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Introduction: Mu opioid receptor gene (OPRM1) variant rs1799971 introduces a CpG site, which may influence DNA methylation (DNAm) and opioid/pain outcomes. Objectives: In this nested analysis, we investigated both OPRM1 A118G genotype and promoter/immediate downstream blood DNAm sequencing data for associations with opioid effects and chronic postsurgical pain (CPSP) in a surgical cohort. Methods: Prospectively recruited opioid naïve patients undergoing Nuss procedure or spinal fusion with rs1799971 genotypes (Illumina arrays), DNAm (next generation enzymatic methylation sequencing at Chr6:154,039,209-154,039,803) and outcomes—opioid analgesia (integrated opioid use 1 pain over postoperative days 0 and 1 normalized to surgery type), safety—respiratory depression (RD) in high opioid use groups, and CPSP (Numerical Rating Scale .3/10 2-12 months postsurgery)—were included. Linear and logistic regression were performed to test genetic and epigenetic associations, adjusted for sociodemographics, cell types, and analgesics. Results: In this cohort (N 5 112; 15.3 6 2.0 years, 50% female, 83% White, 55% had CPSP, 13% had RD), DNAm at Chr6: 154039216-154039217 was associated with CPSP (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.00-1.57; P 5 0.03), Chr6: 154039661-154039662 with acute integrated pain (b 5 220.9, 95% CI, 240.70 to 21.10, P 5 0.04), Chr6:154039520-154039521 (OR, 1.49; 95% CI, 1.09-2.03; P 5 0.01), and Chr6:154039571-154039572 (OR, 1.47; 95% CI, 1.08-2.01; P 5 0.02) with RD. Significant CpG sites were located in Repressed Polycomb chromatin states. Genotype was not associated with DNAm or outcomes. Conclusion: Our analyses support OPRM1 DNAm as predictors of acute and chronic pain/opioid outcomes in children after painful surgery. Study limitations included absent GG genotype, low sequencing coverage, and lack of correction for multiple testing.

BACKGROUND: Unpredictable childhood experiences are an understudied form of early life adversity that impacts neurodevelopment in a sex-specific manner. The neurobiological processes by which exposure to early-life unpredictability impacts development and vulnerability to psychopathology remain poorly understood. The present study investigates the sex-specific consequences of early-life unpredictability on the limbic network, focusing on the hippocampus and the amygdala. METHODS: Participants included 150 youth (54% female). Early life unpredictability was assessed using the Questionnaire of Unpredictability in Childhood (QUIC). Participants engaged in a task-fMRI scan between the ages of 8 and 17 (223 total observations) measuring BOLD responses to novel and familiar scenes. RESULTS: Exposure to early-life unpredictability associated with BOLD contrast (novel vs. familiar) in a sex-specific manner. For males, but not females, higher QUIC scores were associated with lower BOLD activation in response to novel vs. familiar stimuli in the hippocampal head and amygdala. Secondary psychophysiological interaction (PPI) analyses revealed complementary sex-specific associations between QUIC and condition-specific functional connectivity between the right and left amygdala, as well as between the right amygdala and hippocampus bilaterally. CONCLUSION: Exposure to unpredictability in early life has persistent implications for the functional operations of limbic circuits. Importantly, consistent with emerging experimental animal and human studies, the consequences of early life unpredictability differ for males and females. Further, impacts of early-life unpredictability were independent of other risk factors including lower household income and negative life events, indicating distinct consequences of early-life unpredictability over and above more commonly studied types of early life adversity.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) impacts both individual and relational functioning. Veteran couples are at increased risk of relationship distress due to military stressors such as deployment, family reintegration, and traumatic stress. Although both Cognitive-Behavioral Conjoint Therapy (CBCT) and its brief version (bCBCT) consistently have large effects on reducing PTSD symptoms, these treatments have more variable effects on relational outcomes. Given the impact of relationship functioning on the overall health of veterans, improving the effect of PTSD treatments on relationship functioning is an essential area of research. One promising path is the role of MDMA (3,4-methylenedioxymethamphetamine)-assisted therapy in augmenting the relational impact of established therapeutic interventions such as bCBCT. METHOD/DESIGN: This is a single site, open-label study assessing the preliminary efficacy, safety, and acceptability of MDMA-assisted therapy in combination with bCBCT in 8 veterans with PTSD and their intimate partners (N = 16). Therapy teams trained in bCBCT and MDMA-assisted therapy will deliver bCBCT combined with two MDMA sessions and two couple emotion focused integration sessions. PTSD symptom severity and relationship functioning outcomes will be evaluated. CONCLUSION: This is the first study to examine the efficacy of MDMA-assisted bCBCT for improving PTSD and relationship functioning among a sample of U.S. military veterans and their partners. This project could provide an opportunity to pilot a scalable model of treating PTSD within the Veterans Affairs healthcare system and leverage the benefits of MDMA for veterans with PTSD, as well as the downstream benefits to their partner on both individual and relationship functioning. ClinicalTrials.gov Identifier: NCT05979844.

Adverse early-life experiences (ELA) affect a majority of the worlds children. Whereas the enduring impact of ELA on cognitive and emotional health is established, there are no tools to predict vulnerability to ELA consequences in an individual child. Epigenetic markers including peripheral-cell DNA-methylation profiles may encode ELA and provide predictive outcome markers, yet the interindividual variance of the human genome and rapid changes in DNA methylation in childhood pose significant challenges. Hoping to mitigate these challenges we examined the relation of several ELA dimensions to DNA methylation changes and outcome using a within-subject longitudinal design and a high methylation-change threshold. DNA methylation was analyzed in buccal swab/saliva samples collected twice (neonatally and at 12 months) in 110 infants. We identified CpGs differentially methylated across time for each child and determined whether they associated with ELA indicators and executive function at age 5. We assessed sex differences and derived a sex-dependent impact score based on sites that most contributed to methylation changes. Changes in methylation between two samples of an individual child reflected age-related trends and correlated with executive function years later. Among tested ELA dimensions and life factors including income to needs ratios, maternal sensitivity, body mass index and infant sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, high early-life unpredictability interacted with methylation changes to presage executive function. Thus, longitudinal, within-subject changes in methylation profiles may provide a signature of ELA and a potential predictive marker of individual outcome.

