Early production of the passive in two Eastern Bantu languages

The passive construction is acquired relatively late by children learning to speak many languages, with verbal passives not fully acquired till age 6 in English. In other languages it appears earlier, around age 3 or before. Use of passive construction in young children was examined in two Eastern Bantu languages spoken in Kenya (Kiswahili and Kigiriama), both with frequent use of passive. The passive was used productively very early (2;1) in these languages, regardless of the method used to measure productivity. In addition non-actional passives, particularly rare in English and some other European languages, were seen at these early ages. The proportion of verbs that were passive varied between individuals, both in children's speech and in the input to children. Pragmatic and grammatical features of the passive in some languages have previously been suggested to drive early passive acquisition, but these features are not found consistently in the two languages studied here. Findings suggest that the relatively high frequency of input found in these languages is the most plausible reason for early productive use of the passive

Reading and Phonological Awareness in Africa

Literacy levels in Africa are low, and school instruction outcomes are not promising. Africa also has a disproportionate number of unschooled children. Phonological awareness (PA), especially phoneme awareness, is critically associated with literacy, but there is little evidence about whether PA is gained through literacy, schooling, or both, because most children studied are in education and can read at least letters. Our previous study of PA and reading in children in and out of school in Tanzania found that PA was associated with reading ability, not schooling or age, and many unschooled children learned to read. We retested 85 children from the baseline study, on measures of PA and literacy, approximately 2 years later. We found that more unschooled children had now learned to read but PA had generally not improved for these children. Unschooled children were still poorer at PA than schooled children. At 2 years, schooling now independently predicted PA and literacy. PA also predicted literacy and vice versa. Explicit phoneme awareness was again poor, even in accurate readers. More unschooled children have now learned to read, possibly because local literacy is in their first language; however, schooling improves reading and PA

Maternal multiple micronutrient supplementation and other biomedical and socioenvironmental infl uences on children’s cognition at age 9–12 years in Indonesia: follow-up of the SUMMIT randomised trial

Background Brain and cognitive development during the fi rst 1000 days from conception are aff ected by multiple biomedical and socioenvironmental determinants including nutrition, health, nurturing, and stimulation. An improved understanding of the long-term infl uence of these factors is needed to prioritise public health investments to optimise human development. Methods We did a follow-up study of the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind, cluster-randomised trial of maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA) in Indonesia. Of 27 356 live infants from birth to 3 months of age in 2001–04, we re-enrolled 19 274 (70%) children at age 9–12 years, and randomly selected 2879 from the 18 230 who were attending school at a known location. Of these, 574 children were oversampled from mothers who were anaemic or malnourished at SUMMIT enrolment. We assessed the eff ects of MMN and associations of biomedical (ie, maternal and child anthropometry and haemoglobin and preterm birth) and socioenvironmental determinants (ie, parental education, socioeconomic status, home environment, and maternal depression) on general intellectual ability, declarative memory, procedural memory, executive function, academic achievement, fi ne motor dexterity, and socioemotional health. The SUMMIT trial was registered, number ISRCTN34151616. Findings Children of mothers given MMN had a mean score of 0·11 SD (95% CI 0·01–0·20, p=0·0319) higher in procedural memory than those given IFA, equivalent to the increase in scores with half a year of schooling. Children of anaemic mothers in the MMN group scored 0·18 SD (0·06–0·31, p=0·0047) higher in general intellectual ability, similar to the increase with 1 year of schooling. Overall, 18 of 21 tests showed a positive coeffi cient of MMN versus IFA (p=0·0431) with eff ect sizes from 0·00–0·18 SD. In multiple regression models, socioenvironmental determinants had coeffi cients of 0·00–0·43 SD and 22 of 35 tests were signifi cant at the 95% CI level, whereas biomedical coeffi cients were 0·00–0·10 SD and eight of 56 tests were signifi cant, indicating larger and more consistent impact of socioenvironmental factors (p<0·0001). Interpretation Maternal MMN had long-term benefi ts for child cognitive development at 9–12 years of age, thereby supporting its role in early childhood development, and policy change toward MMN. The stronger association of socioenvironmental determinants with improved cognition suggests present reproductive, maternal, neonatal, and child health programmes focused on biomedical determinants might not suffi ciently enhance child cognition, and that programmes addressing socioenvironmental determinants are essential to achieve thriving populations

Williams syndrome: a surprising deficit in oromotor praxis in a population with proficient language production

Williams Syndrome (WS) is a neurodevelopmental disorder of known genetic origin, characterized by serious delays in language onset yet relatively verbose, intelligible and fluent speech in late childhood and adulthood. How do motor abilities relate to language in this group? We investigated planning and co-ordination of the movement of the speech articulators (oromotor praxis) in 28 fluent-speaking individuals with WS, aged between 12–30 years. Results indicate that, despite their fluent language, oromotor praxis was impaired in WS relative to two groups of typically-developing children, matched on either vocabulary or visuospatial ability. These findings suggest that the ability to plan, co-ordinate and execute complex sensorimotor movements contribute to an explanation of the delay in expressive language early in development in this neurodevelopmental disorder. In the discussion, we turn to more general issues of how individual variation in oromotor praxis may account for differences in speech/language production abilities across developmental language disorders

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

BackgroundA safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.MethodsThis analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.FindingsBetween April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.InterpretationChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.FundingUK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials