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Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6-30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior-temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing., (© 2024. The Author(s).)

Introduction: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions., Methods and Analysis: The STREAM project will enrol and assess 4000 children aged 0-6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves., Ethics and Dissemination: Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research-Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health-Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Lay Abstract: Autistic individuals are more likely than non-autistic individuals to experience a mental health condition in their lifetime, and this includes externalising and internalising symptoms. We know very little about how different environments and family conditions impact these symptoms for autistic individuals. Improving our understanding of these relationships is important so that we can identify individuals who may be in greater need of support. In this article, we seek to improve our understanding of how environmental and family conditions impact externalising and internalising symptoms in autistic and non-autistic people. To do this, we conducted analyses with two cohorts in very different settings - in Europe and South Africa - to ensure our findings are globally representative. We used advanced statistical methods to establish environmental and family conditions that were similar to each other, and which could be combined into specific 'factors'. We found that four similar 'factors' could be identified in the two cohorts. These were distinguished by personal characteristics and environmental conditions of individuals, and were named Person Characteristics, Family System, Parental and Material Resources. Interestingly, just 'Family System' was associated with internalising and externalising symptoms, and this was the same in both cohorts. We also found that having high traits of autism impacted this relationship between Family System and mental health conditions with opposite directions in the two settings. These results show that characteristics in the Family System are associated with internalising and externalising symptoms, and autistic persons are particularly impacted, reinforcing the notion that family stressors are important to consider when implementing policy and practice related to improving the mental health of autistic people., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: J.T. has acted as a paid consultant and is a current employee of F. Hoffmann-La Roche AG. T.C. has acted as a paid consultant of F. Hoffmann-La Roche Ltd and Servier and receives royalties for the publication of textbooks for Guilford Press and Sage Publications. J.B. has been in the past 3 years a consultant to/member of advisory boards of/and/or speaker for Janssen Cilag BV, Eli Lilly, Lundbeck, Shire, Roche, Novartis, Medice, and Servier. S.B. receives royalties for the German and Swedish KONTAKT manuals and adaptations of the ADI-R, ADOS, and S.R.S. from Hogrefe Publishers, and has in the past 3 years acted as an author, consultant or lecturer for Medice and Roche. T.B. has served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien and Oxford University Press; the present work is unrelated to these relationships. A.S.J.C. has acted as a paid consultant for F. Hoffman-La Roche and Servier, and has been actively involved in clinical trials managed by both companies. All other authors report no biomedical financial interests or potential conflicts of interest.

Measures of early neuro-cognitive development that are suitable for use in low-resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low-resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non-social stimuli. We recorded simultaneous 20-channel EEG and eye-tracking in 72 children aged 4-12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow-up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye-tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non-social stimuli is feasible in low-resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors., (© 2024 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

Background: Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, and in neurodevelopmental conditions, such as autism., Methods: Using eye-tracking, we measured social attention in a large cohort of autistic (n = 123) and nonautistic females (n = 107), and autistic (n = 330) and nonautistic males (n = 204), aged 6-30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean-static, naturalistic-static, and naturalistic-dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males., Results: In the lean-static stimulus, average face-looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face-looking were seen in autistic vs. nonautistic females, but not males, with face-looking peaking later in the trial in autistic females. In the naturalistic-dynamic stimulus, average face-looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face-looking was associated with higher observer-measured autistic characteristics in autistic females, but not in males., Conclusions: Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face-looking in autistic females. These findings support the role of social attention in the emergence of sex-related differences in autistic characteristics, suggesting an avenue to phenotypic stratification., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Electroencephalography (EEG) has substantial potential value for examining individual differences during early development. Current challenges in developmental EEG research include high dropout rates and low trial numbers, which may in part be due to passive stimulus presentation. Comparability is challenged by idiosyncratic processing pipelines. We present a novel toolbox ("Braintools") that uses gaze-contingent stimulus presentation and an automated processing pipeline suitable for measuring visual processing through low-density EEG recordings in the field. We tested the feasibility of this toolbox in 61 2.5- to 4-year olds, and computed test-retest reliability (1- to 2-week interval) of event-related potentials (ERP) associated with visual (P1) and face processing (N290, P400). Feasibility was good, with 52 toddlers providing some EEG data at the first session. Reliability values for ERP features were moderate when derived from 20 trials; this would allow inclusion of 79% of the 61 toddlers for the P1 and 82% for the N290 and P400. P1 amplitude/latency were more reliable across sessions than for the N290 and P400. Amplitudes were generally more reliable than latencies. Automated and standardized solutions to collection and analysis of event-related EEG data would allow efficient application in large-scale global health studies, opening significant potential for examining individual differences in development., (© 2021 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

Background: Sociocommunicative difficulties, including abnormalities in eye contact, are core diagnostic features of autism spectrum disorder (ASD). Many studies have used eye tracking to measure reduced attention to faces in autistic people; however, most of this work has not taken advantage of eye-tracking temporal resolution to examine temporal profiles of attention., Methods: We used growth curve analysis to model attention to static social scenes as a function of time in a large (N = 650) sample of autistic participants and neurotypical participants across a wide age range (6-30 years)., Results: The model yielded distinct temporal profiles of attention to faces in the groups. Initially, both groups showed a relatively high probability of attending to faces, followed by decline after several seconds. The neurotypical participants, however, were significantly more likely to return their attention to faces in the latter part of each 20-second trial, with increasing probability with age. In contrast, the probability of returning to the face in the autistic participants remained low across development. In participants with ASD, more atypical profiles of attention were associated with lower Vineland Adaptive Behavior Scales communication scores and a higher curvature in one data-driven cluster correlated with symptom severity., Conclusions: These findings show that social attention not only is reduced in ASD, but also differs in its temporal dynamics. The neurotypical participants became more sophisticated in how they deployed their social attention across age, a pattern that was significantly reduced in the participants with ASD, possibly reflecting delayed acquisition of social expertise., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The influence of arousal on visual attention was examined in 6.5-month-old infants (N = 42) in the context of a visual search task. Phasic increases in arousal were induced with brief sounds and measured with pupil dilation. Evidence was found for an inverted U-shaped relation between pupil dilation amplitude and visual orienting, with highest likelihood of a target fixation at intermediate levels of arousal. Effects were similar for facial stimuli and simple objects. Together, these results contribute to our understanding of the relation between arousal and attention in infancy. The study also demonstrates that infants have a bias to orient to human eyes, even when presented in isolation., (© 2018 The Authors. Child Development published by Wiley Periodicals, Inc. on behalf of Society for Research in Child Development.)

Meal intake leads to a significant and prolonged increase in cardiac output to supply the splanchnic vasculature. A meal is associated with sympathetic activation of the cardiovascular system, and food ingestion is correlated with an increase in heart rate, an increase in cardiac stroke volume, and QTc interval shortening for up to 7 hours. Given the complexity of the system, one or several of many mechanisms could explain this observation. The shortening of the QTc interval was correlated with a rise of C-peptide following food ingestion, but the mechanisms by which C-peptide may be involved in the modulation of cardiac repolarization are still unknown. This shortening of the myocardial action potential caused by the ingestion of food was further investigated in the present study by measuring the QRS, J-T peak , and T peak -T end intervals in search of further clues to better understand the underlying mechanisms. A retrospective analysis was conducted based on data collected in a formal thorough QT/QTc study in which 32 subjects received a carbohydrate-rich "continental" breakfast, moxifloxacin without food, and moxifloxacin with food. We assessed the effect of food on T-wave morphology using validated algorithms for measurement of J-T peak and T peak -T end intervals. Our findings demonstrate that a standardized meal significantly shortened J-T peak for 4 hours after a meal and to a much lesser extent and shorter duration (up to 1 hour) prolonged the T peak -T end and QRS intervals. This suggests that the QTc shortening occurs mainly during phase 2 of the cardiac action potential. As there was no corresponding effect on T peak -T end beyond the first hour, we conclude that a meal does not interfere with the outward correcting potassium channels but possibly with Ca 2+ currents. An effect on mainly Ca 2+ aligns well with our understanding of physiology whereby an increase in stroke volume, as observed after a meal, is associated with changes in Ca 2+ cycling in and out of the sarcoplasmic reticulum during cardiac myocyte contraction., (© 2019, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.)

