The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development

Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study

© 2017 Elsevier Ltd Background Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. Methods In this prospective observational study, we included children and adolescents (age

Advance Access published March 30

Summary The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n ¼ 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2-and 4-year reviews under way. Biological samples and measures include: maternal blood, faeces and urine during pregnancy; infant urine, faeces and blood at regular intervals during the first 4 years; lung function at 1 month and 4 years; cardiovascular assessment at 1 month and 4 years; skin-prick allergy testing and food challenge at 1 year; and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [[email protected]]

A prospective observational study to assess the diagnostic accuracy of clinical decision rules for children presenting to emergency departments after head injuries (protocol): The Australasian Paediatric Head Injury Rules Study (APHIRST)

Background: Head injuries in children are responsible for a large number of emergency department visits. Failure to identify a clinically significant intracranial injury in a timely fashion may result in long term neurodisability and death. Whilst cranial computed tomography (CT) provides rapid and definitive identification of intracranial injuries, it is resource intensive and associated with radiation induced cancer. Evidence based head injury clinical decision rules have been derived to aid physicians in identifying patients at risk of having a clinically significant intracranial injury. Three rules have been identified as being of high quality and accuracy: the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) from Canada, the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE) from the UK, and the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury developed by the Pediatric Emergency Care Applied Research Network (PECARN) from the USA. This study aims to prospectively validate and compare the performance accuracy of these three clinical decision rules when applied outside the derivation setting.Methods/design: This study is a prospective observational study of children aged 0 to less than 18 years presenting to 10 emergency departments within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) research network in Australia and New Zealand after head injuries of any severity. Predictor variables identified in CATCH, CHALICE and PECARN clinical decision rules will be collected. Patients will be managed as per the treating clinicians at the participating hospitals. All patients not undergoing cranial CT will receive a follow up call 14 to 90 days after the injury. Outcome data collected will include results of cranial CTs (if performed) and details of admission, intubation, neurosurgery and death. The performance accuracy of each of the rules will be assessed using rule specific outcomes and inclusion and exclusion criteria.Discussion: This study will allow the simultaneous comparative application and validation of three major paediatric head injury clinical decision rules outside their derivation setting.Trial registration: The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)- ACTRN12614000463673 (registered 2 May 2014). © 2014 Babl et al.; licensee BioMed Central Ltd

Are non-constant rates and non-proportional treatment effects accounted for in the design and analysis of randomised controlled trials? A review of current practice

Determination of the characteristics of the sixty-six randomised clinical trials in this review. Dataset containing the final determinations of trial characteristics. (XLS 63 kb

Patterns and predictors of language development from 4 to 7 years in verbal children with and without autism spectrum disorder

This study used a prospective community-based sample to describe patterns and predictors of language development from 4 to 7 years in verbal children (IQ ≥ 70) with autism spectrum disorder (ASD; n = 26–27). Children with typical language (TD; n = 858–861) and language impairment (LI; n = 119) were used for comparison. Children with ASD and LI had similar mean language scores that were lower on average than children with TD. Similar proportions across all groups had declining, increasing and stable patterns. Language progressed at a similar rate for all groups, with progress influenced by IQ and language ability at 4 years rather than social communication skills or diagnosis of ASD. These findings inform advice for parents about language prognosis in ASD

Early-life markers of atherosclerosis using aortic and carotid intima-media thickness: an assessment of methods to account for child size

Background.—Distinguishing pathological from physiological relationships between vessel size and aortic intima-media thickness (aIMT) is an important challenge, especially in growing children. We examined the relationship between childhood vessel diameter and aIMT and assessed common analytic approaches used to address this relationship.Methods.—We analyzed aIMT in two population-derived cohorts; 6-week-old infants and 19-year-olds. We simulated datasets in which we assumed a simple physiological relationship between vessel diameter and aIMT, and then superimposed possible pathological effects on aIMT; (a) intrauterine growth retardation, (b) macrosomia and (c) both intrauterine growth retardation and macrosomia. Using simulated datasets and cohorts, we evaluated analytic strategies including those in which the relationship between vessel diameter and aIMT was (a) ignored, (b) adjusted for by dividing aIMT by weight, or (c) adjusted for using varying regression techniques.Results.—aIMT was found to increase in proportion to vessel diameter in both cohorts (138 μm/mm at 6 weeks and 52 μm/mm at 19 years of age). Simply dividing aIMT by weight produced negative associations with weight across all datasets. By contrast, adjusting for vessel diameter as a covariate enabled accurate distinction of the direction of the association between aIMT and weight in all simulated datasets. These results were replicated in the cohort studies for both aIMT and carotid intima-media thickness.Conclusion.—There is a physiological relationship between vessel diameter and aIMT. Simply dividing aIMT by weight may lead to incorrect assumptions regarding the relationship between weight and aIMT. However, the physiological relationship is appropriately estimated by including vessel diameter as a covariate in regression

Applicability of the CATCH, CHALICE and PECARN paediatric head injury clinical decision rules: Pilot data from a single Australian centre

Background Clinical decision rules (CDRs) for paediatric head injury (HI) exist to identify children at risk of traumatic brain injury. Those of the highest quality are the Canadian assessment of tomography for childhood head injury (CATCH), Children's head injury algorithm for the prediction of important clinical events (CHALICE) and Pediatric Emergency Care Applied Research Network (PECARN) CDRs. They target different cohorts of children with HI and have not been compared in the same setting. We set out to quantify the proportion of children with HI to which each CDR was applicable. Methods Consecutive children presenting to an Australian paediatric Emergency Department with HIs were enrolled. Published inclusion/exclusion criteria and predictor variables from the CDRs were collected prospectively. Using these we determined the frequency with which each CDR was applicable. Results 1012 patients (69.9%) were enrolled with 949 available for analysis. Mean age was 6.8 years (21