Biostatistics in Australia: Directions in the new millennium

The Biostatistics Collaboration of Australia (BCA) was formed in response to a shortage of statisticians seeking careers in the medical and health professions. The Collaboration has been successful in developing postgraduate courses (Graduate Certificate, Graduate Diploma and Masters) offered by a consortium of seven Australian Universities. These courses are available through a distance learning medium. The BCA was successful in securing funding from the Federal government to launch these courses, which commenced in March 2001. Two traineeships by the NSW Department of Health have also been awarded and a third is currently advertised. There has been close collaboration with governments, the pharmaceutical industry and research organisations to ensure that course content reflects practical problems and addresses industry needs. A second objective of the BCA is to provide ongoing workshops for practising biostatisticians to enhance professional development. These workshops serve to ring together biostatisticians from both within Australia and the Asia-Pacific region, providing a forum for discussion of current statistical thinking. (author abstract)

Differentiation of peanut seedborne potyviruses and curcumoviruses by RT-PCR

Seedborne peanut viruses pose important constraints to peanut production and safe movement of germ plasm. They also pose a risk of accidental introduction into previously disease-free regions. We have developed reverse transcription-polymerase chain reaction (RT-PCR) assays based on identical cycling parameters which identified peanut stripe, Peanut mottle, Peanut stunt, and Cucumber mosaic viruses through production of specific DNA fragments of 234 bp, 327 bp, 390 bp, and 133 bp, respectively. Assay sensitivity in the picogram range was achieved. The two potyviruses and two cucumoviruses could be differentiated using duplex RT-PCR assays. These assays should be useful for testing peanut leaves or seeds for virus identification in epidemiological studies, seed testing or in post-entry quarantine.

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.

Reinfection with Schistosoma haematobium following school-based chemotherapy with praziquantel in four highly endemic villages in Côte d'Ivoire

We present the comparative evaluation of school-based chemotherapy with praziquantel on Schistosoma haematobium reinfection patterns, 6, 12, 18 and 24 months after systematic treatment of schoolchildren in four villages of south-central Côte d'Ivoire. At baseline, very high S. haematobium infection prevalences of 88–94% were found in Taabo Village, located adjacent to a large man-made lake, and in Batera and Bodo, where small dams were constructed. In Assinzé, a village with no man-made environmental alterations, the baseline infection prevalence was significantly lower (67%). The parasitological cure rate, assessed 4 weeks after praziquantel administration in the village with the highest prevalence and intensity of infection, was high (82%), and showed a clear association with infection intensity prior to treatment. Six months after chemotherapy, significant reductions in the prevalence and intensity of infection were observed in all villages. However, infection prevalence was again high in Taabo Village (63%) and in Batera (49%). Different patterns of reinfection occurred in the four villages: rapid reinfection in Taabo Village to reach almost baseline infection prevalence 12 months post-treatment; slow but gradual increase in the prevalence and intensity of infection in Bodo; marked increase in prevalence and intensity of infection during the second year of the follow-up in Assinzé; and prevalence and intensity of infection that remained almost constant between 6 and 24 months post-treatment in Batera. Our study confirms that S. haematobium reinfection patterns largely depend on the local epidemiological setting, which is of central importance to tailoring treatment strategies that are well adapted to these different settings.

A genomewide search for type 2 diabetes-susceptibility genes in indigenous Australians

The prevalence of type 2 diabetes among Australian residents is 7.5%; however, prevalence rates up to six times higher have been reported for indigenous Australian communities. Epidemiological evidence implicates genetic factors in the susceptibility of indigenous Australians to type 2 diabetes and supports the hypothesis of the thrifty genotype, but, to date, the nature of the genetic predisposition is unknown. We have ascertained clinical details from a community of indigenous Australian descent in North Stradbroke Island, Queensland. In this population, the phenotype is characterized by severe insulin resistance. We have conducted a genomewide scan, at an average resolution of 10 cM, for type 2 diabetes-susceptibility genes in a large multigeneration pedigree from this community. Parametric linkage analysis undertaken using FASTLINK version 4.1p yielded a maximum two-point LOD score of +2.97 at marker D2S2345. Multipoint analysis yielded a peak LOD score of +3.9

