Sex Specific Behavioral Profiles in Toddlers At Risk for Autism Spectrum Disorders (ASD)

The Positive Predictive Value (PPV) of the Modified Checklist for Autism in Toddlers (M-CHAT), a parent report autism screening tool, is higher for males than for females (Ludwig et al., IMFAR 2011). Given the long waitlists and high costs for ASD evaluations, there is a need to reduce the number of false positive females on the M-CHAT. The current study examined the sex specific clinical profiles of toddlers who received an ASD evaluation based on M-CHAT screen positive status in order to explore potential differences that may contribute to the differential PPV of the M-CHAT in boys and girls. The sample included 250 males and 106 females (mean age=25.3 months, SD=4.6) who were evaluated based on screen positive status on the M-CHAT. Although children with ASD demonstrated greater ASD symptoms, lower IQ and weaker language and motor skills, minimal sex differences were discovered

Social Attribution in Toddlers At Risk for Autism Spectrum Disorder

Autism spectrum disorder (ASD) can now be reliably diagnosed in preverbal toddlers and early diagnosis is becoming more common since the development of early autism screening practices. However, the positive predictive value of widely used screening tools remains low, which leads to a high number of false positive cases requiring further evaluation. Given that access to specialists is limited, there is a pressing need to develop easily accessible and broadly applicable direct measures that will further streamline screening and diagnosis for at risk toddlers. The primary aim of the current study is to examine the utility of a novel, direct measure of social attribution in measuring this skill in toddlers with and without ASD and examining the utility of this measure in reliably identifying ASD in a sample of at risk toddlers with a broad range of verbal and cognitive abilities. Participants include 35 toddlers considered at risk for an ASD (i.e., 15 with ASD, 20 with non-ASD delays; DD) and 22 typically developing (TD) toddlers. Children were presented with two versions of a nonverbal social attribution measure featuring a visual habituation-based violation of expectation paradigm; a live puppet show version previously studied in infant populations and a novel touchscreen adaptation. It was hypothesized that toddlers without a diagnosis of ASD would demonstrate evidence of social attribution whereas children with ASD would demonstrate reduced social attribution. Furthermore, it was predicted that performance would have clinical utility in predicting a diagnosis of ASD and symptom severity. Results indicated that no groups showed gross looking time differences evidencing social attribution, bringing into question whether this paradigm is appropriate for capturing social attribution in this age range. Despite this, toddlers in the TD group demonstrated evidence of social evaluation in the live puppet show task whereas toddlers within the ASD and DD groups did not. Differential habituation characteristics between the DD and TD groups suggest that other factors may have impeded success in the DD group. Future research is warranted to examine whether deficient social evaluation is specific to ASD or characterizes developmental delays more broadly. Findings have implications for future research examining theories of social attribution and informing the use of new technologies in toddler research and clinical tool development

Priming in a shape task but not in a category task under continuous flash suppression

Continuous flash suppression (CFS) is an interocular suppression technique that uses high-contrast masks flashed to one eye to prevent conscious perception of images shown to the other eye. It has become widely used due to its strength and prolonged duration of suppression and its nearly deterministic control of suppression onset and offset. Recently, it has been proposed that action-relevant visual processing ascribed to the dorsal stream remains functional, while processing in the ventral stream is completely suppressed, when stimuli are invisible under CFS. Here we tested the hypothesis that the potentially dorsal-stream-based analysis of prime-stimulus elongation during CFS affects the categorization of manipulable target objects. In two behavioral experiments, we found evidence for priming in a shape task, but none for priming in a category task, when prime stimuli were rendered invisible using CFS. Our results thus support the notion that the representation of CF-suppressed stimuli is more limited than previously thought

Prevalence of Gastrointestinal Symptoms Among Autistic Individuals, With and Without Co-Occurring Intellectual Disability

Gastrointestinal symptoms (GI) are very common among individuals on the autism spectrum. Prior research reports mixed findings regarding whether individuals with autism and co-occurring intellectual disability (ID) have elevated risk of gastrointestinal symptoms relative to individuals with autism alone. GI symptoms can be challenging to assess in individuals with autism spectrum disorder (ASD) and/or ID given challenges with language, communication, and interoception. Prior research has tended to only include individuals with documented presence or absence of GI symptoms or conditions, that is, to exclude observations in which there is uncertainty regarding presence of GI symptoms. Therefore, none of the prior autism studies reported the association between ID and the certainty regarding presence or absence of GI symptoms. The objective of this study was to examine differences in parental certainty and odds of reporting gastrointestinal signs and symptoms among children on the autism spectrum, with and without intellectual disability. Participants were 308 children (36% ID) with a clinical diagnosis of autism spectrum disorder (6-17 years). Parents endorsed whether their child had experienced or displayed a range of signs or symptoms related to GI problems in the past 3 months. Parents of autistic children with ID were less certain about the presence of more subjective symptoms, including abdominal pain, nausea, and bloating. Conversely, certainty regarding more objective signs (e.g., constipation, diarrhea, spitting up, etc.) was not significantly different. More accurate measures for GI signs/symptoms are needed for this population

Analysis of Race and Sex Bias in the Autism Diagnostic Observation Schedule (ADOS-2)

Importance: There are long-standing disparities in the prevalence of autism spectrum disorder (ASD) across race and sex. Surprisingly, few studies have examined whether these disparities arise partially out of systematic biases in the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the reference standard measure of ASD. Objective: To examine differential item functioning (DIF) of ADOS-2 items across sex and race. Design, Setting, and Participants: This is a cross-sectional study of children who were evaluated for ASD between 2014 and 2020 at a specialty outpatient clinic located in the Mid-Atlantic region of the US. Data were analyzed from July 2021 to February 2022. Exposures: Child race (Black/African American vs White) and sex (female vs male). Main Outcomes and Measures: Item-level biases across ADOS-2 harmonized algorithm items, including social affect (SA; 10 items) and repetitive/restricted behaviors (RRBs; 4 items), were evaluated across 3 modules. Measurement bias was identified by examining DIF and differential test functioning (DTF), within a graded response, item response theory framework. Statistical significance was determined by a likelihood ratio χ2 test, and a series of metrics was used to examine the magnitude of DIF and DTF. Results: A total of 6269 children (mean [SD] age, 6.77 [3.27] years; 1619 Black/African American [25.9%], 3151 White [50.3%], and 4970 male [79.4%]), were included in this study. Overall, 16 of 140 ADOS-2 diagnostic items (11%) had a significant DIF. For race, 8 items had a significant DIF, 6 of which involved SA. No single item showed DIF consistently across all modules. Most items with DIF had greater difficulty and poorer discrimination in Black/African American children compared with White children. For sex, 5 items showed significant DIF. DIF was split across SA and RRB. However, hand mannerisms evidenced DIF across all 5 algorithms, with generally greater difficulty. The magnitude of DIF was only moderate to large for 2 items: hand mannerisms (among female children) and repetitive interests (among Black/African American children). The overall estimated effect of DIF on total DTF was not large. Conclusions and Relevance: These findings suggest that the ADOS-2 does not have widespread systematic measurement bias across race or sex. However, the findings raise some concerns around underdetection that warrant further research

A chiral one-dimensional atom using a quantum dot in an open microcavity

In a chiral one-dimensional atom, a photon propagating in one direction interacts with the atom; a photon propagating in the other direction does not. Chiral quantum optics has applications in creating nanoscopic single-photon routers, circulators, phase-shifters, and two-photon gates. Here, we implement chiral quantum optics using a low-noise quantum dot in an open microcavity. We demonstrate the non-reciprocal absorption of single photons, a single-photon diode. The non-reciprocity, the ratio of the transmission in the forward-direction to the transmission in the reverse direction, is as high as 10.7 dB. This is achieved by tuning the photon-emitter coupling in situ to the optimal operating condition (β = 0.5). Proof that the non-reciprocity arises from a single quantum emitter lies in the photon statistics—ultralow-power laser light propagating in the diode’s reverse direction results in a highly bunched output (g(2)(0) = 101), showing that the single-photon component is largely removed

Heterochromatin drives organization of conventional and inverted nuclei [preprint]

The mammalian cell nucleus displays a remarkable spatial segregation of active euchromatic from inactive heterochromatic genomic regions. In conventional nuclei, euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery. In contrast, rod photoreceptors in nocturnal mammals have inverted nuclei, with a dense heterochromatic core and a thin euchromatic outer shell. This inverted architecture likely converts rod nuclei into microlenses to facilitate nocturnal vision, and may relate to the absence of particular proteins that tether heterochromatin to the lamina. However, both the mechanism of inversion and the role of interactions between different types of chromatin and the lamina in nuclear organization remain unknown. To elucidate this mechanism we performed Hi-C and microscopy on cells with inverted nuclei and their conventional counterparts. Strikingly, despite the inversion evident in microscopy, both types of nuclei display similar Hi-C maps. To resolve this paradox we developed a polymer model of chromosomes and found a universal mechanism that reconciles Hi-C and microscopy for both inverted and conventional nuclei. Based solely on attraction between heterochromatic regions, this mechanism is sufficient to drive phase separation of euchromatin and heterochromatin and faithfully reproduces the 3D organization of inverted nuclei. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. To further test our models, we eliminated lamina interactions in models of conventional nuclei and found that this triggers a spontaneous process of inversion that qualitatively reproduces the pathway of morphological changes during nuclear inversion in vivo. Together, our experiments and modeling suggest that interactions among heterochromatic regions are central to phase separation of the active and inactive genome in inverted and conventional nuclei, while interactions with the lamina are essential for building the conventional architecture from these segregated phases. Ultimately our data suggest that an inverted organization constitutes the default state of nuclear architecture

Photon bound state dynamics from a single artificial atom

The interaction between photons and a single two-level atom constitutes a fundamental paradigm in quantum physics. The nonlinearity provided by the atom leads to a strong dependence of the light–matter interface on the number of photons interacting with the two-level system within its emission lifetime. This nonlinearity unveils strongly correlated quasiparticles known as photon bound states, giving rise to key physical processes such as stimulated emission and soliton propagation. Although signatures consistent with the existence of photon bound states have been measured in strongly interacting Rydberg gases, their hallmark excitation-number-dependent dispersion and propagation velocity have not yet been observed. Here we report the direct observation of a photon-number-dependent time delay in the scattering off a single artificial atom—a semiconductor quantum dot coupled to an optical cavity. By scattering a weak coherent pulse off the cavity–quantum electrodynamics system and measuring the time-dependent output power and correlation functions, we show that single photons and two- and three-photon bound states incur different time delays, becoming shorter for higher photon numbers. This reduced time delay is a fingerprint of stimulated emission, where the arrival of two photons within the lifetime of an emitter causes one photon to stimulate the emission of another

Profiles and Correlates of Language and Social Communication Differences Among Young Autistic Children

Delays in early language development are characteristic of young autistic children, and one of the most recognizable first concerns that motivate parents to seek a diagnostic evaluation for their child. Although early language abilities are one of the strongest predictors of long-term outcomes, there is still much to be understood about the role of language impairment in the heterogeneous phenotypic presentation of autism. Using a personcentered, Latent Profile Analysis, we first aimed to identify distinct patterns of language and social communication ability in a clinic-based sample of 498 autistic children, ranging in age from 18 to 60 months (M = 33 mo, SD = 12 mo). Next, a multinomial logistic regression analysis was implemented to examine sociodemographic and child-based developmental differences among the identified language and social communication profiles. Three clinically meaningful profiles were identified from parent-rated and clinician-administered measures: Profile 1 (48% of the sample) “Relatively Low Language and Social Communication Abilities,” Profile 2 (34% of the sample) “Relatively Elevated Language and Social Communication Abilities,” and Profile 3 (18% of the sample) “Informant Discrepant Language and Relatively Elevated Social Communication Abilities.” Overall, young autistic children from the lowest-resource households exhibited the lowest language and social communication abilities, and the lowest non-verbal problem-solving and fine-motor skills, along with more features of attention-deficit/hyperactivity disorder and atypical auditory processing. These findings highlight the need for effective community-based implementation strategies for young autistic children from low-resource households and underrepresented communities to improve access to individualized quality care

A bright and fast source of coherent single photons

A single photon source is a key enabling technology in device-independent quantum communication, quantum simulation for instance boson sampling, linear optics-based and measurement-based quantum computing. These applications involve many photons and therefore place stringent requirements on the efficiency of single photon creation. The scaling on efficiency is an exponential function of the number of photons. Schemes taking full advantage of quantum superpositions also depend sensitively on the coherence of the photons, i.e. their indistinguishability. It is therefore crucial to maintain the coherence over long strings of photons. Here, we report a single photon source with an especially high system efficiency: a photon is created on-demand at the output of the final optical fibre with a probability of 57%. The coherence of the photons is very high and is maintained over a stream consisting of thousands of photons; the repetition rate is in the GHz regime. We break with the established semiconductor paradigms, such as micropillars, photonic crystal cavities and waveguides. Instead, we employ gated quantum dots in an open, tunable microcavity. The gating ensures low-noise operation; the tunability compensates for the lack of control in quantum dot position and emission frequency; the output is very well-matched to a single-mode fibre. An increase in efficiency over the state-of-the-art by more than a factor of two, as reported here, will result in an enormous decrease in run-times, by a factor of $10^{7}$ for 20 photons.Comment: Main text: 5 pages (including 4 figures), Supplementary Information: 8 pages (including 7 figures