The home literacy environment of school-age autistic children with high support needs.

BACKGROUND: As a group, autistic children with high support needs (with adaptive functioning in the range of an intellectual disability) are at risk of significant literacy difficulties. We investigated the parent-reported home literacy environment of this group of children. METHOD: Sixty-two parents of autistic children (4.5 to 18.25 years) attending an autism-specific school completed a home literacy survey reporting on their child's: (1) alphabet knowledge, (2) interest in reading, (3) activities/interactions around books, (4) reading ability, and (5) writing ability. RESULTS: We found significant positive correlations between parent-reported child interest in reading and literacy-related interactions and skills, but not with child age. Children using spoken words to communicate obtained significantly greater scores on four home-literacy subscales, but not on reading interest. CONCLUSIONS: A better understanding of the home literacy activities of autistic children with high-support needs is needed to inform educational practices aimed at promoting literacy development in this vulnerable population.

A Parent-Mediated Anxiety Intervention Specifically Tailored for Autistic Preschoolers: A Pilot Study.

IMPORTANCE: Autistic children experience reduced participation in life activities. One factor that may contribute to their reduced levels of participation is anxiety, which is identified at higher rates among young autistic children than among their neurotypical peers. Anxiety is also strongly associated with sensory overresponsivity and has a considerable impact on daily functioning. OBJECTIVE: To determine the feasibility, acceptability, and usefulness of a small-group, parent-mediated intervention to prevent and reduce anxiety. DESIGN: Pre-post. SETTING: University research center. PARTICIPANTS: Three parents of autistic children (ages 4-7 yr). OUTCOMES AND MEASURES: Parents completed a six-session group training program. Parents completed an anxiety scale for their child before and after parent training. At the end of training, parents participated in a focus group and were interviewed 4 mo after training. RESULTS: Positively received aspects of the intervention were the benefits of a small group, composed of parents of autistic children, run by a facilitator with expertise in autism and anxiety. Parents gained knowledge, resulting in "taking a different approach" with their child and "seeing an interplay between anxiety and autism." After the intervention, parents reported a reduction in children's reported anxiety levels. CONCLUSIONS AND RELEVANCE: Knowledge of autism and anxiety acquired during a parent-mediated group increased parents' understanding of their child's behaviors and assisted them in supporting their child's participation. Further research, including larger studies, is required to determine the effectiveness of this intervention. What This Article Adds: The findings from this research provide preliminary support for the adaptation of an existing parent intervention (Cool Little Kids) to reduce anxiety among autistic children. Parents reported an increased awareness and understanding of anxiety and of the interplay between anxiety and autistic traits. Positionality Statement: This article uses the identity-first language autistic people. This nonableist language describes their strengths and abilities and is a conscious decision. This language is favored by autistic communities and self-advocates and has been adopted by health care professionals and researchers (Bottema-Beutel et al., 2021; Kenny et al., 2016).

Diffusiophoresis of charged colloidal particles in the limit of very high salinity.

Diffusiophoresis is the migration of a colloidal particle through a viscous fluid, caused by a gradient in concentration of some molecular solute; a long-range physical interaction between the particle and solute molecules is required. In the case of a charged particle and an ionic solute (e.g., table salt, NaCl), previous studies have predicted and experimentally verified the speed for very low salt concentrations at which the salt solution behaves ideally. The current study presents a study of diffusiophoresis at much higher salt concentrations (approaching the solubility limit). At such large salt concentrations, electrostatic interactions are almost completely screened, thus eliminating the long-range interaction required for diffusiophoresis; moreover, the high volume fraction occupied by ions makes the solution highly nonideal. Diffusiophoretic speeds were found to be measurable, albeit much smaller than for the same gradient at low salt concentrations.

Bioanalytical strategies in drug discovery and development.

A reliable, rapid, and effective bioanalytical method is essential for the determination of the pharmacokinetic, pharmacodynamic, and toxicokinetic parameters that inform the safety and efficacy profile of investigational drugs. The overall goal of bioanalytical method development is to elucidate the procedure and operating conditions under which a method can sufficiently extract, qualify, and/or quantify the analyte(s) of interest and/or their metabolites for the intended purpose. Given the difference in the physicochemical properties of small and large molecule drugs, different strategies need to be adopted for the development of an effective and efficient bioanalytical method. Herein, we provide an overview of different sample preparation strategies, analytical platforms, as well as procedures for achieving high throughput for bioanalysis of small and large molecule drugs.

Separable effects of the approximate number system, symbolic number knowledge, and number ordering ability on early arithmetic development.

There is evidence that early variations in the development of an approximate number system (ANS) and symbolic number understanding are both influences on the later development of formal arithmetic skills. We report a large-scale (N = 552) longitudinal study of the predictors of arithmetic spanning a critical developmental period (the first 3 years of formal education). Variations in early knowledge of symbolic representations of number and the ordinal associations between them are direct predictors of later arithmetic skills. The development of number ordering ability is in turn predicted by earlier variations in arithmetic, the ANS (numerosity judgments), and rapid automatized naming (RAN). These findings have important implications for theories of numerical and arithmetical development and potentially for the teaching of these skills.

The Production Effect Improves Memory in 7- to 10-Year-Old Children.

The production effect-whereby reading words aloud improves memory for those words relative to reading them silently-was investigated in two experiments with 7- to 10-year-old children residing in Brisbane, Australia. Experiment 1 (n = 41) involved familiar printed words, with words read aloud or silently appearing either in mixed- or blocked-list formats in a within-subject design. Recognition for words read aloud was better than for those read silently, an effect consistent across both list formats. These results were confirmed in Experiment 2 (n = 40) using longer lists of printed novel nonwords. Final analyses indicated that the production effect was comparable for words and nonwords. Findings are discussed in relation to the distinctiveness account and the use of production as a mnemonic in children.

The relationship between numerosity discrimination and arithmetic skill reflects the approximate number system and cannot be explained by inhibitory control.

Numerosity discrimination tasks (judging which of two random dotarrays contains the larger number) have been widely used as a measure of the efficiency of an approximate number system (ANS) and are a correlate of early arithmetic skills. Recently, it has been suggested that the relationship between numerosity discrimination and arithmeticis explained by inhibition rather than the ANS. We assessed this hypothesis in astudy of 496 children (mean age = 81.23 months) using numerosity discrimination tasks that manipulated the congruency between surface area and numerosity. Numerosity discrimination for incongruent arrays (which are postulated to require inhibition due to a conflict between judgments based on surface area rather than numerosity) was more difficult than that for congruent arrays. However, all numerosity discrimination tasks showed substantial correlations with each other and correlated with arithmetic. A latent variable path model showed that a general numerosity judgment factorcorrelated witharithmetic even after controlling for a measure of response inhibition. In contrast, numerosity discrimination for incongruent arrays showed no unique relationship with arithmetic ability. Our results do not support the view that the relationship between numerosity discrimination and arithmetic is largely attributable to inhibition; rather, theyare consistent withthe view that numerosity discrimination tasks tap the operation of an ANS.

A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.

BACKGROUND: A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic (PK) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). METHODS: A PK/pharmacodynamic (PD) model was developed by measuring mucosal tissue concentrations of tenofovir, emtricitabine, their active metabolites (tenofovir diphosphate [TFVdp] and emtricitabine triphosphate [FTCtp], respectively), and competing endogenous nucleotides (dATP and dCTP) in 47 healthy women. TZM-bl and CD4(+) T cells were used to identify 90% effective concentration (EC90) ratios of TFVdp to dATP and FTCtp to dCTP (alone and in combination) for protection against HIV. Monte-Carlo simulations were then performed to identify minimally effective dosing strategies to protect lower female genital tract and colorectal tissues. RESULTS: The colorectal TFVdp concentration was 10 times higher than that in the lower female genital tract, whereas concentrations of endogenous nucleotides were 7-11 times lower. Our model predicted that ≥98% of the population achieved protective mucosal tissue exposure by the third daily dose of tenofovir disoproxil fumarate plus emtricitabine. However, a minimum adherence to 6 of 7 doses/week (85%) was required to protect lower female genital tract tissue from HIV, while adherence to 2 of 7 doses/week (28%) was required to protect colorectal tissue. CONCLUSIONS: This model is predictive of recent PrEP trial results in which 2-3 doses/week was 75%-90% effective in men but ineffective in women. These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies.

The cognitive foundations of early arithmetic skills: It is counting and number judgment, but not finger gnosis, that count.