Identity and genetic diversity of the sorghum ergot pathogen in Australia

Sorghum ergot was first discovered in Australia in 1996. It affects seed production and grain usage in stock feed due to concerns of animal toxicity. Three species of Claviceps are known to cause ergot of sorghum with different epidemiological, animal toxicity, and management implications. Claviceps africana was identified as the causal agent but morphological differences between isolates raised the possibility of more than one species being involved. The major aim of this study was to identify the Claviceps species causing sorghum ergot and to determine the genetic diversity among isolates of the ergot pathogen from Australia and overseas. Symptom development, sequencing of the ITS1 region, and radiolabelled DNA amplification fingerprints (RAF) were used to confirm that ergot of sorghum in Australia is caused by C. africana. The morphology of sphacelia, microconidia, macroconidia, and secondary conidia of all 36 Australian isolates studied matched the description for C. africana and the DNA sequence of the ITS1 region of 2 selected Australian isolates was identical to that of C. africana. Based on RAF analysis of 110 Australian and overseas isolates of Claviceps spp., C. africana isolates could be clearly distinguished (

Cadmium levels in the lung, liver, kidney cortex, and urine samples from Australians without occupational exposure to metals

The authors undertook this study to assess levels of cadmium exposure in the general population. Samples of lung, liver, and kidney were obtained from 61 cadavers (43 males, 18 females; 2-89 yr of age, mean age = 38.5 yr) who died from accidental causes and who were subject to postmortem examinations at the John Tonge Centre for Forensic Sciences, Queensland Health Scientific Services, Brisbane, Australia, in 1997 and 1998. Samples of bladder urine were also obtained from 22 cadavers. Tissue and urine samples were analyzed for cadmium, zinc, and copper with inductively coupled plasm (ICP) mass spectrometry. The overall mean values for cadmium in the lung, liver, and kidney cortex samples were 0.13, 0.95, and 15.45 mug/gm wet tissue weight. The average renal cadmium level in subjects with high lung-cadmium levels (n = 13) was 6 mug/gm wet tissue weight higher than that of similarly aged subjects who had medium lung-cadmium levels (n = 30). In females, the average level of cadmium in the liver was 74% greater than in males, and the average liver cadmium in females with high lung-cadmium levels was 100% higher than in males in the same age range who had the same high lung-cadmium levels. Renal cadmium accumulation tended to be greater in females than in males who were in the same age range and who had similar lung-cadmium levels, a result that suggested that there was a higher absorption rate of cadmium in females. The mean value for a urinary cadmium excretion of 2.30 mug/gm creatinine was found in a subset of samples that had a mean age of 39 yr and a renal cortex cadmium concentration of 18.6 mug/gm wet tissue weight. Urinary cadmium excretion rates were correlated more strongly with lung and kidney cadmium content than with age or liver cadmium levels. The results suggest that urinary cadmium excretion may be increased in smokers and could provide some estimate of body cadmium burdens in future Australian epidemiological studies.

Very limited transmission of FMD following introduction into a sheep flock

IN contrast to previous international experience, sheep played a critical role in the source and spread of foot-andnmouth disease (FNID) in the 2001 outbreak in the UK. At many stages during the outbreak, sheep wvere associated with the emergence of disease in new, that is, previously non-infected, areas, and in areas which had been apparently cleared of disease some weeks or months earlier. Although some information about this disease in sheep is available (Donaldson and Sellers 2000), an understanding of the natural history of FNIF in sheep will be improved based on lessons learned from the 2001 outbreak. This short communication describes an outbreak of FNID in a sheep flock in north-east England, where there was strong epidemiological and laboratory evidence of very limited transmission of disease following introduction.

Selenium content of Australian foods: A review of literature values

The aim of this study was to review the published literature values for the selenium content of Australian foods. A secondary aim was to compare the results for Australian foods with food composition data from international sources to investigate the extent of geographical variation. Published food composition data sources for the selenium content in Australian foods were identified and assessed for data quality using established criteria. The selenium content is available for 148 individual food items. The highest values found are for fish (12.0-63.2 mug/100 g), meats (4.75-37.9 mug/100 g) and eggs (9.00-41.4 mug/100 g), followed by cereals (1.00-20.3 mug/100 g). Moderate levels are seen in dairy products (2.00-7.89 mug/100 g) while most fruits and vegetables have low levels (trace-3.27 mug/100 g). High selenium foods show the greatest level of geographical variation, with foods from the United States generally having higher selenium levels than Australian foods and foods from the United Kingdom and New Zealand having lower levels. This is the first attempt to review the available literature for selenium composition of Australian foods. These data serve as an interim measure for the assessment of selenium intake for use in epidemiological studies of diet-disease relationships. (C) 2002 Published by Elsevier Science Ltd.

Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration - data from Australia and the Netherlands

Back ground. Based on the well-described excess of schizophrenia births in winter and spring, we hypothesised that individuals with schizophrenia (a) would be more likely to be born during periods of decreased perinatal sunshine, and (b) those born during periods of less sunshine would have an earlier age of first registration. Methods. We undertook an ecological analysis of long-term trends in perinatal sunshine duration and schizophrenia birth rates based on two mental health registers (Queensland. Australia n = 6630; The Netherlands n = 24, 474). For each of the 480 months between 1931 and 1970, the agreement between slopes of the trends in psychosis and long-term sunshine duration series were assessed. Age at first registration was assessed by quartiles of long-term trends in perinatal sunshine duration, Males and females were assessed separately. Results. Both the Dutch and Australian data showed a statistically significant association between falling long-term trends in sunshine duration around the time of birth and rising schizophrenia birth rates for males only. In both the Dutch and Australian data there were significant associations between earlier age of first registration and reduced long-term trends in sunshine duration around the time of birth for both males and females, Conclusions. A measure of long-term trends in perinatal sunshine duration was associated with two epidemiological features of schizophrenia in two separate data sets. Exposures related to sunshine duration warrant further consideration in schizophrenia research. (C) 2002 Elsevier Science B.V. All rights reserved.

Towards a taxonomic revision of the genus Echinococcus

Echinococcus remains a significant public health problem worldwide and, in several regions, the aetiological agents of cystic hydatid disease/echinococcosis are extending their range. The taxonomy of Echinococcus has been a controversial issue for decades, but the outcome of recent molecular epidemiological studies has served to reinforce proposals made ten years ago to revise the taxonomy of Echinococcus. A formal nomenclature is essential for effective communication, and provides the stability that underpins epidemiological investigations. It will also serve to recognize the contribution of early taxonomists.

Immune correlate study on human Schistosoma japonicum in a well-defined population in Leyte, Philippines: I. Assessment of 'resistance' versus 'susceptibility' to S-japonicum infection

This study describes the categorical classification of 155 individuals living in an endemic village in Macanip, Leyte, Philippines as 'resistant' or 'susceptible' to Schistosoma japonicum infection using available exposure, infection and reinfection data collected from a 3-year water contact (WC) study. Epidemiological parameters including age, sex, and infection intensities in relation to observed reinfection patterns are also described. This classification was used in subsequent immunological studies described in two accompanying papers to identify protective immune mechanisms among resistant individuals induced by defined candidate vaccine molecules for S. japonicum. The study suggests that individuals who were most vulnerable to rapid reinfection were children belonging to the 5-14 age group. A drop in incidence at age group 15-19 and decreased intensity of infection starting at this age group and older (15+) suggests development of immunity. Controlling for the effect of the other variables, a multivariate analysis showed significant association for sex, in that females were more likely to be resistant. This implies that other than acquired immunity to infection, some age-dependent host factors may also play an important role in the overall changes of reinfection patterns seen in schistosomiasis japonica in this population. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

A rapid method for determining recent sunscreen use in field studies

The role of sunscreens in preventing skin cancer and melanoma is the focus of ongoing research. Currently, there is no objective measure which can be used in field studies to determine whether a person has applied sunscreen to their skin, and researchers must use indirect assessments such as questionnaires. We sought to develop a rapid, non-invasive method for identifying sunscreen on the skin for use in epidemiological studies. Our basic method is to swab the skin, elute any residues which have been adsorbed onto the swab by rinsing in ethanol, and submit the eluted washings for spectrophotometric analysis. In a controlled study, we applied 0.1 ml of sunscreen to a 50 cm(2) grid on both forearms of 21 volunteers. Each forearm was allocated one of 10 different sunscreen brands. The skin was swabbed after intervals of 20 min, 1 h, 2 h and 4 h. In a field study conducted among 12 children aged 2-4 years attending a child care centre, sunscreen was applied to the faces of half the children. Swabs were then taken from the face and back of all children without knowledge of sunscreen status. In the controlled study, sunscreen was clearly detectable up to 2 h after application for all brands containing organic sunscreen, and marginally detectable at 4 h. In the field study, this method correctly identified all children with and without sunscreen. We conclude that spectrophotometric analysis of skin swabs can reliably detect the presence of sunscreen on the skin for up to 2 It after application. (C) 2002 Elsevier Science B.V. All rights reserved.