later. Providing stronger evidence of the directionality of this effect, Study 3 (N = 171) showed that in college students CRP predicted increased social media use in the subsequent week even after controlling for current week's use. Additionally, in exploratory analyses of CRP and different types of social media use in the same week, CRP was only associated with using social media for social interaction and not for other purposes (e.g., entertainment). The present research sheds light on the social effects of inflammation and highlights potential benefits of using social media as a context for studying the impact of inflammation on social motivation and behavior.

Perceived social support-giving moderates the association between social relationships and interleukin-6 levels in blood.

Although positive social relationships are assumed to relate to lower levels of chronic systemic inflammation, the empirical evidence on this association is mixed. This study examines whether perceived social support-giving (i.e., the belief that one can be available to give social support to others, henceforward referred to as perceived support-giving) moderates associations between social relationships and inflammation using data from the longitudinal follow-up of the National Survey of Midlife Development in the U.S. (MIDUS II). Middle-aged adults (N = 1054) completed self-report questionnaires on social integration, perceived support-availability from others, positive relations with others, perceived support-giving, socio-demographic information, and health-related information and provided blood samples for measurement of interleukin-6 (IL-6) as a marker of systemic inflammation. The results showed that perceived support-giving moderated the associations between IL-6 and indicators of positive social relationships, including social integration, perceived support-availability, and positive relations with others. Indicators of positive social relationships were associated with lower IL-6 among individuals higher, but not lower, in perceived support-giving. The moderating effects of perceived support-giving held after adjusting for socio-demographic and health-related covariates. Therefore, positive social relationships are associated with lower IL-6 only for individuals who believe they can give more support in those relationships. In addition, preliminary evidence indicated that the moderating effects of perceived support-giving might be further qualified by gender, being significant only in women.

Racial and Economic Adversity Differences in Stress Markers and Immune Function Among Urban Adolescents.

BACKGROUND: Exposure to racism and associated adversities, such as poverty, is hypothesized to contribute to racial inequities in health via stress and immune pathways. Furthermore, the effects of adversity may be more salient during sensitive developmental periods. Our study examined racial differences in stress and immune biomarkers during adolescence and the effects of exposure to economic adversity at distinct developmental time periods and cumulatively in accounting for potential racial differences. METHODS: Secondary analysis of the Adolescent Health and Development in Context study was conducted. Data were derived from self-administered surveys; interviews; smartphone-based, geographic-explicit ecological momentary assessment; stress biomarkers (evening salivary cortisol over six nights and hair cortisol); and immune biomarkers (salivary shedding of Epstein-Barr virus [EBV] DNA among EBV-positive adolescents). Current socioeconomic status measures included annual household income and caregiver education. Caregivers also reported experiences of bankruptcy, difficulty paying bills, receipt of food stamps/Supplemental Nutrition Assistance Program/electronic benefit transfer, and job loss when the child was of ages birth-5 years, 6-10 years, and 11 years or older. An affirmative response to any item was defined as exposure to economic adversity for that developmental time period (yes/no). A cumulative economic adversity measure was calculated as the sum of exposures across developmental periods (0 = never exposed to 3 = exposed across all time periods). Descriptive and multivariable regression analyses were conducted, accounting for covariates. RESULTS: Black/African American adolescents had higher salivary cortisol concentration, higher hair cortisol concentration, and an increased odd of salivary shedding of EBV DNA compared to White adolescents. Racial differences were not attenuated by the current socioeconomic status or economic adversity (developmental period or cumulatively). DISCUSSION: Our study provides evidence that stress and immune biomarkers differ by race as early as adolescence and may be one pathway through which racism and associated adversities contribute to racial health inequities. Further research on the contribution of multiple adversities beyond poverty to racial inequities in physiological stress and health is critical for informing effective prevention and intervention efforts.

Stereotype threat, trait perseveration, and vagal activity: evidence for mechanisms underpinning health disparities in Black Americans.

