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Additional file 1. Supplementary file 1.

To investigate temperament as an early risk marker for autism spectrum disorder (ASD), we examined parent-reported temperament for high-risk (HR, n = 170) and low-risk (LR, n = 77) siblings at 8, 14, and 24months. Diagnostic assessment was performed at 36 months. Group-based analyses showed linear risk gradients, with more atypical temperament for HR-ASD, followed by HR-Atypical, HR-Typical, and LR siblings. Temperament differed significantly between outcome groups (0.03 ≤ ηp2 ≤ 0.34). Machine learning analyses showed that, at an individual level, HR-ASD siblings could not be identified accurately, whereas HR infants without ASD could. Our results emphasize the discrepancy between group-based and individual-based predictions and suggest that while temperament does not facilitate early identification of ASD individually, it may help identify HR infants who do not develop ASD.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later‐born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near‐infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek‐a‐boo) compared to non‐social images (vehicles) and human vocalizations compared to non‐vocal sounds. At 4–6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced‐reduced activation to visual social stimuli relative to low‐risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS‐TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non‐vocal sounds within left lateralized temporal (aMTG‐STG/pSTS‐TPJ) regions compared with low‐risk infants and high‐risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent‐reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months. Electronic supplementary material The online version of this article (10.1007/s10803-018-3509-x) contains supplementary material, which is available to authorized users.

Highlights • Toddlers with ASD show typical social orienting and positive facial expressions in response to predictable social stimuli. • Variable social stimuli provoke an atypical pattern of reward-seeking behaviour in toddlers with ASD. • Simulated social interaction, made possible by gaze-contingent eye-tracking, shows great potential to probe the conditions under which impaired social interaction emerges in ASD., Several accounts have been proposed to explain difficulties with social interaction in autism spectrum disorder (ASD), amongst which atypical social orienting, decreased social motivation or difficulties with understanding the regularities driving social interaction. This study uses gaze-contingent eye-tracking to tease apart these accounts by measuring reward related behaviours in response to different social videos. Toddlers at high or low familial risk for ASD took part in this study at age 2 and were categorised at age 3 as low risk controls (LR), high-risk with no ASD diagnosis (HR-no ASD), or with a diagnosis of ASD (HR-ASD). When the on-demand social interaction was predictable, all groups, including the HR-ASD group, looked longer and smiled more towards a person greeting them compared to a mechanical Toy (Condition 1) and also smiled more towards a communicative over a non-communicative person (Condition 2). However, all groups, except the HR-ASD group, selectively oriented towards a person addressing the child in different ways over an invariant social interaction (Condition 3). These findings suggest that social interaction is intrinsically rewarding for individuals with ASD, but the extent to which it is sought may be modulated by the specific variability of naturalistic social interaction.

An enhanced ability to detect visual targets amongst distractors, known as visual search (VS), has often been documented in Autism Spectrum Disorders (ASD). Yet, it is unclear when this behaviour emerges in development and if it is specific to ASD. We followed up infants at high and low familial risk for ASD to investigate how early VS abilities links to later ASD diagnosis, the potential underlying mechanisms of this association and the specificity of superior VS to ASD. Clinical diagnosis of ASD as well as dimensional measures of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were ascertained at 3 years. At 9 and 15 months, but not at age 2 years, high-risk children who later met clinical criteria for ASD (HR-ASD) had better VS performance than those without later diagnosis and low-risk controls. Although HR-ASD children were also more attentive to the task at 9 months, this did not explain search performance. Superior VS specifically predicted 3 year-old ASD but not ADHD or anxiety symptoms. Our results demonstrate that atypical perception and core ASD symptoms of social interaction and communication are closely and selectively associated during early development, and suggest causal links between perceptual and social features of ASD. Keywords: Visual search, Visual attention, ASD, ADHD, Infant, Familial risk

Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of ≥100 points or a CDAI score150). The primary end point for the maintenance trial was remission at week 44 (CDAI score150).The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups.Among patients with moderately to severely active Crohn's disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).

The aim of the current paper was to use data from a prospective study to assess the impact of early motor skills on the rate of language development in infants with an older sibling with Autism Spectrum Disorder (ASD), who are at increased risk of developing ASD themselves. Infants were tested prospectively at four points (7, 14, 24 and 36 months), and were assessed for ASD at the last visit. Latent growth curve analysis was used to model rate of language development using the Vineland Adaptive Behavior Scales between 7-36 months in infants at high and low familial risk for ASD. Motor scores from the Mullen Scales of Early Learning at 7 months were used as predictors of language growth. Gross motor scores predicted the subsequent rate of expressive, but not receptive, language development in at-risk siblings who were later diagnosed with ASD. Although the pattern was similar for fine motor skills, the relationship did not reach significance. It seems that early motor delay impacts the rate of development of expressive language, and this may be of particular importance to infants at increased risk of developing ASD.

