The identification of therapeutic targets in metastatic melanoma

Metastatic melanoma, a cancer historically refractory to chemotherapeutic strategies, has a poor prognosis and accounts for the majority of skin cancer related mortality. Although the recent approval of two new drugs combating this disease, Ipilimumab and Vemurafenib (PLX4032), has demonstrated for the first time in decades an improvement in overall survival; the clinical efficacy of these drugs has been marred by severe adverse immune reactions and acquired drug resistance in patients, respectively. Thus, understanding the etiology of metastatic melanoma will contribute to the improvement of current therapeutic strategies while leading to the development of novel drug approaches. In order to identify recurrently mutated genes of therapeutic relevance in metastatic melanoma, a panel of stage III local lymph node melanomas were extensively characterised using high-throughput genomic technologies. This led to the identification of mutations in TFG in 5% of melanomas from a candidate gene sequencing approach using SNP array analysis, 24% of melanomas with mutations in MAP3K5 or MAP3K9 though unbiased whole-exome sequencing strategies, and inactivating mutations in NF1 in BRAF/NRAS wild type tumours though pathway analysis. Lastly, this thesis describes the development of a melanoma specific mutation panel that can rapidly identify clinically relevant mutation profiles that could guide effective treatment strategies through a personalised therapeutic approach. These findings are discussed in respect to a number of important issues raised by this study including the current limitation of next-generation sequencing technology, the difficulty in identifying ‘driver’ mutations critical to the development of melanoma due to high carcinogenic exposure by UV radiation, and the ultimate application of mutation screening in a personalised therapeutic setting. In summary, a number novel genes involved in metastatic melanoma have been identified that may have relevance for current therapeutic strategies in treating this disease.

Incident investigation training needs for the Australasian rail industry

A core component for the prevention of re-occurring incidents within the rail industry is rail safety investigations. Within the current Australasian rail industry, the nature of incident investigations varies considerably between organisations. As it stands, most of the investigations are conducted by the various State Rail Operators and Regulators, with the more major investigations in Australia being conducted or overseen by the Australian Transport Safety Bureau (ATSB). Because of the varying nature of these investigations, the current training methods for rail incident investigators also vary widely. While there are several commonly accepted training courses available to investigators in Australasia, none appear to offer the breadth of development needed for a comprehensive pathway. Furthermore, it appears that no single training course covers the entire breadth of competencies required by the industry. These courses range in duration between a few days to several years, and some were run in-house while others are run by external consultants or registered training organisations. Through consultations with rail operators and regulators in Australasia, this paper will identify capabilities required for rail incident investigation and explore the current training options available for rail incident investigators.

A database for person re-identification in multi-camera surveillance networks

Person re-identification involves recognising individuals in different locations across a network of cameras and is a challenging task due to a large number of varying factors such as pose (both subject and camera) and ambient lighting conditions. Existing databases do not adequately capture these variations, making evaluations of proposed techniques difficult. In this paper, we present a new challenging multi-camera surveillance database designed for the task of person re-identification. This database consists of 150 unscripted sequences of subjects travelling in a building environment though up to eight camera views, appearing from various angles and in varying illumination conditions. A flexible XML-based evaluation protocol is provided to allow a highly configurable evaluation setup, enabling a variety of scenarios relating to pose and lighting conditions to be evaluated. A baseline person re-identification system consisting of colour, height and texture models is demonstrated on this database.

Queensland Emergency Medicine Research Foundation: Special report

The development of any new profession is dependent on the development of a special body of knowledge which is the domain of the profession and key to this is the conduct of research. In 2007, as part of the settlement of an Enterprise Bargaining Agreement and following sustained lobbying by Emergency Physicians, the Queensland Government agreed to establish an Emergency Medicine Research Fund to foster the development of research activities in Emergency Medicine in Queensland. That fund is now managed by the Queensland Emergency Medicine Research Foundation. The aims of this article are to describe the strategic approaches taken by the Foundation and its first three years of experience, to describe the application of research funds and to foreshadow an evaluative framework for determining the strategic value of this community investment. The Foundation has developed a range of personnel and project support funding programs and competition for funding has increased. Ongoing evaluation will seek to determine the effectiveness of this funding strategy on improving the effectiveness of research performance and the clinical and organisational outcomes that may derive from that initiative.

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.

