The appearance of a second genotype of Japanese encephalitis virus in the Australasian region

In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Cidex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TSOO and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

The cloning and characterization of a second alpha-amylase of A-hydrophila JMP636

Aims: The aim of this study was to identify, clone and characterize the second amylase of Aeromonas hydrophila JMP636, AmyB, and to compare it to AmyA. Methods and Results: The amylase activity of A. hydrophila JMP636 is encoded by multiple genes. A second genetically distinct amylase gene, amyB, has been cloned and expressed from its own promoter in Escherichia coli. AmyB is a large alpha-amylase of 668 amino acids. Outside the conserved domains of alpha-amylases there is limited sequence relationship between the two alpha-amylases of A. hydrophila JMP636 AmyA and AmyB. Significant (80%) similarity exists between amyB and an alpha-amylase of A. hydrophila strain MCC-1. Differences in either the functional properties or activity under different environmental conditions as possible explanations for multiple copies of amylases in JMP636 is less likely after an examination of several physical properties, with each of the properties being very similar for both enzymes (optimal pH and temperature, heat instability). However the reaction end products and substrate specificity did vary enough to give a possible reason for the two enzymes being present. Both enzymes were confirmed to be alpha-type amylases. Conclusions: AmyB has been isolated, characterized and then compared to AmyA. Significance and Impact of Study: The amylase phenotype is rarely encoded by more than one enzyme within one strain, this study therefore allows the better understanding of the unusual amylase production by A. hydrophila.

Increase in prevalence of nosocomial non-Candida albicans candidaemia and the association of Candida krusei with fluconazole use

Candida is an important nosocomial pathogen. This study was undertaken to provide information on the rate of candidaemia, to define the risks for candidaemia and to describe and account for the epidemiology of candidaemia at our institution between 1992 and 1999. The overall rate was 0.052 per 1000 patient days and 0.27 per 1000 discharges. The major risks for candidaemia were colonization at a non-sterile site (OR 3.85, 95%CI 1.80-9.09), total parenteral nutrition (TPN) in the absence of neutropenia (OR 11.8, 95%CI 4.5-35.4, P

Thiazolidinediones and type 2 diabetes: new drugs for an old disease

Thiazolidinediones are a new class of drugs for the treatment of type 2 diabetes, and act by improving insulin sensitivity in adipose tissue, liver and skeletal muscle. Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin. There is level II evidence that in patients with inadequate glycaemic control both drugs reduce the level of HbA(1c) and fasting plasma glucose (FPG) when used as monotherapy and in combination with sulfonylurea or metformin or insulin; and both drugs increase levels of HDL and LDL and lower free fatty acid levels, but only pioglitazone significantly lowers triglyceride levels. Both drugs lower fasting insulin and C-peptide levels. In monotherapy, they may be slightly less potent at reducing the level of HbA(1c) than sulfonylureas or metformin. The maximal effect of these agents may not be seen for 6-14 weeks after commencement. Both drugs are well tolerated but liver function must be checked at baseline every second month for the first year, and periodically thereafter. The drugs are currently contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation and in children. The main side effects include weight gain, oedema, and mild dilutional anaemia.

CDT, GGT, and AST as markers of alcohol use: The WHO/ISBRA Collaborative Project

Background: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample. Methods: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS, CDT was assayed using CDTect(TM) and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance. Results: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status. Conclusions: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone, Test interpretation should take account sex, age. and body mass index.

Second primary oesophageal cancer following radiation for breast cancer

The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Does primary medical practitioner involvement with a specialist team improve patient outcomes? A systematic review.

Patients with chronic or complex medical or psychiatric conditions are treated by many practitioners, including general practitioners (GPs). Formal liaison between primary and specialist is often assumed to offer benefits to patients The aim of this study was to assess the efficacy of formal liaison of GPs with specialist service providers on patient health outcomes, by conducting a systematic review of the published literature in MEDLINE, EMBASE, PsychINFO, CINAHL and Cochrane Library databases using the following search terms family physicians': synonyms of 'patient care planning', 'patient discharge' and 'patient care team'; and synonyms of 'randomised controlled trials'. Seven studies were identified, involving 963 subjects and 899 controls. most health outcomes were unchanged, although some physical and functional health outcomes were improved by formal liaison between GPs and specialist services, particularly among chronic mental illness patients. Some health outcomes worsened during the intervention. Patient retention rates within treatment programmes improved with GP involvement, as did patient satisfaction. Doctor (GP and specialist) behaviour changed, with reports of more rational use of resources and diagnostic tests, improved clinical skills, more frequent use of appropriate treatment strategies, and more frequent clinical behaviours designed to detect disease complications Cost effectiveness could not be determined. In conclusion, formal liaison between GPs and specialist services leaves most physical health outcomes unchanged, but improves functional outcomes in chronically mentally ill patients. It may confer modest long-term health benefits through improvements in patient concordance with treatment programmes and more effective clinical practice.

