Familial influences on the full range of variability in attention and activity levels during adolescence: A longitudinal twin study

AbstractTo investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%–73% (attention) and 31%–73% (activity) of the total variance, and shared environmental influences accounted for 0%–22% of the attention variance and 13%–57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.</jats:p

Attention-Deficit/Hyperactivity Disorder, autistic traits, and substance use in Missouri adolescents

Background: Although existing literature demonstrates the association of attention-deficit/hyperactivity disorder (ADHD) with both substance use (SU) and autism spectrum disorder (ASD), few studies have examined rates of SU among adolescents with elevated ASD symptoms, with or without comorbid ADHD. Clinic-based studies suggest a possible protective effect of ASD against SU, but this has not been confirmed in population-based studies.Objective: We examined alcohol, tobacco, and drug use in adolescents with either ADHD, elevated autistic traits, or both as compared with controls.Methods: Subjects (N = 2937) who were 13 to 17 years old from a Missouri population-based large sibship sample were assessed for ADHD, autistic traits, and SU with the use of parent-report questionnaires. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD symptom criterion (Criterion A) was applied to the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) questionnaire item responses to determine ADHD diagnosis. The presence of elevated autistic traits was defined as a raw Social Responsiveness Scale (SRS) score of 62 (95th percentile for this sample) or higher. SU was determined with the use of three items from the Child Behavior Checklist (CBCL). Statistical methods used included logistic and fractional polynomial regression.Results: As compared with controls, adolescents with ADHD were at increased risk for alcohol, tobacco, and drug use whether or not they had elevated autistic traits. Adolescents with elevated autistic traits were at significantly increased risk for drug use other than alcohol and tobacco, even if they did not have ADHD. Among those with raw SRS scores in the range of about 20 (normal) to 80 (consistent with mild to moderate ASD), adolescents with ADHD had higher levels of SU than control individuals with similar levels of autistic traits. However, strong conclusions cannot be drawn regarding individuals with very low or very high SRS scores as a result of sparse data.Conclusions: This study confirms previous research showing an increased risk of SU among adolescents with ADHD. It also provides new information indicating that adolescents with high levels of autistic traits are at elevated risk for alcohol and tobacco use if they have comorbid ADHD; in addition, they may be at high risk for other drug use, even if they do not have comorbid ADHD. Therefore, it should not be assumed that adolescents with mild to moderate ASD have a low risk of SU, especially if ADHD is also present

Attention-Deficit/Hyperactivity Disorder, autistic traits, and substance use in Missouri adolescents

Background: Although existing literature demonstrates the association of attention-deficit/hyperactivity disorder (ADHD) with both substance use (SU) and autism spectrum disorder (ASD), few studies have examined rates of SU among adolescents with elevated ASD symptoms, with or without comorbid ADHD. Clinic-based studies suggest a possible protective effect of ASD against SU, but this has not been confirmed in population-based studies.Objective: We examined alcohol, tobacco, and drug use in adolescents with either ADHD, elevated autistic traits, or both as compared with controls.Methods: Subjects (N = 2937) who were 13 to 17 years old from a Missouri population-based large sibship sample were assessed for ADHD, autistic traits, and SU with the use of parent-report questionnaires. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD symptom criterion (Criterion A) was applied to the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) questionnaire item responses to determine ADHD diagnosis. The presence of elevated autistic traits was defined as a raw Social Responsiveness Scale (SRS) score of 62 (95th percentile for this sample) or higher. SU was determined with the use of three items from the Child Behavior Checklist (CBCL). Statistical methods used included logistic and fractional polynomial regression.Results: As compared with controls, adolescents with ADHD were at increased risk for alcohol, tobacco, and drug use whether or not they had elevated autistic traits. Adolescents with elevated autistic traits were at significantly increased risk for drug use other than alcohol and tobacco, even if they did not have ADHD. Among those with raw SRS scores in the range of about 20 (normal) to 80 (consistent with mild to moderate ASD), adolescents with ADHD had higher levels of SU than control individuals with similar levels of autistic traits. However, strong conclusions cannot be drawn regarding individuals with very low or very high SRS scores as a result of sparse data.Conclusions: This study confirms previous research showing an increased risk of SU among adolescents with ADHD. It also provides new information indicating that adolescents with high levels of autistic traits are at elevated risk for alcohol and tobacco use if they have comorbid ADHD; in addition, they may be at high risk for other drug use, even if they do not have comorbid ADHD. Therefore, it should not be assumed that adolescents with mild to moderate ASD have a low risk of SU, especially if ADHD is also present

Dispensable sequence motifs in the RAG-1 and RAG-2 genes for plasmid V(D)J recombination

As a probe of whether RAG-1 and RAG-2 gene products activate other genes or form part of the recombinase itself, certain mutants of the RAG genes were assayed for their ability to activate variable-diversity-joining region [V(D)J] recombination in a plasmid substrate in fibroblasts. The results indicate that the N-terminal one-third of RAG-1, including a zinc-finger-like domain, and an acidic domain of RAG-2 are dispensable for activating V(D)J recombination in a fibroblast, although they contribute quantitatively. In contrast, deletion of the C-terminal segment of RAG-1, which has homology to a topoisomerase-like protein from yeast, abolished recombination activation. These results do not support the hypothesis that the RAG gene products are transcription factors and suggest the possibility that they are parts of the recombination machinery

Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries

We have recently described an RNA-only gene regulation system for mammalian cells in which inhibition of self-cleavage of an mRNA carrying ribozyme sequences provides the basis for control of gene expression. An important proof of principle for that system was provided by demonstrating the ability of one specific small molecule inhibitor of RNA self-cleavage, toyocamycin, to control gene expression in vitro and vivo. Here, we describe the development of the high-throughput screening (HTS) assay that led to the identification of toyocamycin and other molecules capable of inhibiting RNA self-cleavage in mammalian cells. To identify small molecules that can serve as inhibitors of ribozyme self-cleavage, we established a cell-based assay in which expression of a luciferase (luc) reporter is controlled by ribozyme sequences, and screened 58,076 compounds for their ability to induce luciferase expression. Fifteen compounds able to inhibit ribozyme self-cleavage in cells were identified through this screen. The most potent of the inhibitors identified were toyocamycin and 5-fluorouridine (FUR), nucleoside analogs carrying modifications of the 7-position and 5-position of the purine or pyrimidine bases. Individually, these two compounds were able to induce gene expression of the ribozyme-controlled reporter ∼365-fold and 110-fold, respectively. Studies of the mechanism of action of the ribozyme inhibitors indicate that the compounds must be incorporated into RNA in order to inhibit RNA self-cleavage

A research agenda on Data Supply Chains (DSC)

Competition among organizations supports initiatives and collaborative use of data while creating value based on the strategy and best performance of each data supply chain. Supporting this direction, and building on the theoretical background of the supply chain, we propose the Data Supply Chain (DSC) as a novel concept to aid investigations for data-driven collaboration impacting organizational performance. In this study we initially propose a definition for the DSC paying particular attention to the need for collaboration for the supply chains of data. Furthermore, we develop a conceptual model of DSC collaboration coupling theoretical background of strategy and operations literature including, the resource-based view (RBV), supply chain management (SCM) and collaboration (SCC). Finally, we set propositions and a future research agenda including testing and validating the model fit

Data Supply Chain (DSC): development and validation of a measurement instrument

The volume and availability of data produced and affordably stored has become an important new resource for building organizational competitive advantage. Reflecting this, and expanding the concept of the supply chain, we propose the Data Supply Chain (DSC) as a novel concept to aid investigations into how the interconnected data characteristics relate to and impact organizational performance. Initially, we define the concept and develop a research agenda on DSC coupling theoretical background of strategy and operations literature. Along with the conceptualization, we develop a set of propositions and make suggestions for future research including testing and validating the model fit

Positive Associations of Dietary Intake and Plasma Concentrations of Vitamin E with Skeletal Muscle Mass, Heel Bone Ultrasound Attenuation and Fracture Risk in the EPIC-Norfolk Cohort.

The prevalence of sarcopenia, frailty and fractures is increasing. Prevention options are limited, but dietary factors including vitamin E have the potential to confer some protection. This study investigated cross-sectional associations between dietary and plasma concentrations of vitamin E with indices of skeletal muscle mass (SMM) (n = 14,179 and 4283, respectively) and bone density (n = 14,694 and 4457, respectively) and longitudinal fracture risk (n = 25,223 and 7291, respectively) in European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk participants, aged 39-79 years at baseline. Participants completed a health and lifestyle questionnaire, a 7-day diet diary (7dDD) and had anthropometric measurements taken. Fat-free mass (as a SMM proxy) was measured using bioimpedance and bone density was measured using calcaneal broadband ultrasound attenuation (BUA) and incident fractures over 18.5 years of follow-up. Associations between indices of SMM, BUA and fracture risk were investigated by quintiles of dietary vitamin E intake or plasma concentrations. Positive trends in SMM indices and BUA were apparent across dietary quintiles for both sexes, with interquintile differences of 0.88%-1.91% (p < 0.001), and protective trends for total and hip fracture risk. Circulating plasma α- and γ-tocopherol results matched the overall dietary findings. Dietary vitamin E may be important for musculoskeletal health but further investigation is required to fully understand the relationships of plasma tocopherols.This research was funded by the Medical Research Council, grant numbers MR/N003284/1 and MC-UU_12015/1 and Cancer Research UK, grant number C864/A14136