Aboriginal and Torres Strait Islander absolute cardiovascular risk assessment and management: systematic review of evidence to inform national guidelines

Australia’s absolute cardiovascular disease (CVD) risk assessment algorithm1 first examines whether individuals meet criteria for clinically determined high CVD risk and, in those not meeting these criteria, applies the Framingham Risk Equation to estimate an individual’s risk of having a CVD event in the next 5 years. The same risk equation is used for Aboriginal and Torres Strait Islander people and non-Indigenous Australians, although there is variation in underlying risk across the two populations, with the former experiencing a greater burden of cardiovascular risk factors.This research was funded by a grant from the Australian Government Department of Health

Review of evidence for the alignment of guidelines on Aboriginal and Torres Strait Islander absolute cardiovascular disease risk: A report prepared for the Australian Government Department of Health

Policy context: Cardiovascular disease (CVD) is highly preventable. CVD continues to be the largest contributor to mortality within the Aboriginal and Torres Strait Islander population and rates of CVD are disproportionately higher within the Australian Aboriginal and Torres Strait Islander population compared to the non-Indigenous population. Improving uptake of current evidence based solutions such as the absolute risk approach to CVD within the Aboriginal and Torres Strait Islander population is important to address this disparity. Although there are several tools available supporting an absolute CVD risk approach, clinical uptake is limited due to a number of factors including an outdated continued reliance on the ‘single risk factor’ approach to prevention, diagnosis and treatment of CVD. A major barrier to uptake is inconsistent messages in the current clinical practice guidelines. Key messages: There are three main guidelines on the absolute CVD risk approach for Aboriginal and Torres Strait Islander peoples in Australia: The NVDPA Guidelines for the Management of Absolute Cardiovascular Disease Risk; The Central Australian Rural Practitioners Association Standard Treatment Manual; and the RACGP National Guide to a Preventive Health Assessment for Aboriginal and Torres Strait Islander People. There is considerable alignment between the existing guidelines, including the need for an absolute risk approach, conditions conferring automatic high risk, use of the Framingham risk equation as the basis of calculating absolute risk, and the need to treat people at a greater than 15% risk of a primary CVD event over the next five years. The guidelines diverge materially in relation to four recommendations: 1) the age at which to commence absolute CVD risk assessment; 2) whether or not calculated risk scores should be adjusted upward by 5%; 3) how often CVD risk should be assessed; and 4) treatment targets for blood pressure. Available evidence indicates that CVD events and high absolute CVD risk occurs earlier in Aboriginal and Torres Strait Islander peoples, and that prevention of CVD should also start early. The proportion of Aboriginal and Torres Strait Islander peoples at high absolute CVD risk at the ages of 18-34 years broadly corresponds to the proportion at high risk among the general population aged 45-54 years. Limited evidence suggests that the current risk scores are likely to underestimate risk in Aboriginal and Torres Strait Islander peoples. Specific data on the extent of underestimation and alternative validated risk scores in this population are lacking. There is no primary data on adjusting risk scores upwards by 5% in Aboriginal and Torres Strait Islander people. Frequency of CVD risk assessment should be based on initial level of risk but the optimal interval for risk reassessment at each level of risk is not clear. There is general agreement between the guidelines to lower blood pressure as tolerated but there are inconsistencies in the exact blood pressure target. Evidence suggests that reductions in systolic blood pressure result in proportional reductions in CVD events and all-cause mortality. CVD guidelines could be kept up to date by adopting a ‘living’ guidelines model, but consideration needs to be given to how to identify relevant updated evidence and how to integrate the updates into electronic decision support tools.This research was supported by a grant from the Australian Government Department of Health

The natural history and genotype–phenotype correlations of TMPRSS3 hearing loss:an international, multi-center, cohort analysis

TMPRSS3-related hearing loss presents challenges in correlating genotypic variants with clinical phenotypes due to the small sample sizes of previous studies. We conducted a cross-sectional genomics study coupled with retrospective clinical phenotype analysis on 127 individuals. These individuals were from 16 academic medical centers across 6 countries. Key findings revealed 47 unique TMPRSS3 variants with significant differences in hearing thresholds between those with missense variants versus those with loss-of-function genotypes. The hearing loss progression rate for the DFNB8 subtype was 0.3 dB/year. Post-cochlear implantation, an average word recognition score of 76% was observed. Of the 51 individuals with two missense variants, 10 had DFNB10 with profound hearing loss. These 10 all had at least one of 4 TMPRSS3 variants predicted by computational modeling to be damaging to TMPRSS3 structure and function. To our knowledge, this is the largest study of TMPRSS3 genotype–phenotype correlations. We find significant differences in hearing thresholds, hearing loss progression, and age of presentation, by TMPRSS3 genotype and protein domain affected. Most individuals with TMPRSS3 variants perform well on speech recognition tests after cochlear implant, however increased age at implant is associated with worse outcomes. These findings provide insight for genetic counseling and the on-going design of novel therapeutic approaches.</p

Investigating Instructor Talk in Novel Contexts: Widespread Use, Unexpected Categories, and an Emergent Sampling Strategy.

