How getting noticed helps getting on: successful attention capture doubles children's cooperative play

Cooperative social interaction is a complex skill that involves maintaining shared attention and continually negotiating a common frame of reference. Privileged in human evolution, cooperation provides support for the development of social-cognitive skills. We hypothesize that providing audio support for capturing playmates' attention will increase cooperative play in groups of young children. Attention capture was manipulated via an audio-augmented toy to boost children's attention bids. Study 1 (48 6- to 11-year-olds) showed that the augmented toy yielded significantly more cooperative play in triads compared to the same toy without augmentation. In Study 2 (33 7- to 9-year-olds) the augmented toy supported greater success of attention bids, which were associated with longer cooperative play, associated in turn with better group narratives. The results show how cooperation requires moment-by-moment coordination of attention and how we can manipulate environments to reveal and support mechanisms of social interaction. Our findings have implications for understanding the role of joint attention in the development of cooperative action and shared understanding

An investigation into how children gain vocabulary via storybooks

For many children, storybooks are ubiquitous, forming a unique and special part of their childhood. Storybooks are a critical aspect of young children’s emerging literacy. Exposing them to phoneme word sounds, a rich varied vocabulary and print knowledge. This thesis explores one aspect of the amazing relationship children have with storybooks. Specifically, how do children learn new words from books, and it further discusses the best ways to use storybooks to facilitate this learning. Through the use of purpose-made storybooks, which help to control for all the different book elements (e.g. ensuring the story plot and the words that children were learning were novel). This thesis presents an empirical examination of the cognitive processes that help children learn new words through shared storybook reading. A series of experiments investigate the relationship between repetition of words, sleep consolidation and book formats – and their effects on vocabulary acquisition in 3.5-year-old children. These experiments have allowed us to isolate factors that increase the likelihood of children learning more words, and knowledge that can be used to support children’s vocabulary development. Importantly, we have discovered that children benefit from the same contextually cueing effects as adults supporting Horst, Parsons, and Bryan (2011) theory for repeated effects during repeated book readings. In addition, children demonstrate similar memory consolidation effects as adults when learning immediately proceeds sleep (Stickgold & Walker, 2005a). By examining the effects of rhyme books, we can further contribute to Hayes, Chemelski, and Palmer (1982) levels of processing theory for memory function in children. Overall, this thesis examines how understanding the cognitive processes supported by regular storybook reading can provide benefits for all preschool children, and outlines accessible and feasible techniques to help children’s emergent literacy

Nanoscale surface patterning as a means of controlling protein immobilisation

It would be desirable to synthesise a molecularly imprinted polymer with specific high-affinity protein recognition sites as a durable, cost-effective replacement for antibodies in biotechnology. A novel protein imprinting approach was proposed as an outline for these investigations. The focus of this project was consideration of fundamental aspects of surface nanometer-scale patterning and protein-surface interactions with the aim of preparing an ordered array of surface protein. This was in part achieved during the course of the work. An equilibrium dialysis method was validated for the measurement of ligand-protein binding parameters. Human serum albumin (HSA) and ethacrynic acid (ETH) were chosen as the ligand-protein pair to be surface-immobilised. Molecular modelling suggested a good fit for ethacrynic acid in the covalent HSA binding 'cleft', however, the covalent HSA-ETH complex was not successfully isolated. A derivative of the ligand, ETH-glycine, was synthesised to a very high purity but a low yield. A gas-phase silanisation method was developed to deposit functional aminopropyletriethoxysilane (APS) groups onto silicon wafer surfaces. The dispersion of APS could not be sufficiently controlled, by changing the evaporative distance or the APS evaporation concentration, and hence it was not possible to bring about gold nanoparticle (AuNP) patterning at the nanometer scale using this approach. However AuNP patterning could be achieved by incubating APS monolayer surfaces with different dilutions of a commercially available AuNP solution. Subsequent development of a protein imprinting strategy would require that non-specifically adsorbed HSA can be removed from PNA silicon surfaces. This was found to be difficult to achieve using mild conditions. Controlled gas-phase deposition of APS could not be used to directly facilitate dispersed ligand attachment. AuNP patterning can potentially be used as an indirect method for controlling surface dispersion of immobilised ligand. Controlled surface orientation and patterning of HSA, using the specific interaction with ETH, remains a significant challenge.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Nanoscale surface patterning as a means of controlling protein immobilisation

It would be desirable to synthesise a molecularly imprinted polymer with specific high-affinity protein recognition sites as a durable, cost-effective replacement for antibodies in biotechnology. A novel protein imprinting approach was proposed as an outline for these investigations. The focus of this project was consideration of fundamental aspects of surface nanometer-scale patterning and protein-surface interactions with the aim of preparing an ordered array of surface protein. This was in part achieved during the course of the work. An equilibrium dialysis method was validated for the measurement of ligand-protein binding parameters. Human serum albumin (HSA) and ethacrynic acid (ETH) were chosen as the ligand-protein pair to be surface-immobilised. Molecular modelling suggested a good fit for ethacrynic acid in the covalent HSA binding 'cleft', however, the covalent HSA-ETH complex was not successfully isolated. A derivative of the ligand, ETH-glycine, was synthesised to a very high purity but a low yield. A gas-phase silanisation method was developed to deposit functional aminopropyletriethoxysilane (APS) groups onto silicon wafer surfaces. The dispersion of APS could not be sufficiently controlled, by changing the evaporative distance or the APS evaporation concentration, and hence it was not possible to bring about gold nanoparticle (AuNP) patterning at the nanometer scale using this approach. However AuNP patterning could be achieved by incubating APS monolayer surfaces with different dilutions of a commercially available AuNP solution. Subsequent development of a protein imprinting strategy would require that non-specifically adsorbed HSA can be removed from PNA silicon surfaces. This was found to be difficult to achieve using mild conditions. Controlled gas-phase deposition of APS could not be used to directly facilitate dispersed ligand attachment. AuNP patterning can potentially be used as an indirect method for controlling surface dispersion of immobilised ligand. Controlled surface orientation and patterning of HSA, using the specific interaction with ETH, remains a significant challenge

