Pubmed du 12/02/19

Pubmed du jour

2019-02-12 12:03:50

1. Barone R, Spampinato C, Pino C, Palermo F, Scuderi A, Zavattieri A, Gulisano M, Giordano D, Rizzo R. {{Online comprehension across different semantic categories in preschool children with autism spectrum disorder}}. {PLoS One}. 2019; 14(2): e0211802.

BACKGROUND: Word comprehension across semantic categories is a key area of language development. Using online automated eye-tracking technology to reduce response demands during a word comprehension test may be advantageous in children with autism spectrum disorder (ASD). OBJECTIVES: To measure online accuracy of word recognition across eleven semantic categories in preschool children with ASD and in typically developing (TD) children matched for gender and developmental age. METHODS: Using eye-tracker methodology we measured the relative number of fixations on a target image as compared to a foil of the same category shown simultaneously on screen. This online accuracy measure was considered a measure of word understanding. We tested the relationship between online accuracy and offline word recognition and the effects of clinical variables on online accuracy. Twenty-four children with ASD and 21 TD control children underwent the eye-tracking task. RESULTS: On average, children with ASD were significantly less accurate at fixating on the target image than the TD children. After multiple comparison correction, no significant differences were found across the eleven semantic categories of the experiment between preschool children with ASD and younger TD children matched for developmental age. The ASD group showed higher intragroup variability consistent with greater variation in vocabulary growth rates. Direct effects of non-verbal cognitive levels, vocabulary levels and gesture productions on online word recognition in both groups support a dimensional view of language abilities in ASD. CONCLUSIONS: Online measures of word comprehension across different semantic categories show higher interindividual variability in children with ASD and may be useful for objectively monitor gains on targeted language interventions.

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2. D’Amanda CS, Peay HL, Wheeler AC, Turbitt E, Biesecker BB. {{Fragile X syndrome clinical trials: exploring parental decision-making}}. {J Intellect Disabil Res}. 2019.

BACKGROUND: The objective of this research was to understand parental proxy decision-making for drug trial participation for children with Fragile X syndrome (FXS). Specifically, we aimed to capture preferences, motivations, influencing factors and barriers related to trial involvement among trial joiners and decliners and describe ease of trial decision-making and decisional regret. METHODS: Interviews were conducted with parents from two groups: those who chose to enrol their child with FXS in a trial (N = 16; Joiners) and those who declined trial participation (N = 15; Decliners). Data were coded and interpreted through inductive content analysis. RESULTS: Prominent decisional factors included attitudes about medicating FXS symptoms, potential for direct benefit (primarily evaluated through the degree of match between target outcomes and child symptomatology and drug mechanism), logistical convenience and perceived risks of side effects. The ultimate motivation for participation was potential for direct benefit. None of the parents reported decisional regret, and ease of decision-making ranged from easy to difficult for our participants. CONCLUSIONS: Therapeutic optimism was high among those who elected participation. Parents may benefit from an explanation of the rationale behind chosen outcome variables and may be more interested in trials that target or measure as an exploratory outcome the symptoms they find most concerning. Our findings reinforce the need for future trials to reduce participant inconvenience. Our results contrast with what has previously been observed in parents of children with life-threatening conditions; parents of children with FXS may be more trial risk averse and find trial decisions to be harder. Parents of children with FXS considering trials may benefit from a decisional intervention aimed at deliberating motivations and barriers.

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3. Deneault E, Faheem M, White SH, Rodrigues DC, Sun S, Wei W, Piekna A, Thompson T, Howe JL, Chalil L, Kwan V, Walker S, Pasceri P, Roth FP, Yuen RK, Singh KK, Ellis J, Scherer SW. {{CNTN5(-)(/+)or EHMT2(-)(/+)human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks}}. {eLife}. 2019; 8.

Induced pluripotent stem cell (iPSC)-derived neurons are increasingly used to model Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of penetrant and weaker polygenic risk variants to ASD, ‘isogenic’ iPSC-derived neurons are critical. We developed a set of procedures to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD. Heterozygous de novo and rare-inherited presumed-damaging variants were characterized in ASD risk genes/loci. Combinations of putative etiologic variants (GLI3/KIF21A or EHMT2/UBE2I) in separate families were modeled. We used a multi-electrode array, with patch-clamp recordings, to determine a reproducible synaptic phenotype in 25% of the individuals with ASD (other relevant data on the remaining lines was collected). Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient for CNTN5 or EHMT2. The biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research. Editorial note: This article has been through an editorial process in which authors decide how to respond to the issues raised during peer review. The Reviewing Editor’s assessment is that all the issues have been addressed (see decision letter).

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4. Deneault E, White SH, Rodrigues DC, Ross PJ, Faheem M, Zaslavsky K, Wang Z, Alexandrova R, Pellecchia G, Wei W, Piekna A, Kaur G, Howe JL, Kwan V, Thiruvahindrapuram B, Walker S, Lionel AC, Pasceri P, Merico D, Yuen RKC, Singh KK, Ellis J, Scherer SW. {{Complete Disruption of Autism-Susceptibility Genes by Gene Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons}}. {Stem cell reports}. 2019; 12(2): 427-9.

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5. Gong T, Lundholm C, Rejno G, Bolte S, Larsson H, D’Onofrio BM, Lichtenstein P, Almqvist C. {{Parental asthma and risk of autism spectrum disorder in offspring: a population and family based case-control study}}. {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}. 2019.

BACKGROUND: Associations between parental asthma and prenatal exposure to asthma medications with offspring autism spectrum disorder (ASD) have been reported. However, the associations might be confounded by unmeasured (genetic and shared environmental) familial factors. OBJECTIVE: We investigated the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to beta2-agonists, other asthma medications and offspring ASD using cases and controls selected from the population as well as biological relatives with different degrees of relatedness. METHODS: We included all children (N=1,579,263) born in Sweden 1992-2007. A nested case-control design was used to compare 22,894 ASD cases identified from the National Patient Register to (i) 228,940 age-, county- and sex-matched controls randomly selected from the population, (ii) their eligible full-siblings (n=1,267), (iii) half-siblings (n=1,323), (iv) full-cousins (n=11,477), and (v) half-cousins (n=3,337). Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for ASD in children differentially exposed to parental asthma or prenatal asthma medications. RESULTS: Maternal asthma was associated with increased risk of offspring ASD (OR 1.43, 95% CI 1.38-1.49); there was a weaker association for paternal asthma (OR 1.17, 95% CI 1.11-1.23). The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings (OR 1.20, 95% CI 0.80-1.81), full-cousins (OR 1.28, 95% CI 1.16-1.41), and half-cousins (OR 1.30, 95% CI 1.10-1.54), albeit with wider confidence intervals. Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD. CONCLUSIONS AND CLINICAL RELEVANCE: In this large observational study, parental asthma was associated with slightly elevated risk of ASD in offspring. More specifically, the increased risk by maternal asthma did not seem to be confounded by familial factors. There was no evidence of an association between asthma medications during pregnancy and offspring ASD. This article is protected by copyright. All rights reserved.

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6. Hetzroni OE, Hessler M, Shalahevich K. {{Learning new relational categories by children with autism spectrum disorders, children with typical development and children with intellectual disabilities: effects of comparison and familiarity on systematicity}}. {J Intellect Disabil Res}. 2019.

BACKGROUND: Systematicity principle, used during analogical reasoning, enables building up deeper abstract concepts as part of structure mapping. The purpose of this study was to investigate structure mapping processes that occur during acquisition of new relational categories and to identify the learning patterns and systematicity of children with autism spectrum disorder (ASD) compared with intellectual and developmental disabilities (IDD) and typical development (TD). Comparison effect and level of familiarity were used to investigate structural mapping processes. METHODS: Three groups of 24 children participated in the study. Using a computer program, participants were asked to select a perceptual or relational choice based on one or two standards using illustrations depicting new relational categories in various spatial configurations. Known, partially known and unknown illustrations were used in depicting three levels of familiarity. RESULTS: All three groups selected perceptual choices when one standard was available (no comparison). However, when two standards were available, enabling a comparison, children with IDD and TD increased their tendency for selecting abstract relational categories, while children with ASD did not change their preference and continued selecting perceptual choices. Level of familiarity increased selection of relational choices among children with TD and IDD but not among children with ASD. CONCLUSIONS: Systematicity principle was evident mostly in the selection of relational choices by children with TD and IDD when the illustrations were known or partially known. Hence, even when an opportunity to compare and to use previously known information was available, structure mapping processes and systematicity were implemented to align information among children TD and IDD but failed to assist the learning of new relational categories among children with ASD.

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7. Hswen Y, Gopaluni A, Brownstein JS, Hawkins JB. {{Using Twitter to Detect Psychological Characteristics of Self-Identified Persons With Autism Spectrum Disorder: A Feasibility Study}}. {JMIR mHealth and uHealth}. 2019; 7(2): e12264.

