Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors.

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.

Psychological factors and asthma quality of life: a population based study.

BACKGROUND: Reports of psychological conditions in asthmatic subjects have been limited to certain population groups or convenience samples. A study was undertaken of the prevalence of psychological distress in asthma in the general population and its associations with quality of life. METHODS: The WANTS Health and Well-being Survey is a population household interview survey of adults (age > or =18) in Western Australia, the Northern Territory, and South Australia. Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to two questions: "Have you ever been told by a doctor that you have asthma?" and "Do you still have asthma?" determined current doctor-diagnosed asthma. Other items included the SF-12, the Kessler-10 index of psychological distress, questions on feelings of lack of control in different areas of life, and on mental health conditions. RESULTS: From the available sample of 10 080, 7619 interviews were completed (participation rate 74.8%), with 834 people reporting current doctor-diagnosed asthma (11.2%). Psychological distress was more frequent in those with asthma (17.9% v 12.2%, p<0.01) and a higher proportion with asthma were at higher risk for anxiety or depression (40.5% v 31.2%, p<0.01). Mental health conditions were also more common (16.2% v 10.8%, p<0.01), as was the frequency of those who sometimes or always felt a lack of control over their health (33.5% v 24.3%, p<0.01). People with both asthma and psychological distress had significantly lower scores on the SF-12 physical component summary (PCS) than those with either asthma or distress alone. Among those with psychological distress, mental component summary (MCS) scores did not differ between asthmatic and non-asthmatic respondents. In a multiple regression model the frequency of a feeling of lack of control over health-together with age, family's financial situation, education level, and number of days partially unable to work or perform usual duties-was significantly associated with scores on the PCS (r = 0.73, adjusted r2 = 0.54). CONCLUSION: These results, from a representative population sample, show that psychological distress and decreased feelings of control are common in asthma and are significantly associated with physical health status.

Hormone therapy use after the Women's Health Initiative.

OBJECTIVE: To continue surveillance of hormone therapy (HT) use in an Australian population and to assess the impact of the Women's Health Initiative (WHI) and associated reports on HT use 16 months after the results of the WHI were first reported. METHODS: Data were obtained from the 2003 South Australian Health Omnibus Survey, which involves a representative, population face-to-face interview survey. Data were compared to five surveys undertaken between 1991 and 2000, which had consistent methods and quality-control procedures. A total of 907 interviews were conducted with women over 40 years in their own homes by trained health interviewers. RESULTS: In association with the timing of media reporting of the WHI, current HT use rates dropped from 28% in women over 50 years in 2000 to an estimated 10.2% in 2002. By October 2003, current use rates had returned to 18.8% in this age group. The media had been the main influence in the women's decision-making. Half of those who restarted therapy changed to another type of HT. Only 2.8% changed to an alternative/complementary therapy. CONCLUSIONS: Nearly two-thirds (64%) of those currently using HT in 2002 stopped therapy, mostly in response to the media reporting of the WHI. Nearly half of those who stopped HT in 2002 have since restarted. Media reporting greatly influences the use of hormonal therapies.

Underdiagnosed asthma in South Australia.

BACKGROUND: The prevalence of undiagnosed asthma in the general population and the clinical and demographic characteristics of these patients compared with those with diagnosed asthma are unclear. METHODS: The North West Adelaide Health Survey (NWAHS) is a population household interview survey of adults (age>18 years) in the north western suburbs of Adelaide, South Australia (regional population 0.6 million). Data obtained were weighted to the closest census data to provide population representative estimates. Positive answers to: "Have you ever had asthma?"; "Has it been confirmed by a doctor?"; "Do you still have asthma?" determined current physician diagnosed asthma. A positive bronchodilator response on spirometric testing according to ATS criteria without a physician's diagnosis determined undiagnosed asthma. Other measures included the SF-12 health survey questionnaire, the Selim index of severity of chronic lung disease, skin allergy tests, and demographic data. RESULTS: Of the 3422 individuals interviewed, 2523 (74%) agreed to participate in the clinical assessment. Of these, 292 (11.6%) had asthma, 236 (9.3%) with a doctor's diagnosis of asthma and 56 (2.3%) with undiagnosed asthma defined on spirometric criteria; thus, 19.2% of the total asthma group were undiagnosed. Those undiagnosed were more likely (p<0.05) to be >40 years old, on government benefits, with an income 65 years. Health service use over the previous year was similar for both asthma groups. CONCLUSION: Undiagnosed asthma is common among the Australian population, with a similar clinical spectrum to those with diagnosed asthma.

Hormone replacement therapy use over a decade in an Australian population.

OBJECTIVES: To describe the prevalence of hormone replacement therapy (HRT) during the 1990s in an Australian population and the length of time this therapy has been used. Design Data were obtained from five biennial representative population face-to-face interview surveys of the South Australian population from 1991 to 2000, and an additional telephone survey in 2001. The main surveys used consistent methods and quality control procedures. PARTICIPANTS: Over 3000 South Australian adults were interviewed in their own homes by trained health interviewers in each of the biennial surveys. RESULTS: In 2000, 28% of women aged over 50 were currently using HRT, and ever-use of HRT was 43%. Highest use of HRT was in the 55-59-year age group, where current use was 47% and ever-use was 70%. Among women 55 years and older there was a statistically significant increase in the prevalence of HRT use between 1991 and 2000. Mean length of use in women aged over 55 years increased from 5.4 years in 1991 to 9.6 years in 2000. CONCLUSIONS: Consistent surveillance of the population has shown that HRT use has not increased before age 55, but has greatly increased thereafter. Long-term effects may now be occurring, and further results of current long-term randomized trials are awaited to confirm the overall risk/benefit ratio suggested by observational studies and early results from long-term trials.

Mental health literacy: an impediment to the optimum treatment of major depression in the community.

BACKGROUND: Mental health literacy refers to the knowledge and beliefs about mental disorders which aid their recognition, management and prevention. This study examined the mental health literacy and experience of depression in a random and representative community population. METHODS: The experience of depression and mental health literacy of 3010 subjects from a random and representative population were determined on the basis of responses to the mood module of the PRIME-MD and questions about a vignette of a person with features of major depression. RESULTS: Those with major depression had significantly more personal experience of depression than those with other depressions and those who were not depressed, but there were few significant differences between the groups in terms of mental health literacy. Of those with major depression, 40% considered anti-depressants helpful, but 40% also considered they were harmful. CONCLUSIONS: There is a considerable impediment to the recognition and management of major depression and a need for further community education programs.

Suicidal ideation and health-related quality of life in the community.

OBJECTIVE: To examine the health-related quality of life of people with suicidal ideation in the general community. DESIGN: A Health Omnibus Survey of a random, representative sample of the South Australian population in 1998, conducted by experienced interviewers. SUBJECTS: 3010 people over the age of 15 years. OUTCOME MEASURES: The survey included questions about utilisation of health services and the Short-form Health-related Quality of Life (SF-36) and Assessment of Quality of Life (AQoL) instruments. Suicidal ideation was determined in response to a direct question. RESULTS: 79 (2.6%) subjects reported suicidal ideation in the past two weeks. Compared with those without suicidal ideation, subjects with suicidal ideation reported significantly greater use of general practitioners, psychiatrists, psychologists, social workers and outpatient clinics (P<0.001), community health services and other counsellors (P<0.01), and more hospital admissions (P<0.05). Those subjects also scored significantly poorer on all subscales of both instruments (P<0.001), to the extent that they were below the 4th percentile on the role-emotional and mental health dimensions of the SF-36 and the social relationships, psychological wellbeing and overall scores of the AQoL. CONCLUSIONS: Suicidal ideation is associated with poor health-related quality of life. These results in a random and representative community sample add support to the need to improve targeting of those with suicidal ideation on a population basis with a view to earlier intervention.

Major depression and its associated morbidity and quality of life in a random, representative Australian community sample.