During the first year of life, infants develop the capacity to follow the gaze of others. This behavior allows sharing attention and facilitates language acquisition and cognitive development. This article reviews studies that investigated gaze-following before 12 months of age in typically developing infants and discusses current theoretical perspectives on early GF. Recent research has revealed that early GF is highly dependent on situational constraints and individual characteristics, but theories that describe the underlying mechanisms have partly failed to consider this complexity. We propose a novel framework termed the perceptual narrowing account of GF that may have the potential to integrate existing theoretical accounts., (© International Congress of Infant Studies (ICIS).)

A defective attention to faces and eyes characterizes autism spectrum disorder (ASD), however, the role of contingent information - such as the task instructions - remains still unclear. Our study aimed to investigate the face-orienting response and the subsequent attentive selection in the presence of varying task instructions in individuals with atypical and typical development. Twenty young adults with ASD and 24 young adults with typical development participated in our eye-tracking study. The participants received one of three different instructions at the beginning of each trial and watched scenes of a social interaction. The instructions asked either to find an object (visual-search, VS), to identify which actor was paying attention to the conversation (gaze-reading, GR), or to simply watch the video (free-viewing, FV). We found that the groups did not differ in terms of proportion of first fixations to the face. Nonetheless, average looking time and proportional looking time to faces differed across groups. Furthermore, proportional looking time to faces was task-dependent in the ASD group only, with maximum proportion in the GR and minimum in the VS condition. This result cannot be explained by a lack of an initial bias to orient to the face, since the face-orienting tendency was similar in the ASD and the control group.

Parents and children form a family: their characteristics balance personal and family well-being with healthy levels of stress. Research on parents of children with Autism Spectrum Disorder (ASD) demonstrated that higher levels of parental stress are associated with communication impairment, a core symptom of ASD. The aim of this article is to discuss the connection between non-verbal communication impairment and parental psychological distress, in families with children with ASD. The interaction between atypical communication and distress of parents likely determines a cascade effect on the parent-child dyad; in fact, it decreases the quality and frequency of interactions, preventing the establishment of a healthy parent-child relationship and leading to a series of collateral problems. To this perspective, guiding the parents to reframe their children's atypical communicative behaviour can relieve parental stress and re-program the interactional routine. This observation stresses the importance of interventions centred on the dyad, especially during early development and soon after the diagnosis, when the communicative impairment may be extremely severe., Competing Interests: The authors have declared that no competing interests exist.

Background: Recent investigations suggest a possible common genetic background between Autism Spectrum Disorders (ASD) and Celiac Disease (CD). However, studies regarding this association are scarce and often limited by the small sample sizes and/or large heterogeneity among ASD groups in terms of demographic and clinical features. The present study aims to investigate the overall CD prevalence (biopsy proven-CD patients plus screening detected tTG and EMA positive cases) in a large population of pre-schoolers with ASD referred to a tertiary care University Hospital., Methods: We retrospectively collected data about 382 children (mean age: 46.97 ± 13.55 months; age-range: 18-72 months) consecutively diagnosed as ASD (according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) over the period 2010-2013, and who performed a serological CD screening., Results: The overall CD prevalence was 2.62%, which is statistically significant higher to that reported in the Italian paediatric population (p = 0.0246). Half of these children had no symptoms or risk factors related to CD when they performed the serological screening., Conclusions: If replicated, these data suggest the importance of regular screening for CD in young patients with ASD, and are of relevance for clinical and public health.

Background: Gastrointestinal (GI) symptoms are frequently reported in children with Autism Spectrum Disorder (ASD), and an impact of GI comorbidity on ASD behavioral problems has been hypothesized., Aims: To explore the type and the prevalence of GI symptoms in ASD patients and typical development (TD) controls, and to investigate their possible association with behavioral problems., Methods: A total of 230 preschoolers were included in this study. Specifically, four groups of children were evaluated: ASD individuals suffering from GI symptoms (ASD/GI+), ASD subjects without GI symptoms (ASD/GI-), TD peers with (TD/GI+) and without (TD/GI-) GI symptoms. Parental report of behavioral problems and GI symptoms were assessed through the Child Behavior Check List 1½-5., Results: A significant higher percentage of ASD (37.4%) versus TD (14.8%) with GI symptoms was observed. 'Constipated' and 'Not-Eat' were the most frequent GI symptoms both in ASD and in TD groups, but they were evaluated as more severe in ASD patients. ASD/GI+ children had more anxiety problems, somatic complaints, externalizing and total problems than ASD/GI- individuals. TD/GI+ did not show more behavioral problems than TD/GI-., Conclusion: Development of evidence-based guidelines for identification of GI problems in ASD preschoolers is warranted. GI symptomatology should be accurately assessed, especially in ASD children with anxiety and/or externalizing behavioral problems., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: In patients with postoperative recurrence of Crohn's disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses., Design: Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn's Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0-1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn's disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy., Results: Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects., Conclusions: Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment.

Introduction: Short antiviral therapy has been proposed for patients with chronic hepatitis C, easy genotypes, low fibrosis score, low viral load at baseline, and rapid virological response (RVR). However, this approach is not completely accepted., Objectives: The aims of this study were (a) to evaluate the sustained virological response (SVR) in noncirrhotic patients with genotype 2 or 3, achieving an RVR, randomized to receive pegylated-interferon (IFN) α-2b plus ribavirin for either 16 or 24 weeks and (b) to carry out direct cost analysis comparing patients treated for 16 versus 24 weeks., Results: Of the 142 initially evaluated patients, 130 were enrolled according to the selection criteria, but independent of the viral load. According to the intention-to-treat analysis, SVR was achieved in 104 patients (80%). Logistic regression analysis showed that RVR (P<0.001) and genotype 2 (P<0.03) were the most important factors independently associated with SVR. Among patients with RVR, SVR was comparable between patients treated for 16 weeks and those treated for 24 weeks (86.2 vs. 89.7%, P=NS). The mean direct costs were €4003.7 for patients treated for 16 weeks and €5676.7 for those treated for 24 weeks, with a 30% difference between the two arms., Conclusion: In patients achieving an RVR, a 16-week treatment with pegylated-interferon plus ribavirin was comparable to a 24-week treatment. Short treatment in patients with RVR allows us to save 30% of the direct costs, independent of the viral load at baseline.

Objective: To investigate the incidence and define the diagnostic aspects of intraepithelial squamous cell carcinoma of the oesophagus and to show the trend in its natural history., Design: Analysis of records of more than 31000 upper gastrointestinal endoscopies in a secondary referral centre., Setting: Gastroenterology unit, Italy., Subjects: 23 men and 2 women with endoscopic and histological diagnoses of intraepithelial squamous cell carcinoma of the oesophagus., Results: The incidence was 0.8/1000 patients/year. There was a coexisting oropharyngeal or laryngeal cancer in 17 patients. The endoscopic appearance was of a more or less well-defined hyperaemic area. Lesions progressed to infiltrating carcinoma in a mean of 18.3 months range 11-32)., Conclusions: Intraepithelial squamous cell carcinoma is rare in this population. Endoscopy and histology are essential for diagnosis and staging.

To study the effect of Esaprazole, a new antiulcer drug, on acid, peptic and alkaline secretion a modified gastric acid test was performed in 18 duodenal ulcer patients. Pentagastrin was administered as bolus 30' and 75' after the beginning of the test, followed by Esaprazole 300 mg i.v. at 90'. Gastric juice was collected every 15' for determination of: total volume, volume of non parietal secretion, acid, bicarbonate and pepsin output. Serum pepsinogen group I was determined by radioimmunoassay. Esaprazole had a significant inhibitory effect on the total volume of gastric secretion and on volume of non parietal secretion. Pepsin output and serum pepsinogen group I were not affected by Esaprazole, while bicarbonate secretion was reduced. Antiulcer activity of Esaprazole seems to be due to the reduction of total volume of gastric secretion.