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Murdoch Childrens Research Institute | Date: 2017-05-03

The present invention relates to method of treating and/or preventing inflammation in a subject caused by bacteria that express HtrA. The present invention further relates to immunogenic compositions comprising an HtrA polypeptide or fragment thereof, as well as a therapeutic and/or prophylactic vaccine for treating or preventing disease.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE.2011.2.2-03 | Award Amount: 11.56M | Year: 2012

Nutrition during early development has an important impact on later health, particularly through greater obesity risk, as demonstrated by FP6 EARNEST. EarlyNutrition explores the current key hypotheses on likely causes and pathways to prevention of early life origins of obesity (specifically adiposity) and associated disorders. We bring extraordinary expertise and study populations of 470,000 individuals to investigate: The fuel mediated in utero hypothesis The accelerated postnatal weight gain hypothesis The mismatch hypothesis. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level, and refined strategies for intervention in pregnancy and early post natal life to prevent obesity. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme, we will provide the scientific foundations for evidence based recommendations for optimal EarlyNutrition that incorporate long-term health outcomes, focusing on 4 Target Groups: women before pregnancy; pregnant women; infants (incl. breastfeeding); young children. Evidence is produced from animal and placental studies (Theme 1; T1), prospective cohort studies (T2), and randomised controlled trials in pregnant women and infants (T3). T4 covers scientific strategic integration, recommendation development and dissemination, including systematic reviews and behaviour change approaches. A strong multi-disciplinary team of international leaders in the field including collaborators from USA and Australia achieves balance and complementarity. The projects impact comprises definitive evidence on early nutrition effects on health, enhanced EU and global policies, major economic benefits through obesity prevention and value-added nutritional products, and practical recommendations on optimal nutrition in Target Groups. Wide dissemination will be achieved through active engagement with stakeholders.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-23-2014 | Award Amount: 6.96M | Year: 2015

Childrens health affects the future of Europe children are citizens, future workers, parents and carers. Children are dependent on society to provide effective health services (UN Convention on the Rights of the Child). Models of child primary health care vary widely across Europe based on two broad alternatives (primary care paediatricians or generic family doctors), and a variety of models of school health and adolescent direct access services. There is little research to show which model(s) are best, implying that some are inefficient or ineffective, with sub-optimal outcomes. MOCHA will draw on networks, earlier child health projects and local agents to model and evaluate child primary care in all 30 EU/EEA countries. Scientific partners from 11 European countries, plus partners from Australia and USA, encompassing medicine, nursing, economics, informatics, sociology and policy management, will: Categorise the models, and school health and adolescent services Develop innovative measures of quality, outcome, cost, and workforce of each, and apply them using policy documents, routine statistics, and available electronic data sets Assess effects on equality, and on continuity of care with secondary care. Systematically obtain stakeholder views. Indicate optimal future patterns of electronic records and big data to optimise operation of the model(s). The results will demonstrate the optimal model(s) of childrens primary care with a prevention and wellness focus, with an analysis of factors (including cultural) which might facilitate adoption, and indications for policy makers of both the health and economic gains possible. The project will have a strong dissemination programme throughout to ensure dialogue with public, professionals, policy makers, and politicians. The project will take 42 months (36 of scientific work plus start up and close), and deliver major awareness and potential benefit for European childrens health and healthy society.

Lee M.G.,Murdoch Childrens Research Institute
The Journal of thoracic and cardiovascular surgery | Year: 2012

To determine by 24-hour blood pressure monitoring the risk of hypertension late after coarctation repair in patients with arch hypoplasia. Sixty-two of 116 consecutive patients (age, ≥10 years) who had coarctation repair and were quoted subjectively by the surgeon or the cardiologist to have arch hypoplasia at the time of the repair underwent a transthoracic echocardiogram and 24-hour blood pressure monitoring. Median age at repair was 11 days (range, 6-48 days). Mean preoperative z score of the proximal transverse arch was -2.43 ± 0.46. Eight patients had a repair via sternotomy (6 end-to-side anastomoses, 2 patch repairs) and 54 had a conventional repair via thoracotomy. After a follow-up of 18 ± 5 years, 27% of the patients (17/62) had resting hypertension and 60% (37/62) had abnormal ambulatory blood pressure. Sensitivity of high resting blood pressure in detecting an abnormal 24-hour ambulatory blood pressure was 41%. Twenty patients had arch obstruction at last follow-up. Eighteen of them (90%) had abnormal ambulatory blood pressure. None of the patients operated on with end-to-side repair via sternotomy had reobstruction compared with 33% (18/54) of those repaired via thoracotomy. Patients with a hypoplastic arch operated via thoracotomy have an alarming prevalence of hypertension. Regular follow-up with 24-hour ambulatory blood pressure monitoring is warranted, especially in patients who have had a smaller aortic arch at the time of the initial operation. Crown Copyright © 2012. Published by Mosby, Inc. All rights reserved.

