The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection

Aggression in toddlerhood: the roles of parental beliefs, parenting behavior and precursors of theory of mind

Parental beliefs, parenting behavior, and precursors of theory of mind have been related uniquely to each other and to early aggression, but have not yet been studied simultaneously. The present study combined these risk factors in the prediction of aggression during toddlerhood using a sample of 152 mother–child dyads. At 20 months, mothers' parental beliefs (parental self‐efficacy and perceived parental impact) were examined with the Parental Cognitions and Conduct Toward the Infant Scale. Maternal parenting behavior (sensitivity, intrusiveness, and successful positive engagement) was observed during free play and teaching tasks, and children's precursors of theory of mind were assessed using a visual perspectives task and an imitation task. At 30 months, child aggression was examined using the Child Behavior Checklist. A regression analysis indicated that lower parental self‐efficacy and lower imitation skills predicted more aggressive behavior. When estimating the indirect effects using bootstrapping, a final model was found indicating that lower perceived parental impact was related to less successful positive engagement, which, in turn, was associated with children's poorer imitation abilities which predicted more aggressive behavior. It can be concluded that aggression during toddlerhood is predicted significantly by interrelated parental beliefs, parenting behavior, and children's early social cognitive abilities

Association of proximal elements of social disadvantage with children's language development at 2 years: An analysis of data from the Children in Focus (CiF) sample from the ALSPAC birth cohort

This is the peer reviewed version of the following article: Law, J., Clegg, J., Rush, R., Roulstone, S. & Peters, T. J. (2018) Association of proximal elements of social disadvantage with children's language development at 2 years: An analysis of data from the Children in Focus (CiF) sample from the ALSPAC birth cohort. International Journal of Language & Communication Disorders, which has been published in final form at https://doi.org/10.1111/1460-6984.12442. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Background: An association between social disadvantage and early language development is commonly reported in the literature, but less attention has been paid to the way that different aspects of social disadvantage affect both expressive and receptive language in the first 2 years of life. Aims: To examine the contributions of gender, parental report of early language skills and proximal social variables (the amount of stimulation in the home, the resources available to the child and the attitudes/emotional status of the primary carer and the support available to him/her) controlling for distal social variables (family income and maternal education) to children's expressive and receptive language development at 2 years in a community ascertained population cohort. Methods & Procedures: Data from 1314 children in the Children in Focus (CiF) sample from the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. Multivariable regression models identified the contribution of proximal (what parents do with their children) measures of social disadvantage adjusting for more distal (e.g., family income and material wealth) measures as well as early language development at 15 months to the development of verbal comprehension, expressive vocabulary and expressive grammar (word combinations) at 2 years of age. Outcome & Results: In the final multivariable models gender, earlier language and proximal social factors, co‐varying for distal factors predicted 36% of the variance for expressive vocabulary, 22% for receptive language and 27% for word combinations at 2 years. Language development at 15 months remained a significant predictor of outcomes at 24 months. Environmental factors were associated with both expressive scales but the picture was rather more mixed for receptive language suggesting that there may be different mechanisms underlying the different processes. Conclusions & Implications: This study supports the argument that social advantage makes a strong contribution to children's language development in the early years. The results suggest that what parents/carers do with their children is critical even when structural aspects of social disadvantage such as family income and housing have been taken into consideration although this relationship varies for different aspects of language. This has the potential to inform the targeting of public health interventions focusing on early language and pre‐literacy skills on the one hand and home learning environments on the other and, potentially, the two in combination.54pubpub

Developmental Trajectories in Siblings of Children with Autism: Cognition and Language from 4 Months to 7 Years

We compared the cognitive and language development at 4, 14, 24, 36, 54 months, and 7 years of siblings of children with autism (SIBS-A) to that of siblings of children with typical development (SIBS-TD) using growth curve analyses. At 7 years, 40% of the SIBS-A, compared to 16% of SIBS-TD, were identified with cognitive, language and/or academic difficulties, identified using direct tests and/or parental reports. This sub-group was identified as SIBS-A-broad phenotype (BP). Results indicated that early language scores (14–54 months), but not cognitive scores of SIBS-A-BP and SIBS-A-nonBP were significantly lower compared to the language scores of SIBS-TD, and that the rate of development was also significantly different, thus pinpointing language as a major area of difficulty for SIBS-A during the preschool years

Giving voice: an oral history of speech and language therapy

© 2020 Royal College of Speech and Language Therapists Background: The Royal College of Speech and Language Therapists (RCSLT) celebrates its 75th anniversary in 2020. The historical study of speech and language therapy (SLT) has been very limited. A small number of publications have traced the changes in the profession over time, but to date there has been no comprehensive work undertaken to gain an insight into the experiences of UK speech therapists who entered the newly formed profession after 1945. Aims: To use an oral history methodology to explore the life stories of early members of the profession. Methods & Procedures: Participants were recruited through RCSLT networks. Interviews were held across England and Scotland. Conversations were audio recorded and analysed using thematic network analysis. Archive material was used to complement participants’ narratives. Outcomes & Results: Participants were 19 women who qualified between 1945 and 1968. Three global themes emerged: personal, professional and political stories. On a personal level, each reported steps towards autonomy and agency within the social constraints they experienced. Professionally, all commented on the vast expansion in the range of identifiable clinical fields between 1945, when the first participant qualified, and 2008, when the last participant retired. Politics and social policies impacted upon their lives and, sometimes to their surprise, the participants found themselves campaigning politically in pursuit of fairness for their profession. Conclusions & Implications: This paper offers a unique insight into the challenges and achievements participants experienced over their careers as early practitioners in the UK profession

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo