| 1. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 2. |
- Casey, Maire-Brid, et al.
(author)
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Exercise combined with Acceptance and Commitment Therapy compared with a standalone supervised exercise programme for adults with chronic pain : a randomised controlled trial
- 2022
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:6, s. 1158-1171
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Journal article (peer-reviewed)abstract
- A prospective, 2-armed, parallel group randomised controlled trial (RCT) was conducted to compare the effectiveness of Acceptance and Commitment Therapy (ACT) combined with a supervised exercise programme with a supervised exercise programme alone for adults with chronic pain. One hundred seventy-five participants were individually randomised to receive either the combined Exercise and ACT (ExACT) intervention or supervised exercise alone. Those allocated to the ExACT group attended 8 weekly sessions with a psychologist based on the ACT approach, in addition to supervised exercise classes led by a physiotherapist. The control group attended weekly supervised exercise classes but did not take part in an ACT programme. Both groups were followed up postintervention and again after 12 weeks. The primary outcome was pain interference at 12-week follow-up. Estimates of treatment effects at follow-up were based on intention-to-treat analyses, implemented using a linear mixed-effects model. The findings of this RCT showed no difference in the effectiveness of ExACT, compared with a supervised exercise programme alone for the primary outcome pain interference at 12-week follow-up (mean difference -0.18, 95% confidence interval -0.84 to 0.48, P = 0.59, d = 0.11). ExACT group participants reported superior outcomes for pain self-efficacy, pain catastrophising, and committed action, compared with the control group, but there were no differences between the groups for other secondary outcomes or treatment process measures. Higher levels of treatment satisfaction and global impression of change were reported by ExACT group participants. Exercise combined with Acceptance and Commitment Therapy was not superior to a standalone supervised exercise programme for reducing pain interference in adults with chronic pain.
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| 3. |
- Casey, Máire-Bríd, et al.
(author)
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Exercise combined with Acceptance and Commitment Therapy (ExACT) compared to a supervised exercise programme for adults with chronic pain : study protocol for a randomised controlled trial
- 2018
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 19
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Journal article (peer-reviewed)abstract
- Background: Acceptance and Commitment Therapy (ACT) is a form of cognitive behavioural therapy, which may be beneficial for people with chronic pain. The approach aims to enhance daily functioning through increased psychological flexibility. Whilst the therapeutic model behind ACT appears well suited to chronic pain, there is a need for further research to test its effectiveness in clinical practice, particularly with regards to combining ACT with physical exercise.Methods/design: This prospective, two-armed, parallel-group, single-centre randomised controlled trial (RCT) will assess the effectiveness of a combined Exercise and ACT programme, in comparison to supervised exercise for chronic pain. One hundred and sixty patients, aged 18 years and over, who have been diagnosed with a chronic pain condition by a physician will be recruited to the trial. Participants will be individually randomised to one of two 8-week, group interventions. The combined group will take part in weekly psychology sessions based on the ACT approach, in addition to supervised exercise classes led by a physiotherapist. The control group will attend weekly supervised exercise classes but will not take part in an ACT programme. The primary outcome will be pain interference at 12-week follow-up, measured using the Brief Pain Inventory-Interference Scale. Secondary outcomes will include self-reported pain severity, self-perception of change, patient satisfaction, quality of life, depression, anxiety and healthcare utilisation. Treatment process measures will include self-efficacy, pain catastrophising, fear avoidance, pain acceptance and committed action. Physical activity will be measured using Fitbit ZipTM activity trackers. Both groups will be followed up post intervention and again after 12 weeks. Estimates of treatment effects at follow-up will be based on an intention-to-treat framework, implemented using a linear mixed-effects model. Individual and focus group qualitative interviews will be undertaken with a purposeful sample of participants to explore patient experiences of both treatments.Discussion: To our knowledge, this will be the first RCT to examine whether combining exercise with ACT produces greater benefit for patients with chronic pain, compared to a standalone supervised exercise programme.Trial registration: www.ClinicalTrials.gov, ID: NCT03050528. Registered on 13 February 2017.
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| 4. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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