Instructor Talk-noncontent language used by instructors in classrooms-is a recently defined and promising variable for better understanding classroom dynamics. Having previously characterized the Instructor Talk framework within the context of a single course, we present here our results surrounding the applicability of the Instructor Talk framework to noncontent language used by instructors in novel course contexts. We analyzed Instructor Talk in eight additional biology courses in their entirety and in 61 biology courses using an emergent sampling strategy. We observed widespread use of Instructor Talk with variation in the amount and category type used. The vast majority of Instructor Talk could be characterized using the originally published Instructor Talk framework, suggesting the robustness of this framework. Additionally, a new form of Instructor Talk-Negatively Phrased Instructor Talk, language that may discourage students or distract from the learning process-was detected in these novel course contexts. Finally, the emergent sampling strategy described here may allow investigation of Instructor Talk in even larger numbers of courses across institutions and disciplines. Given its widespread use, potential influence on students in learning environments, and ability to be sampled, Instructor Talk may be a key variable to consider in future research on teaching and learning in higher education

Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics

Medieval knights amid the gum-trees : the experience of European heritage tourism in south-east Queensland, Australia

This paper is interested in the way in which the heritage of another place, time, and culture is repurposed for popular consumption in an experience economy, as well as the way in which the visitors experience their own past and the past of others. We trace the processes of engagement, education and nostalgia that occur when the European heritage is presented in a postcolonial context and an Australian environment. The information presented includes the results of qualitative and quantitative research conducted at the Abbey Museum over the December-Jan. period of 2012-13

Health care with limited resources: Ethics, epidemiology and public policy

All modern societies have a shortage of health care resources, which means that we need to have principles to allocate health care resources fairly when not everyone's needs can be met. In this thesis, I argue that health care prioritisation decisions should be largely made on the basis of two factors: to what extent is health care likely to improve a patient's subjective well-being, and to what extent is health care likely to improve a patient's morally relevant capabilities. I argue for my view through critically engaging with alternative theories about how to allocate health care resources fairly in conditions of scarcity. In Part 1 of this thesis, I consider luck egalitarian principles, which, as I describe in Chapter 1, provide a philosophically nuanced formulation of responsibility-sensitive principles for the allocation of health care resources. Many luck egalitarians argue that those patients who deliberately engage in reasonably avoidable, health-damaging behaviours (such as smoking) should receive lower priority for scarce health care resources than those who do not engage in these behaviours. I reject this view, arguing in Chapter 2 that luck egalitarian principles are too harsh to be a plausible moral way of regulating health care resources. In Chapter 3, I argue that to the extent that luck egalitarian principles are intended to be used in public policy as a way of regulating health care resources, they should be rejected as they would be impractical to implement. In Part 2 of this thesis, I consider other principles (which do not make use of individual responsibility for health behaviours as a rationing criterion) for allocating health care resources fairly in conditions of scarcity. In Chapter 4, I reject the view that health care rationing should be solely determined by market forces, as due to the structural features of health insurance and health care, health care rationing requires some level of government intervention. In Chapter 5, I explain the problems with two metrics, Disability Adjusted Life Years (DALYs) and Quality Adjusted Life Years (QALYs) arguing that they are problematic because they conflate two questions which should often be considered separately: how to evaluate interventions which improve people's quality of life, and how to evaluate interventions which extend people's lifespan. In the final two chapters of this thesis, I argue for my own view of how to fairly allocate health care resources in conditions of scarcity. In Chapter 6, I argue that much of what makes health care morally valuable is the effect that it can have on improving people's capabilities, however, focusing on improving morally valuable capabilities alone cannot provide a full account of how we can make fair health care allocation decisions. This is because capability-based accounts focus on objectively measurable effects of health care, but many effects of health care, such as relieving chronic pain have an inherently subjective component. Thus, these theories do not provide plausible priority to caring for the needs of those in chronic pain and the terminally ill. In Chapter 7, I argue for the importance of including measures of subjective well-being, in addition to capabilities, in considering which health care interventions to prioritise in situations of scarce resources