BACKGROUND: More than 3.5 million Americans live with autism spectrum disorder (ASD). Major challenges persist in diagnosing ASD as no medical test exists to diagnose this disorder. Digital phenotyping holds promise to guide in the clinical diagnoses and screening of ASD. OBJECTIVE: This study aims to explore the feasibility of using the Web-based social media platform Twitter to detect psychological and behavioral characteristics of self-identified persons with ASD. METHODS: Data from Twitter were retrieved from 152 self-identified users with ASD and 182 randomly selected control users from March 22, 2012 to July 20, 2017. We conducted a between-group comparative textual analysis of tweets about repetitive and obsessive-compulsive behavioral characteristics typically associated with ASD. In addition, common emotional characteristics of persons with ASD, such as fear, paranoia, and anxiety, were examined between groups through textual analysis. Furthermore, we compared the timing of tweets between users with ASD and control users to identify patterns in communication. RESULTS: Users with ASD posted a significantly higher frequency of tweets related to the specific repetitive behavior of counting compared with control users (P<.001). The textual analysis of obsessive-compulsive behavioral characteristics, such as fixate, excessive, and concern, were significantly higher among users with ASD compared with the control group (P<.001). In addition, emotional terms related to fear, paranoia, and anxiety were tweeted at a significantly higher rate among users with ASD compared with control users (P<.001). Users with ASD posted a smaller proportion of tweets during time intervals of 00:00-05:59 (P<.001), 06:00-11:59 (P<.001), and 18:00-23.59 (P<.001), as well as a greater proportion of tweets from 12:00 to 17:59 (P<.001) compared with control users. CONCLUSIONS: Social media may be a valuable resource for observing unique psychological characteristics of self-identified persons with ASD. Collecting and analyzing data from these digital platforms may afford opportunities to identify the characteristics of ASD and assist in the diagnosis or verification of ASD. This study highlights the feasibility of leveraging digital data for gaining new insights into various health conditions. Lien vers le texte intégral (Open Access ou abonnement)

8. Kumari D, Gazy I, Usdin K. {{Pharmacological Reactivation of the Silenced FMR1 Gene as a Targeted Therapeutic Approach for Fragile X Syndrome}}. {Brain Sci}. 2019; 9(2).

More than ~200 CGG repeats in the 5′ untranslated region of the FMR1 gene results in transcriptional silencing and the absence of the FMR1 encoded protein, FMRP. FMRP is an RNA-binding protein that regulates the transport and translation of a variety of brain mRNAs in an activity-dependent manner. The loss of FMRP causes dysregulation of many neuronal pathways and results in an intellectual disability disorder, fragile X syndrome (FXS). Currently, there is no effective treatment for FXS. In this review, we discuss reactivation of the FMR1 gene as a potential approach for FXS treatment with an emphasis on the use of small molecules to inhibit the pathways important for gene silencing.

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9. Lin HY, Perry A, Cocchi L, Roberts JA, Tseng WI, Breakspear M, Gau SS. {{Development of frontoparietal connectivity predicts longitudinal symptom changes in young people with autism spectrum disorder}}. {Translational psychiatry}. 2019; 9(1): 86.

Structural neuroimaging studies suggest altered brain maturation in autism spectrum disorder (ASD) compared with typically developing controls (TDC). However, the prognostic value of whole-brain structural connectivity analysis in ASD has not been established. Diffusion magnetic imaging data were acquired in 27 high-functioning young ASD participants (2 females) and 29 age-matched TDC (12 females; age 8-18 years) at baseline and again following 3-7 years. Whole-brain structural connectomes were reconstructed from these data and analyzed using a longitudinal statistical model. We identified distinct patterns of widespread brain connections that exhibited either significant increases or decreases in connectivity over time (p < 0.001). There was a significant interaction between diagnosis and time in brain development (p < 0.001). This was expressed by a decrease in structural connectivity within the frontoparietal network-and its broader connectivity-in ASD during adolescence and early adulthood. Conversely, these connections increased with time in TDC. Crucially, stronger baseline connectivity in this subnetwork predicted a lower symptom load at follow-up (p = 0.048), independent of the expression of symptoms at baseline. Our findings suggest a clinically meaningful relationship between the atypical development of frontoparietal structural connections and the dynamics of the autism phenotype through early adulthood. These results highlight a potential marker of future outcome. Lien vers le texte intégral (Open Access ou abonnement)

