Description:
In this paper global optimisation-based techniques are studied in order to increase the accuracy of medical diagnosis and prognosis with FNA image data from the Wisconsin Diagnostic and Prognostic Breast Cancer databases. First we discuss the problem of determining the most informative features for the classification of cancerous cases in the databases under consideration. Then we apply a technique based on convex and global optimisation to breast cancer diagnosis. It allows the classification of benign cases and malignant ones and the subsequent diagnosis of patients with very high accuracy. The third application of this technique is a method that calculates centres of clusters to predict when breast cancer is likely to recur in patients for which cancer has been removed. The technique achieves higher accuracy with these databases than reported elsewhere in the literature.
Description:
In this paper global optimisation-based techniques are studied in order to increase the accuracy of medical diagnosis and prognosis with FNA image data from the Wisconsin Diagnostic and Prognostic Breast Cancer databases. First we discuss the problem of determining the most informative features for the classification of cancerous cases in the databases under consideration. Then we apply a technique based on convex and global optimisation to breast cancer diagnosis. It allows the classification of benign cases and malignant ones and the subsequent diagnosis of patients with very high accuracy. The third application of this technique is a method that calculates centres of clusters to predict when breast cancer is likely to recur in patients for which cancer has been removed. The technique achieves higher accuracy with these databases than reported elsewhere in the literature.
Description:
For risk analysis of reclaimed water, current animal and toxicity testing may not detect subtle effects such as interactions that could contribute to complex diseases such as cancers that develop over a long period of time. There is a need for assays that can be validated against known human physiological processes. We have previously validated sensitive human cell culture assays for their responsiveness to agents that induce carcinogenesis in vivo. In this initial study we analysed the effects of three batches of reclaimed water on human colonic cells. At concentrations of up to 10-fold, they had no significant effect on the cellular markers, indicating an overall lack of biological activity. The assay has potential but needs to be refined to maximise its sensitivity.
Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
Literature attests to the fact that psychosocial needs for cancer patients are not being adequately addressed. The tools, frameworks and guidelines developed, reflect differing professional perspectives and models of disease. Most studies have usually looked at what is happening from the patient and family's viewpoint in terms of medical and other needs. New national initiatives in psychosocial care include the organisation of nationwide practitioner workshops to encourage the implementation of the Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer. These guidelines focus mainly on the emotional and existential areas of need. The aim of this study was to: understand how a diversity of approaches and professional perspectives play out in everyday practice within a rural context; see how issues of distance and access affect this process; and highlight the deficiencies in the delivery of psychosocial services for cancer patients in rural Victoria. The study involved 59 questionnaire respondents (a 71% response rate), from which two interviews and six focus group discussions were drawn. Key findings were: regional and metropolitan hospitals and specialists not referring for support services; private patients missing out; general practitioners not referring to support services; late referrals to palliative care and district nursing; haphazard continuity of care for support needs of patients; and disputed responsibility for initial assessment.
Description:
Soil and mine waste around historical gold mining sites may have elevated arsenic concentrations. Recent evidence suggests some systemic arsenic absorption by residents in the goldfields region of Victoria, Australia. Victorian Cancer Registry and geochemical data were accessed for an ecological geographical correlation study, 1984-2003. Spatial empirical Bayes smoothing was applied when estimating standardised incidence ratios (SIRs) for cancers in 61 statistical local areas. The derived soil arsenic exposure metric ranged from 1.4 to 1857 mg/kg. Spatial autoregressive modelling detected increases in smoothed SIRs for all cancers of 0.05 (95% confidence interval (CI), 0.02-0.08) and 0.04 (0.01-0.07) per 2.7-fold increase in the natural log-transformed exposure metric for males and females, respectively, in more socioeconomically disadvantaged areas; for melanoma in males (0.05 (0.01-0.08) adjusted for disadvantage) and females (0.05 (0.02-0.09) in disadvantaged areas). Excess risks were estimated for all cancers (relative risk 1.21 (95% CI, 1.15-1.27) and 1.08 (1.03-1.14)), and melanoma (1.52 (1.25-1.85) and 1.29 (1.08-1.55)), for males and females, respectively, in disadvantaged areas in the highest quintile of the exposure metric relative to the lowest. Our findings suggest small but significant increases in past cancer risk associated with increasing soil arsenic in socioeconomically disadvantaged areas and demonstrate the robustness of this geospatial approach. Journal of Exposure Science and Environmental Epidemiology advance online publication, 21 March 2012.
Description:
Soil and mine waste around historical gold mining sites may have elevated arsenic concentrations. Recent evidence suggests some systemic arsenic absorption by residents in the goldfields region of Victoria, Australia. Victorian Cancer Registry and geochemical data were accessed for an ecological geographical correlation study, 1984-2003. Spatial empirical Bayes smoothing was applied when estimating standardised incidence ratios (SIRs) for cancers in 61 statistical local areas. The derived soil arsenic exposure metric ranged from 1.4 to 1857 mg/kg. Spatial autoregressive modelling detected increases in smoothed SIRs for all cancers of 0.05 (95% confidence interval (CI), 0.02-0.08) and 0.04 (0.01-0.07) per 2.7-fold increase in the natural log-transformed exposure metric for males and females, respectively, in more socioeconomically disadvantaged areas; for melanoma in males (0.05 (0.01-0.08) adjusted for disadvantage) and females (0.05 (0.02-0.09) in disadvantaged areas). Excess risks were estimated for all cancers (relative risk 1.21 (95% CI, 1.15-1.27) and 1.08 (1.03-1.14)), and melanoma (1.52 (1.25-1.85) and 1.29 (1.08-1.55)), for males and females, respectively, in disadvantaged areas in the highest quintile of the exposure metric relative to the lowest. Our findings suggest small but significant increases in past cancer risk associated with increasing soil arsenic in socioeconomically disadvantaged areas and demonstrate the robustness of this geospatial approach. Journal of Exposure Science and Environmental Epidemiology advance online publication, 21 March 2012.
Description:
In pattern recognition problems features plays an important role for classification results. It is very important which features are used and how many features are used for the classification process. Most of the real life classification problem uses different category of features. It is desirable to find the optimal combination of features that improves the performance of the classifier. There exists different selection framework that selects the features. Mostly do not incorporate the impact of one category of features on another. Even if they incorporate, they produce conflict between the categories. In this paper we proposed a restricted crossover selection framework which incorporate the impact of different categories on each other, as well as it restricts the search within the category which searching in the global region of the search space. The results obtained by the proposed framework are promising.
Description:
In pattern recognition problems features plays an important role for classification results. It is very important which features are used and how many features are used for the classification process. Most of the real life classification problem uses different category of features. It is desirable to find the optimal combination of features that improves the performance of the classifier. There exists different selection framework that selects the features. Mostly do not incorporate the impact of one category of features on another. Even if they incorporate, they produce conflict between the categories. In this paper we proposed a restricted crossover selection framework which incorporate the impact of different categories on each other, as well as it restricts the search within the category which searching in the global region of the search space. The results obtained by the proposed framework are promising.
Description:
Lung cancer is the leading cause of cancer deaths. Unfortunately, lung cancer is often diagnosed only when it becomes symptomatic or at an advanced stage when few treatment options are available. Hence, a diagnostic test suitable for screening widespread populations is required to enable earlier diagnosis. Analysis of exhaled breath provides a non-invasive method for early detection of lung cancer. Analysis of volatile organic compounds (VOCs) by various mass spectral techniques has identified potential biomarkers of disease. Nevertheless, the metabolic origins and the disease specificity of VOCs need further elucidation. Cell culture metabolomics can be used as a bottom-up approach to identify biomarkers of pathological conditions and can also be used to study the metabolic pathways that produce such compounds. This paper summarizes the current knowledge of lung cancer biomarkers in exhaled breath and emphasizes the critical role of cell culture conditions in determining the VOCs produced in vitro. Hypoxic culture conditions more closely mimic the conditions of cancer cell growth in vivo. We propose that since hypoxia influences cell metabolism and so potentially the VOCs that the cancer cells produce, the cell culture metabolomics projects should consider culturing cancer cells in hypoxic conditions.
Description:
Innate-like T cells, including invariant natural killer T (NKT), mucosal associated invariant T (MAIT) cells or g T cells are associated with regulation of anti-tumour responses in humans and mice, although their exact role remains controversial. We have studied innate-like T cells from tumour infiltrating lymphocytes (TILS), peripheral blood mononuclear cells (PBMCs) and bone marrow (BM) derived cells from patients undergoing treatment for cancer and compared their characteristics to cells from healthy donors. We identifed that the overall frequency of innate-like T cells was variably deficient in patients with blood or solid cancers. Interestingly, the deficiency of innate-like T cells appeared to be more severe than that of other T cells suggesting a specific impact. An increased proportion of activated g T cells and MAIT cells suggested they could have a functional role in responses to cancer cells. Despite the deficiency of these subsets in patient tissue samples, we showed that anti-tumour capacity of innate-like T cells was intact as innate-like T cells in most patient groups had a similar cytokine response to stimulation as cells from healthy donors. Finally, we also showed that innate-like T cells appeared not to broadly recognize cancer cells, as no direct impact was identified in their overall frequency or cytokine expression when exposed to autologous tumour cells, cancer lysates or lipids extracted from patient tumours, or colorectal cancer cell lines. This project was aimed at providing an overview of potential defects in innate-like T cells based on my analysis of a wide range of samples in the Fiona Elsey Cancer Research Institute (FECRI) Tissue Bank. As a result of my studies, we have established a clear understanding of innate cells in cancer, which provides a basis for future studies. Our novel findings include analysis of frequency distribution and functional capacity of MAIT cells in solid tumours other than colorectal cancer and in patients with blood cancers such as chronic lymphocytic leukaemia (CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) or other haematological malignancies, something not previously reported. Taken together, we showed that a deficiency of innate-like T cells is common in patient groups with cancer and could be a risk factor for disease and possibly a target for immunotherapies, but the functional capacity was intact for cytokine responses.
Description:
Doctor of Philosophy
Description:
Innate-like T cells, including invariant natural killer T (NKT), mucosal associated invariant T (MAIT) cells or
Description:
Innate-like T cells, including invariant natural killer T (NKT), mucosal associated invariant T (MAIT) cells or g T cells are associated with regulation of anti-tumour responses in humans and mice, although their exact role remains controversial. We have studied innate-like T cells from tumour infiltrating lymphocytes (TILS), peripheral blood mononuclear cells (PBMCs) and bone marrow (BM) derived cells from patients undergoing treatment for cancer and compared their characteristics to cells from healthy donors. We identifed that the overall frequency of innate-like T cells was variably deficient in patients with blood or solid cancers. Interestingly, the deficiency of innate-like T cells appeared to be more severe than that of other T cells suggesting a specific impact. An increased proportion of activated g T cells and MAIT cells suggested they could have a functional role in responses to cancer cells. Despite the deficiency of these subsets in patient tissue samples, we showed that anti-tumour capacity of innate-like T cells was intact as innate-like T cells in most patient groups had a similar cytokine response to stimulation as cells from healthy donors. Finally, we also showed that innate-like T cells appeared not to broadly recognize cancer cells, as no direct impact was identified in their overall frequency or cytokine expression when exposed to autologous tumour cells, cancer lysates or lipids extracted from patient tumours, or colorectal cancer cell lines. This project was aimed at providing an overview of potential defects in innate-like T cells based on my analysis of a wide range of samples in the Fiona Elsey Cancer Research Institute (FECRI) Tissue Bank. As a result of my studies, we have established a clear understanding of innate cells in cancer, which provides a basis for future studies. Our novel findings include analysis of frequency distribution and functional capacity of MAIT cells in solid tumours other than colorectal cancer and in patients with blood cancers such as chronic lymphocytic leukaemia (CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) or other haematological malignancies, something not previously reported. Taken together, we showed that a deficiency of innate-like T cells is common in patient groups with cancer and could be a risk factor for disease and possibly a target for immunotherapies, but the functional capacity was intact for cytokine responses.
Description:
Doctor of Philosophy
Description:
Innate-like T cells, including invariant natural killer T (NKT), mucosal associated invariant T (MAIT) cells or
Description:
Measurement of apoptotic markers in tumors can be directly correlated with the cell cycle phase using flow cytometry (FCM). The conventional DNA content analysis requires cell permeabilization to stain nuclei with fluorescent probes such as propidium iodide or use of a costly UV-excitation line for Hoechst 33342 probe. The access to FCM is also still limited to centralized core facilities due to its inherent high costs and complex operation. This work describes development and proof-of-concept validation of a portable and user-friendly microfluidic flow cytometer (μFCM) that can perform multivariate real time analysis on live cells using sampling volumes as small as 10 microliters. The μFCM system employs disposable microfluidic cartridges fabricated using injection molding in poly(methylmethacrylate) transparent thermoplastic. Furthermore, the dedicated and miniaturized electronic hardware interface enables up to six parameter detection using a combination of spatially separated solid-state 473 (10 mW) and 640 nm (20 mW) lasers and x-y stage for rapid laser alignment adjustment. We provide new evidence that a simple 2D flow focusing on a chip is sufficient to measure cellular DNA content in live tumor cells using a far-red DNA probe DRAQ5. The feasibility of using the μFCM system for a dose-response profiling of investigational anti-cancer agents on human hematopoietic cancer cells is also demonstrated. The data show that μFCM can provide a viable novel alternative to conventional FCM for multiparameter detection of caspase activation and dissipation of mitochondrial inner membrane potential (ΔΨm) in relation to DNA content (cell cycle phase) in live tumor cells.
Description:
Measurement of apoptotic markers in tumors can be directly correlated with the cell cycle phase using flow cytometry (FCM). The conventional DNA content analysis requires cell permeabilization to stain nuclei with fluorescent probes such as propidium iodide or use of a costly UV-excitation line for Hoechst 33342 probe. The access to FCM is also still limited to centralized core facilities due to its inherent high costs and complex operation. This work describes development and proof-of-concept validation of a portable and user-friendly microfluidic flow cytometer (
Description:
Purpose To explore the experiences of women with breast cancer and pelvic floor (PF) dysfunction and the perceived enablers and barriers to uptake of treatment for PF dysfunction during their recovery. Method Purposive sampling was used to recruit 30 women with a past diagnosis of breast cancer and PF dysfunction. Semi-structured interviews were conducted, and data were analysed inductively to identify new concepts in the experiences of PF dysfunction in women with breast cancer and deductively according to the capability, opportunity, motivation and behaviour (COM-B) framework to identify the enablers and barriers to the uptake of treatment for PF dysfunction in women with breast cancer. Results Participants were aged between 31 and 88 years, diagnosed with stages I–IV breast cancer and experienced either urinary incontinence ( n = 24/30, 80%), faecal incontinence ( n = 6/30, 20%) or sexual dysfunction ( n = 20/30, 67%). They were either resigned to or bothered by their PF dysfunction bother was exacerbated by embarrassment from experiencing PF symptoms in public. Barriers to accessing treatment for PF dysfunction included a lack of awareness about PF dysfunction following breast cancer treatments and health care professionals not focussing on the management of PF symptoms during cancer treatment. An enabler was their motivation to resume their normal pre-cancer lives. Conclusion Participants in this study reported that there needs to be more awareness about PF dysfunction in women undergoing treatment for breast cancer. They would like to receive information about PF dysfunction prior to starting cancer treatment, be screened for PF dysfunction during cancer treatment and be offered therapies for their PF dysfunction after primary cancer treatment. Therefore, a greater focus on managing PF symptoms by clinicians may be warranted in women with breast cancer.
