Molecular genetics of schizophrenia

1. Schizophrenia is a chronic, disabling brain disease that affects approxmately 1% of the world's population. It is characterized by delusions, hallucinations and formal thought disorder, together with a decline in socio-occupational functioning. While the causes for schizophrenia remain unknown, evidence from family, twin and adoption studies clearly demonstrates that it aggregates in families, with this clustering largely attributable to genetic rather than cultural or environmental factors. Identifying the genes involved, however, has proven to be a difficult task because schizophrenia is a complex trait characterized by an imprecise phenotype, the existence of phenocopies and the presence of low disease penetrance, 2. The current working hypothesis for schizophrenia causation is that multiple genes of small to moderate effect confer compounding risk through interactions with each other and with non-genetic risk factors, The same genes may be commonly involved in conferring risk across populations or they may vary in number and strength between different populations. To search for evidence of such genetic loci, both candidate gene and genome-wide linkage studies have been used in clinical cohorts collected from a variety of populations. Collectively, these works provide some evidence for the involvement of a number of specific genes (e.g. the 5-hydroxytryptamine (5-HT) type 2a receptor (5-HT2a) gene and the dopamine D-3 receptor gene) and as yet unidentified factors localized to specific chromosomal regions, including 6p, 6q, 8p, 13q and 22q, These data provide suggestive, but no conclusive, evidence for causative genes. 3. To enable further progress there is a need to: (i) collect fine-grained clinical datasets while searching the schizophrenia phenotype for subgroups or dimensions that may provide a more direct route to causative genes; and (ii) integrate recent refinements in molecular genetic technology, including modern composite marker maps, DNA expression assays and relevant animal models, while using the latest analytical techniques to extract maximum information in order to help distinguish a true result from a false-positive finding.

Increasing profits and reducing risks in crop production using participatory systems simulation approaches

The development of cropping systems simulation capabilities world-wide combined with easy access to powerful computing has resulted in a plethora of agricultural models and consequently, model applications. Nonetheless, the scientific credibility of such applications and their relevance to farming practice is still being questioned. Our objective in this paper is to highlight some of the model applications from which benefits for farmers were or could be obtained via changed agricultural practice or policy. Changed on-farm practice due to the direct contribution of modelling, while keenly sought after, may in some cases be less achievable than a contribution via agricultural policies. This paper is intended to give some guidance for future model applications. It is not a comprehensive review of model applications, nor is it intended to discuss modelling in the context of social science or extension policy. Rather, we take snapshots around the globe to 'take stock' and to demonstrate that well-defined financial and environmental benefits can be obtained on-farm from the use of models. We highlight the importance of 'relevance' and hence the importance of true partnerships between all stakeholders (farmer, scientists, advisers) for the successful development and adoption of simulation approaches. Specifically, we address some key points that are essential for successful model applications such as: (1) issues to be addressed must be neither trivial nor obvious; (2) a modelling approach must reduce complexity rather than proliferate choices in order to aid the decision-making process (3) the cropping systems must be sufficiently flexible to allow management interventions based on insights gained from models. The pro and cons of normative approaches (e.g. decision support software that can reach a wide audience quickly but are often poorly contextualized for any individual client) versus model applications within the context of an individual client's situation will also be discussed. We suggest that a tandem approach is necessary whereby the latter is used in the early stages of model application for confidence building amongst client groups. This paper focuses on five specific regions that differ fundamentally in terms of environment and socio-economic structure and hence in their requirements for successful model applications. Specifically, we will give examples from Australia and South America (high climatic variability, large areas, low input, technologically advanced); Africa (high climatic variability, small areas, low input, subsistence agriculture); India (high climatic variability, small areas, medium level inputs, technologically progressing; and Europe (relatively low climatic variability, small areas, high input, technologically advanced). The contrast between Australia and Europe will further demonstrate how successful model applications are strongly influenced by the policy framework within which producers operate. We suggest that this might eventually lead to better adoption of fully integrated systems approaches and result in the development of resilient farming systems that are in tune with current climatic conditions and are adaptable to biophysical and socioeconomic variability and change. (C) 2001 Elsevier Science Ltd. All rights reserved.