Little is known about how spontaneous attentional deployment differs on a millisecond-level scale in the early development of autism spectrum disorders (ASD). We measured fine-grained eye movement patterns in 6-to 9-month-old infants at high or low familial risk (HR/LR) of ASD while they viewed static images. We observed shorter fixation durations (i.e. the time interval between saccades) in HR than LR infants. Preliminary analyses indicate that these results were replicated in a second cohort of infants. Fixation durations were shortest in those infants who went on to receive an ASD diagnosis at 36 months. While these findings demonstrate early-developing atypicality in fine-grained measures of attentional deployment early in the etiology of ASD, the specificity of these effects to ASD remains to be determined.

Second Symposium on Temperature Measurement in Industry and Science : proceedings : [TEMPMEKO '84], October 16-18, 1984, Suhl, Germany

Temperature measurement : proceedings of International Symposium on Temperature Measurement in Industry and Science, April 16-19, 1986, Beijing, China

TEMPMEKO '90 : 4th International Symposium on Temperature and Thermal Measurements in Industry and Science : pre-prints, September 17-19, 1990, Helsinki, Finland

Temperature : its measurement and control in science and industry, volume 4 : [proceedings of the Fifth Symposium on Temperature], June 21-24, 1971, Washington, D.C., USA

Temperature measurement : proceedings of International Symposium on Temperature Measurement in Industry and Science, April 16-19, 1986, Beijing, China

Temperature : its measurement and control in science and industry, volume five : [proceedings of the Sixth International Temperature Symposium], March 15-18, 1982, Washington, D.C., USA

TEMPMEKO 2001 : 8th International Symposium on Temperature and Thermal Measurements in Industry and Science, June 19-21, 2001, Berlin, Germany

Temperature : its measurement and control in science and industry, volume six : proceedings of the Seventh International Temperature Symposium, April 28-May 1, 1992, Toronto, Ontario, Canada

AIM-92 : proceedings of Australasian Instrumentation and Measurement Conference, November 1992, Auckland, New Zealand

Temperature : its measurement and control in science and industry, volume five : [proceedings of the Sixth International Temperature Symposium], March 15-18, 1982, Washington, D.C., USA

Australasian Instrumentation and Measurement Conference 1989 : advances in the science, technology and engineering of instrumentation : preprints of papers, November 14-17, 1989, Adelaide, Australia

TEMPMEKO 2001 : 8th International Symposium on Temperature and Thermal Measurements in Industry and Science, June 19-21, 2001, Berlin, Germany

Temperature : its measurement and control in science and industry, volume six : proceedings of the Seventh International Temperature Symposium, April 28-May 1, 1992, Toronto, Ontario, Canada

Proceedings of TEMPMEKO '96 : 6th International Symposium on Temperature and Thermal Measurements in Industry and Science, September 10-12, 1996, Torino, Italy

Temperature : its measurement and control in science and industry, volume 4 : [proceedings of the Fifth Symposium on Temperature], June 21-24, 1971, Washington, D.C., USA

Proceedings of TEMPMEKO '99 : the 7th International Symposium on Temperature and Thermal Measurements in Industry and Science, June 1-3, 1999, Delft, The Netherlands

Temperature : its measurement and control in science and industry, volume 4 : [proceedings of the Fifth Symposium on Temperature], June 21-24, 1971, Washington, D.C., USA

Les hasards de la vie ont fait que j'ai entrepris avec Joël Bonnemaison des études de terroir sur l'île de Tongoa (Vanuatu) en 1969-1970. Une des conséquences de notre rencontre fut un débat qui s'est déroulé dans la littérature scientifique au cours des années 1970 sur les processus de migration au Vanuatu. Ce débat a contribué au développement des idées de Bonnemaison sur la façon dont les mouvements de population participent aux transformations culturelles et économiques au sein des sociétés insulaires. Il s'agissait d'une des premières étapes dans l'élaboration de sa réflexion ô combien féconde sur les fondements de l'identité océanienne au tournant du XXè siècle. (Résumé d'auteur)

Theta oscillations (spectral power and connectivity) are sensitive to the social content of an experience in typically developing infants, providing a possible marker of early social brain development. Autism is a neurodevelopmental condition affecting early social behaviour, but links to underlying social brain function remain unclear. We explored whether modulations of theta spectral power and connectivity by naturalistic social content in infancy are related to family history for autism. Fourteen-month-old infants with (family history; FH; N = 75) and without (no family history; NFH; N = 26) a first-degree relative with autism watched social and non-social videos during EEG recording. We calculated theta (4–5 Hz) spectral power and connectivity modulations (social–non-social) and associated them with outcomes at 36 months. We replicated previous findings of increased theta power and connectivity during social compared to non-social videos. Theta modulations with social content were similar between groups, for both power and connectivity. Together, these findings suggest that neural responses to naturalistic social stimuli may not be strongly altered in 14-month-old infants with family history of autism.

We conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7–8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.

Series: Advances in Geophysics