John B Carlin

Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

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Publications (391)1874.23 Total impact

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    ABSTRACT: In cost-effectiveness analyses of drugs or health technologies, estimates of life years saved or quality-adjusted life years saved are required. Randomised controlled trials can provide an estimate of the average treatment effect; for survival data, the treatment effect is the difference in mean survival. However, typically not all patients will have reached the endpoint of interest at the close-out of a trial, making it difficult to estimate the difference in mean survival. In this situation, it is common to report the more readily estimable difference in median survival. Alternative approaches to estimating the mean have also been proposed. We conducted a simulation study to investigate the bias and precision of the three most commonly used sample measures of absolute survival gain - difference in median, restricted mean and extended mean survival - when used as estimates of the true mean difference, under different censoring proportions, while assuming a range of survival patterns, represented by Weibull survival distributions with constant, increasing and decreasing hazards. Our study showed that the three commonly used methods tended to underestimate the true treatment effect; consequently, the incremental cost-effectiveness ratio (ICER) would be overestimated. Of the three methods, the least biased is the extended mean survival, which perhaps should be used as the point estimate of the treatment effect to be inputted into the ICER, while the other two approaches could be used in sensitivity analyses. More work on the trade-offs between simple extrapolation using the exponential distribution and more complicated extrapolation using other methods would be valuable. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Pharmaceutical Statistics 07/2015; DOI:10.1002/pst.1700 · 1.10 Impact Factor
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    ABSTRACT: Perinatal depression is a neglected global health priority, affecting 10–15% of women in high-income countries and a greater proportion in low-income countries. Outcomes for children include cognitive, behavioural, and emotional difficulties and, in low-income settings, perinatal depression is associated with stunting and physical illness. In the Victorian Intergenerational Health Cohort Study (VIHCS), we aimed to assess the extent to which women with perinatal depressive symptoms had a history of mental health problems before conception.
    The Lancet 06/2015; DOI:10.1016/S0140-6736(14)62248-0 · 45.22 Impact Factor
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    ABSTRACT: Children with cardiomyopathy (CM) are at risk of sudden cardiac death (SCD), but the incidence and risk factors for this outcome are not clear. This study sought to determine the incidence and risk factors for SCD in children with varying CM phenotypes from a long-term population-based study of childhood CM. The NACCS (National Australian Childhood Cardiomyopathy Study) is an ongoing longitudinal cohort study including all children in Australia with primary CM who were diagnosed between January 1, 1987, and December 31, 1996, and were <10 years of age. The cumulative incidence and risk factors for SCD within individual CM phenotypes were explored using survival analysis. Of 289 eligible patients, 16 (5.5%) experienced SCD over a median follow-up of 11.9 years (interquartile range: 1.7 to 15.4). The risk of SCD varied according to CM phenotype (p = 0.007). The cumulative incidence of SCD at 15 years was 5% for dilated cardiomyopathy (DCM), 6% for hypertrophic cardiomyopathy (HCM), 12% for restrictive cardiomyopathy, and 23% for left ventricular (LV) noncompaction. Older age at diagnosis, positive family history of CM, and severity of LV dysfunction were related to increased risk of SCD in patients with DCM, and a higher posterior wall thickness Z-score was the sole risk factor identified for patients with HCM. Predictors of SCD include CM phenotype, family history of CM (DCM), severity of systolic dysfunction (DCM), and extent of LV hypertrophy (HCM). Continuing follow-up of this cohort into adulthood is likely to reveal an ongoing risk of SCD. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 06/2015; 65(21):2302-10. DOI:10.1016/j.jacc.2015.03.552 · 15.34 Impact Factor
  • Cattram D. Nguyen · Katherine J. Lee · John B. Carlin
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    ABSTRACT: Multiple imputation is gaining popularity as a strategy for handling missing data, but there is a scarcity of tools for checking imputation models, a critical step in model fitting. Posterior predictive checking (PPC) has been recommended as an imputation diagnostic. PPC involves simulating "replicated" data from the posterior predictive distribution of the model under scrutiny. Model fit is assessed by examining whether the analysis from the observed data appears typical of results obtained from the replicates produced by the model. A proposed diagnostic measure is the posterior predictive "p-value", an extreme value of which (i.e., a value close to 0 or 1) suggests a misfit between the model and the data. The aim of this study was to evaluate the performance of the posterior predictive p-value as an imputation diagnostic. Using simulation methods, we deliberately misspecified imputation models to determine whether posterior predictive p-values were effective in identifying these problems. When estimating the regression parameter of interest, we found that more extreme p-values were associated with poorer imputation model performance, although the results highlighted that traditional thresholds for classical p-values do not apply in this context. A shortcoming of the PPC method was its reduced ability to detect misspecified models with increasing amounts of missing data. Despite the limitations of posterior predictive p-values, they appear to have a valuable place in the imputer's toolkit. In addition to automated checking using p-values, we recommend imputers perform graphical checks and examine other summaries of the test quantity distribution. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Biometrical Journal 05/2015; DOI:10.1002/bimj.201400034 · 1.24 Impact Factor
