The origins of unpredictability in life outcome prediction tasks.

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives.

Associations between middle childhood executive control aspects and adolescent substance use and externalizing and internalizing problems.

This study examines the degree to which two middle childhood executive control aspects, working memory and combined inhibitory control/flexible shifting, predict adolescent substance use and externalizing and internalizing problems. Participants were 301 children (ages 3-6 years; 48.2% male) recruited from a Midwestern city in the United States and followed into adolescence (ages 14-18 years). Working memory had a statistically significant unadjusted association with externalizing problems (r = -.30, p = .003) in a confirmatory factor analysis. Neither factor significantly predicted any of the adolescent outcomes in a structural equation model that adjusted for each EC aspect, sociodemographic covariates, and middle childhood externalizing and internalizing problems. Stronger prediction of EC aspects might not emerge until they become more fully differentiated later in development.

Exploring the Interaction Between Preschool Executive Control and Caregiver Emotion Socialization in Predicting Adolescent Weight Trajectories.

There is a critical need for research examining how neural vulnerabilities associated with obesity, including lower executive control, interact with family factors to impact weight trajectories across adolescence. Utilizing a longitudinal design, the present study investigated caregivers' emotion socialization practices as a moderator of the association between preschool executive control and adolescent body mass index (BMI) trajectories. Participants were 229 youth (Mage = 5.24, SD = 0.03; 47.2% assigned female at birth; 73.8% White, 3.9% Black, 0.4% Asian American, 21.8% multiracial; 12.7% Hispanic) enrolled in a longitudinal study. At preschool-age, participants completed performance-based executive control tasks, and their caregivers reported on their typical emotion-related socialization behaviors (i.e., supportive and nonsupportive responses to children's negative emotions). Participants returned for annual laboratory visits at ages 14 through 17, during which their height and weight were measured to calculate BMI. Although neither preschool executive control nor caregiver emotion-related socialization behaviors were directly associated with BMI growth in adolescence, supportive responses moderated the association between executive control and BMI trajectories. The expected negative association between lower preschool executive control and greater BMI growth was present at below average levels of supportive responses, suggesting that external regulation afforded by supportive responses might reduce risk for adolescent overweight and obesity among children with lower internal self-regulatory resources during preschool. Findings highlight the importance of efforts to bolster executive control early in development and targeted interventions to promote effective caregiver emotion socialization (i.e., more supportive responses) for youth with lower internal self-regulatory abilities to mitigate risk for overweight and obesity and promote health across childhood and adolescence.

Transcriptome studies of congenital heart diseases: identifying current gaps and therapeutic frontiers.

Congenital heart disease (CHD) are genetically complex and comprise a wide range of structural defects that often predispose to - early heart failure, a common cause of neonatal morbidity and mortality. Transcriptome studies of CHD in human pediatric patients indicated a broad spectrum of diverse molecular signatures across various types of CHD. In order to advance research on congenital heart diseases (CHDs), we conducted a detailed review of transcriptome studies on this topic. Our analysis identified gaps in the literature, with a particular focus on the cardiac transcriptome signatures found in various biological specimens across different types of CHDs. In addition to translational studies involving human subjects, we also examined transcriptomic analyses of CHDs in a range of model systems, including iPSCs and animal models. We concluded that RNA-seq technology has revolutionized medical research and many of the discoveries from CHD transcriptome studies draw attention to biological pathways that concurrently open the door to a better understanding of cardiac development and related therapeutic avenue. While some crucial impediments to perfectly studying CHDs in this context remain obtaining pediatric cardiac tissue samples, phenotypic variation, and the lack of anatomical/spatial context with model systems. Combining model systems, RNA-seq technology, and integrating algorithms for analyzing transcriptomic data at both single-cell and high throughput spatial resolution is expected to continue uncovering unique biological pathways that are perturbed in CHDs, thus facilitating the development of novel therapy for congenital heart disease.

Contextualizing the Neural Vulnerabilities Model of Obesity.

In recent years, investigators have focused on neural vulnerability factors that increase the risk of unhealthy weight gain, which has provided a useful organizing structure for obesity neuroscience research. However, this framework, and much of the research it has informed, has given limited attention to contextual factors that may interact with key vulnerabilities to impact eating behaviors and weight gain. To fill this gap, we propose a Contextualized Neural Vulnerabilities Model of Obesity, extending the existing theory to more intentionally incorporate contextual factors that are hypothesized to interact with neural vulnerabilities in shaping eating behaviors and weight trajectories. We begin by providing an overview of the Neural Vulnerabilities Model of Obesity, and briefly review supporting evidence. Next, we suggest opportunities to add contextual considerations to the model, including incorporating environmental and developmental context, emphasizing how contextual factors may interact with neural vulnerabilities to impact eating and weight. We then synthesize earlier models and new extensions to describe a Contextualized Neural Vulnerabilities Model of Obesity with three interacting components-food reward sensitivity, top-down regulation, and environmental factors-all within a developmental framework that highlights adolescence as a key period. Finally, we propose critical research questions arising from the framework, as well as opportunities to inform novel interventions.

Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with a likely oligogenic etiology, but our understanding of the genetic complexities and pathogenic mechanisms leading to HLHS is limited. We performed whole genome sequencing (WGS) on 183 HLHS patient-parent trios to identify candidate genes, which were functionally tested in the Drosophila heart model. Bioinformatic analysis of WGS data from an index family of a HLHS proband born to consanguineous parents prioritized 9 candidate genes with rare, predicted damaging homozygous variants. Of them, cardiac-specific knockdown (KD) of mitochondrial MICOS complex subunit dCHCHD3/6 resulted in drastically compromised heart contractility, diminished levels of sarcomeric actin and myosin, reduced cardiac ATP levels, and mitochondrial fission-fusion defects. These defects were similar to those inflicted by cardiac KD of ATP synthase subunits of the electron transport chain (ETC), consistent with the MICOS complex's role in maintaining cristae morphology and ETC assembly. Five additional HLHS probands harbored rare, predicted damaging variants in CHCHD3 or CHCHD6. Hypothesizing an oligogenic basis for HLHS, we tested 60 additional prioritized candidate genes from these patients for genetic interactions with CHCHD3/6 in sensitized fly hearts. Moderate KD of CHCHD3/6 in combination with Cdk12 (activator of RNA polymerase II), RNF149 (goliath, E3 ubiquitin ligase), or SPTBN1 (ß-Spectrin, scaffolding protein) caused synergistic heart defects, suggesting the likely involvement of diverse pathways in HLHS. Further elucidation of novel candidate genes and genetic interactions of potentially disease-contributing pathways is expected to lead to a better understanding of HLHS and other CHDs.

A Comparison of Task-Based and Questionnaire Assessments of Executive Control Aspects in Relation to Adolescent Marijuana Initiation.

Prior research has linked deficits in executive control (EC) to marijuana use in adolescents but has relied either primarily on adolescent self-report of EC or tasked-based EC, and focused on limited aspects of EC, usually inhibitory control. We examined unique associations of three established aspects of EC (inhibitory control, working memory, and flexible shifting) assessed with both performance on laboratory tasks and self-report in relation to marijuana initiation. Participants were 260 youth (ages 14-18 years) from a small Midwestern city in the United States enrolled in the adolescent phase (beginning in 2017) of an ongoing study of EC development recruited originally between 2006 and 2012 (46% male, 72% European American). The three aspects of executive control were measured in a laboratory setting with well-established performance-based measures and with a psychometrically-sound self-report survey instrument. Youth also provided self-report of marijuana initiation in a phone survey administered during their laboratory visit. Multiple logistic regression analysis indicated that flexible shifting as measured by a performance-based task was negatively and uniquely associated with marijuana initiation (AOR = 0.68, 95% CI = 0.48 - 0.91), and self-reported deficits in inhibitory control were positively associated with marijuana initiation (AOR = 1.92, 95% CI = 1.15 - 3.21). Although larger-scale longitudinal research is needed, findings of this study suggest that screening efforts to identify youth at risk of marijuana initiation might rely on more cost-effective self-report assessment of inhibitory control, but further valuable information can come from more resource-intensive but sensitive performance-based assessment of flexible shifting.

Early executive control buffers risk for adolescent psychopathology during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on youth mental health, and there is a critical need for research examining individual factors that contribute to increased psychopathology during the pandemic. The current study explored whether executive control (EC) abilities in early childhood interact with COVID-related stress to attenuate risk for adolescent psychopathology during the first 6 months of the pandemic. METHODS: Participants were 337 youth (49% female) living in a small midwestern city in the United States. Participants completed EC tasks when they were approximately 4.5 years old as part of a longitudinal study investigating cognitive development. At annual laboratory visits during adolescence and before the pandemic, participants (Mage = 14.57) reported on mental health symptoms. In July and August of 2020, participants (Mage = 16.57) reported on COVID-related stress and depression, anxiety, and trauma symptoms. RESULTS: COVID-related stress was associated with increased internalizing problems after controlling for prepandemic symptom levels. Further, the impact of COVID-related stress on adolescent internalizing problems was moderated by preschool EC, with higher levels of EC buffering the effects of COVID-related stress on adolescent internalizing problems. CONCLUSIONS: Findings highlight the importance of promoting EC early in development, as well as screening for EC deficits and implementing targeted intervention strategies across the lifespan to help reduce the impact of stress on adolescent internalizing problems.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

Does preschool executive control mediate the impact of early environmental unpredictability and deprivation on the general factor of psychopathology a decade later?

BACKGROUND: Although deprivation has been consistently shown to increase risk for psychopathology through impaired executive control, the unique effects of other dimensions of early adversity, such as unpredictability, on executive control development are poorly understood. The current study evaluated whether deprivation and/or unpredictability early in life have unique effects on the general factor of psychopathology through impaired preschool executive control. METHODS: Participants included 312 children (51% female) oversampled for greater sociodemographic risk. Preschool executive control was measured using a battery of nine developmentally appropriate executive control tasks. Dimensions of adversity were measured with observational and caregiver assessments, and psychopathology was measured with caregiver and child reports. RESULTS: In separate models, both deprivation and unpredictability had significant indirect effects on the adolescent general factor of psychopathology through impaired preschool executive control. However, when both dimensions of adversity were included simultaneously, early life deprivation, but not unpredictability, was uniquely associated with the general factor of psychopathology in adolescence through impaired preschool executive control. CONCLUSIONS: Preschool executive control appears to be a transdiagnostic mechanism through which deprivation, but not unpredictability, increases risk for the general factor of psychopathology in adolescence. Results elucidate potential transdiagnostic targets for intervention efforts aimed at reducing the development and maintenance of psychopathology across the life span.

SARS-CoV-2 spike protein-mediated cardiomyocyte fusion may contribute to increased arrhythmic risk in COVID-19.

BACKGROUND: SARS-CoV-2-mediated COVID-19 may cause sudden cardiac death (SCD). Factors contributing to this increased risk of potentially fatal arrhythmias include thrombosis, exaggerated immune response, and treatment with QT-prolonging drugs. However, the intrinsic arrhythmic potential of direct SARS-CoV-2 infection of the heart remains unknown. OBJECTIVE: To assess the cellular and electrophysiological effects of direct SARS-CoV-2 infection of the heart using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS: hiPSC-CMs were transfected with recombinant SARS-CoV-2 spike protein (CoV-2 S) or CoV-2 S fused to a modified Emerald fluorescence protein (CoV-2 S-mEm). Cell morphology was visualized using immunofluorescence microscopy. Action potential duration (APD) and cellular arrhythmias were measured by whole cell patch-clamp. Calcium handling was assessed using the Fluo-4 Ca2+ indicator. RESULTS: Transfection of hiPSC-CMs with CoV-2 S-mEm produced multinucleated giant cells (syncytia) displaying increased cellular capacitance (75±7 pF, n = 10 vs. 26±3 pF, n = 10; P<0.0001) consistent with increased cell size. The APD90 was prolonged significantly from 419±26 ms (n = 10) in untransfected hiPSC-CMs to 590±67 ms (n = 10; P<0.05) in CoV-2 S-mEm-transfected hiPSC-CMs. CoV-2 S-induced syncytia displayed delayed afterdepolarizations, erratic beating frequency, and calcium handling abnormalities including calcium sparks, large "tsunami"-like waves, and increased calcium transient amplitude. After furin protease inhibitor treatment or mutating the CoV-2 S furin cleavage site, cell-cell fusion was no longer evident and Ca2+ handling returned to normal. CONCLUSION: The SARS-CoV-2 spike protein can directly perturb both the cardiomyocyte's repolarization reserve and intracellular calcium handling that may confer the intrinsic, mechanistic substrate for the increased risk of SCD observed during this COVID-19 pandemic.

Childhood executive control and adolescent substance use initiation: the mediating roles of physical and relational aggression and prosocial behavior.

Although predictive associations between childhood executive control (EC) and adolescent substance use have been established in prior research, the developmental pathways involved in these long-term links have not been well understood. The goal of the current study was to investigate the degree to which aggressive behaviors, including both physical and relational aggression, and prosocial behaviors in elementary school operate as developmental pathways between preschool EC and adolescent substance use, while accounting for participants' age, sex, family history of substance use, and family socioeconomic status. Participants were 329 youth (49% male; 63.6% European American) who were recruited to participate in a study between 2006 and 2012 while youth were in preschool and elementary school and followed into adolescence. The sample was recruited from a small Midwestern city in the United States. EC was assessed with performance-based tasks when children were 5 years 3 months. Youth behaviors with peers were reported by teachers when participants were in elementary school. Self-reports of the substance use initiation (e-cigarettes, cigarettes, alcohol, and marijuana) were obtained in adolescence via phone surveys. Mediation analyses revealed a statistically significant indirect effect from preschool EC to adolescent substance use through youth's engagement in relational aggression in elementary school (b = > -0.22 [-0.51; -0.08]; ß = > -0.18). Our results suggest that developmental pathways to adolescent substance use may begin in preschool, setting the stage for susceptibility to engagement in relational aggression, which increases, in turn, youth's likelihood for substance use initiation in adolescence.

Preschool Executive Control, Temperament, and Adolescent Dietary Behaviors.

BACKGROUND: Child temperament styles characterized by increased emotionality or pleasure seeking may increase risk for less healthful eating patterns, while strong executive control (EC) may be protective. The interaction of these characteristics with longitudinal outcomes has not yet been examined. PURPOSE: The aim of this study was to examine the association of preschool temperament and EC, as well as their interaction with adolescent eating. METHODS: Preschoolers (N = 313) were recruited into a longitudinal study, with behavioral measurement of EC at age 5.25 years, temperament assessed multiple times across preschool, and eating outcomes assessed in adolescence (mean age = 15.34 years). RESULTS: Separate latent moderated structural equation models demonstrated that weaker EC was associated with eating less healthful foods, including high sugar foods, sugar-sweetened beverages (SSBs), and convenience foods (p < .05). In the moderation models, negative affectivity temperament was correlated with eating less healthful foods, high sugar foods, and SSBs (p < .05). Children lower in surgency/extraversion temperament were more likely to drink SSBs. There was an interaction between temperament and EC, such that children high in negative affectivity with weaker EC were particularly more likely to consume less healthful foods, high sugar foods, and SSBs (p < .05). There was no interaction of surgency with EC and food consumption. CONCLUSIONS: Child characteristics measured early in development were associated with later adolescent eating behaviors. Adequate EC could be necessary to counteract the drive toward eating associated with temperaments high in negative affectivity.

A preschool temperament style called Negative Affectivity, characterized by high levels of reactivity and negative emotion, predicted eating patterns a decade later. These children were more likely to eat less healthful foods and drink sugary drinks as adolescents. Strong executive function skills were important for redirecting toward healthful eating in children with Negative Affectivity.

Empirical support for a dual process model of the p-factor: Interaction effects between preschool executive control and preschool negative emotionality on general psychopathology.

Recent work indicates that a general factor, often referred to as the p-factor, underlies nearly all forms of psychopathology. Although the criterion validity and utility of this general factor have been well supported, questions remain about the substantive meaning of the p-factor. The purpose of the present longitudinal study was to empirically test the hypothesis that the p-factor reflects dysregulation arising from a combination of high dispositional negative emotionality and low executive control. The current study examined preschool executive control, measured using a battery of 9 developmentally appropriate executive control tasks, as a moderator of the association between preschool negative emotionality and both concurrent and subsequent levels of general psychopathology in preschool and elementary school using a community sample (N = 497). Latent moderated structural equation models demonstrated that preschool executive control significantly moderated the associations between preschool negative emotionality and general psychopathology both in preschool and approximately 5 years later in elementary school. These results suggest that the general factor of psychopathology may reflect dysregulation arising from a tendency to experience high negative affect, without sufficient executive control to effectively down-regulate that affect. This work has important implications for identifying transdiagnostic targets for prevention and intervention efforts, as well as furthering understanding of the substantive meaning and construct validity of the general factor of psychopathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Autologous Umbilical Cord Blood-Derived Mononuclear Cell Therapy Promotes Cardiac Proliferation and Adaptation in a Porcine Model of Right Ventricle Pressure Overload.

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

The roles of sleep and executive function in adolescent nighttime eating.