Ross River virus disease in tropical Queensland: evolution of rheumatic manifestations in an inception cohort followed for six months

Objective: To describe the natural history of rheumatic manifestations of Ross River virus (RRV) disease. Design: Prospective longitudinal clinical review. Setting: North Queensland local government areas of Cairns, Douglas, Mareeba and Atherton during January to May 1998. Participants: General practice patients diagnosed with RRV disease on the basis of symptoms and a positive RRV IgM result. Main outcome measures: Rheumatic symptoms and signs assessed as soon as possible after disease onset and on two subsequent occasions (up to 6.5 months after onset). Results: 57 patients were recruited, 47 of whom were reviewed three times (at means of 1.1, 2.4 and 3.6 months after disease onset). Results are reported for these 47: 46 (98%) complained of joint pain at first review, with the ankles, wrists, fingers, knees and metacarpophalangeal joints (II-IV) most commonly involved. Prevalence of joint pain decreased progressively on second and third reviews, both overall (92% and 68% of patients, respectively), and in the five joints most commonly affected. The prevalence of other common rheumatic symptoms and signs, and use of non-steroidal anti-inflammatory drugs, also progressively declined over the three reviews. Conclusions: Earlier studies may have overestimated the prevalence and duration of symptoms in RRV disease. Progressive resolution over 3-6 months appears usual.

A probabilistic analysis of Clostridium perfringens growth during food service operations

The purpose of this study was threefold: first, the study was designed to illustrate the use of data and information collected in food safety surveys in a quantitative risk assessment. In this case, the focus was on the food service industry; however, similar data from other parts of the food chain could be similarly incorporated. The second objective was to quantitatively describe and better understand the role that the food service industry plays in the safety of food. The third objective was to illustrate the additional decision-making information that is available when uncertainty and variability are incorporated into the modelling of systems. (C) 2002 Elsevier Science B.V. All rights reserved.

Bridging the gap between different statistical approaches: An integrated framework for modelling

This paper proposes a template for modelling complex datasets that integrates traditional statistical modelling approaches with more recent advances in statistics and modelling through an exploratory framework. Our approach builds on the well-known and long standing traditional idea of 'good practice in statistics' by establishing a comprehensive framework for modelling that focuses on exploration, prediction, interpretation and reliability assessment, a relatively new idea that allows individual assessment of predictions. The integrated framework we present comprises two stages. The first involves the use of exploratory methods to help visually understand the data and identify a parsimonious set of explanatory variables. The second encompasses a two step modelling process, where the use of non-parametric methods such as decision trees and generalized additive models are promoted to identify important variables and their modelling relationship with the response before a final predictive model is considered. We focus on fitting the predictive model using parametric, non-parametric and Bayesian approaches. This paper is motivated by a medical problem where interest focuses on developing a risk stratification system for morbidity of 1,710 cardiac patients given a suite of demographic, clinical and preoperative variables. Although the methods we use are applied specifically to this case study, these methods can be applied across any field, irrespective of the type of response.

Determination of regional flow by use of intravascular PET tracers: Microvascular theory and experimental validation for pig livers

Today, the standard approach for the kinetic analysis of dynamic PET studies is compartment models, in which the tracer and its metabolites are confined to a few well-mixed compartments. We examine whether the standard model is suitable for modern PET data or whether theories including more physiologic realism can advance the interpretation of dynamic PET data. A more detailed microvascular theory is developed for intravascular tracers in single-capillary and multiple-capillary systems. The microvascular models, which account for concentration gradients in capillaries, are validated and compared with the standard model in a pig liver study. Methods: Eight pigs underwent a 5-min dynamic PET study after O-15-carbon monoxide inhalation. Throughout each experiment, hepatic arterial blood and portal venous blood were sampled, and flow was measured with transit-time flow meters. The hepatic dual-inlet concentration was calculated as the flow-weighted inlet concentration. Dynamic PET data were analyzed with a traditional single-compartment model and 2 microvascular models. Results: Microvascular models provided a better fit of the tissue activity of an intravascular tracer than did the compartment model. In particular, the early dynamic phase after a tracer bolus injection was much improved. The regional hepatic blood flow estimates provided by the microvascular models (1.3 +/- 0.3 mL min(-1) mL(-1) for the single-capillary model and 1.14 +/- 0.14 min(-1) mL(-1) for the multiple-capillary model) (mean +/- SEM mL of blood min(-1) mL of liver tissue(-1)) were in agreement with the total blood flow measured by flow meters and normalized to liver weight (1.03 +/- 0.12 mL min(-1) mL(-1)). Conclusion: Compared with the standard compartment model, the 2 microvascular models provide a superior description of tissue activity after an intravascular tracer bolus injection. The microvascular models include only parameters with a clear-cut physiologic interpretation and are applicable to capillary beds in any organ. In this study, the microvascular models were validated for the liver and provided quantitative regional flow estimates in agreement with flow measurements.

Escalation of Drug Use in Early-Onset Cannabis Users vs Co-twin Controls

Context Previous studies have reported that early initiation of cannabis (marijuana) use is a significant risk factor for other drug use and drug-related problems. Objective To examine whether the association between early cannabis use and subsequent progression to use of other drugs and drug abuse/dependence persists after controlling for genetic and shared environmental influences. Design Cross-sectional survey conducted in 1996-2000 among an Australian national volunteer sample of 311 young adult (median age, 30 years) monozygotic and dizygotic same-sex twin pairs discordant for early cannabis use (before age 17 years). Main Outcome Measures Self-reported subsequent nonmedical use of prescription sedatives, hallucinogens, cocaine/other stimulants, and opioids; abuse or dependence on these drugs (including cannabis abuse/dependence); and alcohol dependence. Results Individuals who used cannabis by age 17 years had odds of other drug use, alcohol dependence, and drug abuse/dependence that were 2.1 to 5.2 times higher than those of their co-twin, who did not use cannabis before age 17 years. Controlling for known risk factors (early-onset alcohol or tobacco use, parental conflict/separation, childhood sexual abuse, conduct disorder, major depression, and social anxiety) had only negligible effects on these results. These associations did not differ significantly between monozygotic and dizygotic twins. Conclusions Associations between early cannabis use and later drug use and abuse/dependence cannot solely be explained by common predisposing genetic or shared environmental factors. The association may arise from the effects of the peer and social context within which cannabis is used and obtained. In particular, early access to and use of cannabis may reduce perceived barriers against the use of other illegal drugs and provide access to these drugs.

Use of an accelerated chest pain assessment protocol in patients at intermediate risk of adverse cardiac events

Objective: To determine the feasibility, safety and effectiveness of a structured clinical pathway for stratification and management of patients presenting with chest pain and classified as having intermediate risk of adverse cardiac outcomes in the subsequent six months. Design: Prospective clinical audit. Participants and setting: 630 consecutive patients who presented to the emergency department of a metropolitan tertiary care hospital between January 2000 and June 2001 with chest pain and intermediate-risk features. Intervention: Use of the Accelerated Chest Pain Assessment Protocol (ACPAP), as advocated by the Management of unstable angina guidelines - 2000 from the National Heart Foundation and the Cardiac Society of Australia and New Zealand. Main outcome measure: Adverse cardiac events during six-month follow-up. Results: 409 patients (65%) were reclassified as low risk and discharged at a mean of 14 hours after assessment in the chest pain unit. None had missed myocardial infarctions, while three (1%) had cardiac events at six months (all elective revascularisation procedures, with no readmissions with acute coronary syndromes). Another 110 patients (17%) were reclassified as high risk, and 21 (19%) of these had cardiac events (mainly revascularisations) by six months. Patients who were unable to exercise or had non-diagnostic exercise stress test results (equivocal risk) had an intermediate cardiac event rate (8%). Conclusions: This study validates use of ACPAP. The protocol eliminated missed myocardial infarction; allowed early, safe discharge of low-risk patients; and led to early identification and management of high-risk patients.