Eugenics or empowered choice? Community issues arising from prenatal testing

The prevention of inherited disabilities is viewed in two contrasting ways – either as enhancing reproductive choice and improving population health, or as discriminating against disabled community members. We argue that modern clinical genetics, including preimplantation genetic diagnosis (PGD), reflects a persistent and defensible desire by the community to prevent disability, rather than as increasing discrimination or threatening to produce a 'new eugenic' society. Screening should be presented as a distinct issue for decision-making about the prevention or acceptance of disability, rather than as a routinely accepted component of antenatal care. The community must improve its understanding of the experiences of those who manage disability, and continue to debate the issues of discrimination, selective genetic prevention and enhancement, reproductive freedom, and eugenics.

The work of fracture in uniaxial and biaxial oriented unplasticised polyvinylchloride pipes

In oriented unplasticised polyvinylchloride (uPVC) pipes, cracks propagate tangentially rather than through the wall as in conventional pipe. Notched impact, a modified peel test and the specific work of fracture approach have been used to measure fracture toughness of a conventionally extruded, a uniaxially oriented and a biaxially oriented uPVC pipe in different directions. The different failure mode for the oriented pipes was found to result from an order of magnitude increase in the fracture toughness for cracks propagating perpendicular to the orientation direction. Differences in the fracture toughness between the oriented pipes were also related to their molecular orientation. (C) 2002 Elsevier Science Ltd. All rights reserved.

Polarised infrared and differential scanning calorimetry studies on oriented vinyl pipe materials

The molecular orientation in a conventionally extruded PVC pipe, a uniaxially oriented PVC pipe and a biaxially oriented PVC pipe has been studied via Infrared dichroism. The degree of order or crystallinity has also been studied by Differential Scanning Calorimetry and also via Infrared Spectroscopy. The fundamental structural difference between the conventional and oriented pipes was that polymer chains were preferentially aligning in the hoop direction for oriented pipes whereas they were fairly isotropic in the conventional pipe with a slight preferential alignment in the axial direction. Analysis of the C-Cl stretching mode indicated that the uniaxially oriented pipe had much higher alignment of the C-Cl bond in the axial direction than the biaxial pipe, which correlates with higher fracture toughness for circumferential cracking in the biaxial pipe. Both DSC and Infrared spectroscopy detected little change in the crystallinity or order in the oriented pipes compared to the conventionally extruded pipes. (C) 2002 Kluwer Academic Publishers.

Comparison of two population pharmacokinetic programs, NONMEM and P-PHARM, for tacrolimus

Objectives: To compare the population modelling programs NONMEM and P-PHARM during investigation of the pharmacokinetics of tacrolimus in paediatric liver-transplant recipients. Methods: Population pharmacokinetic analysis was performed using NONMEM and P-PHARM on retrospective data from 35 paediatric liver-transplant patients receiving tacrolimus therapy. The same data were presented to both programs. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F). Covariates screened for influence on these parameters were weight, age, gender, post-operative day, days of tacrolimus therapy, transplant type, biliary reconstructive procedure, liver function tests, creatinine clearance, haematocrit, corticosteroid dose, and potential interacting drugs. Results: A satisfactory model was developed in both programs with a single categorical covariate - transplant type - providing stable parameter estimates and small, normally distributed (weighted) residuals. In NONMEM, the continuous covariates - age and liver function tests - improved modelling further. Mean parameter estimates were CL/F (whole liver) = 16.3 1/h, CL/F (cut-down liver) = 8.5 1/h and V/F = 565 1 in NONMEM, and CL/F = 8.3 1/h and V/F = 155 1 in P-PHARM. Individual Bayesian parameter estimates were CL/F (whole liver) = 17.9 +/- 8.8 1/h, CL/F (cutdown liver) = 11.6 +/- 18.8 1/h and V/F = 712 792 1 in NONMEM, and CL/F (whole liver) = 12.8 +/- 3.5 1/h, CL/F (cut-down liver) = 8.2 +/- 3.4 1/h and V/F = 221 1641 in P-PHARM. Marked interindividual kinetic variability (38-108%) and residual random error (approximately 3 ng/ml) were observed. P-PHARM was more user friendly and readily provided informative graphical presentation of results. NONMEM allowed a wider choice of errors for statistical modelling and coped better with complex covariate data sets. Conclusion: Results from parametric modelling programs can vary due to different algorithms employed to estimate parameters, alternative methods of covariate analysis and variations and limitations in the software itself.

Testing the applicability of molecular genetic markers to population analyses of scleratinian corals

The abundance of coral reefs worldwide is in decline, and despite the ecological importance of reefs, only a limited number of DNA markers have been identified for scleractinian coral genetic studies. This paper addresses the search for new coral molecular markers and investigates the applicability of the cytochrome c oxidase subunit I (COI), the internal transcribed spacer region 1 (ITS1), and the pocilloporin gene to the question of intraspecific variation in the scleractinian coral Pocillopora verrucosa along the southeast African coastline. The COI fragment was 710 bp long and was identical for P. verrucosa (n = 10) and P. damicornis (n = 3). Only two different ITS1 sequences were found (differing by 13 bp insertion), but more importantly, 24% of the sequences were heterogenous indicating that different multiple copies of the sequence exist. Pocilloporin is an intronless gene that was absolutely conserved throughout all P. verrucosa populations (n = 50). Thus, the three DNA regions studied appear unsuitable for the population genetic analyses of P. verrucosa.