OBJECTIVE: The objective of this study is to describe health services utilisation and morbidity, including health-related quality of life, in those with major depression in a random and representative sample of the population. METHOD: Data were gathered in a Health Omnibus Survey of the South Australian population. Major depression was delineated on the basis of responses to the Primary Care Evaluation of Mental Disorders. Information about use of health services and absence from usual functioning was collated, and two measures of health-related quality of life, the Short-form Health Status Questionnaire and the Assessment of Quality of Life were also administered. Results of those with major depression were compared with those who had other depressive syndromes and those who had no depression. RESULTS: Those with major depression reported significantly greater use of all health services and poorer functioning in terms of carrying out their normal duties. Similarly, their health-related quality of life was significantly poorer than those with other depressive syndromes, which in turn was significantly poorer than those who were not depressed. Only one-fifth of those with major depression were currently taking antidepressants. CONCLUSIONS: These results are consistent with international studies. In addition to the potential for alleviating the depressive symptomatology of individuals, it is evident that even a modest improvement in functioning with appropriate treatment would have the potential to benefit the Australian community by one billion dollars a year.

Mental health status of the South Australian population.

OBJECTIVE: To determine, by the use of a telephone survey, the mental health status of SA adults (18+ years) using the GHQ-28, SF-12 and self-report as indicators of mental health, and to examine risk factors for mental health morbidity. SAMPLE: A random representative sample of South Australian adults selected from the Electronic White Pages. Overall, 2,501 interviews were conducted (74.0% response rate). RESULTS: Overall, 19.5% of respondents had a mental health problem as determined by the GHQ-28, 11.8% as determined by the mental health component summary score of the SF-12 and 11.9% self-reported a mental health condition. The percentage of people with a mental health problem who had used a psychologist or a psychiatrist in the previous 12 months was 9.6% for people diagnosed by the GHQ-28, 16.2% by SF-12 and 23.7% for self-report. The logistic regression analyses undertaken to describe people with a mental health problem as determined by the GHQ-28 and to describe people who visited a psychologist or psychiatrist produced different age categories, demographic and co-morbidity indicators. Variables found in both analyses included living in the metropolitan area, being economically inactive and being a high user of health services. CONCLUSIONS: One in five South Australian adults has a mental problem. Although the prevalence is higher for younger age groups, older adults are more likely to visit a psychologist or a psychiatrist. IMPLICATIONS: Telephone interviewing produces robust indicators of the prevalence of mental health problems and is a cost-effective way of identifying prevalence estimates or tracking changes over time.

The prevalence of pelvic floor disorders and their relationship to gender, age, parity and mode of delivery.

OBJECTIVE: To define the prevalence of pelvic floor disorders in a non-institutionalised community and to determine the relationship to gender, age, parity and mode of delivery. DESIGN: A representative population survey using the 1998 South Australian Health Omnibus Survey. SAMPLE: Random selection of 4400 households; 3010 interviews were conducted in the respondents' homes by trained female interviewers. This cross sectional survey included men and women aged 15-97 years. RESULTS: The prevalence of all types of self-reported urinary incontinence in men was 4.4% and in women was 35.3% (P<0.001). Urinary incontinence was more commonly reported in nulliparous women than men and increased after pregnancy according to parity and age. The highest prevalence (51.9%) was reported in women aged 70-74 years. The prevalence of flatus and faecal incontinence was 6.8% and 2.3% in men and 10.9% and 3.5% in women, respectively. Pregnancy (> 20 weeks), regardless of the mode of delivery, greatly increased the prevalence of major pelvic floor dysfunction, defined as any type of incontinence, symptoms of prolapse or previous pelvic floor surgery. Multivariate logistic regression showed that, compared with nulliparity, pelvic floor dysfunction was significantly associated with caesarean section (OR 2.5, 95% CI 1.5-4.3), spontaneous vaginal delivery (OR 3.4, 95% CI 2.4-4.9) and at least one instrumental delivery (OR 4.3, 95% CI 2.8-6.6). The difference between caesarean and instrumental delivery was significant (P<0.03) but was not for caesarean and spontaneous delivery. Other associations with pelvic floor morbidity were age, body mass index, coughing, osteoporosis, arthritis and reduced quality of life scores. Symptoms of haemorrhoids also increased with age and parity and were reported in 19.9% of men and 30.2% of women. CONCLUSION: Pelvic floor disorders are very common and are strongly associated with female gender, ageing, pregnancy, parity and instrumental delivery. Caesarean delivery is not associated with a significant reduction in long term pelvic floor morbidity compared with spontaneous vaginal delivery.

Multiple respiratory symptoms predict quality of life in chronic lung disease: a population-based study of Australian adults.

STUDY OBJECTIVES: Previous studies have shown that it is possible to improve the health-related quality of life (HRQoL) of chronic lung disease (CLD) patients without a concurrent change in morbidity. A valid CLD index that discriminates between different levels of CLD severity and is associated with HRQoL status is an important tool for primary care settings. In this study a symptom-based CLD index was assessed for its validity and relationship with HRQoL in a representative Australian population sample. The study also measured the prevalence of self-reported CLD. DESIGN: Representative population survey of adults aged 18 years and over using a multistage, systematic, clustered area sample. SETTING: Metropolitan Adelaide and country centres in South Australia with a population of over 1000 persons. PARTICIPANTS: Three hundred twenty-nine adults with CLD identified through a representative population survey of 3010 South Australians. MEASUREMENTS AND RESULTS: The CLD index and the SF-36 were administered to participants to assess the association between each subscale of the CLD index with each HRQoL scale. The CLD index was also used to assess the prevalence of CLD and the distribution of severity in self-reported CLD in the South Australian population. Each symptom sub-scale of the CLD index was significantly correlated with all scales of the SF-36. The prevalence of CLD as measured by the CLD index was 7.7% (mild), 2.2% (moderate) and 1.0% (severe). CONCLUSIONS: In the Australian context the CLD index is a reliable patient interview instrument that can be used to assess the effects of CLD on general HRQoL, improve assessment, and lead to interventions for physicians and their patients.

Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands.

Recent studies have demonstrated the utility of synthetic combinatorial libraries for the rapid identification of peptide ligands that stimulate clonotypic populations of T cells. Here we screen a decapeptide combinatorial library arranged in a positional scanning format with two different clonotypic populations of CD4+ T cells to identify peptide epitopes that stimulate proliferative responses by these T cells in vitro. An extensive collection of mimic peptide sequences was synthesized and used to explore the fine specificity of TCR/peptide/MHC interactions. We also demonstrate that many of these deduced ligands are not only effective immunogens in vivo, but are capable of inducing T cell responses to the original native ligands used to generate the clones. These results have significant implications for considerations of T cell specificity and the design of peptide vaccines for infectious disease and cancer using clinically relevant T cell clones of unknown specificity.

Reliability of self-reported behavioural health risk factors in a South Australian telephone survey.

OBJECTIVE: To test the reliability of telephone health survey questions. METHOD: A telephone survey on mental health of South Australians in 1997 was re-administered to a random sub-sample of 102 respondents between 32 and 79 days after the original survey. RESULTS: Demographic questions (age, gender, number of adults and children in the household) showed the highest reproducibility and were almost perfect. Questions regarding health risk factors, such as smoking and drinking behaviour, showed substantial to almost perfect agreement. Co-morbidity variables were substantially reproducible where prevalence estimates were not close to zero. CONCLUSIONS: The results were comparable to findings from similar studies associated with the Behavioral Risk Factor Surveillance System (BRFSS) in the United States. The study suggests that the telephone health survey instrument used in South Australia is reliable for estimating health conditions and behaviours in the population.

Hormone replacement therapies in women at risk of cardiovascular disease and osteoporosis in South Australia in 1997.

OBJECTIVE: To describe changes in use of hormone replacement therapy (HRT) in an Australian population and to determine HRT use in women at risk of cardiovascular disease and osteoporotic fracture. DESIGN: Data were derived from the 1997 South Australian Health Omnibus Survey (a representative population survey) and compared with data from 1991, 1993 and 1995 Omnibus Surveys. SETTING: South Australia, 1997. PARTICIPANTS: 1049 women aged 40 years and over from a random selection of 4400 households. RESULTS: Among women aged 55-64 years (and thus likely to be postmenopausal), 60% had used HRT (ever use). Nearly two-thirds of these women used it currently. In this age group, mean length of HRT use had increased to 70 months (median, 60 months). Rates of HRT use had not changed significantly between 1991 and 1997 in women under 55 years, but had increased significantly in women aged 55 years or over (P < or = 0.01). Among women currently using HRT, 5.4% had used testosterone therapy, while 4% used unregistered products purported to contain hormones. Rates of ever use of HRT in women with zero, one, two, or three or more cardiovascular risk factors were 33%, 37%, and 45%, respectively. Among women with a diagnosis of osteoporosis, 52% had used HRT, with a mean length of use of 86 months (median, 60 months). CONCLUSION: HRT use is increasing in older-age groups. Longer-term therapy with potential for primary prevention is now occurring, but half of those with osteoporosis and more than half of those with risk factors for cardiovascular disease have not used HRT.

The epidemiology of hearing impairment in an Australian adult population.

BACKGROUND: This study measured the prevalence of hearing impairment, and major demographic factors that influence the prevalence, in a representative South Australian adult population sample aged > or = 15 years. METHODS: The study group was recruited from representative population surveys of South Australians. Participants in these surveys who reported a hearing disability were then recruited to an audiological study which measured air and bone conduction thresholds. In addition a sample of those people who reported no hearing disability were recruited to the audiological study. RESULTS: The data reported in this study are the first in Australia to assess the prevalence of hearing impairment from a representative population survey using audiological methods. The data show that 16.6% of the South Australian population have a hearing impairment in the better ear at > or = 25 dBHTL and 22.2% in the worse ear at the same level. The results obtained in this representative sample compare well with those obtained in the British Study of Hearing, although some differences were observed. CONCLUSIONS: Overall, there are only a few studies worldwide that have audiologically assessed the impairment of hearing from a representative population sample. The overall prevalence of hearing impairment in Australia is similar to that found in Great Britain, although there are some differences between the estimates of severity of impairment and some sex differences. The corroboration of the two studies reinforces the status of hearing impairment as the most common disability of adulthood. The present study also showed that there are a large number of Australians who may benefit from a more systematic community-based rehabilitation programme including the fitting of hearing aids. Secondly, the study identified the need for health goals and targets for hearing to be based on an epidemiological approach to the problem.

Random digit dialling and Electronic White Pages samples compared: demographic profiles and health estimates.

OBJECTIVE: To compare the methodologies of and health estimates derived from two telephone household survey methods. In particular, to establish if White Pages telephone listings provide a relatively unbiased sampling frame for population health surveys. METHOD: In South Australia in 1998, a health survey questionnaire was administered by telephone to two randomly selected population samples. The first method used EWP (Electronic White Pages, n = 6,012), which contains all listed residential telephone numbers as the sampling frame. The results were compared to a RDD (random digit dialling, n = 3,080) sample where all listed and unlisted telephone numbers were included in the sampling frame. Demographic variables and health estimates were compared between the surveys, and then compared to a 'gold standard' door-to-door household survey conducted concurrently. RESULTS: The response rate for EWP (83.8%) exceeded that of RDD (65.4%). More than four times as many calls were required per completed interview in RDD. Demographic profiles and health estimates were substantially similar. CONCLUSIONS: EWP requires fewer telephone calls and enables approach letters establishing the bona fides of the survey to be sent to each selected address before calling, increasing the response rate. RDD is a more inclusive sampling frame but also includes non-connected and business numbers, and offers no significant advantages in providing health estimates. IMPLICATIONS: There are substantial methodological and cost advantages in using EWP over RDD as the sampling, frame for population health surveys, without introducing significant bias into health estimates.

RBF principal manifolds for process monitoring.

This paper describes a novel means for creating a nonlinear extension of principal component analysis (PCA) using radial basis function (RBF) networks. This algorithm comprises two distinct stages: projection and self-consistency. The projection stage contains a single network, trained to project data from a high- to a low-dimensional space. Training requires solution of a generalized eigenvector equation. The second stage, trained using a novel hybrid nonlinear optimization algorithm, then performs the inverse transformation. Issues relating to the practical implementation of the procedure are discussed, and the algorithm is demonstrated on a nonlinear test problem. An example of the application of the algorithm to data from a benchmark simulation of an industrial overheads condenser and reflux drum rig is also included. This shows the usefulness of the procedure in detecting and isolating both sensor and process faults. Pointers for future research in this area are also given.