Topical application of retinyl propionate, 4 hexyl resorcinol, and niacinamide reverses molecular and clinical features of ageing.

OBJECTIVE: Topical tretinoin is the mainstay of treatment for photoageing, despite the risk of skin irritation. Cosmetic combination anti-ageing formulations may offer similar efficacy to tretinoin, while improving on tolerability. We aim to demonstrate facial appearance benefits of a novel triple-active cosmetic formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide and to identify transcriptomic biomarkers underpinning these benefits. METHODS: A cosmetic prototype formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide was evaluated ex vivo and in a clinical study. For ex vivo experiments, the cosmetic formulation was applied for 3 days to healthy surgical discard skin from female donors aged 31-51 years, with tissues harvested for gene expression and histologic analyses. In the clinical study, females aged 47-66 years with moderate-to-severe overall visual photodamage on the face applied either topical 0.02% tretinoin or the cosmetic formulation to the face for 16 weeks and to forearms for 1 week, with forearm biopsies taken for gene expression analyses. Visual grading for facial photodamage and VISIA-CR images was taken throughout the clinical study. Safety was visually assessed during site visits, and adverse event monitoring was conducted throughout. RESULTS: Gene expression analyses in both studies revealed modulation of pathways associated with skin rejuvenation, with several genes of interest identified due to being implicated in ageing and differentially expressed following the application of the cosmetic formulation. Reversal of a consensus skin ageing gene signature was observed with the cosmetic formulation and tretinoin in the ex vivo and clinical studies. Both the cosmetic formulation and tretinoin clinically improved the overall appearance of photoageing, crow's feet, lines, wrinkles, and pores. Adverse event reporting showed that the cosmetic formulation caused less skin irritation than tretinoin. CONCLUSION: In a double-blind clinical study, the novel triple-active cosmetic combination formulation improved the visual appearance of photoageing similarly to prescription tretinoin. The cosmetic formulation and tretinoin reversed a consensus gene signature associated with ageing. Together with adverse event reporting, these results suggest that the cosmetic formulation may be a well-tolerated and efficacious alternative to tretinoin for improving the visual features of photoageing.

OBJECTIF: Le trétinoine topique est le pilier du traitement du photovieillissement, malgré le risque d'irritation cutanée. Les formulations cosmétiques combinés anti­âge peuvent offrir une efficacité similaire à la trétinoine, tout en améliorant la tolérance. Notre objectif est de démontrer les avantages esthétiques pour l'apparence du visage d'une nouvelle formulation cosmétique triple active contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide, et d'identifier les biomarqueurs transcriptomiques sous­jacents à ces avantages. MÉTHODES: Une formulation cosmétique prototype contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide a été évaluée ex vivo et lors d'une étude clinique. Pour les expériences ex vivo, la formulation cosmétique a été appliquée pendant 3 jours sur des peaux saines issues de donatrices âgées de 31 à 51 ans, avec prélèvement de tissus pour l'analyse de l'expression génique et l'histologie. Dans l'étude clinique, des femmes âgées de 47 à 66 ans présentant un photovieillissement visuel global modéré a sévère sur le visage ont appliqué soit du trétinoine topique à 0.02%, soit la formulation cosmétique sur le visage pendant 16 semaines et sur les avant­bras pendant 1 semaine, avec des biopsies d'avant­bras prélevées pour l'analyse de l'expression génique. L'évaluation visuelle du photovieillissement facial et les images VISIA­CR ont été réalisées tout au long de l'étude clinique. La sécurité a été évaluée visuellement lors des visites sur site, et une surveillance des événements indésirables a été effectuée. RÉSULTATS: Les analyses de l'expression génique dans les deux études ont révélé une modulation des voies associées au rajeunissement cutané, avec plusieurs gènes d'intérêts identifiés en raison de leur implication dans le vieillissement et de leur expression différentielle suite à l'application de la formulation cosmétique. Une inversion de la signature génique du vieillissement cutané consensuelle a été observée avec la formulation cosmétique et la trétinoine dans les études ex vivo et cliniques. La formulation cosmétique et la trétinoine ont toutes deux amélioré cliniquement l'apparence globale du photovieillissement, des pattes d'oie, des ridules, des rides et des pores. Les rapports sur les événements indésirables ont montré que la formulation cosmétique provoquait moins d'irritation cutanée que la trétinoine. CONCLUSION: Dans une étude clinique en double aveugle, la nouvelle formulation cosmétique triple active a amélioré l'apparence visuelle du photovieillissement de manière similaire à la trétinoine sur ordonnance. La formulation cosmétique et la trétinoine ont inversé une signature génique consensuelle associée au vieillissement. En tenant compte des rapports sur les événements indésirables, ces résultats suggèrent que la formulation cosmétique pourrait constituer une alternative bien tolérée et efficace à la trétinoine pour améliorer les caractéristiques visuelles du photovieillissement.

Use of the Capability, Opportunity and Motivation Behaviour model (COM-B) to Understand Interventions to Support Physical Activity Behaviour in People with Stroke: An Overview of Reviews.

OBJECTIVE: Physical activity in people with stroke remains low despite considerable research. This overview aimed to provide high-level synthesis and aid clinical decision-making. The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to classify interventions to understand which components improve physical activity behaviour in people with stroke. DATA SOURCES: CINAHL, Cochrane Database, MEDLINE, PEDro, PsychINFO, SPORTDiscus. REVIEW METHODS: A systematic search was conducted (November 2023) to identify reviews of interventions to improve physical activity in people with stroke. Results were screened and assessed for eligibility. Participant characteristics, intervention classification using COM-B, and effect of intervention were extracted. Quality was assessed using AMSTAR2, and Corrected Cover Analysis for study overlap. Narrative synthesis was used to understand components of interventions to improve physical activity behaviour. RESULTS: 1801 references were screened and 29 full-text references assessed for eligibility. Twenty reviews were included. Quality ranged from critically low (n = 3) to high (n = 10). Study overlap calculated using corrected cover area indicated slight overlap (0.028) and minimal reporting bias.The majority of participants were mobile with mild stroke and community dwelling. Twenty-three interventions were classified using COM-B. Three of twelve interventions classified to one aspect of the COM-B were effective. Fourteen of sixteen effective interventions combined at least two COM-B elements, ten of these combined capability and motivation. CONCLUSION: Interventions including at least two elements of the COM-B are most likely to improve physical activity in mobile stroke survivors. Further research is needed to understand physical activity behaviour in those with moderate to severe stroke.

Infants who develop autism show smaller inventories of deictic and symbolic gestures at 12 months of age.

Gestures are an important social communication skill that infants and toddlers use to convey their thoughts, ideas, and intentions. Research suggests that early gesture use has important downstream impacts on developmental processes, such as language learning. However, autistic children are more likely to have challenges in their gestural development. The current study expands upon previous literature on the differences in gesture use between young autistic and non-autistic toddlers by collecting data using a parent-report questionnaire called the MCDI-Words and Gestures at three time points, 12, 18, and 24 months of age. Results (N = 467) showed that high-likelihood infants who later met diagnostic criteria for ASD (n = 73 HL-ASD) have attenuated gesture growth from 12 to 24 months for both deictic gestures and symbolic gestures when compared to high-likelihood infants who later did not meet criteria for ASD (n = 249 HL-Neg) and low-likelihood infants who did not meet criteria for ASD (n = 145 LL-Neg). Other social communicative skills, like play behaviors and imitation, were also found to be impacted in young autistic children when compared to their non-autistic peers. Understanding early differences in social communication growth before a formal autism diagnosis can provide important insights for early intervention.

Effect of Exercise Training on Peak Aerobic Power After Heart Transplantation: A Brief Review.

Heart transplantation (HTP) is a life-saving therapy for selected individuals with end-stage refractory heart failure. Despite improvements in quality of life and survival, HTP recipients' peak aerobic power (peak VO2) remains up to 50% lower than age-matched healthy control subjects owing to abnormal cardiovascular and skeletal muscle function. Currently, little is known regarding the effect of exercise training (ET) to improve peak VO2 after HTP. This brief review aims to summarise existing evidence regarding the role of ET on peak VO2 and its determinants, highlights the upper limits of endurance performance in highly trained HTP athletes, and identifies areas for future HTP exercise rehabilitation research.

Contingent conversations build more than language: How communicative interactions in toddlerhood relate to preschool executive function skills.

High-quality communicative interactions between caregivers and children provide a foundation for children's social and cognitive skills. Although most studies examining these types of interactions focus on child language outcomes, this paper takes another tack. It examines whether communicative, dyadic interactions might also relate to child executive function (EF) skills and whether child language might mediate this relation. Using a subset of data from the NICHD Study of Early Child Care and Youth Development, dyadic interactions between 2-year-olds and their mothers were coded for three behaviors: symbol-infused joint engagement, routines and rituals, and fluency and connectedness. Child language was assessed at age 3 and three facets of EF (self-regulation, sustained attention, and verbal working memory) were assessed at age 4.5. Structural equation modeling showed that dyadic interaction related to later child sustained attention and verbal working memory, indirectly through child language and directly related with child self-regulation. This suggests that communicative interactions with caregivers that include both verbal and non-verbal elements relate to child EF, in part through child language. Our findings have implications for the role of caregiver interactions in the development of language and cognitive skills more broadly. RESEARCH HIGHLIGHTS: Using structural equation modeling, we examined how communicative interactions between caregivers and toddlers relate to preschool executive function skills Communicative interactions relate to later language which in turn relates to sustained attention and verbal working memory in preschool Communicative interactions relate directly to self-regulation in preschool Associations between communicative interactions, language, and executive function vary across facets of executive function and may not be unidirectional.

Assessment of CAR-T Cell-Mediated Cytotoxicity in 3D Microfluidic Cancer Co-Culture Models for Combination Therapy.

Chimeric antigen receptor (CAR)-T cell therapy is efficacious against many haematological malignancies, but challenges remain when using this cellular immunotherapy for treating solid tumours. Classical 2D in vitro models fail to recapitulate the complexity of the tumour microenvironment, whilst in vivo models, such as patient-derived xenografts, are costly and labour intensive. Microfluidic technologies can provide miniaturized solutions to assess CAR-T therapies in 3D complex preclinical models of solid tumours. Here, we present a novel microfluidic immunoassay for the evaluation of CAR-T cell cytotoxicity and targeting specificity on 3D spheroids containing cancer cells and stromal cells. Monitoring the interaction between CAR-T cells and spheroid co-cultures, we show that CAR-T cells home towards target-expressing cancer cells and elicit a cytotoxic effect. Testing CAR-T cells in combination therapies, we show that CAR-T cell cytotoxicity is enhanced with anti-PD-L1 therapy and carboplatin chemotherapy. We propose this proof-of-concept microfluidic immunoassay as a material-saving, pre-clinical screening tool for quantification of cell therapy efficacy.

Self-Assembling Protein Surfaces for In Situ Capture of Cell-Free-Synthesized Proteins.

We present a new method for the surface capture of proteins in cell-free protein synthesis (CFPS). We demonstrate the spontaneous self-assembly of the protein BslA into functionalizable surfaces on the surface of a CFPS reaction chamber. We show that proteins can be covalently captured by such surfaces, using "Catcher/Tag" technology. Importantly, proteins of interest can be captured either when synthesised in situ by CFPS above the BslA surfaces, or when added as pure protein. The simplicity and cost efficiency of this method suggest that it will find many applications in cell-free-based methods.

Alteration of barrier properties, stratum corneum ceramides and microbiome composition in response to lotion application on cosmetic dry skin.

Xerosis, commonly referred to as dry skin, is a common dermatological condition affecting almost a third of the population. Successful treatment of the condition traditionally involves the application of cosmetic products facilitating the moisturisation of the skin with a range of ingredients including glycerol and fatty acids. While the effectiveness of these treatments is not in question, limited information exists on the impact on the skin microbiome following use of these products and the improvement in skin hydration. Here, we describe improvements in skin barrier properties together with increased levels of cholesterol, ceramides and long-chain fatty acids following application of Body Lotion. Concomitant alterations in the skin microbiome are also seen via 16S rRNA metataxonomics, in combination with both traditional and novel informatics analysis. Following 5 weeks of lotion use, beneficial skin bacteria are increased, with improvements in microbiome functional potential, and increases in pathways associated with biosynthesis of multiple long chain fatty acids.

Infant vocalizing and phenotypic outcomes in autism: Evidence from the first 2 years.

Infant vocalizations are early-emerging communicative markers shown to be atypical in autism spectrum disorder (ASD), but few longitudinal, prospective studies exist. In this study, 23,850 infant vocalizations from infants at low (LR)- and high (HR)-risk for ASD (HR-ASD = 23, female = 3; HR-Neg = 35, female = 13; LR = 32, female = 10; 80% White; collected from 2007 to 2017 near Philadelphia) were analyzed at 6, 12, and 24 months. At 12 months, HR-ASD infants produced fewer vocalizations than HR-Neg infants. From 6 to 24 months, HR-Neg infants demonstrated steeper vocalization growth compared to HR-ASD and LR infants. Finally, among HR infants, vocalizing at 12 months was associated with language, social phenotype, and diagnosis at age 2. Infant vocalizing is an objective behavioral marker that could facilitate earlier detection of ASD.

Are early social communication skills a harbinger for language development in infants later diagnosed autistic?-A longitudinal study using a standardized social communication assessment.

The early emergence of social communication challenges and their impact on language in infants later diagnosed with autism has sparked many early intervention programs that target social communication skills. While research has consistently shown lower scores on social communication assessments in the first year of life, there is limited research at 12-months exploring associations between different dimensions of social communication and later language. Understanding associations between early social communication skills and language would enhance our ability to choose high priority intervention goals that will impact downstream language skills. The current study used a standardized assessment to profile social communication skills across 516 infants with a high (HL) or low likelihood (LL-Neg) for autism (84% White, 60% Male), based on the presence of a sibling with autism in the family. The primary aim of the study was to profile social communication skill development in the second year of life and to evaluate associations between social communication skills and later language. HL infants who met criteria for autism (HL-ASD, N = 81) demonstrated widespread reductions in social communication skills at 12-months compared to HL infants who did not meet criteria for autism (HL-Neg, N = 277) and LL-Neg (N = 158) infants. Across all infants in the study, those with better social communication skills at 12-months had better language at 24-months. However, within group analyses indicated that infants who met criteria for autism did not show this developmental coupling until 24-months-of-age at which point social communication was positively associated with downstream language skills. The cascading pattern of reduced social communication skills as well as overall significant positive associations with later language provide further evidence for the need to support developing social communication skills prior to formal autism diagnosis, a goal that could possibly be reached through pre-emptive interventions.

Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences.

Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome's role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics.

Beyond talk: Contributions of quantity and quality of communication to language success across socioeconomic strata.

Infants from low-socioeconomic status (SES) households hear a projected 30 million fewer words than their higher-SES peers. In a recent study, Hirsh-Pasek et al. (Psychological Science, 2015; 26: 1071) found that in a low-income sample, fluency and connectedness in exchanges between caregivers and toddlers predicted child language a year later over and above quantity of talk (Hirsh-Pasek et al., Psychological Science, 2015; 26: 1071). Here, we expand upon this study by examining fluency and connectedness in two higher-SES samples. Using data from the NICHD Study of Early Child Care and Youth Development, we sampled 20 toddlers who had low, average, and high language outcomes at 36 months from each of 2 groups based on income-to-needs ratio (INR; middle and high) and applied new coding to the mother-toddler interaction at 24 months. In the high-INR group, the quality of mother-toddler interaction at 24 months accounted for more variability in language outcomes a year later than did quantity of talk, quality of talk, or sensitive parenting. These results could not be accounted for by child language ability at 24 months. These effects were not found in the middle-INR sample. Our findings suggest that when the quality of interaction, fluency and connectedness, predicts language outcomes, it is a robust relation, but it may not be universal.

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

OBJECTIVE: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life. METHODS: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age. RESULTS: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus). CONCLUSIONS: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.

Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy.

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.

Tezacaftor and ivacaftor for the treatment of cystic fibrosis.

Introduction: Cystic fibrosis (CF) is a complex, multi-system, genetic disease affecting over 70,000 people worldwide. The underlying defect is a mutation in the CFTR gene. Dysfunctional CFTR protein results in abnormal anion movement across epithelial membranes in affected organs. There has been a paradigm shift in CF treatment over the last decade with the advent of CFTR modulation, treatments which target this underlying genetic defect and have the potential to change the course of CF clinical disease.Areas covered: Available CFTR modulators in current clinical practice are reviewed in this article, with a direct comparison and summary of relevant pivotal clinical trials. The approval of ivacaftor and subsequent development of lumacaftor and tezacaftor dual combinations represents an exciting development in CF management in recent years.Expert opinion: Tezacaftor/ivacaftor (tez/iva) appears to have a more favorable adverse event and drug-drug interaction profile than lumacaftor/ivacaftor. Tez/iva has been approved, alongside Phe508del, for a large number of 'residual function' CFTR mutations, with some based on response to in vitro culture. Dual therapy with tez/iva has paved the way for triple CFTR modulation currently in clinical trials with an ultimate view to provide modulation therapy to the majority of CF genotypes in the future.

Community-Based, Caregiver-Implemented Early Language Intervention in High-Risk Families: Lessons Learned.

BACKGROUND: High-quality, early caregiver-child interaction facilitates language, cognitive, and health outcomes. Children in low socioeconomic status households experience less frequent and lower-quality language interactions on average than their middle to high socioeconomic status peers. Early caregiver-implemented intervention may help to improve outcomes for these children. OBJECTIVES: This article describes how we used community-based participatory research (CBPR) to develop and implement a community-based, caregiver-implemented early language intervention, including the challenges, solutions, and lessons learned in the process of CBPR. METHODS: We adopted an ethnographic approach to document and analyze our CBPR experiences in multiple phases of the project, including intervention design, training, implementation, and evaluation. LESSONS LEARNED: Developing the CBPR partnership, co-designing and implementing the study, and managing systems- level concerns like obtaining funding were central challenges for the researcher-community team. CONCLUSIONS: The CBPR model enhances early language intervention research by facilitating understanding of families in underserved communities and increasing the cultural relevancy of intervention materials.

Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups.

OBJECTIVES: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization. MATERIALS AND METHODS: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes. RESULTS: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively. CONCLUSION: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.

Early language exposure supports later language skills in infants with and without autism.

The way that parents communicate with their typically developing infants is associated with later infant language development. Here we aim to show that these associations are observed in infants subsequently diagnosed with autism spectrum disorder (ASD). This study had three groups: high-familial-risk infants who did not have ASD (n = 46); high-familial-risk infants who had ASD (n = 14); and low-familial-risk infants who exhibited typical development (n = 36). All-day home language recordings were collected at 9 and 15 months, and language skills were assessed at 24 months. Across all infants in the study, including those with ASD, a richer home language environment (e.g., hearing more adult words and experiencing more conversational turns) at 9 and 15 months was associated with better language skills. Higher parental educational attainment was associated with a richer home language environment. Mediation analyses showed that the effect of education on child language skills was explained by the richness of the home language environment. Exploratory analyses revealed that typically developing infants experience an increase in caregiver-child conversational turns across 9-15 months, a pattern not seen in children with ASD. The current study shows that parent behavior during the earliest stages of life can have a significant impact on later development, highlighting the home language environment as means to support development in infants with ASD. Autism Res 2019, 12: 1784-1795. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: It has long been understood that caregiver speech supports language skills in typically developing infants. In this study, parents of infants who were later diagnosed with ASD and parents of infants in the control groups completed all-day home language recordings. We found that for all infants in our study, those who heard more caregiver speech had better language skills later in life. Parental education level was also related to how much caregiver speech an infant experienced.

The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants.

The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive-classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD.