According to a recent influential proposal, several phenotypic features of autism spectrum disorder (ASD) may be accounted for by differences in predictive skills between individuals with ASD and neurotypical individuals. In this systematic review, we describe results from 47 studies that have empirically tested this hypothesis. We assess the results based on two observable aspects of prediction: learning a pairing between an antecedent and a consequence and responding to an antecedent in a predictive manner. Taken together, these studies suggest distinct differences in both predictive learning and predictive response. Studies documenting differences in learning predictive pairings indicate challenges in detecting such relationships especially when predictive features of an antecedent have low salience or consistency, and studies showing differences in habituation and perceptual adaptation suggest low‐level predictive processing differences in ASD. These challenges may account for the observed differences in the influence of predictive priors, in spontaneous predictive movement or gaze, and in social prediction. An important goal for future research will be to better define and constrain the broad domain‐general hypothesis by testing multiple types of prediction within the same individuals. Additional promising avenues include studying prediction within naturalistic contexts and assessing the effect of prediction‐based intervention on supporting functional outcomes for individuals with ASD. Lay Summary Researchers have suggested that many features of autism spectrum disorder (ASD) may be explained by differences in the prediction skills of people with ASD. We review results from 47 studies. These studies suggest that ASD may be associated with differences in the learning of predictive pairings (e.g., learning cause and effect) and in low‐level predictive processing in the brain (e.g., processing repeated sounds). These findings lay the groundwork for research that can improve our understanding of ASD and inform interventions. Autism Res 2021, 14: 604–630. © 2021 International Society for Autism Research and Wiley Periodicals LLC
Efforts to develop a better diagnostic assay for bovine tuberculosis have shown that the sensitivity and specificity of an assay can be improved by the use of two or more antigens. As reported here, we developed a multiplex chemiluminescent immunoassay that can simultaneously detect antibody activity to 25 antigens in a single well in a 96-well plate array format. The chemiluminescent signal is captured with a digital imaging system and analyzed with a macro program that tracks each serum for its pattern of antibody activity for Mycobacterium bovis antigens. The comparison of sera from 522 infected and 1,489 uninfected animals showed that a sensitivity of 93.1% and a specificity of 98.4% can be achieved with a combination of antigens. The assay system is rapid and can be automated for use in a centralized laboratory.Bovine tuberculosis (bTB) continues to be a zoonotic disease affecting multiple species, including humans (3, 9, 21, 26). The disease has been difficult to control in livestock because of the lack of an effective vaccine, the presence of wildlife reservoirs, and the lack of a diagnostic assay with sufficient sensitivity and specificity to detect animals at all stages of infection. Currently, the primary methods used for the detection of TB in humans and ruminants include the measurement of a delayedtype hypersensitivity (skin test) to purified protein derivative (PPD) and an indirect in vitro assay that measures the concentration of gamma interferon (IFN-␥) produced in response to stimulation with PPD (22,30,31). Although the methods have proven useful in controlling bTB, they lack sensitivity and specificity because of a cross-reactive immune response to Tand B-cell epitopes conserved on orthologous molecules present in nonpathogenic mycobacteria and Mycobacterium avium subsp. paratuberculosis (reviewed in references 8, 23, and 27). To obviate this problem, an extensive effort has been under way to identify and characterize antigens unique to Mycobacterium bovis that could be used in a diagnostic assay. To date, studies have shown that the antibody response to M. bovis is not uniform, with no evidence of a dominant persistent response to a single antigen (reviewed in references 4, 7, and 8) at any stage of infection (2,19). This finding has suggested that some type of a multiplex assay is needed to detect animals at different stages of infection (1, 2). However, the necessity of using multiple antigens in an assay has introduced another challenge. The evaluation of the standard type of enzymelinked immunosorbent assay (ELISA) has shown that sensitivity and specificity are reduced when multiple antigens are combined for analysis in a single well, thus limiting the way a conventional ELISA can be used (20). To address this problem, we developed a multiplex assay that can simultaneously detect and analyze the response to multiple antigens spotted in a single well in a 96-well plate array format. We demonstrate the enhanced diagnostic power of a multiplex antigen approach over that of the industry-stand...
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