Disentangling syntactic, semantic and pragmatic impairments in ASD : elicited production of passives

Children with ASD and an IQ-matched control group of typically developing (TD) children completed an elicited-production task which encouraged the production of reversible passive sentences (e.g., “Bob was hit by Wendy”). Although the two groups showed similar levels of correct production, the ASD group produced a significantly greater number of “reversal” errors (e.g., “Wendy was hit by Bob”, when, in fact Wendy hit Bob) than the TD group (who, when they did not produce correct passives, instead generally produced semantically appropriate actives; e.g., “Wendy hit Bob”). These findings suggest that the more formal elements of syntax are spared relative to more semantic/pragmatic/narrative aspects (e.g., manipulating thematic roles) in at least high-functioning children with ASD

Children Use Statistics and Semantics in the Retreat from Overgeneralization

How do children learn to restrict their productivity and avoid ungrammatical utterances? The present study addresses this question by examining why some verbs are used with un- prefixation (e.g., unwrap) and others are not (e.g., *unsqueeze). Experiment 1 used a priming methodology to examine children's (3–4; 5–6) grammatical restrictions on verbal un- prefixation. To elicit production of un-prefixed verbs, test trials were preceded by a prime sentence, which described reversal actions with grammatical un- prefixed verbs (e.g., Marge folded her arms and then she unfolded them). Children then completed target sentences by describing cartoon reversal actions corresponding to (potentially) un- prefixed verbs. The younger age-group's production probability of verbs in un- form was negatively related to the frequency of the target verb in bare form (e.g., squeez/e/ed/es/ing), while the production probability of verbs in un- form for both age groups was negatively predicted by the frequency of synonyms to a verb's un- form (e.g., release/*unsqueeze). In Experiment 2, the same children rated the grammaticality of all verbs in un- form. The older age-group's grammaticality judgments were (a) positively predicted by the extent to which each verb was semantically consistent with a semantic “cryptotype” of meanings - where “cryptotype” refers to a covert category of overlapping, probabilistic meanings that are difficult to access - hypothesised to be shared by verbs which take un-, and (b) negatively predicted by the frequency of synonyms to a verb's un- form. Taken together, these experiments demonstrate that children as young as 4;0 employ pre-emption and entrenchment to restrict generalizations, and that use of a semantic cryptotype to guide judgments of overgeneralizations is also evident by age 6;0. Thus, even early developmental accounts of children's restriction of productivity must encompass a mechanism in which a verb's semantic and statistical properties interact

Inhibitory Control Predicts Grammatical Ability

We present evidence that individual variation in grammatical ability can be predicted by individual variation in inhibitory control. We tested 81 5-year-olds using two classic tests from linguistics and psychology (Past Tense and the Stroop). Inhibitory control was a better predicator of grammatical ability than either vocabulary or age. Our explanation is that giving the correct response in both tests requires using a common cognitive capacity to inhibit unwanted competition. The implications are that understanding the developmental trajectory of language acquisition can benefit from integrating the developmental trajectory of non-linguistic faculties, such as executive control

Acquiring and processing verb argument structure : distributional learning in a miniature language

Adult knowledge of a language involves correctly balancing lexically-based and more language-general patterns. For example, verb argument structures may sometimes readily generalize to new verbs, yet with particular verbs may resist generalization. From the perspective of acquisition, this creates significant learnability problems, with some researchers claiming a crucial role for verb semantics in the determination of when generalization may and may not occur. Similarly, there has been debate regarding how verb-specific and more generalized constraints interact in sentence processing and on the role of semantics in this process. The current work explores these issues using artificial language learning. In three experiments using languages without semantic cues to verb distribution, we demonstrate that learners can acquire both verb-specific and verb-general patterns, based on distributional information in the linguistic input regarding each of the verbs as well as across the language as a whole. As with natural languages, these factors are shown to affect production, judgments and real-time processing. We demonstrate that learners apply a rational procedure in determining their usage of these different input statistics and conclude by suggesting that a Bayesian perspective on statistical learning may be an appropriate framework for capturing our findings

Single cell derived mRNA signals across human kidney tumors.

Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer

Moving liquids with light: Photoelectrowetting on semiconductors

Liquid transport in microchip-based systems is important in many areas such as Laboratory-on-a-chip, Microfluidics and Optofluidics. Actuation of liquids in such systems is usually achieved using either mechanical displacement11 or via energy conversion e.g. electrowetting which modifies wetting. However, at the moment there is no clear way of actuating a liquid using light. Here, by linking semiconductor physics and wetting phenomenon a brand new effect "photoelectrowetting" is demonstrated for a droplet of conducting liquid resting on an insulator-semiconductor stack. Optical generation of carriers in the space-charge region of the underlying semiconductor alters the capacitance of the insulator-semiconductor stack; the result of this is a modification of the wetting contact angle of the droplet upon illumination. The effect is demonstrated using commercial silicon wafers, both n- and p-type having a doping range spanning four orders of magnitude (6\times1014-8\times1018 cm-3), coated with a commercial fluoropolymer insulating film (Teflon\textregistered). Impedance measurements confirm that the observations are semiconductor space-charge related effects. The impact of the work could lead to new silicon-based technologies in the above mentioned areas

Simple mindreading abilities predict complex theory of mind: developmental delay in autism spectrum disorders

Theory of Mind (ToM) is impaired in individuals with Autism Spectrum Disorders (ASD). The aims of this study were to: i) examine the developmental trajectories of ToM abilities in two different mentalizing tasks in children with ASD compared to TD children; and ii) to assess if a ToM simple test known as Eyes-test could predict performance on the more advanced ToM task, i.e. Comic Strip test. Based on a sample of 37 children with ASD and 55 TD children, our results revealed slower development at varying rates in all ToM measures in children with ASD, with delayed onset compared to TD children. These results could stimulate new treatments for social abilities, which would lessen the social deficit in ASD

Do two and three year old children use an incremental first-NP-as-agent bias to process active transitive and passive sentences? : A permutation analysis

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investi-gated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence struc-ture conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year