‘I never realised everybody felt as happy as I do when I am around autistic people’: A thematic analysis of autistic adults’ relationships with autistic and neurotypical friends and family

AbstractMany autistic people are motivated to have friends, relationships and close family bonds, despite the clinical characterisation of autism as a condition negatively affecting social interaction. Many first-hand accounts of autistic people describe feelings of comfort and ease specifically with other autistic people. This qualitative research explored and contrasted autistic experiences of spending social time with neurotypical and autistic friends and family. In total, 12 autistic adults (10 females, aged 21–51) completed semi-structured interviews focused on time spent with friends and family; positive and negative aspects of time spent with neurotypical and autistic friends and family; and feelings during and after spending time together. Three themes were identified: cross-neurotype understanding, minority status and belonging. Investigation of these themes reveals the benefits of autistic people creating and maintaining social relationships with other autistic people, in a more systematic way than previous individual reports. They highlight the need for autistic-led social opportunities and indicate benefits of informal peer support for autistic adults.Lay abstractAlthough autistic people may struggle to interact with others, many autistic people have said they find interacting with other autistic people more comfortable. To find out whether this was a common experience, we did hour-long interviews with 12 autistic adults. We asked them questions about how it feels when spending time with their friends and family, and whether it felt different depending on whether the friends and family were autistic or neurotypical. We analysed the interviews and found three common themes in what our participants said. First, they found spending with other autistic people easier and more comfortable than spending time with neurotypical people, and felt they were better understood by other autistic people. Second, autistic people often felt they were in a social minority, and in order to spend time with neurotypical friends and family, they had to conform with what the neurotypical people wanted and were used to. Third, autistic people felt like they belonged with other autistic people and that they could be themselves around them. These findings show that having time with autistic friends and family can be very beneficial for autistic people and played an important role in a happy social life

Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: Implications for molecular diagnosis

Phospholipase associated neurodegeneration (PLAN) comprises a heterogeneous group of autosomal recessive neurological disorders caused by mutations in the PLA2G6 gene. Direct gene sequencing detects 85% mutations in infantile neuroaxonal dystrophy. We report the novel use of multiplex ligation-dependent probe amplification (MLPA) analysis to detect novel PLA2G6 duplications and deletions. The identification of such copy number variants (CNVs) expands the PLAN mutation spectrum and may account for up to 12.5% of PLA2G6 mutations. MLPA should thus be employed to detect CNVs of PLA2G6 in patients who show clinical features of PLAN but in whom both disease-causing mutations cannot be identified on routine sequencin

Autistic peer-to-peer information transfer is highly effective

AbstractEffective information transfer requires social communication skills. As autism is clinically defined by social communication deficits, it may be expected that information transfer between autistic people would be particularly deficient. However, the Double Empathy theory would suggest that communication difficulties arise from a mismatch in neurotype; and thus information transfer between autistic people may be more successful than information transfer between an autistic and a non-autistic person. We investigate this by examining information transfer between autistic adults, non-autistic adults and mixed autistic-with-non-autistic pairs. Initial participants were told a story which they recounted to a second participant, who recounted the story to a third participant and so on, along a ‘diffusion chain’ of eight participants (n = 72). We found a significantly steeper decline in detail retention in the mixed chains, while autistic chains did not significantly differ from non-autistic chains. Participant rapport ratings revealed significantly lower scores for mixed chains. These results challenge the diagnostic criterion that autistic people lack the skills to interact successfully. Rather, autistic people effectively share information with each other. Information transfer selectively degrades more quickly in mixed pairs, in parallel with a reduction in rapport.Lay abstractSharing information with other people relies on the ability to communicate well. Autism is defined clinically by deficits in social communication. It may therefore be expected that autistic people find it difficult to share information with other people. We wanted to find out whether this was the case, and whether it was different when autistic people were sharing information with other autistic people or with non-autistic people. We recruited nine groups, each with eight people. In three of the groups, everyone was autistic; in three of the groups, everyone was non-autistic; and three of the groups were mixed groups where half the group was autistic and half the group was non-autistic. We told one person in each group a story and asked them to share it with another person, and for that person to share it again and so on, until everyone in the group had heard the story. We then looked at how many details of the story had been shared at each stage. We found that autistic people share information with other autistic people as well as non-autistic people do with other non-autistic people. However, when there are mixed groups of autistic and non-autistic people, much less information is shared. Participants were also asked how they felt they had got on with the other person in the interaction. The people in the mixed groups also experienced lower rapport with the person they were sharing the story with. This finding is important as it shows that autistic people have the skills to share information well with one another and experience good rapport, and that there are selective problems when autistic and non-autistic people are interacting

Altered apoptotic profiles in irradiated patients with increased toxicity.