High unpredictability has emerged as a dimension of early-life adversity that may contribute to a host of deleterious consequences later in life. Early-life unpredictability affects development of limbic and reward circuits in both rodents and humans, with a potential to increase sensitivity to stressors and mood symptoms later in life. Here, we examined the extent to which unpredictability during childhood was associated with changes in mood symptoms (anhedonia and general depression) after two adult life stressors, combat deployment and civilian reintegration, which were assessed ten years apart. We also examined how perceived stress and social support mediated and /or moderated links between childhood unpredictability and mood symptoms. To test these hypotheses, we leveraged the Marine Resiliency Study, a prospective longitudinal study of the effects of combat deployment on mental health in Active-Duty Marines and Navy Corpsman. Participants (N = 273) were assessed for depression and anhedonia before (pre-deployment) and 3-6 months after (acute post-deployment) a combat deployment. Additional assessment of depression and childhood unpredictability were collected 10 years post-deployment (chronic post-deployment). Higher childhood unpredictability was associated with higher anhedonia and general depression at both acute and chronic post-deployment timepoints (βs ≥ 0.16, ps ≤.007). The relationship between childhood unpredictability and subsequent depression at acute post-deployment was partially mediated by lower social support (b = 0.07, 95% CI [0.03, 0.15]) while depression at chronic post-deployment was fully mediated by a combination of lower social support (b = 0.14, 95% CI [0.07, 0.23]) and higher perceived stress (b = 0.09, 95% CI [0.05, 0.15]). These findings implicate childhood unpredictability as a potential risk factor for depression in adulthood and suggest that increasing the structure and predictability of childhood routines and developing social support interventions after life stressors could be helpful for preventing adult depression.

BackgroundAnhedonia, an impairment in the motivation for or experience of pleasure, is a well-established transdiagnostic harbinger and core symptom of mental illness. Given increasing recognition of early life origins of mental illness, we posit that anhedonia should, and could, be recognized earlier if appropriate tools were available. However, reliable diagnostic instruments prior to childhood do not currently exist.MethodsWe developed an assessment instrument for anhedonia/reward processing in infancy, the Infant Hedonic/Anhedonic Processing Index (HAPI-Infant). Exploratory factor and psychometric analyses were conducted using data from 6- and 12-month-old infants from two cohorts (N = 188, N = 212). Then, associations were assessed between infant anhedonia and adolescent self-report of depressive symptoms.ResultsThe HAPI-Infant (47-items), exhibited excellent psychometric properties. Higher anhedonia scores at 6 (r = 0.23, p

BackgroundThe effects of aging on circadian patterns of behavior are insufficiently described. To address this, we characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults both overall, and in relation, to sociodemographic characteristics.MethodsWe examined cross-sectional associations between RAR and age, sex, race, education, multimorbidity burden, financial, work, martial, health, and smoking status using assessments of older adults with wrist-worn free-living actigraphy data (N=820, Age=76.4 yrs, 58.2% women) participating in the Study of Muscle, Mobility and Aging (SOMMA). RAR parameters were determined by mapping an extension to the traditional cosine curve to activity data. Functional principal component analysis determined variables accounting for variance.ResultsAge was associated with several metrics of dampened RAR; women had stronger and more robust RAR vs. men (all P < 0.05). Total activity (56%) and time of activity (20%) accounted for most the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (P

We have reconstructed baseline δ15N and δ13C of export production at Kingman Reef in the Central Equatorial Pacific (CEP) at sub-decadal resolution, nearly continuously over the last 2000 years. The changes in δ15N reflects the strength of the North Equatorial Counter Current (NECC) relative to the South Equatorial Current (SEC), and to a lesser extent, the North Equatorial Current (NEC). Seasonal to multi-decadal variation in the strength of these currents, through the redistribution of heat, have global climate impacts and influence marine and terrestrial ecosystems. We use modern El Niño-La Nina dynamics and the Tropical Pacific Decadal Variability (TPDV) pattern, which is defined in the CEP, as a framework for analyzing the isotopic data. The CEP δ15N and δ13C records exhibit multi-decadal (50-60 year) variability consistent with TPDV. A large multi-centennial feature in the CEP δ15N data, within age-model uncertainties, is consistent with one of the prolonged dry-pluvial sequences in the American west at the end of the Medieval Climate Anomaly, where low TPDV is correlated with drier conditions. This unique record shows that the strength of the NECC, as reflected in baseline δ15N and δ13C, has at quasi-predictable intervals throughout the late Holocene, toggled the phytoplankton community between prokaryotes and picoplankton versus eukaryotes.

BackgroundPatterns of sensory inputs early in life play an integral role in shaping the maturation of neural circuits, including those implicated in emotion and cognition. In both experimental animal models and observational human research, unpredictable sensory signals have been linked to aberrant developmental outcomes, including poor memory and effortful control. These findings suggest that sensitivity to unpredictable sensory signals is conserved across species and sculpts the developing brain. The current study provides a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. We tested these associations in three independent cohorts to probe the generalizability of associations across continents and cultures.MethodThe three prospective longitudinal cohorts were based in Orange, USA (n = 163, 47.2 % female, Mage = 1 year); Turku, Finland (n = 239, 44.8 % female, Mage = 5 years); and Irvine, USA (n = 129, 43.4 % female, Mage = 9.6 years). Unpredictability of maternal sensory signals was quantified during free-play interactions. Child internalizing behaviors were measured via parent report (Orange & Turku) and child self-report (Irvine).ResultsEarly life exposure to unpredictable maternal sensory signals was associated with greater child fearfulness/anxiety in all three cohorts, above and beyond maternal sensitivity and sociodemographic factors. The association between unpredictable maternal sensory signals and child sadness/depression was relatively weaker and did not reach traditional thresholds for statistical significance.LimitationsThe correlational design limits our ability to make causal inferences.ConclusionsFindings across the three diverse cohorts suggest that unpredictable maternal signals early in life shape the development of internalizing behaviors, particularly fearfulness and anxiety.

BACKGROUND: Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing. METHODS: A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings. RESULTS: Prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. Both prenatal negative mood level and entropy were associated with the amplitude of low frequency fluctuations of the salience network. Latent class analysis yielded 2 profiles based on changes in network integrity across all functional magnetic resonance imaging sequences. The profile that exhibited little variation in network connectivity (i.e., inflexibility) consisted of adolescents who were exposed to higher negative maternal mood levels and more entropy. CONCLUSIONS: These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.