Sickle cell anaemia and severe P. falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT)

Background: Sickle cell anaemia (SCA) has historically been associated with high levels of childhood mortality in Africa. Although malaria has a major contribution to this mortality, to date, the clinical pathology of malaria among children with SCA has been poorly described. We aimed to explore the relationship between SCA and Plasmodium falciparum malaria in further detail by investigating the burden and severity of malaria infections among children recruited with severe anaemia to the TRACT trial of blood transfusion in Africa. Methods: This study is a post-hoc secondary analysis of the TRACT trial data, conducted after trial completion. TRACT was an open-label, multicentre, factorial, randomised controlled trial enrolling children aged 2 months to 12 years who presented with severe anaemia (haemoglobin <6·0 g/dL) to four hospitals in Africa. This secondary analysis is restricted to Uganda, where the birth prevalence of SCA is approximately 1% and malaria transmission is high. Children were classified as normal (HbAA), heterozygous (HbAS), or homozygous (HbSS; SCA) for the rs334 A→T sickle mutation in HBB following batch-genotyping by PCR at the end of the trial. To avoid confounding from SCA-specific medical interventions, we considered children with an existing diagnosis of SCA (known SCA) separately from those diagnosed at the end of the trial (unknown SCA). The outcomes considered in this secondary analysis were measures of P falciparum parasite burden, features of severe malaria, and mortality at day 28 in malaria-positive children. Findings: Between Sept 17, 2014, and May 15, 2017, 3944 children with severe anaemia were enrolled into the TRACT trial. 3483 children from Uganda were considered in this secondary analysis. Overall, 1038 (30%) of 3483 Ugandan children had SCA. 1815 (78%) of 2321 children without SCA (HbAA) tested positive for P falciparum malaria, whereas the prevalence was significantly lower in children with SCA (347 [33%] of 1038; p<0·0001). Concentrations of plasma P falciparum histidine-rich protein 2 (PfHRP2), a marker of the total burden of malaria parasites within an individual, were significantly lower in children with either known SCA (median 8 ng/mL; IQR 0–57) or unknown SCA (7 ng/mL; 0–50) than in HbAA children (346 ng/mL; 21–2121; p<0·0001). In contrast to HbAA children, few HbSS children presented with classic features of severe and complicated malaria, but both the frequency and severity of anaemia were higher in HbSS children. We found no evidence for increased mortality at day 28 in those with SCA compared with those without SCA overall (hazard ratios 1·07 [95% CI 0·31–3·76] for known SCA and 0·67 [0·15–2·90] for unknown SCA). Interpretation: The current study suggests that children with SCA are innately protected against classic severe malaria. However, it also shows that even low-level infections can precipitate severe anaemic crises that would likely prove fatal without rapid access to blood transfusion services

Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 2; peer review: 1 approved with reservations]

BACKGROUND: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. METHODS: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. DISCUSSION: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. REGISTRATION: ISRCTN49726849 (27th October 2017)

Transfusion management of severe anaemia in African children: a consensus algorithm

The phase III Transfusion and Treatment of severe anaemia in African Children Trial(TRACT) found that conservative management of uncomplicated severe anaemia (haemoglobin(Hb)4-6g/dl) was safe and that transfusion volume(20 versus30 mls/kg whole blood equivalent)for children with severe anaemia (Hb37.5oC). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all children (3196) receiving an initial transfusion, there was no evidence that nutritional status, presence of shock, malaria parasite burden, or sickle cell disease status influenced outcomes, or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating 3 additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practic

Family group conference provision in UK local authorities and associations with children looked after rates

Family group conferences (FGCs) in child welfare share decision-making with family members by bringing the immediate and wider family together to make a plan to meet a child’s needs. This paper reports survey findings on FGC provision in the UK in 2022 and explores whether in England the presence of an FGC service and the rate of FGC provision is associated with the rate of children in care, entering care, in kinship foster care and leaving care. Seventy-nine per cent (n = 167) of local authorities in the UK provided FGCs to families, and 14 per cent (n = 29) did not. Services that were more established offered a more diverse range of FGCs. The introduction of FGCs in English local authorities was associated with a higher rate of children in care, but also higher rates of kinship foster care, a key goal of FGCs where it is not possible for children to stay with their parents. Higher rates of FGCs were associated with more children leaving care, possibly due to reunification with birth families. To understand in more detail, the circumstances of children in and leaving care in local authorities with FGCs, individual data linkage studies are needed

Transfusion Volume for Children with Severe Anemia in Africa

BACKGROUND Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level. METHODS In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim–sulfamethoxazole. The primary outcome was 28-day mortality. RESULTS A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P=0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. CONCLUSIONS Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.