Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life.

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings. The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother. The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks' gestation. Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants' development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively. Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04). The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

Lessons from Grassroots Efforts to Increase Gender-Affirming Medical Care for Transgender and Gender Diverse Youth in the Community Health Care Setting.

Increasingly, transgender and gender diverse (TGD) youth are seeking gender-affirming medical care. Most multidisciplinary gender-affirming pediatric clinics are located in academic facilities in urban areas. To improve access to care and advance the field, grassroots establishment-without targeted funding or explicitly trained gender health providers-of multidisciplinary gender health clinics in rural and community health care settings can increase care access and lay the foundation for dedicated funding, staff, and clinic space. In this perspective piece, we share our grassroots process of establishing a multidisciplinary gender health clinic in the community setting, highlighting critical turning points that facilitated our clinic's rapid growth. Our experience can provide important lessons learned for community health care systems seeking to establish programs that will serve TGD youth.

Exploring development of infant gaze, affect, and object exploration in a primarily Latino sample.

Infants demonstrate rapid development across the first years of life, which underlies increased human interactions that promote social-emotional development. In particular, gaze, affect, and object exploration are early indicators of engagement and show rapid changes in the first year of life. However, current understanding on developmental trajectories during infancy often comes from majority white, non-Hispanic/Latino samples. This longitudinal study explored the development of infant gaze, affect, and object exploration across 2-18 months of age in a sample of primarily Latino infants drawn from a pediatric community clinic. Videos of mother-infant play when infants were 2, 6, 9, 12 and 18 months were coded for durations of three types of behaviors: gaze, affect, and object exploration. Additionally, mother-infant play videos when the infant was 24 months of age were coded for joint engagement. Descriptive statistics for the three behavior types were obtained at each timepoint, and repeated measures analysis of covariance investigated the development of behaviors from timepoint to timepoint. Latent growth curve analyses were conducted to analyze developmental trajectories of capacities across 2-18 months, as well as development in relation to joint engagement at 24 months. Results indicate an important development period from 2 to 6 months of infants' life, unique developmental patterns of specific behaviors, and heterogeneity in gaze development in the sample and across ages. Overall, this study provides an important description of development within mother-infant play in a primarily Latino sample.

Analysis and novel methods for capture of normative eye-tracking data in 2.5-month old infants.

Development of attention systems is essential for both cognitive and social behavior maturation. Visual behavior has been used to assess development of these attention systems. Yet, given its importance, there is a notable lack of literature detailing successful methods and procedures for using eye-tracking in early infancy to assess oculomotor and attention dynamics. Here we show that eye-tracking technology can be used to automatically record and assess visual behavior in infants as young as 2.5 months, and present normative data describing fixation and saccade behavior at this age. Features of oculomotor dynamics were analyzed from 2.5-month old infants who viewed videos depicting live action, cartoons, geometric shapes, social and non-social scenes. Of the 54 infants enrolled, 50 infants successfully completed the eye-tracking task and high-quality data was collected for 32 of those infants. We demonstrate that modifications specifically tailored for the infant population allowed for consistent tracking of pupil and corneal reflection and minimal data loss. Additionally, we found consistent fixation and saccade behaviors across the entire six-minute duration of the videos, indicating that this is a feasible task for 2.5-month old infants. Moreover, normative oculomotor metrics for a free-viewing task in 2.5-month old infants are documented for the first time as a result of this high-quality data collection.

Maternal stress and development of infant attention to threat-related facial expressions.

Attentional biases to threat-related stimuli, such as fearful and angry facial expressions, are important to survival and emerge early in development. Infants demonstrate an attentional bias to fearful facial expressions by 5-7 months of age and an attentional bias toward anger by 3 years of age that are modulated by experiential factors. In a longitudinal study of 87 mother-infant dyads from families predominantly experiencing low income, we examined whether maternal stress and depressive symptoms were associated with trajectories of attentional biases to threat, assessed during an attention disengagement eye-tracking task when infants were 6-, 9-, and 12-month old. By 9 months, infants demonstrated a generalized bias toward threat (both fearful and angry facial expressions). Maternal perceived stress was associated with the trajectory of the bias toward angry facial expressions between 6 and 12 months. Specifically, infants of mothers with higher perceived stress exhibited a greater bias toward angry facial expressions at 6 months that decreased across the next 6 months, compared to infants of mothers with lower perceived stress who displayed an increased bias to angry facial expressions over this age range. Maternal depressive symptoms and stressful life events were not associated with trajectories of infant attentional bias to anger or fear. These findings highlight the role of maternal perceptions of stress in shaping developmental trajectories of threat-alerting systems.

Science Autonomy for Ocean Worlds Astrobiology: A Perspective.

