Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

Molecular characterisation of environmental enterococci derived from water samples and assessment of associated public health hazards

Enterococci are versatile Gram-positive bacteria that can survive under extreme conditions. Most enterococci are non-virulent and found in the gastrointestinal tract of humans and animals. Other strains are opportunistic pathogens that contribute to a large number of nosocomial infections globally. Epidemiological studies demonstrated a direct relationship between the density of enterococci in surface waters and the risk of swimmer-associated gastroenteritis. The distribution of infectious enterococcal strains from the hospital environment or other sources to environmental water bodies through sewage discharge or other means, could increase the prevalence of these strains in the human population. Environmental water quality studies may benefit from focusing on a subset of Enterococcus spp. that are consistently associated with sources of faecal pollution such as domestic sewage, rather than testing for the entire genus. E. faecalis and E. faecium are potentially good focal species for such studies, as they have been consistently identified as the dominant Enterococcus spp. in human faeces and sewage. On the other hand enterococcal infections are predominantly caused by E. faecalis and E. faecium. The characterisation of E. faecalis and E. faecium is important in studying their population structures, particularly in environmental samples. In developing and implementing rapid, robust molecular genotyping techniques, it is possible to more accurately establish the relationship between human and environmental enterococci. Of particular importance, is to determine the distribution of high risk enterococcal clonal complexes, such as E. faecium clonal complex 17 and E. faecalis clonal complexes 2 and 9 in recreational waters. These clonal complexes are recognized as particularly pathogenic enterococcal genotypes that cause severe disease in humans globally. The Pimpama-Coomera watershed is located in South East Queensland, Australia and was investigated in this study mainly because it is used intensively for agriculture and recreational purposes and has a strong anthropogenic impact. The primary aim of this study was to develop novel, universally applicable, robust, rapid and cost effective genotyping methods which are likely to yield more definitive results for the routine monitoring of E. faecalis and E. faecium, particularly in environmental water sources. To fullfill this aim, new genotyping methods were developed based on the interrogation of highly informative single nucleotide polymorphisms (SNPs) located in housekeeping genes of both E. faecalis and E. faecium. SNP genotyping was successfully applied in field investigations of the Coomera watershed, South-East Queensland, Australia. E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles respectively. This study showed the high longitudinal diversity of E. faecalis and E. faecium over a period of two years, and both human-related and human-specific SNP profiles were identified. Furthermore, 4.25% of E. faecium strains isolated from water was found to correspond to the important clonal complex-17 (CC17). Strains that belong to CC17 cause the majority of hospital outbreaks and clinical infections globally. Of the six sampling sites of the Coomera River, Paradise Point had the highest number of human-related and human-specific E. faecalis and E. faecium SNP profiles. The secondary aim of this study was to determine the antibiotic-resistance profiles and virulence traits associated with environmental E. faecalis and E. faecium isolates compared to human pathogenic E. faecalis and E. faecium isolates. This was performed to predict the potential health risks associated with coming into contact with these strains in the Coomera watershed. In general, clinical isolates were found to be more resistant to all the antibiotics tested compared to water isolates and they harbored more virulence traits. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). However, tetracycline, gentamicin, ciprofloxacin and ampicillin resistance was observed in water isolates. The virulence gene esp was the most prevalent virulence determinant observed in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium), and this gene has been described as a human-specific marker used for microbial source tracking (MST). The presence of esp in water isolates (16.36% of E. faecalis and 19.14% of E. faecium) could be indicative of human faecal contamination in these waterways. Finally, in order to compare overall gene expression between environmental and clinical strains of E. faecalis, a comparative gene hybridization study was performed. The results of this investigation clearly demonstrated the up-regulation of genes associated with pathogenicity in E. faecalis isolated from water. The expression study was performed at physiological temperatures relative to ambient temperatures. The up-regulation of virulence genes demonstrates that environmental strains of E. faecalis can pose an increased health risk which can lead to serious disease, particularly if these strains belong to the virulent CC17 group. The genotyping techniques developed in this study not only provide a rapid, robust and highly discriminatory tool to characterize E. faecalis and E. faecium, but also enables the efficient identification of virulent enterococci that are distributed in environmental water sources.

A tissue engineering solution for segmental defect regeneration in load-bearing long bones

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

The applicability of aesthetic knowledge in organizational decision making processes

We argue that aesthetic knowledge, which is a form of tacit knowledge of beauty and related concepts, is an important, yet under-researched, topic in the study of organizational decision making processes. The significance of aesthetic knowledge for decision making processes is derived from its universal application by humans to commonplace practices; its use as the basis of decision criteria in complex situations to which the effective application of logic and reason is difficult; and its role both in assisting cognition in general and in enabling the choice of solutions generated from rational decision making processes. Despite its importance, the empirical research examining the application of aesthetic knowledge in organizational decision making processes is limited. Further detailed study of aesthetic knowledge in the context of organizational decision making processes is required to extend the recent movement in the field aimed at examining the role that extrarational, human-centered factors play in organizational decisions.

Isolation and functional characterisation of banana phytoene synthase genes as potential cisgenes

Carotenoids occur in all photosynthetic organisms where they protect photosystems from auto-oxidation, participate in photosynthetic energy-transfer and are secondary metabolites. Of the more than 600 known plant carotenoids, few can be converted into vitamin A by humans and so these pro-vitamin A carotenoids (pVAC) are important in human nutrition. Phytoene synthase (PSY) is a key enzyme in the biosynthetic pathway of pVACs and plays a central role in regulating pVAC accumulation in the edible portion of crop plants. Bananas are a major commercial crop and serve as a staple crop for more than 30 million people. There is natural variation in fruit pVAC content across different banana cultivars, but this is not well understood. Therefore, we isolated PSY genes from banana cultivars with relatively high (cv. Asupina) and low (cv. Cavendish) pVAC content. We provide evidence that PSY in banana is encoded by two paralogs (PSY1 and PSY2), each with a similar gene structure to homologous genes in other monocots. Further, we demonstrate that PSY2 is more highly expressed in fruit pulp compared to leaf. Functional analysis of PSY1 and PSY2 in rice callus and E. coli demonstrate that both genes encode functional enzymes, and that Asupina PSYs have approximately twice the enzymatic activity of the corresponding Cavendish PSYs. These results suggest that differences in PSY enzyme activity contribute significantly to the differences in Asupina and Cavendish fruit pVAC content. Importantly, Asupina PSY genes could potentially be used to generate new cisgenic or intragenic banana cultivars with enhanced pVAC content.

Bi-objective bundle adjustment: towards large-scale visual sea-floor mapping with a minimal sensor suite

Visual sea-floor mapping is a rapidly growing application for Autonomous Underwater Vehicles (AUVs). AUVs are well-suited to the task as they remove humans from a potentially dangerous environment, can reach depths human divers cannot, and are capable of long-term operation in adverse conditions. The output of sea-floor maps generated by AUVs has a number of applications in scientific monitoring: from classifying coral in high biological value sites to surveying sea sponges to evaluate marine environment health.

Towards spontaneous facial expression recognition in real-world video

Facial expression is an important channel of human social communication. Facial expression recognition (FER) aims to perceive and understand emotional states of humans based on information in the face. Building robust and high performance FER systems that can work in real-world video is still a challenging task, due to the various unpredictable facial variations and complicated exterior environmental conditions, as well as the difficulty of choosing a suitable type of feature descriptor for extracting discriminative facial information. Facial variations caused by factors such as pose, age, gender, race and occlusion, can exert profound influence on the robustness, while a suitable feature descriptor largely determines the performance. Most present attention on FER has been paid to addressing variations in pose and illumination. No approach has been reported on handling face localization errors and relatively few on overcoming facial occlusions, although the significant impact of these two variations on the performance has been proved and highlighted in many previous studies. Many texture and geometric features have been previously proposed for FER. However, few comparison studies have been conducted to explore the performance differences between different features and examine the performance improvement arisen from fusion of texture and geometry, especially on data with spontaneous emotions. The majority of existing approaches are evaluated on databases with posed or induced facial expressions collected in laboratory environments, whereas little attention has been paid on recognizing naturalistic facial expressions on real-world data. This thesis investigates techniques for building robust and high performance FER systems based on a number of established feature sets. It comprises of contributions towards three main objectives: (1) Robustness to face localization errors and facial occlusions. An approach is proposed to handle face localization errors and facial occlusions using Gabor based templates. Template extraction algorithms are designed to collect a pool of local template features and template matching is then performed to covert these templates into distances, which are robust to localization errors and occlusions. (2) Improvement of performance through feature comparison, selection and fusion. A comparative framework is presented to compare the performance between different features and different feature selection algorithms, and examine the performance improvement arising from fusion of texture and geometry. The framework is evaluated for both discrete and dimensional expression recognition on spontaneous data. (3) Evaluation of performance in the context of real-world applications. A system is selected and applied into discriminating posed versus spontaneous expressions and recognizing naturalistic facial expressions. A database is collected from real-world recordings and is used to explore feature differences between standard database images and real-world images, as well as between real-world images and real-world video frames. The performance evaluations are based on the JAFFE, CK, Feedtum, NVIE, Semaine and self-collected QUT databases. The results demonstrate high robustness of the proposed approach to the simulated localization errors and occlusions. Texture and geometry have different contributions to the performance of discrete and dimensional expression recognition, as well as posed versus spontaneous emotion discrimination. These investigations provide useful insights into enhancing robustness and achieving high performance of FER systems, and putting them into real-world applications.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.

A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics.

The idea that microbes induce disease has steered medical research toward the discovery of antibacterial products for the prevention and treatment of microbial infections. The twentieth century saw increasing dependency on antimicrobials as mainline therapy accentuating the notion that bacterial interactions with humans were to be avoided or desirably controlled. The last two decades, though, have seen a refocusing of thinking and research effort directed towards elucidating the critical inter-relationships between the gut microbiome and its host that control health/wellness or disease. This research has redefined the interactions between gut microbes and vertebrates, now recognizing that the microbial active cohort and its mammalian host have shared co-evolutionary metabolic interactions that span millennia. Microbial interactions in the gastrointestinal tract provide the necessary cues for the development of regulated pro- and anti-inflammatory signals that promotes immunological tolerance, metabolic regulation and other factors which may then control local and extra-intestinal inflammation. Pharmacobiotics, using nutritional and functional food additives to regulate the gut microbiome, will be an exciting growth area of therapeutics, developing alongside an increased scientific understanding of gut-microbiome symbiosis in health and disease.

Environmental rights or a right to the environment? Exploring the nexus between human rights and environmental protection.

The importance of the environment to the fulfilment of human rights is widely accepted at international law. What is less well-accepted is the proposition that we, as humans, possess rights to the environment beyond what is necessary to support our basic human needs. The suggestion that a human right to a healthy environment may be emerging at international law raises a number of theoretical and practical challenges for human rights law, with such challenges coming from both within and outside the human rights discourse. It is argued that human rights law can make a positive contribution to environmental protection, but the precise nature of the connection between the environment and human rights warrants more critical analysis. This short paper considers the different ways that the environment is conceptualised in international human rights law and analyses the proposition that a right to a healthy environment is emerging. It identifies some of the challenges which would need to be overcome before such a right could be recognised, including those which draw on the disciplines of deep ecology and earth jurisprudence.

The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations

Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression.

Wolbachia-mediated resistance to dengue virus infection and death at the cellular level

Dengue is currently the most important arthropod-borne viral disease of humans. Recent work has shown dengue virus displays limited replication in its primary vector, the mosquito Aedes aegypti, when the insect harbors the endosymbiotic bacterium Wolbachia pipientis. Wolbachia-mediated inhibition of virus replication may lead to novel methods of arboviral control, yet the functional and cellular mechanisms that underpin it are unknown.

Pregnancy losses in young Australian women : findings from the Australian Longitudinal Study on Women's Health

INTRODUCTION: Little research has examined recognized pregnancy losses in a general population. Data from an Australian cohort study provide an opportunity to quantify this aspect of fecundity at a population level. METHOD: Participants in the Australian Longitudinal Study on Women's Health who were aged 28-33 years in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants were categorized according to the recognized outcome of their pregnancies, including live birth, miscarriage/stillbirth, termination/ectopic, or no pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%) was as common as termination (16%). For women aged 28-33 years who had ever been pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss only (18%); and birth and loss (32%), of which half (16%) were birth and miscarriage. A comparison between first miscarriage and first birth (no miscarriage) showed that most first miscarriages occurred in women aged 18-23 years who also reported a first birth at the same survey (15%). Half (51%) of all first births and first miscarriages in women aged 18-19 ended in miscarriage. Early childbearers (<28 years) often had miscarriages around the same time period as their first live birth, suggesting proactive family formation. Delayed childbearers (32-33 years) had more first births than first miscarriages. CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in the general population because they indicate successful conception and maintenance of pregnancy to varying reproductive endpoints.

Infertility, medical advice and treatment with fertility hormones and/or in vitro fertilisation: a population perspective from the Australian Longitudinal Study on Women's Health

OBJECTIVE: To identify the factors associated with infertility, seeking advice and treatment with fertility hormones and/or in vitro fertilisation (IVF) among a general population of women. METHODS: Participants in the Australian Longitudinal Study on Women's Health aged 28-33 years in 2006 had completed up to four mailed surveys over 10 years (n=9,145). Parsimonious multivariate logistic regression was used to identify the socio-demographic, biological (including reproductive histories), and behavioural factors associated with infertility, advice and hormonal/IVF treatment. RESULTS: For women who had tried to conceive or had been pregnant (n=5,936), 17% reported infertility. Among women with infertility (n=1031), 72% (n=728) sought advice but only 50% (n=356) used hormonal/IVF treatment. Women had higher odds of infertility when: they had never been pregnant (OR=7.2, 95% CI 5.6-9.1) or had a history of miscarriage (OR range=1.5-4.0) than those who had given birth (and never had a miscarriage or termination). CONCLUSION: Only one-third of women with infertility used hormonal and/or IVF treatment. Women with PCOS or endometriosis were the most proactive in having sought advice and used hormonal/IVF treatment. IMPLICATIONS: Raised awareness of age-related declining fertility is important for partnered women aged approximately 30 years to encourage pregnancy during their prime reproductive years and reduce the risk of infertility.

Fear, voice, and the environment in Sonya Hartnett's Forerst and The Midnight Zoo

Subtle is not a word that is normally associated with Sonya Hartnett’s style. Rather, she is known for her stark, bold approach. However, when it comes to the Australian environment, Hartnett is indeed subtle in her approach. Hartnett has set in play a new, almost posthumanist style of writing about the nonhuman. The Australian landscape and environment has always figured prominently in Australian literature for both adults and children but Hartnett has taken this writing in a totally different direction. This article looks at two of Hartnett's novels, Forest and The Midnight Zoo, and examines how Hartnett offers new and exciting avenues of thought regarding the place of humans in that environment.