Description:
Purpose To explore the experiences of women with breast cancer and pelvic floor (PF) dysfunction and the perceived enablers and barriers to uptake of treatment for PF dysfunction during their recovery. Method Purposive sampling was used to recruit 30 women with a past diagnosis of breast cancer and PF dysfunction. Semi-structured interviews were conducted, and data were analysed inductively to identify new concepts in the experiences of PF dysfunction in women with breast cancer and deductively according to the capability, opportunity, motivation and behaviour (COM-B) framework to identify the enablers and barriers to the uptake of treatment for PF dysfunction in women with breast cancer. Results Participants were aged between 31 and 88 years, diagnosed with stages I–IV breast cancer and experienced either urinary incontinence ( n = 24/30, 80%), faecal incontinence ( n = 6/30, 20%) or sexual dysfunction ( n = 20/30, 67%). They were either resigned to or bothered by their PF dysfunction bother was exacerbated by embarrassment from experiencing PF symptoms in public. Barriers to accessing treatment for PF dysfunction included a lack of awareness about PF dysfunction following breast cancer treatments and health care professionals not focussing on the management of PF symptoms during cancer treatment. An enabler was their motivation to resume their normal pre-cancer lives. Conclusion Participants in this study reported that there needs to be more awareness about PF dysfunction in women undergoing treatment for breast cancer. They would like to receive information about PF dysfunction prior to starting cancer treatment, be screened for PF dysfunction during cancer treatment and be offered therapies for their PF dysfunction after primary cancer treatment. Therefore, a greater focus on managing PF symptoms by clinicians may be warranted in women with breast cancer.
Description:
Advances in machine intelligence have provided a whole new window of opportunities in medical research. Building a fully automated computer aided diagnostic system for digital mammograms is just one of them. Given some success with semi-automated systems earlier, a fully automated CAD system is just another step forward. A proper combination of a feature selection model and a classifier for those areas of a mammogram marked by radiologists has been very successful. However a fully automated system with only two modules is a time consuming process as the suspicious areas in a mammogram can be quite small when compared to the whole image. Thus an additional clustering process can help in reducing the time complexity of the overall process. In this paper we propose a fast clustering process to identify suspicious areas. Another novelty of this paper is a multi-category feature selection approach. The choice of features to represent the patterns affects several aspects of pattern recognition problems such as accuracy, required learning time and the required number of samples. In this paper we propose a hybrid canonical based feature extraction technique as a combination of an evolutionary algorithm based classifier with a feed forward MLP model.
Description:
Introduction Many disability prevention strategies are focused on acute injuries and brief illness episodes, but there will be growing challenges for employers to manage circumstances of recurrent, chronic, or fluctuating symptoms in an aging workforce. The goal of this article is to summarize existing peer-review research in this area, compare this with employer discourse in the grey literature, and recommend future research priorities. Methods The authors participated in a year-long sponsored collaboration that ultimately led to an invited 3-day conference, “Improving Research of Employer Practices to Prevent Disability”, held October 14–16, 2015, in Hopkinton, Massachusetts, USA. The collaboration included a topical review of the scientific and industry literature, group discussion to identify key areas and challenges, drafting of initial documents, and feedback from peer researchers and a special panel of experts with employer experience. Results Cancer and mental illness were chosen as examples of chronic or recurring conditions that might challenge conventional workplace return-to-work practices. Workplace problems identified in the literature included fatigue, emotional exhaustion, poor supervisor and co-worker support, stigma, discrimination, and difficulties finding appropriate accommodations. Workplace intervention research is generally lacking, but there is preliminary support for improving workplace self-management strategies, collaborative problem-solving, and providing checklists and other tools for job accommodation, ideas echoed in the literature directed toward employers. Research might be improved by following workers from an earlier stage of developing workplace concerns. Conclusions Future research of work disability should focus on earlier identification of at-risk workers with chronic conditions, the use of more innovative and flexible accommodation strategies matched to specific functional losses, stronger integration of the workplace into on-going rehabilitation efforts, and a better understanding of stigma and other social factors at work.