10. Mirza R, Sharma B. {{Benefits of Fenofibrate in prenatal valproic acid-induced autism spectrum disorder related phenotype in rats}}. {Brain Res Bull}. 2019.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with two major behavioral symptoms i.e. repetitive behavior and social-communication impairment. The unknown etiology of ASD is responsible for the difficulty in identifying the possible therapeutic modulators for ASD. Valproic acid (VPA) is an anticonvulsant drug in both human and rodents with teratogenic effects during pregnancy. Therefore, prenatal exposure of VPA induced autism spectrum disorder like phenotypes in both human and rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is widely localized in the brain. This research investigates the utility of fenofibrate, a selective agonist of PPAR-alpha in prenatal VPA-induced experimental ASD in Wistar rats. The prenatal VPA has induced social impairment (three chambers social behavior apparatus), repetitive behavior (Y-maze), hyperlocomotion (actophotometer), anxiety (elevated plus maze) and low exploratory activity (hole board test). Also, prenatal VPA treated rats have shown higher levels of oxidative stress (increased in thiobarbituric acid reactive species and decreased in reduced glutathione level) and inflammation (increased in interleukin-6, tumor necrosis factor-alpha and decreased in interleukin-10) in the cerebellum, brainstem and prefrontal cortex. Treatment with fenofibrate significantly attenuated prenatal VPA-induced social impairment, repetitive behavior, hyperactivity, anxiety, and low exploratory activity. Furthermore, fenofibrate also decreased the prenatal VPA-induced oxidative stress and inflammation in brain regions. Hence, it may be concluded that fenofibrate may provide neurobehavioral and biochemical benefits in prenatal VPA-induced autism phenotypes in rats.

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11. Pecorelli A, Cervellati C, Cordone V, Amicarelli F, Hayek J, Valacchil G. {{13-HODE, 9-HODE and ALOX15 as potential players in Rett syndrome OxInflammation}}. {Free radical biology & medicine}. 2019.

Mutations in the MECP2 gene are the main cause of Rett syndrome (RTT), a pervasive neurodevelopmental disorder, that shows also multisystem disturbances associated with a metabolic component. The aim of this study was to investigate whether an increased production of oxidized linoleic acid metabolites, specifically 9- and 13-hydroxyoctadecadienoic acids (HODEs), can contribute to the altered the redox and immune homeostasis, suggested to be involved in RTT. Serum levels of 9- and 13-HODEs were elevated in RTT and associated with the expression of arachidonate 15-Lipoxygenase (ALOX15) in peripheral blood mononuclear cells (PBMCs). Omega-3 polyunsaturated fatty acids supplementation has shown to lower HODEs levels in RTT. Statistically significant correlation was demonstrated between the increased plasma HODEs levels and the lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Collectively, these findings reinforce the concept of the key role played by lipid peroxidation in RTT, and the possible ability of omega-3 polyunsaturated fatty acids supplementation in improving the oxinflammation status in RTT.

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12. Peisley M, Foster TM, Sargisson RJ. {{Reinforcing the prospective remembering of children with autism spectrum disorder}}. {Journal of applied behavior analysis}. 2019.

Prospective memory is remembering to carry out a behavior on a particular occasion or at a specific time in the future. This form of remembering is critical for the daily functioning of children with autism spectrum disorder (ASD) and their functional independence from caregivers. We used a single-subject design to investigate whether reinforcement increased the accuracy of prospective remembering in the context of a computerized board game, Virtual Week, of four 6- to 7-year-old children diagnosed with ASD. Reinforcement increased accuracy for all participants compared to baseline performance and effects were maintained after reinforcement was discontinued for three of four children. This is the first study of which we are aware to use a reinforcement-based behavioral intervention to improve the prospective remembering of children with ASD. Limitations and areas for future research are discussed.

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13. Rosman NP. {{Childhood disintegrative disorder: part of the autism spectrum?}}. {Dev Med Child Neurol}. 2019.

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14. Tillmann J, San Jose Caceres A, Chatham CH, Crawley D, Holt R, Oakley B, Banaschewski T, Baron-Cohen S, Bolte S, Buitelaar JK, Durston S, Ham L, Loth E, Simonoff E, Spooren W, Murphy DG, Charman T. {{Investigating the factors underlying adaptive functioning in autism in the EU-AIMS Longitudinal European Autism Project}}. {Autism Res}. 2019.

