Optimization of humanized IgGs in glycoengineered Pichia pastoris.

As the fastest growing class of therapeutic proteins, monoclonal antibodies (mAbs) represent a major potential drug class. Human antibodies are glycosylated in their native state and all clinically approved mAbs are produced by mammalian cell lines, which secrete mAbs with glycosylation structures that are similar, but not identical, to their human counterparts. Glycosylation of mAbs influences their interaction with immune effector cells that kill antibody-targeted cells. Here we demonstrate that human antibodies with specific human N-glycan structures can be produced in glycoengineered lines of the yeast Pichia pastoris and that antibody-mediated effector functions can be optimized by generating specific glycoforms. Glycoengineered P. pastoris provides a general platform for producing recombinant antibodies with human N-glycosylation.

Stereotypy in young children with autism and typically developing children.

Although stereotypy is one of the key diagnostic features of autism, few studies have compared stereotypic behavior in children with autism and typically developing children. The present study employed direct observational measurement methods to assess levels of stereotypic behavior in 2-, 3- and 4-year-old children with autism or pervasive developmental disorder - not otherwise specified (PDD-NOS) and age-matched typically developing peers. Thirty children with autism or PDD-NOS and 30 typically developing children participated. Each child's performance of several early learning and play skills was assessed using a direct observational assessment protocol developed for children with autism who were entering early intensive behavioral treatment. Duration of episodes of vocal and motor stereotypy was recorded from a videotaped 10 min portion of that assessment session. Results indicated that the 2-year-old children with autism or PDD-NOS had somewhat higher levels of stereotypic behavior than the typically developing 2-year-olds, while the 3- and 4-year-old children with autism or PDD-NOS displayed substantially higher levels stereotypic behavior than their same-age peers.

Behavioral assessment of joint attention: a methodological report.

This paper describes a highly structured assessment protocol with objective behavioral measures for joint attention responding and initiation. The assessment was given to 26 children diagnosed with autism spectrum disorders and 21 typically developing children, aged two to four years. Interobserver agreement was high for all behavioral measures. Children with autism had relatively minor deficits in joint attention responding and more severe deficits in joint attention initiation, relative to typically developing children. These results replicate those reported in previous research. The protocol can be used reliably to assess behavior indicative of joint attention responding and initiation in typically developing children and children with autism.

Toward a behavioral analysis of joint attention.

Joint attention (JA) initiation is defined in cognitive-developmental psychology as a child's actions that verify or produce simultaneous attending by that child and an adult to some object or event in the environment so that both may experience the object or event together. This paper presents a contingency analysis of gaze shift in JA initiation. The analysis describes reinforcer-establishing and evocative effects of antecedent objects or events, discriminative and conditioned reinforcing functions of stimuli generated by adult behavior, and socially mediated reinforcers that may maintain JA behavior. A functional analysis of JA may describe multiple operant classes. The paper concludes with a discussion of JA deficits in children with autism spectrum disorders and suggestions for research and treatment.

Social validation of the New England Center For Children--Core Skills Assessment.

We investigated the social validity of the NECC Core Skills Assessment (NECC-CSA) with parents and professionals as participants. The NECC-CSA is a measurement tool consisting of direct and indirect measures of skills important to all individuals with autism, across the lifespan. Participants (N = 245) were provided with a list of 66 skills, 47 of which were Core Skills from the NECC-CSA, and were asked to indicate which items they considered to be foundational. Participants endorsed items from the NECC-CSA as foundational skills, more than they endorsed the other items. Differences between parents and professionals are described and detailed with respect to individual assessment items. The NECC-CSA consists of socially validated skills that can be taken as a starting point for programs of instruction for individuals with ASDs.

Using video modeling to teach reciprocal pretend play to children with autism.

The purpose of the present study was to use video modeling to teach children with autism to engage in reciprocal pretend play with typically developing peers. Scripted play scenarios involving various verbalizations and play actions with adults as models were videotaped. Two children with autism were each paired with a typically developing child, and a multiple-probe design across three play sets was used to evaluate the effects of the video modeling procedure. Results indicated that both children with autism and the typically developing peers acquired the sequences of scripted verbalizations and play actions quickly and maintained this performance during follow-up probes. In addition, probes indicated an increase in the mean number of unscripted verbalizations as well as reciprocal verbal interactions and cooperative play. These findings are discussed as they relate to the development of reciprocal pretend-play repertoires in young children with autism.