Purpose: A retrospective study of radiation-induced apoptosis in CD4 and CD8 T-lymphocytes, from 12 cancer patients who displayed enhanced toxicity to radiation therapy and 9 ataxia telangiectasia patients, was performed to test for altered response compared to healthy blood-donors and normal cancer patients. Methods and Materials: Three milliliters of heparinized blood from each donor was sent via express post to the Paul Scherrer Institute (PSI) for subsequent examination. The blood was diluted 1:10 in RPMI medium, irradiated with 0-, 2-, or 9-Gy X-rays, and incubated for 48 h. CD4 and CD8 T-lymphocytes were then labeled using FITC-conjugated antibodies, erythrocytes were lysed, and the DNA stained with propidium iodide. Subsequently, cells were analyzed using a Becton Dickinson FACScan flow cytometer. Radiation-induced apoptosis was recognized in leukocytes as reduced DNA content attributed to apoptosis-associated changes in chromatin structure. Apoptosis was confirmed by light microscopy, electron microscopy, and by the use of commercially available apoptosis detection kits (in situ nick translation and Annexin V). Data from hypersensitive individuals were compared to a standard database of 105 healthy blood-donors, and a database of 48 cancer patient blood donors who displayed normal toxicity to radiation therapy. To integrate radiosensitivity results from CD4 and CD8 T-lymphocytes after 2 and 9 Gy, z-score analyses were performed. Results: A cohort of 12 hypersensitive patients was evaluated; 8 showed enhanced early toxicity, 3 showed enhanced late toxicity, and 1 showed both. The cohort displayed less radiation-induced apoptosis (21.8 s) than average age-matched donors. A cohort of 9 ataxia telangiectasia homozygotes displayed even less apoptosis (23.6 s). Conclusion: The leukocyte apoptosis assay appears to be a useful predictor of individuals likely to display increased toxicity to radiation therapy; however, validation of this requires a prospective study. © 1999 Elsevier Science Inc

Open Science in Experimental Autism Research: A Replication Study of Information Transfer Within and Between Autistic and Non-Autistic People

Information sharing depends on successful communication. Because autism is clinically defined by social communication deficits, autistic people may be expected to be less effective at sharing information, particularly with one another.  In 2020, we published a paper indicating that it is the mismatch between autistic and non-autistic people, rather than autism itself, that degrades information sharing. We used an experimental diffusion chain methodology to examine information transfer in groups of autistic people, groups of non-autistic people, and mixed groups of autistic and non-autistic people. The first participant in each group was told a story which they recounted to a second participant, who recounted it to the third participant and so on, along a “diffusion chain” of eight participants (n = 72). Retention of details within the mixed chain showed a significantly steeper decline than the autistic and mixed chains, which did not significantly differ from each other.  These results challenge the diagnostic criterion of inherent social deficits in autism, demonstrate that autistic social behaviour can include effective communication and social interaction, and suggest that social difficulties in autism are contextual rather than absolute. Although these findings have profound implications for practitioners, educators, clinicians and psychologists, pushing for dramatic change in policy and practice is premature without a replication establishing these effects as robust and meaningful. Importantly, a failure to replicate would still yield novel insights into interactions between autistic and non-autistic people that could be applied to practice across services.  We are embarking on an open-science replication of this study in a larger (n = 324) and more diverse sample, across three international sites, to determine whether these findings are replicable in new samples. We hypothesise that we will replicate the original finding, showing that social interactions are facilitated in an autistic group of participants.  Our increased sample size will allow for the identification of moderating demographic factors, and potential communicative mechanisms that facilitate or impede interaction between and within diagnostic groups. Additionally, we will explore whether informing participants of the diagnostic status of participants in their chain affects information transfer and rapport, and whether transfer differs for fictional and factual information.  This study was funded as part of an Open Science Initiative; our protocols will be pre-registered on the Open Science Framework, and we have a Registered Report currently under review. It is the first Open Science endeavour of this team, and we look forward to the opportunity to discuss this work with the Edinburgh Open Science community. We will present a short summary of the results from the first study and a detailed account of the planned replication, drawn from our Registered Report (currently under review at Nature Human Behaviour

Neurotype-Matching, but Not Being Autistic, Influences Self and Observer Ratings of Interpersonal Rapport

The Double Empathy Problem suggests that communicative difficulties between autistic and non-autistic people are due to bi-directional differences in communicative style and a reciprocal lack of understanding. If true, there should be increased similarity in interaction style, resulting in higher rapport during interactions between pairs of the same neurotype. Here, we provide two empirical tests of rapport, with data revealing whether self- and observer- rated rapport varies depending on the match or mismatch in autism status within a pair. An additional opportunity afforded by these data is to examine the effect of the autism status of the rater on the perceived rapport between matched and mismatched pairs. In Study 1 72 participants were allocated to one of three dyad conditions: autistic pairs (n = 24), non-autistic pairs (n = 24) and mixed pairs (n = 12 autistic; n = 12 non-autistic). Each participant completed three semi-structured interactions with their partner, rating rapport after each interaction. Non-autistic pairs experienced higher self-rated rapport than mixed and autistic pairs, and autistic pairs experienced higher rapport than mixed pairs. In Study 2 (n = 80) autistic and non-autistic observers rated interactional rapport while watching videoed interactions between autistic pairs, non-autistic pairs, and mixed pairs (n = 18, a subset of participants in Study 1). Mixed pairs were rated significantly lower on rapport than autistic and non-autistic pairs, and autistic pairs were rated more highly for rapport than non-autistic pairs. Both autistic and non-autistic observers show similar patterns in how they rate the rapport of autistic, non-autistic, and mixed pairs. In summary, autistic people experience high interactional rapport when interacting with other autistic people, and this is also detected by external observers. Rather than autistic people experiencing low rapport in all contexts, their rapport ratings are influenced by a mismatch of diagnosis. These findings suggest that autistic people possess a distinct mode of social interaction style, rather than demonstrating social skills deficits. These data are considered in terms of their implications for psychological theories of autism, as well as practical impact on educational and clinical practice

How successfully do autistic and non-autistic raters guess the diagnostic status of autistic and non-autistic people having conversations?

Recent research has shown that interactions between autistic people do not evidence the same social communication difficulties seen during interactions between autistic and non-autistic people. To examine whether the social context of an interaction also affects observers’ ability to identify autism in others, we showed autistic and non-autistic raters videos (rater n=78; 39 autistic) and pictures (rater n=54; 27 autistic) of autistic and non-autistic people interacting (in both own-neurotype and mixed pairs), and asked the raters to identify whether each member of the pair was autistic. Raters were able to identify autistic individuals in the stimuli at rates above chance, and pair type, stimulus type, and rater neurotype all affected identification accuracy. Notably, raters were least accurate at identifying autistic individuals within autistic pairs, often assuming both individuals were non-autistic (therefore performing below chance). This suggests that observers’ ability to identify autistic people does depend on social context

IGF2BP3 as a Prognostic Biomarker in Well-Differentiated/Dedifferentiated Liposarcoma.

BACKGROUND: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. METHODS: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. RESULTS: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034). CONCLUSION: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival

Clinical Factors That Affect the Establishment of Soft Tissue Sarcoma Patient-Derived Orthotopic Xenografts: A University of California, Los Angeles, Sarcoma Program Prospective Clinical Trial.

PURPOSE: Given the diverse and aggressive nature of soft tissue sarcomas (STSs), a need exists for more-precise therapy. Patient-derived orthotopic xenografts (PDOXs) provide a unique platform for personalized treatment. Thus, identification of patient and treatment factors that predict PDOX establishment is important. This study assessed the feasibility of incorporating PDOXs into the clinical setting and identifying factors associated with PDOX establishment. PATIENTS AND METHODS: From May 2015 to May 2016, 107 patients with biopsy-proven or potential STS were enrolled. Tumor samples were obtained intraoperatively and orthotopically implanted into nude mice in the corresponding anatomic location. PDOXs were considered established after engraftment and serial passage. Factors associated with establishment were analyzed by logistic regression and time to establishment by time-to-event analysis. RESULTS: Only high-grade tumors established (32 of 72 [44.4%]). The establishment rate (ER) varied by neoadjuvant therapy and treatment response, with the highest ER among untreated high-grade tumors (26 of 42 [61.9%]). Tumors exposed to radiation preoperatively did not establish (zero of 11 [0%]), and tumors exposed to neoadjuvant chemotherapy had a lower ER(31.9%) than untreated tumors. Only STSs with minimal pathologic response to neoadjuvant treatment (≤ 30%) established a PDOX (six of 18 [33.3%]). Median establishment time was 54 days, which varied by neoadjuvant therapy but was not statistically significant (P = .180). CONCLUSION: To our knowledge, in the largest STS PDOX study to date, we demonstrate a 62% ER among untreated high-grade tumors with a median establishment time of 54 days. Neoadjuvant therapy, particularly radiation, and pathologic response to treatment were associated with a reduced rate of PDOX establishment