Astrobiology missions to ocean worlds in our solar system must overcome both scientific and technological challenges due to extreme temperature and radiation conditions, long communication times, and limited bandwidth. While such tools could not replace ground-based analysis by science and engineering teams, machine learning algorithms could enhance the science return of these missions through development of autonomous science capabilities. Examples of science autonomy include onboard data analysis and subsequent instrument optimization, data prioritization (for transmission), and real-time decision-making based on data analysis. Similar advances could be made to develop streamlined data processing software for rapid ground-based analyses. Here we discuss several ways machine learning and autonomy could be used for astrobiology missions, including landing site selection, prioritization and targeting of samples, classification of "features" (e.g., proposed biosignatures) and novelties (uncharacterized, "new" features, which may be of most interest to agnostic astrobiological investigations), and data transmission.

Quantifying Therapists' Activities during Sensory Integration Treatment for Young Children with Autism.

AIMS: There is limited research on the type and quantity of actions (activities) occupational therapy practitioners utilize when providing sensory integration treatment to children with Autism Spectrum Disorders (ASD). METHODS: A coding scheme identifying specific aspects of sensory integration treatment was developed and used to analyze 34 videos of 9 children with ASD, aged between 18 and 56 months, treated by 8 occupational therapists. Occupational therapists providing sensory integration treatment to children with ASD were behaviorally coded and rated using Observer XT, a software package designed for analysis of behavioral processes. RESULTS: Verbal communications, including offers, positive commands, and feedback, to facilitate engagement were the most frequent actions enacted by therapists. Proprioceptive activities were the most frequent sensory opportunities presented. Therapists received high ratings for sensitivity qualities. CONCLUSIONS: The number of sensory opportunities and interactions the therapists provided suggest concordance with sensory integration treatment components in the clinical setting. General impression ratings indicate engagement between child and therapist may be an important aspect of sensory integration treatment for young children with ASD. Quantification of therapists' actions can provide insight into the moment-to-moment decision-making and relationships between therapist and child during daily practice of sensory integration treatment.

Environmental Epigenetics of Diesel Particulate Matter Toxicogenomics.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by disruptions in social communication and behavioral flexibility. Both genetic and environmental factors contribute to ASD risk. Epidemiologic studies indicate that roadway vehicle exhaust and in utero exposure to diesel particulate matter (DPM) are associated with ASD. Using the Comparative Toxicogenomics Database (CTD), we identified genes connected to DPM exposure and ASD, extracted the known enhancers/promoters of the identified genes, and integrated this with Assay for Transposase Accessible Chromatin (ATAC-seq) data from DPM-exposed human neural progenitor cells. Enhancer/promoter elements with significantly different chromosome accessibility revealed enriched DNA sequence motifs with transcription factor binding sites for EGR1. Variant extraction for linkage disequilibrium blocks of these regions followed by analysis through Genome Wide Association Studies (GWAS) revealed multiple neurological trait associations including exploratory eye movement and brain volume measurement. This approach highlights the effects of pollution on the regulatory regions of genes implicated in ASD by genetic studies, indicating convergence of genetic and environmental factors on molecular networks that contribute to ASD. Integration of publicly available data from the CTD, cell culture exposure studies, and phenotypic genetics synergize extensive evidence of chemical exposures on gene regulation for altered brain development.

An exploratory study of predictors of cognition in two low-income samples of infants across the first year of life.

OBJECTIVE: In this exploratory longitudinal study we assessed cognitive development in a community sample of infants born into predominantly low-income families from two different urban sites, to identify family and community factors that may associate with outcomes by 1 year of age. METHOD: Infant-mother dyads (n = 109) were recruited in Boston and Los Angeles community pediatric practices. Infant cognition was measured using the Mullen Scales of Early Learning when the infant was aged 2, 6, 9, and 12 months. Longitudinal linear mixed effects modeling and linear regression models explored potential predictors of cognitive outcomes. RESULTS: Cognitive scores were lower than the reference population mean at both 6 and 12 months. There were site differences in demographics and cognitive performance. Maternal education predicted expressive language in Boston, and speaking Spanish and lower rates of community poverty were associated with greater increases in overall cognition in Los Angeles. CONCLUSION: This exploratory study identified a number of drivers of child development that are both shared across cohorts and unique to specific community samples. Factors influencing heterogeneity within and across populations both may be important contributors to prevention and intervention in supporting healthy development among children.

Adapting social conditioned place preference for use in young children.

