Accelerated Partial Breast Irradiation (APBI) : a review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

Accurate urban road model reconstruction from high resolution remotely sensed imagery based on Support Vector Machine and Gabor filters

In this paper, we presented an automatic system for precise urban road model reconstruction based on aerial images with high spatial resolution. The proposed approach consists of two steps: i) road surface detection and ii) road pavement marking extraction. In the first step, support vector machine (SVM) was utilized to classify the images into two categories: road and non-road. In the second step, road lane markings are further extracted on the generated road surface based on 2D Gabor filters. The experiments using several pan-sharpened aerial images of Brisbane, Queensland have validated the proposed method.

Prevalence and determinants of the health promotion and risk reduction practices of younger female survivors of breast cancer

This thesis describes a discrete component of a larger mixed-method (survey and interview) study that explored the health-promotion and risk-reduction practices of younger premenopausal survivors of ovarian, breast and haematological cancers. This thesis outlines my distinct contribution to the larger study, which was to: (1) Produce a literature review that thoroughly explored all longer-term breast cancer treatment outcomes, and which outlined the health risks to survivors associated with these; (2) Describe and analyse the health-promotion and risk-reduction behaviours of nine younger female survivors of breast cancer as articulated in the qualitative interview dataset; and (3) Test the explanatory power of the Precede-Proceed theoretical framework underpinning the study in relation to the qualitative data from the breast cancer cohort. The thesis reveals that breast cancer survivors experienced many adverse outcomes as a result of treatment. While they generally engaged in healthy lifestyle practices, a lack of knowledge about many recommended health behaviours emerged throughout the interviews. The participants also described significant internal and external pressures to behave in certain ways because of the social norms surrounding the disease. This thesis also reports that the Precede-Proceed model is a generally robust approach to data collection, analysis and interpretation in the context of breast cancer survivorship. It provided plausible explanations for much of the data in this study. However, profound sociological and psychological implications arose during the analysis that were not effectively captured or explained by the theories underpinning the model. A sociological filter—such as Turner’s explanation of the meaning of the body and embodiment in the social sphere (Turner, 2008)—and the psychological concerns teased out in Mishel’s (1990) Uncertainty in Illness Theory, provided a useful dimension to the findings generated through the Precede-Proceed model. The thesis concludes with several recommendations for future research, clinical practice and education in this context.

Vision only pose estimation and scene reconstruction on airborne platforms

We aim to demonstrate unaided visual 3D pose estimation and map reconstruction using both monocular and stereo vision techniques. To date, our work has focused on collecting data from Unmanned Aerial Vehicles, which generates a number of significant issues specific to the application. Such issues include scene reconstruction degeneracy from planar data, poor structure initialisation for monocular schemes and difficult 3D reconstruction due to high feature covariance. Most modern Visual Odometry (VO) and related SLAM systems make use of a number of sensors to inform pose and map generation, including laser range-finders, radar, inertial units and vision [1]. By fusing sensor inputs, the advantages and deficiencies of each sensor type can be handled in an efficient manner. However, many of these sensors are costly and each adds to the complexity of such robotic systems. With continual advances in the abilities, small size, passivity and low cost of visual sensors along with the dense, information rich data that they provide our research focuses on the use of unaided vision to generate pose estimates and maps from robotic platforms. We propose that highly accurate (�5cm) dense 3D reconstructions of large scale environments can be obtained in addition to the localisation of the platform described in other work [2]. Using images taken from cameras, our algorithm simultaneously generates an initial visual odometry estimate and scene reconstruction from visible features, then passes this estimate to a bundle-adjustment routine to optimise the solution. From this optimised scene structure and the original images, we aim to create a detailed, textured reconstruction of the scene. By applying such techniques to a unique airborne scenario, we hope to expose new robotic applications of SLAM techniques. The ability to obtain highly accurate 3D measurements of an environment at a low cost is critical in a number of agricultural and urban monitoring situations. We focus on cameras as such sensors are small, cheap and light-weight and can therefore be deployed in smaller aerial vehicles. This, coupled with the ability of small aerial vehicles to fly near to the ground in a controlled fashion, will assist in increasing the effective resolution of the reconstructed maps.

Persistent ocean monitoring with underwater gliders : towards accurate reconstruction of dynamic ocean processes

Ocean processes are dynamic and complex events that occur on multiple different spatial and temporal scales. To obtain a synoptic view of such events, ocean scientists focus on the collection of long-term time series data sets. Generally, these time series measurements are continually provided in real or near-real time by fixed sensors, e.g., buoys and moorings. In recent years, an increase in the utilization of mobile sensor platforms, e.g., Autonomous Underwater Vehicles, has been seen to enable dynamic acquisition of time series data sets. However, these mobile assets are not utilized to their full capabilities, generally only performing repeated transects or user-defined patrolling loops. Here, we provide an extension to repeated patrolling of a designated area. Our algorithms provide the ability to adapt a standard mission to increase information gain in areas of greater scientific interest. By implementing a velocity control optimization along the predefined path, we are able to increase or decrease spatiotemporal sampling resolution to satisfy the sampling requirements necessary to properly resolve an oceanic phenomenon. We present a path planning algorithm that defines a sampling path, which is optimized for repeatability. This is followed by the derivation of a velocity controller that defines how the vehicle traverses the given path. The application of these tools is motivated by an ongoing research effort to understand the oceanic region off the coast of Los Angeles, California. The computed paths are implemented with the computed velocities onto autonomous vehicles for data collection during sea trials. Results from this data collection are presented and compared for analysis of the proposed technique.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Design and implementation of the Exercise for Health trial – a pragmatic exercise intervention for women with breast cancer

Background Exercise for Health was a pragmatic, randomised, controlled trial comparing the effect of an eight-month exercise intervention on function, treatment-related side effects and quality of life following breast cancer, compared with usual care. The intervention commenced six weeks post-surgery, and two modes of delivering the same intervention was compared with usual care. The purpose of this paper is to describe the study design, along with outcomes related to recruitment, retention and representativeness, and intervention participation. Methods: Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensland, Australia, were eligible to participate. Consenting women were randomised to a face-to-face-delivered exercise group (FtF, n=67), telephone-delivered exercise group (Tel, n=67) or usual care group (UC, n=60) and were assessed pre-intervention (5-weeks post-surgery), mid-intervention (6 months post-surgery) and 10 weeks post-intervention (12 months post-surgery). Each intervention arm entailed 16 sessions with an Exercise Physiologist. Results: Of 318 potentially eligible women, 63% (n=200) agreed to participate, with a 12-month retention rate of 93%. Participants were similar to the Queensland breast cancer population with respect to disease characteristics, and the randomisation procedure was mostly successful at attaining group balance, with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics. Median participation was 14 (min, max: 0, 16) and 13 (min, max: 3, 16) intervention sessions for the FtF and Tel, respectively, with 68% of those in Tel and 82% in FtF participating in at least 75% of sessions. Discussion: Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women. Future work, designed to inform translation into practice, will evaluate the quality of life, clinical, psychosocial and behavioural outcomes associated with each mode of delivery.

Post-disaster housing reconstruction : challenges for community participation

The extant literature suggests that community participation is an important ingredient for the successful delivery of post-disaster housing reconstruction projects. Even though policy-makers, international funding bodies and non-governmental organisations broadly appreciate the value of community participation, post-disaster reconstruction practices systematically fail to follow, or align with, existing policy statements. Research into past experiences has led many authors to argue that post-disaster reconstruction is the least successful physically visible arena of international cooperation. Why is the principle of community participation not evident in the veracity of reconstructions already carried out on the ground? This paper discusses and develops the concepts of, and challenges to, community participation and the subsequent negative and positive effects on post-disaster reconstruction projects outcomes.

Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.

Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR

Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.