Following on from ideas developed by Gerstmann, a body of work has suggested that impairments in finger gnosis may be causally related to children's difficulties in learning arithmetic. We report a study with a large sample of typically developing children (N=197) in which we assessed finger gnosis and arithmetic along with a range of other relevant cognitive predictors of arithmetic skills (vocabulary, counting, and symbolic and nonsymbolic magnitude judgments). Contrary to some earlier claims, we found no meaningful association between finger gnosis and arithmetic skills. Counting and symbolic magnitude comparison were, however, powerful predictors of arithmetic skills, replicating a number of earlier findings. Our findings seriously question theories that posit either a simple association or a causal connection between finger gnosis and the development of arithmetic skills.

A Longitudinal Analysis of Mothers' Parenting Stress and Internalizing and Externalizing Behavior of Young Children on the Autism Spectrum.

We investigated longitudinal relations between internalizing, externalizing, and total behaviors that challenge in young children on the autism spectrum and mothers' parenting stress. Participants included 93 mothers of children on the autism spectrum aged 27.89-65.84 months, who completed questionnaires on maternal parenting stress, and children's internalizing (anxiety), externalizing (disruptive), and total behaviors that challenge. Data were collected on early intervention program intake and approximately one year later. Cross-sectional findings indicated small to medium effect size associations between internalizing and externalizing behavior and parenting stress. However, cross-lagged structural equation models found that neither internalizing nor externalizing behavior predicted later parenting stress, nor the reverse. Significant stability effects were found for measures of child internalizing (anxiety), externalizing (disruptive), and total behaviors, and parenting stress. Relations between behaviors that challenge and parenting stress over time were non-significant in our models that controlled for stability of behaviors and parenting stress over time. Implications for research and clinical practice, in understanding and targeting the persistence of behaviors that challenge and parenting stress, are discussed.

Prevention and Reduction of Anxiety in Autistic Preschoolers Through an Autism-Specific Parent-Mediated Intervention: A Pilot Randomised Controlled Trial Evaluating Short and Longer Term Outcomes.

Anxiety is a common co-occurring condition for autistic preschoolers. Whilst there has been extensive research evaluating anxiety prevention/reduction interventions for neurotypical preschoolers, such research is limited for autistic children. Fifty-seven parents of autistic 4-5-year olds, with varying levels of anxiety, participated in a randomised controlled trial of an autism-specific, parent-mediated intervention (CLK-CUES) to prevent or reduce anxiety in autistic preschoolers. Baseline, short-term (post-intervention) and longer term (12 months follow-up) assessments included child anxiety (ASC-ASD-P and PAS-R), intolerance of uncertainty, and parent well-being. (Trial registration ACTRN12620001322921). There were no reports of harmful effects of the intervention or trial. Linear mixed models show a significant group x time interaction for ASC-ASD-P Total score and the Uncertainty subscale with medium and large effect sizes. Post-hoc analyses show a significant decline for only the intervention group in anxiety (specifically, anxiety around uncertainty) from pre-post intervention, maintained at one year follow-up. There was no change on the PAS-R or other ASC-ASD-P subscales. CLK-CUES shows promise as a way to prevent and reduce anxiety in young autistic children, specifically anxiety related to uncertainty. Trials with larger samples are warranted. Findings also highlight the importance of using measures designed for autistic children.

The relationshipbetween anxiety and social outcomes in autistic children and adolescents: A meta-analysis.

Anxiety is one of the most frequently reported co-occurring conditions for autistic children and adolescents. The relationship between anxiety and social outcomes in autistic youth has been the focus of a range of studies, with mixed results. This meta-analysis aimed to identify the strength of the association between anxiety and a frequently researched social outcome (social competence) in autistic young people and whether that association is influenced by individual or research design factors. A previous preregistered systematic review was updated with a search of the same three databases (CINAHL, ERIC, and PsycINFO) as the original review. Through this, 20 studies with sufficient data on a neurotypically-defined measure of social competence and anxiety were identified. Results were synthesised using a mixed effects model. The meta-analysis on 2,321 participants (from 22 samples) highlighted wide heterogeneity in results. The findings show that anxiety has a significant, small negative impact on social competence (d = - 0.48; 95% CI = - 0.71, - 0.26), meaning that as scores on measures of anxiety increase, scores on measures of social competence decrease. This relationship between anxiety and social competence was moderated by age, becoming weaker as age increased. Whilst this is an important finding for supporting mental health and well-being of autistic young people, the large amount of variance left unexplained suggests that multiple factors, including the use of measures designed for neurotypical people and the potential impact of camouflaging on such measures, need to be considered in future designs.

Single and multiple dose pharmacokinetics of maraviroc in saliva, semen, and rectal tissue of healthy HIV-negative men.

BACKGROUND: Antiretroviral pharmacology in seminal plasma (SP) and rectal tissue (RT) may provide insight into antiretroviral resistance and the prevention of sexual transmission of human immunodeficiency virus (HIV). Saliva may be of utility for noninvasively measuring adherence. METHODS: A pharmacokinetic study was performed in 12 HIV-negative men receiving maraviroc 300 mg twice daily for 8 days. Seven time-matched pairs of blood plasma (BP) and saliva samples were collected over 12 h on day 1 (PK1) and days 7 and 8 (PK2). One RT sample from each subject was collected during PK1 and PK2. Two SP samples were collected from each subject during PK1, and 6 SP samples were collected from each subject during PK2. RESULTS: SP AUCs were ∼50% lower than BP. However, protein binding in SP ranged from 4% to 25%, resulting in protein-free concentrations >2-fold higher than BP. RT AUCs were 7.5- to 26-fold higher than BP. Maraviroc saliva AUCs were ∼70% lower than BP, but saliva concentrations correlated with BP (r(2) = 0.58). CONCLUSIONS: More pharmacologically available maraviroc was found in SP than BP. High RT concentrations are promising for preventing rectal HIV acquisition. Saliva correlation with BP suggests that this may be useful for monitoring adherence. CLINICAL TRIALS REGISTRATION: NCT00775294.

Macroscopic liquid crystal response to isolated DNA helices.

Nematic liquid crystals (LC) were exposed to isolated DNA molecules extended on a surface that imparted a negligible influence on the LC orientation. Although single-stranded DNA aligned the LC in the extension direction, double-stranded DNA (dsDNA) caused alignment at an oblique angle, providing a characteristic response to the chiral dsDNA helix that was readily observed optically. The intrinsic amplification due to LC orientational correlations enabled a macroscopic visible response to a single molecule of extended dsDNA.

Leptin, fat mass, and bone mineral density in healthy pre- and postmenopausal women.

The purpose was to examine relationships between age, fat mass, and bone mineral density (BMD) with resting leptin levels in premenopausal and postmenopausal women. Young (aged 18-30 yr, n=30) and estrogen-deficient postmenopausal (aged 55-75 yr, n=43) women were recruited. Total body and segmental fat mass and bone-free lean body mass (BFLBM) and total body, lumbar spine, and proximal femur BMD were assessed using dual-energy X-ray absorptiometry. Serum-resting, fasted leptin levels were measured by Immunoradiometric Assay (IRMA), and leptin-to-fat mass ratios were calculated. Young and older women had similar amounts of BFLBM, but older women had greater (p<0.05) amounts of fat mass and 35% higher leptin levels. Age differences in leptin concentrations were no longer significant after controlling for fat mass. Older women had significantly (p<0.05) lower hip BMD values. Age was negatively related (r=-0.29, p<0.05) to leptin:trunk fat ratio. Increases in fat mass, not menopause per se, contributes to higher leptin levels in older women. Relationships between leptin and BMD may be age dependent.

Protocol for a longitudinal study investigating the role of anxiety on academic outcomes in children on the autism spectrum.

BACKGROUND: Children on the autism spectrum are consistently reported to underachieve compared to ability. In typically developing children, anxiety is a strong predictor of poor school performance. Despite the high prevalence of anxiety disorders among children on the spectrum, the impact of their anxiety on academic achievement is under-researched. The main aim of this project is to determine the moderating role anxiety may have in the development of academic learning behaviours (academic enablers) in children on the spectrum. This project addresses a gap in knowledge about the possible associations between anxiety and academic achievement in children on the spectrum. Understanding these associations opens up the possibility of new intervention pathways to enhance academic outcomes through anxiety reduction/prevention. METHODS: This longitudinal study will aim to recruit 64 children on the spectrum aged 4-5 years and their parents. Information will be gathered from children, parents and teachers. Children will be randomly assigned to one of two conditions in order to experimentally manipulate anxiety levels in the sample: experimental (to receive an anxiety reduction/prevention program, N = 32) or control (no intervention/treatment as usual, N = 32). The primary outcome measures are child academic skills and enabling behaviours assessed using the Academic Competence Evaluation Scales and the WIAT-II. Anxiety will be assessed through parent and teacher report. Assessments will be conducted at baseline, post-experimental manipulation of anxiety, and within the first year of formal schooling. It is hypothesised that anxiety will moderate the relationship between autism characteristics and academic enablers. DISSEMINATION: Results will be disseminated through peer-reviewed manuscripts and conference presentations. Lay summaries will be provided to all participants and available on the research centre website.

Learning correspondences between magnitudes, symbols and words: Evidence for a triple code model of arithmetic development.

According to the Triple Code Model, early arithmetic development depends on learning the mappings between non-verbal representations of magnitude (quantity) and symbolic verbal (number words) and visual (Arabic numerals) representations of number. We examined this hypothesis in a sample of 166 4- to 7-year old children. Children completed 4 paired-associate learning tasks and a broad range of measures assessing early numerical (symbolic and non-symbolic magnitude comparison, digit writing, arithmetic) and reading skills (letter-sound knowledge, phoneme awareness, rapid automatized naming, word reading). A path model showed that paired-associate learning tasks involving mapping magnitudes onto verbal or visual stimuli predicted arithmetic performance over and above other well-established predictors. This relationship was specific to arithmetic and, consistent with the Triple Code Model, highlights that mapping between non-symbolic magnitude representations and the corresponding symbolic forms (verbal and visual) is important to the development of arithmetic skills.

Stage 1 Registered Report: The relationship between handedness and language ability in children.

Weak or inconsistent hand preference may be a risk factor for developmental language delay.  This study will test the extent to which variations in language skills are associated with the strength of hand preference. Data are drawn from a large sample (n = 569) of 6- to 7-year-old children unselected for ability, assessed at two time points, 6 months apart. Hand preference is assessed using the Quantitative Hand Preference task (QHP) and five uni-manual motor tasks. Language skills (expressive and receptive vocabulary, receptive grammar, and morphological awareness) are assessed with standardized measures. If weak cerebral lateralisation (as assessed by the QHP task) is a risk factor for language difficulties, it should be possible to detect such effects in the large representative sample of children examined here.

Data on numerosity discrimination, inhibition and arithmetic during the early school years.

Participants consisted of 496 children (mean age = 6 years; 9 months) recruited from 11 schools in Brisbane, Australia. Children were assessed on the addition and subtraction subtests of the Test of Basic Arithmetic and Number Skills (TOBANS), an adapted version of the Head-Toes-Knees-Shoulders task to measure inhibition, numerosity discrimination using eight subtests varying ratio (2:3 or 5:6) and congruency, and non-verbal cognitive ability using an adapted version of Raven's Coloured Progressive Matrices. Information on children's demographics (gender, English as an additional language, and learning difficulty status) is also provided. All assessments were administered during the second year of formal schooling (i.e. Grade 1). Findings regarding the impact of inhibition on the relation between numerosity discrimination and arithmetic are reported elsewhere [1].

Stage 2 Registered Report: There is no appreciable relationship between strength of hand preference and language ability in 6- to 7-year-old children.

Background: Weak or inconsistent hand preference has been postulated to be a risk factor for developmental language delay. Following on from our Registered Stage 1 report this study assessed the extent to which variations in language skills are associated with the strength of hand preference. Methods: Data are drawn from a large sample ( N = 569) of 6- to 7-year-old children unselected for ability, assessed at two time points, 6 months apart. Hand preference was assessed using the Quantitative Hand Preference (QHP) task and five uni-manual motor tasks. Language skills (expressive and receptive vocabulary, receptive grammar, and morphological awareness) were assessed with standardized measures. Results: We found QHP scores did not distinguish children with weaker language skills from those with stronger language skills and the correlation between QHP scores and language ability was negligible in this study. Hand preference on the QHP task was significantly stronger among right-handed than left-handed children and left-handed children were typically inconsistent in the hand used across different tasks.  Conclusions: The findings presented here fail to provide any support for the theory that weak cerebral lateralisation (as assessed here by the QHP task) places children at risk of language difficulties . Stage 1 report:  https://doi.org/10.12688/wellcomeopenres.15077.1.