Contextualising merit and integrity within human research

The first consideration of any Australian Human Research Ethics Committee should be to satisfy itself that the project before them is worth undertaking. If the project does not add to the body of knowledge, if it does not improve social welfare or individual wellbeing then the use of human participants, their tissue or their data must be questioned. Sometimes, however, committees are criticised for appearing to adopt the role of scientific review committees. The intent of this paper is to provide researchers with an understanding of the ethical importance of demonstrating the merit of their research project and to help them develop protocols that show ethics committees that adequate attention has been paid to this central tenet in dealing ethically with human research participants. Any person proposing human research must be prepared to show that it is worthwhile. This paper will clarify the relationship between research merit and integrity, research ethics and the responsibilities of human research ethics committees.

Tissue engineering of a morphologically and functionally intact humanized bone organ for bone metastasis research

The aim of this thesis was to establish an individualized, patient-specific diagnostic and therapeutic preclinical disease model for bone metastasis research. Tissue engineering of humanized bone within mice allowed the development of a humanized immune system in the host animal. This novel platform makes it possible to analyze the growth of human cancer cells in human bone in the presence of human immune cells.

Comparison of human and animal Chlamydia pneumoniae responses to interferon gamma and penicillin treatment

This thesis has made a significant contribution to future chlamydial research by uncovering the chlamydial pathogenic mechanisms which will potentially help in the development of targeted vaccine against the pathogen. This thesis has made important new contributions to our understanding of Chlamydia pneumoniae specific adaptations to stress responses and has provided new perspectives on the survival of this successful pathogen. This thesis has used two well established microbial stressors and has identified major differences in stress responses between human and animal Chlamydia pneumoniae isolates.

A Comparison of Methods for Describing Irregular Animal Growth and Testing for Treatment Effects

In many designed experiments with animals liveweight is recorded several times during the trial. Such data are commonly referred to as repeated measures data. An aim of such experiments is generally to compare the growth patterns for the applied treatments. This paper discusses some of the methods of analysing repeated measures data and illustrates the use of cubic smoothing splines to describe irregular cattle growth data. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Effect of an interactive therapeutic robotic animal on engagement, mood states, agitation and psychotropic drug use in people with dementia: A cluster-randomised controlled trial protocol

Introduction: Apathy, agitated behaviours, loneliness and depression are common consequences of dementia. This trial aims to evaluate the effect of a robotic animal on behavioural and psychological symptoms of dementia in people with dementia living in long-term aged care. Methods and analysis: A cluster-randomised controlled trial with three treatment groups: PARO (robotic animal), Plush-Toy (non-robotic PARO) or Usual Care (Control). The nursing home sites are Australian Government approved and accredited facilities of 60 or more beds. The sites are located in South-East Queensland, Australia. A sample of 380 adults with a diagnosis of dementia, aged 60 years or older living in one of the participating facilities will be recruited. The intervention consists of three individual 15 min non-facilitated sessions with PARO or Plush- Toy per week, for a period of 10 weeks. The primary outcomes of interest are improvement in agitation, mood states and engagement. Secondary outcomes include sleep duration, step count, change in psychotropic medication use, change in treatment costs, and staff and family perceptions of PARO or Plush-Toy. Video data will be analysed using Noldus XT Pocket Observer; descriptive statistics will be used for participants’ demographics and outcome measures; cluster and individual level analyses to test all hypotheses and Generalised Linear Models for cluster level and Generalised Estimation Equations and/or Multi-level Modeling for individual level data. Ethics and dissemination: The study participants or their proxy will provide written informed consent. The Griffith University Human Research Ethics Committee has approved the study (NRS/03/14/HREC). The results of the study will provide evidence of the efficacy of a robotic animal as a psychosocial treatment for the behavioural and psychological symptoms of dementia. Findings will be presented at local and international conference meetings and published in peer-reviewed journals.

The influence of animal mobility on the assumption of uniform distances in aerial line-transect surveys

Line-transect distance sampling is a widely used method for estimating animal density from aerial surveys. Analysis of line-transect distance data usually relies on a requirement that the statistical distribution of distances of animal groups from the transect line is uniform. We show that this requirement is satisfied by the survey design if all other assumptions of distance sampling hold, but it can be violated by consistent survey problems such as responsive movement of the animals towards or away from the observer. We hypothesise that problems with the uniform requirement are unlikely to be encountered for immobile taxa, but might become substantial for species of high mobility. We test evidence for non-uniformity using double-observer distance data from two aerial surveys of five species with a spectrum of mobility capabilities and tendencies. No clear evidence against uniformity was found for crabeater seals or emperor penguins on the pack-ice in East Antarctica, while minor non-uniformity consistent with responsive movement up to 30 m was found for Adelie penguins. Strong evidence of either non-uniformity or a failure of the capture-recapture validating method was found for eastern grey kangaroos and red kangaroos in Queensland.

Management of mould mite Tyrophagus putrescentiae (Schrank) (Acarina: Acaridae): A case study in stored animal feed

An integrated pest management (IPM) strategy was developed to manage infestations of mould mite Tyrophagus putrescentiae (Schrank) in stored animal feed, due to the increasing importance of these mites as pests of feed processing and storage facilities in Australia. This strategy involved several aspects such as limiting the moisture content of the processed feed to 12%, admixing vegetable oil to some feed (2% w/w), strict hygiene practice in and around the processing and storage facility, and rejection of infested grain at the receiving point. Additionally, seven contact insecticides and the fumigant phosphine were evaluated for their effectiveness against the mould mite to assess their potential integration into the IPM strategy. Among them, pyrethrin synergised with piperonyl butoxide, the insect growth regulator s-methoprene and a newly developed bacterium-based material spinosad controlled the mites. Moreover, the fumigant phosphine at 1 mg/litre over a six days exposure period also controlled these mites. So far, the IPM strategy, without any involvement of insecticides or fumigant has resulted in a complete eradication of the mite population in this particular case of stored animal feed.

A strategic approach to mitigating the impacts of wild canids: proposed activities of the Invasive Animals Cooperative Research Centre

Wild canids (wild dogs and European red foxes) cause substantial losses to Australian livestock industries and environmental values. Both species are actively managed as pests to livestock production. Contemporaneously, the dingo proportion of the wild dog population, being considered native, is protected in areas designated for wildlife conservation. Wild dogs particularly affect sheep and goat production because of the behavioural responses of domestic sheep and goats to attack, and the flexible hunting tactics of wild dogs. Predation of calves, although less common, is now more economically important because of recent changes in commodity prices. Although sometimes affecting lambing and kidding rates, foxes cause fewer problems to livestock producers but have substantial impacts on environmental values, affecting the survival of small to medium-sized native fauna and affecting plant biodiversity by spreading weeds. Canid management in Australia relies heavily on the use of compound 1080-poisoned baits that can be applied aerially or by ground. Exclusion fencing, trapping, shooting, livestock-guarding animals and predator calling with shooting are also used. The new Invasive Animals Cooperative Research Centre has 40 partners representing private and public land managers, universities, and training, research and development organisations. One of the major objectives of the new IACRC is to apply a strategic approach in order to reduce the impacts of wild canids on agricultural and environmental values in Australia by 10%. In this paper, the impacts, ecology and management of wild canids in Australia are briefly reviewed and the first cooperative projects that will address IACRC objectives for improving wild dog management are outlined.

Male traits and herd reproductive capability in tropical beef cattle. 1. Experimental design and animal measures

Research into the genetics of whole herd profitability has been a focus of the Beef Cooperative Research Centre for Beef Genetic Technologies over the past decade and it has been identified that measures of male reproduction may offer a potential indirect means of selecting for improved female reproduction. This paper describes the experimental design and provides a descriptive analysis of an array of male traits in Brahman and Tropical Composite genotypes managed under the medium to high stress, semi-extensive to extensive production systems of northern Australia. A total of 1639 Brahman and 2424 Tropical Composite bulls with known pedigrees, bred and raised in northern Australia, were evaluated for a comprehensive range of productive and reproductive traits. These included blood hormonal traits (luteinising hormone, inhibin and insulin-like growth factor-I); growth and carcass traits (liveweight, body condition score, ultrasound scanned 12-13th rib fat, rump P8 fat, eye muscle area and hip height); adaptation traits (flight time and rectal temperature); and a bull breeding soundness evaluation (leg and hoof conformation, sheath score, length of everted prepuce, penile anatomy, scrotal circumference, semen mass activity, sperm motility and sperm morphology). Large phenotypic variation was evident for most traits, with complete overlap between genotypes, indicating that there is likely to be a significant opportunity to improve bull fertility traits through management and bull selection.

Food-borne pathogens - a key issue for all food animal industries

The modern consumer has an attitude that food safety is non-negotiable issue – the consumer simply demands food to be safe. Yet, at the same time, the modern consumer has an expectation that the food safety is the responsibility of others – the primary producer, the processing company, the supermarket, commercial food handlers and so on. Given this environment, all food animal industries have little choice but to regard food safety as a key issue. As an example, the chicken meat industry, via the two main industry funding bodies – the Rural Industries Research and Development Corporation (Chicken Meat) and the Poultry CRC – has a comprehensive research program that seeks to focus on reducing the risks of food-borne diseases at all points of the food processing chain – from the farm to the processing plant. The scale of the issue for all industries can be illustrated by an analysis of the problem of campylobacterosis – a major food-borne disease. It has been estimated that there are around 230,000 cases of campylobacterosis per year. In 1995, it was estimated that each case of food-borne campylobacterosis in the USA was costing between $(US) 350-580. Hence, a reasonable conservative estimate is that each Australian case in 2010 would result in a cost of around $500 (this includes hospital, medication and lost productivity costs). Hence, this single food-borne agent could be costing Australian society around $115 million annually. In the light of these types of estimated costs for just one food-borne pathogen, it is easy to understand the importance that all food animal industries place on food safety.

The application of one health approaches to henipavirus research

Henipaviruses cause fatal infection in humans and domestic animals. Transmission from fruit bats, the wildlife reservoirs of henipaviruses, is putatively driven (at least in part) by anthropogenic changes that alter host ecology. Human and domestic animal fatalities occur regularly in Asia and Australia, but recent findings suggest henipaviruses are present in bats across the Old World tropics. We review the application of the One Health approach to henipavirus research in three locations: Australia, Malaysia and Bangladesh. We propose that by recognising and addressing the complex interaction among human, domestic animal and wildlife systems, research within the One Health paradigm will be more successful in mitigating future human and domestic animal deaths from henipavirus infection than alternative single-discipline approaches. © Springer-Verlag Berlin Heidelberg 2013.

Evaluation and histological examination of a Campylobacter fetus subsp. venerealis small animal infection model

Bovine genital campylobacteriosis (BGC), caused by Campylobacter fetus subsp. venerealis, is associated with production losses in cattle worldwide. This study aimed to develop a reliable BGC guinea pig model to facilitate future studies of pathogenicity, abortion mechanisms and vaccine efficacy. Seven groups of five pregnant guinea pigs (1 control per group) were inoculated with one of three strains via intra-peritoneal (IP) or intra-vaginal routes. Samples were examined using culture, PCR and histology. Abortions ranged from 0 to 100 and re-isolation of causative bacteria from sampled sites varied with strain, dose of bacteria and time to abortion. Histology indicated metritis and placentitis, suggesting that the bacteria induce inflammation, placental detachment and subsequent abortion. Variation of virulence between strains was observed and determined by culture and abortion rates. IP administration of C. fetus subsp. venerealis to pregnant guinea pigs is a promising small animal model for the investigation of BGC abortion.

Probiotics modify tight junction proteins in an animal model of non-alcoholic fatty liver disease

Objectives We have investigated the effects of a multi–species probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high fat diet/obesity induced liver steatosis. Methods Three groups of C57B1/6J mice were fed either a standard chow or a high fat diet for 20 weeks, while a third group was fed a high fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks. Serum, liver and large bowel samples were collected for analysis. Results The expression of the tight junction proteins ZO-1 and ZO-2 was reduced (p < 0.05) in high fat diet fed mice compared to chow fed mice. Probiotic supplementation helped to maintain tight ZO-1 and ZO-2 expression compared with the high fat diet group (p < 0.05), but did not restore ZO-1 or ZO-2 expression compared with chow fed mice. Mice fed a high fat diet ± probiotics had significant steatosis development compared to chow fed mice (p < 0.05); steatosis was less severe in the probiotics group compared to the high fat diet group. Hepatic triglycerides concentration was higher in mice fed a high fat diet ± probiotics compared to the chow group (p < 0.05), and was lower in the probiotics group compared to the high fat diet group (p < 0.05). Compared to chow fed mice, serum glucose and cholesterol concentrations, and the activity of alanine transaminase were higher (p < 0.05), whereas serum triglyceride concentration was lower (p < 0.05) in mice fed a high fat diet ± probiotics. Conclusions Supplementation with a multi-species probiotic formulation helped to maintain tight junction proteins ZO-1 and ZO-2, and reduced hepatic triglyceride concentrations compared with a HFD alone.

Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.