BackgroundFalls in the older population are a major public health concern. While many physiological and environmental factors have been associated with fall risk, muscle mitochondrial energetics has not yet been investigated.MethodsIn this analysis, 835 Study of Muscle, Mobility and Aging (SOMMA) participants aged 70-94 were surveyed for number of falls (total), recurrent falls (2+), and fall-related injuries over the past 12 months at baseline and again after one year. Skeletal muscle energetics were assessed at baseline in vivo using 31P Magnetic Resonance Spectroscopy (MRS) after an acute bout of exercise (ATPmax) and ex vivo by High Resolution Respirometry (HRR) of permeabilized muscle fibers from the vastus lateralis (MaxOXPHOS).ResultsAt least one fall was reported in 28.7% of SOMMA participants in the first year of the study, with 12% of older adults reporting recurrent falls (2+). Individuals who experienced recurrent falls had a slower 400m walk gait speed (1.0 ± 0.2 vs. 1.1 ± 0.2, p

BACKGROUND: Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world's children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure. Here, we examined the relation of several dimensions of ELA to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes in the hope of mitigating the above challenges. METHODS: We analyzed DNA methylation in buccal swab samples collected twice for each of 110 infants: neonatally and at 12 months. We identified CpGs differentially methylated across time, calculated methylation changes for each child, and determined whether several indicators of ELA associated with changes of DNA methylation for individual infants. We then correlated select dimensions of ELA with methylation changes as well as with measures of executive function at age 5 years. We examined for sex differences, and derived a sex-dependent 'impact score' based on sites that most contributed to the methylation changes. FINDINGS: Setting a high threshold for methylation changes, we discovered that changes in methylation between two samples of an individual child reflected age-related trends towards augmented methylation, and also correlated with executive function years later. Among the tested factors and ELA dimensions, including income to needs ratios, maternal sensitivity, body mass index and sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, an interaction was observed between a measure of high early-life unpredictability and methylation changes, in presaging executive function. INTERPRETATION: These findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. Future studies are required to determine if the methylation profile changes identified here provide a predictive marker of vulnerabilities to poorer cognitive and emotional outcomes.

We describe important and common management and labor needs across more than 80 federal agencies as identified by the annual Federal Employee Viewpoint Survey (FEVS) and offer evidence-based interventions for addressing them based on organizational science research. Our recommendations have the synergistic goals of improving employee wellbeing, employee productivity, and agency performance and innovation, which will result in increased agency efficiency and effectiveness for the taxpayer. Specifically, we describe empirical findings and offer suggestions for interventions to improve (a) employee motivation through engagement, empowerment, and embeddedness; (b) employee voice; and (c) within- and across-unit cooperation, communication, and collaboration. We offer recommendations that are sufficiently general to be relevant to many agencies, while also being concrete and actionable. We also offer suggestions for associated research that could be conducted in federal agencies interested in these topics.

Background: Emotional circuit maturation is shaped by sensory signals in the environment during early life. For example, unpredictable parental and environmental sensory signals (high entropy) during early life result in increased hippocampal synaptic pruning and enduring changes in emotional circuitry in rodents. In humans, exposure to such high entropy during infancy is associated with deficits in memory and executive control during childhood and adolescence. Maturation of emotional circuitry is dependent on the integration of numerous processes in several circuits, all involving the paraventricular nucleus of the thalamus (PVT). Indeed, there is growing evidence that the PVT contributes to storing memories of salient experiences over long durations, such as memories of early life adversity. However, PVT connectivity in humans has not yet been evaluated prior to adulthood, and the impact of early life entropy on the development of PVT connectivity to key nodes of emotional circuitry during childhood and adolescence is largely unknown.Methods: Maternal sensory signals during mother-child interaction were video-recorded and coded at 6 and 12 months age. The predictability of these signals during the interaction was characterized by calculating state transition probabilities (likelihood the mother would change from one sensory signal to another), computing the entropy associated with the transition probabilities, and averaging between the two sessions (as previously described). Two fMRI imaging sessions were conducted during childhood and early adolescence (n = 37, 16 females, 21 males, 9-13.7 years). Six bilateral regions of interest were selected a priori based on the PVT circuitry in rodent literature, including: the anterior cingulate cortex (ACC), amygdala, bed nucleus of the stria terminalis (BNST), hippocampus, locus coeruleus, lateral hypothalamus (LH), and nucleus accumbens (NAc). Measures of functional connectivity between these regions and the PVT were considered in six independent mixed effects models testing for a main effect of entropy adjusted for age at scan and sex.Results: There was a negative association of entropy with the functional connectivity between the PVT and bilateral LH (T-stat = -2.71, p-uncorrected = 0.0089) and BNST (T-stat = -2.22, p-uncorrected = 0.0308). Functional connectivity between the PVT and NAc (T-stat = 2.65, p-uncorrected = 0.0105) and between the PVT and ACC (T-stat = 2.62, p-uncorrected = 0.0114) was higher in females compared to males of the same age.Conclusions: Unpredictable maternal signals during infancy, reflected here as high entropy, may contribute to the development of PVT functional connectivity to the LH and BNST. In rodents, the lateral hypothalamus to PVT projection plays a role in arousal and reward learning, while the BNST to PVT connections may contribute to anxiety behaviors. The sex effects observed here may be due to sex-differences in pubertal timing during adolescence. Future work will employ large, publicly available datasets to further characterize the development of PVT circuitry and its putative role in mediating the effects of diverse early-life factors in the development of mental illness.Keywords: Paraventricular Nucleus of the Thalamus, Entropy, Unpredictability, Resting State Functional Connectivity, Early-Life ExperienceDisclosure: Nothing to disclose.

BACKGROUND: Aging is associated with declines in circadian functions. The effects of aging on circadian patterns of behavior are insufficiently described. We characterized age-specific features of rest-activity rhythms (RAR) in community dwelling older adults, both overall, and in relation, to sociodemographic characteristics. METHODS: We analyzed baseline assessments of older adults with wrist-worn free-living wrist-worn actigraphy data (N=820, Age=76.4 yrs, 58.2% women) participating in the Study of Muscle, Mobility and Aging (SOMMA). We applied an extension to the traditional cosine curve to map RAR to activity data, calculating the parameters: rhythmic strength (amplitude); robustness (pseudo-F statistic); and timing of peak activity (acrophase). We also used function principal component analysis to determine 4 components describing underlying patterns of activity accounting for RAR variance. Linear models were used to examine associations between RAR and sociodemographic variables. RESULTS: Age was associated with several metrics of dampened RAR; women had stronger and more robust RAR metrics vs. men (all P < 0.05). Total activity (56%) and time of activity (20%) accounted for most the RAR variance. Compared to the latest decile of acrophase, those in the earliest decile had higher average amplitude (P