Articulation in property programs : an international multi-campus tertiary model

This paper will present program developers and institutional administrators with a program delivery model suitable for cross cultural international delivery developing students from industry through to master’s level tertiary qualifications. The model was designed to meet the needs of property professionals from an industry where technical qualifications are the norm and tertiary qualifications are emerging. A further need was to develop and deliver a program that enhanced the University’s current program profile in both the domestic and international arenas. Early identification of international educational partners, industry need and the ability to service the program were vital to the successful development of Master of Property program. The educational foundations of the program rest in educational partners, local tutorial support, international course management, cultural awareness of and in content, online communication fora, with a delivery focus on problem-based learning, self-directed study, teamwork and the development of a global understanding and awareness of the international property markets. In enrolling students from a diverse cultural background with technical qualifications and/or extensive work experience there are a number of educational barriers to be overcome for all students to successfully progress and complete the program. These barriers disappear when the following mechanisms are employed: individual student pathways, tutorial support by qualified peers, enculturation into tertiary practice, assessment tasks that recognise cultural norms and values, and finally that value is placed on the experiential knowledge, cultural practices and belief systems of the students.

Preface to special issue on digital human modelling for vehicle design and manufacturing

The automotive industry has been the focus of digital human modeling (DHM) research and application for many years. In the highly competitive marketplace for personal transportation, the desire to improve the customer’s experience has driven extensive research in both the physical and cognitive interaction between the vehicle and its occupants. Human models provide vehicle designers with tools to view and analyze product interactions before the first prototypes are built, potentially improving the design while reducing cost and development time. The focus of DHM research and applications began with prediction and representation of static postures for purposes of driver workstation layout, including assessments of seat adjustment ranges and exterior vision. Now DHMs are used for seat design and assessment of driver reach and ingress/egress. DHMs and related simulation tools are expanding into the cognitive domain, with computational models of perception and motion, and into the dynamic domain with models of physical responses to ride and vibration. Moreover, DHMs are now widely used to analyze the ergonomics of vehicle assembly tasks. In this case, the analysis aims to determine whether workers can be expected to complete the tasks safely and with good quality. This preface provides a review of the literature to provide context for the nine new papers presented in this special issue.

The development of a supportive care needs assessment tool for Indigenous people with cancer

Background: Little is known about the supportive care needs of Indigenous people with cancer and to date, existing needs assessment tools have not considered cultural issues for this population. We aimed to adapt an existing supportive care needs assessment tool for use with Indigenous Australians with cancer. Methods: Face-to-face interviews with Indigenous cancer patients (n = 29) and five focus groups with Indigenous key-informants (n = 23) were conducted to assess the face and content validity, cultural acceptability, utility and relevance of the Supportive Care Needs Survey - Short Form 34 (SCNS-SF34) for use with Indigenous patients with cancer. Results: All items from the SCNS-SF34 were shortened and changed to use more appropriate language (e.g. the word 'anxiety' was substituted with 'worry'). Seven questions were omitted (e.g. items on death and future considerations) as they were deemed culturally inappropriate or irrelevant and 12 items were added (e.g. accessible transport). Optional instructions were added before the sexual items. The design and response format of the SCNS-SF34 was modified to make it easier to use for Indigenous cancer patients. Given the extensive modifications to the SCNS-SF34 and the liklihood of a different factor structure we consider this tool to be a new tool rather than a modification. The Supportive care needs assessment tool for Indigenous people (SCNAT-IP) shows promising face and content validity and will be useful in informing services where they need to direct their attention for these patients. Conclusions: Indigenous people with cancer have language, customs and specific needs that are not accommodated within the standard SCNS-SF34. Our SCNAT-IP improves acceptability, relevance and face validity for Indigenous-specific concerns. Our SCNAT-IP will allow screening for supportive care needs that are specific to Indigenous cancer patients' and greatly inform targeted policy development and practice.

Accident risk identification and its impact analyses for strategic construction safety management

The study presented in this paper reviewed 9,358 accidents which occurred in the U.S. construction industry between 2002 and 2011, in order to understand the relationships between the risk factors and injury severity (e.g. fatalities, hospitalized injuries, or non-hospitalized injuries) and to develop a strategic prevention plan to reduce the likelihood of fatalities where an accident is unavoidable. The study specifically aims to: (1) verify the relationships among risk factors, accident types, and injury severity, (2) determine significant risk factors associated with each accident type that are highly correlated to injury severity, and (3) analyze the impact of the identified key factors on accident and fatality occurrence. The analysis results explained that safety managers’ roles are critical to reducing human-related risks—particularly misjudgement of hazardous situations—through safety training and education, appropriate use of safety devices and proper safety inspection. However, for environment-related factors, the dominant risk factors were different depending on the different accident types. The outcomes of this study will assist safety managers to understand the nature of construction accidents and plan for strategic risk mitigation by prioritizing high frequency risk factors to effectively control accident occurrence and manage the likelihood of fatal injuries on construction sites.