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    ABSTRACT: There is substantial interest in studying lung function in infants, to better understand the early life origins of chronic lung diseases such as asthma. Multiple breath washout (MBW) is a technique for measuring lung function that has been adapted for use in infants. Respiratory sighs occur frequently in young infants during natural sleep, and in accordance with current MBW guidelines, result in exclusion of data from a substantial proportion of testing cycles. We assessed how sighs during MBW influenced the measurements obtained using data from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part of the wash-in phase (before the last 5 breaths) were not associated with differences in standard MBW measurements compared with tests without sighs. In contrast, sighs that occurred during the washout were associated with a small but discernible increase in magnitude and variability. For example, the mean lung clearance index increased by 0.36 (95% CI: 0.11-0.62) and variance increased by a multiplicative factor of 2 (95% CI: 1.6-2.5). The results suggest it is reasonable to include MBW data from testing cycles where a sigh occurs during the wash-in phase, but not during washout, of MBW. By recovering data that would otherwise have been excluded, we estimate a boost of about 10% to the final number of acceptable tests and 6% to the number of individuals successfully tested. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    04/2015; 3(4). DOI:10.14814/phy2.12347
  • Jock Lawrie · John B. Carlin · Andrew B. Forbes
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    ABSTRACT: Stepped wedge randomized trials are increasingly popular. Here we derive the optimal design for a fixed number of periods; this does not allocate an equal number of cluster units to each treatment sequence as might otherwise have been expected.
    Statistics [?] Probability Letters 04/2015; 99:210-214. DOI:10.1016/j.spl.2015.01.024 · 0.53 Impact Factor
  • Kim Mulholland · John Carlin · Trevor Duke · Martin Weber
    The Lancet Respiratory Medicine 03/2015; 3(3). DOI:10.1016/S2213-2600(15)00032-6 · 9.63 Impact Factor
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    ABSTRACT: 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 = 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 [peter.vuillermin@deakin.edu.au]. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    International Journal of Epidemiology 03/2015; DOI:10.1093/ije/dyv026 · 9.20 Impact Factor
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    ABSTRACT: 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.
    03/2015; 4(3):e34. DOI:10.1038/cti.2015.2
  • Pediatrics 01/2015; 135(2). DOI:10.1542/peds.2014-1832 · 5.30 Impact Factor
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    ABSTRACT: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 01/2015; 14(3). DOI:10.1016/j.jcf.2014.12.007 · 3.82 Impact Factor
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    ABSTRACT: As there is limited knowledge regarding the longitudinal development and early ontogeny of naı ̈ve and regulatory CD4+ T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naı ̈ve (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 naı ̈ ve and regulatory CD4+ T-cell populations was determined by flow cytometry, and the thymic and central naı ̈ve 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 naı ̈ ve (CD45RA+), and of these, ~ 80% had a thymic naı ̈ ve phenotype (CD31+ and high TREC), with the remainder already central naı ̈ve cells (CD31− and low TREC). During the first year of life, the naı ̈ve CD4+ T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naı ̈ve T regulatory cells (rTreg; CD4+CD45RA+FoxP3+) and activated Treg (aTreg, CD4+CD45RA−FoxP3high) increased markedly. The ratio of thymic to central naı ̈ve 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.
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    ABSTRACT: Objectives: To describe the incidence rate and clinical outcomes of intussusception in Australia in children aged <24 months prior to the use of rotavirus vaccines in Australia, and to explore associations between patient characteristics and outcomes in children with intussusception.Methods: This study used Australian national hospital discharge data on intussusception from July 2000 to June 2006 for children aged <24 months and data from the Australian Bureau of Statistics (ABS) as a proxy for population numbers to estimate incidence. Logistic regression was used to examine associations between patient characteristics (age, sex, ethnicity) and outcomes (length of hospital stay >2 days and the need for surgical intervention).Results: The overall incidence rate of intussusception was 5.4 per 10,000 child-years in children under 24 months (95%CI 5.17–5.70). There was a declining rate over the study period (p<0.001). Age at time of intussusception was strongly associated with length of hospital stay and surgery.Conclusions: This study provides an estimate of the pre-rotavirus vaccine incidence of intussusception across Australia, which is important for monitoring the occurrence of intussusceptions post the introduction of rotavirus vaccine.
    Australian and New Zealand Journal of Public Health 12/2014; 39(1). DOI:10.1111/1753-6405.12297 · 1.90 Impact Factor
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    Kim Mulholland · John B Carlin · Trevor Duke · Martin Weber
    The Lancet Respiratory Medicine 11/2014; 2(12). DOI:10.1016/S2213-2600(14)70273-5 · 9.63 Impact Factor
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    ABSTRACT: Background: Neonatal illness is a leading cause of death worldwide; sepsis is one of the main contributors. The etiologies of community-acquired neonatal bacteremia in developing countries have not been well characterized. Methods: Infants <2 months of age brought with illness to selected health facilities in Bangladesh, Bolivia, Ghana, India, Pakistan and South Africa were evaluated, and blood cultures taken if they were considered ill enough to be admitted to hospital. Organisms were isolated using standard culture techniques. Results: Eight thousand eight hundred and eighty-nine infants were recruited, including 3177 0–6 days of age and 5712 7–59 days of age; 10.7% (947/8889) had a blood culture performed. Of those requiring hospital management, 782 (54%) had blood cultures performed. Probable or definite pathogens were identified in 10.6% including 10.4% of newborns 0–6 days of age (44/424) and 10.9% of infants 7–59 days of age (39/358). Staphylococcus aureus was the most commonly isolated species (36/83, 43.4%) followed by various species of Gram-negative bacilli (39/83, 46.9%; Acinetobacter spp., Escherichia coli and Klebsiella spp. were the most common organisms). Resistance to second and third generation cephalosporins was present in more than half of isolates and 44% of the Gram-negative isolates were gentamicin-resistant. Mortality rates were similar in hospitalized infants with positive (5/71, 7.0%) and negative blood cultures (42/557, 7.5%). Conclusions: This large study of young infants aged 0–59 days demonstrated a broad array of Gram-positive and Gram-negative pathogens responsible for community-acquired bacteremia and substantial levels of antimicrobial resistance. The role of S. aureus as a pathogen is unclear and merits further investigation.
    The Pediatric Infectious Disease Journal 11/2014; 34(1). DOI:10.1097/INF.0000000000000549 · 3.14 Impact Factor
  • Helena Romaniuk · George C Patton · John B Carlin
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    ABSTRACT: Multiple imputation has entered mainstream practice for the analysis of incomplete data. We have used it extensively in a large Australian longitudinal cohort study, the Victorian Adolescent Health Cohort Study (1992-2008). Although we have endeavored to follow best practices, there is little published advice on this, and we have not previously examined the extent to which variations in our approach might lead to different results. Here, we examined sensitivity of analytical results to imputation decisions, investigating choice of imputation method, inclusion of auxiliary variables, omission of cases with excessive missing data, and approaches for imputing highly skewed continuous distributions that are analyzed as dichotomous variables. Overall, we found that decisions made about imputation approach had a discernible but rarely dramatic impact for some types of estimates. For model-based estimates of association, the choice of imputation method and decisions made to build the imputation model had little effect on results, whereas estimates of overall prevalence and prevalence stratified by subgroup were more sensitive to imputation method and settings. Multiple imputation by chained equations gave more plausible results than multivariate normal imputation for prevalence estimates but appeared to be more susceptible to numerical instability related to a highly skewed variable.
    American Journal of Epidemiology 10/2014; 180(9). DOI:10.1093/aje/kwu224 · 4.98 Impact Factor
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    ABSTRACT: Objective Cardiorespiratory fitness and adiposity may influence cardiovascular risk through their effects on inflammation. The long-term effects of these modifiable factors on adult inflammation remain uncertain. The associations of childhood and adulthood cardiorespiratory fitness and adiposity with adult inflammation (C-reactive protein (CRP), fibrinogen) were examined.Methods1,976 children examined in 1985 and re-examined as young adults in 2004-2006 were included. Cardiorespiratory fitness and adiposity were assessed at both waves. CRP and fibrinogen were measured at follow-up.ResultsHigher childhood fitness was associated with lower adult inflammation in both sexes. After adjusting for childhood adiposity, the association with CRP attenuated in males, but remained in females (average reduction of CRP 18.1% (95% CI 11.3-24.4%) per 1-SD increase in childhood fitness). Higher adult fitness, adjusting for childhood fitness (an increase in fitness from childhood to adulthood), was associated with lower adult CRP in females and lower fibrinogen in males. Higher childhood and adulthood adiposity (an increase in adiposity from childhood to adulthood) were associated with higher adult inflammation in both sexes.Conclusions Prevention programs to increase fitness and reduce adiposity in childhood, and maintain a favorable fitness and weight into adulthood, may lead to reduction in adult systemic inflammation.
    Obesity 10/2014; 22(12). DOI:10.1002/oby.20871 · 4.39 Impact Factor
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    ABSTRACT: Background It is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the “Hobart method”) has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial. Methods/design This is a multicentre, randomised, masked, controlled trial in preterm infants 25–28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017. Discussion Minimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25–28 weeks gestation. Trial registration Australia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.
    BMC Pediatrics 08/2014; 14(1):213. DOI:10.1186/1471-2431-14-213 · 1.92 Impact Factor
  • Drug and Alcohol Dependence 07/2014; 140:e46. DOI:10.1016/j.drugalcdep.2014.02.147 · 3.28 Impact Factor
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    ABSTRACT: Objectives To determine whether bronchoalveolar lavage (BAL)-directed therapy for infants and young children with cystic fibrosis (CF), rather than standard therapy, was justified on the grounds of a decrease in average costs and whether the use of BAL reduced treatment costs associated with hospital admissions. Study design Costs were assessed in a randomized controlled trial conducted in Australia and New Zealand on infants diagnosed with CF after newborn screening and assigned to receive either BAL-directed or standard therapy until they reached 5 years of age. A health care funder perspective was adopted. Resource use measurement was based on standardized data collection forms administered for patients across all sites. Unit costs were obtained primarily from government schedules. Results Mean costs per child during the study period were Australian dollars (AUD)92 860 in BAL-directed therapy group and AUD90 958 in standard therapy group (mean difference AUD1902, 95% CI AUD-27 782 to 31 586, P = .90). Mean hospital costs per child during the study period were AUD57 302 in the BAL-directed therapy group and AUD66 590 in the standard therapy group (mean difference AUD-9288; 95% CI AUD-35 252 to 16 676, P = .48). Conclusions BAL-directed therapy did not result in either lower mean hospital admission costs or mean costs overall compared with managing patients with CF by a standard protocol based upon clinical features and oropharyngeal culture results alone. Following on our previous findings that BAL-directed treatment offers no clinical advantage over standard therapy at age 5 years, flexible bronchoscopy with BAL cannot be recommended for the routine management of preschool children with CF on the basis of overall cost savings.
    Journal of Pediatrics 07/2014; 165(3). DOI:10.1016/j.jpeds.2014.05.031 · 3.74 Impact Factor