Individuals with autism spectrum disorder (ASD) exhibit significant impairments in adaptive functioning that impact on their ability to meet the demands of everyday life. A recurrent finding is that there is a pronounced discrepancy between level of cognitive ability and adaptive functioning, and this is particularly prominent among higher-ability individuals. However, the key clinical and demographic associations of these discrepancies remain unclear. This study included a sample of 417 children, adolescents, and adults with ASD as part of the EU-AIMS LEAP cohort. We examined how age, sex, IQ, levels of ASD symptom and autistic trait severity and psychiatric symptomatology are associated with adaptive functioning as measured by the Vineland Adaptive Behavior Scales-Second Edition and IQ-adaptive functioning discrepancies. Older age, lower IQ and higher social-communication symptoms were associated with lower adaptive functioning. Results also demonstrate that older age, higher IQ and higher social-communication symptoms are associated with greater IQ-adaptive functioning discrepancy scores. By contrast, sensory ASD symptoms, repetitive and restricted behaviors, as well as symptoms of attention deficit/hyperactivity disorder (ADHD), anxiety and depression, were not associated with adaptive functioning or IQ-adaptive functioning discrepancy scores. These findings suggest that it is the core social communication problems that define ASD that contribute to adaptive function impairments that people with ASD experience. They show for the first time that sensory symptoms, repetitive behavior and associated psychiatric symptoms do not independently contribute to adaptive function impairments. Individuals with ASD require supportive interventions across the lifespan that take account of social-communicative ASD symptom severity. Autism Res 2019, 00: 1-13. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: This study investigated key clinical and demographic associations of adaptive functioning impairments in individuals with autism. We found that older age, lower IQ and more severe social-communicative symptoms, but not sensory or repetitive symptoms or co-occurring psychiatric symptoms, are associated with lower adaptive functioning and greater ability-adaptive function discrepancies. This suggests that interventions targeting adaptive skills acquisition should be flexible in their timing and intensity across developmental periods, levels of cognitive ability and take account of social-communicative ASD symptom severity.

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15. Togo S, Itahashi T, Hashimoto R, Cai C, Kanai C, Kato N, Imamizu H. {{Fourth finger dependence of high-functioning autism spectrum disorder in multi-digit force coordination}}. {Sci Rep}. 2019; 9(1): 1737.

A number of studies have reported that the digit ratio 2D:4D (length of the second finger divided by length of the fourth finger) is smaller (longer fourth digit) in autism spectrum disorder (ASD) than in typically developed (TD) controls. Because form and function are closely related in biological systems, we hypothesized that the 4D dominance occurs in not only finger morphology but also physical performance in ASD. Individuals with ASD and TD controls participated in a multi-digit force-producing task. Individuals with ASD showed a significant 4D dependence compared to TD controls in the task. We found a significant correlation between 4D dependence and scores of the standard diagnostic instrument across individuals with ASD. Our analysis of functional connectivity in resting-state functional MRI suggests that connectivity between the visual cortex and the cerebellum contributes to the 4D dependence. Collectively, these results extend the 2D:4D ratio beyond being a morphological marker to being involved in motor functions in the form of 4D dependence in a multi-digit force task.

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16. van den Boomen C, Fahrenfort JJ, Snijders TM, Kemner C. {{Slow segmentation of faces in Autism Spectrum Disorder}}. {Neuropsychologia}. 2019.

Atypical visual segmentation, affecting object perception, might contribute to face processing problems in Autism Spectrum Disorder (ASD). The current study investigated impairments in visual segmentation of faces in ASD. Thirty participants (ASD: 16; Control: 14) viewed texture-defined faces, houses, and homogeneous images, while electroencephalographic and behavioral responses were recorded. The ASD group showed slower face-segmentation related brain activity and longer segmentation reaction times than the control group, but no difference in house-segmentation related activity or behavioral performance. Furthermore, individual differences in face-segmentation but not house-segmentation correlated with score on the Autism Quotient. Segmentation is thus selectively impaired for faces in ASD, and relates to the degree of ASD traits. Face segmentation relates to recurrent connectivity from the fusiform face area (FFA) to the visual cortex. These findings thus suggest that atypical connectivity from the FFA might contribute to delayed face processing in ASD.

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17. Vernon TW, Holden AN, Barrett AC, Bradshaw J, Ko JA, McGarry ES, Horowitz EJ, Tagavi DM, German TC. {{A Pilot Randomized Clinical Trial of an Enhanced Pivotal Response Treatment Approach for Young Children with Autism: The PRISM Model}}. {J Autism Dev Disord}. 2019.

