In Whose Interest? The Need for Consistency in to Whom, and about Whom, Australian Public Interest Whistleblowers can make Protected Disclosures

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In Whose Interest? The Need for Consistency in to Whom, and about Whom, Australian Public Interest Whistleblowers can make Protected Disclosures

Since the 1990s Australia’s nine jurisdictions have passed (or, in the case of the Northern Territory, proposed to pass) public sector whistleblower legislation. The legislation, which reflects different political origins and legislative aims, is not consistent in many respects and there are few common tests across the jurisdictions. This article analyses two issues - who the Australian whistleblowercan disclose to, and who the whistleblower can make protected disclosures about. The examination of these issues indicates inconsistencies in the public law whistleblower laws enacted since the 1990s. This inconsistency is not sensible in Australia’s national economy, where an employee in one State can make a protected disclosure, but an employee in another cannot make the same disclosure. This article supports the election commitment of the Rudd federal government in 2007 to introduce best practice federal whistleblowing legislation which will hopefully overcome shortcomings analysed in this article

The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis

Rhodococcus equi (R. equi) is an important pulmonary pathogen in foals that often leads to the death of the horse. The bacterium harbors a virulence plasmid that encodes numerous virulence-associated proteins (Vaps) including VapA that is essential for intracellular survival inside macrophages. However, little is known about the precise function of VapA. Here, we demonstrate that VapA causes perturbation to late endocytic organelles with swollen endolysosome organelles having reduced Cathepsin B activity and an accumulation of LBPA, LC3 and Rab7. The data are indicative of a loss of endolysosomal function, which leads cells to upregulate lysosome biogenesis to compensate for the loss of functional endolysosomes. Although there is a high degree of homology of the core region of VapA to other Vap proteins, only the highly conserved core region of VapA, and not VapD of VapG, gives the observed effects on endolysosomes. This is the first demonstration of how VapA works and implies that VapA aids R. equi survival by reducing the impact of lysosomes on phagocytosed bacteria

Assessing methods for dealing with treatment switching in clinical trials: A follow-up simulation study

When patients randomised to the control group of a randomised controlled trial are allowed to switch onto the experimental treatment, intention-to-treat analyses of the treatment effect are confounded because the separation of randomised groups is lost. Previous research has investigated statistical methods that aim to estimate the treatment effect that would have been observed had this treatment switching not occurred and has demonstrated their performance in a limited set of scenarios. Here, we investigate these methods in a new range of realistic scenarios, allowing conclusions to be made based upon a broader evidence base. We simulated randomised controlled trials incorporating prognosis-related treatment switching and investigated the impact of sample size, reduced switching proportions, disease severity, and alternative data-generating models on the performance of adjustment methods, assessed through a comparison of bias, mean squared error, and coverage, related to the estimation of true restricted mean survival in the absence of switching in the control group. Rank preserving structural failure time models, inverse probability of censoring weights, and two-stage methods consistently produced less bias than the intentionto-treat analysis. The switching proportion was confirmed to be a key determinant of bias: sample size and censoring proportion were relatively less important. It is critical to determine the size of the treatment effect in terms of an acceleration factor (rather than a hazard ratio) to provide information on the likely bias associated with rank-preserving structural failure time model adjustments. In general, inverse probability of censoring weight methods are more volatile than other adjustment methods

Cognitive performance profiles by latent classes of drug use

Background and Objectives: The relationship between substance use and cognitive deficits is complex and requires innovative methods to enhance understanding. The present study is the first to use LCA to examine associations of drug use patterns with cognitive performance. Methods: Cocaine/heroin users (N = 552) completed questionnaires, and cognitive measures. LCA identified classes based on past-month drug use and adjusted for probabilities of group membership when examining cognitive performance. Latent indicators were: alcohol (ALC), cigarettes (CIG), marijuana (MJ), crack smoking (CS), nasal heroin (NH), injection cocaine (IC), injection heroin (IH), and injection speedball (IS). Age and education were included as covariates in model creation. Results: Bootstrap likelihood ratio test (BLRT) supported a 5-class model. Prevalent indicators (estimated probability of over 50%) for each class are as follows: “Older Nasal Heroin/Crack Smokers” (ONH/CS, n = 166.9): ALC, CIG, NH, CS; “Older, Less Educated Polysubstance” (OLEP, n = 54.8): ALC, CIG, CS, IH, IC, and IS; “Younger Multi-Injectors” (MI, n = 128.7): ALC, CIG, MJ, IH, IC, and IS; “Less Educated Heroin Injectors” (LEHI, n = 87.4): CIG, IH; and “More Educated Nasal Heroin” users (MENH, n = ALC, CIG, NH. In general, all classes performed worse than established norms and older, less educated classes performed worse, with the exception that MENH demonstrated worse cognitive flexibility than YMI. Discussion and Conclusions: This study demonstrated novel applications of a methodology for examining complicated relationships between polysubstance use and cognitive performance. Scientific Significance: Education and/or nasal heroin use are associated with reduced cognitive flexibility in this sample of inner city drug users

The effectiveness and satisfaction of web-based physiotherapy in people with spinal cord injury: a pilot randomised controlled trial

Study Design: Pilot randomised controlled trial. Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy for people with Spinal Cord Injury (SCI). Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. Methods: Twenty-four participants were recruited and randomised to receive eight weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based upon participant’s abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant were more pronounced for the 6 minute walk test. Participants were positive about using web-based physiotherapy and stated they would be happy to use it again and would recommend it to others. Overall it was rated as either good or excellent. Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention, rated the programme highly and beneficial for health and well-being at various states post injury. The results of this study warrant further work with a more homogenous sample

Neuropathologic Burden and Dementia in Nonagenarians and Centenarians

Background and objectivesThe aim of this study was to compare 2 large clinicopathologic cohorts of participants aged 90+ and to determine whether the association between neuropathologic burden and dementia in these older groups differs substantially from those seen in younger-old adults.MethodsAutopsied participants from The 90+ Study and Adult Changes in Thought (ACT) Study community-based cohort studies were evaluated for dementia-associated neuropathologic changes. Associations between neuropathologic variables and dementia were assessed using logistic or linear regression, and the weighted population attributable fraction (PAF) per type of neuropathologic change was estimated.ResultsThe 90+ Study participants (n = 414) were older (mean age at death = 97.7 years) and had higher amyloid/tau burden than ACT <90 (n = 418) (mean age at death = 83.5 years) and ACT 90+ (n = 401) (mean age at death = 94.2 years) participants. The ACT 90+ cohort had significantly higher rates of limbic-predominant age-related TDP-43 encephalopathy (LATE-NC), microvascular brain injury (μVBI), and total neuropathologic burden. Independent associations between individual neuropathologic lesions and odds of dementia were similar between all 3 groups, with the exception of μVBI, which was associated with increased dementia risk in the ACT <90 group only (odds ratio 1.5, 95% CI 1.2-1.8, p < 0.001). Weighted PAF scores indicated that eliminating μVBI, although more prevalent in ACT 90+ participants, would have little effect on dementia. Conversely, eliminating μVBI in ACT <90 could theoretically reduce dementia at a similar rate to that of AD neuropathologic change (weighted PAF = 6.1%, 95% CI 3.8-8.4, p = 0.001). Furthermore, reducing LATE-NC in The 90+ Study could potentially reduce dementia to a greater degree (weighted PAF = 5.1%, 95% CI 3.0-7.3, p = 0.001) than either ACT cohort (weighted PAFs = 1.69, 95% CI 0.4-2.7).DiscussionOur results suggest that specific neuropathologic features may differ in their effect on dementia among nonagenarians and centenarians from cohorts with different selection criteria and study design. Furthermore, microvascular lesions seem to have a more significant effect on dementia in younger compared with older participants. The results from this study demonstrate that different populations may require distinct dementia interventions, underscoring the need for disease-specific biomarkers