Publication Stats

21k Citations
1,874.23 Total Impact Points

Institutions

  • 2000–2015
    • Murdoch Childrens Research Institute
      • • Clinical Epidemiology & Biostatistics (CEBU)
      • • Research Group for Healthy Mothers Healthy Families
      • • Centre for Adolescent Health
      Melbourne, Victoria, Australia
  • 1992–2015
    • The Royal Children's Hospital
      • • Department of Allergy and Immunology
      • • Clinical Epidemiology and Biostatistics Unit (CEBU)
      • • Centre for Adolescent Health
      • • Department of Respiratory Medicine
      Melbourne, Victoria, Australia
  • 1991–2015
    • University of Melbourne
      • • Department of Paediatrics
      • • Department of Psychiatry
      Melbourne, Victoria, Australia
  • 2010
    • University of Bristol
      • Faculty of Medicine and Dentistry
      Bristol, England, United Kingdom
  • 2002–2010
    • University of New South Wales
      • National Drug and Alcohol Research Centre
      Kensington, New South Wales, Australia
  • 2009
    • Ministry of Health, Fiji
      Suva City, Central, Fiji
  • 2008
    • Sydney Children's Hospital
      Sydney, New South Wales, Australia
  • 2007
    • University of Queensland
      • Institute for Molecular Bioscience
      Brisbane, Queensland, Australia
    • Biomedical Informatics Centre
      Chandigarh, Chandīgarh, India
    • National Maternity Hospital
      Dublin, Leinster, Ireland
  • 2006
    • Alfred Hospital
      • Department of Allergy, Immunology & Respiratory Medicine (AIRmed)
      Melbourne, Victoria, Australia
    • Cancer Council Victoria
      • Centre for Behavioural Research in Cancer
      Melbourne, Victoria, Australia
  • 2005
    • University of Adelaide
      Tarndarnya, South Australia, Australia
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2000–2003
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
  • 1998
    • Victoria University Melbourne
      Melbourne, Victoria, Australia