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Cancer is a complex disease in which cells acquire many genetic and epigenetic alterations. We have examined how three types of alterations, mutations in tumor suppressor genes, changes in an imprinted locus, and polymorphic loci, interact to affect tumor susceptibility in a mouse model of neurofibromatosis type 1 (NF1). Mutations in tumor suppressor genes such as TP53 and in oncogenes such as KRAS have major effects on tumorigenesis due to the central roles of these genes in cell proliferation and cell survival. Imprinted genes expressed from only one parental chromosome affect tumorigenesis if their monoallelic expression is lost or duplicated. Because imprinted loci are within regions deleted or amplified in cancer, the parental origin of genomic rearrangements could affect tumorigenesis. Gene polymorphisms can vary tumor incidence by affecting rate-limiting steps in tumorigenesis within tumor cells or surrounding stroma. In our mouse model of NF1, the incidence of tumors mutant for the tumor suppressor genes Nf1 and Trp53 is strongly modified by a linked imprinted locus acting epistatically on two unlinked polymorphic loci, Nstr1 and Nstr2. This interaction of an imprinted locus and polymorphic susceptibility loci has profound implications for human mapping studies where the parental contribution of alleles is often unknown. (Cancer Res 2006; 66(1): 62-8)

Supplementary Figure 2 from An Imprinted Locus Epistatically Influences Nstr1 and Nstr2 to Control Resistance to Nerve Sheath Tumors in a Neurofibromatosis Type 1 Mouse Model

Supplementary Tables 1-2 from An Imprinted Locus Epistatically Influences Nstr1 and Nstr2 to Control Resistance to Nerve Sheath Tumors in a Neurofibromatosis Type 1 Mouse Model

Supplementary Figure 1 from An Imprinted Locus Epistatically Influences Nstr1 and Nstr2 to Control Resistance to Nerve Sheath Tumors in a Neurofibromatosis Type 1 Mouse Model

This protocol details the steps necessary to isolate circulating plasma extracellular vesicles (EVs) from human peripheral blood samples. This protocol utilizes an automated fraction collector (AFC) and qEV size-exclusion chromatography columns from IZON Science. This is intended to serve as the first step in the workflow for EV quantification along with “Measurement of extracellular vesicles with tunable resistance pulse sensing (TRPS).”

This study examined prosody through characterization of acoustic properties of the speech of individuals with ASD and their parents, during narration. A subset of utterances were low-pass filtered and rated for differences in intonation, speech rate, and rhythm. Listener ratings were minimally related to acoustic measures, underscoring the complexity of atypical prosody in ASD. Acoustic analyses revealed greater utterance-final fundamental frequency excursion size and slower speech rate in the ASD group. Slower speech rate was also evident in the ASD parent group, particularly parents with the broad autism phenotype. Overlapping prosodic differences in ASD and ASD Parent groups suggest that prosodic differences may constitute an important phenotype contributing to ASD features and index genetic liability to ASD among first-degree relatives.

Background Families of individuals with autism spectrum disorder (ASD) face distinct challenges, and there is a need for research that attends specifically to the family. Despite the recognition of reciprocal influences in the family, research on families of individuals with ASD has tended to focus on child effects within a dyadic subsystem and not necessarily family effects. Thus, this review focuses on whether and how family processes are associated with the behavioral, social, and/or emotional development of individuals with ASD. Method A scoping review was conducted to synthesize existing empirical literature regarding links from family functioning to individual outcomes. Family systems approaches are used along with ecological models to provide an inclusive, guiding framework for research design and interpretation of findings in family-based ASD research. Results Results suggest that family-wide factors such as adaptability, cohesion, social support, dynamics, and functioning may be important for child development. However, the heterogeneity of the body of literature reviewed makes definitive conclusions difficult. Conclusions Recommendations for future research, including the need for theoretically grounded, developmentally appropriate, models that highlight the unique strengths, challenges, and cultural influences of families of an individual with ASD are discussed.