BACKGROUND: Effortful control, or the regulation of thoughts and behaviour, is a potential target for preventing childhood obesity. OBJECTIVES: To assess effortful control in infancy through late childhood as a predictor of repeated measures of body mass index (BMI) from infancy through adolescence, and to examine whether sex moderates the associations. METHODS: Maternal report of offspring effortful control and measurements of child BMI were obtained at 7 and 8 time points respectively from 191 gestational parent/child dyads from infancy through adolescence. General linear mixed models were used. RESULTS: Effortful control at 6 months predicted BMI trajectories from infancy through adolescence, F(5,338) = 2.75, p = 0.03. Further, when effortful control at other timepoints were included in the model, they added no additional explanatory value. Sex moderated the association between 6-month effortful control and BMI, F(4, 338) = 2.59, p = 0.03, with poorer infant effortful control predicting higher BMI in early childhood for girls, and more rapid increases in BMI in early adolescence for boys. CONCLUSIONS: Effortful control in infancy was associated with BMI over time. Specifically, poor effortful control during infancy was associated with higher BMI in childhood and adolescence. These findings support the argument that infancy may be a sensitive window for the development of later obesity.

BACKGROUND: Falls occur annually in 25% of adults aged ≥65 years. Fall-related injuries are increasing, highlighting the need to identify modifiable risk factors. METHODS: Role of fatigability on prospective, recurrent, and injurious fall risk was examined in 1 740 men aged 77-101 years in the Osteoporotic Fractures in Men Study. The 10-item Pittsburgh Fatigability Scale measured perceived physical and mental fatigability (0-50/subscale) at Year 14 (2014-16); established cut-points identified men with more severe perceived physical (≥15, 55.7%), more severe mental (≥13, 23.7%) fatigability, or having both (22.8%). Prospective, recurrent (≥2), and injurious falls were captured by triannual questionnaires ≥1 year after fatigability assessment; risk of any fall was estimated with Poisson generalized estimating equations, and likelihood of recurrent/injurious falls with logistic regression. Models adjusted for age, health conditions, and other confounders. RESULTS: Men with more severe physical fatigability had a 20% (p = .03) increased fall risk compared with men with less physical fatigability, with increased odds of recurrent and injurious falls, 37% (p = .04) and 35% (p = .035), respectively. Men with both more severe physical and mental fatigability had a 24% increased risk of a prospective fall (p = .026), and 44% (p = .045) increased odds of recurrent falling compared with men with less severe physical and mental fatigability. Mental fatigability alone was not associated with fall risk. Additional adjustment for previous fall history attenuated associations. CONCLUSIONS: More severe fatigability may be an early indicator to identify men at high risk for falls. Our findings warrant replication in women, as they have higher rates of fatigability and prospective falls.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

Heatwaves in California manifest as both dry and humid events. While both forms have become more prev-alent, recent studies have identified a shift toward more humid events. Understanding the complex interactions of each heatwave type with the urban heat island is crucial for impacts but remains understudied. Here, we address this gap by contrasting how dry versus humid heatwaves shape the intraurban heat of the greater Los Angeles area. We used a consecu-tive contrasting set of heatwaves from 2020 as a case study: a prolonged humid heatwave in August and an extremely dry heatwave in September. We used MERRA-2 reanalysis data to compare mesoscale dynamics, followed by high-resolution Weather Research and Forecasting modeling over urbanized Southern California. We employ moist thermodynamic varia-bles to quantify heat stress and perform spatial clustering analysis to characterize the spatiotemporal intraurban variability. We find that, despite temperatures being 108 6 38C hotter in the September heatwave, the wet-bulb temperature, closely related to the risk of human heat stroke, was higher in August. While dry and humid heat display different spatial patterns, three distinct spatial clusters emerge based on nonheatwave local climates. Both types of heatwaves diminish the intraur-ban heat stress variability. Valley areas such as San Bernardino and Riverside experience the worst impacts, with up to 68 6 0.58C of additional heat stress during heatwave nights. Our results highlight the need to account for the disparity in small-scale heatwave patterns across urban neighborhoods in designing policies for equitable climate action.

PurposeIn 2020, racially/ethnically minoritized (REMD) youth faced the "dual pandemics" of COVID-19 and racism, both significant stressors with potential for adverse mental health effects. The current study tested whether short- and long-term trajectories of depressive symptoms from before to during the COVID-19 pandemic differed between REMD adolescents who did and did not endorse exposure to COVID-19-era-related racism (i.e., racism stemming from conditions created or exacerbated by the COVID-19 pandemic).MethodsA community sample of 100 REMD adolescents enrolled in an ongoing longitudinal study of mental health was assessed before and during the COVID-19 pandemic. Participants were 51% girls, mean age = 16, standard deviation = 2.7, and identified as Latinx/Hispanic (48%), Multiethnic (34%), Asian American (12%), and Black (6%).ResultsREMD adolescents' depressive symptoms were elevated during the COVID-19 pandemic compared to pre-pandemic levels, and increases were more pronounced over time for those who endorsed exposure to COVID-19-era-related racism. In general, Asian American participants endorsed racism experiences at the highest rates compared to others, including being called names (42%), people acting suspicious around them (33%), and being verbally threatened (17%). Additionally, more than half of Black and Asian American participants reported worry about experiencing racism related to the COVID-19 pandemic, even if they had not experienced it to date.DiscussionREMD adolescents are at increased risk for depressive symptoms related to converging stressors stemming from the COVID-19 pandemic and pandemic-related racism, which has the potential to widen racial/ethnic mental health disparities faced by the REMD youth.

Preconception and prenatal stress impact fetal and infant development, and women of color are disproportionately exposed to sociocultural stressors like discrimination and acculturative stress. However, few studies examine links between mothers exposure to these stressors and offspring mental health, or possible mitigating factors. Using linear regression, we tested associations between prenatally assessed maternal acculturative stress and discrimination on infant negative emotionality among 113 Latinx/Hispanic, Asian American, Black, and Multiethnic mothers and their children. Additionally, we tested interactions between stressors and potential pre- and postnatal resilience-promoting factors: community cohesion, social support, communalism, and parenting self-efficacy. Discrimination and acculturative stress were related to more infant negative emotionality at approximately 12 months old (M = 12.6, SD = .75). In contrast, maternal report of parenting self-efficacy when infants were 6 months old was related to lower levels of infant negative emotionality. Further, higher levels of parenting self-efficacy mitigated the relation between acculturative stress and negative emotionality. Preconception and prenatal exposure to sociocultural stress may be a risk factor for poor offspring mental health. Maternal and child health researchers, policymakers, and practitioners should prioritize further understanding these relations, reducing exposure to sociocultural stressors, and promoting resilience.

BackgroundA standardized protocol for electroencephalography (EEG) under standing sedation for the investigation of epilepsy in foals is needed.Hypothesis/objectivesTo evaluate a modified standardized EEG protocol under standing sedation using sublingual detomidine hydrochloride in Egyptian Arabian foals.AnimalsNineteen foals (controls, 9; juvenile idiopathic epilepsy [JIE], 10).MethodsDescriptive clinical study. Foals were classified as controls or epileptic based on history or witnessed seizures and neurological examination. Foals were sedated using sublingual detomidine hydrochloride at a dosage of 0.08 mg/kg to avoid stress associated with injectable sedation. Once foals appeared sedated with their heads low to the ground and with wide base stance (30 minutes), topical lidocaine hydrochloride was applied at the determined locations of EEG electrodes. Fifteen minutes were allowed for absorption and electrodes were placed, protected, and EEG recording performed.ResultsLevel of sedation was considered excellent with no need of redosing. The EEG recording lasted from 27 to 51 minutes and provided interpretable data. Epileptic discharges (ED) were noted predominantly in the central-parietal region in 9 of 10 epileptic foals. Photic stimulation triggered ED in 7 of 10 epileptic foals and in none of the controls. Foals were not oversedated and recovered uneventfully.Conclusions and clinical importanceSublingual detomidine hydrochloride is a safe, painless, simple, and effective method of sedation for EEG recording in foals. Sublingual sedation allowed the investigation of cerebral electrical activity during states of sleep and arousal, and during photic stimulation for the investigation of epilepsy in foals.

Capitalizing on a longitudinal cohort followed from gestation through adolescence (201 mother-child dyads), we investigate the contributions of severity and stability of both maternal depressive and perceived stress symptoms to adolescent psychopathology. Maternal depressive and perceived stress trajectories from pregnancy through adolescence were identified with latent class growth analyses, and associations with adolescent internalizing and externalizing symptoms were examined. For both depression and stress, the most common trajectory group comprised mothers displaying stable and low symptom levels over time, and adolescents of these mothers had the fewest internalizing and externalizing symptoms. Maternal membership to one or more aberrant trajectory groups predicted higher levels of internalizing and externalizing symptoms, determined by both maternal and adolescent self-report. This study indicates that profiles of multiple indicators of maternal psychopathology assessed across childhood, beginning prenatally, can provide critical additional insight into child psychopathology risk.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth mixture modeling (GGMM)2 and then used to predict child growth patterns using multilevel modeling. Infants of mothers who had flat cortisol trajectories, characterized by relatively high cortisol in early gestation that plateaus by mid-gestation, experienced more rapid increases in BMIP from birth to 6 months, and had higher BMIPs at 3 and 6 months, than infants whose mothers had the typical slow cortisol rise over gestation, or steep (rapidly accelerating) trajectories. These results suggest that it is not just the total amount of maternal cortisol in pregnancy that shapes early infant growth, but instead the timing and trajectory of prenatal cortisol exposure. To better understand the early origins of obesity risk, future research is needed to investigate the factors that shape mothers prenatal cortisol trajectories.

BACKGROUND: The impact of undernutrition in dogs with protein-losing enteropathy (PLE) caused by inflammatory enteritis, intestinal lymphangiectasia, or both and which variables are most predictive of outcome are unknown. OBJECTIVES: Develop an undernutrition screening score (USS) for use at the time of diagnosis of PLE in dogs, which is predictive of outcome. ANIMALS: Fifty-seven dogs with PLE prospectively recruited from 3 referral hospitals in the United Kingdom. METHODS: An USS based on the presence and severity of 5 variables: appetite, weight loss, and body, muscle, and coat condition and scored out of 15, with higher scores reflecting worse undernutrition, was calculated at the time of diagnosis. Follow-up information was obtained for at least 6 months. RESULTS: Dogs that failed to achieve clinical remission within 6 months had higher USS at diagnosis compared with dogs that achieved remission (median, 7.5; range, 2-14 and median, 5; range, 0-14, respectively). The USS at diagnosis gave an area under the receiver operating characteristic curve (AUC) of 0.656 for predicting nonclinical remission within 6 months, whereas a score consisting of just epaxial muscle loss and coat condition resulted in a larger AUC of 0.728. CONCLUSIONS AND CLINICAL IMPORTANCE: Of the 5 variables assessed in the USS, a combination of epaxial muscle loss and coat condition was most predictive of not achieving clinical remission within 6 months in dogs with PLE. Additional studies will help determine the effect of changes in USS and the 5 associated variables after diagnosis on outcome variables in these dogs.

This qualitative study examined world language (WL) educators’ perceptions of equity in WL education. Using a sociocultural framework that emphasized the relationship between structures and agency, the analysis revealed that WL educators perceived key equity issues to include: a lack of access to WL study related to students’ race, socioeconomic status, and disability; world language teacher shortages; and a lack of culturally relevant, engaging curriculum. The participants described ways that they drew on their agency to effect change through professional development, curricular redesign, advocating for multilingual families, and engaging in efforts to overhaul policy and other institutional structures. The discussion and implications illuminate a need for a more systemic response to issues of WL access, equity, and inclusion that will require collaboration and action by educators, stakeholders, policymakers, and professional organizations.

Research suggests that perspective-taking in children is associated with greater cognitive and emotion understanding as well as parent use of mental state language—words concerning inner mental states or feelings. However, prior research shows conflicting results on which categories of mental state language—cognition (e.g., think, know), emotion (e.g., happy), or desire (e.g., want)—facilitate children’s perspective-taking. The current study examines the relationship between parent mental state language and children’s perspective-taking.We are coding parent mental state language categories from a wordless book task with two-year-old children and assessing children’s perspective-taking using a card task (Flavell et al., 1981). Preliminary results (N=19, planned 41) show that, on average, parents use more cognition words per session than desire words and, on average, children score at chance on the perspective-taking task. Differences between mental state categories on children’s perspective-taking skills as well as individual variability will be analyzed.

BackgroundLower physical activity (PA) is associated with greater perceived fatigability, a person-centered outcome. The association between change in PA and fatigability with advanced age has yet to be established.MethodsCommunity-dwelling older men (N = 1 113, age = 84.1 ± 3.9 years at Year 14) had free-living PA assessed using SenseWear Armband prospectively at Year 7 (2007-2009) and Year 14 (2014-2016) of Osteoporotic Fractures in Men Study, a longitudinal cohort established in 2000 (baseline). We categorized percent changes in PA into groups (large decline → large increase) for 4 metrics: step count, light intensity PA (LIPA, metabolic equivalents [METs] >1.5 to 1.5).ResultsMen declined 2 336 ± 2 546 (34%) steps/d, 24 ± 31 (25%) LIPA min/d, 33 ± 58 (19%) MVPA min/d, and increased 40 ± 107 (6%) SB min/d over 7.2 ± 0.7 years. Compared to large decline (% change less than -50%), those that maintained or increased step count had 3-8 points lower PFS Physical scores; those who maintained or increased LIPA and MVPA had 2-3 and 2-4 points lower PFS Physical scores, respectively (all p ≤ .01). Associations were similar, but smaller, for PFS Mental scores.ConclusionOlder men who maintained or increased PA had lower fatigability, independent of initial PA. Our findings inform the types and doses of PA that should be targeted to reduce fatigability in older adults.

BackgroundInvasive species threaten the productivity and stability of natural and managed ecosystems. Predicting the spread of invaders, which can aid in early mitigation efforts, is a major challenge, especially in the face of climate change. While ecological niche models are effective tools to assess habitat suitability for invaders, such models have rarely been created for invasive pest species with rapidly expanding ranges. Here, we leveraged a national monitoring effort from 543 sites over 3 years to assess factors mediating the occurrence and abundance of brown marmorated stink bug (BMSB, Halyomorpha halys), an invasive insect pest that has readily established throughout much of the United States.ResultsWe used maximum entropy models to estimate the suitable habitat of BMSB under several climate scenarios, and generalized boosted models to assess environmental factors that regulated BMSB abundance. Our models captured BMSB distribution and abundance with high accuracy, and predicted a 70% increase in suitable habitat under future climate scenarios. However, environmental factors that mediated the geographical distribution of BMSB were different from those driving abundance. While BMSB occurrence was most affected by winter precipitation and proximity to populated areas, BMSB abundance was influenced most strongly by evapotranspiration and solar photoperiod.ConclusionOur results suggest that linking models of establishment (occurrence) and population dynamics (abundance) offers a more effective way to forecast the spread and impact of BMSB and other invasive species than simply occurrence-based models, allowing for targeted mitigation efforts. Implications of distribution shifts under climate change are discussed. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Children exposed to prenatal maternal psychological distress are at elevated risk for a range of adverse outcomes; however, it remains poorly understood whether postnatal influences can ameliorate impairments related to prenatal distress. The current study evaluated if sensitivematernal care during the first postnatal year could mitigate child cognitive and emotional impairments associated with prenatal psychological distress. Prenatal maternal psychological distress was assessed via self-reports of anxiety, depression, and perceived stress for 136 mothers at five prenatal and four postpartum time points. Quality of maternal care (sensitivity to nondistress, positive regard, and intrusiveness reverse-scored) were assessed during a mother-child play interaction at 6 and 12 months. Child cognitive function and negative emotionality were assessed at 2 years, using The Bayley Scales and the Early Childhood Behavior Questionnaire. Elevated prenatal distress was associated with poorer child cognitive function and elevated negative emotionality. Children exposed to elevated prenatal maternal distress did not, however, display these outcomes if they received high-quality caregiving. Specifically, maternal care moderated the relation between prenatal psychological distress and child cognitive function and negative emotionality. This association remained after consideration of postnatal maternal psychological distress and relevant covariates. Sensitive maternal care was associated with altered offspring developmental trajectories, supporting child resilience following prenatal distress exposure.

BackgroundRecent studies in both human and experimental animals have identified fragmented and unpredictable parental and environmental signals as a novel source of early-life adversity. Early-life unpredictability may be a fundamental developmental factor that impacts brain development, including reward and emotional memory circuits, affecting the risk for psychopathology later in life. Here, we tested the hypothesis that self-reported early-life unpredictability is associated with psychiatric symptoms in adult clinical populations.MethodsUsing the newly validated Questionnaire of Unpredictability in Childhood, we assessed early-life unpredictability in 156 trauma-exposed adults, of which 65% sought treatment for mood, anxiety, and/or posttraumatic stress disorder (PTSD) symptoms. All participants completed symptom measures of PTSD, depression and anhedonia, anxiety, alcohol use, and chronic pain. Relative contributions of early-life unpredictability versus childhood trauma and associations with longitudinal outcomes over a 6-month period were determined.ResultsEarly-life unpredictability, independent of childhood trauma, was significantly associated with higher depression, anxiety symptoms, and anhedonia, and was related to higher overall symptom ratings across time. Early-life unpredictability was also associated with suicidal ideation, but not alcohol use or pain symptoms.ConclusionsEarly-life unpredictability is an independent and consistent predictor of specific adult psychiatric symptoms, providing impetus for studying mechanisms of its effects on the developing brain that promote risk for psychopathology.

BackgroundThe Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) is a new iteration of prior National Heart, Lung, and Blood Institute (NHLBI) REDS programs that focus on improving transfusion recipient outcomes across the lifespan as well as the safety and availability of the blood supply.Study design and methodsThe US program includes blood centers and hospitals (22 including 6 free-standing Children's hospitals) in four geographic regions. The Brazilian program has 5 participating hemocenters. A Center for Transfusion Laboratory Studies (CTLS) and a Data Coordinating Center (DCC) support synergistic studies and activities over the 7-year REDS-IV-P program.ResultsThe US is building a centralized, vein-to-vein (V2V) database, linking information collected from blood donors, their donations, the resulting manufactured components, and data extracts from hospital electronic medical records of transfused and non-transfused patients. Simultaneously, the Brazilian program is building a donor, donation, and component database. The databases will serve as the backbone for retrospective and prospective observational studies in transfusion epidemiology, transfusion recipient outcomes, blood component quality, and emerging blood safety issues. Special focus will be on preterm infants, patients with sickle cell disease, thalassemia or cancer, and the effect of donor biologic variability and component manufacturing on recipient outcomes. A rapid response capability to emerging safety threats has resulted in timely studies related to Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2).ConclusionsThe REDS-IV-P program endeavors to improve donor-recipient-linked research with a focus on children and special populations while also maintaining the flexibility to address emerging blood safety issues.