Nighttime eating has been associated with obesity, inflammation, and poor nutritional intake, yet correlates of this behavior are understudied in pediatric populations and among adolescents in particular. The current study examines modifiable factors related to nighttime eating, including sleep parameters and regulatory abilities-as well as the interplay between these constructs-in adolescents. A total of 223 adolescents (Mage = 15.32 years, 52.9 % female, 15.7 % classified as overweight, 21.1 % had obesity) wore ActiGraph devices to measure sleep and were instructed to complete three 24-h dietary recall measures over a two-week period. Participants also completed self-report measures of executive function. Greater variability in sleep duration was consistently associated with higher average calorie, sugar, and fat consumption after 8, 9, and 10 PM. The main effect of global executive function on all nighttime eating measures was nonsignificant, and executive function did not moderate relationships between sleep parameters and nighttime eating measures. Since adolescents' eating habits may set the stage for lifelong dietary practices, efforts to ensure consistent sleep duration may reduce risk for nighttime eating in this nutritionally vulnerable population.

Uncoupling of Proliferative Capacity from Developmental Stage During Directed Cardiac Differentiation of Pluripotent Stem Cells.

Lineage-specific differentiation of human-induced pluripotent stem cells (hiPSCs) into cardiomyocytes (CMs) offers a patient-specific model to dissect development and disease pathogenesis in a dish. However, challenges exist with this model system, such as the relative immaturity of iPSC-derived CMs, which evoke the question of whether this model faithfully recapitulates in vivo cardiac development. As in vivo cardiac developmental stage is intimately linked with the proliferative capacity (or maturation is inversely correlated to proliferative capacity), we sought to understand how proliferation is regulated during hiPSC CM differentiation and how it compares with in vivo mouse cardiac development. Using standard Chemically Defined Media 3 differentiation, gene expression profiles demonstrate that hiPSC-derived cardiomyocytes (hiPSC-CMs) do not progress past the equivalent of embryonic day 14.5 of murine cardiac development. Throughout differentiation, overall DNA synthesis rapidly declines with <5% of hiPSC-CMs actively synthesizing DNA at the end of the differentiation period despite their immaturity. Bivariate cell cycle analysis demonstrated that hiPSC-CMs have a cell cycle profile distinct from their non-cardiac counterparts from the same differentiation, with significantly fewer cells within G1 and a marked accumulation of cells in G2/M than their non-cardiac counterparts throughout differentiation. Pulse-chase analysis demonstrated that non-cardiac cells progressed completely through the cell cycle within a 24-h period, whereas hiPSC-CMs had restricted progression with only a small proportion of cells undergoing cytokinesis with the remainder stalling in late S-phase or G2/M. This cell cycle arrest phenotype is associated with abbreviated expression of cell cycle promoting genes compared with expression throughout murine embryonic cardiac development. In summary, directed differentiation of hiPSCs into CMs uncouples the developmental stage from cell cycle regulation compared with in vivo mouse cardiac development, leading to a premature exit of hiPSC-CMs from the cell cycle despite their relative immaturity.

Executive control throughout elementary school: Factor structure and associations with early childhood executive control.

This study examined the factor structure of executive control throughout elementary school, as well as associations between executive control abilities in preschool and elementary school. Data were drawn from a longitudinal study of executive control development in a community sample of children (N = 294; 53% female, 47% male) oversampled for low family income (25.4% below poverty line; Mincome = $46,638; SD = $33,256). The sample was representative of the Midwestern city in which the study was conducted in terms of race (71.4% White, 24.5% multiracial, 3.7% Black, and .3% Asian American) and ethnicity (14% Hispanic). Children completed a battery of ten performance-based tasks assessing executive control abilities in grades 1 (Mage = 7.08 years), 2 (Mage = 8.04 years), 3 (Mage = 9.02 years), and 4 (Mage = 9.98 years). Confirmatory factor analysis supported a two-factor structure at each grade with factors representing working memory and inhibitory control/flexible shifting. Measurement invariance testing revealed partial scalar (indicator intercepts) invariance for working memory and partial metric (indicator loadings) and partial scalar invariance for inhibitory control/flexible shifting. Preschool executive control (age 4.5 years), represented by a unitary latent factor, significantly predicted working memory (ßs = .79, .72, .81, .66) and inhibitory control/flexible shifting (ßs = .69, .64, .63, .62) factors in grades 1 through 4. Follow-up analyses indicated that the findings were not attributable to general cognitive ability. Findings support greater separability of executive control components in elementary school versus preschool, and considerable continuity of executive control from preschool through elementary school. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Identifying gaps in parental support for families of children with hypoplastic left heart syndrome.

PURPOSE: The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome. DESIGN AND METHODS: Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings. RESULTS: Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team's open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team's anticipation of parental emotional needs and provision of coping resources (p = 0.003). CONCLUSIONS: Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience. PRACTICE IMPLICATIONS: Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.