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Background: Current physical activity guidelines may be insufficient to address health consequences in a world increasing in sedentary behavior. Physical activity is a key lifestyle factor to promote healthy aging, but few studies examine activity in conjunction with sitting. We examine how activity intensity and sitting behavior influence health and the extent to which physical activity might counter sitting., Methods: We analyzed data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) in adults aged 28-49 years (M = 33.16, SD = 4.93). We fit a linear mixed-effect model for body mass index (BMI) and total cholesterol/high-density lipoprotein ratio (TC/HDL). Leveraging the co-twin control approach, we explore the trade-off between sitting and physical activity., Results: Across established adulthood, TC/HDL and BMI demonstrated increasing age trends with prolonged sitting and vigorous activity inversely associated. Moreover, after considering sitting time, we found an age-equivalent benefit of vigorous exercise where those performing 30 minutes daily had expected TC/HDL and BMI estimates that mirrored sedentary individuals 5 and 10 years younger, respectively. Co-twin control analysis suggests partial exposure effects for TC/HDL, indicating greater vigorous activity may counter sitting-health effects but with diminishing returns., Conclusions: Our findings support the counteracting influence of prolonged sitting and physical activity on indicators of cardiovascular and metabolic health. A compensating role of vigorous activity on sitting health links is indicated while reducing sitting time appears paramount. Public health initiatives should consider sitting and vigorous activity in tandem in guidelines to promote health maintenance and combat accelerated aging., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bruellman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pubertal development has short- and long-term effects on psychological adjustment. Many studies of long-term effects rely on retrospective measurement of pubertal timing, but such measures often reflect different aspects of puberty than those assessed in adolescence, raising questions about the utility and interpretation of retrospective reports. The present study leveraged longitudinal data collected in adolescence and established adulthood to determine: (1) the correspondence between pubertal timing indexed from logistic growth curves of self-reported physical development assessed contemporaneously across adolescence and pubertal timing indexed relative to peers assessed retrospectively in adulthood; (2) the associations between the two pubertal timing measures and psychological adjustment; and (3) potential recall biases. Participants were 748 individuals (50.1% female; 91.6% White) from two longitudinal studies who reported on their pubertal development annually from Grades 3-9, psychological adjustment (age at sexual initiation, substance use, depression) in late adolescence, and retrospective pubertal timing in established adulthood ( M age = 32.76; SD = 4.43). Results indicate moderate-to-high convergence between retrospective and contemporaneous indices. Most participants, especially women, had the same pubertal timing classification (i.e., early, on time, or late), but early-maturing adolescents often recalled on-time development as adults. Retrospective and contemporaneous indices were associated with psychological adjustment in similar ways, with some attenuation in the retrospective measure, especially for men. There was little evidence of recall bias due to age at retrospective assessment or time since puberty. Findings generally support the use of retrospective pubertal timing measures, with the recognition that some relations with adjustment may be weakened. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: This study investigates the relationship between cognitive functioning and 59 modifiable and intrinsic factors at the cusp of midlife., Methods: We analyzed data from 1221 participants in the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; M age  = 33.20, %Female = 52.74). We assessed the impact of 59 factors on cognitive functioning using regularized regression and co-twin control models, controlling for earlier-life cognitive functioning and gray matter volume., Results: Eight robust factors were identified, including education attainment, cognitive complexity, purpose-in-life, and smoking status. Twins reporting higher levels of cognitive complexity and purpose-in-life showed better cognitive performance than their cotwin, while smoking was negatively associated. Using meta-analytically derived effect size threshold, we additionally identified that twins experiencing more financial difficulty tend to perform less well compared with their cotwin., Discussion: The findings highlight the early midlife link between cognitive functioning and lifestyle/psychological factors, beyond prior cognitive performance, brain status, genetic and familial confounders. Our results further highlight the potential of established adulthood as a crucial window for dementia prevention interventions targeting lifestyle and psychosocial factors., Highlights: Cog complexity(+), purpose-in-life(+) were associated with cognition in early midlife.Smoking(-) was also associated with cognition in early midlife.Results were consistent controlling for genetic and environmental confounds.Association between EA and cognition might be mostly genetic and familial confounded., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the Supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The internalizing construct captures shared variance underlying risk for mood and anxiety disorders. Internalizing factors based on diagnoses (or symptoms) of major depressive disorder (MDD) and generalized anxiety disorder (GAD) are well established. Studies have also integrated self-reported measures of associated traits (e.g., questionnaires assessing neuroticism, worry, and rumination) onto these factors, despite having not tested the assumption that these measures truly capture the same sets of risk factors. This study examined the overlap among both sets of measures using converging approaches. First, using genomic structural equation modeling, we constructed internalizing factors based on genome-wide association studies (GWASs) of internalizing diagnoses (e.g., MDD) and traits associated with internalizing (neuroticism, loneliness, and reverse-scored subjective well-being). Results indicated the two factors were highly ( r g = .79) but not perfectly genetically correlated ( r g < 1.0, p < .001). Second, we constructed similar latent factors in a combined twin/adoption sample of adults from the Colorado Adoption/Twin Study of Lifespan Behavioral Development and Cognitive Aging. Again, both factors demonstrated strong overlap at the level of genetic ( r g = .76, 95% confidence interval [CI] [0.40, 0.97]) and nonshared environmental influences ( r e = .80, 95% CI [0.53, 1.0]). Shared environmental influences were estimated near zero for both factors. Our findings are consistent with current frameworks of psychopathology, though they suggest there are some unique genetic influences captured by internalizing diagnosis compared to trait measures, with potentially more nonadditive genetic influences on trait measures. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objectives: Frailty is not an end state of aging, but rather represents physiological vulnerability across multiple systems that unfolds across adulthood. However, examinations of frailty at the midlife transition, and how frailty may impact other age-sensitive traits, such as processing speed (PS), remain scarce. Our research aims were to examine frailty and frailty-speed associations before midlife, a ripe developmental period for healthy aging interventions., Methods: Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (N = 1,215; Mage = 33.23 years; standard deviation = 4.98), we constructed 25-item (FI25) and 30-item (FI30) frailty indices. PS was measured using the Colorado Perceptual Speed task and WAIS-III Digit Symbol (DS) subtest. Multilevel models accounted for clustering among siblings and adjusted for sex, race, ethnicity, adoption status, educational attainment, and age., Results: Reliability of FI measures was apparent from strong intraclass correlations (ICCs) among identical twin siblings, although ICC patterns across all siblings suggested that FI variability may include nonadditive genetic contributions. Higher FI was associated with poorer PS performance but was significant for DS only (BFI25 = -1.17, p = .001, d = -0.12; BFI30 = -1.21, p = .001, d = -0.12). Furthermore, the negative frailty-DS association was moderated by age (BFI25×age = -0.14, p = .042; BFI30×age=-0.19, p = .008) where increasingly worse performance with higher frailty emerged at older ages., Discussion: Frailty is evident before midlife and associated with poorer PS, an association that magnifies with age. These findings help elucidate the interrelationship between indicators of frailty and cognitive performance for adults approaching midlife, an understudied period within life-span development., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study investigated the relationship between mathematics difficulties and psychopathology in a large community sample ( N = 881) of youth (8-18 years of age) in the United States. The primary aims of the study were to (a) test the associations between mathematics difficulties and specific components of internalizing, externalizing, attention, and social problems; (b) examine potential age and gender differences; and (c) investigate the longitudinal relationship between mathematics and psychopathology using 5-year follow-up data. Results indicated that individuals with mathematics difficulties exhibited elevations in most dimensions of psychopathology, including anxiety, depression, externalizing behaviors, attention problems, and social problems. Furthermore, mathematics impairment was associated with internalizing problems, rule-breaking behaviors, inattention, and social problems even after controlling for comorbid reading difficulties. Results suggested that the associations between mathematics and psychopathology are generally similar in males and females. Finally, preliminary longitudinal evidence suggested that initial mathematics difficulties predicted elevations of conduct disorder, rule-breaking behavior, inattention, hyperactivity, and social problems at follow-up, with several of these associations remaining significant even after controlling for initial reading. In contrast, there was no significant association between initial mathematics ability and internalizing symptoms at follow-up, demonstrating some amelioration of internalizing symptoms over time.