Objective: Black Americans (BAs) are at an elevated risk for morbidity and mortality in comparison to White Americans (WAs). Racial stressors are a common occurrence in American culture and is theorized to contribute to these disparities. When race-focused, stereotype threat (ST) is considered to be a factor that is detrimental to health in BAs; however few studies have directly investigated the impact of a ST manipulation on physiological function. Furthermore, it is proposed that racial stressors such as ST may have prolonged effects when more likely to perseverate (e.g. rumination) over the stressor and thus, those with greater trait perseveration may be more affected by ST. We sought to explore the impact of ST and trait perseveration on changes in vagus nerve activity - an indication of adaptive psychological and physiological well-being - as indexed by vagally mediated heart rate variability (vmHRV). Design: Forty-three (24 females, mean age of 20, standard deviation of 3 years) apparently healthy BA individuals were randomly assigned to one of three experimental conditions in which they received either implicit (subtle), explicit (blatant), or no ST priming (control condition), prior to completing a cognitive task. Resting vmHRV was assessed both at baseline (pre-task) and recovery (post-task). Results: BAs in the explicit ST condition exhibited the greatest decrease in vmHRV in comparison to the control group from pre- to post-task. BAs with moderate to high levels of trait perseveration showed the greatest decrease in vmHRV from pre- to post-task in comparison to those with lower levels of trait perseveration and BAs in the control group. Conclusion: These data suggest that racial ST, especially when explicit and coupled with trait perseveration, can decrease vagal activity, as indexed by decreased vmHRV, which when experienced frequently can have significant consequences for health and longevity in BAs.

First Results from the DEAP-3600 Dark Matter Search with Argon at SNOLAB.

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31 keV_{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44} cm^{2} for a 100 GeV/c^{2} WIMP mass (90% C.L.).

Over-the-Counter Relief From Pains and Pleasures Alike: Acetaminophen Blunts Evaluation Sensitivity to Both Negative and Positive Stimuli.

Acetaminophen, an effective and popular over-the-counter pain reliever (e.g., the active ingredient in Tylenol), has recently been shown to blunt individuals' reactivity to a range of negative stimuli in addition to physical pain. Because accumulating research has shown that individuals' reactivity to both negative and positive stimuli can be influenced by a single factor (an idea known as differential susceptibility), we conducted two experiments testing whether acetaminophen blunted individuals' evaluations of and emotional reactions to both negative and positive images from the International Affective Picture System. Participants who took acetaminophen evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared with participants who took a placebo. Participants in the acetaminophen condition also rated both negative and positive stimuli as less emotionally arousing than did participants in the placebo condition (Studies 1 and 2), whereas nonevaluative ratings (extent of color saturation in each image; Study 2) were not affected by drug condition. These findings suggest that acetaminophen has a general blunting effect on individuals' evaluative and emotional processing, irrespective of negative or positive valence.

Oxytocin receptor gene (OXTR) is related to psychological resources.

Psychological resources--optimism, mastery, and self-esteem--buffer the deleterious effects of stress and are predictors of neurophysiological and psychological health-related outcomes. These resources have been shown to be highly heritable, yet the genetic basis for this heritability remains unknown. Here, we report a link between the oxytocin receptor (OXTR) SNP rs53576 and psychological resources, such that carriers of the "A" allele have lower levels of optimism, mastery, and self-esteem, relative to G/G homozygotes. OXTR was also associated with depressive symptomatology. Mediation analysis indicates that the effects of OXTR on depressive symptoms may be largely mediated by the influence of OXTR on psychological resources.

Donor age and early graft failure after lung transplantation: a cohort study.

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction (PGD). The rate of 1-year graft failure was similar among recipients of lungs from donors age 18-64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56-64 years had increased rates of 1-year graft failure (p-values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.

Neural sensitivity to social rejection is associated with inflammatory responses to social stress.

Although stress-induced increases in inflammation have been implicated in several major disorders, including cardiovascular disease and depression, the neurocognitive pathways that underlie inflammatory responses to stress remain largely unknown. To examine these processes, we recruited 124 healthy young adult participants to complete a laboratory-based social stressor while markers of inflammatory activity were obtained from oral fluids. A subset of participants (n = 31) later completed an fMRI session in which their neural responses to social rejection were assessed. As predicted, exposure to the laboratory-based social stressor was associated with significant increases in two markers of inflammatory activity, namely a soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII) and interleukin-6 (IL-6). In the neuroimaging subsample, greater increases in sTNFalphaRII (but not IL-6) were associated with greater activity in the dorsal anterior cingulate cortex and anterior insula, brain regions that have previously been associated with processing rejection-related distress and negative affect. These data thus elucidate a neurocognitive pathway that may be involved in potentiated inflammatory responses to acute social stress. As such, they have implications for understanding how social stressors may promote susceptibility to diseases with an inflammatory component.

Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33-q34. In the present study, endoglin, a transforming growth factor beta (TGF-beta) binding protein, was analysed as a candidate gene for the disorder based on chromosomal location, expression pattern and function. We have identified mutations in three affected individuals: a C to G substitution converting a tyrosine to a termination codon, a 39 base pair deletion and a 2 basepair deletion which creates a premature termination codon. We have identified endoglin as the HHT gene mapping to 9q3 and have established HHT as the first human disease defined by a mutation in a member of the TGF-beta receptor complex.

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.

Everyday perceptions of safety and racial disparities in hair cortisol concentration.

OBJECTIVE: Black-White disparities in physiological stress during adolescence are increasingly evident but remain incompletely understood. We examine the role of real-time perceptions of safety in the context of everyday routines to gain insight into the sources of observed adolescent racial differences in chronic stress as measured by hair cortisol concentration (HCC). METHOD: We combined social survey, ecological momentary assessment (EMA), and hair cortisol data on 690 Black and White youth ages 11-17 from wave 1 of the Adolescent Health and Development in Context (AHDC) study to investigate racial differences in physiological stress. Individual-level, reliability-adjusted measures of perceived unsafety outside the home were drawn from a week-long smartphone-based EMA and tested for association with hair cortisol concentration. RESULTS: We observed a statistically significant interaction (p < .05) between race and perceptions of unsafety. For Black youth, perceived unsafety was associated with higher HCC (p < .05). We observed no evidence of an association between perceptions of safety and expected HCC for White youth. For youth who perceive their out-of-home activity locations to be consistently safe, the racial difference in expected HCC was not statistically significant. At the high end of perceived unsafety, however, Black-White differences in HCC were pronounced (0.75 standard deviations at the 95th percentile on perceived unsafety; p < .001). DISCUSSION: These findings call attention to the role of everyday perceptions of safety across non-home routine activity contexts in explaining race differences in chronic stress as assessed by hair cortisol concentrations. Future research may benefit from data on in situ experiences to capture disparities in psychological and physiological stress.

Social status modulates neural activity in the mentalizing network.

The current research explored the neural mechanisms linking social status to perceptions of the social world. Two fMRI studies provide converging evidence that individuals lower in social status are more likely to engage neural circuitry often involved in 'mentalizing' or thinking about others' thoughts and feelings. Study 1 found that college students' perception of their social status in the university community was related to neural activity in the mentalizing network (e.g., DMPFC, MPFC, precuneus/PCC) while encoding social information, with lower social status predicting greater neural activity in this network. Study 2 demonstrated that socioeconomic status, an objective indicator of global standing, predicted adolescents' neural activity during the processing of threatening faces, with individuals lower in social status displaying greater activity in the DMPFC, previously associated with mentalizing, and the amygdala, previously associated with emotion/salience processing. These studies demonstrate that social status is fundamentally and neurocognitively linked to how people process and navigate their social worlds.

Hypoalbuminemia and early mortality after lung transplantation: a cohort study.

Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable-adjusted associations between serum albumin and the rate of death after transplantation. The median follow-up time was 2.7 years. Those with severe (0.5-2.9 g/dL) and mild hypoalbuminemia (3.0-3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12-1.62) and 1.15 (95% CI: 1.04-1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1-year and overall mortality rate ratios were 1.48 (95% CI: 1.21-1.81) and 1.26 (95% CI: 1.11-1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.

Maternal and offspring dopamine D4 receptor genotypes interact to influence juvenile impulsivity in vervet monkeys.

The merging of psychological and genetic methodologies has led to an increasing appreciation of environmental moderators of the relationships between genotype and phenotype. Here we used a nonhuman-primate model to study the moderating effect of the mother's genotype on the association of a dopamine D4 receptor (DRD4) gene polymorphism with juvenile impulsivity, assessed in a standardized social-challenge test. The results showed that juvenile carriers of the rare 5-repeat variant of the exon III 48-base-pair repeat polymorphism scored significantly higher in social impulsivity than juveniles homozygous for the common 6-repeat allele. In addition, juvenile genotype interacted with maternal genotype to influence impulsivity, with the highest rates of impulsivity found in variant offspring with variant mothers. These results highlight the importance of considering the genotype of the parents in studies of early experience and vulnerability genes for impulsivity-related traits.