Towards a molecular epidemiology of alcohol dependence analysing the interplay of genetic and environmental risk factors

Background Progress in identifying genetic factors protective against alcohol dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. Aims To integrate analysis of research into the genetics of alcoholism. Method Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed. Results In men, effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. Conclusions The early onset and strong familial aggregation of AlcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

Complete genomic sequence of the Australian south-west genotype of Sindbis virus: Comparisons with other Sindbis strains and identification of a unique deletion in the 3 '-untranslated region

Our previous studies have shown that two distinct genotypes of Sindbis (SIN) virus occur in Australia. One of these, the Oriental/Australian type, circulates throughout most of the Australian continent, whereas the recently identified south-west (SW) genetic type appears to be restricted to a distinct geographic region located in the temperate south-west of Australia. We have now determined the complete nucleotide and translated amino acid sequences of a SW isolate of SIN virus (SW6562) and performed comparative analyses with other SIN viruses at the genomic level. The genome of SW6562 is 11,569 nucleotides in length, excluding the cap nucleotide and poly (A) tail. Overall this virus differs from the prototype SIN virus (strain AR339) by 23% in nucleotide sequence and 12.5% in amino acid sequence. Partial sequences of four regions of the genome of four SW isolates were determined and compared with the corresponding sequences from a number of SIN isolates from different regions of the World. These regions are the non-structural protein (nsP3), the E2 gene, the capsid gene, and the repeated sequence elements (RSE) of the 3'UTR. These comparisons revealed that the SW SIN viruses were more closely related to South African and European strains than to other Australian isolates of SIN virus. Thus the SW genotype of SIN virus may have been introduced into this region of Australia by viremic humans or migratory birds and subsequently evolved independently in the region. The sequence data also revealed that the SW genotype contains a unique deletion in the RSE of the 3'UTR region of the genome. Previous studies have shown that deletions in this region of the SIN genome can have significant effects on virus replication in mosquito and avian cells, which may explain the restricted distribution of this genotype of SIN virus.

Genetic and environmental sources of covariance between reading tests used in neuropsychological assessment and IQ subtests

In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test [CCRT], [Beardsall, L., and Huppert, F. A. ( 1994). J. Clin. Exp. Neuropsychol. 16: 232 - 242], Schonell Graded Word Reading Test [SGWRT], [ Schonell, F. J., and Schonell, P. E. ( 1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.]) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press.] and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) [Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation]. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years ( mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors ( Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor ( accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor ( explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor ( explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.

Variation in body size and sexual dimorphism across geographical and environmental space in the frogs Limnodynastes tasmaniensis and L. peronii

This study aimed to identify potential factors responsible for geographically structured morphological variation within the widespread Australian frogs Limnodynastes tasmaniensis Gunther and L. peronii Dumeril & Bibron. There was support for James's rule, and both latitude and present climate explained large amounts of the variation in body size and shape (particularly in L. peronii). There was also some support for the influence of several biogeographical barriers. Finally, both species were sexually dimorphic for body size and the degree of sexual size dimorphism (SSD) varied geographically. Climate was an important explanation for SSD variation in L. peronii, while latitude was most important for L. tasmaniensis. Geographical variations in sexual selection via male-male physical competition and climate-related resources are suggested as potential explanations for SSD variation in L. peronii. (C) 2004 The Linnean Society of London.

Teamwork in Health and Rehabilitation Sciences: Evaluation of a multiprofessional workshop

This paper outlines a multiprofessional education workshop piloted and subsequently conducted with a cohort of 81 graduate entry students of occupational therapy, physiotherapy, speech pathology and audiology. The rationale for, and format of, the workshop is outlined, followed by comparisons between students' knowledge about teamwork prior to and after the four-hour workshop. The workshop was based on a real case scenario of a child with Developmental Coordination Disorder (DCD). Students completed pre- and post-workshop questionnaires about their knowledge of DCD, teamwork and the roles of various professionals and parents; and a post-workshop questionnaire about their views regarding the utility of the workshop, its strengths, and learning outcomes. The evaluation indicated that the workshop was overwhelmingly successful from the students' perspective in: (1) enhancing their understanding about DCD and its multifaceted impact on school age children; (2) developing a deeper appreciation of the importance of teamwork itself; (3) refining their understanding of their own profession's role and (4) developing an appreciation of the role of other professions and parents in working with children with complex needs, and their families. Limitations of this study and directions for future research are discussed.

Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1 induced alterations in neuronal excitability: A comparison with other osmotic agents and free radical scavengers

The basis for the neuroprotectant effect of D-mannitol in reducing the sensory neurological disturbances seen in ciguatera poisoning, is unclear. Pacific ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was reversed by hyperosmolar 50 MM D-mannitol. However, using electron paramagnetic resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate hydroxyl free radicals at concentrations of toxin that caused profound effects on neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons revealed that both hyper- and iso-osmolar 50 MM D-mannitol prevented the membrane depolarisation and repetitive firing of action potentials induced by P-CTX-1. In addition, both hyper- and iso-osmolar 50 MM D-mannitol prevented the hyperpolarising shift in steady-state inactivation and the rise in leakage current through tetrodotoxin (TTX)-sensitive Na-v channels, as well as the increased rate of recovery from inactivation of TTX-resistant Nav channels induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition of peak TTX-sensitive and TTX-resistant I-Na amplitude by P-CTX-1. Additional experiments using hyper- and isoosmolar D-sorbitol, hyperosmolar sucrose and the free radical scavenging agents Trolox (R) and L-ascorbic acid showed that these agents, unlike D-mannitol, failed to prevent the effects of P-CTX-1 on spike electrogenesis and Na-v channel gating. These selective actions of D-mannitol indicate that it does not act purely as an osmotic agent to reduce swelling of nerves, but involves a more complex action dependent on the Nav channel subtype, possibly to alter or reduce toxin association. (c) 2005 Elsevier Ltd. All rights reserved.

Prospective study of individual, social, and environmental predictors of physical activity: women's leisure running

Background: Understanding and influencing the determinants of physical activity is an important public health challenge. We used prospective data to examine the influence of individual, social, and environmental factors on physical activity behaviour, using regular running as the behavioural model. Methods: Over 500 middle-aged women completed two consecutive questionnaires in 2000 and 2002. Logistic regression analyses were used to examine factors predicting adoption of and regression from regular leisure-time running during the follow-up. Results: Women who frequently used behavioural change skills were more likely to adopt regular running (OR=4.0, CI=1.7-9.5). There was an interaction between the enjoyment of running and family support: those who rated enjoyment of running high and reported high family support were less likely to adopt running (OR= 0.2, CI = 0.1-0.5). Women who reported infrequent use of motives were more likely (OR = 3.3, CI = 1.6-6.9) to regress from regular running. There was an interaction between perceived health and the neighbourhood environment: those who perceived themselves to be in poor health and had an unattractive neighbourhood were more likely (OR = 2.7, CI = 0.9-8.3) to regress from regular running. Conclusions: Behavioural skills and enjoyment may be of particular importance for the adoption of regular activity; social support and an aesthetically attractive neighbourhood are likely to have a key role in encouraging maintenance. (c) 2004 Elsevier Ltd. All rights reserved.

Optimising profitability and environmental trade-offs in managing cropping systems using differential evolution

Whilst traditional optimisation techniques based on mathematical programming techniques are in common use, they suffer from their inability to explore the complexity of decision problems addressed using agricultural system models. In these models, the full decision space is usually very large while the solution space is characterized by many local optima. Methods to search such large decision spaces rely on effective sampling of the problem domain. Nevertheless, problem reduction based on insight into agronomic relations and farming practice is necessary to safeguard computational feasibility. Here, we present a global search approach based on an Evolutionary Algorithm (EA). We introduce a multi-objective evaluation technique within this EA framework, linking the optimisation procedure to the APSIM cropping systems model. The approach addresses the issue of system management when faced with a trade-off between economic and ecological consequences.