Much debate has concerned the separability of executive function abilities and intelligence, with some evidence that the 2 constructs are genetically indistinguishable in children and adolescents but phenotypically and genetically distinct in older adolescents and adults. The current study leveraged data from twin and adoption studies to examine executive function's genetic structure in adulthood ( M = 33.15 years, SD = 4.96) and its overlap with intelligence. 1,238 individuals (170 MZ twin pairs, 154 DZ twin pairs, 95 biological sibling pairs, 80 adoptive sibling pairs, and 240 unpaired individuals) completed 6 executive function tasks as well as the Weschler Adult Intelligence Scale-III as part of the Colorado Adoption/Twin study of Life span behavioral development and cognitive aging (CATSLife). Results replicated the unity/diversity model of executive function that distinguishes general executive function abilities (Common EF) from abilities specific to working memory updating (Updating-specific) and mental set shifting (Shifting-specific). In the final model, broad-sense heritability was high for Common EF (h² = .72), Updating-specific (h² = 1.0), and Shifting-specific (h² = .60) factors, as well as for full-scale intelligence (h² = .74). Intelligence was phenotypically and genetically correlated with Common EF ( r = .49, broad-sense r g = .44) and Updating-specific ( r = .60, r g = .69) abilities. This study represents the first executive function study to apply the adoption design. Leveraging the combined twin and adoptive design allowed us to estimate both additive and nonadditive genetic effects underlying these associations. These findings highlight the commonality and separability of executive function and intelligence. Common EF abilities are distinct from intelligence in adulthood, with intelligence also strongly associated with Updating-specific abilities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence., Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument., Results: The meta-analysis of overall internalizing symptoms (INT overall ) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n effective  = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|r g | > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |r g | = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa., Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

An interaction between socioeconomic status (SES) and the heritability of IQ, such that the heritability of IQ increases with higher SES, has been reported in some US twin studies, although not in others, and has generally been absent in studies outside the US (England, Europe, Australia). Is such an interaction present in US adoption studies? Data from two such studies, the Texas and the Colorado Adoption Projects, were examined, involving 238-469 adopted children given IQ tests at various ages. A mini multi-level analysis was made of the prediction of the IQs by the SES of the rearing home (a composite of parental education and occupation), by the birth mother's intelligence, and by the interaction of the two. Neither study showed any substantial heritability × SES interaction: the effect size estimates in units comparable to twin moderation models were negative (- 0.042 and - 0.004), and the meta-analytic estimate for the combined analysis was - 0.27 (SE = 0.042) with a 95% confidence interval of - 0.109 to 0.054. Thus, while we cannot rule out positive moderation based on our two studies, the joint agreement across these studies, and with the non-US twin studies, warrants attention in further research. SES may not fully capture proximal familial-environmental aspects that moderate child IQ., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Research on the influence of cannabis use on anthropometrics, cardiovascular and pulmonary function, and other indicators of physical health has reported mixed results. We examined whether cannabis frequency is associated with physical health outcomes phenotypically and after controlling for shared genetic and environmental factors via a longitudinal co-twin control design., Methods: We tested the phenotypic associations of adolescent, young adult, and adult cannabis frequency with adult physical health. Next, we ran multilevel models to test if significant phenotypic associations remained at the between-family and within-twin pair levels. Participants include 677 individual twins (308 twin pairs) aged 25-35., Results: At the phenotypic level, adolescent cannabis use was associated with less adult exercise engagement (b = - 0.846 min, p = .000). Adult cannabis use was associated with a lower resting heart rate (HR; b = - 0.170 bpm, p = .001) and more frequent appetite loss (b = 0.018, p = .000). Only between-family effects were significant for adolescent cannabis use and exercise engagement (b = - 1.147 min, p = .000) and adult cannabis use and appetite loss frequency (b = 0.041, p = .002). The total within-twin (b = - 0.184, p = .014), MZ only (b = - 0.304, p = .003), and between-family effects (b = - 0.164, p = .025) were significant between adult cannabis use and a lower resting HR, which persisted after controlling for familial confounds and other substance use., Conclusions: The associations between cannabis use with exercise engagement and frequency of appetite loss are explained by familial confounding while the association between cannabis use and resting HR was not. These results do not support a causal association between cannabis use once a week and poorer physical health effects among adults aged 25-35., (Published by Elsevier B.V.)

The objective of this study was to evaluate the association between perceived neighborhood stressors, encompassing negative perceived neighborhood characteristics, and specific cognitive abilities in adulthood. We conducted a coordinated analysis across three studies of adults in the United States and found that perceived neighborhood stressors were consistently associated with poorer performance on attention-demanding cognitive tasks. We specifically found that perceived neighborhood stressors were associated with lower performance in spatial abilities, working memory, and executive function but not perceptual speed, and that the effect was most consistent for lower perceived neighborhood safety followed by lower perceived aesthetic quality, greater perceived neighborhood crime, and lower perceived neighborhood cohesion. These results highlight the importance of the psychosocial neighborhood context for cognitive health in adulthood., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pubertal timing matters for psychological development. Early maturation in girls is linked to risk for depression and externalizing problems in adolescence and possibly adulthood, and early and late maturation in boys are linked to depression. It is unclear whether pubertal timing uniquely predicts problems; it might instead mediate the continuity of behavior problems from childhood to adolescence or create psychological risk specifically in youth with existing problems, thus moderating the link. We investigated these issues in 534 girls and 550 boys, measuring pubertal timing by a logistic model fit to annual self-report measures of development and, in girls, age at menarche. Prepuberty internalizing and externalizing behavior problems were reported by parents. Adolescent behavior problems were reported by parents and youth. As expected, behavior problems were moderately stable. Pubertal timing was not predicted by childhood problems, so it did not mediate the continuity of behavior problems from childhood to adolescence. Pubertal timing did not moderate links between early and later problems for girls. For boys, early maturation accentuated the link between childhood problems and adolescent substance use. Overall, the replicated links between puberty and behavior problems appear to reflect the unique effects of puberty and child behavior problems on the development of adolescent behavior problems.

The human bronchial epithelium is an important barrier tissue that is damaged or pathologically altered in various acute and chronic respiratory conditions. To represent the epithelial component of respiratory disease, it is essential to use a physiologically relevant model of this tissue. The human bronchial epithelium is a highly organized tissue consisting of a number of specialized cell types. Primary human bronchial epithelial cells (HBEC) can be differentiated into a mucociliated tissue in air-liquid interface (ALI) cultures using appropriately supplemented media under optimized growth conditions. We compared the histology, ciliary length, and function, diffusion, and barrier properties of HBEC from donors with no respiratory disease grown in two different media, PneumaCult-ALI or Bronchial Epithelial Differentiation Medium (BEDM). In the former group, HBEC have a more physiological pseudostratified morphology and mucociliary differentiation, including increased epithelial thickness, intracellular expression of airway-specific mucin protein MUC5AC, and total expression of cilia basal-body protein compared with cells from the same donor grown in the other medium. Baseline expression levels of inflammatory mediators, thymic stromal lymphopoietin (TSLP), soluble ST2, and eotaxin-3 were lower in PneumaCult-ALI. Additionally, the physiological cilia beat frequency and electrical barrier properties with transepithelial electrical resistance were significantly different between the two groups. Our study has shown that these primary cell cultures from the same donor grown in the two media possess variable structural and functional characteristics. Therefore, it is important to objectively validate primary epithelial cell cultures before experimentation to ensure they are appropriate to answer a specific scientific question.

Conditions such as asthma and inflammatory bowel disease are characterized by aberrant smooth muscle contraction. It has proven difficult to develop human cell-based models that mimic acute muscle contraction in 2D in vitro cultures due to the nonphysiological chemical and mechanical properties of lab plastics that do not allow for muscle cell contraction. To enhance the relevance of in vitro models for human disease, we describe how functional 3D smooth muscle tissue that exhibits physiological and pharmacologically relevant acute contraction and relaxation responses can be reproducibly fabricated using a unique microfluidic 3D bioprinting technology. Primary human airway and intestinal smooth muscle cells were printed into rings of muscle tissue at high density and viability. Printed tissues contracted to physiological concentrations of histamine (0.01-100 μM) and relaxed to salbutamol, a pharmacological compound used to relieve asthmatic exacerbations. The addition of TGFβ to airway muscle rings induced an increase in unstimulated muscle shortening and a decreased response to salbutamol, a phenomenon which also occurs in chronic lung diseases. Results indicate that the 3D bioprinted smooth muscle is a physiologically relevant in vitro model that can be utilized to study disease pathways and the effects of novel therapeutics on acute contraction and chronic tissue stenosis., (© 2019 Federation of American Societies for Experimental Biology.)

The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941-949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351-357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.

The purpose of this update is to provide the most current information about both the Colorado Adoption Project (CAP) and the Longitudinal Twin Study (LTS) and to introduce the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife), a product of their merger and a unique study of lifespan behavioral development and cognitive aging. The primary objective of CATSLife is to assess the unique saliency of early childhood genetic and environmental factors to adult cognitive maintenance and change, as well as proximal influences and innovations that emerge across development. CATSLife is currently assessing up to 1600 individuals on the cusp of middle age, targeting those between 30 and 40 years of age. The ongoing CATSLife data collection is described as well as the longitudinal data available from the earlier CAP and LTS assessments. We illustrate CATSLife via current projects and publications, highlighting the measurement of genetic, biochemical, social, sociodemographic and environmental indices, including geospatial features, and their impact on cognitive maintenance in middle adulthood. CATSLife provides an unparalleled opportunity to assess prospectively the etiologies of cognitive change and test the saliency of early childhood versus proximal influences on the genesis of cognitive decline.

