Development and validation of the Early Executive Functions Questionnaire: A carer‐administered measure of Executive Functions suitable for 9‐ to 30‐month‐olds

Executive functions (EFs) enable us to control our attention and behavior in order to set and work toward goals. Strong EF skills are linked to better academic performance, and greater health, wealth, and happiness in later life. Research into EF development has been hampered by a lack of scalable measures suitable for infancy through to toddlerhood. The 31-item Early Executive Functions Questionnaire (EEFQ) complements temperament measures by targeting cognitive and regulatory capabilities. Exploratory Factor Analysis (n = 486 8- to 30-month-olds) and Confirmatory Factor Analysis (n = 317 9- to 30-month-olds) indicate Inhibitory Control, Flexibility, and Working Memory items load onto a common “Cognitive Executive Function (CEF)” factor, while Regulation items do not. The CEF factor shows strong factorial measurement invariance for sex, and partial strong factorial measurement invariance for age. CEF and Regulation scores show limited floor and ceiling effects, good internal consistency, short-term stability, and convergent validity with carer-report measures of attentional control. The EEFQ is sensitive to developmental change. Results indicate that the widely overlooked period between late infancy and early toddlerhood may be a sensitive period for EF development. The low-resource demands of the EEFQ afford the possibility to study emergent EFs at scale; opening up new opportunities in basic developmental and intervention research

Studies on the Flagellar Attachment of African Trypanosomes

Attachment of trypanosomes by the flagellum to a host internal surface is believed to represent an important stage in the development of these parasites in their vectors. This thesis is concerned with an investigation into various aspects of the flagellar attachment of Trypanosoma congolense epimastigotes. The morphology of the attachment is described in both the tsetse fly labrum and in vitro where the epimastigotes attach to the plastic wall of the culture flask. Epimastigotes attach to the substratum at one or more sites along the length of the flagellum. At the attachment site the flagellar membrane is extended from the axis and an electron dense, hemidesmosome-like plaque (approx. 35nm wide) forms on the cytoplasmic face of the membrane. 5nm fiIaiments converge on the plaque and associate with similar filaments emanating from flagellum-cell body attachment plaques. Filaments form at the attachment site soon after contact with the substratum. Plaques form subsequently and become more compact with advancing epimastigote age. An extracellular gap (15nm) is present between flagellum and substratum. Ruthenium red binding in this gap indicates that glycoproteins are situated there. Differentiated attachment plaques appear to be specific to attached epimastigotes and are absent from detached epimastigotes. They are absent from the flagella of bloodstream trypomastigotes of T. congolense even though the flagellar tip of this stage in the tryp-anosome's life cycle attaches the parasite to the endothelium of bloodvessel walls. The necessity of attachment for epimastigote proliferation and for differentiation of the mammal-infecting metacyclic stage from the epimastigote has been examined. Prevention of epimastigote attachment by shaking cultures or growing trypanosomes on a polypropylene substratum does not affect the rate of epimastigote division. Metacyclogenesis does not occur in unattached trypanosomes, however, suggesting that, in this species, attachment is a necessary prerequisite for this developmental step. Interference reflection microscopy has been used to visualize the effect on extracellular gap width of agents added to the culture medium. An increase in gap width following trypsinization on addition of Concanavalin A, Lentil lectin and Wheatgerm Agglutinin indicate that protein, D-mannose and N-acetyl-D-glucosamine are present in this location. External serum concentration, monovalent ion concentrations and the presence of tunicamycin have little effect on the interfer-ometry pattern. Tunicamycin insensitivity reflects a lack of glycoprotein turnover at the site. Divalent cation removal decreases the gap width. The binding of epimastigotes to positively charged Sephadex beads indicates a net negative surface charge. This charge maybe less negative in the region of the attachment as binding to positively charged beads is reduced at the flagellar tip. Indirect immunofluorescence and indirect immunogold electron microscopical cytochemistry indicate that the proteins actin, vinculin, filamin, intermediate filament proteins and desmoplakins (found associated with morphologically similar metazoan cell attachment structures - hemidesmosomes and focal adhesions) are absent from the epimastigote attachment. Immunofluorescence reactions suggest that actin and intermediate filaments are present in these cells but not localized in their distribution. Confirmation of the presence of these proteins can be obtained with SDS-PAGE and associated Western blotting experiments of both whole cell and cytoskeleton preparations. Comparative 2D-gel electrophoresis of attached and unattached whole epimastigotes and cytoskeletons shows the presence of a novel group of proteins (approx. Mr=70kd) in attached preparations. It is suggested that these proteins maybe involved in the attachment complex

Moulding environmental contexts to optimise neurodiverse executive function performance and development: a goodness-of-fit account

