The impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy on survival in patients with a history of breast cancer – a population-based data linkage study

Prophylactic surgery including hysterectomy and bilateral salpingo-oophorectomy (BSO) is recommended in BRCA positive women, while in women from the general population, hysterectomy plus BSO may increase the risk of overall mortality. The effect of hysterectomy plus BSO on women previously diagnosed with breast cancer is unknown. We used data from a population-base data linkage study of all women diagnosed with primary breast cancer in Queensland, Australia between 1997 and 2008 (n=21,067). We fitted flexible parametric breast cancer specific and overall survival models with 95% confidence intervals (also known as Royston-Parmar models) to assess the impact of risk-reducing surgery (removal of uterus, one or both ovaries). We also stratified analyses by age 20-49 and 50-79 years, respectively. Overall, 1,426 women (7%) underwent risk-reducing surgery (13% of premenopausal women and 3% of postmenopausal women). No women who had risk-reducing surgery, compared to 171 who did not have risk-reducing surgery developed a gynaecological cancer. Overall, 3,165 (15%) women died, including 2,195 (10%) from breast cancer. Hysterectomy plus BSO was associated with significantly reduced risk of death overall (adjusted HR = 0.69, 95% CI 0.53-0.89; P =0.005). Risk reduction was greater among premenopausal women, whose risk of death halved (HR, 0.45; 95% CI, 0.25-0.79; P < 0.006). This was largely driven by reduction in breast cancer-specific mortality (HR, 0.43; 95% CI, 0.24-0.79; P < 0.006). This population-based study found that risk-reducing surgery halved the mortality risk for premenopausal breast cancer patients. Replication of our results in independent cohorts, and subsequently randomised trials are needed to confirm these findings.

A retrospective cohort study of Acticoat™ versus Silvazine™ in a paediatric population

We wished to determine whether changing our centre's practice of using Acticoat instead of Silvazine as our first-line burns dressing provided a better standard of care in terms of efficacy, cost and ease of use. A retrospective cohort study was performed examining 328 Silvazine treated patients from January 2000 to June 2001 and 241 Acticoat treated patients from July 2002 to July 2003. During those periods the respective dressings were used exclusively. There was no significant difference in age, %BSA and mechanism of burn between the groups. In the Silvazine group, 25.6% of children required grafting compared to 15.4% in the Acticoat group (p=0.001). When patients requiring grafting were excluded, the time taken for re-epithelialisation in the Acticoat group (14.9 days) was significantly less than that for the Silvazine group (18.3 days), p=0.047. There were more wounds requiring long term scar management in the Silvazine group (32.6%) compared to the Acticoat group (29.5%), however this was not significant. There was only one positive blood culture in each group, indicating that both Silvazine and Acticoat are potent antimicrobial agents. The use of Acticoat as our primary burns dressing has dramatically changed our clinical practice. Inpatients are now only 18% of the total admissions, with the vast majority of patients treated on an outpatient basis. In terms of cost, Acticoat was demonstrated to be less expensive over the treatment period than Silvazine . We have concluded that Acticoat is a safe, cost-effective, efficacious dressing that reduces the time for re-epithelialisation and the requirement for grafting and long term scar management, compared to Silvazine.

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting A hospital alcohol and drug out-patient clinic. Participants Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings Positive (β = −0.29, P < 0.001) and negative (β = −0.19, P < 0.001) cannabis outcome expectancies were associated significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully mediated the association between negative expectancy and weekly consumption [95% confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of positive expectancy on weekly consumption (95% CI = 0.06, 0.17). Conclusions Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief that he or she can abstain from cannabis use) mediates part of the association between cannabis outcome expectancies (perceived consequences of cannabis use) and cannabis use.

Serum HE4 as a prognostic marker in endometrial cancer : a population based study

Objective HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort. Methods Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann–Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan–Meier and Cox multivariate regression analyses. Results Median CA125 and HE4 levels were higher in stage III and IV tumours (p < 0.001) and in tumours with outer-half myometrial invasion (p < 0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC) = 0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC = 0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR = 2.40, 95% CI 1.19–4.83, p = 0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR = 2.86, 95% CI 1.25–6.51, p = 0.012). Conclusion These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.

Co-morbidity of depression and anxiety in common age-related eye diseases : a population-based study of 662 adults

This study examined the prevalence of co-morbid age-related eye disease and symptoms of depression and anxiety in late life, and the relative roles of visual function and disease in explaining symptoms of depression and anxiety. A community-based sample of 662 individuals aged over 70 years was recruited through the electoral roll. Vision was measured using a battery of tests including high and low contrast visual acuity, contrast sensitivity, motion sensitivity, stereoacuity, Useful Field of View, and visual fields. Depression and anxiety symptoms were measured using the Goldberg scales. The prevalence of self-reported eye disease [cataract, glaucoma, or age-related macular degeneration (AMD)] in the sample was 43.4%, with 7.7% reporting more than one form of ocular pathology. Of those with no eye disease, 3.7% had clinically significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3% among those with glaucoma, and 10.5% for AMD. Generalized linear models adjusting for demographics, general health, treatment, and disability examined self-reported eye disease and visual function as correlates of depression and anxiety. Depressive symptoms were associated with cataract only, AMD, comorbid eye diseases and reduced low contrast visual acuity. Anxiety was significantly associated with self-reported cataract, and reduced low contrast visual acuity, motion sensitivity and contrast sensitivity. We found no evidence for elevated rates of depressive or anxiety symptoms associated with self-reported glaucoma. The results support previous findings of high rates of depression and anxiety in cataract and AMD, and in addition show that mood and anxiety are associated with objective measures of visual function independently of self-reported eye disease. The findings have implications for the assessment and treatment of mental health in the context of late-life visual impairment...

An R2R3 MYB transcription factor determines red petal colour in an Actinidia (kiwifruit) hybrid population

Background Red colour in kiwifruit results from the presence of anthocyanin pigments. Their expression, however, is complex, and varies among genotypes, species, tissues and environments. An understanding of the biosynthesis, physiology and genetics of the anthocyanins involved, and the control of their expression in different tissues, is required. A complex, the MBW complex, consisting of R2R3-MYB and bHLH transcription factors together with a WD-repeat protein, activates anthocyanin 3-O-galactosyltransferase (F3GT1) to produce anthocyanins. We examined the expression and genetic control of anthocyanins in flowers of Actinidia hybrid families segregating for red and white petal colour. Results Four inter-related backcross families between Actinidia chinensis Planch. var. chinensis and Actinidia eriantha Benth. were identified that segregated 1:1 for red or white petal colour. Flower pigments consisted of five known anthocyanins (two delphinidin-based and three cyanidin-based) and three unknowns. Intensity and hue differed in red petals from pale pink to deep magenta, and while intensity of colour increased with total concentration of anthocyanin, no association was found between any particular anthocyanin data and hue. Real time qPCR demonstrated that an R2R3 MYB, MYB110a, was expressed at significant levels in red-petalled progeny, but not in individuals with white petals. A microsatellite marker was developed that identified alleles that segregated with red petal colour, but not with ovary, stamen filament, or fruit flesh colour in these families. The marker mapped to chromosome 10 in Actinidia. The white petal phenotype was complemented by syringing Agrobacterium tumefaciens carrying Actinidia 35S::MYB110a into the petal tissue. Red pigments developed in white petals both with, and without, co-transformation with Actinidia bHLH partners. MYB110a was shown to directly activate Actinidia F3GT1 in transient assays. Conclusions The transcription factor, MYB110a, regulates anthocyanin production in petals in this hybrid population, but not in other flower tissues or mature fruit. The identification of delphinidin-based anthocyanins in these flowers provides candidates for colour enhancement in novel fruits.

An assessment of the geographical scale of recurrent gene flow in wild populations of two species of Mekong River carps (Henicorhynchus spp.)

The Mekong is the most productive river fishery in the world, and such as, the Mekong River Basin (MRB) is very important to very large human populations across the region as a source of revenue (through fishing and marketing of aquatic resources products) and as the major source for local animal protein. Threats to biodiversity in the MRB, either to the fishery sector itself or to other sectors are a major concern, even though currently, fisheries across this region are still very productive. If not managed properly however, fish population declines will cause significant economic impact and affect livelihoods of local people and will have a major impact on food security and nutrition. Biodiversity declines will undoubtedly affect food security, income and socio-economic status of people in the MRB that depend on aquatic resources. This is an indicator of unsustainable development and hence should be avoided. Genetic diversity (biodiversity) that can be measured using techniques based on DNA markers; refers to variation within and among populations within the same species or reproductive units. In a population, new genetic variation is generated by sexual recombination contributed by individuals with mutations in genes and chromosomes. Over time, populations of a species that are not reproducing together will diverge as differential impacts of selection and genetic drift change their genetic attributes. For mud carp (Henicorhynchus spp.), understanding the status of breeding units in the MRB will be important for their long term persistence, sustainability and for implementing effective management strategies. Earlier analysis of stock structure in two economically important mud carp species (Henicorhynchus siamensis and H. lobatus) in the MRB completed with mtDNA markers identified a number of populations of both species where gene flow had apparently been interrupted or reduced but applying these data directly to management unit identification is potentially compromised because information was only available about female dispersal patterns. The current study aimed to address this problem and to fully assess the extent of current gene flow (nDNA) and reproductive exchange among selected wild populations of two species of carp (Henicorhynchus spp.) of high economic importance in the MRB using combined mtDNA and nDNA markers. In combination, the data can be used to define effective management units for each species. In general, nDNA diversity for H. lobatus (with average allelic richness (A) 7.56 and average heterozygosity (Ho) 0.61) was very similar to that identified for H. siamensis (A = 6.81 and Ho = 0.75). Both mud carp species show significant but low FST estimates among populations as a result of lower genetic diversity among sampled populations compared with genetic diversity within populations that may potentially mask any 'real' population structure. Overall, population genetic structure patterns from mtDNA and nDNA in both Henicorhynchus species were largely congruent. Different population structures however, were identified for the two Henicorhynchus species across the same geographical area. Apparent co-similarity in morphology and co-distribution of these two relatively closely related species does not apparently imply parallel evolutionary histories. Differences in each species population structure likely reflect historical drainage rearrangement of the Mekong River. The data indicate that H. siamensis is likely to have occupied the Mekong system for much longer than has H. lobatus in the past. Two divergent stocks were identified for H. lobatus in the MRB below the Khone Falls while a single stock had been evident in the earlier mtDNA study. This suggests that the two Henicorhynchus species may possess different life history traits and that different patterns of gene flow has likely influenced modern genetic structure in these close congeners. In combination, results of the earlier mtDNA and the current study have implications for effective management of both Henicorhynchus species across the MRB. Currently, both species are essentially treated as a single management unit in this region. This strategy may be appropriate for H. lobatus as a single stock was evident in the main stream of the MRB, but may not be appropriate for H. siamensis as more than a single stock was identified across the same range for this species. Management strategies should consider this difference to conserve overall biodiversity (local discrete populations) and this will include maintaining natural habitat and migration pathways, provision of fish sanctuaries (refuges) and may also require close monitoring of any stock declines, a signal that may require effective recovery strategies.

Mapping a candidate gene (MdMYB10) for red flesh and foliage colour in apple

BACKGROUND Integrating plant genomics and classical breeding is a challenge for both plant breeders and molecular biologists. Marker-assisted selection (MAS) is a tool that can be used to accelerate the development of novel apple varieties such as cultivars that have fruit with anthocyanin through to the core. In addition, determining the inheritance of novel alleles, such as the one responsible for red flesh, adds to our understanding of allelic variation. Our goal was to map candidate anthocyanin biosynthetic and regulatory genes in a population segregating for the red flesh phenotypes. RESULTS We have identified the Rni locus, a major genetic determinant of the red foliage and red colour in the core of apple fruit. In a population segregating for the red flesh and foliage phenotype we have determined the inheritance of the Rni locus and DNA polymorphisms of candidate anthocyanin biosynthetic and regulatory genes. Simple Sequence Repeats (SSRs) and Single Nucleotide Polymorphisms (SNPs) in the candidate genes were also located on an apple genetic map. We have shown that the MdMYB10 gene co-segregates with the Rni locus and is on Linkage Group (LG) 09 of the apple genome. CONCLUSION We have performed candidate gene mapping in a fruit tree crop and have provided genetic evidence that red colouration in the fruit core as well as red foliage are both controlled by a single locus named Rni. We have shown that the transcription factor MdMYB10 may be the gene underlying Rni as there were no recombinants between the marker for this gene and the red phenotype in a population of 516 individuals. Associating markers derived from candidate genes with a desirable phenotypic trait has demonstrated the application of genomic tools in a breeding programme of a horticultural crop species.

Test-retest reliability of four physical activity measures used in population surveys

Accurate monitoring of prevalence and trends in population levels of physical activity (PA) is a fundamental public health need. Test-retest reliability (repeatability) was assessed in population samples for four self-report PA measures: the Active Australia survey (AA, N=356), the short International Physical Activity Questionnaire (IPAQ, N=104), the physical activity items in the Behavioral Risk Factor Surveillance System (BRFSS, N=127) and in the Australian National Health Survey (NHS, N=122). Percent agreement and Kappa statistics were used to assess reliability of classification of activity status as 'active', 'insufficiently active' or 'sedentary'. Intraclass correlations (ICCs) were used to assess agreement on minutes of activity reported for each item of each survey and for total minutes. Percent agreement scores for activity status were very good on all four instruments, ranging from 60% for the NHS to 79% for the IPAQ. Corresponding Kappa statistics ranged from 0.40 (NHS) to 0.52 (AA). For individual items, ICCs were highest for walking (0.45 to 0.78) and vigorous activity (0.22 to 0.64) and lowest for the moderate questions (0.16 to 0.44). All four measures provide acceptable levels of test-retest reliability for assessing both activity status and sedentariness, and moderate reliability for assessing total minutes of activity.

Physical activity and population health outcomes

SMA members Neville Owen, Adrian Bauman, Wendy Brown and Stewart Trost have recently been awarded two NHMRC grants for research which will focus on understanding and influencing physical activity to improve population health outcomes. They were awarded under the Capital Building for Population Health scheme and the Program Grants scheme. The total value of the grants is 86.5 million over five years. The new grants will allow the researchers to conduct rigorous behavioural and epidemiological research which will inform the development of innovative primary and secondary prevention initiatives and determine their effectiveness. This is important, because physical activity is significantly implicated in the prevention and management of established chronic health problems such as cardiovascular disease, type 2 diabetes, osteoporosis and some forms of cancer. It also has a key role to play in addressing the growing epidemic of childhood and adult obesity, and in the maintenance of functional well-being with age. However, in recent years, physical activity levels in Australia have declined, indicating that the net sum of all our efforts to encourage physical activity participation require renewed and innovative efforts. The proposed research programs will be based on the researchers' cross-disciplinary backgrounds in exercise physiology, psychology, health promotion and epidemiology, and will be integrated across four main domains:..

Advances in population surveillance for physical activity and sedentary behavior : reliability and validity of time use surveys

Many countries conduct regular national time use surveys, some of which date back as far as the 1960s. Time use surveys potentially provide more detailed and accurate national estimates of the prevalence of sedentary and physical activity behavior than more traditional self-report surveillance systems. In this study, the authors determined the reliability and validity of time use surveys for assessing sedentary and physical activity behavior. In 2006 and 2007, participants (n = 134) were recruited from work sites in the Australian state of New South Wales. Participants completed a 2-day time use diary twice, 7 days apart, and wore an accelerometer. The 2 diaries were compared for test-retest reliability, and comparison with the accelerometer determined concurrent validity. Participants with similar activity patterns during the 2 diary periods showed reliability intraclass correlations of 0.74 and 0.73 for nonoccupational sedentary behavior and moderate/vigorous physical activity, respectively. Comparison of the diary with the accelerometer showed Spearman correlations of 0.57-0.59 and 0.45-0.69 for nonoccupational sedentary behavior and moderate/vigorous physical activity, respectively. Time use surveys appear to be more valid for population surveillance of nonoccupational sedentary behavior and health-enhancing physical activity than more traditional surveillance systems. National time use surveys could be used to retrospectively study nonoccupational sedentary and physical activity behavior over the past 5 decades.

Compliance with physical activity guidelines : prevalence in a population of children and youth

PURPOSE To use objective monitoring of physical activity to determine the percentages of children and youth in a population that met physical activity guidelines. METHODS A total of 375 students in grades 1–12 wore an accelerometer (CSA 7164) for seven consecutive days. Bouts of continuous activity and accumulation of minutes spent in physical activity at various intensities were calculated to determine how many students met three physical activity guidelines. RESULTS Over 90% of students met Healthy People 2010, Objective 22.6 and nearly 70% met the United Kingdom Expert Consensus Group guideline, both of which recommend daily accumulation of moderate physical activity. Less than 3% met Healthy People 2010, Objective 22.7, which calls for bouts of continuous vigorous physical activity. For the United Kingdom Expert Consensus Group guideline, compliance decreased markedly with age, but gender differences were not statistically significant. CONCLUSIONS Prevalence estimates for compliance with national physical activity guidelines varied markedly for the three guidelines examined. Objective monitoring of physical activity in youth appears to be feasible and may provide more accurate prevalence rates than self-report measures.

Test-retest reliability of physical activity measures used in Australian population surveys

PURPOSE Accurate monitoring of prevalence and trends in population levels of physical activity is fundamental to the planning of health promotion and disease-prevention strategies. Test-retest reliability (repeatability) was assessed for four self-report measures of physical activity commonly used in population surveys: the Active Australia survey (AA, N=356), the short form of the International Physical Activity Questionnaire (IPAQ-S, N=104), the physical activity items in the Behavioral Risk Factor Surveillance System (BRFSS, N=127) and the physical activity items in the Australian National Health Survey (NHS, N=122). METHODS Percent agreement and Kappa statistics were used to assess the reliability of classification of activity status (where ‘active’= 150 minutes of activity per week) and sedentariness (where ‘sedentary’ = reporting no physical activity). Intraclass correlations (ICCs) were used to assess agreement on minutes of activity reported for each item of each survey and on total minutes reported in each survey. RESULTS Percent agreement scores for both activity status and sedentariness were very good on all four instruments. Overall the percent agreement between repeated surveys was between 73% (NHS) and 87% (IPAQ) for the criterion measure of achieving 150 minutes per week, and between 77% (NHS) and 89% (IPAQ) for the criterion of being sedentary. Corresponding Kappa statistics ranged from 0.46 (NHS) to 0.61 (AA) for activity status and from 0.20 (BRFSS) to 0.52 (AA) for sedentariness. For the individual items ICCs were highest for walking (0.45 to 0.56) and vigorous activity (0.22 to 0.64) and lowest for the moderate questions (0.16 to 0.44). CONCLUSION All four measures provide acceptable levels of test-retest reliability for assessing both activity status and sedentariness, and moderate reliability for assessing total minutes of activity. Supported by the Australian Commonwealth Department of Health and Ageing.