What's in a voice? Prosody as a test case for the Theory of Mind account of autism

The human voice conveys a variety of information about people's feelings, emotions and mental states. Some of this information relies on sophisticated Theory of Mind (ToM) skills, whilst others are simpler and do not require ToM. This variety provides an interesting test case for the ToM account of autism, which would predict greater impairment as ToM requirements increase. In this paper, we draw on psychological and pragmatic theories to classify vocal cues according to the amount of mindreading required to identify them. Children with a high functioning Autism Spectrum Disorder and matched controls were tested in three experiments where the speakers' state had to be extracted from their vocalizations. Although our results confirm that people with autism have subtle difficulties dealing with vocal cues, they show a pattern of performance that is inconsistent with the view that atypical recognition of vocal cues is caused by impaired ToM

Children with Autism do not Show Sequence Effects with Auditory Stimuli

Categorization decisions that reflect constantly changing memory representations may be an important adaptive response to dynamic environments. We assessed one such influence from memory, sequence effects, on categorization decisions made by individuals with autism. A model of categorization (i.e. Memory and Contrast model, Stewart, Brown, & Chater, 2002) assumes that contextual influences in the form of sequence effects drive categorization performance in individuals with typical development. Difficulties with contextual processing in autism, described by the weak central coherence account (Frith, 1989; Frith & Happé, 1994) imply reduced sequence effects for this participant group. The experiment reported here tested this implication. High functioning children and adolescents with autism (aged 10 to 15 years), matched on age and IQ with typically developing children, completed a test that measures sequence effects (i.e. category contrast effect task, Stewart et al., 2002) using auditory tones. Participants also completed a pitch discrimination task to measure any potential confound arising from possible enhanced discrimination sensitivity within the ASD group. The typically developing group alone demonstrated a category contrast effect. The data suggest that this finding cannot be attributed readily to participant group differences in discrimination sensitivity, perseveration, difficulties on the associated binary categorization task, or greater reliance upon long term memory. We discuss the broad methodological implication that comparison between autism and control group responses to sequential perceptual stimuli may be confounded by the influence of preceding trials. We also discuss implications for the weak central coherence account and models of typical cognition

A reference architecture for multi-level SLA management

There is a global trend towards service-orientation, both for organizing business interactions but also in modern IT architectures. At the business-level, service industries are becoming the dominating sector in which solutions are flexibly composed out of networked services. At the IT level, the paradigms of Service-Oriented Architecture and Cloud Computing realize service-orientation for both software and infrastructure services. Again, flexible composition across different layers is a major advantage of this paradigm. Service Level Agreements (SLA) are a common approach for specifying the exact conditions under which services are to be delivered and, thus, are a prerequisite for supporting the flexible trading of services. However, typical SLAs are just specified at a single layer and do not allow service providers to manage their service stack accordingly. They have no insight on how SLAs at one layer translate to metrics or parameters at the various lower layers of the service stack. In this paper, we present a reference architecture for a multi-level SLA management framework. We discuss the fundamental concepts and detail the main architectural components and interfaces. Furthermore, we show how the framework can be flexibly used for different industrial scenarios

Developmental dynamics of two bipotent thymic epithelial progenitor types

T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. Here we combine scRNA-seq and a new CRISPR–Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity

Autism in England: assessing underdiagnosis in a population- based cohort study of prospectively collected primary care data

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59–72% of autistic people, 0.77%–2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services. Funding: Dunhill Medical Trust, Economic and Social Research Council, Medical Research Council, National Institute for Health Research, the Wellcome Trust, and the Royal College of Psychiatrists.</p

The diagnosis of mental disorders: the problem of reification

A pressing need for interrater reliability in the diagnosis of mental disorders emerged during the mid-twentieth century, prompted in part by the development of diverse new treatments. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition answered this need by introducing operationalized diagnostic criteria that were field-tested for interrater reliability. Unfortunately, the focus on reliability came at a time when the scientific understanding of mental disorders was embryonic and could not yield valid disease definitions. Based on accreting problems with the current DSM-fourth edition (DSM-IV) classification, it is apparent that validity will not be achieved simply by refining criteria for existing disorders or by the addition of new disorders. Yet DSM-IV diagnostic criteria dominate thinking about mental disorders in clinical practice, research, treatment development, and law. As a result, the modernDSMsystem, intended to create a shared language, also creates epistemic blinders that impede progress toward valid diagnoses. Insights that are beginning to emerge from psychology, neuroscience, and genetics suggest possible strategies for moving forward

Social anxiety in adult males with autism spectrum disorders

Background: Psychiatric conditions, notably anxiety, commonly co-occur with autism spectrum disorders (ASD). Method: This study investigated self-reported behavioural, cognitive and affective symptoms of social anxiety (SA) in 50 adult males with ASD. Associations between SA, core ASD symptoms and facets of neuropsychological functioning were also examined. Results: Twenty-six participants (52%) endorsed levels of SA that exceeded the suggested caseness threshold for social anxiety disorder. Categorical and dimensional data analyses indicated that there were no relationships between SA symptoms, present-state or childhood ASD symptom-severity, or measures of socio-emotional processing in this sample. Conclusions: Study findings suggest that severity of SA is not merely a reflection of ASD symptom-severity. Further research is needed to ascertain the prevalence of SA in adult ASD epidemiological samples, and identify causal and maintaining mechanisms for these co-morbid symptoms

Phylogenetic and molecular analysis of hydrogen-producing green algae

A select set of microalgae are reported to be able to catalyse photobiological H2 production from water. Based on the model organism Chlamydomonas reinhardtii, a method was developed for the screening of naturally occurring H2-producing microalgae. By purging algal cultures with N2 in the dark and subsequent illumination, it is possible to rapidly induce photobiological H2 evolution. Using NMR spectroscopy for metabolic profiling in C. reinhardtii, acetate, formate, and ethanol were found to be key compounds contributing to metabolic variance during the assay. This procedure can be used to test algal species existing as axenic or mixed cultures for their ability to produce H2. Using this system, five algal isolates capable of H2 production were identified in various aquatic systems. A phylogenetic tree was constructed using ribosomal sequence data of green unicellular algae to determine if there were taxonomic patterns of H2 production. H2-producing algal species were seen to be dispersed amongst most clades, indicating an H2-producing capacity preceded evolution of the phylum Chlorophyta

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism

Spatial interactions in agent-based modeling

Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution of economic activities, - out of equilibrium. The Eurace@Unibi Model, an agent-based macroeconomic model with spatial structure, is used to illustrate the potential of such an approach for spatial policy analysis.Comment: 26 pages, 5 figures, 105 references; a chapter prepared for the book "Complexity and Geographical Economics - Topics and Tools", P. Commendatore, S.S. Kayam and I. Kubin, Eds. (Springer, in press, 2014