Autism spectrum disorder (ASD), a condition defined along a continuum of socio-communicative difficulties, is associated with unique patterns of memory functioning including difficulties with autobiographical memory (AM). AM refers to memory for information related to the self and personally experienced events and has a strong social function. The current paper reviews empirical studies assessing AM among individuals with ASD across the lifespan. Results support that both children and adults with ASD manifest AM difficulties characterized by (a) reduced specificity, (b) less elaborated and detailed AM narratives, (c) lower AM coherence, and (d) increased reliance on scaffolding for retrieval. Individuals with ASD also demonstrate intact AM for certain memory indices and show evidence of using compensatory strategies to facilitate retrieval. Results are interpreted in relation to models of typically developing AM and broad memory theory, as well as models of information processing specific to ASD. To advance knowledge of how AM develops within the context of ASD, a developmental psychopathology perspective is applied to the consideration of candidate processes underlying developing AM among individuals with ASD. Future research should consider support for mechanisms that promote AM performance at multiple ecological levels. Limitations, clinical implications for intervention, and future directions are discussed.

In this study, we employed an eye-gaze paradigm to explore whether children (ages 8–12) and adolescents (ages 12–18) with autism spectrum disorders (ASDs) are able to use prosodic cues to determine the syntactic structure of an utterance. Persons with ASD were compared to typically developing (TD) peers matched on age, IQ, gender, and receptive language abilities. The stimuli were syntactically ambiguous but had a prosodic break that indicated the appropriate interpretation (feel the frog … with the feathervs.feel … the frog with the feather). We found that all groups were equally sensitive to the initial prosodic cues that were presented. Children and teens with ASD used prosody to interpret the ambiguous phrase as rapidly and efficiently as their TD peers. However, when a different cue was presented in subsequent trials, the younger ASD group was more likely to respond in a manner consistent with the initial prosodic cue rather than the new one. Eye-tracking data indicated that both younger groups (ASD and TD) had trouble shifting their interpretation as the prosodic cue changed, but the younger TD group was able to overcome this interference and produce an action consistent with the prosodic cue.

This pilot study evaluated a novel intervention designed to reduce social anxiety and improve social/vocational skills for adolescents with autism spectrum disorder (ASD). The intervention utilized a shared interest in robotics among participants to facilitate natural social interaction between individuals with ASD and typically developing (TD) peers. Eight individuals with ASD and eight TD peers ages 12-17 participated in a weeklong robotics camp, during which they learned robotic facts, actively programmed an interactive robot, and learned "career" skills. The ASD group showed a significant decrease in social anxiety and both groups showed an increase in robotics knowledge, although neither group showed a significant increase in social skills. These initial findings suggest that this approach is promising and warrants further study.

This study examined the measurement tools and target symptoms/skills used to assess treatment response during Autism Spectrum Disorder (ASD) intervention trials from 2001 through 2010. Data from 195 prospective trials were analyzed. There were 289 unique measurement tools, of which 61.6 % were used only once, and 20.8 % were investigator-designed. Only three tools were used in more than 2 % of the studies, and none were used in more than 7 % of studies. Studies investigated an average of 11.4 tool-symptom combinations per trial, with as many as 45 in one study. These results represent a lack of consistency in outcome measurements in ASD intervention trials. These findings highlight the need to set guidelines for appropriate outcome measurement in the ASD field.

Prosody production atypicalities are a feature of autism spectrum disorders (ASDs), but behavioral measures of performance have failed to provide detail on the properties of these deficits. We used acoustic measures of prosody to compare children with ASDs to age-matched groups with learning disabilities and typically developing peers. Overall, the group with ASD had longer utterance durations on multiple subtests on a test of prosodic abilities, and both the ASD and learning disabilities groups had higher pitch ranges and pitch variance than the typically developing group on one subtest. Acoustic differences were present even when the prosody was used correctly. These findings represent differences in the fine details of the acoustic output beyond its functional interpretation inbothclinical groups.

This paper examined the fundamental frequency variation in the narratives of individuals with high-functioning autism (HFA) and typical controls matched on age, IQ, and verbal abilities. Study 1 found increased fundamental frequency variation in the speech of 21 children and adolescents with HFA when compared to 21 typical controls. Study 2 replicated the findings from Study 1 with a younger sample of 17 children with HFA and 17 typical controls. In addition, Study 1 found evidence that acoustic measurements of prosody were related to clinical judgments of autism-specific communication impairments, although this was not replicated in Study 2. Taken together, these studies provide evidence for differences in expressive prosody in individuals with HFA that can be measured objectively.

In this article, we comment on specific aspects of Peppé (Peppé, 2009). In particular, we address the assessment and treatment of prosody in clinical settings and discuss current theory on neurological models of prosody. We argue that in order for prosodic assessment instruments and treatment programs to be clinical effective, we need assessment instruments that: (1) have a representative normative comparison sample and strong psychometric properties; (2) are based on empirical information regarding the typical sequence of prosodic acquisition and are sensitive to developmental change; (3) meaningfully subcategorize various aspects of prosody; (4) use tasks that have ecological validity; and (5) have clinical properties, such as length and ease of administration, that allow them to become part of standard language assessment batteries. In addition, we argue that current theories of prosody processing in the brain are moving toward network models that involve multiple brain areas and are crucially dependent on cortical communication. The implications of these observations for future research and clinical practice are outlined.

Previous research has found few quantitative differences between children with high-functioning autism spectrum disorders (ASDs) and well-matched controls in the length, complexity, and structure of their narratives. Researchers have noted, however, that narratives of children with ASDs have an unusual and idiosyncratic nature. This study provides an analysis of narratives in 17 children with high-functioning ASDs and 17 typically developing children matched on age, gender, language abilities, and cognitive abilities. We examined story recall and narrative coherence. The study revealed no group differences in story length or syntactic complexity. Children with ASDs also did not differ from controls in their use of the gist of a story to aid recall, or in their sensitivity to the importance of story events. Children with ASDs did, however, produce narratives that were significantly less coherent than the narratives of controls. Children with ASDs appeared less likely to use the gist of the story to organize their narratives coherently. These findings are discussed with regard to their relationship to other cognitive and linguistic difficulties of children with ASDs.

Robotics and human-robot interaction (HRI) are growing fields that may benefit from an expanded perspective stimulated by more interdisciplinary contributions. One way to achieve this goal is to attract non-traditional students from the social sciences and humanities into these fields. This present paper describes two educational initiatives that focused on teaching non-engineering students about robotics and HRI. In one initiative, a group of younger students, including those with autism spectrum disorder (ASD), received hands-on experience with robotics in a context that was not overly technical, while in the other initiative, college students in the social sciences and humanities learned about basic HRI concepts and developed robotics applications. Themes common to both initiatives were to reach non-technical students who are not traditional targets for robotics education and to focus their learning on creating interactive sequences for robots based on key HRI design considerations rather than on the underlying mechanical and electrical details related to how those sequences are enacted inside the robot. Both initiatives were successful in terms of producing desired learning outcomes and fostering participant enjoyment.

Despite anecdotal evidence of relative visuospatial processing strengths in individuals with reading disability (RD), only a few studies have assessed the presence or the extent of these putative strengths. The current study examined the cognitive and neural bases of visuospatial processing abilities in adolescents with RD relative to typically developing (TD) peers. Using both cognitive tasks and functional magnetic resonance imaging (fMRI) we contrasted printed word recognition with non-language visuospatial processing tasks. Behaviorally, lower reading skill was related to a visuospatial processing advantage (shorter latencies and equivalent accuracy) on a geometric figure processing task, similar to findings shown in two published studies. FMRI analyses revealed key group by task interactions in patterns of cortical and subcortical activation, particularly in frontostriatal networks, and in the distributions of right and left hemisphere activation on the two tasks. The results are discussed in terms of a possible neural tradeoff in visuospatial processing in RD.

