Monash University

About: Monash University is a education organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 35920 authors who have published 100681 publications receiving 3027002 citations.

Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

Abstract: Aicardi-Goutieres syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutieres syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

Resistance: a constructive tool for change management

Abstract: Traditionally, resistance has been cast as adversarial ‐ the enemy of change that must be defeated if change is to be successful. While it is apparent that classical management theory viewed resistance in such a manner, recent literature contains much evidence that suggests resistance may indeed be useful and is not to be simply discounted. Present day suggestions and prescriptions for managing resistance have evidently disregarded this research and left little room for utility in resistance. This paper argues that the difficulty of organisational change is often exacerbated by the mismanagement of resistance derived from a simple set of assumptions that misunderstand resistance’s essential nature. It is suggested that management may greatly benefit from techniques that carefully manage resistance to change by looking for ways of utilising it rather than overcoming it.

Parameterisation and evaluation of a Bayesian network for use in an ecological risk assessment

Abstract: Catchment managers face considerable challenges in managing ecological assets. This task is made difficult by the variable and complex nature of ecological assets, and the considerable uncertainty involved in quantifying how various threats and hazards impact upon them. Bayesian approaches have the potential to address the modelling needs of environmental management. However, to date many Bayesian networks (Bn) developed for environmental management have been parameterised using knowledge elicitation only. Not only are these models highly qualitative, but the time and effort involved in elicitation of a complex Bn can often be overwhelming. Unfortunately in environmental applications, data alone are often too limited for parameterising a Bn. Consequently, there is growing interest in how to parameterise Bns using both data and elicited information. At present, there is little formal guidance on how to combine what can be learned from the data with what can be elicited. In a previous publication we proposed a detailed methodology for this process, focussing on parameterising and evaluating a Bn. In this paper, we further develop this methodology using a risk assessment case study, with the focus being on native fish communities in the Goulburn Catchment (Victoria, Australia).