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = -0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Illness behaviors-or responses to bodily symptoms-predict individuals' recovery and functioning; however, there has been little research on the early life personality antecedents of illness behavior. This study's primary aims were to evaluate (a) childhood temperament traits (i.e., emotionality and sociability) as predictors of adult illness behaviors, independent of objective health; and (b) adult temperament traits for mediation of childhood temperament's associations., Method: Participants included 714 (53% male; 350 adoptive family and 364 control family) children and siblings from the Colorado Adoption Project (CAP; Plomin & DeFries, 1983). Structural regression analyses evaluated paths from childhood temperament to illness behavior (i.e., somatic complaints, sick days, and medication use) at two adulthood assessments (CAP years 21 and 30). Analyses controlled for participant age, sex, family type (adoptive or control), adopted status, parent education/occupation, and middle childhood illnesses, doctor visits, and life events stress., Results: Latent illness behavior factors were established across 2 adulthood assessments. Multilevel path analyses revealed that higher emotionality (fearfulness) in adulthood-but not childhood temperament-predicted higher levels of illness behavior at both assessments. Lastly, lower emotionality-fearfulness partially mediated the effect of higher childhood sociability on adult illness behavior., Conclusions: Results suggest the importance of childhood illness experiences and adult emotionality (fearfulness) in shaping illness behavior in early adulthood. They also suggest a small, protective role of childhood sociability on reduced trait fearfulness in adulthood. These findings broaden our understanding of the prospective links between temperament and illness behavior development, suggesting distinct associations from early life illness experiences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Current definitions of specific learning disability (SLD) identify a heterogeneous population that includes individuals with weaknesses in reading, math, or writing, and these academic difficulties often co-occur in many of the same individuals. The Colorado Learning Disabilities Research Center (CLDRC) is an interdisciplinary, multisite research program that uses converging levels of analysis to understand the genetic and environmental etiology, neuropsychology, and developmental outcomes of SLDs in reading (RD), math (MD), and writing (WD), along with the comorbidity between these SLDs and other developmental disorders. The latest results from the CLDRC twin study suggest that shared genetic influences contribute to the significant covariance between all aspects of reading (word reading, reading fluency, and reading comprehension) and math (calculations, math fluency, and word problems), and distinct genetic or environmental influences also contribute to weaknesses in each specific academic domain. RD and MD are associated with a range of negative outcomes on both concurrent measures and measures of functional outcomes completed 5 years after the twins were first assessed. Over the next several years the CLDRC will continue to expand on this work by administering a comprehensive test battery that includes measures of all dimensions of academic achievement that are described in current definitions of SLD and incorporating these measures in new neuroimaging and molecular genetic studies., (© 2019 Wiley Periodicals, Inc.)

3D bioprinting offers the opportunity to automate the process of tissue engineering, which combines biomaterial scaffolds and cells to generate substitutes for diseased or damaged tissues. These bioprinting methods construct tissue replacements by positioning cells encapsulated in bioinks into specific locations in the resulting constructs. Human induced pluripotent stem cells (hiPSCs) serve as an important tool when engineering neural tissues. These cells can be expanded indefinitely and differentiated into the cell types found in the central nervous systems, including neurons. One common method for differentiating hiPSCs into neural tissue requires the formation of aggregates inside of defined diameter microwells cultured in chemically defined media. However, 3D bioprinting of such hiPSC-derived aggregates has not been previously reported in the literature, as it requires the development of specialized bioinks for supporting cell survival and differentiation into mature neural phenotypes. Here we detail methods including preparing base material components of the bioink, producing the bioink, and the steps involved in printing 3D neural tissues derived from hiPSC-derived neural aggregates using Aspect Biosystems' novel RX1 printer and their lab-on-a-printer (LOP) technology.

The present study prospectively evaluated cumulative early life perceived stress in relation to differential change in memory and perceptual speed from middle childhood to early adulthood. We aimed to identify periods of cognitive development susceptible to the effects of perceived stress among both adopted and nonadopted individuals. The sample consisted of participants in the Colorado Adoption Project (CAP, N = 690). Structured latent growth curves were fit to 4 memory outcomes as well as 1 perceptual speed outcome, which described nonlinear change between ages 9 and 30. Both adoption status and cumulative perceived stress indices served as predictors of the latent curves. The perceived stress indices were constructed from the Brooks-Gunn Life Events Scale for Adolescents, and reflected "upsettingness" ratings associated with the occurrence of particular life events during middle childhood (ages 9 to 12) and adolescence (ages 13 to 16). For memory and perceptual speed, cumulative perceived stress did not predict differential cognitive gains. However, differences in perceptual speed trajectories between nonadopted and adopted individuals were observed, with adopted individuals showing smaller gains. Although these findings provide no evidence that emergent variability in memory and perceptual speed trajectories by age 30 are explained by cumulative perceptions of stress in childhood and adolescence, further investigations regarding potential vulnerability across the life span are warranted. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Background: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology., Methods: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression. Genes were grouped according to their role in airway dysfunction: airway smooth muscle contraction, cytoskeleton structure and regulation, epithelial barrier function, innate and adaptive immunity, fibrosis and remodeling, and epigenetics., Results: Differential gene expression and gene co-expression analyses were used to identify disease associated changes in the airways of asthmatics. There was significantly decreased abundance of integrin beta 6 and Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1) in the airways of asthmatics, genes which are known to play an important role in barrier function. Significantly elevated levels of Collagen Type 1 Alpha 1 (COL1A1) and COL3A1 which have been shown to modulate cell proliferation and inflammation, were found in asthmatic airways. Additionally, we identified patterns of differentially co-expressed genes related to pathways involved in virus recognition and regulation of interferon production. 7 of 8 pairs of differentially co-expressed genes were found to contain CCCTC-binding factor (CTCF) motifs in their upstream promoters., Conclusions: Changes in the abundance of genes involved in cell-cell and cell-matrix interactions could play an important role in regulating inflammation and remodeling in asthma. Additionally, our results suggest that alterations to the binding site of the transcriptional regulator CTCF could drive changes in gene expression in asthmatic airways. Several asthma susceptibility loci are known to contain CTCF motifs and so understanding the role of this transcription factor may expand our understanding of asthma pathophysiology and therapeutic options.

Because of recent concerns about the replication of published results in the behavioral and biomedical sciences (Ioannidis, PLoS Medicine, Vol. 2, 2005, p. e124; Open Science Collaboration, Science, Vol. 349, 2015, p. 943; Pashler & Wagenmakers, Perspectives on Psychological Science, Vol. 7, 2012, pp. 528-530), we have conducted a replication of our recently published analyses of longitudinal reading performance and attention deficit-hyperactivity disorder data from twin pairs selected for reading difficulties (Wadsworth et al., Twin Research and Human Genetics, Vol. 18, 2015, pp. 755-761). Results obtained from univariate and bivariate (DeFries & Fulker, Behavior Genetics, Vol. 15, 1985, pp. 467-473; Acta Geneticae Medicae et Gemellologiae: Twin Research, Vol. 37, 1988, pp. 205-216) analyses of data from a subset of twin pairs tested in the International Longitudinal Twin Study of Early Reading Development at post-4th grade, and its continuation into high school at post-9th grade, were compared to those from our previous report. Similar measures of reading performance, the same measures of inattention and hyperactivity/impulsivity, and similar selection criteria were used in the two studies. In general, the patterns of results obtained from these two independent studies were highly similar. Thus, these results clearly illustrate the principle that findings from studies in quantitative behavioral genetics often replicate (Plomin et al., Perspectives on Psychological Science, Vol. 11, 2016, pp. 3-23).

Although cross-sectional twin studies have assessed the genetic and environmental etiologies of substance use during adolescence and early adulthood, comparisons of results across different samples, measures, and cohorts are problematic. While several longitudinal twin studies have investigated these issues, few corroborating adoption studies have been conducted. The current study is the first to estimate the magnitude of genetic, shared environmental, and non-shared environmental influences on substance use (cigarettes, alcohol, and marijuana) from ages 14 to 18 years, using a prospective longitudinal adoption design. Adoptive and control sibling correlations provided substantial evidence for early genetic effects on cigarette, alcohol, and marijuana use/no use. Shared environmental effects were relatively modest, except for alcohol use, which showed increases in late adolescence (age 17 to 18 years). Sibling similarity for quantity/frequency of use also support additive genetic influences across adolescence, with some shared environmental influences for all three substances. To test the stability of these influences across time, a series of independent pathway models were run to explore common and age-specific influences. For all substances, there were minimal age-specific additive genetic and shared environmental influences on quantity/frequency of use. Further, there was a trend toward increasing genetic influences on cigarette and alcohol use across ages. Genetic influences on marijuana were important early, but did not contribute substantially at age 17 and 18 years. Overall, the findings indicate that genetic influences make important contributions to the frequency/quantity of substance use in adolescence, and suggest that new genetic influences may emerge in late adolescence for cigarette and alcohol use.

Although previous research has shown cognitive skills to be important predictors of reading ability in children, the respective roles for genetic and environmental influences on these relations is an open question. The present study explored the genetic and environmental etiologies underlying the relations between selected executive functions and cognitive abilities (working memory, inhibition, processing speed, and naming speed) with 3 components of reading ability (word reading, reading comprehension, and listening comprehension). Twin pairs drawn from the Colorado Front Range (n = 676; 224 monozygotic pairs; 452 dizygotic pairs) between the ages of 8 and 16 (M = 11.11) were assessed on multiple measures of each cognitive and reading-related skill. Each cognitive and reading-related skill was modeled as a latent variable, and behavioral genetic analyses estimated the portions of phenotypic variance on each latent variable due to genetic, shared environmental, and nonshared environmental influences. The covariance between the cognitive skills and reading-related skills was driven primarily by genetic influences. The cognitive skills also shared large amounts of genetic variance, as did the reading-related skills. The common cognitive genetic variance was highly correlated with the common reading genetic variance, suggesting that genetic influences involved in general cognitive processing are also important for reading ability. Skill-specific genetic variance in working memory and processing speed also predicted components of reading ability. Taken together, the present study supports a genetic association between children's cognitive ability and reading ability., ((c) 2016 APA, all rights reserved).)

Approximately 60% of children with reading difficulties (RD) meet criteria for at least one co-occurring disorder. The most common of these, attention deficit-hyperactivity disorder (ADHD), occurs in 20-40% of individuals with RD. Recent studies have suggested that genetic influences are responsible. To assess the genetic etiologies of RD and the comorbidity of RD and two ADHD symptom dimensions -- inattention (IN) and hyperactivity/impulsivity (H/I) -- we are conducting the first longitudinal twin study of RD and ADHD. Data from twin pairs in which at least one member of the pair met criteria for proband status for RD at initial assessment, and were reassessed 5 years later, were subjected to DeFries-Fulker (DF) analysis. Analyses of reading composite data indicated that over 60% of the proband deficit at initial assessment was due to genetic influences, and that reading deficits at follow-up were due substantially to the same genetic influences. When a bivariate DF model was fitted to reading performance and IN data, genetic influences accounted for 60% of contemporaneous comorbidity and over 60% of the longitudinal relationship. In contrast, analysis of the comorbidity between reading performance and H/I indicated that common genetic influences accounted for only about 20% of the contemporaneous and about 10% of the longitudinal relationships. Results indicate that (1) genetic influences on RD are substantial and highly stable; (2) the comorbidity between RD and IN is due largely to genetic influences, both contemporaneously and longitudinally; and (3) genetic influences contribute significantly less to the comorbidity between RD and H/I.

Genetic influences on adolescent psychological development are likely to be mediated and moderated by pubertal hormones. Combining genetic analyses with advanced models of pubertal development, we extended work on the measurement and psychological significance of puberty. We examined how genetic and environmental influences on puberty vary by the way that development is described (logistic versus linear models versus traditional methods) and the different aspects of puberty (adrenarche vs. gonadarche), and how genes and environment contribute to the covariation between different descriptions and aspects of puberty, and between pubertal development and behavior problems (substance use, age at sexual initiation). We also considered how puberty moderated the heritability of psychological outcomes (internalizing and externalizing problems), and sex differences. Participants from the Colorado Longitudinal Twin Study (403 girls, 395 boys) reported their pubertal development annually from ages 9 through 15; they and their parents reported their behavior in mid-to-late adolescence. There was a large genetic contribution to pubertal timing for both sexes no matter how it was measured, but findings for pubertal tempo varied by method. Genetic covariation accounted for most of the phenotypic correlations among different indicators of pubertal timing, and between pubertal timing and psychological outcome. We consider the implications of our results for understanding how pubertal hormones mediate or moderate genetic and environmental influences on psychological development.