Executive functions (EFs) provide a top-down response to stimuli and events in pursuit of a goal. We argue that the extent to which an individual's environment is enriching and a good fit for them influences whether their performance at that moment is towards their upper- or lower-limit of EF ability. We outline the implications of this for interpreting measures of EF. We next argue that a child's sensitivity to the environment, and their caregivers' ability to modulate the environment to improve goodness-of-fit, influences the cumulative effects of the environment in shaping that child's actualised EF ability (the performance level shown in day-to-day situations), and thus their skill development. We therefore recommend that EF interventions be designed to improve children's actualised EF ability by improving their day-to-day environment, while simultaneously helping children modulate their physiological response to environmental challenges, and providing opportunities to practise EF skills in ecologically-valid contexts

Biophysical and cellular insights into the membrane insertion mechanism of CLIC1

Chloride intracellular channel 1 (CLIC1) is a human protein expressed in the cytosol that has a remarkable feature – it can transition into an active chloride channel in nuclear, endoplasmic reticulum or plasma membranes. This metamorphic nature makes CLIC1 a potential drug target as overexpression of the membrane channel form in cells is implicated in neurodegenerative disease progression and tumour proliferation especially in cancers with poor prognosis such as glioblastomas. The mechanism of CLIC1 activation and membrane insertion, as well as the oligomerisation state and structure of the channel, still remain elusive, therefore my PhD focuses on deciphering more information about how and why CLIC1 forms a chloride channel. Combining biophysical and microscopy techniques we have discovered that, upon binding to divalent cations Ca2+ and Zn2+, CLIC1 relocalises and inserts into the plasma membrane to form an active chloride channel in both in vitro and in vivo experiments. Previous literature heavily implicates the role of cysteine oxidation in CLIC1 channel formation but the use of solution NMR studies confirmed that both the soluble and membrane bound forms of CLIC1 are in the same oxidation state, further supporting the hypothesis divalent cations are the trigger for this translocation from a cytosolic globular protein to integral membrane chloride channel. The identification of the molecular switch that promotes CLIC1 membrane insertion is a significant discovery as it provides a model that can enable mechanistic studies of CLIC1 translocation and structural investigation of the channel form, known to have clinical relevance. Additional research focused on how CLIC1 interacts with divalent cations in a cellular environment aiming to elucidate information about the conformational changes the protein undergoes in vivo

Concurrent and longitudinal associations between touchscreen use and executive functions at preschool-age

Introduction: The prevalence of touchscreen devices has recently risen amongst young children. Some evidence suggests that increased touchscreen use may be negatively related to preschool-age children's executive functions (EFs). However, it has been argued that actively interacting with touchscreen devices (e.g., via creative apps for drawing) could better support EF development compared to passive use (e.g., watching videos). There is a pressing need to understand whether the type of use can explain potential associations between touchscreen use and EF. Methods: By following up longitudinally on an infant sample, now aged 42-months (N = 101), the current study investigates the relative contributions of passive and active touchscreen use, measured concurrently at 42-months and longitudinally from 10-to-42-months, on parent-reported EFs. Results: A multivariate multiple regression found no significant negative associations between touchscreen use and preschool EF. There was a significant positive association between active touchscreen use at 42-months and the BRIEF-P Flexibility Index. Discussion: The lack of significant negative associations found is consistent with an earlier study's findings in the same sample at infancy, suggesting that the moderate levels of early touchscreen use in this sample are not significantly associated with poorer EF, at least up to preschool-age

Associations between touchscreen exposure and hot and cool inhibitory control in 10-month-old infants

Touchscreen use amongst young children has proliferated in recent years, yet little is known about the association between daily touchscreen exposure and inhibitory control in the first year of life. Previous research has found a negative association between the amount of television viewing and inhibitory control in early childhood, but it is unclear whether negative associations with screen use extend to touchscreens. The current study presents an exploratory analysis of the cross-sectional associations between inhibitory control and the amount of touchscreen use amongst 10-month-olds (n = 128–156). Touchscreen exposure was assessed via parent-report. In order to include a range of “hot” and “cool” aspects of inhibitory control, these skills were assessed using lab-based response inhibition and prohibition tasks as well as parent-reported observations of infants’ inhibitory control abilities and broader regulatory behaviors. A “Cognitive Executive Function (EEFQ-CEF)” score (encompassing Inhibitory Control, Flexibility, and Working Memory items) was included as a secondary broader executive function construct to examine whether effects showed specificity to inhibitory control rather than executive functions more generally. Correlation analyses indicated no association between touchscreen exposure and the four indices of IC. However, a positive association was found for the amount of touchscreen exposure and EEFQ-CEF once accounting for sociodemographic variables. The implications of these findings and future directions are discussed

Feasibility and acceptability of a parent-toddler programme to support the development of executive functions in children at elevated likelihood of autism or ADHD: pilot findings

