A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

Population structure of Bactrocera dorsalis s.s., B. papayae and B. philippinensis (Diptera: Tephritidae) in southeast Asia: evidence for a single species hypothesis using mitochondrial DNA and wingshape data

Background Bactrocera dorsalis s.s. is a pestiferous tephritid fruit fly distributed from Pakistan to the Pacific, with the Thai/Malay peninsula its southern limit. Sister pest taxa, B. papayae and B. philippinensis, occur in the southeast Asian archipelago and the Philippines, respectively. The relationship among these species is unclear due to their high molecular and morphological similarity. This study analysed population structure of these three species within a southeast Asian biogeographical context to assess potential dispersal patterns and the validity of their current taxonomic status. Results Geometric morphometric results generated from 15 landmarks for wings of 169 flies revealed significant differences in wing shape between almost all sites following canonical variate analysis. For the combined data set there was a greater isolation-by-distance (IBD) effect under a ‘non-Euclidean’ scenario which used geographical distances within a biogeographical ‘Sundaland context’ (r2 = 0.772, P < 0.0001) as compared to a ‘Euclidean’ scenario for which direct geographic distances between sample sites was used (r2 = 0.217, P < 0.01). COI sequence data were obtained for 156 individuals and yielded 83 unique haplotypes with no correlation to current taxonomic designations via a minimum spanning network. BEAST analysis provided a root age and location of 540kya in northern Thailand, with migration of B. dorsalis s.l. into Malaysia 470kya and Sumatra 270kya. Two migration events into the Philippines are inferred. Sequence data revealed a weak but significant IBD effect under the ‘non-Euclidean’ scenario (r2 = 0.110, P < 0.05), with no historical migration evident between Taiwan and the Philippines. Results are consistent with those expected at the intra-specific level. Conclusions Bactrocera dorsalis s.s., B. papayae and B. philippinensis likely represent one species structured around the South China Sea, having migrated from northern Thailand into the southeast Asian archipelago and across into the Philippines. No migration is apparent between the Philippines and Taiwan. This information has implications for quarantine, trade and pest management.

Anthropogenic landscape change promotes asymmetric dispersal and limits regional patch occupancy in a spatially structured bird population

1. Local extinctions in habitat patches and asymmetric dispersal between patches are key processes structuring animal populations in heterogeneous environments. Effective landscape conservation requires an understanding of how habitat loss and fragmentation influence demographic processes within populations and movement between populations. 2. We used patch occupancy surveys and molecular data for a rainforest bird, the logrunner (Orthonyx temminckii), to determine (i) the effects of landscape change and patch structure on local extinction; (ii) the asymmetry of emigration and immigration rates; (iii) the relative influence of local and between-population landscapes on asymmetric emigration and immigration; and (iv) the relative contributions of habitat loss and habitat fragmentation to asymmetric emigration and immigration. 3. Whether or not a patch was occupied by logrunners was primarily determined by the isolation of that patch. After controlling for patch isolation, patch occupancy declined in landscapes experiencing high levels of rainforest loss over the last 100 years. Habitat loss and fragmentation over the last century was more important than the current pattern of patch isolation alone, which suggested that immigration from neighbouring patches was unable to prevent local extinction in highly modified landscapes. 4. We discovered that dispersal between logrunner populations is highly asymmetric. Emigration rates were 39% lower when local landscapes were fragmented, but emigration was not limited by the structure of the between-population landscapes. In contrast, immigration was 37% greater when local landscapes were fragmented and was lower when the between-population landscapes were fragmented. Rainforest fragmentation influenced asymmetric dispersal to a greater extent than did rainforest loss, and a 60% reduction in mean patch area was capable of switching a population from being a net exporter to a net importer of dispersing logrunners. 5. The synergistic effects of landscape change on species occurrence and asymmetric dispersal have important implications for conservation. Conservation measures that maintain large patch sizes in the landscape may promote asymmetric dispersal from intact to fragmented landscapes and allow rainforest bird populations to persist in fragmented and degraded landscapes. These sink populations could form the kernel of source populations given sufficient habitat restoration. However, the success of this rescue effect will depend on the quality of the between-population landscapes.

Spatial inequalities in colorectal and breast cancer survival : premature deaths and associated factors

This study examines the influence of cancer stage, distance to treatment facilities and area disadvantage on breast and colorectal cancer spatial survival inequalities. We also estimate the number of premature deaths after adjusting for cancer stage to quantify the impact of spatial survival inequalities. Population-based descriptive study of residents aged <90 years in Queensland, Australia diagnosed with primary invasive breast (25,202 females) or colorectal (14,690 males, 11,700 females) cancers during 1996-2007. Bayesian hierarchical models explored relative survival inequalities across 478 regions. Cancer stage and disadvantage explained the spatial inequalities in breast cancer survival, however spatial inequalities in colorectal cancer survival persisted after adjustment. Of the 6,019 colorectal cancer deaths within 5 years of diagnosis, 470 (8%) were associated with spatial inequalities in non-diagnostic factors, i.e. factors beyond cancer stage at diagnosis. For breast cancers, of 2,412 deaths, 170 (7%) were related to spatial inequalities in non-diagnostic factors. Quantifying premature deaths can increase incentive for action to reduce these spatial inequalities.

Socioeconomic differences in takeaway food consumption among adults

Background In Australia and other developed countries, there are consistent and marked socioeconomic inequalities in health. Diet is a major contributing factor to the poorer health of lower socioeconomic groups: the dietary patterns of disadvantaged groups are least consistent with dietary recommendations for the prevention of diet-related chronic diseases compared with their more advantaged counterparts. Part of the reason that lower socioeconomic groups have poorer diets may be their consumption of takeaway foods. These foods typically have nutrient contents that fail to comply with the dietary recommendations for the prevention of chronic disease and associated risk factors. A high level of takeaway food consumption, therefore, may negatively influence overall dietary intakes and, consequently, lead to adverse health outcomes. Despite this, little attention has focused on the association between socioeconomic position (SEP) and takeaway food consumption, with the limited number of studies showing mixed results. Additionally, studies have been limited by only considering a narrow range of takeaway foods and not examining how different socioeconomic groups make choices that are more (or less) consistent with dietary recommendations. While a large number of earlier studies have consistently reported socioeconomically disadvantaged groups consume a lesser amount of fruit and vegetables, there is limited knowledge about the role of takeaway food in socioeconomic variations in fruit and vegetable intake. Furthermore, no known studies have investigated why there are socioeconomic differences in takeaway food consumption. The aims of this study are to: examine takeaway food consumption and the types of takeaway food consumed (healthy and less healthy) by different socioeconomic groups, to determine whether takeaway food consumption patterns explain socioeconomic variations in fruit and vegetable intake, and investigate the role of a range of psychosocial factors in explaining the association between SEP and takeaway food consumption and the choice of takeaway food. Methods This study used two cross-sectional population-based datasets: 1) the 1995 Australian National Nutrition Survey (NNS) which was conducted among a nationally representative sample of adults aged between 25.64 years (N = 7319, 61% response rate); and 2) the Food and Lifestyle Survey (FLS) which was conducted by the candidate and was undertaken among randomly selected adults aged between 25.64 years residing in Brisbane, Australia in 2009 (N = 903, 64% response rate). The FLS extended the NNS in several ways by describing current socioeconomic differences in takeaway food consumption patterns, formally assessing the mediated effect of takeaway food consumption to socioeconomic inequalities in fruit and vegetable intake, and also investigating whether (and which) psychosocial factors contributed to the observed socioeconomic variations in takeaway food consumption patterns. Results Approximately 32% of the NNS participants consumed takeaway food in the previous 24 hours and 38% of the FLS participants reported consuming takeaway food once a week or more. The results from analyses of the NNS and the FLS were somewhat mixed; however, disadvantaged groups were likely to consume a high level of �\less healthy. takeaway food compared with their more advantaged counterparts. The lower fruit and vegetable intake among lower socioeconomic groups was partly mediated by their high consumption of �\less healthy. takeaway food. Lower socioeconomic groups were more likely to have negative meal preparation behaviours and attitudes, and weaker health and nutrition-related beliefs and knowledge. Socioeconomic differences in takeaway food consumption were partly explained by meal preparation behaviours and attitudes, and these factors along with health and nutrition-related beliefs and knowledge appeared to contribute to the socioeconomic variations in choice of takeaway foods. Conclusion This thesis enhances our understanding of socioeconomic differences in dietary behaviours and the potential pathways by describing takeaway food consumption patterns by SEP, explaining the role of takeaway food consumption in socioeconomic inequalities in fruit and vegetable intake, and identifying the potential impact of psychosocial factors on socioeconomic differences in takeaway food consumption and the choice of takeaway food. Some important evidence is also provided for developing policies and effective intervention programs to improve the diet quality of the population, especially among lower socioeconomic groups. This thesis concludes with a discussion of a number of recommendations about future research and strategies to improve the dietary intake of the whole population, and especially among disadvantaged groups.

Seasonal variation in cardiovascular disease risk factors in a subarctic population : the Tromso Study 1979-2008

Background Seasonal changes in cardiovascular disease (CVD) risk factors may be due to exposure to seasonal environmental variables like temperature and acute infections or seasonal behavioural patterns in physical activity and diet. Investigating the seasonal pattern of risk factors should help determine the causes of the seasonal pattern in CVD. Few studies have investigated the seasonal variation in risk factors using repeated measurements from the same individual, which is important as individual and population seasonal patterns may differ. Methods The authors investigated the seasonal pattern in systolic and diastolic blood pressure, heart rate, body weight, total cholesterol, triglycerides, high-density lipoprotein cholesterol, C reactive protein and fibrinogen. Measurements came from 38 037 participants in the population-based cohort, the Tromsø Study, examined up to eight times from 1979 to 2008. Individual and population seasonal patterns were estimated using a cosinor in a mixed model. Results All risk factors had a highly statistically significant seasonal pattern with a peak time in winter, except for triglycerides (peak in autumn), C reactive protein and fibrinogen (peak in spring). The sizes of the seasonal variations were clinically modest. Conclusions Although the authors found highly statistically significant individual seasonal patterns for all risk factors, the sizes of the changes were modest, probably because this subarctic population is well adapted to a harsh climate. Better protection against seasonal risk factors like cold weather could help reduce the winter excess in CVD observed in milder climates.

Identifying familiarity to facilitate intuitive interaction for older adults

Almost every nation on the planet is experiencing increases in both the number and proportion of older adults. Research has shown that older adults use technology less intuitively than younger adults, and have more difficulty with using products effectively. With an ever-increasing population of older adults, it is necessary to understand why they often struggle to use technology, which is becoming more and more important in day to day living. Intuitive use of products is grounded in familiarity and prior experience. The aims of this research were twofold: (i) to examine the differences in familiarity between younger and older adults, to see if this could explain the difficulties faced by some older adults; (ii) to develop investigational methods to assist designers in identifying familiarity in prospective users. Two empirical studies were conducted. The first experiment was conducted in the field with 32 participants, divided across four age groups (18 – 44, 45 – 59, 60 – 74, and 75+). This experiment was conducted in the participants’ homes, with a product they were familiar with. Familiarity was measured through the analysis of data collected through interviews, observation and retrospective protocol. The results of this study show that the youngest group demonstrated significantly higher levels of familiarity with products they own than the 60 – 74 and the 75+ age groups. There were no significant differences between the 18 – 44 age group and the 45 – 59 age group and there were also no significant differences between the three oldest age groups. The second experiment was conducted with 32 participants, across the same four age groups. Four everyday products were used in this experiment. The results of Experiment 2 show that, with previously unused products, younger adults demonstrate significantly higher levels of familiarity than the three older age groups. The three oldest age groups had no significant differences between them. The results of these two studies show that younger adults are more familiar with contemporary products than older adults. They also demonstrate that in terms of familiarity, older adults do not differ significantly as they get older. The results also show that the 45 – 59 age group demonstrate higher levels of familiarity with products they have owned, in comparison with those they have not. The two older age groups did not demonstrate such differences. This suggests that interacting with products over time increases familiarity more for middle-aged adults than for older adults. As a result of this research, a method that can be used by designers to identify potential users’ product familiarity has been identified. This method is easy to use, quick, low cost, highly mobile, flexible, and allows for easy data collection and analysis. A tool has been designed that assists designers and researchers to use the method. Designers can use the knowledge gained from this tool, and integrate it into the design process, resulting in more intuitive products. Such products may lead to improvements in the quality of life of older adults, as a result of improved societal integration, better health management, and more widespread use of communications technology.

A cross sectional observational study of child restraint use in Queensland following changes in legislation

As part of an evaluation of the 2010 legislation for child vehicle occupants in Queensland, road-side observations of private passenger vehicles were used to estimate the proportions of children 0-under 7 years travelling in each of the 5 different restraint types (eg. forward facing child restraint). Data was collected in 4 major population centres: Brisbane, Sunshine Coast, Mackay and Townsville. Almost all children were restrained (95.1%, 95% CI 94.3-95.9%), with only 3.3% (95% CI 2.6-4.0%) clearly unrestrained and 44 (1.6%, 95% CI 1.1-2.1%) for whom restraint status could not be determined (‘unknown’). However, around 24.0% (95 CI 21.8-26.2%) of the target-aged children were deemed inappropriately restrained, primarily comprised of 3-6 year olds in seatbelts (18.7% of the 0-6 year olds, 95% CI 16.3-21.1%) or unrestrained (3.7% of the 0-6 year olds, 95% CI 2.5-4.9%) instead of booster seats. In addition, compliance appeared significantly lower for some regional locations where the proportion of children observed as completely unrestrained was relatively high and of concern

Development of self-efficacy questionnaire for Chinese family caregivers

The purpose of this study was to develop a Self-Efficacy Questionnaire for Chinese Family Caregivers. Semi-structured interviews with 10 family caregivers of people with dementia were conducted to explore how Chinese caregivers manage caregiving and what difficulties they face. The findings of the study assisted in the development of the instrument. Five categories of caregiver behaviours were identified from the qualitative data: gathering information about treatment, symptoms, and health care; obtaining support; responding to behaviour disturbances; managing household, personal, and medical care; and managing distress associated with caregiving. The challenges of caregiving were also identified, including deterioration of care recipients, particularly their behaviour disturbances, a shortage of supportive resources, stigmatization of dementia among the general population, as well as increased distress and decreased social activities due to increased care demand. The findings were used to develop the Self-Efficacy Questionnaire for Chinese Family Caregivers, and 35 items comprising five subscales (representing the above five categories of caregiver behaviour) were generated.

School-aged workers : industrial citizens in waiting?

While the literature points to significant shifts in young peoples’ labour market participation and the social, economic and political context in which this has occurred, it tells us little about whether and in what sense young people can be considered as industrial citizens. We explored the notion of youth citizenship using data derived from 48 focus groups conducted with 216 young people (13-16 years of age) at 19 high schools in Australia. The findings reveal the ways in which several key dimensions of industrial citizenship come to be shaped and have implications for addressing the vulnerability of youth in employment and informing policy and action.

Clines in cuticular hydrocarbons in two Drosophila species with independent population histories

We took a comparative approach utilizing clines to investigate the extent to which natural selection may have shaped population divergence in cuticular hydrocarbons (CHCs) that are also under sexual selection in Drosophila. We detected the presence of CHC clines along a latitudinal gradient on the east coast of Australia in two fly species with independent phylogenetic and population histories, suggesting adaptation to shared abiotic factors. For both species, significant associations were detected between clinal variation in CHCs and temperature variation along the gradient, suggesting temperature maxima as a candidate abiotic factor shaping CHC variation among populations. However, rainfall and humidity correlated with CHC variation to differing extents in the two species, suggesting that response to these abiotic factors may vary in a species-specific manner. Our results suggest that natural selection, in addition to sexual selection, plays a significant role in structuring among-population variation in sexually selected traits in Drosophila.

Pregnancy losses in young Australian women : findings from the Australian Longitudinal Study on Women's Health

INTRODUCTION: Little research has examined recognized pregnancy losses in a general population. Data from an Australian cohort study provide an opportunity to quantify this aspect of fecundity at a population level. METHOD: Participants in the Australian Longitudinal Study on Women's Health who were aged 28-33 years in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants were categorized according to the recognized outcome of their pregnancies, including live birth, miscarriage/stillbirth, termination/ectopic, or no pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%) was as common as termination (16%). For women aged 28-33 years who had ever been pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss only (18%); and birth and loss (32%), of which half (16%) were birth and miscarriage. A comparison between first miscarriage and first birth (no miscarriage) showed that most first miscarriages occurred in women aged 18-23 years who also reported a first birth at the same survey (15%). Half (51%) of all first births and first miscarriages in women aged 18-19 ended in miscarriage. Early childbearers (<28 years) often had miscarriages around the same time period as their first live birth, suggesting proactive family formation. Delayed childbearers (32-33 years) had more first births than first miscarriages. CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in the general population because they indicate successful conception and maintenance of pregnancy to varying reproductive endpoints.

Depression: an emotional obstacle to seeking medical advice for infertility

Objective: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. Design: Longitudinal cohort study.Setting Population based.Patient(s) Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936).Intervention(s) None.Main Outcome Measure(s) Infertility, not seeking medical advice. Result(s): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. Conclusion(s): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility.

National Institute for Clinical Studies Report for Phase 1, Evidence Uptake Network : Best Practice Community Care for Clients with Chronic Venous Leg Ulcers

Chronic leg ulcers cause significant pain, cost, decreased quality of life and morbidity for a considerable segment of the older population (Graham et al., 2003a). At any given time the prevalence of patients with open leg ulcers receiving treatment is between 0.11% - 0.18% (Briggs & Closs 2003). Chronic leg ulcers occur in approximately 1 - 2% of the over 60 population in the US, UK, Europe and Australia (Baker & Stacey 1994; Johnson 1995; Lees & Lambert 1992; Margolis et al. 2002). Considerable research has been undertaken to determine the best treatment practices that will aid in the management and the healing of these ulcers, and practical and effective strategies and techniques for healing venous leg ulcers have been trialled to demonstrate their beneficial effects (Nelson et al. 2004; Cullum et al. 2001)...