Autonomy support has been found to be critical for typically developing children, but not as much is known about its importance for children with Autism Spectrum Disorder (ASD). The current study examined the relationship between autonomy support, self-determination, scholastic competence and social acceptance in ASD. Twenty-six participants with high-functioning ASD completed self-report measures related to autonomy support, friendship, and academics. We found that greater teacher autonomy support was related to higher self-determination in school, and in turn, higher scholastic competence. Self-determination in friendship did not function as a mediator between mother/father autonomy support and social acceptance, but self-determination in friendship was significantly related to social acceptance. This study highlights the importance of fostering self-determination in both the academic and social lives of individuals with ASD. Future studies should examine best practices for incorporating autonomy support into existing scholastic settings and interventions.

Children with Autism Spectrum Disorders (ASD) often have comorbid psychopathology in addition to socialcommunication difficulties. Social anxiety is of particular interest because it has been linked to downstream deficits in social functioning. Bellini found a link between social skills, temperament, and the development of social anxiety. The current paper examines whether negative affectivity moderates the relationship between social skills and social anxiety. Twenty-five high-functioning children diagnosed with ASD were administered self and parent report questionnaires measuring pragmatics ability, socialization behaviors, negative affectivity, and social anxiety. High negative affectivity was related to social anxiety, and moderated the relationship between socialization behaviors and social anxiety. Pragmatics ability was not related to social anxiety. Together, these results indicate that negative affectivity is an important factor in the relationship between social skills and social anxiety, and that not all social skills deficits contribute to social anxiety.

In research, it has been difficult to characterize the prosodic production differences that have been observed clinically in Autism Spectrum Disorders (ASD). Moreover, the nature of these differences has been particularly hard to identify. This study examined one possible contributor to these perceived differences: motor planning. We examined the ability of children and adolescents with ASD to imitate prosodic patterns in comparison to a group with learning disabilities (LD) and a typically-developing (TD) comparison group. Overall, we found that both the ASD and LD groups were significantly worse at perceiving and imitating prosodic patterns than the TD comparison group. Similar to previous studies using non-imitative speech, participants with ASD showed a significantly longer duration of utterances than the two comparison groups when attempting to imitate an intonation pattern. The implications of differences in duration of utterances are discussed. This study also highlights the importance of using clinical comparison groups in studies of language performance in individuals with ASD.

We examined peer-reviewed studies in order to understand the current status of empirically based evidence on the clinical applications of robots in the diagnosis and treatment of Autism Spectrum Disorders (ASD). Studies are organized into four broad categories: (a) the response of individuals with ASD to robots or robot-like behavior in comparison to human behavior, (b) the use of robots to elicit behaviors, (c) the use of robots to model, teach, and/or practice a skill, and (d) the use of robots to provide feedback on performance. A critical review of the literature revealed that most of the findings are exploratory and have methodological limitations that make it difficult to draw firm conclusions about the clinical utility of robots. Finally, we outline the research needed to determine the incremental validity of this technique.

We explore how implicit associations with the label "autism" influence how people with the diagnosis are represented and perceived. A recent trend in public discourse has been to add descriptors to autism, such as "high-functioning" or "spectrum," possibly to minimize the perceived stigma associated with the diagnosis. We examined the colors used by researchers in poster graphs to represent the term autism. Research has indicated that the color red has implicit negative associations when evaluation of competence is salient. We found that red was used more often for groups with an autism label than other groups. Further, the use of red was less frequent when there were qualifiers for autism such as "high-functioning," "spectrum," or for Asperger syndrome. We assert that this pattern is evidence of implicit, negative societal associations with the word autism that influence discourse on the diagnosis.

This report describes the development of a prototypical Wizard of Oz, graphical user interface to wirelessly control a small, humanoid robot (Aldebaran Nao) during a therapy session for children with Autism Spectrum Disorders (ASD). The Dynamically Operated Manually Executed Robot interface (DOMER) enables an operator to initiate pre-developed behavior sequences for the robot as well as access the text-to-speech capability of the robot in real-time interactions between children with ASD and their therapist. Preliminary results from a pilot study suggest that the interface enables the operator to control the robot with sufficient fidelity such that the robot can provide positive feedback, practice social dialogue, and play the game, "Simon Says" in a convincing and engaging manner.

OBJECTIVE:: The purpose of this study was to determine the cost-effectiveness of requiring all recreational hockey players to wear facial protection. METHODS:: The authors randomly surveyed recreational hockey players at two indoor hockey rinks in Evendale, Ohio. Data were collected on face protection, injuries, demographic variables and attitudes about protective gear from 11/2005 to 03/2006. RESULTS:: We surveyed 190 players. The mean age was 34 +/- 8.7 years and 99% were male. The average hockey experience was 17 years. Forty-six percent of respondents reported at least one serious hockey injury in the last five years. Twenty-four percent of the surveyed population chose to not wear face protection (46/190). The average cost of face protection was $48. The cost to purchase two shields for the 46 players would be $4416. Individuals with face protection reported significantly more sprains and strains that resulted in significantly more physician office visits and specialty physician visits. The extra physician visits would add approximately $4590 for the 46 people needing face protection. Those with face protection reported significantly fewer facial lacerations and facial bone fractures. Requiring face protection should prevent seven facial lacerations and three facial bone fractures over five years. The savings would be approximately $15,000. The net savings by requiring face protection would be $6,000/5 years. In our population, with 24% choosing to not wear face protection, requiring face protection would save $250/5 years/person needing protection. CONCLUSION:: It is cost-effective to require facial protection in all recreational hockey players. Language: en

Innate immune responses provide the host with its first line of defense against infections. Signals generated by subsets of lymphocytes, including NK cells, NKT cells, and APC during this early host response determine the nature of downstream adaptive immune responses. In the present study, we have examined the role of innate NK cells in an autoimmune model through the use of primary immunization with the myelin oligodendrocyte glycoprotein peptide to induce experimental autoimmune encephalomyelitis (EAE). Our studies have shown that in vivo depletion of NK cells can affect the adaptive immune responses, because NK cells were found to regulate the degree of clinical paralysis and to alter immune adaptive responses to the myelin oligodendrocyte glycoprotein peptide. The requirement for NK cells was reflected by changes in the T cell responses and diminished clinical disease seen in mice treated with anti-NK1.1, anti-asialo GM1, and selected Ly49 subtype-depleted mice. In addition to alteration in T cell responses, the maturational status of dendritic cells in lymph nodes was altered both quantitatively and qualitatively. Finally, examination of TCR Vβ usage of the brain lymphocytes from EAE mice indicated a spectra-type change in receptor expression in NK- depleted mice as compared with non-NK-depleted EAE mice. These findings further establish a recently postulated link between NK cells and the generation of autoreactive T cells.

We examine the referential choices (pronouns/zeros vs. names/descriptions) made during a narrative by high-functioning children and adolescents with autism and a well-matched typically developing control group. The process of choosing appropriate referring expressions has been proposed to depend on two areas of cognitive functioning: (a) judging the attention and knowledge of one's interlocutor, and (b) the use of memory and attention mechanisms to represent the discourse situation. We predicted possible group differences, since autism is often associated with deficits in (a) mentalizing and (b) memory and attention, as well as a more general tendency to have difficulty with the pragmatic aspects of language use. Results revealed that some of the participants with autism were significantly less likely to produce pronouns or zeros in some discourse contexts. However, the difference was only one of degree. Overall, all participants in our analysis exhibited fine-grained sensitivity to the discourse context. Furthermore, referential choices for all participants were modulated by factors related to the cognitive effort of language production.

Individuals with autism exhibit significant impairments in prosody production, yet there is a paucity of research on prosody comprehension in this population. The current study adapted a psycholinguistic paradigm to examine whether individuals with autism are able to use prosody to resolve syntactically ambiguous sentences. Participants were 21 adolescents with high-functioning autism (HFA), and 22 typically developing controls matched on age, IQ, receptive language, and gender. The HFA group was significantly less likely to use prosody to disambiguate syntax, but scored comparably to controls when syntax alone or both prosody and syntax indicated the correct response. These findings indicate that adolescents with HFA have difficulty using prosody to disambiguate syntax in comparison to typically developing controls, even when matched on chronological age, IQ, and receptive language. The implications of these findings for how individuals with autism process language are discussed.

Insitu borehole P- and S-wave velocity measurements were collected in three borings located within the Waste Treatment Plant (WTP) boundaries at the Hanford Site, southeastern Washington. Geophysical data acquisition was performed between August and October of 2006 by Rob Steller, Charles Carter, Antony Martin and John Diehl of GEOVision. Data analysis was performed by Rob Steller and John Diehl, and reviewed by Antony Martin of GEOVision, and report preparation was performed by John Diehl and reviewed by Rob Steller. The work was performed under subcontract with Battelle, Pacific Northwest Division with Marty Gardner as Battelle’s Technical Representative and Alan Rohay serving as the Technical Administrator for Pacific Northwest National Laboratory (PNNL). This report describes the field measurements, data analysis, and results of this work.

Mucosal tolerance to E-selectin has been shown to prevent stroke and reduce brain infarcts in experimental stroke models. However, the effective E-selectin dose range required to achieve mucosal tolerance and the precise mechanisms of neuroprotection remain unclear. We sought to examine the mechanisms of cytoprotection using gene expression profiling of tissues in the setting of mucosal tolerance and inflammatory challenge. Using spontaneously hypertensive rats (SHRs), we achieved immune tolerance with 0.1 to 5 μg E-selectin per nasal instillation and observed a dose-related anti-E-selectin immunoglobulin G antibody production. We also show the distinct patterns of gene expression changes in the brain and spleen with the different tolerizing doses and lipopolysaccharide (LPS) exposure. Prominent differences were seen with such genes as insulin-like growth factors in the brain and downregulation of those encoding the major histocompatibility complex class I molecules in the spleen. In all, mucosal tolerance to E-selectin and subsequent exposure to LPS resulted in significant tissue changes. These changes, while giving an insight to the underlying mechanisms, serve as possible targets for future studies to facilitate translation to human clinical trials.

Purpose:Pragmatic language disorders (PLDs) are difficult to diagnose in a cost-effective manner, and there are few assessment tools that yield quantitative data. This investigation was designed to determine whether two formal assessment tools would differentiate PLDs in children with autism spectrum disorders (ASDs) from controls matched on verbal IQ and language fundamentals.Method:Thirty-four matched participants were given the Test of Pragmatic Language (TOPL; D. Phelps-Terasaki & T. Phelps-Gunn, 1992) and the Strong Narrative Assessment Procedure (SNAP; C. J. Strong, 1998).Results:Participants with ASDs had significantly poorer scores than controls on the TOPL. On the SNAP, the children with ASDs performed similarly to controls on syntax, cohesion, story grammar, and completeness of episodes. The controls performed significantly better only on the ability to answer inferential questions.Clinical Implications:The TOPL was effective in differentiating PLDs in children with ASDs when performance was compared to matched controls. The SNAP did not clearly differentiate language problems in these two groups. Research is needed to develop formal assessment tools that target the unique language disabilities of high-functioning individuals with ASDs.

This paper presents the findings and recommendations of the User Scenario Work Group (USWG) in identifying a baseline of current practices within the geo-professional community and prioritizing desired functional requirements in the development of a comprehensive geotechnical information management system. This work was conducted as an initial phase of a larger project to demonstrate the effectiveness of a web based virtual data center for the dissemination of geotechnical data from multiple linked databases of various government and private sector organizations. An online survey was administered over the course of several months to practitioners across the nation. The results from the survey were compiled and examined to provide direction to the other project teams in the development if user-driven prototype data system.

Proceedings of sessions of Geo-Denver 2000, held in Denver, Colorado, August 5-8, 2000. Sponsored by the Geo-Institute of ASCE. This Geotechnical Special Publication contains 16 papers presenting recent advances in and practical applications of geophysical methods to solve construction-related problems or to facilitate the construction process. Geophysical techniques can assist the construction industry in many ways, before, during, and after construction. Preconstruction activities presented include utility engineering, site reconnaissance, and anomaly detection. During construction, geophysical techniques used as economical and rapid quality control or process control tools are represented. The use of geophysical methods after the completion of the project is demonstrated as a means to monitor the overall health or determine the causes or consequences of localized or general construction problems.