BackgroundThe Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood donors in 6 US metropolitan regions to estimate the extent of SARS-CoV-2 infections over time.MethodsDuring March-August 2020, approximately ≥1000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences compared with the general population. Seroprevalence was compared with reported coronavirus disease 2019 (COVID-19) case rates over time.ResultsFor all regions, seroprevalence was

Black Americans are overrepresented in Veteran and non-Veteran homeless populations. Community integration remains a problem for many Veterans after they obtain housing, and Black Veterans may encounter additional difficulties due to systemic racism. However, no prior study has specifically examined whether there are racial differences in community integration; similarly, no study has considered racial differences in psychosocial correlates of community integration in homeless Veterans. Knowledge of these factors could inform the development of culturally congruent rehabilitative interventions for Black Veterans. Semi-structured clinical interviews were administered to Black (N = 99) and White (N = 49) homeless Veterans to examine relations among psychiatric symptoms, motivation, and community integration domains (e.g., social integration, work productivity, and independent living). There were no significant racial differences in independent living or work productivity. Black Veterans had better social integration with family compared to White Veterans. In addition, psychiatric symptoms were more strongly correlated with social integration for Black than White Veterans. The association between motivation and work productivity was also stronger for Black Veterans. Recovery-oriented interventions could harness family connections and better target psychiatric symptoms to improve community integration for Black Veterans. Work productivity may improve from interventions aimed at enhancing motivation for Black Veterans.

BackgroundThe COVID-19 era is a time of unprecedented stress, and there is widespread concern regarding its short- and long-term mental health impact. Adolescence is a sensitive period for the emergence of latent psychopathology vulnerabilities, often activated by environmental stressors. The present study examined COVID-19's impact on adolescent depression and possible influences of different domains of social connectedness (loneliness, social media use, social video game time, degree of social activity participation).MethodsA community sample of 175 adolescents (51% boys, mean age = 16.01 years) completed questionnaires once before and twice during the COVID-19 pandemic. Piecewise growth modeling examined the acute (7 weeks) and persistent (8 months) effects of COVID-19 on depressive symptoms, and differences across sex and social connectedness.ResultsSignificant increases in depressive symptoms followed pandemic onset for boys and girls. However, this increase was earlier and more pronounced among girls than boys, whose depression only increased significantly during the persistent period and to a lesser degree. Trajectories of depression were influenced by loneliness and social connections.LimitationsMost participants had economic stability and minimal exposure to the virus. Exacerbation of depressive symptoms may be more severe in higher risk populations.ConclusionsAdolescent depression levels have increased during COVID-19, and are higher for girls and those who are lonely. Enhanced screening and management for adolescent depression and social connectedness could play a critical role in mitigating the negative mental health fallout of COVID-19 and future pandemics within this population.

Objective: The current study examines how maternal depressive symptoms relate to child psychopathology when structured via the latent bifactor model of psychopathology, a new organizational structure of psychopathological symptoms consisting of a general common psychopathology factor (p-factor) and internalizing- and externalizing-specific risk.Method: Maternal report of depressive symptoms (Beck Depression Inventory - II) and child psychopathological symptoms (Child Behavior Checklist and Children's Behavior Questionnaire) were provided by 554 mother-child pairs. Children in the sample were 7.7 years old on average (SD = 1.35, range = 5-11 years), and were 49.8% female, 46% Latinx, and 67% White, 6% Black, 5% Asian/Pacific Islander, and 21% multiracial.Results: Maternal depressive symptoms were positively associated with the child p-factor but not with the internalizing- or externalizing-specific factors. We did not find evidence of sex/gender or race/ethnicity moderation when using latent factors of psychopathology. Consistent with past research, maternal depressive symptoms were positively associated with internalizing and externalizing composite scores on the Child Behavior Checklist.Conclusions: Findings suggest that maternal depressive symptoms are associated with transdiagnostic risk for broad child psychopathology (p-factor). Whereas the traditional Achenbach-style approach of psychopathological assessment suggests that maternal depressive symptoms are associated with both child internalizing and externalizing problems, the latent bifactor model suggests that these associations may be accounted for by risk pathways related to the p-factor rather than internalizing or externalizing specific risk. We discuss clinical and research implications of using a latent bifactor structure of psychopathology to understand how maternal depression may impact children's mental health.

OBJECTIVE: Examine the association between personality measures and perceived mental fatigability. METHODS: We performed a cross-sectional analysis in N=1670 men, age 84.3±4.1 years. Multivariable linear regression models were used to examine the covariate adjusted association between personality measures (conscientiousness, optimism, goal reengagement, and goal disengagement) and perceived mental fatigability (measured with the validated 10-item Pittsburgh Fatigability Scale, PFS). RESULTS: One standard deviation lower conscientiousness (β=-0.91, p

Exposure to early life adversity has long term consequences on cognitive function. Most research has focused on understanding components of early life adversities that contribute to later risk, including poverty, trauma, maltreatment, and neglect. Whereas these factors, in the aggregate, explain a significant proportion of emotional and cognitive problems, there are serious gaps in our ability to identify potential mechanisms by which early life adversities might promote vulnerability or resilience. Here we discuss early life exposure to unpredictable signals from the caretaker as an understudied type of adversity that is amenable to prevention and intervention. We employ a translational approach to discover underlying neurobiological mechanisms by which early life exposure to unpredictable signals sculpts the developing brain. First, we review evidence that exposure to unpredictable signals from the parent during sensitive periods impacts development of neural circuits. Second, we describe a method for characterizing early life patterns of sensory signals across species. Third, we present published and original data illustrating that patterns of maternal care predict memory function in humans, non-human primates, and rodents. Finally, implications are discussed for identifying individuals at risk so that early preventive-intervention can be provided.

Unpredictability is increasingly recognized as a primary dimension of early life adversity affecting lifespan mental health trajectories; screening for these experiences is therefore vital. The Questionnaire of Unpredictability in Childhood (QUIC) is a 38-item tool that measures unpredictability in childhood in social, emotional and physical domains. The available evidence indicates that exposure to unpredictable experiences measured with the QUIC predicts internalizing symptoms including depression and anxiety. The purpose of the present study was to validate English and Spanish brief versions (QUIC-5) suitable for administration in time-limited settings (e.g., clinical care settings, large-scale epidemiological studies). Five representative items were identified from the QUIC and their psychometric properties examined. The predictive validity of the QUIC-5 was then compared to the QUIC by examining mental health in four cohorts: (1) English-speaking adult women assessed at 6-months postpartum (N = 116), (2) English-speaking male veterans (N = 95), (3) English-speaking male and female adolescents (N = 155), and (4) Spanish-speaking male and female adults (N = 285). The QUIC-5 demonstrated substantial variance in distributions in each of the cohorts and is correlated on average 0.84 (r's = 0.81-0.87) with the full 38-item version. Furthermore, the QUIC-5 predicted internalizing symptoms (anxiety and depression) in all cohorts with similar effect sizes (r's = 0.16-0.39; all p's < 0.05) to the full versions (r's = 0.19-0.42; all p's < 0.05). In sum, the QUIC-5 exhibits good psychometric properties and is a valid alternative to the full QUIC. These findings support the future use of the QUIC-5 in clinical and research settings as a concise way to measure unpredictability, identify risk of psychopathology, and intervene accordingly.

ObjectiveThis study examined whether perceived neighborhood cohesion (the extent to which neighbors trust and count on one another) buffers against the mental health effects of the 2020 COVID-19 pandemic.MethodsThe XXX University National COVID-19 and Mental Health Study surveyed US adults (N = 3965; M age = 39 years), measuring depressive symptoms, staying home more during than before the 2020 pandemic, and perceived neighborhood cohesion.ResultsA series of linear regressions indicated that perceiving one's neighborhood as more cohesive was not only associated with fewer depressive symptoms, but also attenuated the relationship between spending more time at home during the pandemic and depressive symptoms. These relationships persisted even after taking into account several individual-level sociodemographic characteristics as well as multiple contextual features, i.e., median household income, population density, and racial/ethnic diversity of the zip codes in which participants resided.ConclusionsNeighborhood cohesion may be leveraged to mitigate pandemic impacts on depressive symptoms.

ObjectiveTo estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth.Study designRetrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24 hours beforehand.ResultsData from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P 45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8).ConclusionsThere is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

BackgroundRegional left ventricular (LV) mechanics in mitral regurgitation (MR) patients, and local changes in function after transcatheter mitral valve implantation (TMVI) have yet to be evaluated. Herein, we introduce a method for creating high resolution maps of endocardial function from 4DCT images, leading to detailed characterization of changes in local LV function. These changes are particularly interesting when evaluating the effect of the Tendyne™ TMVI device in the region of the epicardial pad.MethodsRegional endocardial shortening from CT (RSCT) was evaluated in Tendyne (Abbott Medical) TMVI patients with 4DCT exams pre- and post-implantation. Regional function was evaluated in 90 LV segments (5 longitudinal × 18 circumferential). LV volumes and ejection fraction (EF) were also computed. A reproducibility study was performed in a subset of patients to determine the precision of RSCT measurements in this population.ResultsBaseline and local changes in RSCT post TMVI were highly variable and extremely spatially heterogeneous. Both inter- and intra-observer variability were low and demonstrated the high precision of RSCT for evaluating regional LV function.ConclusionRSCT is a reproducible metric which can be evaluated in patients with highly abnormal regional LV function and geometry. After TMVI, significant spatially heterogeneous changes in RSCT were observed in all subjects; therefore, it is unlikely that the functional state of TMVI patients can be fully described by changes in LV volume or EF. Measurement of RSCT provides precise characterization of the spatially heterogeneous effects of MR and TMVI on LV function and remodeling.

We describe important and common management and labor needs across more than 80 federal agencies as identified by the annual Federal Employee Viewpoint Survey (FEVS) and offer evidence-based interventions for addressing them based on organizational science research. Our recommendations have the synergistic goals of improving employee wellbeing, employee productivity, and agency performance and innovation, which will result in increased agency efficiency and effectiveness for the taxpayer. Specifically, we describe empirical findings and offer suggestions for interventions to improve (a) employee motivation through engagement, empowerment, and embeddedness; (b) employee voice; and (c) within- and across-unit cooperation, communication, and collaboration. We offer recommendations that are sufficiently general to be relevant to many agencies, while also being concrete and actionable. We also offer suggestions for associated research that could be conducted in federal agencies interested in these topics.

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1-3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1-3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1-3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1-3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

ObjectiveInformation about the adverse effects of the COVID-19 pandemic on adolescent and adult mental health is growing, yet the impacts on preschool children are only emerging. Importantly, environmental factors that augment or protect from the multidimensional and stressful influences of the pandemic on emotional development of young children are poorly understood.MethodsDepressive symptoms in 169 preschool children (mean age 4.1 years) were assessed with the Preschool Feelings Checklist during a state-wide stay-at-home order in Southern California. Mothers (46% Latinx) also reported on externalizing behaviors with the Strengths & Difficulties Questionnaire. To assess the role of environmental factors in child mental health we examined household income, food insecurity, parental essential worker status and loss of parental job, as well as preservation of the structure of children's daily experiences with the Family Routines Inventory.ResultsSixty-one percent of families' incomes were below the living wage and 50% had at least one parent who was an essential worker. Overall, preschoolers' depressive and externalizing symptoms were elevated compared to pre-COVID norms. Practice of family routines robustly predicted better child mental health, and this protective effect persisted after covarying income, dual-parent status and food insecurity as well as maternal depression and stress.ConclusionThe stress of the COVID-19 pandemic is exacting a significant toll on the mental health of preschool children. Importantly, maintaining a structured, predicable home environment by adherence to family routines appears to mitigate these adverse effects, providing empiric basis for public health recommendations.

The 2017–2027 National Academies' Decadal Survey, Thriving on Our Changing Planet, recommended Surface Biology and Geology (SBG) as a “Designated Targeted Observable” (DO). The SBG DO is based on the need for capabilities to acquire global, high spatial resolution, visible to shortwave infrared (VSWIR; 380–2500 nm; ~30 m pixel resolution) hyperspectral (imaging spectroscopy) and multispectral midwave and thermal infrared (MWIR: 3–5 μm; TIR: 8–12 μm; ~60 m pixel resolution) measurements with sub-monthly temporal revisits over terrestrial, freshwater, and coastal marine habitats. To address the various mission design needs, an SBG Algorithms Working Group of multidisciplinary researchers has been formed to review and evaluate the algorithms applicable to the SBG DO across a wide range of Earth science disciplines, including terrestrial and aquatic ecology, atmospheric science, geology, and hydrology. Here, we summarize current state-of-the-practice VSWIR and TIR algorithms that use airborne or orbital spectral imaging observations to address the SBG DO priorities identified by the Decadal Survey: (i) terrestrial vegetation physiology, functional traits, and health; (ii) inland and coastal aquatic ecosystems physiology, functional traits, and health; (iii) snow and ice accumulation, melting, and albedo; (iv) active surface composition (eruptions, landslides, evolving landscapes, hazard risks); (v) effects of changing land use on surface energy, water, momentum, and carbon fluxes; and (vi) managing agriculture, natural habitats, water use/quality, and urban development. We review existing algorithms in the following categories: snow/ice, aquatic environments, geology, and terrestrial vegetation, and summarize the community-state-of-practice in each category. This effort synthesizes the findings of more than 130 scientists.