Early Indicators of Autism Spectrum Disorders in the Second Year of Life

Three groups of 18 children were selected for this study, one group with autism spectrum disorders (ASD), one group with developmental delays in which ASD was ruled out (DD), and one group with typical development (TD), from a pool of 3026 children who were screened with the Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP, Wetherby & Prizant, 2002) Infant-Toddler Checklist under 24 months of age. The CSBS DP Behavior Sample was videotaped on selected children as a second-level evaluation during the second year of life. The Infant-Toddler Checklist had a sensitivity and specificity of 88.9% for this sample of children. Significant group differences were found on the Infant-Toddler Checklist and the Behavior Sample, however, these differences did not distinguish children with ASD and DD with high accuracy. The videotapes of the Behavior Sample were reanalyzed to identify red flags of ASD. Nine red flags differentiated children in the ASD group from both the DD and TD groups and four red flags differentiated children in the ASD Group from the TD group but not the DD group. These 13 red flags were found to discriminate the three groups with a correct classification rate of 94.4%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44624/1/10803_2004_Article_492544.pd

Intracellular \u3cem\u3eSalmonella\u3c/em\u3e delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity

Introduction: Immunotherapies have shown great promise, but are not effective for all tumors types and are effective in less than 3% of patients with pancreatic ductal adenocarcinomas (PDAC). To make an immune treatment that is effective for more cancer patients and those with PDAC specifically, we genetically engineered Salmonella to deliver exogenous antigens directly into the cytoplasm of tumor cells. We hypothesized that intracellular delivery of an exogenous immunization antigen would activate antigen-specific CD8 T cells and reduce tumors in immunized mice. Methods: To test this hypothesis, we administered intracellular delivering (ID) Salmonella that deliver ovalbumin as a model antigen into tumor-bearing, ovalbumin-vaccinated mice. ID Salmonella delivers antigens by autonomously lysing in cells after the induction of cell invasion. Results: We showed that the delivered ovalbumin disperses throughout the cytoplasm of cells in culture and in tumors. This delivery into the cytoplasm is essential for antigen cross-presentation. We showed that co-culture of ovalbumin-recipient cancer cells with ovalbumin-specific CD8 T cells triggered a cytotoxic T cell response. After the adoptive transfer of OT-I CD8 T cells, intracellular delivery of ovalbumin reduced tumor growth and eliminated tumors. This effect was dependent on the presence of the ovalbumin-specific T cells. Following vaccination with the exogenous antigen in mice, intracellular delivery of the antigen cleared 43% of established KPC pancreatic tumors, increased survival, and prevented tumor re-implantation. Discussion: This response in the immunosuppressive KPC model demonstrates the potential to treat tumors that do not respond to checkpoint inhibitors, and the response to re-challenge indicates that new immunity was established against intrinsic tumor antigens. In the clinic, ID Salmonella could be used to deliver a protein antigen from a childhood immunization to refocus pre-existing T cell immunity against tumors. As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients

What Our Hands Say: Exploring Gesture Use in Subgroups of Children With Language Delay

Purpose The aim of this study was to investigate whether children with receptive-expressive language delay (R/ELD) and expressive-only language delay (ELD) differ in their use of gesture; to examine relationships between their use of gesture, symbolic comprehension, and language; to consider implications for assessment and for the nature of problems underlying different profiles of early language delay. Method Twelve children with ELD (8 boys, 4 girls) and 10 children with R/ELD (8 boys, 2 girls), aged 2–3 years, were assessed on measures of gesture use and symbolic comprehension. Results Performance of the R/ELD group was significantly poorer than performance of the ELD group on measures of gesture and symbolic comprehension. Gesture use and symbolic comprehension were significantly associated with receptive language, but associations with expressive language were not significant. Conclusions Findings of this study support previous research pointing to links between gesture and language development, and more specifically, between delays in gesture, symbolic understanding, and receptive rather than expressive language. Given potentially important implications for the nature of problems underlying ELD and R/ELD, and for assessment of children with language delay, this preliminary study invites further investigation comparing the use of different gesture types in samples of children matched on age and nonverbal IQ