The present study explored the environmental and genetic etiologies of the longitudinal relations between prereading skills and reading and spelling. Twin pairs (n = 489) were assessed before kindergarten (M = 4.9 years), post-first grade (M = 7.4 years), and post-fourth grade (M = 10.4 years). Genetic influences on five prereading skills (print knowledge, rapid naming, phonological awareness, vocabulary, and verbal memory) were primarily responsible for relations with word reading and spelling. However, relations with post-fourth-grade reading comprehension were due to both genetic and shared environmental influences. Genetic and shared environmental influences that were common among the prereading variables covaried with reading and spelling, as did genetic influences unique to verbal memory (only post-fourth-grade comprehension), print knowledge, and rapid naming., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Reading comprehension is a foundational academic skill and significant attention has focused on reading development. This report is the first to examine the stability and change in genetic and environmental influences on reading comprehension across Grades 1 to 6. This developmental range is particularly important because it encompasses the timespan in which most children move from learning how to read to using reading for learning. Longitudinal simplex models were fitted separately for two independent twin samples (N = 706; N = 976). Results suggested that the shared environment contributed to variance in early but not later reading. Instead, stability in reading development was largely mediated by continuous genetic influences. Thus, although reading is clearly a learned skill and the environment remains important for reading development, individual differences in reading comprehension appear to be also influenced by a core of genetic stability that persists through the developmental course of reading.

Research on the role of puberty in adolescent psychological development requires attention to the meaning and measurement of pubertal development. Particular questions concern the utility of self-report, the need for complex models to describe pubertal development, the psychological significance of pubertal timing vs. tempo, and sex differences in the nature and psychological significance of pubertal development. We used longitudinal self-report data to model linear and logistic trajectories of pubertal development, and used timing and tempo estimates from these models, and from traditional approaches (age at menarche and time from onset of breast development to menarche), to predict psychological outcomes of internalizing and externalizing behavior problems, and early sexual activity. Participants (738 girls, 781 boys) reported annually from ages 9 through 15 on their pubertal development, and they and their parents reported on their behavior in mid-to-late adolescence and early adulthood. Self-reports of pubertal development provided meaningful data for both boys and girls, producing good trajectories, and estimates of individuals' pubertal timing and tempo. A logistic model best fit the group data. Pubertal timing was estimated to be earlier in the logistic compared to linear model, but linear, logistic, and traditional estimates of pubertal timing correlated highly with each other and similarly with psychological outcomes. Pubertal tempo was not consistently estimated, and associations of tempo with timing and with behavior were model dependent. Advances in modeling facilitate the study of some questions about pubertal development, but assumptions of the models affect their utility in psychological studies., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Objective: The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this., Methods: This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 μg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum., Results: Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response., Conclusion: Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling.

Interferon-α (IFN-α) is essential for antiviral immunity, but in the absence of matrix metalloproteinase-12 (MMP-12) or IκBα (encoded by NFKBIA) we show that IFN-α is retained in the cytosol of virus-infected cells and is not secreted. Our findings suggest that activated IκBα mediates the export of IFN-α from virus-infected cells and that the inability of cells in Mmp12(-/-) but not wild-type mice to express IκBα and thus export IFN-α makes coxsackievirus type B3 infection lethal and renders respiratory syncytial virus more pathogenic. We show here that after macrophage secretion, MMP-12 is transported into virus-infected cells. In HeLa cells MMP-12 is also translocated to the nucleus, where it binds to the NFKBIA promoter, driving transcription. We also identified dual-regulated substrates that are repressed both by MMP-12 binding to the substrate's gene exons and by MMP-12-mediated cleavage of the substrate protein itself. Whereas intracellular MMP-12 mediates NFKBIA transcription, leading to IFN-α secretion and host protection, extracellular MMP-12 cleaves off the IFN-α receptor 2 binding site of systemic IFN-α, preventing an unchecked immune response. Consistent with an unexpected role for MMP-12 in clearing systemic IFN-α, treatment of coxsackievirus type B3-infected wild-type mice with a membrane-impermeable MMP-12 inhibitor elevates systemic IFN-α levels and reduces viral replication in pancreas while sparing intracellular MMP-12. These findings suggest that inhibiting extracellular MMP-12 could be a new avenue for the development of antiviral treatments.

IQ predicts many measures of life success, as well as trajectories of brain development. Prolonged cortical thickening observed in individuals with high IQ might reflect an extended period of synaptogenesis and high environmental sensitivity or plasticity. We tested this hypothesis by examining the timing of changes in the magnitude of genetic and environmental influences on IQ as a function of IQ score. We found that individuals with high IQ show high environmental influence on IQ into adolescence (resembling younger children), whereas individuals with low IQ show high heritability of IQ in adolescence (resembling adults), a pattern consistent with an extended sensitive period for intellectual development in more-intelligent individuals. The pattern held across a cross-sectional sample of almost 11,000 twin pairs and a longitudinal sample of twins, biological siblings, and adoptive siblings.

This first cross-country twin study of individual differences in reading growth from post-kindergarten to post-second grade analyzed data from 487 twin pairs from the United States, 267 twin pairs from Australia, and 280 twin pairs from Scandinavia. Data from two reading measures were fit to biometric latent growth models. Individual differences for the reading measures at post-kindergarten in the United States and Australia were due primarily to genetic influences and to both genetic and shared environmental influences in Scandinavia. In contrast, individual differences in growth generally had large genetic influences in all countries. These results suggest that genetic influences are largely responsible for individual differences in early reading development. In addition, the timing of the start of formal literacy instruction may affect the etiology of individual differences in early reading development but have only limited influence on the etiology of individual differences in growth., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Identical and fraternal twins (N=540, age 8 to 18 years) were tested on three different measures of writing (Woodcock-Johnson III Tests of Achievement-Writing Samples and Writing Fluency; Handwriting Copy from the Group Diagnostic Reading and Aptitude Achievement Tests), three different language skills (phonological awareness, rapid naming, and vocabulary), and three different reading skills (word recognition, spelling, and reading comprehension). Substantial genetic influence was found on two of the writing measures, writing samples and handwriting copy, and all of the language and reading measures. Shared environment influences were generally not significant, except for Vocabulary. Non-shared environment estimates, including measurement error, were significant for all variables. Genetic influences among the writing measures were significantly correlated (highest between the speeded measures writing fluency and handwriting copy), but there were also significant independent genetic influences between copy and samples and between fluency and samples. Genetic influences on writing were significantly correlated with genetic influences on all of the language and reading skills, but significant independent genetic influences were also found for copy and samples, whose genetic correlations were significantly less than 1.0 with the reading and language skills. The genetic correlations varied significantly in strength depending on the overlap between the writing, language, and reading task demands. We discuss implications of our results for education, limitations of the study, and new directions for research on writing and its relations to language and reading.