Spittle A.,Murdoch Childrens Research Institute
Cochrane database of systematic reviews (Online) | Year: 2012

Infants born preterm are at increased risk of developing cognitive and motor impairments compared with infants born at term. Early developmental interventions have been used in the clinical setting with the aim of improving the overall functional outcome for these infants. However, the long-term benefit of these programmes remains unclear. To review the effectiveness of early developmental intervention post-discharge from hospital for preterm (< 37 weeks) infants on motor or cognitive development. The Cochrane Neonatal Review group search strategy was used to identify randomised and quasi-randomised controlled trials of early developmental interventions post hospital discharge. Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL, PsycINFO and EMBASE (1966 through to October 2012). Studies included had to be randomised or quasi-randomised controlled trials of early developmental intervention programmes that began within the first 12 months of life for infants born at < 37 weeks with no major congenital abnormalities. Intervention could commence as an inpatient; however, a post-discharge component was necessary to be included in this review. The outcome measures were not pre-specified other than that they had to assess cognitive ability, motor ability or both. The rates of cerebral palsy were also documented. Data were extracted and entered by two independent review authors. Cognitive and motor outcomes were pooled in four age groups - infancy (zero to < three years), pre-school age (three to < five years), school age (five to 17 years) and adulthood (≥ 18 years). Meta-analysis was carried out using RevMan 5.1 to determine the effects of early developmental intervention at each age range. Subgroup analysis was carried out in relation to gestational age, birthweight, brain injury, commencement of intervention and focus of intervention. Twenty-one studies met the inclusion criteria (3133 randomised patients). Only 10 of these studies were RCTs with appropriate allocation concealment. There was variability with regard to the focus and intensity of the intervention, subject characteristics and in length of follow-up. Meta-analysis concluded that intervention improved cognitive outcomes at infant age (developmental quotient (DQ): standardised mean difference (SMD) 0.31 standard deviations (SD); 95% confidence interval (CI) 0.13 to 0.50; P < 0.001; 13 studies; 2147 patients), and pre-school age (intelligence quotient (IQ); SMD 0.45 SD; 95% CI 0.34 to 0.57; P < 0.001; six studies; 1276 patients). However, this effect was not sustained at school age (IQ: SMD 0.25 SD; 95% CI -0.10 to 0.61; P = 0.16; five studies; 1242 patients). There was significant heterogeneity between studies for cognitive outcomes at infant and school ages. In regards to motor outcomes, meta-analysis of 10 studies showed a significant effect in favour of early developmental interventions; however, the effect was small (motor scale developmental quotient (DQ): SMD 0.10 SD; 95% CI 0.00 to 0.19; P = 0.04; 10 studies; 1745 patients). There was no effect on the rate of cerebral palsy in survivors; risk ratio (RR) 0.89; 95% CI 0.55 to 1.44; five studies; 737 patients). There was little evidence for a positive effect on motor outcomes in the long term, with only five of the included studies reporting outcomes at pre-school or school age. Early intervention programmes for preterm infants have a positive influence on cognitive and motor outcomes during infancy, with the cognitive benefits persisting into pre-school age. There is a great deal of heterogeneity between studies due to the variety of early developmental intervention programmes trialled and gestational ages of the preterm infants included, which limits the comparisons of intervention programmes. Further research is needed to determine which early developmental interventions are the most effective at improving cognitive and motor outcomes, and on the longer-term effects of these programmes.

Farlie P.G.,Murdoch Childrens Research Institute
American Journal of Medical Genetics, Part C: Seminars in Medical Genetics | Year: 2013

Pierre Robin sequence (PRS) is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate and glossoptosis leading to life-threatening obstructive apnea and feeding difficulties during the neonatal period. The respiratory issues require careful management and in severe cases may require extended stays in neonatal intensive care units and surgical intervention such as lengthening the lower jaw or tracheotomy to relieve airway obstruction. These feeding and respiratory complications frequently continue well into childhood, affecting not only growth and development but also impacting on long term educational attainment. The diagnosis of PRS depends on readily recognizable clinical features but the phenotypic similarity of many PRS individuals conceals considerable etiological heterogeneity. Defects in the growth of the mandible sit at the core of PRS and the natural history of PRS can be classified into two major streams: primary defects of mandibular outgrowth and elongation and issues that are external to the mandibular skeleton but that secondarily impact on its growth. These altered developmental trajectories appear to be driven by a range of influences including defects in cartilage growth, neuromuscular function and fetal constraint. Various genetic and cytogenetic associations have been made with PRS and the diversity of these associations highlights the fact that there are numerous ways to arrive at this common phenotypic endpoint. © 2013 Wiley Periodicals, Inc.

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