OBJECTIVE: Social-emotional processing is key to daily interactions and routines, yet a challenging construct to quantify. Measuring social and emotional processing in young children, children with language impairments, or non-verbal children, presents additional challenges. This study addresses a pressing need for tools to probe internal responses such as feelings, drives, and motivations that do not rely on intact language skills. METHODS: In this study, we extend our recent success of inducing conditioned place preference (CPP) in children to demonstrate the success of using a social unconditioned stimulus in the CPP paradigm in both typically developing children (n = 36) and in children with a diagnosis of autism spectrum disorder (n = 14). RESULTS: This is the first study to demonstrate successful social conditioned place preference in the human population. Both typically developing children and children with autism spectrum disorder demonstrate significant social conditioned place preference by spending significantly more time in the room paired with social interaction following training. CONCLUSIONS: Significant heterogeneity of CPP scores in both groups of children indicates that social motivation is expressed along a continuum, and that the CPP paradigm may provide a more comprehensive characterization of social motivation beyond a diagnosis of an autism spectrum disorder for each child.

Association of Perceived Maternal Stress During the Perinatal Period With Electroencephalography Patterns in 2-Month-Old Infants.

Importance: Variation in child responses to adversity creates a clinical challenge to identify children most resilient or susceptible to later risk for disturbances in cognition and health. Advances in establishing scalable biomarkers can lead to early identification and mechanistic understanding of the association of early adversity with neurodevelopment. Objectives: To examine whether maternal reports of stress are associated with patterns in resting electroencephalography at 2 months of age and whether unique electroencephalographic profiles associated with risk and resiliency factors can be identified. Design, Setting, and Participants: For this cohort study, a population-based sample of 113 mother-infant dyads was recruited from January 1, 2016, to March 1, 2018, during regularly scheduled pediatric visits before infants were 2 months of age from 2 primary care clinics in Boston, Massachusetts, and Los Angeles, California, that predominantly serve families from low-income backgrounds. Data are reported from a single time point, when infants were aged 2 months, of an ongoing cohort study longitudinally following the mother-infant dyads. Exposures: Maternal reported exposure to stressful life events and perceived stress. Main Outcomes and Measures: Spectral power (absolute and relative) in different frequency bands (Δ, θ, low and high α, ß, and γ) from infant resting electroencephalography (EEG) and EEG profiles across frequency bands determined by latent profile analysis. Results: Of 113 enrolled infants, 70 (mean [SD] age, 2.42 [0.37] months; 35 girls [50%]) provided usable EEG data. In multivariable hierarchical linear regressions, maternal perceived stress was significantly and negatively associated with absolute ß (ß = -0.007; 95% CI, -0.01 to -0.001; semipartial r = -0.25) and γ power (ß = -0.008; 95% CI, -0.01 to -0.002; semipartial r = -0.28). Maternal educational level was significantly and positively associated with power in high α, ß, and γ bands after adjusting for covariates (high school: γ: ß = 0.108; 95% CI, 0.014-0.203; semipartial r = -0.236; associate's degree or higher: high α: ß = 0.133; 95% CI, 0.018-0.248; semipartial r = 0.241; ß: ß = 0.167; 95% CI, 0.055-0.279; semipartial r = 0.309; and γ: ß = 0.183; 95% CI, 0.066-0.299; semipartial r = 0.323). Latent profile analysis identified 2 unique profiles for absolute and relative power. Maternal perceived stress (ß = 0.13; 95% CI, 0.01-0.25; adjusted odds ratio [AOR], 1.14; 95% CI, 1.01-1.28) and maternal educational level (high school: ß = 3.00; 95% CI, 0.35-5.65; AOR, 20.09; 95% CI, 1.42-283.16; associate's degree or higher: ß = 4.12; 95% CI, 1.45-6.79; AOR, 61.56; 95% CI, 4.28-885.01) were each associated with unique profile membership. Conclusions and Relevance: These findings suggest that unique contributions of caregiver stress and maternal educational level on infant neurodevelopment are detectable at 2 months; EEG might be a promising tool to identify infants most susceptible to parental stress and to reveal mechanisms by which neurodevelopment is associated with adversity. Additional studies validating subgroups across larger cohorts with different stressors and at different ages are required before use at the individual level in clinical settings.

When in doubt, sit quietly: A qualitative investigation of experienced therapists' perceptions of self-disclosure.

Using consensual qualitative research (CQR), we analyzed 13 interviews of experienced psychotherapists about general intentions for therapist self-disclosure (TSD), experiences with successful TSDs, experiences with unsuccessful TSDs, and instances of unmanifested urges to disclose. For TSD generally (i.e., not about a specific instance), typical intentions were to facilitate exploration and build and maintain the therapeutic relationship. Therapists typically reported becoming more comfortable using TSD over time. In successful TSDs, the typical content was accurate, relevant similarities between therapist and client; typical consequences were positive. In unsuccessful TSDs, the typical antecedent was countertransference reactions; the typical intention was to provide support; typical content involved therapists mistakenly perceiving similarities with clients; and the general consequences were negative. In instances when therapists repressed the urge to disclose, the typical antecedent was countertransference and the content typically seemed relevant to the client's issues. We conclude that effective use of TSD requires general attunement to the client's dynamics, attunement to the client's readiness in the moment, ability to manage countertransference, and ability to use a specific TSD appropriately. Implications for practice, training, and research are discussed. (PsycINFO Database Record

Therapists-in-training experiences of working with transfer clients: One relationship terminates and another begins.

Data from interviews with 12 graduate-level trainees about their experiences of working with clients who had been transferred to them from another therapist were analyzed using consensual qualitative research. Trainees reported a range of helpful and hindering aspects about the transfer experience related to the client (e.g., client had experienced a prior termination and transfer, client had severe character pathology), the prior therapist (e.g., prior therapist prepared client for transfer, prior therapists did not process their termination with client), themselves (e.g., participant was open to addressing grief, participant was fearful of rejection), supervision (e.g., the supervisor provided important feedback on dealing with loss, the supervisor failed to address the unique nature of transferring), training (e.g., there was not adequate readings on termination and transfer, there was no readings on transfers), and clinic practices (e.g., meeting with the prior therapist and current therapist facilitated process, having clients end treatment with debt hindered the development of the new relationship). Participants also provided recommendations for improving the transfer process. Implications of these findings for clinical practice, training, and research are addressed. (PsycINFO Database Record

Complete or partial reduction of the Met receptor tyrosine kinase in distinct circuits differentially impacts mouse behavior.

BACKGROUND: Our laboratory discovered that the gene encoding the receptor tyrosine kinase, MET, contributes to autism risk. Expression of MET is reduced in human postmortem temporal lobe in autism and Rett Syndrome. Subsequent studies revealed a role for MET in human and mouse functional and structural cortical connectivity. To further understand the contribution of Met to brain development and its impact on behavior, we generated two conditional mouse lines in which Met is deleted from select populations of central nervous system neurons. Mice were then tested to determine the consequences of disrupting Met expression. METHODS: Mating of Emx1 (cre) and Met (fx/fx) mice eliminates receptor signaling from all cells arising from the dorsal pallium. Met (fx/fx) and Nestin (cre) crosses result in receptor signaling elimination from all neural cells. Behavioral tests were performed to assess cognitive, emotional, and social impairments that are observed in multiple neurodevelopmental disorders and that are in part subserved by circuits that express Met. RESULTS: Met (fx/fx) /Emx1 (cre) null mice displayed significant hypoactivity in the activity chamber and in the T-maze despite superior performance on the rotarod. Additionally, these animals showed a deficit in spontaneous alternation. Surprisingly, Met (fx/fx; fx/+) /Nestin (cre) null and heterozygous mice exhibited deficits in contextual fear conditioning, and Met (fx/+) /Nestin (cre) heterozygous mice spent less time in the closed arms of the elevated plus maze. CONCLUSIONS: These data suggest a complex contribution of Met in the development of circuits mediating social, emotional, and cognitive behavior. The impact of disrupting developmental Met expression is dependent upon circuit-specific deletion patterns and levels of receptor activity.

Partnering With Patients, Families, and Communities.

BACKGROUND AND OBJECTIVES: Collaborating with patients, families, and communities is a core principle of family medicine. However, the health care system in the United States has grown increasingly complex, fragmented, and difficult to navigate. This system, focused on disease-specific care delivered by specialists, often treats patients as the objects of care rather than as partners in care. Family Medicine for America's Health (FMAHealth) offers an opportunity to challenge the status quo in collaborative care through enhanced patient outreach and community engagement. With a central focus on improving health and achieving the Triple Aim, the FMAHealth initiative recognizes that successful transformation of the US health care system requires collaborative partnerships between clinicians, patients, families, and communities. Patient and population-level outcomes can be improved through shared decision making; application of new technology; and authentic partnerships with patient, families, and communities. Broader collaboration in practice transformation, research, and policymaking can lead to identification of common goals and mutually embraced transformation. The discipline of family medicine aspires to encourage patients, families, and communities to demand change as consumers, as citizens, and as voters.

Conditioned place preference successfully established in typically developing children.

Affective processing, known to influence attention, motivation, and emotional regulation is poorly understood in young children, especially for those with neurodevelopmental disorders characterized by language impairments. Here we faithfully adapt a well-established animal paradigm used for affective processing, conditioned place preference (CPP) for use in typically developing children between the ages of 30-55 months. Children displayed a CPP, with an average 2.4 fold increase in time spent in the preferred room. Importantly, associative learning as assessed with CPP was not correlated with scores on the Mullen Scales of Early Learning (MSEL), indicating that CPP can be used with children with a wide range of cognitive skills.