Identification of long intergenic region sequences involved in maize streak virus replication

The main cis-acting control regions for replication of the single-stranded DNA genome of maize streak virus (MSV) are believed to reside within an approximately 310 nt long intergenic region (LIR). However, neither the minimum LIR sequence required nor the sequence determinants of replication specificity have been determined experimentally. There are iterated sequences, or iterons, both within the conserved inverted-repeat sequences with the potential to form a stem-loop structure at the origin of virion-strand replication, and upstream of the rep gene TATA box (the rep-proximal iteron or RPI). Based on experimental analyses of similar iterons in viruses from other geminivirus genera and their proximity to known Rep-binding sites in the distantly related mastrevirus wheat dwarf virus, it has been hypothesized that the iterons may be Rep-binding and/or -recognition sequences. Here, a series of LIR deletion mutants was used to define the upper bounds of the LIR sequence required for replication. After identifying MSV strains and distinct mastreviruses with incompatible replication-specificity determinants (RSDs), LIR chimaeras were used to map the primary MSV RSD to a 67 nt sequence containing the RPI. Although the results generally support the prevailing hypothesis that MSV iterons are functional analogues of those found in other geminivirus genera, it is demonstrated that neither the inverted-repeat nor RPI sequences are absolute determinants of replication specificity. Moreover, widely divergent mastreviruses can trans-replicate one another. These results also suggest that sequences in the 67 nt region surrounding the RPI interact in a sequence-specific manner with those of the inverted repeat.

International students using online information resources to learn : complex experience and learning needs

This paper reports the findings of a qualitative study which investigated 25 international students’ use of online information resources for study purposes at two Australian universities. Using an expanded critical incident approach, the study viewed international students through an information literacy lens, as information-using learners. The findings are presented in two complementary parts: as a word picture that describes their whole experience of using online information resources to learn; and as a tabulated set of critical findings that summarises their associated information literacy learning needs. The word picture shows international students’ resource use as a complex interplay of eight inter-related elements: students; information-learning environment; interactions (with online resources); strengths-challenges; learning-help; affective responses; reflective responses; cultural-linguistic dimensions. In using online resources, the international students experience an array of strengths and challenges, and an apparent information literacy imbalance between their more developed information skills and less developed critical information use. The critical findings about information literacy needs provide a framework for developing an inclusive informed learning approach that responds to international students’ complex information using experiences and needs. While the study is situated in Australia, the findings are of potential interest to educators, information professionals and researchers worldwide who seek to support learning in culturally diverse higher education contexts.

Ageing out of place: health and well-being needs and access to home and aged care services for recently arrived older refugees in Melbourne, Australia

Recently arrived older refugees in resettlement countries are a particularly vulnerable population who face many risks to their health and well-being, and many challenges in accessing services.This paper reports on a project undertaken in Victoria,Australia to explore the needs of older people from 14 recently arrived refugee communities, and the barriers to their receiving health and aged care. Findings from consultations with community workers and service providers highlight the key issues of isolation, family conflict and mental illness affecting older refugees, and point to ways in which policy-makers and service providers can better respond to these small but deserving communities.

Why do policy decision-makers opt for command and control environmental regulation? An economic analysis with special reference to Sri Lanka

This chapter examines why policy decision-makers opt for command and control environmental regulation despite the availability of a plethora of market-based instruments which are more efficient and cost-effective. Interestingly, Sri Lanka has adopted a wholly command and control system, during both the pre and post liberalisation economic policies. This chapter first examines the merits and demerits of command and control and market-based approaches and then looks at Sri Lanka’s extensive environmental regulatory framework. The chapter then examines the likely reasons as to why the country has gone down the path of inflexible regulatory measures and has become entrenched in them. The various hypotheses are discussed and empirical evidence is provided. The chapter also discusses the consequences of an environmentally slack economy and policy implications stemming from adopting a wholly regulatory approach. The chapter concludes with a discussion of the main results.

Identification of GABA receptors in chick cornea

Purpose: The cornea has an important role in vision, is highly innervated and many neurotransmitter receptors are present, e.g., muscarine, melatonin, and dopamine receptors. γ-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the retina and central nervous system, but it is unknown whether GABA receptors are present in cornea. The aim of this study was to determine if GABA receptors are located in chick cornea. Methods: Corneal tissues were collected from 25, 12-day-old chicks. Real time PCR, western blot, and immunohistochemistry were used to determine whether alpha1 GABAA, GABAB, and rho1 GABAC receptors were expressed and located in chick cornea. Results: Corneal tissue was positive for alpha1 GABAA and rho1 GABAC receptor mRNA (PCR) and protein (western blot) expression but was negative for GABAB receptor mRNA and protein. Alpha1 GABAA and rho1 GABAC receptor protein labeling was observed in the corneal epithelium using immunohistochemistry. Conclusions: These investigations clearly show that chick cornea possesses alpha1 GABAA, and rho1 GABAC receptors, but not GABAB receptors. The purpose of the alpha1 GABAA and rho1 GABAC receptors in cornea is a fascinating unexplored question.