Consensus neuropathological diagnosis of common dementia syndromes: testing and standardising the use of multiple diagnostic criteria

The aim of this study was to assess the variation between neuropathologists in the diagnosis of common dementia syndromes when multiple published protocols are applied. Fourteen out of 18 Australian neuropathologists participated in diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides from multiple brain regions were sent to participants who were asked for case diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and variability were determined using percentage agreement and kappa statistics. Using CERAD criteria, there was a high inter-rater agreement for cases with probable and definite Alzheimer's disease but low agreement for cases with possible Alzheimer's disease. Braak staging and the application of criteria for dementia with Lewy bodies also resulted in high inter-rater agreement. There was poor agreement for the diagnosis of frontotemporal dementia and for identifying small vessel disease. Participants rarely diagnosed more than one disease in any case. To improve efficiency when applying multiple diagnostic criteria, several simplifications were proposed and tested on 5 of the original 210 cases. Inter-rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy bodies significantly improved. Further development of simple and accurate methods to identify small vessel lesions and diagnose frontotemporal dementia is warranted.

Testing landscape metrics as indicators of habitat loss and fragmentation in continuous eucalypt forests (Queensland, Australia)

Landscape metrics are widely applied in landscape ecology to quantify landscape structure. However, many are poorly tested and require rigorous validation if they are to serve as reliable indicators of habitat loss and fragmentation, such as Montreal Process Indicator 1.1e. We apply a landscape ecology theory, supported by exploratory and confirmatory statistical techniques, to empirically test landscape metrics for reporting Montreal Process Indicator 1.1e in continuous dry eucalypt forests of sub-tropical Queensland, Australia. Target biota examined included: the Yellow-bellied Glider (Petaurus australis); the diversity of nectar and sap feeding glider species including P. australis, the Sugar Glider P. breviceps, the Squirrel Glider P. norfolcensis, and the Feathertail Glider Acrobates pygmaeus; six diurnal forest birds species; total diurnal bird species diversity; and the density of nectar-feeding diurnal bird species. Two scales of influence were considered: the stand-scale (2 ha), and a series of radial landscape extents (500 m - 2 km; 78 - 1250 ha) surrounding each fauna transect. For all biota, stand-scale structural and compositional attributes were found to be more influential than landscape metrics. For the Yellow-bellied Glider, the proportion of trace habitats with a residual element of old spotted-gum/ironbark eucalypt trees was a significant landscape metric at the 2 km landscape extent. This is a measure of habitat loss rather than habitat fragmentation. For the diversity of nectar and sap feeding glider species, the proportion of trace habitats with a high coefficient of variation in patch size at the 750 m extent was a significant landscape metric. None of the landscape metrics tested was important for diurnal forest birds. We conclude that no single landscape metric adequately captures the response of the region's forest biota per se. This poses a major challenge to regional reporting of Montreal Process Indicator 1.1e, fragmentation of forest types.

A subset-oriented algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries

Libraries of cyclic peptides are being synthesized using combinatorial chemistry for high throughput screening in the drug discovery process. This paper describes the min_syn_steps.cpp program (available at http://www.imb.uq.edu.au/groups/smythe/tran), which after inputting a list of cyclic peptides to be synthesized, removes cyclic redundant sequences and calculates synthetic strategies which minimize the synthetic steps as well as the reagent requirements. The synthetic steps and reagent requirements could be minimized by finding common subsets within the sequences for block synthesis. Since a brute-force approach to search for optimum synthetic strategies is impractically large, a subset-orientated approach is utilized here to limit the size of the search. (C) 2002 Elsevier Science Ltd. All rights reserved.

Testing the link between the latitudinal gradient in species richness and rates of molecular evolution

Numerous hypotheses have been proposed to explain latitudinal gradients in species richness, but all are subject to ongoing debate. Here we examine Rohde's (1978, 1992) hypothesis, which proposes that climatic conditions at low latitudes lead to elevated rates of speciation. This hypothesis predicts that rates of molecular evolution should increase towards lower latitudes, but this prediction has never been tested. We discuss potential links between rates of molecular evolution and latitudinal diversity gradients, and present the first test of latitudinal variation in rates of molecular evolution. Using 45 phylogenetically independent, latitudinally separated pairs of bird species and higher taxa, we compare rates of evolution of two mitochondrial genes and DNA-DNA hybridization distances. We find no support for an effect of latitude on rate of molecular evolution. This result casts doubt on the generality of a key component of Rohde's hypothesis linking climate and speciation.

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was student-oriented, ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experience first-hand work in a research laboratory. Our philosophy is a cradle-to-grave approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.