Suicide in urban New South Wales, Australia 1985-1994: Socio-economic and migrant interactions

Variation of suicide with socio-economic status (SES) in urban NSW (Australia) during 1985-1994, by sex and country or region of birth, was examined using Poisson regression analysis of vital statistics and population data (age greater than or similar to 15 yr). Quintiles of SES were defined by municipality of residence and comparisons of suicide by SES were adjusted for age and country (or region) of birth (COB), and examined by COB. Risk of suicide in females was 28% that of males for all adults and 21% for youth (age 15-24 yr). Suicide risk was lower in males from southern Europe, Middle East and Asia, and higher in northern and eastern European males, compared to the Australian-born. Risks for suicide increased significantly with decreasing SES in males, but not in females. The relationship of male suicide and SES was stronger when controlled for COB. For males, the relative risk of suicide, adjusted for age and COB, was 66% higher in the lowest SES quintile compared to the highest quintile, and 39% higher for youth (age 15-24 yr). For male suicide, the population attributable fraction for SES (less than the highest quintile) was 27%. Analysis of SES differentials in male suicide according to COB indicated a significant inverse suicide gradient in relation to SES for the Australian-born and those burn in New Zealand and the United Kingdom or fire. but not in non-English speaking COB groups, except for Asia. For Australian-born males, suicide risk was 71% higher in the lowest SES group (compared to the highest), adjusted for age. These findings indicate that SES plays an important role in male suicide rates among the Australian-born and migrants from English-speaking countries and Asia, and among youth; but not in female suicide, nor suicide in most non-English speaking migrant groups. Reduction in SES differentials through economic and social policies may reduce male suicide in lower SES groups and should be seen to be at least as important as individual level interventions. (C) 1998 Elsevier Science Ltd. All rights reserved.

Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales

Objective: This study examines the variation in coronary heart disease (CHD) mortality and acute myocardial infarction (AMI) by socio-economic status (SES), country of birth (COB) and geography (urban/rural) in the total population of New South Wales (Australia) in 1991-95. Method: CHD deaths and AMI are from complete enumerations of deaths and hospital admissions, respectively; and population denominators are from census information. Data are examined separately by sex, and comparisons of SES groups (based on municipalities), COB and region are analysed using Poisson regression, after adjustment for age. Results: The study identified higher risk for AMI admissions and CHD mortality in lower SES populations with significant linear trends, for both sexes, adjusted for age, region and COB. According to the population attributable fractions (PAF), 23-41% of the risk of CHD occurrence is due to SES lower than the highest quartile. The higher age-adjusted risk for CHD occurrence in rural and remote populations for both sexes, compared with urban communities, was lessened by adjustment for COB, and all but abolished when also adjusted for SES. COB analysis indicated significantly lower age-adjusted AMI admissions and CHD mortality compared with the Australian-born, Conclusions: Higher risks for CHD in rural populations compared with the capital city (Sydney) are due, in part, to lower SES, lesser migrant composition. Implications: Strategies for reducing CHD differentials should consider demographic factors and the fundamental need to reduce socio-economic inequalities, as well as targeting appropriate prevention measures.

Women drivers' behaviour, socio-demographic characteristics and accidents

The purpose of this study was to examine factors which affect driving behaviour and accident rates in women in Australia. Two groups of women (aged 18-23 and 45-50 years) participating in the Australian Longitudinal Study on Women's Health, completed a mailed questionnaire on driver behaviour and road accidents. Self reported accident rates in the last 3 years were 1.87 per 100 000 km for the young drivers (n = 1199) and 0.59 per 100 000 km for the mid-age drivers (n = 1564); most accidents involved damage only, not injury. Mean scores for lapses obtained using the Driver Behaviour Questionnaire, were similar in the two age groups and similar to those found in other studies. In contrast, scores for errors and violations for the young women were higher than for the mid-age group and previous reports using the same instruments. Riskier driving behaviour among young women was associated with stress and habitual alcohol consumption. In the mid-age group, poorer driver behaviour scores were related to higher levels of education, feeling rushed, higher habitual alcohol consumption and lower life satisfaction scores. Accident rates in both groups were significantly related to lapses. Women born in non-English speaking countries had significantly higher risk of accidents compared to Australian-born women: relative risk = 3.40, 95% confidence interval (1.93, 5.98) for the young drivers; relative risk = 1.77, 95% confidence interval (1.11, 2.83) for mid-age drivers. These findings support the need for road safety campaigns targeted at young women to reduce dangerous driving practices, such as speeding,'tail gating' and overtaking on the inside. There is also a need for further research to understand how lifestyle characteristics are associated with higher risk of accidents and to explore factors which might account for the higher risk for women drivers who were born overseas. (C) 1999 Elsevier Science Ltd. All rights reserved.

Patterns of alcohol consumption in young Australian women: socio-demographic factors, health-related behaviours and physical health

Objective: To determine which sociodemographic factors. health-related behaviours and physical health conditions are associated with non-drinking, binge drinking and hazardous/harmful drinking in young Australian women. Methods: Cross-sectional data were obtained from the baseline survey of 14,762 young women (aged 18-23 years) enrolled in the Women's Health Australia study in 1996. Associations between a range of drinking patterns and sociodemographic factors, health-related behaviours and health conditions were examined. Results: Half the women were 'low intake' drinkers, a third 'rarely drank' and 9% were non-drinkers; however, 70% reported binge drinking with one-quarter of the binge drinkers doing so at least weekly. Nondrinkers were more likely than drinkers to be married, pregnant, non-smokers, born in non-English speaking countries, to live in the Northern Territory, and to have lower levels of education, employment, and private health insurance. Low intake/binge weekly' drinkers (12%) and 'hazardous/ harmful' drinkers (5%) were more likely than 'low risk' drinkers to be unmarried; to live in shared accommodation, alone or with their parents; to live in rural or remote areas; to have ever had any sexually transmitted infection; to be current smokers or ex-smokers and to have used unhealthy weight-control practices. Conclusions: The results confirm findings from other countries about the importance of social conditions as determinants of alcohol consumption by young women. Implications: Health promotion to reduce young women's alcohol consumption needs to be carefully targeted to take account of their demographies, living environments and beliefs.

Variation in mortality rates in Australia: correlation with Indigenous status, remoteness and socio-economic deprivation

Background The aim of this study was to study ecological correlations between age-adjusted all-cause mortality rates in Australian statistical divisions and (1) the proportion of residents that self-identify as Indigenous, (2) remoteness, and (3) socio-economic deprivation. Methods All-cause mortality rates for 57 statistical divisions were calculated and directly standardized to the 1997 Australian population in 5-year age groups using Australian Bureau of Statistics (ABS) data. The proportion of residents who self-identified as Indigenous was obtained from the 1996 Census. Remoteness was measured using ARIA (Accessibility and Remoteness Index for Australia) values. Socioeconomic deprivation was measured using SEIFA (Socio-Economic index for Australia) values from the ABS. Results Age-standardized all-cause mortality varies twofold from 5.7 to 11.3 per 1000 across Australian statistical divisions. Strongest correlation was between Indigenous status and mortality (r = 0.69, p < 0.001). correlation between remoteness and mortality was modest (r = 0.39, p = 0.002) as was correlation between socio-economic deprivation and mortality (r = -0.42, p = 0.001). Excluding the three divisions with the highest mortality, a multiple regression model using the logarithm of the adjusted mortality rate as the dependent variable showed that the partial correlation (and hence proportion of the variance explained) for Indigenous status was 0.03 (9 per cent; p = 0.03), for SEIFA score was -0.17 (3 per cent; p = 0.22); and for remoteness was -0.22 (5 per cent; p = 0.13). Collectively, the three variables studied explain 13 per cent of the variability in mortality. Conclusions Ecological correlation exists between all-cause mortality, Indigenous status, remoteness and disadvantage across Australia. The strongest correlation is with indigenous status, and correlation with all three characteristics is weak when the three statistical divisions with the highest mortality rates are excluded. intervention targeted at these three statistical divisions could reduce much of the variability in mortality in Australia.

Mental health and socio-economic variations in Australian suicide

This paper investigates the relationship between suicide rates and prevalence of mental disorder and suicide attempts, across socio-economic status (SES) groups based on area of residence. Australian suicide data (1996-1998) were analysed in conjunction with area-based prevalences of mental disorder derived from the National Survey of Mental Health and Well-Being (1997). Poisson regression models of suicide risk included age, quintile of area-based SES, urban-rural residence, and country of birth (COB), with males and females analysed separately. Analysis focussed on the association between suicide and prevalences of (ICD-10) affective disorders, anxiety disorders, substance use disorders and suicide attempts by SES group. Prevalences of other psychiatric symptomatology, substance use problems, health service utilisation, stressful life-events and personality were also investigated. Significant increasing gradients were evident from high to low SES groups for prevalences of affective disorders, anxiety disorders (females only), and substance use disorders (males only); sub-threshold drug and alcohol problems and depression; and suicide attempts and suicide (males only). Prevalences of mental disorder, other sub-threshold mental health items and suicide attempts were significantly associated with suicide, but in most cases associations were reduced in magnitude and became statistically non-significant after adjustment for COB, urban-rural residence, and SES. For male suicide the relative risk (RR) in the lowest SES group compared to the highest was 1.40 (95% CI 1.29-1.52, p < 0.001) for all ages, and 1.46 (95% CI 1.27-1.67, p < 0.001) for male youth (20-34 years). This relationship was not substantially modified in males when regression models included prevalences of affective disorders, and other selected mental health variables and demographic factors. From a population perspective, SES remained significantly associated with suicide after controlling for the prevalence of mental disorders and other psychiatric symptomatology. Mental conditions and previous suicidal behaviour may play an intermediary role between SES and suicide, but this study suggests that an independent relationship between suicide and SES also exists. (c) 2005 Elsevier Ltd. All rights reserved.

Which aspects of socio-economic status are related to health in mid-aged and older women?

A population-based study was conducted to validate gender- and age-specific indexes of socio-economic status (SES) and to investigate the associations between these indexes and a range of health outcomes in 2 age cohorts of women. Data from 11,637 women aged 45 to 50 and 9,5 10 women aged 70 to 75 were analyzed. Confirmatory factor analysis produced four domains of SES among the mid-aged cohort (employment, family unit, education, and migration) and four domains among the older cohort (family unit, income, education, and migration). Overall, the results supported the factor structures derived from another population-based study (Australian Bureau of Statistics, 1995), reinforcing the argument that SES domains differ across age groups. In general, the findings also supported the hypotheses that women with low SES would have poorer health outcomes than higher SES women, and that the magnitude of these effects would differ according to the specific SES domain and by age group, with fewer and smaller differences observed among older women. The main exception was that in the older cohort, the education domain was significantly associated with specific health conditions. Results suggest that relations between SES and health are highly complex and vary by age, SES domain, and the health outcome under study.

The population structure of Plasmodium falciparum and Plasmodium vivax during an epidemic of malaria in the eastern highlands of Papua New Guinea

Although most of the Papua New Guinea highlands are too high for stable malaria transmission, local epidemics are a regular feature of the region. Few detailed descriptions of such epidemics are available, however. We describe the investigation of a malaria epidemic in the Obura Valley, Eastern Highlands Province, Papua New Guinea. Of the 244 samples examined by microscopy, 6.6% were positive for Plasmodium falciparum only, 9.4% were positive for Plasmodium vivax only, and 1.2% were mixed infections. MSP2 and MSP3alpha genotyping and AMA1 sequencing were used to determine the genetic variation present in a sample of P. falciparum and P. vivax infections. The P. vivax infections were found to be genetically highly diverse. In contrast, all P. falciparum samples were of a single genotype. This striking difference in genetic diversity suggests endemic, low-level local transmission for P. vivax but an outside introduction of P. falciparum as the most likely source of the epidemic.

Family average income and body mass index above the healthy weight range among urban and rural residents in regional Mainland China

Objective: To explore the relationship between family average income (FAI; an index of socio-economic status) and body mass index (BMI; a widely used, inexpensive indicator of weight status) above the healthy weight range in a region of Mainland China. Design: Population-based cross-sectional study, conducted between October 1999 and March 2000 on a sample of regular local residents aged 35 years or older who were selected by random cluster sampling. Setting: Forty-five administrative villages selected from three urban districts and two rural counties of Nanjing municipality, Mainland China, with a regional population of 5.6 million. Subjects: In total, 29 340 subjects participated; 67.7% from urban and 32.3% from rural areas; 49.8% male and 50.2% female. The response rate among eligible participants was 90.1%. Results: The proportion of participants classified as overweight was 30.5%, while 7.8% were identified as obese. After adjusting for possible confounding variables (age, gender, area of residence, educational level, occupational and leisure-time physical activity, daily vegetable consumption and frequency of red meat intake), urban participants were more likely to be overweight or obese relative to their rural counterparts, more women than men were obese, and participants in the lowest FAI tertile were the least likely to be above the healthy weight range. Conclusions: The proportion of adults with BMI above the healthy weight range was positively related to having a higher socio-economic status (indexed by FAI) in a regional Chinese population.

Smoking and parenting among males in low socio-economic occupations

The role of fatherhood in family life has been accentuated as a consequence of societal change. This change, combined with knowledge about the harmful consequences of passive smoking, has focused attention on males who smoke and are the partners of pregnant women. Of particular interest are low socio-economic groups because of their higher smoking rates. This study examines smoking and parenting in a sample of 561 males in semi-skilled and unskilled occupations (with pregnant partners) who were recruited into a self-help smoking cessation programme. Parenting related variables predicted smoking cessation, particularly knowledge about passive smoking. A high level of knowledge about the effects of passive smoking on a baby was associated with one or more quit attempts early in the partner's pregnancy and smoking cessation. Confidence to quit during the pregnancy was also associated with smoking cessation. These results could be incorporated into smoking cessation and antenatal programmes to improve the health of families.

Effect of different preparation routes on the structure and properties of rigid polyurethane-layered silicate nanocomposites

To identify the effect of reactive preparation on the structure and properties of rigid polyurethane (PU)layered silicate nanocomposite, a range of nanocomposites were prepared by combining the various precursors in different sequences. The morphology of the samples was characterized by XRD and TEM. Tensile properties and dynamic mechanical thermal properties were measured. The reactions between the layered silicates and PU precursors were monitored via FTIR to gain an understanding of the participation of nanofiller in the polymerization reaction, and the impact of this on system stoichiometry. The XRD and TEM results provided evidence that morphology can differ significantly if different synthesis methods are used. However, the mechanical properties are dominated by the stoichiometry imbalance induced by the addition of the layered silicates. (c) 2006 Wiley Periodicals, Inc.