The symptoms of autism spectrum disorder are conceptualized to alter the quality of parent-children interactions, exposure to social learning exchanges, and ultimately the course of child development. There is evidence that modifying the procedures of Pivotal Response Treatment (PRT) to explicitly target social motivation enhances child engagement and parent-child synchrony in moment-by-moment exchanges. However, it is unclear if these within session improvements ultimately yield favorable developmental outcomes over time. The current investigation presents feasibility, utility, and preliminary efficacy data of a pilot randomized clinical trial (RCT) of a Pivotal Response Intervention for Social Motivation (PRISM) model. Data on participant factors, treatment protocol acceptability, and outcome variance and effect size are highly favorable and support the pursuit of a future, large scale RCT.

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18. Williams NJ, Frank HE, Frederick L, Beidas RS, Mandell DS, Aarons GA, Green P, Locke J. {{Organizational culture and climate profiles: relationships with fidelity to three evidence-based practices for autism in elementary schools}}. {Implementation science : IS}. 2019; 14(1): 15.

BACKGROUND: Implementation researchers have typically studied organizational culture and climate by testing whether individual dimensions are linked to the implementation of evidence-based practices (EBPs) rather than examining how the overarching social context influences implementation. This approach may limit implementation theory and strategy development to the extent that individual dimensions of culture and climate interact, mutually reinforce or counteract one another, or exhibit non-linear relationships. This study tests whether empirically identifiable culture and climate profiles emerge in a sample of organizations and examines how these profiles relate to EBP fidelity and work attitudes that support EBP sustainment, focusing on three EBPs for youth with autism delivered in schools as an example. METHODS: The study included 65 elementary schools in the U.S. that implemented three EBPs-discrete trial training, pivotal response training, and visual schedules-for youth with autism. Organizational culture and climate and work attitudes were assessed using the Organizational Social Context measure at the beginning of the school year. Observations of EBP fidelity occurred mid school-year. We used bias-adjusted stepwise latent profile modeling to (1) identify subpopulations of schools that share similar culture and climate profiles, and (2) test for mean differences across profiles in observed EBP fidelity and teacher and staff work attitudes. RESULTS: Controlling for region, four profiles best characterized the organizational cultures and climates of schools. Teachers and staff in schools with a comprehensive profile (high proficiency culture, positive climate) exhibited higher fidelity to two of three EBPs (d’s = .95 to 1.64) and reported superior work attitudes (d’s = .71 to 1.93) than teachers and staff in all other schools. Teachers and staff in supportive schools (low rigidity culture, positive climate) had better work attitudes, but not better fidelity, than those in schools with indifferent (low culture/climate, elevated stress) and constrained (high rigidity and resistance, high stress) profiles. CONCLUSIONS: Organizational culture and climate profiles are a strong predictor of EBP fidelity and work attitudes that support EBP sustainment, highlighting the importance of an organization’s overarching social context when developing implementation theory and strategies. Strategies that foster a comprehensive profile may improve EBP implementation.

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19. Zhai Q, Cen S, Jiang J, Zhao J, Zhang H, Chen W. {{Disturbance of trace element and gut microbiota profiles as indicators of autism spectrum disorder: A pilot study of Chinese children}}. {Environmental research}. 2019; 171: 501-9.

Autism spectrum disorder (ASD) is a neuro-developmental disorder that is characterized by impairments of reciprocal social interaction and restricted stereotyped repetitive behavior. The goal of the present study was to investigate the trace element and gut microbiota profiles of Chinese autistic children and screen out potential metallic or microbial indicators of the disease. One hundred and thirty-six children (78 with ASD and 58 healthy controls) aged from 3 to 7 years were enrolled. The levels of lead, cadmium, arsenic, copper, zinc, iron, mercury, calcium and magnesium in hair samples from the children were analyzed. Fecal samples were also collected and the children’s gut microbiota profiles were characterized by 16s rRNA sequencing. Concentrations of lead, arsenic, copper, zinc, mercury, calcium and magnesium were significantly higher in the ASD group than in the control group. Linear discriminant analysis effect size analysis indicated that the relative abundance of nine genera was increased in the autistic children. Redundancy analysis showed that arsenic and mercury were significantly associated with Parabacteroides and Oscillospira in the gut. A random forest model was trained with high accuracy (84.00%) and the metallic and microbial biomarkers of ASD were established. Our results indicate significant alterations in the trace element and gut microbiota profiles of Chinese children with ASD and reveal the potential pathogenesis of this disease in terms of metal metabolism and gut microecology.

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