Construction and validation of an developmental profile assessment tool for children with autistic spectrum disorder

Nos últimos anos a investigação tem dado particular relevância às alterações do Processamento Sensorial nas crianças com perturbações do espectro do autismo (PEA) e a literatura refere que entre 42% a 88% das crianças com PEA apresentam este tipo de disfunção. Nesta linha foi definido um projeto de investigação centrado na construção de uma escala que avalie a tradicional tríade que caracteriza as crianças com PEA (Interação, Comunicação e Comportamento e interesses repetitivos e estereotipados), enriquecida pela inclusão de um novo domínio: o Processamento Sensorial. Com a construção e validação desta escala pretendemos que pais e profissionais utilizem colaborativamente um instrumento de avaliação da intervenção que lhes permita monitorizar o processo de apoio e adequar as suas práticas. Neste artigo descrevemos os procedimentos e os resultados das sucessivas fases de construção do instrumento, desde as análises iniciais mais qualitativas até aos estudos centrados na análise quantitativa dos itens.During the last few years, research has focused on changes in Sensory Processing in children with Autistic Spectrum Disorder (ASD). As a result, literature has shown that between 42% and 88% of children with ASD present this type of disorder. Based on these findings, a research project was designed centring on the construction of a tool to assess the traditional triad that characterizes children with ASD (Interaction, Communication and Behaviour and Repetitive and Stereotyped Interests), to which was added a new domain: Sensory Processing. By constructing and validating this assessment tool, the intention is for parents and professionals to collaboratively apply this intervention assessment instrument in order to monitor the support process and adapt their practices. In this paper, we describe procedures and results of the successive stages entailed in constructing this instrument, from the first primarily qualitative analyses up to the studies centred on the quantitative item analysis.Fundação para a Ciência e Tecnologia (FCT)ABPEE - Associação Brasileira de Pesquisadores em Educação EspecialConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPESMinistério da Educação - BrasilMinistério da Ciência e da Tecnologia - BrasilGoverno Federal - Brasi

Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases

Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Toward Innovative, Cost-Effective, and Systemic Solutions to Improve Outcomes and Well-Being of Military Families Affected by Autism Spectrum Disorder

The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit

Play and Developmental Outcomes in Infant Siblings of Children with Autism

We observed infant siblings of children with autism later diagnosed with ASD (ASD siblings; n = 17), infant siblings of children with autism with and without other delays (Other Delays and No Delays siblings; n = 12 and n = 19, respectively) and typically developing controls (TD controls; n = 19) during a free-play task at 18 months of age. Functional, symbolic, and repeated play actions were coded. ASD siblings showed fewer functional and more non-functional repeated play behaviors than TD controls. Other Delays and No Delays siblings showed more non-functional repeated play than TD controls. Group differences disappeared with the inclusion of verbal mental age. Play as an early indicator of autism and its relationship to the broader autism phenotype is discussed

Using video modeling to teach complex social sequences to children with autism

This study comprised of two experiments was designed to teach complex social sequences to children with autism. Experimental control was achieved by collecting data using means of within-system design methodology. Across a number of conditions children were taken to a room to view one of the four short videos of two people engaging in a simple sequence of activities. Then, each child’s behavior was assessed in the same room. Results showed that this video modeling procedure enhanced the social initiation skills of all children. It also facilitated reciprocal play engagement and imitative responding of a sequence of behaviors, in which social initiation was not included. These behavior changes generalized across peers and maintained after a 1- and 2-month follow-up period

Brief Report: Question-Asking and Collateral Language Acquisition in Children with Autism

The literature suggests children with autism use communication primarily for requests and protests, and almost never for information-seeking. This study investigated whether teaching “Where” questions using intrinsic reinforcement procedures would produce the generalized use of the question, and whether concomitant improvements in related language structures, provided as answers to the children’s questions, would occur. In the context of a multiple baseline across participants design, data showed that the children could rapidly acquire and generalize the query, and that there were collateral improvements in the children’s use of language structures corresponding to the answers to the questions the children asked. The results are discussed in the context of teaching child initiations to improve linguistic competence in children with autism