This first Japanese twin study of early literacy development investigated the extent to which genetic and environmental factors influence individual differences in prereading skills in 238 pairs of twins at 42 months of age. Twin pairs were individually tested on measures of phonological awareness, kana letter name/sound knowledge, receptive vocabulary, visual perception, nonword repetition, and digit span. Results obtained from univariate behavioral-genetic analyses yielded little evidence for genetic influences, but substantial shared-environmental influences, for all measures. Phenotypic confirmatory factor analysis suggested three correlated factors: phonological awareness, letter name/sound knowledge, and general prereading skills. Multivariate behavioral genetic analyses confirmed relatively small genetic and substantial shared environmental influences on the factors. The correlations among the three factors were mostly attributable to shared environment. Thus, shared environmental influences play an important role in the early reading development of Japanese children.

This paper describes the Colorado Adoption Project (CAP), an ongoing genetically informative longitudinal study of behavioral development. We describe the features of the adoption design used in CAP, and discuss how this type of design uses data from both parent-offspring and related- versus unrelated-sibling comparisons to estimate the importance of genetic and shared environmental influences for resemblance among family members. The paper provides an overview of CAP's history, how subjects were ascertained, recruited, and retained, and the domains of assessment that have been explored since the CAP's initiation in 1975. Findings from some representative papers that make use of data from CAP participants illustrate the study's multifaceted nature as a parent-offspring and sibling behavioral genetic study, a study that parallels a complimentary twin study, a longitudinal study of development, a source of subjects for molecular genetic investigation, and a study of the outcomes of the adoption process itself. As subjects assessed first at age 1 approach age 40, we hope the CAP will establish itself as the first prospective adoption study of lifespan development.

Human beings come in all shapes and sizes. Heterogeneity makes life interesting, but leads to inter-individual variation in disease susceptibility and response to therapy. One major health challenge is to develop "personalised medicine"; therapeutic interventions tailored to an individual to ensure optimal treatment of disease. Asthma is a heterogeneous disease with several different phenotypes triggered by multiple gene-environment interactions. Inhaled corticosteroids and β2-agonists have been the mainstay asthma therapies for 30 years, but they are not effective in all patients, while high costs and side-effects also drive the need for better targeted treatment of asthma. Pharmacogenetics is the study of variations in the genetic code for proteins in signaling pathways targeted by pharmacological therapies. Biomarkers are biological markers obtained from patients that can aid in asthma diagnosis, prediction of treatment response, and monitoring of disease control. This review presents a broad discussion of the use of genetic profiling and biomarkers to better diagnose, monitor, and tailor the treatment of asthmatics. We also discuss possible future developments in personalised medicine, including the construction of artificially engineered airway tissues containing a patient's own cells for use as personalised drug-testing tools.

We explored the etiology of individual differences in reading development from post-kindergarten to post-4 th grade by analyzing data from 487 twin pairs tested in Colorado. Data from three reading measures and one spelling measure were fit to biometric latent growth curve models, allowing us to extend previous behavioral genetic studies of the etiology of early reading development at specific time points. We found primarily genetic influences on individual differences at post-1 st grade for all measures. Genetic influences on variance in growth rates were also found, with evidence of small, nonsignificant, shared environmental influences for two measures. We discuss our results, including their implications for educational policy.

The genetic factor structure of a range of learning measures was explored in twin children, recruited in preschool and followed to Grade 2 (total N = 2084). Measures of orthographic learning and word reading were included in the analyses to determine how these patterned with the learning processes. An exploratory factor analysis of the genetic correlations among the variables indicated a three-factor model. Vocabulary tests loaded on the first factor, the Grade 2 measures of word reading and orthographic learning, plus preschool letter knowledge, loaded on the second, and the third was characterized by tests of verbal short-term memory. The three genetic factors correlated, with the second (print) factor showing the most specificity. We conclude that genetically-influenced learning processes underlying print-speech integration, foreshadowed by preschool letter knowledge, have a degree of independence from genetic factors affecting spoken language. We also argue that the psychology and genetics of associative learning be afforded a more central place in studies of reading (dis)ability, and suggest some links to molecular studies of the genetics of learning.

This paper describes the Colorado Adoption Project (CAP), a longitudinal study in behavioral development, and discusses how adoption studies may be used to assess genetic and environmental etiologies of individual differences for important developmental outcomes. Previous CAP research on adjustment outcomes in childhood and adolescence which found significant interactions, including gene-environment interactions, is reviewed. New research suggests mediating effects of menarche and religiosity on age at first sex in this predominantly middle-class, Caucasian sample.

While allergies are very common, affecting ∼40% of the population in most Western countries, only a proportion of allergic people develop asthma. This highlights the importance of tissue and cell specific mechanisms that contribute to the disease. As the interface between the inhaled environment and the internal environment of the lung, the epithelium normally possesses numerous mechanisms to maintain an effective protective barrier. However, the inability of the airway epithelium of asthmatics to effectively defend the lung against normally innocuous inhaled agents strongly suggests that asthma must involve defects in the epithelial barrier rather than being primarily an allergic disease. Evidence is accumulating that in asthma, the epithelium does not go through normal stages of development and differentiation and as a consequence, remain somewhat "immature". This in turn leads to a chronic cycle of dysregulated damage and repair which ultimately impacts on the airways function by increasing inflammation, but also by initiating processes that ultimately lead to changes to the structure and function of the airway., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Adopted children show more problem behaviors than nonadopted children. Given that internationally-adopted individuals show earlier puberty than non-adopted individuals, and early puberty is associated with problem behaviors in nonadopted youth, we analyzed data from domestic adoptees to determine whether problem behaviors could be explained by differences in pubertal timing. Relative to nonadopted controls (n = 153), domestically-adopted girls (n = 121) had earlier menarche, earlier sexual initiation, and more conduct disorder symptoms. Age at menarche partially mediated the relation of adoptive status to sexual initiation, but not to conduct disorder symptoms. Extending findings from international adoptees, results show that domestic adoption is also linked to earlier puberty, and suggest early puberty as one mechanism linking adoption to problematic outcomes.

