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1.  A new perspective on Hsp104-mediated propagation and curing of the yeast prion [PSI+] 
Prion  2012;6(3):234-239.
Most prions in yeast form amyloid fibrils that must be severed by the protein disaggregase Hsp104 to be propagated and transmitted efficiently to newly formed buds. Only one yeast prion, [PSI+], is cured by Hsp104 overexpression. We investigated the interaction between Hsp104 and Sup35, the priongenic protein in yeast that forms the [PSI+] prion.1 We found that a 20-amino acid segment within the highly-charged, unstructured middle domain of Sup35 contributes to the physical interaction between the middle domain and Hsp104. When this segment was deleted from Sup35, the efficiency of [PSI+] severing was substantially reduced, resulting in larger Sup35 particles and weakening of the [PSI+] phenotype. Furthermore, [PSI+] in these cells was completely resistant to Hsp104 curing. The affinity of Hsp104 was considerably weaker than that of model Hsp104-binding proteins and peptides, implying that Sup35 prions are not ideal substrates for Hsp104-mediated remodeling. In light of this finding, we present a modified model of Hsp104-mediated [PSI+] propagation and curing that requires only partial remodeling of Sup35 assembled into amyloid fibrils.
PMCID: PMC3399534  PMID: 22561166
molecular chaperone; prion; protein aggregation; protein folding; yeast
2.  A Multi-stage System for the Automated Detection of Epileptic Seizures in Neonatal EEG 
This paper describes the design and test results of a 3-stage automated system for neonatal EEG seizure detection. Stage I of the system is the initial detection stage, and identifies overlapping 5-s segments of suspected seizure activity in each EEG channel. In Stage II, the detected segments from Stage I are spatiotemporally clustered to produce multi-channel candidate seizures. In Stage III, the candidate seizures are processed further using measures of quality and context-based rules to eliminate false candidates. False candidates due to artifacts and commonly occurring EEG background patterns such as bifrontal delta activity are also rejected. Seizures at least 10 s in duration are considered for reporting results.
The testing data consisted of recordings of 28 seizure subjects (34 hrs of data) and 48 non-seizure subjects (87 hrs of data) obtained in the neonatal intensive care unit. The data were not edited to remove artifacts and were identical in every way to data normally processed visually. The system was able to detect seizures of widely varying morphology with an average detection sensitivity of almost 80% and a subject sensitivity of 96%, in comparison to a team of clinical neurophysiologists who had scored the same recordings. The average false detection rate obtained in non-seizure subjects was 0.74 per hr.
PMCID: PMC2760540  PMID: 19602985
EEG; neonatal; epileptic; seizure; detection; automated
3.  The geographic distribution of private health insurance in Australia in 2001 
Private health insurance has been a major focus of Commonwealth Government health policy for the last decade. Over this period, the Howard government introduced a number of policy changes which impacted on the take up of private health insurance. The most expensive of these was the introduction of the private health insurance rebate in 1997, which had an estimated cost of $3 billion per annum.
This article uses information on the geographic distribution of the population with private health insurance cover to identify associations between rates of private health insurance cover and socioeconomic status. The geographic analysis is repeated with survey data on expenditure on private health insurance, to provide an estimate of the rebate flowing to different socioeconomic groups.
The analysis highlights the strong association between high rates of private health insurance cover and high socioeconomic status and shows the substantial transfer of funds, under the private health insurance rebate, to those living in areas of highest socioeconomic status, compared with those in areas of lower socioeconomic status, and in particular those in the most disadvantaged areas. The article also provides estimates of private health insurance cover by federal electorate, emphasising the substantial gaps in cover between Liberal Party and Australian Labor Party seats.
The article concludes by discussing implications of the uneven distribution of private health insurance cover across Australia for policy formation. In particular, the study shows that the prevalence of private health insurance is unevenly distributed across Australia, with marked differences in prevalence in rural and urban areas, and substantial differences by socioeconomic status. Policy formation needs to take this into account. Evaluating the potential impact of changes in private health insurance requires more nuanced consideration than has been implied in the rhetoric about private health insurance over the last decade.
