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Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules.
Pneumonia is a leading cause of childhood mortality with Streptococcus pneumoniae a major contributor. Pneumococcal conjugate vaccines (PCVs) have been introduced into immunisation programs in many low- to middle-income countries yet there is a paucity of data evaluating the effectiveness in these settings. We assess the effectiveness of 13-valent PCV against hypoxic pneumonia, hospitalisation and other clinical endpoints in children <5 years living in Eastern Highlands Province, Papua New Guinea).
To assess the degree to which timely audiological assessment of congenital hearing loss is achieved at our institution - Perth Children's Hospital, Western Australia, and to review cases which breached this timeframe in order to address barriers to timely assessment. The benchmark used to determine timely assessment is that set out by The Joint Committee on Infant Hearing (JCIH) in which diagnostic audiological testing occurs by three months of age for those who do not pass newborn hearing screening.
Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them.
Childhood dementias are a group of rare and ultra-rare paediatric conditions clinically characterised by enduring global decline in central nervous system function, associated with a progressive loss of developmentally acquired skills, quality of life and shortened life expectancy. Traditional research, service development and advocacy efforts have been fragmented due to a focus on individual disorders, or groups classified by specific mechanisms or molecular pathogenesis.
Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected.
Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs associated with body mass index, 10 with waist circumference and 9 with subcutaneous fat thickness.
Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar.
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT.
ClC-7 is a chloride-proton antiporter of the CLC protein family. In complex with its accessory protein Ostm-1, ClC-7 localizes to lysosomes and to the osteoclasts' ruffled border, where it plays a critical role in acidifying the resorption lacuna during bone resorption. Gene inactivation in mice causes severe osteopetrosis, neurodegeneration, and lysosomal storage disease. Mutations in the human CLCN7 gene are associated with diverse forms of osteopetrosis.
Upper and lower airways are conserved in their transcriptional composition, and variations associated with disease are present in both nasal and tracheal epithelium
We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues
Here we focus on the problem of prioritising variants with respect to the observed disease phenotype
Our results identify a pretreatment tumor microenvironment that predicts response to immune checkpoint blockade, which can be therapeutically attained
Researchers have found kids who experience repeat ear infections in infancy have a much higher risk of ongoing problems with ear infections in later childhood
The Djaalinj Waakinj (Listening, Talking) Ear Portal project commenced in 2020 to evaluate an equitable ear and hearing care pathway for Aboriginal children residing in the metropolitan area of Perth.
Chris Deborah Peter Natasha Valerie Brennan-Jones Lehmann Richmond Morrison Swift PhD AO, MBBS, MSc MBBS MRCP(UK) FRACP Head, Ear and Hearing Health
Deborah Hannah Lehmann Moore AO, MBBS, MSc OAM BSc (Hons) GradDipClinEpi PhD Honorary Emeritus Fellow Head, Infectious Diseases Research 08 6319 1427
Otitis media (OM, middle ear infections) and the consequent hearing loss are major concerns for Aboriginal people and OM can seriously impact on children’s learning potential which in turn will impact on life as an adult.
Deborah Peter Lehmann Richmond AO, MBBS, MSc MBBS MRCP(UK) FRACP Honorary Emeritus Fellow Head, Vaccine Trials Group Honorary Emeritus Fellow Head,