The present study explored whether different executive control and speed measures (working memory, inhibition, processing speed, and naming speed) independently predict individual differences in word reading and reading comprehension. Although previous studies suggest these cognitive constructs are important for reading, the authors analyze the constructs simultaneously to test whether each is a unique predictor. Latent variables from 483 participants (ages 8-16 years) were used to portion each cognitive and reading construct into its unique and shared variance. In these models 2 specific issues are addressed: (a) Given that the wide age range may span the theoretical transition from "learning to read" to "reading to learn," the authors first test whether the relation between word reading and reading comprehension is stable across 2 age groups (ages 8-10 and 11-16); and (b) the main theoretical question of interest: whether what is shared and what is separable for word reading and reading comprehension are associated with individual differences in working memory, inhibition, and measures of processing and naming speed. The results indicated that (a) the relation between word reading and reading comprehension is largely invariant across the age groups, and (b) working memory and general processing speed, but not inhibition or the speeded naming of non-alphanumeric stimuli, are unique predictors of both word reading and comprehension, with working memory equally important for both reading abilities and processing speed more important for word reading. These results have implications for understanding why reading comprehension and word reading are highly correlated yet separable, (. (PsycINFO Database Record (c) 2012 APA, all rights reserved).)

Reading performance data from 254 pairs of identical (MZ) and 420 pairs of fraternal (DZ) twins, 8.0 to 20.0 years of age, were subjected to multiple regression analyses. An extension of the DeFries-Fulker (DF) analysis (DeFries & Fulker, 1985, 1988) that facilitated inclusion of data from 303 of their nontwin siblings was employed. In addition to providing estimates of heritability, this analysis yields a test of the difference between shared environmental influences for twins versus siblings (Astrom et al., 2011). Results suggest that proband reading deficits are due substantially to genetic factors (.67 ± .07, p < .001), and that shared environmental influences are significantly higher for members of twin pairs than for those of twins and their nontwin siblings (viz., .25 versus .17, p = .02).

The augmented multiple regression model for the analysis of data from selected twin pairs was extended to facilitate analyses of data from twin pairs and nontwin siblings. Fitting this extended model to data from both selected twin pairs and siblings yields direct estimates of heritability (h2) and the difference between environmental influences shared by members of twin pairs and those of sib or twin-sib pairs (i.e., c2(t) - c2 (s)). When this model was fitted to reading performance data from 293 monozygotic and 436 dizygotic pairs selected for reading difficulties, and 291 of their nontwin siblings, h2 = .48 ± .22, p = .03, and c2 (t) - c2 (s) = .22 ± .12, p = .06. Although the test for differential shared environmental influences is only marginally significant, the results of this analysis suggest that environmental influences on reading performance that are shared by members of twin pairs (.36) may be substantially greater than those for less contemporaneous twin-sibling pairs (.14).

Reading difficulties are both heritable and stable; however, little is known about the etiology of this stability. Results from a preliminary analysis of data from 56 twin pairs who participated in the Colorado Longitudinal Twin Study of Reading Disability (Astrom et al., Twin Res Hum Genet 10:434-439, 2007) suggested that about two-thirds of the proband deficit at follow-up was due to genetic factors that also influenced deficits at their initial assessment. Although our proband sample is now nearly twice as large, it is still relatively small; thus, to increase power, we subjected data from probands, co-twins and their nontwin siblings to a novel extension of DeFries-Fulker analysis (DeFries and Fulker, Behav Genet 15:467-473, 1985; DeFries and Fulker, Acta Genet Med Gemellol, 37, 205-216, 1988). In addition to providing estimates of univariate and bivariate heritability, this analysis facilitates a test of the difference between shared environmental influences for twins versus siblings. Longitudinal composite reading performance scores at 10.6 and 15.5 years of age, on average, were analyzed from 33 MZ and 64 DZ twin pairs in which at least one member of each pair had reading difficulties, and from 44 siblings of the probands. Scores were highly stable (.86 ± .03, across probands, co-twins and siblings) and heritability of the group deficit at initial assessment was .67 ± .22. Longitudinal bivariate heritability was .59 ± .21, suggesting that nearly 60% of the proband reading deficit at follow-up is due to genetic factors that influenced reading difficulties at the initial assessment. However, tests for special twin environmental influences were nonsignificant.

The present study compared the level of conduct problems at age 17 in a large, non-clinical sample of adopted participants placed in infancy and children in non-adoptive families matched to the adoptive families on demographic characteristics. Higher levels of adolescent and parent adoption satisfaction were associated with lower levels of conduct problems. Gender by adoption status interactions were not significant. However, female adopted participants had higher levels of conduct problems than female non-adopted participants, whereas male adopted and non-adopted participants had similar levels of conduct problems. In the overall sample, differences between adopted and matched control participants on all conduct problem measures were nonsignificant.

Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and create personalized treatment regimes. Asthma is a heterogeneous disease with several different phenotypes, generally triggered by multiple gene-environment interactions. Pulmonary function tests are most often used objectively to confirm the diagnosis. However, airflow obstruction can be variable and thus missed using spirometry. Furthermore, lung function measurements may not reflect the precise underlying pathological processes responsible for different phenotypes. Inhaled corticosteroids and β(2)-agonists have been the mainstay of asthma therapy for over 30 years, but the heterogeneity of the disease means not all asthmatics respond to the same treatment. High costs and undesired side effects of drugs also drive the need for better targeted treatment of asthma. Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment. This review focuses on biomarkers of airway inflammation which may help us to identify, monitor, and guide treatment of asthmatics. We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine. We discuss the inherent limitations and benefits of using biomarkers in a heterogeneous disease such as asthma. We also discuss how we may modify our study designs to improve the identification and potential use of potential biomarkers in asthma.