PMCID: PMC3224949  PMID: 19686590
4.  The SmpB-tmRNA Tagging System Plays Important Roles in Streptomyces coelicolor Growth and Development 
PLoS ONE  2009;4(2):e4459.
The ssrA gene encodes tmRNA that, together with a specialized tmRNA-binding protein, SmpB, forms part of a ribonucleoprotein complex, provides a template for the resumption of translation elongation, subsequent termination and recycling of stalled ribosomes. In addition, the mRNA-like domain of tmRNA encodes a peptide that tags polypeptides derived from stalled ribosomes for degradation. Streptomyces are unique bacteria that undergo a developmental cycle culminating at sporulation that is at least partly controlled at the level of translation elongation by the abundance of a rare tRNA that decodes UUA codons found in a relatively small number of open reading frames prompting us to examine the role of tmRNA in S. coelicolor. Using a temperature sensitive replicon, we found that the ssrA gene could be disrupted only in cells with an extra-copy wild type gene but not in wild type cells or cells with an extra-copy mutant tmRNA (tmRNADD) encoding a degradation-resistant tag. A cosmid-based gene replacement method that does not include a high temperature step enabled us to disrupt both the ssrA and smpB genes separately and at the same time suggesting that the tmRNA tagging system may be required for cell survival under high temperature. Indeed, mutant cells show growth and sporulation defects at high temperature and under optimal culture conditions. Interestingly, even though these defects can be completely restored by wild type genes, the ΔssrA strain was only partially corrected by tmRNADD. In addition, wildtype tmRNA can restore the hygromycin-resistance to ΔssrA cells while tmRNADD failed to do so suggesting that degradation of aberrant peptides is important for antibiotic resistance. Overall, these results suggest that the tmRNA tagging system plays important roles during Streptomyces growth and sporulation under both normal and stress conditions.
PMCID: PMC2635970  PMID: 19212432
5.  Metropolitan income inequality and working-age mortality: A cross-sectional analysis using comparable data from five countries 
The relationship between income inequality and mortality has come into question as of late from many within-country studies. This article examines the relationship between income inequality and working-age mortality for metropolitan areas (MAs) in Australia, Canada, Great Britain, Sweden, and the United States to provide a fuller understanding of national contexts that produce associations between inequality and mortality. An ecological cross-sectional analysis of income inequality (as measured by median share of income) and working-age (25–64) mortality by using census and vital statistics data for 528 MAs (population >50,000) from five countries in 1990–1991 was used. When data from all countries were pooled, there was a significant relationship between income inequality and mortality in the 528 MAs studied. A hypothetical increase in the share of income to the poorest half of households of 1% was associated with a decline in working-age mortality of over 21 deaths per 100,000. Within each country, however, a significant relationship between inequality and mortality was evident only for MAs in the United States and Great Britain. These two countries had the highest average levels of income inequality and the largest populations of the five countries studied. Although a strong ecological association was found between income inequality and mortality across the 528 MAs, an association between income inequality and mortality was evident only in within-country analyses for the two most unequal countries: the United States and Great Britain. The absence of an effect of metropolitan-scale income inequality on mortality in the more egalitarian countries of Canada. Australia, and Sweden is suggestive of national-scale policies in these countries that buffer hypothetical effects of income inequality as a determinant of population health in industrialized economies.
PMCID: PMC3456629  PMID: 15738331
Australia; Canada; Great Britain; Income inequality; Mortality; Sweden; United States
6.  The socioeconomic gradient and chronic illness and associated risk factors in Australia 
To examine the prevalence of major chronic diseases and their risk factors in different socioeconomic groups in the Australian population, in order to highlight the need for public policy initiatives to reduce socioeconomic inequalities in health.
Data were provided by the Australian Bureau of Statistics (ABS) from the 2001 National Health Survey (NHS) for selected chronic diseases and associated risk factors. Conditions selected were those, which form the National Health Priority Area (NHPA) conditions (other than injury, which has not been included in this paper, with its focus on chronic disease); plus other 'serious' chronic conditions, in line with the classification developed by Mathers; and for which sufficient cases were available for analysis by socioeconomic status. Indirectly age-standardised prevalence rates were calculated by broad age group for Australia and for five groups of socioeconomic status; rate ratios were calculated to show variations in prevalence between these groups.
Significant socioeconomic inequalities were evident for many of the major chronic diseases; the largest was for diabetes mellitus (at ages 25 to 64 years); and for many diseases, there was also a strong, continuous socioeconomic gradient in the rates.
Circulatory system diseases (in particular, hypertensive disease) and digestive system diseases also exhibited a strong differential in the 25 to 64 year age group.
In the 65 years and over age group, the strongest inequalities were evident for mental and behavioural problems, diabetes (with a continuous socioeconomic gradient in rates) and respiratory system diseases.
A number of risk factors for chronic diseases, namely self-reported smoking, alcohol misuse, physical inactivity and excess weight showed a striking association with socioeconomic status, in particular for people who were smokers and those who did not exercise.
This analysis shows that the prevalence of chronic disease varies across the socioeconomic gradient for a number of specific diseases, as well as for important disease risk factors. Therefore, any policy interventions to address the impact of chronic disease, at a population level, need to take into account these socioeconomic inequalities.
PMCID: PMC546403  PMID: 15679942
7.  Unpacking analyses relying on area-based data: are the assumptions supportable? 
In the absence in the major Australian administrative health record collections of a direct measure of the socioeconomic status of the individual about whom the event is recorded, analysis of the association between the health status, use of health services and socioeconomic status of the population relies an area-based measure of socioeconomic status.
This paper explores the reliability of the area of address (at the levels typically available in administrative data collections) as a proxy measure for socioeconomic disadvantage. The Western Australian Data Linkage System was used to show the extent to which hospital inpatient separation rates for residents of Perth vary by socioeconomic status of area of residence, when calculated at various levels of aggregation of area, from smallest (Census Collection District) to largest (postcode areas and Statistical Local Areas). Results are also provided of the reliability, over time, of the address as a measure of socioeconomic status.
There is a strong association between the socioeconomic status of the usual address of hospital inpatients at the smallest level in Perth, and weaker associations when the data are aggregated to larger areas. The analysis also shows that a higher proportion of people from the most disadvantaged areas are admitted to hospital than from the most well-off areas (13% more), and that these areas have more separations overall (47% more), as a result of larger numbers of multiple admissions.
Of people admitted to hospital more than once in a five year period, four out of five had not moved address by the time of their second episode. Of those who moved, the most movement was within, or between, areas of similar socioeconomic status, with people from the most well off areas being the least likely to have moved.
Postcode level and SLA level data provide a reliable, although understated, indication of socioeconomic disadvantage of area. The majority of Perth residents admitted to hospital in Western Australia had the same address when admitted again within five years. Of those who moved address, the majority had moved within, or between, areas of similar socioeconomic status.
Access to data about individuals from the Western Australian Data Linkage System shows that more people from disadvantaged areas are admitted to a hospital, and that they have more episodes of hospitalisation. Were data to be available across Australia on a similar basis, it would be possible to undertake research of greater policy-relevance than is currently possible with the existing separations-based national database.
PMCID: PMC543455  PMID: 15588302
8.  Effects of training students to identify the semantic base of prose materials 
Feedback and feedback plus points toward a course grade were applied to the attentional behaviors (defined as the ability to identify the semantic base of text passages) of 30 undergraduate students participating in a reading comprehension development program. Correct underlining was increased, extraneous underlining was decreased, and postreading comprehension test scores improved as a result of the procedures. Scores on a standardized test of reading comprehension also increased significantly.
PMCID: PMC1308171  PMID: 16795637
reading; recall; information processing; feedback; college students
9.  The effectiveness of reinforcement and practice for enhancing the creative writing of elementary school children1 
PMCID: PMC1311432
creativity; writing; classroom management; teaching methods

Results 1-10 (10)