This study reports feasibility, fidelity and acceptability of a pilot of START; a 12-week parent-toddler, group-based, neurodiversity-affirming programme aiming to support executive function development in toddlers at elevated likelihood of autism or ADHD. After 4 days' training, community early years practitioner pairs delivered START to 13 UK families with a toddler showing elevated autistic traits, or with a parent or sibling with autism or ADHD, in groups of 6 and 7. Sessions were audio-recorded and rated by practitioners and researchers regarding the extent to which programme and session aims were met. Practitioners' reflections on strengths and challenges in session delivery, adaptations to the session plan and researchers' observations from the audio recordings were probed in weekly debrief calls, and one-to-one interviews at programme end-point. Recruitment and retention were monitored. Parent participants were asked to complete a feedback questionnaire after each session. Results show recruitment to the programme is feasible, but a large minority of parents experience barriers to regular attendance, which is a challenge for achieving exposure targets. Practitioners delivered the programme to a high quality and at least partially met programme and session-specific aims in every session. The most significant barrier to fully meeting session aims was families' late arrival. Parents reported regularly engaging with the suggested activities at home and found the sessions useful, although not all parents responded each week. Overall, the results of this small-scale pilot indicate START is feasible and acceptable as a parent-mediated programme to support toddlers at elevated likelihood of autism or ADHD to thrive

Do pre-schoolers with high touchscreen use show executive function differences?

The recent increase in children's use of digital media, both TV and touchscreen devices (e.g., tablets and smartphones), has been associated with developmental differences in Executive Functions (EF). It has been hypothesised that early exposure to attention-commanding and contingent stimulation provided by touchscreens may increase reliance on bottom-up perceptual processes and limit the opportunity for practice of voluntary (i.e., top-down) attention leading to differences in EF. This study tests the concurrent and longitudinal associations between touchscreen use (high use, HU ≥ 15 min/day; low use, LU < 15 min/day), and two components of EF (working-memory/cognitive-flexibility, and impulse/self-control), building explicitly on recent developmental models that point to a bidimensional structure of EF during toddlerhood and pre-school years. A longitudinal sample of 46 3.5-year-olds (23 girls) was tested on a battery of lab-based measures and matched at 12 months on a range of background variables including temperament. Touchscreen HU showed significantly reduced performance in lab-based Working Memory/Cognitive Flexibility, although this became non-significant when controlling for background TV. Impulse/Self-control was not significantly associated with touchscreen use but was negatively associated with non-child-directed television. Our results provide partial support for the hypothesis that using touchscreen devices might reduce capacity for top-down behaviour control, and indicate that broader media environment may be implicated in early executive function development. However, it may also be the case that individuals who are predisposed towards exogenous stimulation are more drawn to screen use. Future studies are needed to replicate findings, demonstrate causality, and investigate bidirectionality

Intimate partner violence identified through routine antenatal screening and maternal and perinatal health outcomes

Background: This study investigated the association between intimate partner violence (IPV) identified on routine prenatal screening and perinatal outcomes for mother and infant. Methods: Routinely collected perinatal data for a cohort of all women and their infants born in public health facilities in Sydney (Australia) over the period 2014-2016 (N = 52,509) were analysed to investigate the risk of adverse maternal and perinatal outcomes associated with a history of IPV. The association between an affirmative response on prenatal IPV screening and low birth weight (LBW) < 2.5 kg, preterm birth < 37 weeks, breastfeeding indicators and postnatal depressive symptoms (PND) was investigated in a series of logistic regression models. Results: IPV was associated with an increased risk of PND (OR = 2.53, 95% CI 1.76-3.63), not breastfeeding at birth (OR = 1.65, 95% CI 1.30-2.09), non-exclusive breastfeeding at discharge (OR = 1.66, 95% CI 1.33-2.07) and first post-natal visit (OR = 1.54, 95% CI 1.24-1.91). Self-reported fear of a partner was strongly associated with an increased risk of PND (OR = 3.53, 95% CI 2.50-5.00), and also LBW (OR = 1.58, 95% CI 1.12-2.22), preterm birth (OR = 1.38, 95% CI 1.08-1.76), lack of early initiation of breastfeeding (OR = 1.67, 95% CI 1.28-2.17), non-exclusive breastfeeding at discharge from hospital (OR = 1.60, 95% CI 1.24-2.06) and at the first post-natal visit (OR = 1.27, 95% CI 0.99-3.04). Conclusions: IPV reported at the time of pregnancy was associated with adverse infant and maternal health outcomes. Although women may be disinclined to report IPV during pregnancy, universal, routine antenatal assessment for IPV is essential for early identification and appropriate management to improve maternal and newborn health

Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits.

BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms