Publications by authors named "John Wray"

30 Publications

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The Power of Playgroups: Key components of supported and therapeutic playgroups from the perspective of parents.

Aust Occup Ther J 2020 Nov 22. Epub 2020 Nov 22.

School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia.

Introduction: Playgroups are community-based programs for children and families aiming to improve child outcomes, enhance family and community networks and increase parenting capacity. Despite the prevalence of playgroups in Australian communities there is a lack of research clearly articulating the key components of playgroups, specifically from the perspective of parents attending these groups. This study aimed to identify the key components of supported and therapeutic playgroups impacting on perceived effectiveness from the perspective of parents with a child with a developmental delay and/or disability.

Methods: This study explored the experiences of 23 parents attending supported or therapeutic playgroups using a qualitative interpretive phenomenological approach. Data were collected through three focus groups and seven individual interviews and analysed using Colaizzi's (1978) qualitative method of data analysis.

Results: Findings indicated playgroup components that most strongly impacted on perceived effectiveness were feeling accepted; providing opportunities for child development, socialisation and enjoyment; and enhancing parental knowledge and skills. Findings reinforced the importance of family centred practice and facilitating peer support for families of children with developmental delay and/or disability.

Conclusion: Supported and therapeutic playgroups emerged as a valuable model for parents of children with developmental delays and/or disabilities but require an interplay of specific facilitator, parent and child characteristics to be effective. This study contributes to the understanding of key components of successful supported and therapeutic playgroup models, highlighting the importance of engaging consumers in developing evidence-based meaningful interventions for children with developmental delay and/or disabilities and their families.
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http://dx.doi.org/10.1111/1440-1630.12708DOI Listing
November 2020

Investigating associations between birth order and autism diagnostic phenotypes.

J Child Psychol Psychiatry 2020 Nov 8. Epub 2020 Nov 8.

Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.

Background: Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First- and later-born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample.

Methods: Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1-18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling's birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity.

Results: Adaptive functioning and intelligence scores decreased with increasing birth order, with later-born children more likely to have an intellectual disability. Compared to first-born children with siblings, first-born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning.

Conclusions: These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.
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http://dx.doi.org/10.1111/jcpp.13349DOI Listing
November 2020

Randomised Controlled Trial of a Therapeutic Playgroup for Children with Developmental Delays.

J Autism Dev Disord 2020 Jul 4. Epub 2020 Jul 4.

School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia.

A single-blind randomised control trial investigated the effectiveness of the Learn, Engage and Play (LEaP) playgroup. Seventy-one children with developmental delay were randomly allocated to an 8-week LEaP playgroup or control group and followed up at 12 and 28 weeks. On the primary outcome measure, LEaP demonstrated significant within group changes at 28 weeks (parenting distress p = 0.018) but no between group changes. On secondary outcome measures, at 12 weeks LEaP produced significantly better outcomes than control in goal achievement (performance p = 0.022; function p = 0.008) and family-support (p = 0.024), with LEaP continuing to demonstrate significantly better goal achievement (child performance p = 0.042; function p = 0.012) at 28 weeks. Findings indicate LEaP may assist in improving family-support and goal achievement outcomes for children with developmental delays.
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http://dx.doi.org/10.1007/s10803-020-04580-7DOI Listing
July 2020

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population-based analysis.

J Child Psychol Psychiatry 2020 Sep 10;61(9):1030-1042. Epub 2020 Feb 10.

Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.

Objective: Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD.

Method: Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM-IV-TR criteria on a 4-point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms.

Results: The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non-significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests.

Conclusions: The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.
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http://dx.doi.org/10.1111/jcpp.13203DOI Listing
September 2020

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial.

JAMA 2019 10;322(16):1561-1569

University of Sydney School of Medicine, Sydney, New South Wales, Australia.

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain.

Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders.

Design, Setting, And Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017.

Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks.

Main Outcomes And Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables.

Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21).

Conclusions And Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference.

Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.
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http://dx.doi.org/10.1001/jama.2019.14685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806436PMC
October 2019

Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort.

Autism Res 2020 02 18;13(2):298-306. Epub 2019 Oct 18.

Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.

Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged ≤6 years (N = 2,084; 81.2% males, 18.8% females). Prevalence of motor difficulties was quantified based on scores from the motor domain of the Vineland and then compared to other domains of functioning within the Vineland (communication, daily living, and socialization), the DSM criteria, intellectual level, age, and gender. Scores on the Vineland indicated that 35.4% of the sample met criteria for motor difficulties (standard score <70), a rate almost as common as intellectual impairment (37.7%). Motor difficulties were reported by diagnosing clinicians in only 1.34% of cases. Motor difficulties were common in those cases meeting diagnostic criteria for impairments in nonverbal behavior and the presence of restricted and repetitive behaviors. The prevalence of motor difficulties also increased with increasing age of diagnosis (P < 0.001). Findings from the present study highlight the need for further consideration of motor difficulties as a distinct specifier within the diagnostic criteria for ASD. Autism Res 2020, 13: 298-306. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this population-based cohort that included 2,084 children with autism aged ≤6 years, over one-third met the criteria for motor difficulties, a rate almost as common as intellectual disability. This study demonstrates that motor difficulties are a prominent feature of the autism phenotype requiring further consideration in both the diagnostic criteria and evaluation of autism.
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http://dx.doi.org/10.1002/aur.2230DOI Listing
February 2020

Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial.

Lancet Child Adolesc Health 2019 09 16;3(9):605-615. Epub 2019 Jul 16.

Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia.

Background: Great interest exists in the potential efficacy of prediagnostic interventions within the autism spectrum disorder prodrome, but available evidence relates to children at high familial risk. We aimed to test the efficacy of a pre-emptive intervention designed for infants showing early behavioural signs of autism spectrum disorder.

Methods: In this single-blind, randomised controlled trial done at two specialist centres in Australia, infants aged 9-14 months were enrolled if they were showing at least three early behavioural signs of autism spectrum disorder on the Social Attention and Communication Surveillance-Revised (SACS-R) 12-month checklist. Infants were randomly assigned (1:1) to receive a parent-mediated video-aided intervention (iBASIS-VIPP) or treatment as usual. Group allocation was done by minimisation, stratified by site, sex, age, and the number of SACS-R risk behaviours. Assessments were done at baseline (before treatment allocation) and at the 6 month endpoint. The primary outcome was Autism Observation Scale for Infants (AOSI), which measures early behavioural signs associated with autism spectrum disorder. Secondary outcomes were a range of infant and caregiver outcomes measured by Manchester Assessment of Caregiver-Infant interaction (MACI), Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd edition (VABS-2), MacArthur-Bates Communicative Development Inventory (MCDI), and Parenting Sense of Competence (PSOC) scale. This trial is registered with Australian New Zealand Clinical Trials Registry, number ANZCTR12616000819426.

Findings: Between June 9, 2016, and March 30, 2018, 103 infants were randomly assigned, 50 to the iBASIS-VIPP group and 53 to the treatment-as-usual group. After the intervention, we observed no significant differences between groups on early autism spectrum disorder behavioural signs measured by the AOSI (difference estimate -0·74, 95% CI -2·47 to 0·98). We also observed no significant differences on secondary outcomes measuring caregiver non-directiveness (0·16, -0·33 to 0·65), caregiver sensitive responding (0·24, -0·15 to 0·63), and infant attentiveness (-0·19, -0·63 to 0·25) during parent-child interactions (MACI), as well as on researcher-administered measures of receptive (1·30, -0·48 to 3·08) and expressive language (0·54, -0·73 to 1·80), visual reception (0·31, -0·77 to 1·40), and fine motor skills (0·55, -0·32 to 1·41) using the MSEL. Compared with the treatment-as-usual group, the iBASIS-VIPP group had lower infant positive affect (-0·69, -1·27 to -0·10) on the MACI, but higher caregiver-reported receptive (37·17, 95% CI 10·59 to 63·75) and expressive vocabulary count (incidence rate ratio 2·31, 95% CI 1·22 to 4·33) on MCDI, and functional language use (difference estimate 6·43, 95% CI 1·06 to 11·81) on VABS. There were no significant group differences on caregiver-reported measures of MCDI infant gesture use (3·22, -0·60 to 7·04) and VABS social behaviour (3·28, -1·43 to 7·99). We observed no significant differences between groups on self-reported levels of parenting satisfaction (difference estimate 0·21, 95% CI -0·09 to 0·52), interest (-0·23, -0·62 to 0·16) and efficacy (-0·08, -0·38 to 0·22) on PSOC.

Interpretation: A pre-emptive intervention for the autism spectrum disorder prodrome had no immediate treatment effect on early autism spectrum disorder symptoms, the quality of parent-child interactions, or researcher-administered measures of developmental skills. However, we found a positive effect on parent-rated infant communication skills. Ongoing follow-up of this infant cohort will assess longer-term developmental effects.

Funding: Western Australia Children's Research Fund, Autism Cooperative Research Centre, La Trobe University, and Angela Wright Bennett Foundation.
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http://dx.doi.org/10.1016/S2352-4642(19)30184-1DOI Listing
September 2019

The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis.

Autism 2020 01 19;24(1):221-232. Epub 2019 Jun 19.

Telethon Kids Institute, The University of Western Australia, Australia.

'High functioning autism' is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants ( = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence ( = 1041) or absence ( = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group's adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that 'high functioning autism' is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice.
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http://dx.doi.org/10.1177/1362361319852831DOI Listing
January 2020

Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.

Mol Genet Genomic Med 2019 02 4;7(2):e00507. Epub 2019 Jan 4.

Curtin Health Innovation Research Institute and Sarich Neuroscience Institute, Curtin University, Crawley, Western Australia, Australia.

Background: Chromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.2 genomic disorder region.

Methods: We describe thirteen individuals from six families, each with atypical nested duplications within the central 22q11.2 region between LCR22B and LCR22D. We then compared the molecular and clinical data for patients from this study and the few reported atypical duplication cases, to the cases with larger typical duplications between LCR22A and LCR22D. Further, we analyzed genes with the nested region to identify candidates highly enriched in human brain tissues.

Results: We observed that atypical nested duplications are heterogeneous in size, often familial, and associated with incomplete penetrance and highly variable clinical expressivity. We found that the nested atypical duplications are a possible risk factor for neurodevelopmental phenotypes, particularly for autism spectrum disorder (ASD), speech and language delay, and behavioral abnormalities. In addition, we analyzed genes within the nested region between LCR22B and LCR22D to identify nine genes (ZNF74, KLHL22, MED15, PI4KA, SERPIND1, CRKL, AIFM3, SLC7A4, and BCRP2) with enriched expression in the nervous system, each with unique spatiotemporal patterns in fetal and adult brain tissues. Interestingly, PI4KA is prominently expressed in the brain, and this gene is included either partially or completely in all of our subjects.

Conclusion: Our findings confirm variable expressivity and incomplete penetrance for atypical nested 22q11.2 duplications and identify genes such as PI4KA to be directly relevant to brain development and disorder. We conclude that further work is needed to elucidate the basis of variable neurodevelopmental phenotypes and to exclude the presence of a second disorder. Our findings contribute to the genotype-phenotype data for atypical nested 22q11.2 duplications, with implications for genetic counseling.
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http://dx.doi.org/10.1002/mgg3.507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393688PMC
February 2019

What makes playgroups therapeutic? A scoping review to identify the active ingredients of therapeutic and supported playgroups.

Scand J Occup Ther 2019 Mar 9;26(2):81-102. Epub 2018 Oct 9.

a School of Occupational Therapy, Social Work and Speech Pathology , Curtin University , Perth , Australia.

Background: Supported and therapeutic playgroups aim to support and strengthen vulnerable children and families by increasing parenting capacity, parent-child interaction, enhancing child outcomes and promoting community networks. This review aimed to comprehensively scope the literature to identify the "active ingredients" of supported and therapeutic playgroups.

Method: A systematic search of grey and scholarly literature was conducted using Medline, PyschINFO, EMBASE, ERIC, CINAHL, MedNar, Informit, Scopus, Libraries of Australia and Trove. Articles were included if they: i) defined playgroup as a group of children and actively involved caregivers; ii) described a therapeutic playgroup or supported playgroup model; iii) targeted children prior to school age; and iv) measured the impact of playgroups. A total of 36 articles met the inclusion criteria. Qualitative data was synthesised using a meta-ethnography approach with findings charted against a conceptual model of engagement. Quantitative data was synthesised using descriptive statistics.

Results: The findings identified that emotional, practical and informational components of playgroups strongly reflect family centred practice, self-efficacy theory and peer-support principles.

Conclusion: Therapeutic and supported playgroups are complex interventions, with numerous interacting components that make them beneficial for children and families. This review is the first to identify the "active ingredients" of playgroups with findings informing the design of future playgroups for vulnerable children and families.
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http://dx.doi.org/10.1080/11038128.2018.1498919DOI Listing
March 2019

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder.

Mol Autism 2017 2;8:63. Epub 2017 Dec 2.

Autism Clinic for Translational Research, Brain and Mind Centre, Central Clinical School, Sydney Medical School, University of Sydney, 100 Mallett Street, Camperdown, New South Wales 2050 Australia.

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits.

Methods: Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD.

Results: Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1β, IL-8, MIP-1β, and VEGF, in females, but not in males.

Conclusions: Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD.
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http://dx.doi.org/10.1186/s13229-017-0176-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5712192PMC
February 2018

Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses.

Autism Res 2017 Jan 19;10(1):179-187. Epub 2017 Jan 19.

Telethon Kids Institute, The University of Western Australia, 100 Roberts Rd, Subiaco, 6009, Western Australia, Australia.

The increasing prevalence of Autism Spectrum Disorders (ASD) may in part be due to a shift in the diagnostic threshold that has led to individuals with a less severe behavioral phenotype receiving a clinical diagnosis. This study examined whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder. Data were from a prospective register of new diagnoses in Western Australia (n = 1252). From 2000 to 2006, we examined differences in both the percentage of newly diagnosed cases that met each criterion as well as severity ratings of the behaviors observed (not met, partially met, mild/moderate and extreme). Linear regression determined there was a statistically significant reduction from 2000 to 2006 in the percentage of new diagnoses meeting two of 12 criteria. There was also a reduction across the study period in the proportion of new cases rated as having extreme severity on six criteria. There was a reduction in the proportion of individuals with three or more criteria rated as extreme from 2000 (16.0%) to 2006 (1.6%), while percentage of new cases with no "extreme" rating on any criteria increased from 58.5% to 86.6% across the same period. This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria. A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses. Autism Res 2017, 10: 179-187. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/aur.1740DOI Listing
January 2017

Obesity and associated factors in youth with an autism spectrum disorder.

Autism 2016 11 17;20(8):916-926. Epub 2016 Feb 17.

Telethon Kids Institute, Australia.

Weight status on children and youth with autism spectrum disorder is limited. We examined the prevalence of overweight/obesity in children and youth with autism spectrum disorder, and associations between weight status and range of factors. Children and youth with autism spectrum disorder aged 2-16 years (n = 208) and their parents participated in this study. Body mass index was calculated using the Centers for Disease Control and Prevention growth charts and the International Obesity Task Force body mass index cut-offs. The Autism Diagnostic Observation Schedule was administered. Parents completed questionnaires about socio-demographics, diagnosed comorbidities, sleep disturbances, social functioning and medication of youth with autism spectrum disorder. The prevalence of overweight/obesity in participants with autism spectrum disorder was 35%. One quarter of obese children and youth (25.6%) had obese parents. There was a significant association between children and youth's body mass index and maternal body mass index (r = 0.25, n = 199, p < 0.001). The gender and age, parental education, family income, ethnicity, autism spectrum disorder severity, social functioning, psychotropic and complementary medication use of children and youth with autism spectrum disorder were not statistically associated with their weight status. Findings suggest the need for clinical settings to monitor weight status of children and youth with autism spectrum disorder in a bid to manage or prevent overweight/obesity in this population. Incorporating a family system approach to influence health behaviours among children and youth with autism spectrum disorder especially for specific weight interventions is warranted and should be further explored.
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http://dx.doi.org/10.1177/1362361315616345DOI Listing
November 2016

Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism.

Trials 2014 Jun 16;15:230. Epub 2014 Jun 16.

Centre for Research into Adolescent's Health (CRASH), Sydney Children's Hospital Network, Westmead Sydney Medical School, The University of Sydney, Hawkesbury Road, 2145 Sydney, Australia.

Background: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored.

Methods/design: The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government's National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression.

Discussion: The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD.

Trial Registration: Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.
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http://dx.doi.org/10.1186/1745-6215-15-230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067505PMC
June 2014

A "bottom-up" approach to aetiological research in autism spectrum disorders.

Front Hum Neurosci 2013 19;7:606. Epub 2013 Sep 19.

School of Psychology, The University of Western Australia , Perth, WA , Australia ; Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia , Perth, WA , Australia.

Autism spectrum disorders (ASD) are currently diagnosed in the presence of impairments in social interaction and communication, and a restricted range of activities and interests. However, there is considerable variability in the behaviors of different individuals with an ASD diagnosis. The heterogeneity spans the entire range of IQ and language abilities, as well as other behavioral, communicative, and social functions. While any psychiatric condition is likely to incorporate a degree of heterogeneity, the variability in the nature and severity of behaviors observed in ASD is thought to exceed that of other disorders. The current paper aims to provide a model for future research into ASD subgroups. In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively. The findings from this "proof of principle" paper provide support for this "bottom-up" approach as a feasible method for creating homogenous groups.
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http://dx.doi.org/10.3389/fnhum.2013.00606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777013PMC
September 2013

Brief report: do the nature of communication impairments in autism spectrum disorders relate to the broader autism phenotype in parents?

J Autism Dev Disord 2013 Dec;43(12):2984-9

Neurocognitive Developmental Unit, School of Psychology, University of Western Australia, M304, 35 Stirling Highway, Crawley, WA, 6009, Australia,

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband communication difficulties. ASD probands with at least one BAP parent (identified using the Autism Spectrum Quotient) had greater structural and pragmatic language difficulties (assessed using the Children's Communication Checklist-2) than ASD probands with no BAP parent. This finding provides support for the position that genetic liability for ASD is associated with increased communication difficulties across structural and pragmatic domains.
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http://dx.doi.org/10.1007/s10803-013-1838-3DOI Listing
December 2013

Recording a history of alcohol use in pregnancy: an audit of knowledge, attitudes and practice at a child development service.

J Popul Ther Clin Pharmacol 2012 23;19(2):e227-33. Epub 2012 Jun 23.

Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia.

Aims: To assess the effectiveness of alcohol documentation, examining medical correspondence and medical files of patients referred to the State Child Development Service (SCDS) and (ii) To measure the knowledge, attitudes and clinical practice of health practitioners working at the child development service (CDS) in relation to asking about alcohol use in pregnancy.

Methods: Written documentation for children attending the State Child Development Centre (SCDC) in Western Australia were examined for documentation of alcohol use during pregnancy; a random sample of 40 medical records were examined and all correspondence authored by every paediatrician for the calendar year 2006 (n=210) were reviewed. (ii) A survey was completed of staff at the CDS, to assess their knowledge, attitudes, and clinical practice and their perceived importance of asking about alcohol and other drug use.

Results: Review of all written documentation, of both files and paediatric correspondence, found only three letters recording alcohol use in pregnancy; two of the letters recorded the index child displaying stigmata consistent with prenatal alcohol exposure, yet Fetal Alcohol Spectrum Disorders (FASD) were not considered within the concluding differential diagnoses. 56% of responding CDS staff (73% response) agreed it was important to ask about alcohol use when taking a pregnancy history, 20% indicated they routinely asked about alcohol exposure and 35% of staff said they never asked about alcohol use. 60% of the CDS staff completing the survey would welcome a proven technique to ask about alcohol use.

Conclusions: There is a gap in clinical practice within this CDS in asking and/or recording information about alcohol use in pregnancy. The majority of CDS staff who completed the survey agreed that asking about alcohol use in pregnancy was important and welcomed a proven technique to do so.
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November 2012

Intravenous secretin for autism spectrum disorders (ASD).

Cochrane Database Syst Rev 2012 Apr 18(4):CD003495. Epub 2012 Apr 18.

Department of DevelopmentalMedicine, Royal Children’sHospital, Parkville, Australia.

Background: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence.

Objectives: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005.

Search Methods: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies.

Selection Criteria: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported.

Data Collection And Analysis: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms.

Main Results: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD.

Authors' Conclusions: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.
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http://dx.doi.org/10.1002/14651858.CD003495.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154585PMC
April 2012

No association between early gastrointestinal problems and autistic-like traits in the general population.

Dev Med Child Neurol 2011 May 21;53(5):457-62. Epub 2011 Mar 21.

Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Crawley, WA, Australia.

Aim: The aim of this study was to determine whether gastrointestinal problems in early childhood relate to autistic-like traits in a general population sample.

Method: The parents of 804 children (442 females; 362 males) reported at 1-, 2-, 3-, and 5-year follow-ups whether their child had been taken to a hospital, general practitioner, or health clinic for any of five gastrointestinal symptoms: (1) constipation; (2) diarrhoea; (3) abdominal bloating, discomfort, or irritability; (4) gastro-oesophageal reflux or vomiting; and (5) feeding issues or food selectivity. Parents also reported whether their child had received the measles, mumps, and rubella vaccination. Autistic-like traits were measured when the children had reached early adulthood (mean age 19 y 7 mo; SD 0.63 y) using a self-report questionnaire, the Autism Spectrum Quotient (AQ).

Results: There was no statistically significant difference in AQ scores between those who had (n=133) and those who had not (n=671) experienced early gastrointestinal symptoms. χ(2) analyses revealed that the children with early gastrointestinal problems were no more likely to be represented in the upper quintile of scores on any of the AQ scales. The measles, mumps, and rubella vaccination was unrelated to gastrointestinal symptoms or AQ scores.

Interpretation: Parent-reported gastrointestinal problems in early childhood are unrelated to self-reported autistic-like traits in the general population.
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http://dx.doi.org/10.1111/j.1469-8749.2011.03915.xDOI Listing
May 2011

Digestive enzyme supplementation for autism spectrum disorders: a double-blind randomized controlled trial.

J Autism Dev Disord 2010 Sep;40(9):1131-8

State Child Development Centre, West Perth, WA, Australia.

To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating Scales, Additional Rating Scales of other symptoms by parents and therapists, and monthly completion of the Rescorla Language Development Survey. Compared with placebo, treatment with enzyme was not associated with clinically significant improvement in behaviour, food variety, gastrointestinal symptoms, sleep quality, engagement with therapist, or the Language Development Survey Vocabulary or Sentence Complexity Scores. A small statistically significant improvement on enzyme therapy was seen for the food variety scores. No clinically significant effect improvement of autism symptoms with enzyme use was shown with this trial, however, possible effects on improvement in food variety warrants further detailed investigation.
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http://dx.doi.org/10.1007/s10803-010-0974-2DOI Listing
September 2010

The prevalence of autism in Australia. Can it be established from existing data?

J Paediatr Child Health 2008 Sep 28;44(9):504-10. Epub 2008 Jun 28.

Sydney Children's Hospital, Sydney, Australia.

Aim: To assess whether existing data collection mechanisms can provide accurate and sufficient information about the prevalence of autism in Australia.

Methods: Summary data about the number of children aged 0-16 years known to have an autism spectrum disorder (ASD) were gathered from State and Territory health, disability, education sources and autism associations. Summary data were also provided by national sources. Initial contact was made by letter, and follow-up was undertaken by telephone or email.

Results: For the years 2003-2004, the estimated prevalence of autism for 6- to 12-year-olds ranged from 9.6 to 40.8/10 000 for the State and Territory data, and from 12.1 to 35.7/10 000 for the national data. There was a similar variation in prevalence estimates for children aged 0-5 and 13-16 years. There was also a variation in prevalence estimates between age groups.

Conclusion: Inconsistencies in autism prevalence estimates calculated from existing data sources suggest that further efforts are needed to ensure the collection of reliable information about the prevalence of ASD for national, State and Territory use. Existing data systems need to be improved or additional data systems need to be developed to ensure the collection of reliable information. Reliable and consistent ASD prevalence data would ensure that services are being provided to those who need them and would enhance the opportunities to undertake meaningful population-based research.
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http://dx.doi.org/10.1111/j.1440-1754.2008.01331.xDOI Listing
September 2008

Oppositional defiant disorder.

Aust Fam Physician 2008 Jun;37(6):402-5

State Child Development Centre, Western Australia.

Background: Oppositional defiant disorder (ODD) is defined as a repetitive and persistent pattern of opposition, defiant, disobedient and disruptive behaviours toward authority figures persisting for at least 6 months.

Objective: This article reviews the nature of ODD, its relationship to attention deficit hyperactivity disorder and conduct disorder, and considers the management options available to general practitioners.

Discussion: Many of the behaviours required to meet this diagnosis are not uncommon in the preschool child or adolescent. However, in children with ODD the behaviours are persistent, cause significant distress to the family system, and impact on the child's social and educational functioning. Oppositional defiant disorder usually presents in the preschool years, although it may become evident during adolescence. There is strong evidence that early intervention to increase positive factors in family relationships and to increase both the parents' and child's skill levels can assist in the prevention of more serious disorders and mental health issues.
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June 2008

Management of assessments and diagnoses for children with autism spectrum disorders: the Western Australian model.

Med J Aust 2008 Mar;188(5):288-91

Telethon Institute for Child Health Research, School of Population Health, University of Western Australia, and Child and Adolescent Health Service, Princess Margaret Hospital for Children, Perth, WA, Australia.

Autism spectrum disorders (ASDs) are severe developmental conditions that require specialised intervention and lifelong support. Recent increases in ASD prevalence have prompted new initiatives in Western Australia to improve the consistency of assessments and to more accurately monitor diagnostic trends within the population. WA has implemented statewide guidelines for the assessment of ASDs, has developed an open forum for clinicians to discuss issues relating to the assessment process, and supports a statewide register of newly diagnosed cases. These initiatives have led to improved consistency across assessments, allowed analysis of diagnoses over time, and promoted cohesiveness among autism assessors. These strategies potentially provide an alternative model for other states and territories that wish to strengthen and assimilate ASD assessments.
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http://dx.doi.org/10.5694/j.1326-5377.2008.tb01623.xDOI Listing
March 2008

Dental restoration with amalgam was not worse than resin composite material for children's health.

Authors:
John Wray

Evid Based Med 2006 Dec;11(6):183

Childrens Health Service, Perth, Western Australia, Australia.

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http://dx.doi.org/10.1136/ebm.11.6.183DOI Listing
December 2006

Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment.

Proc Natl Acad Sci U S A 2006 Nov 9;103(47):17713-7. Epub 2006 Nov 9.

Max Planck Institute of Molecular Physiology, Department of Physical Biochemistry, 44227 Dortmund, Germany.

Myosin II is the major component of the muscle thick filament. It consists of two N-terminal S1 subfragments ("heads") connected to a long dimeric coiled-coil rod. The rod is in itself twofold symmetric, but in the filament, the two heads point away from the filament surface and are therefore not equivalent. This breaking of symmetry requires the initial section of the rod, subfragment 2 (S2), to be relatively flexible. S2 is an important functional element, involved in various mechanisms by which the activity of smooth and striated muscle is regulated. We have determined crystal structures of the 126 N-terminal residues of S2 from human cardiac beta-myosin II (S2-Delta), of both WT and the disease-associated E924K mutant. S2-Delta is a straight parallel dimeric coiled coil, but the N terminus of one chain is disordered in WT-S2-Delta due to crystal contacts, indicative of unstable local structure. Bulky noncanonical side chains pack into a/d positions of S2-Delta's N terminus, leading to defined local asymmetry and axial stagger, which could induce nonequivalence of the S1 subfragments. Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state. The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C.
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http://dx.doi.org/10.1073/pnas.0606741103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693812PMC
November 2006

7. Language disorders and autism.

Med J Aust 2005 Apr;182(7):354-60

c/o State Child Development Centre, Women's and Children's Health Service, West Perth, WA, Australia.

Early diagnosis of language disorders and autism is important, and early intervention for autism and some language disorders makes a difference. Developmental surveillance of children to detect these disorders should be a routine part of medical practice. The persistence and pervasiveness of communication and socialising deficits differentiate children with autism from those with specific developmental language disorders. Hearing and vision assessment is essential in any communication disorder. Interventions, targeted to identified areas of need, should encompass communication enhancement, behavioural therapy, educational modification, parent education and family support. Pharmacological interventions have an important but discrete role in autism, but there are no magic bullets. It is important to remember that the normal childhood illnesses occur in children with developmental disorders. Parents should be directed to reliable websites on the Internet, and given information and books to read as well as phone numbers of relevant services (eg, autism associations). There is a need for increased government financial support for early intervention programs.
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http://dx.doi.org/10.5694/j.1326-5377.2005.tb06737.xDOI Listing
April 2005

Incidence of autism spectrum disorders in children in two Australian states.

Med J Aust 2005 Feb;182(3):108-11

Children's Hospital at Westmead, Sydney, NSW.

Aim: To ascertain the incidence of autism spectrum disorders in Australian children.

Setting: New South Wales (NSW) and Western Australia (WA), July 1999 to December 2000.

Design: Data were obtained for WA from a prospective register and for NSW by active surveillance.

Main Outcome Measures: Newly recognised cases of autism spectrum disorders (defined as autistic disorder, Asperger disorder and pervasive developmental disorder not otherwise specified [PDD-NOS]) in children aged 0-14 years; incidence was estimated in 5-year age bands (0-4 years, 5-9 years, 10-14 years).

Results: In WA, 252 children aged 0-14 years were identified with autism spectrum disorder (169 with autistic disorder and 83 with Asperger disorder or PDD-NOS). Comparable figures in NSW were 532, 400 and 132, respectively. Most children were recognised with autistic disorder before school age (median age, 4 years in WA and 3 years in NSW). Incidence of autistic disorder in the 0-4-years age group was 5.5 per 10,000 in WA (95% CI, 4.5-6.7) and 4.3 per 10,000 in NSW (95% CI, 3.8-4.8). Incidence was lower in older age groups. The ratio of all autism spectrum disorders to autistic disorder alone was 1.5:1 in WA and 1.3:1 in NSW, and rose with age (1.8:1 and 2.9:1 in 10-14-year-olds in WA and NSW, respectively).

Conclusions: These are the first reported incidence rates for autism for a large Australian population and are similar to rates reported from the United Kingdom. Ongoing information gathering in WA and repeat active surveillance in NSW will help to monitor any future changes.
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http://dx.doi.org/10.5694/j.1326-5377.2005.tb06608.xDOI Listing
February 2005

The serine acetyltransferase gene family in Arabidopsis thaliana and the regulation of its expression by cadmium.

Plant Mol Biol 2003 Mar;51(4):589-98

Agriculture and Environment Division, IACR-Rothantsted, Harpenden, Hertfordshire, AL5 2JQ, UK.

Expression of the serine acetyltransferase (SAT) gene family from Arabidopsis thaliana was investigated in response to treatment with the heavy metal cadmium (Cd). A fourth member of the SAT gene family, Sat-106, was also cloned and the complete SAT gene family from A. thaliana is discussed. Northern analysis of the gene family revealed tissue-specific expression patterns for each isogene. A. thaliana plants grown under 50 microM CdCl2 for a 24 h time course were also used for northern analysis. Expression of all SAT genes was increased to some extent by Cd treatment. Sat-5 expression showed particularly high levels of induction in the leaves of treated plants and was chosen for study by in situ hybridisation. Sat-5 expression was induced in the root and stem cortex and the leaf lamella and trichomes in response to heavy metal stress. SAT and its product O-acetylserine have previously been shown to be implicated in the control of sulphate reduction and cysteine biosynthesis in plants. These results suggest that specific SAT isoforms have a role in increasing cysteine production under conditions of heavy-metal stress when increased biosynthesis of glutathione and phytochelatins is required for detoxification purposes.
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http://dx.doi.org/10.1023/a:1022349623951DOI Listing
March 2003

Gamma-amido-ATP stabilizes a high-fluorescence state of myosin subfragment 1.

FEBS Lett 2002 May;518(1-3):97-100

Abteilung Biophysik, Max-Planck-Institut für Medizinische Forschung, Jahnstr. 29, 69120, Heidelberg, Germany.

On binding to myosin subfragment 1 (S1), the gamma-amido derivative of ATP (ATPgammaNH2), an isomer of adenosine 5'-[beta,gamma-imido]-triphosphate (AMPPNP), induces a larger increase in the intrinsic (tryptophan) fluorescence than is seen with ATP. A binding constant of 1.7x10(7) M(-1) was measured for ATPgammaNH2, compared to 2.1-2.4x10(7) M(-1) for AMPPNP. ATPgammaNH2 was hydrolyzed only very slowly by S1. ATPgammaNH2 appears to stabilize the 'closed' conformation of S1, and does so without cleavage of the beta-gamma phosphate bond. The dissociation of actin-S1 by ATPgammaNH2 and that of S1.ATPgammaNH2 by actin are both strikingly slow.
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http://dx.doi.org/10.1016/s0014-5793(02)02654-6DOI Listing
May 2002