| 1. |
- Charman, Tony, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : clinical characterisation.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers.METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms.RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females.CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials.
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| 2. |
- Loth, Eva, et al.
(författare)
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The EU-AIMS Longitudinal European Autism Project (LEAP) : design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders.
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD.METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability.RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted).CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.
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| 3. |
- Mason, L., et al.
(författare)
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Preference for biological motion is reduced in ASD : implications for clinical trials and the search for biomarkers
- 2021
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Ingår i: Molecular Autism. - : Springer Nature. - 2040-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology.Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL).Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline.Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons.Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.
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| 4. |
- Gutierrez, Julian, et al.
(författare)
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Nash Equilibrium and Bisimulation Invariance
- 2019
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Ingår i: Logical Methods in Computer Science. - 1860-5974. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Game theory provides a well-established framework for the analysis of concurrent and multi-agent systems. The basic idea is that concurrent processes (agents) can be understood as corresponding to players in a game; plays represent the possible computation runs of the system; and strategies define the behaviour of agents. Typically, strategies are modelled as functions from sequences of system states to player actions. Analysing a system in such a setting involves computing the set of (Nash) equilibria in the concurrent game. However, we show that, with respect to the above model of strategies (arguably, the "standard" model in the computer science literature), bisimilarity does not preserve the existence of Nash equilibria. Thus, two concurrent games which are behaviourally equivalent from a semantic perspective, and which from a logical perspective satisfy the same temporal logic formulae, may nevertheless have fundamentally different properties (solutions) from a game theoretic perspective. Our aim in this paper is to explore the issues raised by this discovery. After illustrating the issue by way of a motivating example, we present three models of strategies with respect to which the existence of Nash equilibria is preserved under bisimilarity. We use some of these models of strategies to provide new semantic foundations for logics for strategic reasoning, and investigate restricted scenarios where bisimilarity can be shown to preserve the existence of Nash equilibria with respect to the conventional model of strategies in the computer science literature.
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| 5. |
- Parsons, Simon, et al.
(författare)
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Intention reconsideration in theory and practice
- 2000
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Ingår i: Proceedings of the 14th European conference on artificial intelligence. ; , s. 378-382
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Konferensbidrag (refereegranskat)abstract
- Autonomous agents operating in complex dynamic environments need the ability to integrate robust plan execution with higher level reasoning. This paper describes work to combine low level navigation techniques drawn from mobile robotics with deliberation techniques drawn from intelligent agents. In particular, we discuss the combination of a navigation system based on fuzzy logic with a deliberator based on the belief/desire/intention (BDI) model. We discuss some of the subtleties involved in this integration, and illustrate it with an example.
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| 6. |
- Parsons, Simon, et al.
(författare)
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Robots with the best of intentions
- 1999
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Ingår i: Artificial intelligence today. - Berlin : Springer. - 3540664289 ; , s. 329-338
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Intelligent mobile robots need the ability to integrate robust navigation facilities with higher level reasoning. This paper is an attempt at combining results and techniques from the areas of robot navigation and of intelligent agency. We propose to integrate an existing navigation system based on fuzzy logic with a deliberator based on the so-called BDI model. We discuss some of the subtleties involved in this integration, and illustrate it on a simulated example. Experiments on a real mobile robot are under way
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| 7. |
- Ågotnes, Thomas, et al.
(författare)
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Knowledge and Ability
- 2015
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Ingår i: Handbook of Epistemic Logic. - : College Publications. - 9781848901582 ; , s. 543-589
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Bokkapitel (refereegranskat)abstract
- In this chapter we relate epistemic logics with logics for strategic ability developed and studied in computer science, artificial intelligence and multi-agent systems. We discuss approaches from philosophy and artificial intelligence to modelling the interaction of agents’ knowledge and abilities and then focus on concurrent game models and the alternating-time temporal logic ATL. We show how ATL enables reasoning about agents’ coalitional abilities to achieve qualitative objectives in concurrent game models, first assuming complete information and then under incomplete information and uncertainty about the structureof the game model. We then discuss epistemic extensions of ATL enabling explicit reasoning about the interaction of knowledge and strategic abilities on different epistemic levels, leading inter alia to the notion of constructive knowledge.
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